Search results for: heat shock protein

Authors: S. G. Vasantharaju, Viswanath Guptha, Raghavendra Shetty

Abstract:

Introduction: Aminophylline is a methylxanthine derivative belonging to the class bronchodilator. From the literature survey, reported methods reveals the solid phase extraction and liquid liquid extraction which is highly variable, time consuming, costly and laborious analysis. Present work aims to develop a simple, highly sensitive, precise and accurate high-performance liquid chromatography method for the quantification of Aminophylline in rat plasma samples which can be utilized for preclinical studies. Method: Reverse Phase high-performance liquid chromatography method. Results: Selectivity: Aminophylline and the internal standard were well separated from the co-eluted components and there was no interference from the endogenous material at the retention time of analyte and the internal standard. The LLOQ measurable with acceptable accuracy and precision for the analyte was 0.5 µg/mL. Linearity: The developed and validated method is linear over the range of 0.5-40.0 µg/mL. The coefficient of determination was found to be greater than 0.9967, indicating the linearity of this method. Accuracy and precision: The accuracy and precision values for intra and inter day studies at low, medium and high quality control samples concentrations of aminophylline in the plasma were within the acceptable limits Extraction recovery: The method produced consistent extraction recovery at all 3 QC levels. The mean extraction recovery of aminophylline was 93.57 ± 1.28% while that of internal standard was 90.70 ± 1.30%. Stability: The results show that aminophylline is stable in rat plasma under the studied stability conditions and that it is also stable for about 30 days when stored at -80˚C. Pharmacokinetic studies: The method was successfully applied to the quantitative estimation of aminophylline rat plasma following its oral administration to rats. Discussion: Preclinical studies require a rapid and sensitive method for estimating the drug concentration in the rat plasma. The method described in our article includes a simple protein precipitation extraction technique with ultraviolet detection for quantification. The present method is simple and robust for fast high-throughput sample analysis with less analysis cost for analyzing aminophylline in biological samples. In this proposed method, no interfering peaks were observed at the elution times of aminophylline and the internal standard. The method also had sufficient selectivity, specificity, precision and accuracy over the concentration range of 0.5 - 40.0 µg/mL. An isocratic separation technique was used underlining the simplicity of the presented method.

Keywords: Aminophyllin, preclinical pharmacokinetics, rat plasma, RPHPLC

Procedia PDF Downloads 197

Authors: Tais Basaco, Stefanie Pektor, Josue A. Moreno, Matthias Miederer, Andreas Türler

Abstract:

Radiopharmaceuticals based in monoclonal anti-body (mAb) via chemical linkers have become a potential tool in nuclear medicine because of their specificity and the large variability and availability of therapeutic radiometals. It is important to identify the conjugation sites and number of attached chelator to mAb to obtain radioimmunoconjugates with required immunoreactivity and radiostability. Girentuximab antibody (G250) is a potential candidate for radioimmunotherapy of clear cell carcinomas (RCCs) because it is reactive with CAIX antigen, a transmembrane glycoprotein overexpressed on the cell surface of most ( > 90%) (RCCs). G250 was conjugated with the bifunctional chelating agent DOTA (1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid) via a benzyl-thiocyano group as a linker (p-SCN-Bn-DOTA). DOTA-G250 conjugates were analyzed by size exclusion chromatography (SE-HPLC) and by electrophoresis (SDS-PAGE). The potential site-specific conjugation was identified by liquid chromatography–mass spectrometry (LC/MS-MS) and the number of linkers per molecule of mAb was calculated using the molecular weight (MW) measured by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The average number obtained in the conjugates in non-reduced conditions was between 8-10 molecules of DOTA per molecule of mAb. The average number obtained in the conjugates in reduced conditions was between 1-2 and 3-4 molecules of DOTA per molecule of mAb in the light chain (LC) and heavy chain (HC) respectively. Potential DOTA modification sites of the chelator were identified in lysine residues. The biological activity of the conjugates was evaluated by flow cytometry (FACS) using CAIX negative (SKRC-18) and CAIX positive (SKRC-52). The DOTA-G250 conjugates were labelled with 177Lu with a radiochemical yield > 95% reaching specific activities of 12 MBq/µg. The stability in vitro of different types of radioconstructs was analyzed in human serum albumin (HSA). The radiostability of 177Lu-DOTA-G250 at high specific activity was increased by addition of sodium ascorbate after the labelling. The immunoreactivity was evaluated in vitro and in vivo. Binding to CAIX positive cells (SK-RC-52) at different specific activities was higher for conjugates with less DOTA content. Protein dose was optimized in mice with subcutaneously growing SK-RC-52 tumors using different amounts of 177Lu- DOTA-G250.

Keywords: mass spectrometry, monoclonal antibody, radiopharmaceuticals, radioimmunotheray, renal cancer

Procedia PDF Downloads 280

Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

Abstract:

Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

Procedia PDF Downloads 45

Authors: S. K. Ghosh, C. Srivastava, P. K. Limaye, V. Kain

Abstract:

Electroplated hard chromium is widely known in coatings and surface finishing, automobile and aerospace industries because of its excellent hardness, wear resistance and corrosion properties. However, its precursor, Cr+6 is highly carcinogenic in nature and a consensus has been adopted internationally to eradicate this coating technology with an alternative one. The search for alternate coatings to electroplated hard chrome is continuing worldwide. Various alloys and nanocomposites like Co-W alloys, Ni-Graphene, Ni-diamond nanocomposites etc. have already shown promising results in this regard. Basically, in this study, electroless Ni-P alloys with excellent corrosion resistance was taken as the base matrix and incorporation of tungsten as third alloying element was considered to improve the hardness and wear resistance of the resultant alloy coating. The present work is focused on the preparation of Ni–W–P coatings by electrodeposition with different content of phosphorous and its effect on the electrochemical, mechanical and tribological performances. The results were also compared with Ni-W alloys. Composition analysis by EDS showed deposition of Ni-32.85 wt% W-3.84 wt% P (designated as Ni-W-LP) and Ni-18.55 wt% W-8.73 wt% P (designated as Ni-W-HP) alloy coatings from electrolytes containing of 0.006 and 0.01M sodium hypophosphite respectively. Inhibition of tungsten deposition in the presence of phosphorous was noted. SEM investigation showed cauliflower like growth along with few microcracks. The as-deposited Ni-W-P alloy coating was amorphous in nature as confirmed by XRD investigation and step-wise crystallization was noticed upon annealing at higher temperatures. For all the coatings, the nanohardness was found to increase after heat-treatment and typical nanonahardness values obtained for 400°C annealed samples were 18.65±0.20 GPa, 20.03±0.25 GPa, and 19.17±0.25 for alloy coatings Ni-W, Ni-W-LP and Ni-W-HP respectively. Therefore, the nanohardness data show very promising results. Wear and coefficient of friction data were recorded by applying a different normal load in reciprocating motion using a ball on plate geometry. Post experiment, the wear mechanism was established by detail investigation of wear-scar morphology. Potentiodynamic measurements showed coating with a high content of phosphorous was most corrosion resistant in 3.5wt% NaCl solution.

