Search results for: aryl hydrocarbon receptor (AhR)

Authors: Lea Boidin, Martha Baydoun, Bertrand Leroux, Olivier Morales, Samir Acherar, Celine Frochot, Nadira Delhem

Abstract:

Ovarian cancer (OC) is one of the most defying diseases in gynecologic oncology. Even though surgery remains crucial in the therapy of patients with primary ovarian cancer, recurrent recidivism calls for the development of new therapy protocols to propose for patients dealing with this cancer. FRα is described as a tumor‐associated antigen in OC, where FRα expression is usually linked with more poorly differentiated, aggressive tumors. The Photodynamic treatment (PDT) available data have shown improvements in the uptake of small tumors and in the induction of a proper anti-tumoral immune response. In order to target specifically peritoneal metastatis, which overexpress FRα, a new-patented PS coupled with folic acid has been developed in our team. Herein we propose PDT using this new patented PS for PDT applied in an in vivo mice model. The efficacy of the treatment was evaluated in mice without and with PBMC reconstitution. Mice were divided into four groups: Non-Treated, PS, Light Only, and PDT Treated and subjected to illumination by laser set at 668nm with a duration of illumination of 45 minutes (or 1 min of illumination followed by 2 minutes of pause repeated 45 times). When mice were not reconstituted and after fractionized PDT protocol, a significant decrease in the tumor volume was noticed. An induction in the anti-tumoral cytokine IFNγ chaperoned this decrease while a subsequent inhibition in the cytokine TGFβ. Even more crucial, when mice were reconstituted and upon PDT, the fold of tumor decrease was even higher. An immune response was activated decoded with an increase in NK, CD3 +, LT helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFNγ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation. Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of ovarian cancer. The interest in using PDT in this case, goes beyond the local induction of tumor apoptosis only, but can promote subsequent anti-tumor response. Most of the therapies currently used to treat ovarian cancer, have an uncooperative outcomes on the host immune response. The readiness of a tumor adjuvant treatment like PDT adequate in eliminating the tumor and in concert stimulating anti-tumor immunity would be weighty.

Keywords: folate receptor, ovarian cancer, photodynamic therapy, humanized mice model

Procedia PDF Downloads 110

Authors: Muhammad Zaman Shakir, Mingfa Yao, Zohaib Iqbal

Abstract:

This study proposed four Jet fuel surrogate (S1, S2 S3, and 4) with careful selection of seven large hydrocarbon fuel components, ranging from C₉-C₁₆ of higher molecular weight and higher boiling point, adapting the standard molecular distribution size of the actual jet fuel. The surrogate was composed of seven components, including n-propyl cyclohexane (C₉H₁₈), n- propylbenzene (C₉H₁₂), n-undecane (C₁₁H₂₄), n- dodecane (C₁₂H₂₆), n-tetradecane (C₁₄H₃₀), n-hexadecane (C₁₆H₃₄) and iso-cetane (iC₁₆H₃₄). The skeletal jet fuel surrogate reaction mechanism was developed by two approaches, firstly based on a decoupling methodology by describing the C₄ -C₁₆ skeletal mechanism for the oxidation of heavy hydrocarbons and a detailed H₂ /CO/C₁ mechanism for prediction of oxidation of small hydrocarbons. The combined skeletal jet fuel surrogate mechanism was compressed into 128 species, and 355 reactions and thereby can be used in computational fluid dynamics (CFD) simulation. The extensive validation was performed for individual single-component including ignition delay time, species concentrations profile and laminar flame speed based on various fundamental experiments under wide operating conditions, and for their blended mixture, among all the surrogate, S1 has been extensively validated against the experimental data in a shock tube, rapid compression machine, jet-stirred reactor, counterflow flame, and premixed laminar flame over wide ranges of temperature (700-1700 K), pressure (8-50 atm), and equivalence ratio (0.5-2.0) to capture the properties target fuel Jet-A, while the rest of three surrogate S2, S3 and S4 has been validated for Shock Tube ignition delay time only to capture the ignition characteristic of target fuel S-8 & GTL, IPK and RP-3 respectively. Based on the newly proposed HyChem model, another four surrogate with similar components and composition, was developed and parallel validations data was used as followed for previously developed surrogate but at high-temperature condition only. After testing the mechanism prediction performance of surrogates developed by the decoupling methodology, the comparison was done with the results of surrogates developed by the HyChem model. It was observed that all of four proposed surrogates in this study showed good agreement with the experimental measurements and the study comes to this conclusion that like the decoupling methodology HyChem model also has a great potential for the development of oxidation mechanism for heavy alkanes because of applicability, simplicity, and compactness.

Keywords: computational fluid dynamics, decoupling methodology Hychem, jet fuel, surrogate, skeletal mechanism

Procedia PDF Downloads 136

Authors: Tatiana Marques Pessanha, Aurora Perez-Gramatges, Regina Sandra Veiga Nascimento

Abstract:

Emulsions are commonly used in applications involving oil/water dispersions, where handling of interfaces becomes a crucial aspect. The use of emulsion technology has greatly evolved in the last decades to suit the most diverse uses, ranging from cosmetic products and biomedical adjuvants to complex industrial fluids. The stability of these emulsions is influenced by factors such as the amount of oil, size of droplets and emulsifiers used. While commercial surfactants are typically used as emulsifiers to reduce interfacial tension, and therefore increase emulsion stability, these organic amphiphilic compounds are often toxic and expensive. A suitable alternative for emulsifiers can be obtained from the chemical modification of polysaccharides. Our group has been working on modification of polysaccharides to be used as additives in a variety of fluid formulations. In particular, we have obtained promising results using chitosan, a natural and biodegradable polymer that can be easily modified due to the presence of amine groups in its chemical structure. In this way, it is possible to increase both the hydrophobic and hydrophilic character, which renders a water-soluble, amphiphilic polymer that can behave as an emulsifier. The aim of this work was the synthesis of chitosan derivatives structurally modified to act as surfactants in stable oil-in-water. The synthesis of chitosan derivatives occurred in two steps, the first being the hydrophobic modification with the insertion of long hydrocarbon chains, while the second step consisted in the cationization of the amino groups. All products were characterized by infrared spectroscopy (FTIR) and carbon magnetic resonance (13C-NMR) to evaluate the cationization and hydrofobization degrees. These modified polysaccharides were used to formulate oil-in water (O:W) emulsions with different oil/water ratios (i.e 25:75, 35:65, 60:40) using mineral paraffinic oil. The formulations were characterized according to the type of emulsion, density and rheology measurements, as well as emulsion stability at high temperatures. All emulsion formulations were stable for at least 30 days, at room temperature (25°C), and in the case of the high oil content emulsion (60:40), the formulation was also stable at temperatures up to 100°C. Emulsion density was in the range of 0.90-0.87 s.g. The rheological study showed a viscoelastic behaviour in all formulations at room temperature, which is in agreement with the high stability showed by the emulsions, since the polymer acts not only reducing interfacial tension, but also forming an elastic membrane at the oil/water interface that guarantees its integrity. The results obtained in this work are a strong evidence of the possibility of using chemically modified polysaccharides as environmentally friendly alternatives to commercial surfactants in the stabilization of oil-in water formulations.