Keywords: corrosion, electrodeposition, nanohardness, Ni-W-P alloy coating

Procedia PDF Downloads 328

Authors: A. Gramza-Michałowska, J. Skręty, M. Antczak, J. Kobus-Cisowska, D. Kmiecik, J. Korczak, Kulczyński Bartosz

Abstract:

Background: Modern consumer highly appreciates the correlation between eating habits and health. Intensified research showed many proofs confirming that food besides its basic nutritional function, possess also significant prophylactic and therapeutic potential. Preventive potential of selected food is commonly used as improvement factor of patients life standard. World Health Organization indicates that diabetes (Diabetes mellitus) and obesity are two of the most common and dangerous diseases. Diet therapy is an element of diabetes education program and a part of healing process, allowing maintaining and remaining the optimal metabolic state of the system. It must be remembered that diabetes treatment should be individualized to each patient. One of highly recommended vegetable for diabetes is asparagus (Asparagus officinalis L.), low calories common plant, growing in European countries. Objective: To propose the technology of unsweetened muesli production with addition of new components, we investigated the effects of selected vegetable addition on antioxidative capacity and consumer’s acceptance of muesli as representative of breakfast product. Methods: Muesli was formulated from a composition of oat flakes, flaxseed, bran, carrots, broccoli and asparagus. Basic composition of muesli was evaluated as content of protein, lipids, fatty acid composition, ash, selected minerals and caloricity. Antioxidant capacity of muesli was evaluated with use radical scavenging methods (DPPH, ABTS), ORAC value and PCL - photochemiluminescence antiradical potential. Proposed muesli as new product was also characterized with sensory analysis, which included color, scent, taste, consistency and overall acceptance of a product. Results: Results showed that addition of freeze-dried asparagus into muesli allowed to lower the fat content and caloricity of a product according to the base product. No significant loss in antioxidant potential was evaluated, also the sensory value of a product was not negative. Conclusion: Designed muesli would be an answer for obese people looking for healthy snack during the daytime. Results showed that product with asparagus addition would be accepted by the consumers and because of its antidiabetic potential could be a n important factor in prevention of diabetes or obesity. Financial support by the UE Project no PO IG 01.01.00.00-061/09

Keywords: muesli, vegetables, asparagus, antioxidant potential, lipids

Procedia PDF Downloads 290

Authors: Samuel Abebe Ebebo

Abstract:

Scale precipitation causes a major issue for geothermal power plants because it reduces the production rate of geothermal energy. Each geothermal power plant's different chemical and physical conditions can cause the scale to precipitate under a particular set of fluid-rock interactions. Depending on the mineral, it is possible to have scale in the production well, steam separators, heat exchangers, reinjection wells, and everywhere in between. The scale consists mainly of smectite and trace amounts of chlorite, magnetite, quartz, hematite, dolomite, aragonite, and amorphous silica. The smectite scale is one of the difficult scales at injection wells in geothermal power plants. X-ray diffraction and chemical composition identify this smectite as Stevensite. The characteristics and the scale of each injection well line are different depending on the fluid chemistry. The smectite scale has been widely distributed in pipelines and surface plants. Mineral water equilibrium showed that the main factors controlling the saturation indices of smectite increased pH and dissolved Mg concentration due to the precipitate on the equipment surface. This study aims to characterize the scales and geothermal fluids collected from the Onuma geothermal power plant in Akita Prefecture, Japan. Field tests were conducted on October 30–November 3, 2021, at Onuma to determine the pH control methods for preventing magnesium silicate scaling, and as exemplified, the formation of magnesium silicate hydrates (M-S-H) with MgO to SiO2 ratios of 1.0 and pH values of 10 for one day has been studied at 25 °C. As a result, M-S-H scale formation could be suppressed, and stevensite formation could also be suppressed when we can decrease the pH of the fluid by less than 8.1, 7.4, and 8 (at 97 °C) in the fluid from O-3Rb and O-6Rb, O-10Rg, and O-12R, respectively. In this context, the scales and fluids collected from injection wells at a geothermal power plant in Japan were analyzed and characterized to understand the formation conditions of Mg-silicate scales with on-site synthesis experiments. From the results of the characterizations and on-site synthesis experiments, the inhibition method of their scale formation is discussed based on geochemical modeling in this study.

Keywords: magnesium silicate, scaling, inhibitor, geothermal power plant

Procedia PDF Downloads 39

Authors: M. Sakthivel, A. Devaki, D. Balasubramanyam, P. Kumarasamy, A. Raja, R. Anilkumar, H. Gopi

Abstract:

The New Zealand White breed of rabbit is one of the most commonly used, well adapted exotic breeds in India. Earlier studies were limited only to analyze the environmental factors affecting the growth and reproductive performance. In the present study, the population of the New Zealand White rabbits in a closed herd was evaluated for its genetic structure. Data on pedigree information (n=2508) for 18 years (1995-2012) were utilized for the study. Pedigree analysis and the estimates of population genetic parameters based on gene origin probabilities were performed using the software program ENDOG (version 4.8). The analysis revealed that the mean values of generation interval, coefficients of inbreeding and equivalent inbreeding were 1.489 years, 13.233 percent and 17.585 percent, respectively. The proportion of population inbred was 100 percent. The estimated mean values of average relatedness and the individual increase in inbreeding were 22.727 and 3.004 percent, respectively. The percent increase in inbreeding over generations was 1.94, 3.06 and 3.98 estimated through maximum generations, equivalent generations, and complete generations, respectively. The number of ancestors contributing the most of 50% genes (fₐ₅₀) to the gene pool of reference population was 4 which might have led to the reduction in genetic variability and increased amount of inbreeding. The extent of genetic bottleneck assessed by calculating the effective number of founders (fₑ) and the effective number of ancestors (fₐ), as expressed by the fₑ/fₐ ratio was 1.1 which is indicative of the absence of stringent bottlenecks. Up to 5th generation, 71.29 percent pedigree was complete reflecting the well-maintained pedigree records. The maximum known generations were 15 with an average of 7.9 and the average equivalent generations traced were 5.6 indicating of a fairly good depth in pedigree. The realized effective population size was 14.93 which is very critical, and with the increasing trend of inbreeding, the situation has been assessed to be worse in future. The proportion of animals with the genetic conservation index (GCI) greater than 9 was 39.10 percent which can be used as a scale to use such animals with higher GCI to maintain balanced contribution from the founders. From the study, it was evident that the herd was completely inbred with very high inbreeding coefficient and the effective population size was critical. Recommendations were made to reduce the probability of deleterious effects of inbreeding and to improve the genetic variability in the herd. The present study can help in carrying out similar studies to meet the demand for animal protein in developing countries.

Keywords: effective population size, genetic structure, pedigree analysis, rabbit genetics

Procedia PDF Downloads 271

Authors: Assabo Mohamed, Bile Mohamed, Ali Farah, Isman Souleiman, Olga Alos Ramos, Marie Cadet

Abstract:

The life of a nuclear power plant is regularly punctuated by short or long period outages to carry out maintenance operations and/or nuclear fuel reloading. During these stops periods, it is essential to conserve all the secondary circuit equipment to avoid corrosion priming. This kind of circuit is one of the main components of a nuclear reactor. Indeed, the conservation materials on shutdown of a nuclear unit improve circuit performance and reduce the maintenance cost considerably. This study is a part of the optimization of the dry preservation of equipment from the water station of the nuclear reactor. The main objective is to provide tools to guide Electricity Production Nuclear Centre (EPNC) in order to achieve the criteria required by the chemical specifications of conservation materials. A theoretical model of drying exchangers of water station is developed by the software Engineering Equation Solver (EES). It used to size requirements and air quality needed for dry conservation of equipment. This model is based on heat transfer and mass transfer governing the drying operation. A parametric study is conducted to know the influence of aerothermal factor taking part in the drying operation. The results show that the success of dry conservation of equipment of the secondary circuit of nuclear reactor depends strongly on the draining, the quality of drying air and the flow of air injecting in the secondary circuit. Finally, theoretical case study performed on EES highlights the importance of mastering the entire system to balance the air system to provide each exchanger optimum flow depending on its characteristics. From these results, recommendations to nuclear power plants can be formulated to optimize drying practices and achieve good performance in the conservation of material from the water at the stop position.