Keywords: emulsion, polymer, polysaccharide, stability, chemical modification

Procedia PDF Downloads 353

Authors: Manali Jain, Neeta Singh, Raunaq Fatima, Soniya Nityanand, Mandakini Pradhan, Chandra Prakash Chaturvedi

Abstract:

Isolated Congenital Heart Defect (ICHD) is the major cause of neonatal death worldwide among all forms of CHDs. A significant proportion of fetuses with ICHD die in the neonatal period if no treatment is provided. Recently, stem cell therapies have emerged as a potential approach to ameliorate ICHD in children. ICHD is characterized by cardiac structural abnormalities during embryogenesis due to alterations in the cardiomyogenic properties of a pool of cardiac progenitors/ stem cells associated with fetal heart development. The stem cells present in the amniotic fluid (AF) are of fetal origin and may reflect the physiological and pathological changes in the fetus during embryogenesis. Therefore, in the present study, the cardiomyogenic potential of AF-MSCs derived from fetuses with ICHD (ICHD AF-MSCs) has been evaluated and compared with that of AF-MSCs of structurally normal fetuses (normal AF-MSCs). Normal and ICHD AF-MSC were analyzed for the expression of cardiac progenitor markers viz., stage-specific embryonic antigen-1 (SSEA-1), vascular endothelial growth factor 2 (VEGFR-2) and platelet-derived growth factor receptor-alpha (PDGFR-α) by flow cytometry. The immunophenotypic characterization revealed that ICHD AF-MSCs have significantly lower expression of cardiac progenitor markers VEGFR-2 (0.14% ± 0.6 vs.48.80% ± 0.9; p <0.01), SSEA-1 (70.86% ± 2.4 vs. 88.36% ±2.7; p <0.01), and PDGFR-α (3.92% ± 1.8 vs. 47.59% ± 3.09; p <0.01) in comparison to normal AF-MSCs. Upon induction with 5’-azacytidine for 21 days, ICHD AF-MSCs showed a significantly down-regulated expression of cardiac transcription factors such as GATA-4 (0.4 ± 0.1 vs. 6.8 ± 1.2; p<0.01), ISL-1 (2.3± 0.6 vs. 14.3 ± 1.12; p<0.01), NK-x 2-5 (1.1 ± 0.3 vs. 14.1 ±2.8; p<0.01), TBX-5 (0.4 ± 0.07 vs. 4.4 ± 0.3; p<0.001), and TBX-18 (1.3 ± 0.2 vs. 4.19 ± 0.3; p<0.01) when compared with the normal AF-MSCs. Furthermore, immunocytochemical staining revealed that both types of AF-MSCs could differentiate into cardiovascular lineages and express cardiomyogenic, endothelial, and smooth muscle actin markers, viz., cardiac troponin (cTNT), CD31, and alpha-smooth muscle actin (α-SMA). However, normal AF-MSCs showed an enhanced expression of cTNT (p<0.001), CD31 (p<0.01), and α-SMA (p<0.05), compared to ICHD AF-MSCs. Overall, these results suggest that the ICHD-AF-MSCs have a defective cardiomyogenic differentiation potential and that the defects in these stem cells may have a role in the pathogenesis of ICHD.

Keywords: amniotic fluid, cardiomyogenic potential, isolated congenital heart defect, mesenchymal stem cells

Procedia PDF Downloads 102

Authors: Avtandil Okrostsvaridze, Salome Gogoladze

Abstract:

In the light of exhaustion of hydrocarbon reserves of new energy resources, its search is of vital importance problem for the modern civilization. At the time of energy resource crisis, the radioactive element thorium (232Th) is considered as the main energy resource for the future of our civilization. Modern industry uses thorium in high-temperature and high-tech tools, but the most important property of thorium is that like uranium it can be used as fuel in nuclear reactors. However, thorium has a number of advantages compared to this element: Its concentration in the earth crust is 4-5 times higher than uranium; extraction and enrichment of thorium is much cheaper than of uranium; it is less radioactive; its waste products complete destruction is possible; thorium yields much more energy than uranium. Nowadays, developed countries, among them India and China, have started intensive work for creation of thorium nuclear reactors and intensive search for thorium reserves. It is not excluded that in the next 10 years these reactors will completely replace uranium reactors. Thorium ore mineralization is genetically related to alkaline-acidic magmatism. Thorium accumulations occur as in endogen marked as in exogenous conditions. Unfortunately, little is known about the reserves of this element in Georgia, as planned prospecting-exploration works of thorium have never been carried out here. Although, 3 ore occurrences of this element are detected: 1) In the Greater Caucasus Kakheti segment, in the hydrothermally altered rocks of the Lower Jurassic clay-shales, where thorium concentrations varied between 51 - 3882g/t; 2) In the eastern periphery of the Dzirula massif, in the hydrothermally alteration rocks of the cambrian quartz-diorite gneisses, where thorium concentrations varied between 117-266 g/t; 3) In active contact zone of the Eocene volcanites and syenitic intrusive in Vakijvari ore field of the Guria region, where thorium concentrations varied between 185 – 428 g/t. In addition, geological settings of the areas, where thorium occurrences were fixed, give a theoretical basis on possible accumulation of practical importance thorium ores. Besides, the Black Sea Guria region magnetite sand which is transported from Vakijvari ore field, should contain significant reserves of thorium. As the research shows, monazite (thorium containing mineral) is involved in magnetite in the form of the thinnest inclusions. The world class thorium deposit concentrations of this element vary within the limits of 50-200 g/t. Accordingly, on the basis of these data, thorium resources found in Georgia should be considered as perspective ore deposits. Generally, we consider that complex investigation of thorium should be included into the sphere of strategic interests of the state, because future energy of Georgia, will probably be thorium.

Keywords: future energy, Georgia, ore field, thorium

Procedia PDF Downloads 492

Authors: Shengnan Chen, Shuhua Wang

Abstract:

Successful production of hydrocarbon from unconventional tight oil reserves has changed the energy landscape in North America. The oil contained within these reservoirs typically will not flow to the wellbore at economic rates without assistance from advanced horizontal well and multi-stage hydraulic fracturing. Efficient and economic development of these reserves is a priority of society, government, and industry, especially under the current low oil prices. Meanwhile, society needs technological and process innovations to enhance oil recovery while concurrently reducing environmental impacts. Recently, big data analysis and artificial intelligence become very popular, developing data-driven insights for better designs and decisions in various engineering disciplines. However, the application of data mining in petroleum engineering is still in its infancy. The objective of this research aims to apply intelligent data analysis and data-driven models to exploit unconventional oil reserves both efficiently and economically. More specifically, a comprehensive database including the reservoir geological data, reservoir geophysical data, well completion data and production data for thousands of wells is firstly established to discover the valuable insights and knowledge related to tight oil reserves development. Several data analysis methods are introduced to analysis such a huge dataset. For example, K-means clustering is used to partition all observations into clusters; principle component analysis is applied to emphasize the variation and bring out strong patterns in the dataset, making the big data easy to explore and visualize; exploratory factor analysis (EFA) is used to identify the complex interrelationships between well completion data and well production data. Different data mining techniques, such as artificial neural network, fuzzy logic, and machine learning technique are then summarized, and appropriate ones are selected to analyze the database based on the prediction accuracy, model robustness, and reproducibility. Advanced knowledge and patterned are finally recognized and integrated into a modified self-adaptive differential evolution optimization workflow to enhance the oil recovery and maximize the net present value (NPV) of the unconventional oil resources. This research will advance the knowledge in the development of unconventional oil reserves and bridge the gap between the big data and performance optimizations in these formations. The newly developed data-driven optimization workflow is a powerful approach to guide field operation, which leads to better designs, higher oil recovery and economic return of future wells in the unconventional oil reserves.

Keywords: big data, artificial intelligence, enhance oil recovery, unconventional oil reserves

Procedia PDF Downloads 283

Authors: Triveni Gogoi, Rima Chatterjee

Abstract:

Shear wave velocity (Vs) estimation is an important approach in the seismic exploration and characterization of a hydrocarbon reservoir. There are varying methods for prediction of S-wave velocity, if recorded S-wave log is not available. But all the available methods for Vs prediction are empirical mathematical models. Shear wave velocity can be estimated using P-wave velocity by applying Castagna’s equation, which is the most common approach. The constants used in Castagna’s equation vary for different lithologies and geological set-ups. In this study, multiple regression analysis has been used for estimation of S-wave velocity. The EMERGE module from Hampson-Russel software has been used here for generation of S-wave log. Both single attribute and multi attributes analysis have been carried out for generation of synthetic S-wave log in Upper Assam basin. Upper Assam basin situated in North Eastern India is one of the most important petroleum provinces of India. The present study was carried out using four wells of the study area. Out of these wells, S-wave velocity was available for three wells. The main objective of the present study is a prediction of shear wave velocities for wells where S-wave velocity information is not available. The three wells having S-wave velocity were first used to test the reliability of the method and the generated S-wave log was compared with actual S-wave log. Single attribute analysis has been carried out for these three wells within the depth range 1700-2100m, which corresponds to Barail group of Oligocene age. The Barail Group is the main target zone in this study, which is the primary producing reservoir of the basin. A system generated list of attributes with varying degrees of correlation appeared and the attribute with the highest correlation was concerned for the single attribute analysis. Crossplot between the attributes shows the variation of points from line of best fit. The final result of the analysis was compared with the available S-wave log, which shows a good visual fit with a correlation of 72%. Next multi-attribute analysis has been carried out for the same data using all the wells within the same analysis window. A high correlation of 85% has been observed between the output log from the analysis and the recorded S-wave. The almost perfect fit between the synthetic S-wave and the recorded S-wave log validates the reliability of the method. For further authentication, the generated S-wave data from the wells have been tied to the seismic and correlated them. Synthetic share wave log has been generated for the well M2 where S-wave is not available and it shows a good correlation with the seismic. Neutron porosity, density, AI and P-wave velocity are proved to be the most significant variables in this statistical method for S-wave generation. Multilinear regression method thus can be considered as a reliable technique for generation of shear wave velocity log in this study.

Keywords: Castagna's equation, multi linear regression, multi attribute analysis, shear wave logs

Procedia PDF Downloads 229

Authors: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht

Abstract:

One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.

Keywords: bioengineering, cancer, nanomedicine, polymer chemistry

Procedia PDF Downloads 141

Authors: E. Salem

Abstract:

Combustion has been used for a long time as a means of energy extraction. However, in recent years, there has been a further increase in air pollution, through pollutants such as nitrogen oxides, acid etc. In order to solve this problem, there is a need to reduce carbon and nitrogen oxides through learn burning modifying combustors and fuel dilution. A numerical investigation has been done to investigate the effectiveness of several reduced mechanisms in terms of computational time and accuracy, for the combustion of the hydrocarbons/air or diluted with hydrogen in a micro combustor. The simulations were carried out using the ANSYS Fluent 19.1. To validate the results “PREMIX and CHEMKIN” codes were used to calculate 1D premixed flame based on the temperature, composition of burned and unburned gas mixtures. Numerical calculations were carried for several hydrocarbons by changing the equivalence ratios and adding small amounts of hydrogen into the fuel blends then analyzing the flammable limit, the reduction in NOx and CO emissions, then comparing it to experimental data. By solving the conservations equations, several global reduced mechanisms (2-9-12) were obtained. These reduced mechanisms were simulated on a 2D cylindrical tube with dimensions of 40 cm in length and 2.5 cm diameter. The mesh of the model included a proper fine quad mesh, within the first 7 cm of the tube and around the walls. By developing a proper boundary layer, several simulations were performed on hydrocarbon/air blends to visualize the flame characteristics than were compared with experimental data. Once the results were within acceptable range, the geometry of the combustor was modified through changing the length, diameter, adding hydrogen by volume, and changing the equivalence ratios from lean to rich in the fuel blends, the results on flame temperature, shape, velocity and concentrations of radicals and emissions were observed. It was determined that the reduced mechanisms provided results within an acceptable range. The variation of the inlet velocity and geometry of the tube lead to an increase of the temperature and CO2 emissions, highest temperatures were obtained in lean conditions (0.5-0.9) equivalence ratio. Addition of hydrogen blends into combustor fuel blends resulted in; reduction in CO and NOx emissions, expansion of the flammable limit, under the condition of having same laminar flow, and varying equivalence ratio with hydrogen additions. The production of NO is reduced because the combustion happens in a leaner state and helps in solving environmental problems.

Keywords: combustor, equivalence-ratio, hydrogenation, premixed flames

Procedia PDF Downloads 114

Authors: Szymon Kuczynski

Abstract:

Poland is characterized by the presence of numerous sedimentary basins and hydrocarbon provinces. Since 2006 exploration for hydrocarbons in Poland become gradually more focus on new unconventional targets, particularly on the shale gas potential of the Upper Ordovician and Lower Silurian in the Baltic-Podlasie-Lublin Basin. The first forecast prepared by US Energy Information Administration in 2011 indicated to 5.3 Tcm of natural gas. In 2012, Polish Geological Institute presented its own forecast which estimated maximum reserves on 1.92 Tcm. The difference in the estimates was caused by problems with calculations of the initial amount of adsorbed, as well as free, gas trapped in shale rocks (GIIP - Gas Initially in Place). This value is dependent from sorption capacity, gas saturation and mutual interactions between gas, water, and rock. Determination of the reservoir type in the initial exploration phase brings essential knowledge, which has an impact on decisions related to the production. The study of porosity impact for phase envelope shift eliminates errors and improves production profitability. Confinement phenomenon affects flow characteristics, fluid properties, and phase equilibrium. The thermodynamic behavior of confined fluids in porous media is subject to the basic considerations for industrial applications such as hydrocarbons production. In particular the knowledge of the phase equilibrium and the critical properties of the contained fluid is essential for the design and optimization of such process. In pores with a small diameter (nanopores), the effect of the wall interaction with the fluid particles becomes significant and occurs in shale formations. Nano pore size is similar to the fluid particles’ diameter and the area of particles which flow without interaction with pore wall is almost equal to the area where this phenomenon occurs. The molecular simulation studies have shown an effect of confinement to the pseudo critical properties. Therefore, the critical parameters pressure and temperature and the flow characteristics of hydrocarbons in terms of nano-scale are under the strong influence of fluid particles with the pore wall. It can be concluded that the impact of a single pore size is crucial when it comes to the nanoscale because there is possible the above-described effect. Nano- porosity makes it difficult to predict the flow of reservoir fluid. Research are conducted to explain the mechanisms of fluid flow in the nanopores and gas extraction from porous media by desorption.