Keywords: dry conservation, optimization, sizing, water station

Procedia PDF Downloads 242

Authors: T. Hamaishi, Y. Morinaga, H. Morita

Abstract:

Introduction: Rice consumption in Japan has decreased, and Japanese government has recommended use of rice flour in order to expand the consumption of rice. There are two major protein components present in flour, called gliadin and glutenin. Gluten forms when water is added to flour and is mixed. As mixing continues, glutenin interacts with gliadin to form viscoelastic matrix of gluten. Rice flour bread does not expand as much as wheat flour bread. Because rice flour is not included gluten, it cannot construct gluten network in the dough. In recent years, some food additives have been used for dough-improving agent in bread making, especially surfactants has effect in order to improve dough extensibility. Therefore, we focused to fatty acid salt which is one of anionic surfactants. Fatty acid salt is a salt consist of fatty acid and alkali, it is main components of soap. According to JECFA(FAO/WHO Joint Expert Committee on Food Additives), salts of Myristic(C14), Palmitic(C16) and Stearic(C18) could be used as food additive. They have been evaluated ADI was not specified. In this study, we investigated to improving bread-making properties of rice flour dough adding fatty acid salt. Materials and methods: The sample of fatty acid salt is myristic (C14) dissolved in KOH solution to a concentration of 350 mM and pH 10.5. Rice dough was consisted of 100 g of flour using rice flour and wheat gluten, 5 g of sugar, 1.7 g of salt, 1.7g of dry yeast, 80 mL of water and fatty acid salt. Mixing was performed for 500 times by using hand. The concentration of C14K in the dough was 10 % relative to flour weight. Amount of gluten in the dough was 20 %, 30 % relative to flour weight. Dough expansion ability test was performed to measure physical property of bread dough according to the methods of Baker’s Yeast by Japan Yeast Industry Association. In this test, 150 g of dough was filled from bottom of the cylinder and fermented at 30 °C，85 % humidity for 120 min on an incubator. The height of the expansion in the dough was measured and determined its expansion ability. Results and Conclusion: Expansion ability of rice dough with gluten content of 20 %, 30% showed 316 mL, 341 mL for 120 min. When C14K adding to the rice dough, dough expansion abilities were 314 mL, 368 mL for 120 min, there was no significant difference. Conventionally it has been known that the rice flour dough contain gluten of 20 %. The considerable improvement of dough expansion ability was achieved when added C14K to wheat flour. The experimental result shows that c14k adding to the rice dough with gluten content more than 20 % was not improving bread-making properties. In conclusion, rice bread made with gluten content more than 20 % without C14K has been suggested to contribute to the formation of the sufficient gluten network.

Keywords: expansion ability, fatty acid salt, gluten, rice flour dough

Procedia PDF Downloads 225

Authors: Gunjan Razdan, Priyanka Sreenath, Jagannath Behera, S. K. Mishra, Sunil Mehra

Abstract:

Uttar Pradesh is one of the poor performing states with high Malnutrition and Anaemia among adolescent girls resulting in high MMR, IMR and low birth weight rate. The rate of anaemia among adolescent girls has doubled in the past decade. Adolescents gain around 15-20% of their optimum height, 25-50% of the ideal adult weight and 45% of the skeletal mass by the age of 19. Poor intake of energy, protein and other nutrients is one of the factors for malnutrition and anaemia. METHODS: The cross-sectional survey using a mixed method (quantitative and qualitative) was adopted in this study. The respondents (adolescents, parents and frontline health workers) were selected randomly from 30 villages and surveyed through a semi-structured questionnaire for qualitative information and FGDs and IDIs for qualitative information. A 24 hours dietary recall method was adopted to estimate their dietary practices. A total of 1069 adolescent girls, 1067 boys, 1774 parents and 69 frontline functionaries were covered under the study. Percentages and mean were calculated for quantitative variable, and content analysis was carried out for qualitative data. RESULTS: Over 80 % of parents provided assertions that they understood the term balanced diet and strongly felt that their children were having balanced diet. However, only negligible 1.5 % of parents could correctly recount essential eight food groups and 22% could tell about four groups which was the minimum response expected to say respondents had fair knowledge on a balanced diet. Only 10 percent of parents could tell that balanced diet helps in physical and mental growth and only 2% said it has a protective role. Besides, qualitative data shows that the perception regarding balanced diet is having costly food items like nuts and fruits. The dietary intake of adolescents is very low despite the increased iron needs associated with physical growth and puberty.The consumption of green leafy vegetables (less than 35 %) and citrus fruits (less than 50%) was found to be low. CONCLUSIONS: The assertions on an understanding of term balanced diet are contradictory to the actual knowledge and practices. Knowledge on essential food groups and nutrients is crucial to inculcate healthy eating practices among adolescents. This calls for comprehensive communication efforts to improve the knowledge and dietary practices among adolescents.

Keywords: anemia, knowledge, malnutrition, perceptions

Procedia PDF Downloads 378

Authors: Dmitry V. Pasynkov, Ivan A. Egoshin, Alexey A. Kolchev, Ivan V. Kliouchkin

Abstract:

In most cases, typical cysts are easily recognized at ultrasonography. The specificity of this method for typical cysts reaches 98%, and it is usually considered as gold standard for typical cyst diagnosis. However, it is necessary to have all the following features to conclude the typical cyst: clear margin, the absence of internal echoes and dorsal acoustic enhancement. At the same time, not every breast cyst is typical. It is especially characteristic for protein-contained cysts that may have significant internal echoes. On the other hand, some solid lesions (predominantly malignant) may have cystic appearance and may be falsely accepted as cysts. Therefore we tried to develop the automatic method of cystic and solid breast lesions differentiation. Materials and methods. The input data were the ultrasonography digital images with the 256-gradations of gray color (Medison SA8000SE, Siemens X150, Esaote MyLab C). Identification of the lesion on these images was performed in two steps. On the first one, the region of interest (or contour of lesion) was searched and selected. Selection of such region is carried out using the sigmoid filter where the threshold is calculated according to the empirical distribution function of the image brightness and, if necessary, it was corrected according to the average brightness of the image points which have the highest gradient of brightness. At the second step, the identification of the selected region to one of lesion groups by its statistical characteristics of brightness distribution was made. The following characteristics were used: entropy, coefficients of the linear and polynomial regression, quantiles of different orders, an average gradient of brightness, etc. For determination of decisive criterion of belonging to one of lesion groups (cystic or solid) the training set of these characteristics of brightness distribution separately for benign and malignant lesions were received. To test our approach we used a set of 217 ultrasonic images of 107 cystic (including 53 atypical, difficult for bare eye differentiation) and 110 solid lesions. All lesions were cytologically and/or histologically confirmed. Visual identification was performed by trained specialist in breast ultrasonography. Results. Our system correctly distinguished all (107, 100%) typical cysts, 107 of 110 (97.3%) solid lesions and 50 of 53 (94.3%) atypical cysts. On the contrary, with the bare eye it was possible to identify correctly all (107, 100%) typical cysts, 96 of 110 (87.3%) solid lesions and 32 of 53 (60.4%) atypical cysts. Conclusion. Automatic approach significantly surpasses the visual assessment performed by trained specialist. The difference is especially large for atypical cysts and hypoechoic solid lesions with the clear margin. This data may have a clinical significance.

Keywords: breast cyst, breast solid lesion, differentiation, ultrasonography

Procedia PDF Downloads 247

Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson

Abstract:

MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.

Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3

Procedia PDF Downloads 225

Authors: Nattaporn Khanoonkon, Rangrong Yoksan, Amod A. Ogale

Abstract:

Polyethylene (PE) is one of the most petroleum-based thermoplastic materials used in many applications including packaging due to its cheap, light-weight, chemically inert and capable to be converted into various shapes and sizes of products. Although PE is a commercially potential material, its non-biodegradability caused environmental problems. At present, bio-based polymers become more interesting owing to its bio-degradability, non-toxicity, and renewability as well as being eco-friendly. Thermoplastic starch (TPS) is a bio-based and biodegradable plastic produced from the plasticization of starch under applying heat and shear force. In many researches, TPS was blended with petroleum-based polymers including PE in order to reduce the cost and the use of those polymers. However, the phase separation between hydrophobic PE and hydrophilic TPS limited the amount of TPS incorporated. The immiscibility of two different polarity polymers can be diminished by adding compatibilizer. PE-based compatibilizers, e.g. polyethylene-grafted-maleic anhydride, polyethylene-co-vinyl alcohol, etc. have been applied for the PE/TPS blend system in order to improve their miscibility. Until now, there is no report about the utilization of starch-based compatibilizer for PE/TPS blend system. The aims of the present research were therefore to synthesize a new starch-based compatibilizer, i.e. stearic acid-grafted starch (SA-g-starch) and to study the effect of SA-g-starch on chemical interaction, morphological properties, tensile properties and water vapor as well as oxygen barrier properties of the PE/TPS blend films. PE/TPS blends without and with incorporating SA-g-starch with a content of 1, 3 and 5 part(s) per hundred parts of starch (phr) were prepared using a twin screw extruder and then blown into films using a film blowing machine. Incorporating 1 phr and 3 phr of SA-g-starch could improve miscibility of the two polymers as confirmed from the reduction of TPS phase size and the good dispersion of TPS phase in PE matrix. In addition, the blend containing SA-g-starch with contents of 1 phr and 3 phr exhibited higher tensile strength and extensibility, as well as lower water vapor and oxygen permeabilities than the naked blend. The above results suggested that SA-g-starch could be potentially applied as a compatibilizer for the PE/TPS blend system.

Keywords: blend, compatibilizer, polyethylene, thermoplastic starch

Procedia PDF Downloads 413

Authors: Saule Musabekova

Abstract:

Achievements of modern science, especially genetics, led to a sharp intensification of the process of proof. Footprints, subjected to destruction-related cause-effect relationships, are sources of evidentiary information on the circumstances it was committed and the persons committed it. Currently, with the overall growth in the number of crimes against sexual inviolability or sexual freedom, and increased the proportion of the crimes where to destroy the traces of the crime perpetrators different detergents are used. A characteristic feature of modern synthetic detergents is the presence of biological additives - enzymes that break down and gradually destroy stains of protein origin. To study the nature of the influence of modern washing powders semen stains were put kinds of fabrics and prepared in advance stained sperm of men of different groups according to ABO system. For research washing machines of known manufacturers of household appliances have been used with different production characteristics, in which the test was performed and the washing of various kinds of fabrics with semen stains. After washing the tissue with spots were tested for the presence of semen stains visually preserved, establishing in them surviving sperm or their elements, we studied the possibilities of the group diagnostics on the system ABO or molecular-genetic identification. The subsequent study of these spots by morphological method showed that 100% detection of morphological sperm cells - sperm is not possible. As a result, in 30% of further studies of these traces gave weakly positive results are obtained with an immunoassay test PSA SEMIQUANT. It is noted that the percentage of positive results obtained in the study of semen traces disposed on natural fiber fabrics is higher than sperm traces disposed on synthetic fabrics. Study traces of semen, confirmed by PSA - test 3% possible to establish a genetic profile of the person and obtain any positive findings of the molecular genetic examination. In other cases, it was not a sufficient amount of material for DNA identification. Results of research and the practical expert study found, in most cases, the conclusions of the identification of sperm traces do not seem possible. This a consequence of exposure to semen traces on the material evidence of biological additives contained in modern detergents and further the influence of other effective methods. Resulting in DNA has undergone irreversible changes (degradation) under the influence of external human factors. Using molecular genetic methods can partially solve the problems arising in the study of unlaundered physical evidence for the disclosure and investigation of crimes.

Keywords: study of sperm, modern detergents, washing powders, forensic medicine

Procedia PDF Downloads 279

Authors: Supanan Chansap, Werachon Cheukamud, Pornanan Kueakhai, Narin Changklungmoa

Abstract:

Fasciola species (Fasciola spp.) is caused fasciolosis in ruminants such as cattle, sheep, and buffalo. Fasciola gigantica (F.gigantica) commonly infects tropical regions. Fasciola hepatica (F.hepatica) in temperate regions. Liver fluke infection affects livestock economically, for example, reduced milk and meat production, weight loss, sterile animals. Currently, Triclabendazole is used to treat liver flukes. However, liver flukes have also been found to be resistant to drugs in countries. Therefore, vaccination is an attractive alternative to prevent liver fluke infection. Peptide vaccines are new vaccine technologies that mimic epitope antigens that trigger an immune response. An interesting antigen used in vaccine production is catepsin L, a family of proteins that play an important role in the life of the parasite in the host. This study aims to identify immunogenic regions of protein and construct a multi-epidetope vaccine using an immunoinformatic tool. Fasciola gigantica Cathepsin L1 (FgCatL1), Fasciola gigantica Cathepsin L1G (FgCatL1G), and Fasciola gigantica Cathepsin L1H (FgCatL1H) were predicted B-cell and Helper T lymphocytes (HTL) by Immune Epitope and Analysis Resource (IEDB) servers. Both B-cell and HTL epitopes aligned with cathepsin L of the host and Fasciola hepatica (F. hepatica). Epitope groups were selected from non-conserved regions and overlapping sequences with F. hepatica. All overlapping epitopes were linked with the GPGPG and KK linker. GPGPG linker was linked between B-cell epitope. KK linker was linked between HTL epitope and B-cell and HTL epitope. The antigenic scores of multi-epitope peptide vaccine was 0.7824. multi-epitope peptide vaccine was non-allergen, non-toxic, and good soluble. Multi-epitope peptide vaccine was predicted tertiary structure and refinement model by I-Tasser and GalaxyRefine server, respectively. The result of refine structure model was good quality that was generated by Ramachandran plot analysis. Discontinuous and linear B-cell epitopes were predicted by ElliPro server. Multi-epitope peptide vaccine model was two and seven of discontinuous and linear B-cell epitopes, respectively. Furthermore, multi-epitope peptide vaccine was docked with Toll-like receptor 2 (TLR-2). The lowest energy ranged from -901.3 kJ/mol. In summary, multi-epitope peptide vaccine was antigenicity and probably immune response. Therefore, multi-epitope peptide vaccine could be used to prevent F. gigantica infections in the future.

Keywords: fasciola gigantica, Immunoinformatic tools, multi-epitope, Vaccine

Procedia PDF Downloads 53

Authors: Bisemiire Anthony,

Abstract:

PESH Poultry is a business project proposed specifically to solve unemployment and income-related problems affecting the youths in the Busia district. The project is intended to transform the life of the youth in terms of economic, social and behavioral, as well as the domestic well-being of the community at large. PESH Poultry is a start-up poultry farm that will be engaged in the keeping of poultry birds, broilers and layers for the production of quality and affordable poultry meat and eggs respectively and other poultry derivatives targeting consumers in eastern Uganda, for example, hotels, restaurants, households and bakeries. We intend to use a semi-intensive system of farming, where water and some food are provided in a separate nighttime shelter for the birds; our location will be in Lumino, Busia district. The poultry project will be established and owned by Bisemiire Anthony, Nandera Patience, Naula Justine, Bwire Benjamin and other investors. The farm will be managed and directed by Nandera Patience, who has five years of work experience and business administration knowledge. We will sell poultry products, including poultry eggs, chicken meat, feathers and poultry manure. We also offer consultancy services for poultry farming. Our eggs and chicken meat are hygienic, rich in protein and high quality. We produce processes and packages to meet the standard organization of Uganda and international standards. The business project shall comprise five (5) workers on the key management team who will share various roles and responsibilities in the identified business functions such as marketing, finance and other related poultry farming activities. PESH Poultry seeks 30 million Ugandan shillings in long-term financing to cover start-up costs, equipment, building expenses and working capital. Funding for the launch of the business will be provided primarily by equity from the investors. The business will reach positive cash flow in its first year of operation, allowing for the expected repayment of its loan obligations. Revenue will top UGX 11,750,000, and net income will reach about UGX115 950,000 in the 1st year of operation. The payback period for our project is 2 years and 3 months. The farm plans on starting with 1000 layer birds and 1000 broiler birds, 20 workers in the first year of operation.

Keywords: chicken, pullets, turkey, ducks

Procedia PDF Downloads 61

Authors: Gizaw Mamo Gebeyehu, Marianna Pap, Geza Makkai, Tibor Z. Janosi, Shima Rashidian, Tibor A. Rauch

Abstract:

Sepsis poses a significant global health threat, necessitating extensive exploration of indicators tied to its pathological mechanisms and multi-organ dysfunction. While murine studies have shed light on sepsis, the intricate cellular and molecular landscape in human sepsis remains enigmatic. Exploring the influence of activated monocyte-derived exosomes in sepsis sheds light on a promising pathway for understanding the intricate cellular and molecular mechanisms involved in this condition in humans. In sepsis, exosome-borne mRNA and miRNA orchestrate immune response gene expression in recipient cells. Yet, the specifics of exosome-mediated cell-to-cell communication, especially how mRNA cargoes modulate gene expression in recipient cells, remain poorly understood. This study aims to elucidate the precise molecular pathways through which exosomal mRNA cargo, particularly MAFB, contributes to the developing sepsis-induced molecular aberrations in liver tissues, employing rigorously defined cell culture conditions. THP-1 cells were treated with LPS to induce changes in exosomal RNA profiles. Exosomes were isolated and characterized using microscopy and mass spectrometry. RNA was extracted from exosomes and sequenced. The most abundant exosomal mRNAs were subjected to GO analysis for functional annotation analysis and KEGG database analysis to identify the involved enriched pathways. PCR (Polymerase Chain Reaction), RNA sequencing, and Western blotting were involved to analyze changes in gene expression, protein levels, and signaling pathways within the liver cells( HepG2) after exposure to exosomal MAFB. This study pinpoints exosomal MAFB as a potential key regulator linked to liver cell damage during sepsis, along with associated genes (miR155HG, H3F3A, and possibly JARD2) forming a crucial molecular pathway contributing to liver cell injury, Together, these elements indicate a vital molecular pathway that plays a significant role in the emergence of liver cell injury during sepsis.. These findings suggest the importance of further research on these components for potential therapeutic interventions in managing acute liver damage in sepsis.

Keywords: sepsis, exososome, exosomal MAFB, LPS-induced THP-1 cells, RNA profiles, sepsis-triggered liver injury

Procedia PDF Downloads 41

Authors: Shalini Arora, Sri Sivakumar

Abstract:

The deep removal of high molecular weight sulphur compounds (e.g., 4,6, dimethyl dibenzothiophene) is challenging due to their steric hindrance. Hydrogenation desulfurization (HYD) pathway is the main pathway to remove these sulfur compounds, and it is mainly governed by the number of type 2 sites. The formation of type 2 sites can be enhanced by modulating the pore structure and the interaction between the active metal and support. To this end, we report the enhanced HDS catalytic activity of ultrasmall NiMo supported on amorphous alumina (A-Al₂O₃) catalysts by one pot colloidal synthesis method followed by calcination and sulfidation. The amorphous alumina (A-Al₂O₃) was chosen as the support due to its lower surface energy, better physicochemical properties, and enhanced acidic sites (due to the dominance of tetra and penta coordinated [Al] sites) than crystalline alumina phase. At 20% metal oxide composition, NiMo supported on A-Al₂O₃ catalyst showed 1.4 and 1.2 times more reaction rate constant and turn over frequency (TOF) respectively than the conventional catalyst (wet impregnated NiMo catalysts) for HDS reaction of dibenzothiophene reactant molecule. A-Al₂O₃ supported catalysts represented enhanced type 2 sites formation (because this catalystpossesses higher sulfidation degree (80%) and NiMoS sites (19.3 x 10¹⁷ sites/mg) with desired optimum stacking degree (2.5) than wet impregnated catalyst at same metal oxide composition 20%) along with higher active metal dispersion, Mo edge site fraction. The experimental observations were also supported by DFT simulations. Lower heat of adsorption (< 4.2 ev for MoS2 interaction and < 3.15 ev for Ni doped MoS2 interaction) values for A-Al₂O₃ confirmed the presence of weaker metal-support interaction in A-Al₂O₃ in contrast to crystalline ℽ-Al₂O3. The weak metal-support interaction for prepared catalysts clearly suggests the higher formation of type 2 sites which leads to higher catalytic activity for HDS reaction.

Keywords: amorphous alumina, colloidal, desulfurization, metal-support interaction

Procedia PDF Downloads 244

Authors: Patience Manjengwa-Hungwe, Carmen White

Abstract:

Background: Odyssean malaria refers to malaria acquired by infected mosquito bites from malaria endemic to non-endemic regions by mechanical modes of transport, such as airplanes, water vessels, trains and vehicles. Odyssean Malaria is rare and is characterised by absence of travel history to malaria endemic areas. As not anticipated in non-endemic areas, late diagnosis and treatment lead to a high case fatality rate. On 26 September 2014, the Outbreak Response Unit at the National Institute of Communicable Diseases was notified of a suspected death from Odyssean Malaria in Johannesburg, Gauteng Province, a non-endemic area. The main objective of this investigation was to identify the etiological agent's mode and source of transmission. Methods: Epidemiological surveys were conducted with the deceased’s family and clinical details were obtained from doctors who treated the victim in Southrand, Johannesburg. Blood samples were collected prior to death and sent to the National Health Laboratory Services, Johannesburg laboratory for a full blood count, urea electrolytes, creatinine, and C-reactive protein. Environmental assessments and entomological investigations, including collection of mosquito and larvae, were conducted at the deceased’s home and surrounding areas and sent to the laboratory for analysis. Results: Epidemiological surveys revealed no travel history, no mechanical transmission through blood transfusion and no previous possible exposure of the victim to malaria mosquitoes. Laboratory findings indicated that the platelet count was low. A further smear revealed that the malaria parasite was present and malaria antigen for P. falciparum was positive. Entomological findings revealed that none of the six adult or larval mosquitoes collected on site were malaria vectors. Dumping sites found at the back of the house were identified as possible sites where mosquitoes from endemic places could possibly breed. Conclusion: Given that there was no travel history or the possibility of mechanical transmission (blood transfusion or needle), the research team concluded that it is highly probable that the infection was acquired through an infective Anopheles mosquito inadvertently translocated from a Malaria endemic area by mechanical modes of transport. We recommend that clinicians in non-endemic malaria areas be aware of this type of malaria and test for malaria in patients showing malaria-like symptoms.