Keywords: adsorption, capillary condensation, phase envelope, nanopores, unconventional natural gas

Procedia PDF Downloads 337

Authors: Hemin Yuan, Yun Wang, Xiangchun Wang

Abstract:

Gas hydrate is drawing attention due to the fact that it has an enormous amount all over the world, which is almost twice the conventional hydrocarbon reserves, making it a potential alternative source of energy. It is widely distributed in permafrost and continental ocean shelves, and many countries have launched national programs for investigating the gas hydrate. Gas hydrate is mainly explored through seismic methods, which include bottom simulating reflectors (BSR), amplitude blanking, and polarity reverse. These seismic methods are effective at finding the gas hydrate formations but usually contain large uncertainties when applying to invert the micro-scale petrophysical properties of the formations due to lack of constraints. Rock physics modeling links the micro-scale structures of the rocks to the macro-scale elastic properties and can work as effective constraints for the seismic methods. A number of rock physics models have been proposed for gas hydrate modeling, which addresses different mechanisms and applications. However, these models are generally not well classified, and it is confusing to determine the appropriate model for a specific study. Moreover, since the modeling usually involves multiple models and steps, it is difficult to determine the source of uncertainties. To solve these problems, we summarize the developed models/methods and make four classifications of the models according to the hydrate micro-scale morphology in sediments, the purpose of reservoir characterization, the stage of gas hydrate generation, and the lithology type of hosting sediments. Some sub-categories may overlap each other, but they have different priorities. Besides, we also analyze the priorities of different models, bring up the shortcomings, and explain the appropriate application scenarios. Moreover, by comparing the models, we summarize a general workflow of the modeling procedure, which includes rock matrix forming, dry rock frame generating, pore fluids mixing, and final fluid substitution in the rock frame. These procedures have been widely used in various gas hydrate modeling and have been confirmed to be effective. We also analyze the potential sources of uncertainties in each modeling step, which enables us to clearly recognize the potential uncertainties in the modeling. In the end, we explicate the general problems of the current models, including the influences of pressure and temperature, pore geometry, hydrate morphology, and rock structure change during gas hydrate dissociation and re-generation. We also point out that attenuation is also severely affected by gas hydrate in sediments and may work as an indicator to map gas hydrate concentration. Our work classifies rock physics models of gas hydrate into different categories, generalizes the modeling workflow, analyzes the modeling uncertainties and potential problems, which can facilitate the rock physics characterization of gas hydrate bearding sediments and provide hints for future studies.

Keywords: gas hydrate, rock physics model, modeling classification, hydrate morphology

Procedia PDF Downloads 158

Authors: Wei-Ju Huang, Hung-Pin Hsu

Abstract:

[Background] In congestive heart failure (CHF), it has always been the principle of clinical treatment to control the water retention mechanism in the body to prevent excessive fluid retention. Early control of sympathetic nerves, Renin-Angiotensin-Aldosterone system (RAA system, RAAS), or strengthening of Atrial Natriuretic Peptide (ANP) was the point. In RAA system, related hormones, such as angiotensin, or enzymes in the pathway, such as ACE-I, can be used with corresponding inhibitors to reduce water content.[Aim] In recent years, clinical studies have pointed out that if different mechanisms are combined, the control effect seems to be better. For example, recent studies showed that ENTRESTO, a combination of Sacubitril and Valsartan, is a good new drug for CHF. Sacubitril is a prodrug. After activation, it can inhibit neprilysin and act as a neprilysin inhibitor (ARNI) to reduce the breakdown of natriuretic peptides(ANP). Valsartan is a kind of angiotensin receptor blocker (ARB), both of which are used to treat heart failure at the same time, have excellent curative effects.[Materials and Methods] Considering the side effects of this drug, coughing and a few cases of diarrhea were observed. However, the effect of this drug on the patient's intestinal tract has not been confirmed. On the other hand, studies have pointed out that ANP supplement can improve the CHF and increase the inhibitory effect on cancer cells. Therefore, the purpose of this study is to use a special microbial detection method to prove that whether oral drugs have an effect on microorganisms.The experimental method uses Nissui Compact Dry to observe the situation in different types of microorganisms. After the drug is dissolved in water, it is implanted in a petri dish, and the presence of different microorganisms is detected through different antibody reactions to confirm whether the drug has some toxicology in the gut.[Results and Discussion]From the above experimental results, it can be known that among the effects of Sacubitril and Valsartan on the basic microbial flora of the human body, low doses had no significant effect on Escherichia coli or intestinal bacteria. If Sacubitril or Valsartan with a high concentration of 3mg/ml is used alone or under the stimulation of a high concentration of the two drugs, it has a significant inhibitory effect on Escherichia coli. However, in terms of the effect on intestinal bacteria, high concentration of Sacubitril has a more significant inhibitory effect on intestinal bacteria, while high concentration of Valsartan has a less significant inhibitory effect on intestinal bacteria. The inhibitory effect of the combination of the two drugs on intestinal bacteria is also less significant.[Conclusion]The results of this study can be used as a further reference for the possible side effects of the clinical use of Sacubitril and Valsartan on the intestinal tract of patients,

Keywords: sacubitril, valsartan, entresto, congestive heart failure (CHF)

Procedia PDF Downloads 67

Authors: Brian Chi Yan Cheng, Hui Guo, Tao Su, Xiu‐qiong Fu, Ting Li, Zhi‐ling Yu

Abstract:

Rheumatoid arthritis (RA) affects around 1% of the globe population. Yet, there is still no cure for RA. Toll-like receptor 4 (TLR4) signalling has been found to be involved in the pathogenesis of RA, making it a potential therapeutic target for RA treatment. A herbal formula (RL) consisting of fruits of Rosa Multiflora (Eijitsu rose) and flowers of Lonicera Japonica (Japanese honeysuckle) has been used in treating various inflammatory disorders for more than a thousand year. Both of them are rich sources of nutrients and bioactive phytochemicals, which can be used in producing different food products and supplements. In this study, we would evaluate the anti-arthritic effect of RL on collagen-induced arthritis (CIA) in rats and investigate the involvement of TLR4 signaling in the mode of action of RL. Anti-arthritic efficacy was evaluated using CIA rats induced by bovine type II collagen. The treatment groups were treated with RL (82.5, 165, and 330 mg/kg bw per day, p.o.) or positive control indomethacin (0.25 mg/kg bw per day, p.o.) for 35 days. Clinical signs (hind paw volume and arthritis severity scores), changes in serum inflammatory mediators, pro-/antioxidant status, histological and radiographic changes of joints were investigated. Spleens and peritoneal macrophages were used to determine the effects of RL on innate and adaptive immune responses in CIA rats. The involvement of TLR4 signalling pathways in the anti-arthritic effect of RL was examined in cartilage tissue of CIA rats, murine RAW264.7 macrophages and human THP-1 monocytic cells. The severity of arthritis in the CIA rats was significantly attenuated by RL. Antioxidant status, histological score and radiographic score were efficiently improved by RL. RL could also dose-dependently inhibit pro-inflammatory cytokines in serum of CIA rats. RL significantly inhibited the production of various pro-inflammatory mediators, the expression and/or activity of the components of TLR4 signalling pathways in animal tissue and cell lines. RL possesses anti-arthritic effect on collagen-induced arthritis in rats. The therapeutic effect of RL may be related to its inhibition on pro-inflammatory cytokines in serum. The inhibition of the TAK1/NF-κB and TAK1/MAPK pathways participate in the anti-arthritic effects of RL. This provides a pharmacological justification for the dietary use of RL in the control of various arthritic diseases. Further investigation should be done to develop RL into a anti-arthritic food products and/or supplements.

Keywords: japanese honeysuckle, rheumatoid arthritis, rosa multiflora, rosehip

Procedia PDF Downloads 432

Authors: W. Mohammedsaeed, A. J. Mcbain, S. M. Cruickshank, C. A. O’Neill

Abstract:

Many studies have demonstrated the importance of probiotics and their potential therapeutic effects within the gut. Recently, the possible therapeutic effects of probiotics in other tissues have also begun to be investigated. Comparatively few studies have evaluated the use of topical probiotics in relation to the skin. In this study, we have conducted preliminary investigations into whether a well-known probiotic, Lactobacillus rhamnosus GG (LGG), can increase the rate of re-epithelialization in a model wound. Full-thickness skin was obtained from individuals undergoing elective cosmetic surgery. This skin was wounded using excisional punch and cultured using a serum-free medium, either in the presence or absence of L. rhamnosus GG lysate. Histological staining of the sections was performed with Haematoxylin& Eosin E to quantify “epithelial tongue length”. This is the length of the new epithelial ‘tongue’ that grows and covers the exposed dermis at the inner wound edges. The length of the new epithelial ‘tongue’ was compared in untreated section and section treated with and L. rhamnosus GG made using108CFU/ml bacterial cells. L. rhamnosus GG lysate enhanced significantly the re-epithelialisation of treated wounds compared with that of untreated wounds (P=0.005, n=3). Tongue length, at day 1 was 7.55μm 0.15, at day 3 it was 18.5μm 0.25 and at day 7 was 22.9μm 0.35. These results can be compared with untreated cultures in which tongue length was 3.25μm 0.35, day 3 was 9.65μm 0.25 and day 7 was 13.5μm 0.15 post-wounding. In ex-vivo proliferation and migration cells were measured by determining the expression of nuclear proliferation marker Ki-67 and the expression of Phosphorylated cortactin respectively demonstrated that L. rhamnosus GG significantly increased NHEK proliferation and migration rates relative to controls. However, the dominant mechanism was migration because in ex-vivo skin treated with the L. rhamnosus GG up-regulated the gene expression of the chemokine receptor and ligands CXCR2 and CXCL2 comparing with controls (P=0.02, P=0.03 respectively, n=3). High levels of CXCL2/CXCL2 have already been implicated in multiple aspects of stimulation of wound healing through activation of keratinocyte migration. These data demonstrate that lysates from Lactobacillus rhamnosus GG increase re-epithelialization by stimulation of keratinocyte migration. The current study identifies the partial mechanism that contribute to stimulating the wound-healing process ex vivo in response to L. rhamnosus GG lysate is an increase in the production of CXCL2/ CXCR2 in ex vivo models. The use of probiotic lysates potentially offers new options to develop treatments that could improve wound healing.

Keywords: Lactobacillus rhamnosus GG, wounds, migration, lysate

Procedia PDF Downloads 329

Authors: Ghirmay Teklemicheal, Samsom Mehari, Sara Tesfay

Abstract:

Objectives: A total of 1074 suspected chikungunya cases were reported in Tesseney Province, Gash Barka region, Eritrea, during an outbreak. This study was aimed to assess the possible association of chikungunya severity among ABO blood groups and other potential determinants. Methods: A sex-matched and age-matched case-control study was conducted during the outbreak. For each case, one control subject had been selected from the mild Chikungunya cases. Along the same line of argument, a second control subject had also been designated through which neighborhood of cases were analyzed, scrutinized, and appeared to the scheme of comparison. Time is always the most sacrosanct element in pursuance of any study. According to the temporal calculation, this study was pursued from October 15, 2018, to November 15, 2018. Coming to the methodological dependability, calculating odds ratios (ORs) and conditional (fixed-effect) logistic regression methods were being applied. As a consequence of this, the data was analyzed and construed on the basis of the aforementioned methodological systems. Results: In this outbreak, 137 severe suspected chikungunya cases and 137 mild chikungunya suspected patients, and 137 controls free of chikungunya from the neighborhood of cases were analyzed. Non-O individuals compared to those with O blood group indicated as significant with a p-value of 0.002. Separate blood group comparison among A and O blood groups reflected as significant with a p-value of 0.002. However, there was no significant difference in the severity of chikungunya among B, AB, and O blood groups with a p-value of 0.113 and 0.708, respectively, and a strong association of chikungunya severity was found with hypertension and diabetes (p-value of < 0.0001); whereas, there was no association between chikungunya severity and asthma with a p-value of 0.695 and also no association with pregnancy (p-value =0.881), ventilator (p-value =0.181), air conditioner (p-value = 0.247), and didn’t use latrine and pit latrine (p-value = 0.318), among individuals using septic and pit latrine (p-value = 0.567) and also among individuals using flush and pit latrine (p-value = 0.194). Conclusions: Non- O blood groups were found to be at risk more than their counterpart O blood group individuals with severe form of chikungunya disease. By the same token, individuals with chronic disease were more prone to severe forms of the disease in comparison with individuals without chronic disease. Prioritization is recommended for patients with chronic diseases and non-O blood group since they are found to be susceptible to severe chikungunya disease. Identification of human cell surface receptor(s) for CHIKV is quite necessary for further understanding of its pathophysiology in humans. Therefore, molecular and functional studies will necessarily be helpful in disclosing the association of blood group antigens and CHIKV infections.

Keywords: Chikungunya, Chikungunya virus, disease outbreaks, case-control studies, Eritrea

Procedia PDF Downloads 162

Authors: Ahmad Kayvani Fard, Gordon Mckay, Muataz Hussien

Abstract:

Adsorption/sorption is believed to be one of the optimal processes for the removal of heavy metals from water due to its low operational and capital cost as well as its high removal efficiency. Different materials have been reported in literature as adsorbent for heavy metal removal in waste water such as natural sorbents, organic polymers (synthetic) and mineral materials (inorganic). The selection of adsorbents and development of new functional materials that can achieve good removal of heavy metals from water is an important practice and depends on many factors, such as the availability of the material, cost of material, and material safety and etc. In this study we reported the synthesis of doped Activated carbon and Carbon nanotube (CNT) with different loading of metal oxide nanoparticles such as Fe2O3, Fe3O4, Al2O3, TiO2, SiO2 and Ag nanoparticles and their application in removal of heavy metals, hydrocarbon, and organics from waste water. Commercial AC and CNT with different loadings of mentioned nanoparticle were prepared and effect of pH, adsorbent dosage, sorption kinetic, and concentration effects are studied and optimum condition for removal of heavy metals from water is reported. The prepared composite sorbent is characterized using field emission scanning electron microscopy (FE-SEM), high transmission electron microscopy (HR-TEM), thermogravimetric analysis (TGA), X-ray diffractometer (XRD), the Brunauer, Emmett and Teller (BET) nitrogen adsorption technique, and Zeta potential. The composite materials showed higher removal efficiency and superior adsorption capacity compared to commercially available carbon based adsorbent. The specific surface area of AC increased by 50% reaching up to 2000 m2/g while the CNT specific surface area of CNT increased by more than 8 times reaching value of 890 m2/g. The increased surface area is one of the key parameters along with surface charge of the material determining the removal efficiency and removal efficiency. Moreover, the surface charge density of the impregnated CNT and AC have enhanced significantly where can benefit the adsorption process. The nanoparticles also enhance the catalytic activity of material and reduce the agglomeration and aggregation of material which provides more active site for adsorbing the contaminant from water. Some of the results for treating wastewater includes 100% removal of BTEX, arsenic, strontium, barium, phenolic compounds, and oil from water. The results obtained are promising for the use of AC and CNT loaded with metal oxide nanoparticle in treatment and pretreatment of waste water and produced water before desalination process. Adsorption can be very efficient with low energy consumption and economic feasibility.