Keywords: Odyssean Malaria, vector Bourne, malaria, epidemiological surveys

Procedia PDF Downloads 320

Authors: Kyung Jin Kim, Jiwon Kwak, Jae-Hoon Lee, Soo Suk Lee

Abstract:

MicroRNAs (miRNA) are a class of endogenous, single-stranded, small, and non-protein coding RNA molecules typically 20-25 nucleotides long. They are thought to regulate the expression of other genes in a broad range by binding to 3’- untranslated regions (3’-UTRs) of specific mRNAs. The detection of miRNAs is very important for understanding of the function of these molecules and in the diagnosis of variety of human diseases. However, detection of miRNAs is very challenging because of their short length and high sequence similarities within miRNA families. So, a simple-to-use, low-cost, and highly sensitive method for the detection of miRNAs is desirable. In this study, we demonstrate a novel bi-directional extension (BDE) assay. In the first step, a specific linear RT primer is hybridized to 6-10 base pairs from the 3’-end of a target miRNA molecule and then reverse transcribed to generate a cDNA strand. After reverse transcription, the cDNA was hybridized to the 3’-end which is BDE sequence; it played role as the PCR template. The PCR template was amplified in an SYBR green-based quantitative real-time PCR. To prove the concept, we used human brain total RNA. It could be detected quantitatively in the range of seven orders of magnitude with excellent linearity and reproducibility. To evaluate the performance of BDE assay, we contrasted sensitivity and specificity of the BDE assay against a commercially available poly (A) tailing method using miRNAs for let-7e extracted from A549 human epithelial lung cancer cells. The BDE assay displayed good performance compared with a poly (A) tailing method in terms of specificity and sensitivity; the CT values differed by 2.5 and the melting curve showed a sharper than poly (A) tailing methods. We have demonstrated an innovative, cost-effective BDE assay that allows improved sensitivity and specificity in detection of miRNAs. Dynamic range of the SYBR green-based RT-qPCR for miR-145 could be represented quantitatively over a range of 7 orders of magnitude from 0.1 pg to 1.0 μg of human brain total RNA. Finally, the BDE assay for detection of miRNA species such as let-7e shows good performance compared with a poly (A) tailing method in terms of specificity and sensitivity. Thus BDE proves a simple, low cost, and highly sensitive assay for various miRNAs and should provide significant contributions in research on miRNA biology and application of disease diagnostics with miRNAs as targets.

Keywords: bi-directional extension (BDE), microRNA (miRNA), poly (A) tailing assay, reverse transcription, RT-qPCR

Procedia PDF Downloads 140

Authors: Namrata Khatri

Abstract:

The rapid growth of cities is transforming the urban environment and posing significant challenges for environmental quality. This study examines the urban environment of Belagavi in Karnataka, India, using geostatistical methods to assess the spatial pattern and land use distribution of the city and to evaluate the quality of the urban environment. The study is driven by the necessity to assess the environmental impact of urbanisation. Satellite data was utilised to derive information on land use and land cover. The investigation revealed that land use had changed significantly over time, with a drop in plant cover and an increase in built-up areas. High-resolution satellite data was also utilised to map the city's open areas and gardens. GIS-based research was used to assess public green space accessibility and to identify regions with inadequate waste management practises. The findings revealed that garbage collection and disposal techniques in specific areas of the city needed to be improved. Moreover, the study evaluated the city's thermal environment using Landsat 8 land surface temperature (LST) data. The investigation found that built-up regions had higher LST values than green areas, pointing to the city's urban heat island (UHI) impact. The study's conclusions have far-reaching ramifications for urban planners and politicians in Belgaum and other similar cities. The findings may be utilised to create sustainable urban planning strategies that address the environmental effect of urbanisation while also improving the quality of life for city dwellers. Satellite data and high-resolution satellite pictures were gathered for the study, and remote sensing and GIS tools were utilised to process and analyse the data. Ground truthing surveys were also carried out to confirm the accuracy of the remote sensing and GIS-based data. Overall, this study provides a complete assessment of Belgaum's environmental quality and emphasizes the potential of remote sensing and geographic information systems (GIS) approaches in environmental assessment and management.

Keywords: environmental quality, UEQ, remote sensing, GIS

Procedia PDF Downloads 53

Authors: S. K. Sharma, P. Kumar, Pratibha Singh

Abstract:

Consumption of SNACK is growing its popularity every day in India and a broad range of these items are available in the market. The end user interest in ready-to-eat snack foods is constantly growing mainly due to their ease, ample accessibility, appearance, taste and texture. Food extrusion has been practiced for over fifty years. Its role was initially limited to mixing and forming cereal products. Although thermoplastic extrusion has been successful for starch products, extrusion of proteins has achieved only limited success. In this study, value-added extruded prawn product was prepared with prawn flavor powder and corn flour using a twin-screw extruder. Prawn flavor concentrates prepared from fresh prawn head (Solenocera indica). To prepare flavor concentrate prawn head washed with potable water and blended with 200ml 3% salt solution per 250gm head weight to make the slurry, which was further put in muslin cloth and boiled with salt and starch solution for 10 minutes, cooled to room temperature and filtered, starch added to the filtrate and made into powder in an electrically drier at 43-450c. The mixture was passed through the twin-screw extruder (co-rotating twin screw extruder - basic technology Pvt. Ltd., Kolkata) which was operated at a particular speed of rotation, die diameter, temperature, moisture, and fish powder concentration. Many trial runs were conducted to set up the process variables. The different extrudes produced after each trail were examined for the quality and characteristics. The effect of temperature, moisture, screw speed, protein, fat, ash and thiobarbituric acid (TBA) number and expansion ratio were studied. In all the four trials, moisture, temperature, speed and die diameter used was 20%, 100°C, 350 rpm and 4 mm, respectively. The ratio of prawn powder and cornstarch used in different trials ranged between 2:98 and 10:90. The storage characteristics of the final product were studied using three different types of packaging under nitrogen flushing, i.e. a- 12-pm polyester, 12-pm metalized polyester, 60-11m polyethylene (metalized polyester a), b- 12-11m metalized polyester, 37.5-11m polyethylene (metalized polyester b), c- 12-11m polyethylene, 9-11m aluminium foil, 37.5-11m polyethylene (aluminium foil). The organoleptic analysis was carried out on a 9-point hedonic scale. The study revealed that the fried product packed in aluminum foil under nitrogen flushing would remain acceptable for more than three months.

Keywords: extruded product, prawn flavor, twin-screw extruder, storage characteristics

Procedia PDF Downloads 118

Authors: Virendra Nath, Vipin Kumar

Abstract:

Background: TypeII Diabetes mellitus is a foremost health problem worldwide, predisposing to increased mortality and morbidity. Undesirable effects of the current medications have prompted the researcher to develop more potential drug(s) against the disease. The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptors family and take part in a vital role in the regulation of metabolic equilibrium. They can induce or repress genes associated with adipogenesis, lipid, and glucose metabolism. Aims: Investigation of PPARα/γ agonistic hits were screened by hierarchical virtual screening followed by molecular dynamics simulation and knowledge-based structure-activity relation (SAR) analysis using approved PPAR α/γ dual agonist. Methods: The PPARα/γ agonistic activity of compounds was searched by using Maestro through structure-based virtual screening and molecular dynamics (MD) simulation application. Virtual screening of nuclear-receptor ligands was done, and the binding modes with protein-ligand interactions of newer entity(s) were investigated. Further, binding energy prediction, Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit along with the structural comparative analysis of approved PPARα/γ agonists with screened hit was done for knowledge-based SAR. Results and Discussion: The silicone chip-based approach recognized the most capable nine hits and had better predictive binding energy as compared to the reference drug compound (Tesaglitazar). In this study, the key amino acid residues of binding pockets of both targets PPARα/γ were acknowledged as essential and were found to be associated in the key interactions with the most potential dual hit (ChemDiv-3269-0443). Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit and found root mean square deviation (RMSD) stabile around 2Å and 2.1Å, respectively. Frequency distribution data also revealed that the key residues of both proteins showed maximum contacts with a potent hit during the MD simulation of 20 nanoseconds (ns). The knowledge-based SAR studies of PPARα/γ agonists were studied using 2D structures of approved drugs like aleglitazar, tesaglitazar, etc. for successful designing and synthesis of compounds PPARγ agonistic candidates with anti-hyperlipidimic potential.