Keywords: carbon nanotube, activated carbon, adsorption, heavy metal, water treatment

Procedia PDF Downloads 234

Authors: D. Pradhan, G. Tripathy, S. Pradhan

Abstract:

Objectives: Imperviousness gainst estrogen treatments is a noteworthy reason for infection backslide and mortality in estrogen receptor alpha (ERα)- positive breast diseases. Tamoxifen or estrogen withdrawal builds the reliance of breast malignancy cells on INT3 flagging. Here, we researched the commitment of Quercetin and INT3 motioning in endocrine-safe breast tumor cells. Methods: We utilized two models of endocrine treatments safe (ETR) breast tumor: Tamoxifen-safe (TamR) and long haul estrogen-denied (LTED) MCF7 cells. We assessed the transitory and intrusive limit of these cells by Transwell cells. Articulation of epithelial to mesenchymal move (EMT) controllers and in addition INT3 receptors and targets were assessed by constant PCR and western smudge investigation. Besides, we tried in-vitro hostile to Quercetin monoclonal Antibodies (mAbs) and Gamma Secretase Inhibitors (GSIs) as potential EMT inversion remedial specialists. At last, we created stable Quercetin overexpressing MCF7 cells and assessed their EMT components and reaction to Tamoxifen. Results: We found that ETR cells procured an Epithelial to Mesenchymal move (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we distinguished more elevated amount of INT3 however lower levels of INT1 and INT3 proposing a change to motioning through distinctive INT3 receptors after obtaining of resistance. Against Quercetin monoclonal antibodies and the GSI PF03084014 were powerful in obstructing the Quercetin/INT3 pivot and in part repressing the EMT process. As a consequence of this, cell relocation and attack were weakened and the immature microorganism like populace was essentially decreased. Hereditary hushing of Quercetin and INT3 prompted proportionate impacts. At long last, stable overexpression of Quercetin was adequate to make MCF7 lethargic to Tamoxifen by INT3 initiation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives intrusive conduct. Hostile to Quercetin mAbs and GSI PF03084014 lessen articulation of EMT particles decreasing cell obtrusiveness. Quercetin overexpression instigates Tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and INT3 warrants further clinical Correlation as substantial restorative methodologies in endocrine-safe breast.

Keywords: endocrine, epithelial, mesenchymal, INT3, quercetin, MCF7

Procedia PDF Downloads 305

Authors: A. N. Kurbanova, G. K. Sugurbekova, N. K. Akhmetov

Abstract:

The asphaltenes are heavy fraction of crude oil. Asphaltenes on oilfield is known for its ability to plug wells, surface equipment and pores of the geologic formations. The present research is devoted to the deasphalting of crude oil as the initial stage refining oil. Solvent deasphalting was conducted by extraction with organic solvents (cyclohexane, carbon tetrachloride, chloroform). Analysis of availability of metals was conducted by ICP-MS and spectral feature at deasphalting was achieved by FTIR. High contents of asphaltenes in crude oil reduce the efficiency of refining processes. Moreover, high distribution heteroatoms (e.g., S, N) were also suggested in asphaltenes cause some problems: environmental pollution, corrosion and poisoning of the catalyst. The main objective of this work is to study the effect of deasphalting process crude oil to improve its properties and improving the efficiency of recycling processes. Experiments of solvent extraction are using organic solvents held in the crude oil JSC “Pavlodar Oil Chemistry Refinery. Experimental results show that deasphalting process also leads to decrease Ni, V in the composition of the oil. One solution to the problem of cleaning oils from metals, hydrogen sulfide and mercaptan is absorption with chemical reagents directly in oil residue and production due to the fact that asphalt and resinous substance degrade operational properties of oils and reduce the effectiveness of selective refining of oils. Deasphalting of crude oil is necessary to separate the light fraction from heavy metallic asphaltenes part of crude oil. For this oil is pretreated deasphalting, because asphaltenes tend to form coke or consume large quantities of hydrogen. Removing asphaltenes leads to partly demetallization, i.e. for removal of asphaltenes V/Ni and organic compounds with heteroatoms. Intramolecular complexes are relatively well researched on the example of porphyinous complex (VO2) and nickel (Ni). As a result of studies of V/Ni by ICP MS method were determined the effect of different solvents-deasphalting – on the process of extracting metals on deasphalting stage and select the best organic solvent. Thus, as the best DAO proved cyclohexane (C6H12), which as a result of ICP MS retrieves V-51.2%, Ni-66.4%? Also in this paper presents the results of a study of physical and chemical properties and spectral characteristics of oil on FTIR with a view to establishing its hydrocarbon composition. Obtained by using IR-spectroscopy method information about the specifics of the whole oil give provisional physical, chemical characteristics. They can be useful in the consideration of issues of origin and geochemical conditions of accumulation of oil, as well as some technological challenges. Systematic analysis carried out in this study; improve our understanding of the stability mechanism of asphaltenes. The role of deasphalted crude oil fractions on the stability asphaltene is described.

Keywords: asphaltenes, deasphalting, extraction, vanadium, nickel, metalloporphyrins, ICP-MS, IR spectroscopy

Procedia PDF Downloads 242

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 252

Authors: S. Pradhan, D. Pradhan, G. Tripathy

Abstract:

Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

Procedia PDF Downloads 311

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 78

Authors: Maki Mizogami, Hironori Tsuchiya, Yoshiroh Hayabuchi, Kenji Shigemi

Abstract:

Since drugs exhibit significant structure-dependent differences in activity and toxicity, their differentiation based on the mechanism of action should have implications for comparative drug efficacy and safety. We aimed to differentiate drug stereoisomers by their stereostructure-selective membrane interactions underlying pharmacological and toxicological effects. Biomimetic lipid bilayer membranes were prepared with phospholipids and sterols (either cholesterol or epicholesterol) to mimic the lipid compositions of neuronal and cardiomyocyte membranes and to provide these membranes with the chirality. The membrane preparations were treated with different classes of stereoisomers at clinically- and pharmacologically-relevant concentrations (25-200 μM), followed by measuring fluorescence polarization to determine the membrane interactivity of drugs to change the physicochemical property of membranes. All the tested drugs acted on lipid bilayers to increase or decrease the membrane fluidity. Drug stereoisomers could not be differentiated when interacting with the membranes consisting of phospholipids alone. However, they stereostructure-selectively interacted with neuro-mimetic and cardio-mimetic membranes containing 40 mol% cholesterol ((3β)-cholest-5-en-3-ol) to show the relative potencies being local anesthetic R(+)-bupivacaine > rac-bupivacaine > S(‒)-bupivacaine, α2-adrenergic agonistic D-medetomidine > rac-medetomidine > L-medetomidine, β-adrenergic antagonistic R(+)-propranolol > rac-propranolol > S(–)-propranolol, NMDA receptor antagonistic S(+)-ketamine > rac-ketamine, analgesic monoterpenoid (+)-menthol > (‒)-menthol, non-steroidal anti-inflammatory S(+)-ibuprofen > rac-ibuprofen > R(‒)-ibuprofen, and bioactive flavonoid (+)-epicatechin > (‒)-epicatechin. All of the order of membrane interactivity were correlated to those of beneficial and adverse effects of the tested stereoisomers. In contrast, the membranes prepared with epicholesterol ((3α)-chotest-5-en-3-ol), an epimeric form of cholesterol, reversed the rank order of membrane interactivity to be S(‒)-enantiomeric > racemic > R(+)-enantiomeric bupivacaine, L-enantiomeric > racemic > D-enantiomeric medetomidine, S(–)-enantiomeric > racemic > R(+)-enantiomeric propranolol, racemic > S(+)-enantiomeric ketamine, (‒)-enantiomeric > (+)-enantiomeric menthol, R(‒)-enantiomeric > racemic > S(+)-enantiomeric ibuprofen, and (‒)-enantiomeric > (+)-enantiomeric epicatechin. The opposite configuration allows drug molecules to interact with chiral sterol membranes enantiomer-selectively. From the comparative results, it is speculated that a 3β-hydroxyl group in cholesterol is responsible for the enantioselective interactions of drugs. In conclusion, the differentiation of drug stereoisomers by their stereostructure-selective membrane interactions would be useful for designing and predicting drugs with higher activity and/or lower toxicity.

Keywords: chiral membrane, differentiation, drug stereoisomer, enantioselective membrane interaction

Procedia PDF Downloads 223

Authors: S. V. Kuznetsov, M. N. Mayakova, V. Yu. Proydakova, V. V. Pavlov, A. S. Nizamutdinov, O. A. Morozov, V. V. Voronov, P. P. Fedorov

Abstract:

Increase in the share of electricity received by conversion of solar energy results in the reduction of the industrial impact on the environment from the use of the hydrocarbon energy sources. One way to increase said share is to improve the efficiency of solar energy conversion in silicon-based solar panels. Such efficiency increase can be achieved by transferring energy from sunlight-insensitive areas of work of silicon solar panels to the area of their photoresistivity. To achieve this goal, a transition to new luminescent materials with the high quantum yield of luminescence is necessary. Improvement in the quantum yield can be achieved by quantum cutting, which allows obtaining a quantum yield of down conversion of more than 150% due to the splitting of high-energy photons of the UV spectral range into lower-energy photons of the visible and near infrared spectral ranges. The goal of present work is to test approach of excitation through sensibilization of 4f-4f fluorescence of Yb3+ by various RE ions absorbing in UV and Vis spectral ranges. One of promising materials for quantum cutting luminophores are fluorides. In our investigation we have developed synthesis of nano- and submicron powders of calcium fluoride and strontium doped with rare-earth elements (Yb: Ce, Yb: Pr, Yb: Eu) of controlled dimensions and shape by co-precipitation from water solution technique. We have used Ca(NO3)2*4H2O, Sr(NO3)2, HF, NH4F as precursors. After initial solutions of nitrates were prepared they have been mixed with fluorine containing solution by dropwise manner. According to XRD data, the synthesis resulted in single phase samples with fluorite structure. By means of SEM measurements, we have confirmed spherical morphology and have determined sizes of particles (50-100 nm after synthesis and 150-300 nm after calcination). Temperature of calcination appeared to be 600°C. We have investigated the spectral-kinetic characteristics of above mentioned compounds. Here the diffuse reflection and laser induced fluorescence spectra of Yb3+ ions excited at around 4f-4f and 4f-5d transitions of Pr3+, Eu3+ and Ce3+ ions in the synthesized powders are reported. The investigation of down conversion luminescence capability of synthesized compounds included measurements of fluorescence decays and quantum yield of 2F5/2-2F7/2 fluorescence of Yb3+ ions as function of Yb3+ and sensitizer contents. An optimal chemical composition of CaF2-YbF3- LnF3 (Ln=Ce, Eu, Pr), SrF2-YbF3-LnF3 (Ln=Ce, Eu, Pr) micro- and nano- powders according to criteria of maximal IR fluorescence yield is proposed. We suppose that investigated materials are prospective in solar panels improvement applications. Work was supported by Russian Science Foundation grant #17-73- 20352.

Keywords: solar cell, fluorides, down-conversion luminescence, maximum quantum yield

Procedia PDF Downloads 272

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 103

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 139

Authors: Muhammed Ertugrul Celoglu, Beyza Furtana, Mehmet Yilmaz, Baha Vural Kok

Abstract:

Biomass, which is considered to be one of the largest renewable energy sources in the world, has a potential to be utilized as a bitumen additive after it is processed by a wide variety of thermochemical methods. Furthermore, biomasses are renewable in short amounts of time, and they possess a hydrocarbon structure. These characteristics of biomass promote their usability as additives. One of the most common ways to create materials with significant economic values from biomasses is the processes of pyrolysis. Pyrolysis is defined as the process of an organic matter’s thermochemical degradation (carbonization) at a high temperature and in an anaerobic environment. The resultant liquid substance at the end of the pyrolysis is defined as bio-oil, whereas the resultant solid substance is defined as biochar. Olive pomace is the resultant mildly oily pulp with seeds after olive is pressed and its oil is extracted. It is a significant source of biomass as the waste of olive oil factories. Because olive pomace is waste material, it could create problems just as other waste unless there are appropriate and acceptable areas of utilization. The waste material, which is generated in large amounts, is generally used as fuel and fertilizer. Generally, additive materials are used in order to improve the properties of bituminous binders, and these are usually expensive materials, which are produced chemically. The aim of this study is to investigate the usability of biochars obtained after subjecting olive pomace and smashed olive seeds, which are considered as waste materials, to pyrolysis as additives in bitumen modification. In this way, various ways of use will be provided for waste material, providing both economic and environmental benefits. In this study, olive pomace and smashed olive seeds were used as sources of biomass. Initially, both materials were ground and processed through a No.50 sieve. Both of the sieved materials were subjected to pyrolysis (carbonization) at 400 ℃. Following the process of pyrolysis, bio-oil and biochar were obtained. The obtained biochars were added to B160/220 grade pure bitumen at 10% and 15% rates and modified bitumens were obtained by mixing them in high shear mixtures at 180 ℃ for 1 hour at 2000 rpm. Pure bitumen and four different types of bitumen obtained as a result of the modifications were tested with penetration, softening point, rotational viscometer, and dynamic shear rheometer, evaluating the effects of additives and the ratios of additives. According to the test results obtained, both biochar modifications at both ratios provided improvements in the performance of pure bitumen. In the comparison of the test results of the binders modified with the biochars of olive pomace and smashed olive seed, it was revealed that there was no notable difference in their performances.

Keywords: bituminous binders, biochar, biomass, olive pomace, pomace, pyrolysis

Procedia PDF Downloads 132

Authors: Sayem Zafar, Mahmood Rahi

Abstract:

Rigorous international maritime regulations are in place to limit boat and ship hydrocarbon emissions. The global sustainability goals are reducing the fuel consumption and minimizing the emissions from the ships and boats. These maritime sustainability goals have attracted a lot of research interest. Energy harvesting and storage system is designed in this study based on hybrid renewable and conventional energy systems. This energy harvesting and storage system is designed for marine applications, such as, boats and small ships. These systems can be utilized for mobile use or off-grid remote electrification. This study analyzed the use of micro power generation for boats and small ships. The energy harvesting and storage system has two distinct systems i.e. dockside shore-based system and on-board system. The shore-based system consists of a small wind turbine, photovoltaic (PV) panels, small gas turbine, hydrogen generator and high-pressure hydrogen storage tank. This dockside system is to provide easy access to the boats and small ships for supply of hydrogen. The on-board system consists of hydrogen storage tanks and fuel cells. The wind turbine and PV panels generate electricity to operate electrolyzer. A small gas turbine is used as a supplementary power system to contribute in case the hybrid renewable energy system does not provide the required energy. The electrolyzer performs the electrolysis on distilled water to produce hydrogen. The hydrogen is stored in high-pressure tanks. The hydrogen from the high-pressure tank is filled in the low-pressure tanks on-board seagoing vessels to operate the fuel cell. The boats and small ships use the hydrogen fuel cell to provide power to electric propulsion motors and for on-board auxiliary use. For shore-based system, a small wind turbine with the total length of 4.5 m and the disk diameter of 1.8 m is used. The small wind turbine dimensions make it big enough to be used to charge batteries yet small enough to be installed on the rooftops of dockside facility. The small dimensions also make the wind turbine easily transportable. In this paper, PV, sizing and solar flux are studied parametrically. System performance is evaluated under different operating and environmental conditions. The parametric study is conducted to evaluate the energy output and storage capacity of energy storage system. Results are generated for a wide range of conditions to analyze the usability of hybrid energy harvesting and storage system. This energy harvesting method significantly improves the usability and output of the renewable energy sources. It also shows that small hybrid energy systems have promising practical applications.