Keywords: computational, diabetes, PPAR, simulation

Procedia PDF Downloads 75

Authors: Santi Maneewatchararangsri, Wanpen Chaicumpa, Patcharin Saengjaruk, Urai Chaisri

Abstract:

Leptospirosis is a globally neglected disease that continues to be a significant public health and veterinary burden, with millions of cases reported each year. Early and accurate differential diagnosis of leptospirosis from other febrile illnesses and the development of a broad spectrum of leptospirosis vaccines are needed. The LipL32 outer membrane lipoprotein is a member of Leptospira adhesive matrices and has been found to exert hemolytic activity to erythrocytes in vitro. Therefore, LipL32 is regarded as a potential target for diagnosis, broad-spectrum leptospirosis vaccines, and for passive immunotherapy. In this study, we established LipL32-specific mouse monoclonal antibodies, mAbLPF1 and mAbLPF2, and their respective mouse- and humanized-engineered single chain variable fragment (ScFv). Their antibodies’ neutralizing activities against Leptospira-mediated hemolysis in vitro, and the therapeutic efficacy of mAbs against heterologous Leptospira infected hamsters were demonstrated. The epitope peptide of mAb LPF1 was mapped to a non-contiguous carboxy-terminal β-turn and amphipathic α-helix of LipL32 structure contributing to phospholipid/host cell adhesion and membrane insertion. We found that the mAbLPF2 epitope was located on the interacting loop of peptide binding groove of the LipL32 molecule responsible for interactions with host constituents. Epitope sequences are highly conserved among Leptospira spp. and are absent from the LipL32 superfamily of other microorganisms. Both epitopes are surface-exposed, readily accessible by mAbs, and immunogenic. However, they are less dominant when revealed by LipL32-specific immunoglobulins from leptospirosis-patient sera and rabbit hyperimmune serum raised by whole Leptospira. Our study also demonstrated an adhesion inhibitory activity of LipL32 protein to host membrane components and cells mediated by mAbs as well as an anti-hemolytic activity of the respective antibodies. The therapeutic antibodies, particularly the humanized-ScFv, have a potential for further development as non-drug therapeutic agent for human leptospirosis, especially in subjects allergic to antibiotics. The epitope peptides recognized by two therapeutic mAbs have potential use as tools for structure-function studies. Finally, protective peptides may be used as a target for epitope-based vaccines for control of leptospirosis.

Keywords: leptospira lipl32-specific antibodies, therapeutic epitopes, epitopes characterization, immunotherapy

Procedia PDF Downloads 276

Authors: Chanchal Biswas, Anrin Bhattacharyya, Gopes Chandra Das, Mahua Ghosh Chaudhuri, Rajib Dey

Abstract:

Boiler coals with low fixed carbon and higher ash content have always challenged the metallurgists to develop a suitable method for their utilization. In the present study, an attempt is made to establish an energy effective method for the reduction of iron ore fines in the form of nuggets by using ‘Syngas’. By devolatisation (expulsion of volatile matter by applying heat) of boiler coal, gaseous product (enriched with reducing agents like CO, CO2, H2, and CH4 gases) is generated. Iron ore nuggets are reduced by this syngas. For that reason, there is no direct contact between iron ore nuggets and coal ash. It helps to control the minimization of the sulphur intake of the reduced nuggets. A laboratory scale devolatisation furnace designed with reduction facility is evaluated after in-depth studies and exhaustive experimentations including thermo-gravimetric (TG-DTA) analysis to find out the volatile fraction present in boiler grade coal, gas chromatography (GC) to find out syngas composition in different temperature and furnace temperature gradient measurements to minimize the furnace cost by applying one heating coil. The nuggets are reduced in the devolatisation furnace at three different temperatures and three different times. The pre-reduced nuggets are subjected to analytical weight loss calculations to evaluate the extent of reduction. The phase and surface morphology analysis of pre-reduced samples are characterized using X-ray diffractometry (XRD), energy dispersive x-ray spectrometry (EDX), scanning electron microscopy (SEM), carbon sulphur analyzer and chemical analysis method. Degree of metallization of the reduced nuggets is 78.9% by using boiler grade coal. The pre-reduced nuggets with lesser sulphur content could be used in the blast furnace as raw materials or coolant which would reduce the high quality of coke rate of the furnace due to its pre-reduced character. These can be used in Basic Oxygen Furnace (BOF) as coolant also.

Keywords: alternative ironmaking, coal gasification, extent of reduction, nugget making, syngas based DRI, solid state reduction

Procedia PDF Downloads 246

Authors: Pallavi Gajjar, Vinayak Malhotra

Abstract:

Rockets have been known to have played a predominant role in spacecraft propulsion. The quintessential aspect of combustion-related requirements of a rocket engine is the minimization of the surrounding risks/hazards. Over time, it has become imperative to understand the combustion rate variation in presence of external energy source(s). Rocket propulsion represents a special domain of chemical propulsion assisted by high speed flows in presence of acoustics and thermal source(s). Jet noise leads to a significant loss of resources and every year a huge amount of financial aid is spent to prevent it. External heat source(s) induce high possibility of fire risk/hazards which can sufficiently endanger the operation of a space vehicle. Appreciable work had been done with justifiable simplification and emphasis on the linear variation of external energy source(s), which yields good physical insight but does not cater to accurate predictions. Present work experimentally attempts to understand the correlation between inter-energy conversions with the non-linear placement of external energy source(s). The work is motivated by the need to have better fire safety and enhanced combustion. The specific objectives of the work are a) To interpret the related energy transfer for combustion in presence of alternate external energy source(s) viz., thermal and acoustic, b) To fundamentally understand the role of key controlling parameters viz., separation distance, the number of the source(s), selected configurations and their non-linear variation to resemble real-life cases. An experimental setup was prepared using incense sticks as potential fuel and paraffin wax candles as the external energy source(s). The acoustics was generated using frequency generator, and source(s) were placed at selected locations. Non-equidistant parametric experimentation was carried out, and the effects were noted on regression rate changes. The results are expected to be very helpful in offering a new perspective into futuristic rocket designs and safety.