Keywords: energy harvesting, fuel cell, hybrid energy system, hydrogen, wind turbine

Procedia PDF Downloads 137

Authors: Ankita Singh, Chandan Gorain, Amirul I. Mallick

Abstract:

Successful adherence of the mucosal epithelial cells is the key early step for Campylobacter jejuni pathogenesis (C. jejuni). A set of Surface Exposed Colonization Proteins (SECPs) are among the major factors involved in host cell adherence and invasion of C. jejuni. Among them, constitutively expressed surface-exposed lipoprotein adhesin of C. jejuni, JlpA, interacts with intestinal heat shock protein 90 (hsp90α) and contributes in disease progression by triggering pro-inflammatory response via activation of NF-κB and p38 MAP kinase pathway. Together with its ability to express in the bacterial surface, higher sequence conservation and predicted predominance of several B cells epitopes, JlpA protein reserves its potential to become an effective vaccine candidate against wide range of Campylobacter sps including C. jejuni. Given that chickens are the primary sources for C. jejuni and persistent gut colonization remain as major cause for foodborne pathogenesis to humans, present study explicitly used chickens as model to test the immune-protective efficacy of JlpA protein. Taking into account that gastrointestinal tract is the focal site for C. jejuni colonization, to extrapolate the benefit of mucosal (intragastric) delivery of JlpA protein, a food grade Nisin inducible Lactic acid producing bacteria, Lactococcus lactis (L. lactis) was engineered to express recombinant JlpA protein (rJlpA) in the surface of the bacteria. Following evaluation of optimal surface expression and functionality of recombinant JlpA protein expressed by recombinant L. lactis (rL. lactis), the immune-protective role of intragastric administration of live rL. lactis was assessed in commercial broiler chickens. In addition to the significant elevation of antigen specific mucosal immune responses in the intestine of chickens that received three doses of rL. lactis, marked upregulation of Toll-like receptor 2 (TLR2) gene expression in association with mixed pro-inflammatory responses (both Th1 and Th17 type) was observed. Furthermore, intragastric delivery of rJlpA expressed by rL. lactis, but not the injectable form, resulted in a significant reduction in C. jejuni colonization in chickens suggesting that mucosal delivery of live rL. lactis expressing JlpA serves as a promising vaccine platform to induce strong immune-protective responses against C. jejuni in chickens.

Keywords: chickens, lipoprotein adhesion of Campylobacter jejuni, immuno-protection, Lactococcus lactis, mucosal delivery

Procedia PDF Downloads 139

Authors: Beate Englich, Linda Schlittenbauer, Christiane Pfeifer, Isabel Kratochvil, Michael Borte, Gabriele I. Stangl, Martin von Bergen, Thorsten Reemtsma, Irina Lehmann, Kristin M. Junge

Abstract:

The worldwide production of endocrine disrupting compounds (EDC) has risen dramatically over the last decades, as so has the prevalence for obesity. Many EDCs are believed to contribute to this obesity epidemic, by enhancing adipogenesis or disrupting relevant metabolism. This effect is most tremendous in the early prenatal period when priming effects find a highly vulnerable time window. Therefore, we investigate the impact of parabens on childhood overweight development and adipogenesis in general. Parabens are ester of 4-hydroxy-benzoic acid and part of many cosmetic products or food packing. Therefore, ubiquitous exposure can be found in the westernized world, with exposure already starting during the sensitive prenatal period. We assessed maternal cosmetic product consumption, prenatal paraben exposure and infant BMI z-scores in the prospective German LINA cohort. In detail, maternal urinary concentrations (34 weeks of gestation) of methyl paraben (MeP), ethyl paraben (EtP), n-propyl paraben (PrP) and n-butyl paraben (BuP) were quantified using UPLC-MS/MS. Body weight and height of their children was assessed during annual clinical visits. Further, we investigated the direct influence of those parabens on adipogenesis in-vitro using a human mesenchymal stem cell (MSC) differentiation assay to mimic a prenatal exposure scenario. MSC were exposed to 0.1 – 50 µM paraben during the entire differentiation period. Differentiation outcome was monitored by impedance spectrometry, real-time PCR and triglyceride staining. We found that maternal cosmetic product consumption was highly correlated with urinary paraben concentrations at pregnancy. Further, prenatal paraben exposure was linked to higher BMI Z-scores in children. Our in-vitro analysis revealed that especially the long chained paraben BuP stimulates adipogenesis by increasing the expression of adipocyte specific genes (PPARγ, ADIPOQ, LPL, etc.) and triglyceride storage. Moreover, we found that adiponectin secretion is increased whereas leptin secretion is reduced under BuP exposure in-vitro. Further mechanistic analysis for receptor binding and activation of PPARγ and other key players in adipogenesis are currently in process. We conclude that maternal cosmetic product consumption is linked to prenatal paraben exposure of children and contributes to the development of infant overweight development by triggering key pathways of adipogenesis.

Keywords: adipogenesis, endocrine disruptors, paraben, prenatal exposure

Procedia PDF Downloads 272

Authors: Adonis Menezes, J. C. Passos

Abstract:

The current panorama of technology in heat transfer and the scarcity of information about the convective boiling of CO₂ and hydrocarbon in small diameter channels motivated the development of this work. Among non-halogenated refrigerants, CO₂/ R744 has distinct thermodynamic properties compared to other fluids. The R744 presents significant differences in operating pressures and temperatures, operating at higher values compared to other refrigerants, and this represents a challenge for the design of new evaporators, as the original systems must normally be resized to meet the specific characteristics of the R744, which creates the need for a new design and optimization criteria. To carry out the convective boiling tests of CO₂, an experimental apparatus capable of storing (m= 10kg) of saturated CO₂ at (T = -30 ° C) in an accumulator tank was used, later this fluid was pumped using a positive displacement pump with three pistons, and the outlet pressure was controlled and could reach up to (P = 110bar). This high-pressure saturated fluid passed through a Coriolis type flow meter, and the mass velocities varied between (G = 20 kg/m².s) up to (G = 1000 kg/m².s). After that, the fluid was sent to the first test section of circular cross-section in diameter (D = 4.57mm), where the inlet and outlet temperatures and pressures, were controlled and the heating was promoted by the Joule effect using a source of direct current with a maximum heat flow of (q = 100 kW/m²). The second test section used a cross-section with multi-channels (seven parallel channels) with a square cross-section of (D = 2mm) each; this second test section has also control of temperature and pressure at the inlet and outlet as well as for heating a direct current source was used, with a maximum heat flow of (q = 20 kW/m²). The fluid in a biphasic situation was directed to a parallel plate heat exchanger so that it returns to the liquid state, thus being able to return to the accumulator tank, continuing the cycle. The multi-channel test section has a viewing section; a high-speed CMOS camera was used for image acquisition, where it was possible to view the flow patterns. The experiments carried out and presented in this report were conducted in a rigorous manner, enabling the development of a database on the convective boiling of the R744 in macro and micro channels. The analysis prioritized the processes from the beginning of the convective boiling until the drying of the wall in a subcritical regime. The R744 resurfaces as an excellent alternative to chlorofluorocarbon refrigerants due to its negligible ODP (Ozone Depletion Potential) and GWP (Global Warming Potential) rates, among other advantages. The results found in the experimental tests were very promising for the use of CO₂ in micro-channels in convective boiling and served as a basis for determining the flow pattern map and correlation for determining the heat transfer coefficient in the convective boiling of CO₂.

Keywords: convective boiling, CO₂/R744, macro-channels, micro-channels

Procedia PDF Downloads 142