Keywords: combustion, acoustic energy, external energy sources, regression rate

Procedia PDF Downloads 121

Authors: Achiron Anat, Mathilda Mandel, Mayust Sue, Achiron Reuven, Gurevich Michael

Abstract:

Introduction: As coronavirus disease 2019 (COVID-19) vaccination is currently spreading around the world, it is of importance to assess the ability of multiple sclerosis (MS) patients to mount an appropriate immune response to the vaccine in the context of disease-modifying treatments (DMT’s). Objectives: Evaluate immunity generated following COVID-19 vaccination in MS patients, and assess factors contributing to protective humoral and cellular immune responses in MS patients vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus infection. Methods: Review our recent data related to (1) the safety of PfizerBNT162b2 COVID-19 mRNA vaccine in adult MS patients; (2) the humoral post-vaccination SARS-CoV2 IgG response in MS vaccinees using anti-spike protein-based serology; and (3) the cellular immune response of memory B-cells specific for SARS-CoV-2 receptor-binding domain (RBD) and memory T-cells secreting IFN-g and/or IL-2 in response to SARS-CoV2 peptides using ELISpot/Fluorospot assays in MS patients either untreated or under treatment with fingolimod, cladribine, or ocrelizumab; (4) covariate parameters related to mounting protective immune responses. Results: COVID-19 vaccine proved safe in MS patients, and the adverse event profile was mainly characterised by pain at the injection site, fatigue, and headache. Not any increased risk of relapse activity was noted and the rate of patients with acute relapse was comparable to the relapse rate in non-vaccinated patients during the corresponding follow-up period. A mild increase in the rate of adverse events was noted in younger MS patients, among patients with lower disability, and in patients treated with DMTs. Following COVID-19 vaccination protective humoral immune response was significantly decreased in fingolimod- and ocrelizumab- treated MS patients. SARS-CoV2 specific B-cell and T-cell cellular responses were respectively decreased. Untreated MS patients and patients treated with cladribine demonstrated protective humoral and cellular immune responses, similar to healthy vaccinated subjects. Conclusions: COVID-19 BNT162b2 vaccine proved as safe for MS patients. No increased risk of relapse activity was noted post-vaccination. Although COVID-19 vaccination is new, accumulated data demonstrate differences in immune responses under various DMT’s. This knowledge can help to construct appropriate COVID-19 vaccine guidelines to ensure proper immune responses for MS patients.

Keywords: covid-19, vaccination, multiple sclerosis, IgG

Procedia PDF Downloads 120

Authors: He Zhang, Jianxin Yi

Abstract:

As a clean energy, hydrogen shows many advantages such as renewability, high heat value, and extensive sources and may play an important role in the future society. However, hydrogen is a combustible gas because of its low ignition energy (0.02mJ) and wide explosive limit (4% ~ 74% in air). It is very likely to cause fire hazard or explosion once leakage is happened and not detected in time. Mixed-potential type sensor has attracted much attention in monitoring and detecting hydrogen due to its high response, simple support electronics and long-term stability. Typically, this kind of sensor is consisted of a sensing electrode (SE), a reference electrode (RE) and a solid electrolyte. The SE and RE materials usually display different electrocatalytic abilities to hydrogen. So hydrogen could be detected by measuring the EMF change between the two electrodes. Previous reports indicate that a high-performance sensing electrode is important for improving the sensing characteristics of the sensor. In this report, a planar type mixed-potential hydrogen sensor using La₀.₈Sr₀.₂Cr₀.₅Mn₀.₅O₃₋δ (LSCM) as SE, Pt as RE and yttria-stabilized zirconia (YSZ) as solid electrolyte was developed. The reason for selecting LSCM as sensing electrode is that it shows the high electrocatalytic ability to hydrogen in solid oxide fuel cells. The sensing performance of the fabricated LSCM/YSZ/Pt sensor was tested systemically. The experimental results show that the sensor displays high response to hydrogen. The response values for 100ppm and 1000ppm hydrogen at 450 ºC are -70 mV and -118 mV, respectively. The response time is an important parameter to evaluate a sensor. In this report, the sensor response time decreases with increasing hydrogen concentration and get saturated above 500ppm. The steady response time at 450 ºC is as short as 4s, indicating the sensor shows great potential in practical application to monitor hydrogen. An excellent response repeatability to 100ppm hydrogen at 450 ˚C and a good sensor reproducibility among three sensors were also observed. Meanwhile, the sensor exhibits excellent selectivity to hydrogen compared with several interfering gases such as NO₂, CH₄, CO, C₃H₈ and NH₃. Polarization curves were tested to investigate the sensing mechanism and the results indicated the sensor abide by the mixed-potential mechanism.

Keywords: fire hazard, H₂ sensor, mixed-potential, perovskite

Procedia PDF Downloads 158

Authors: Mohammed H. Karim, Bestoon M. Faraj

Abstract:

Introduction: instrument separation is a common challenge in the endodontic field. Various techniques and technologies have been developed to improve the retrieval success rate. This study aimed to compare the effectiveness of a Dynamic Navigation System (DNS) and a three-dimensional microscope in retrieving broken rotary NiTi files when using trepan burs and the extractor system. Materials and Methods: Thirty maxillary first bicuspids with sixty separate roots were split into two comparable groups based on a comprehensive Cone-Beam Computed Tomography (CBCT) analysis of the root length and curvature. After standardised access opening, glide paths, and patency attainment with the K file (sizes 10 and 15), the teeth were arranged on 3D models (three per quadrant, six per model). Subsequently, controlled-memory heat-treated NiTi rotary files (#25/0.04) were notched 4 mm from the tips and fractured at the apical third of the roots. The C-FR1 Endo file removal system was employed under both guidance to retrieve the fragments, and the success rate, canal aberration, treatment time and volumetric changes were measured. The statistical analysis was performed using IBM SPSS software at a significance level of 0.05. Results: The microscope-guided group had a higher success rate than the DNS guidance, but the difference was insignificant (p > 0.05). In addition, the microscope-guided drills resulted in a substantially lower proportion of canal aberration, required less time to retrieve the fragments and caused a minor change in the root canal volume (p < 0.05). Conclusion: Although dynamically guided trephining with the extractor can retrieve separated instruments, it is inferior to three-dimensional microscope guidance regarding treatment time, procedural errors, and volume change.

Keywords: dynamic navigation system, separated instruments retrieval, trephine burs and extractor system, three-dimensional video microscope

Procedia PDF Downloads 71

Authors: Claudio Lamilla, Andrés Santos, Vicente Llanquinao, Jocelyn Hermosilla, Leticia Barrientos

Abstract:

The industry in general is very interested in improving and optimizing industrial processes in order to reduce the costs involved in obtaining raw materials and production. Thus, an interesting and cost-effective alternative is the incorporation of bioactive metabolites in such processes, being an example of this enzymes which catalyze efficiently a large number of enzymatic reactions of industrial and biotechnological interest. In the search for new sources of these active metabolites, Antarctica is one of the least explored places on our planet where the most drastic cold conditions, salinity, UVA-UVB and liquid water available are present, features that have shaped all life in this very harsh environment, especially bacteria that live in different Antarctic ecosystems, which have had to develop different strategies to adapt to these conditions, producing unique biochemical strategies. In this work the production of cellulolytic enzymes of seven bacterial strains isolated from marine sediments at different sites in the Antarctic was evaluated. Isolation of the strains was performed using serial dilutions in the culture medium at M115°C. The identification of the strains was performed using universal primers (27F and 1492R). The enzyme activity assays were performed on R2A medium, carboxy methyl cellulose (CMC)was added as substrate. Degradation of the substrate was revealed by adding Lugol. The results show that four of the tested strains produce enzymes which degrade CMC substrate. The molecular identifications, showed that these bacteria belong to the genus Streptomyces and Pseudoalteromonas, being Streptomyces strain who showed the highest activity. Only some bacteria in marine sediments have the ability to produce these enzymes, perhaps due to their greater adaptability to degrade at temperatures bordering zero degrees Celsius, some algae that are abundant in this environment and have cellulose as the main structure. The discovery of new enzymes adapted to cold is of great industrial interest, especially for paper, textiles, detergents, biofuels, food and agriculture. These enzymes represent 8% of industrial demand worldwide and is expected to increase their demand in the coming years. Mainly in the paper and food industry are required in extraction processes starch, protein and juices, as well as the animal feed industry where treating vegetables and grains helps improve the nutritional value of the food, all this clearly puts Antarctic microorganisms and their enzymes specifically as a potential contribution to industry and the novel biotechnological applications.

Keywords: antarctic, bacteria, biotechnological, cellulolytic enzymes

Procedia PDF Downloads 274