Search results for: orphan nuclear receptors
269 Fine Characterization of Glucose Modified Human Serum Albumin by Different Biophysical and Biochemical Techniques at a Range
Authors: Neelofar, Khursheed Alam, Jamal Ahmad
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Protein modification in diabetes mellitus may lead to early glycation products (EGPs) or amadori product as well as advanced glycation end products (AGEs). Early glycation involves the reaction of glucose with N-terminal and lysyl side chain amino groups to form Schiff’s base which undergoes rearrangements to form more stable early glycation product known as Amadori product. After Amadori, the reactions become more complicated leading to the formation of advanced glycation end products (AGEs) that interact with various AGE receptors, thereby playing an important role in the long-term complications of diabetes. Millard reaction or nonenzymatic glycation reaction accelerate in diabetes due to hyperglycation and alter serum protein’s structure, their normal functions that lead micro and macro vascular complications in diabetic patients. In this study, Human Serum Albumin (HSA) with a constant concentration was incubated with different concentrations of glucose at 370C for a week. At 4th day, Amadori product was formed that was confirmed by colorimetric method NBT assay and TBA assay which both are authenticate early glycation product. Conformational changes in native as well as all samples of Amadori albumin with different concentrations of glucose were investigated by various biophysical and biochemical techniques. Main biophysical techniques hyperchromacity, quenching of fluorescence intensity, FTIR, CD and SDS-PAGE were used. Further conformational changes were observed by biochemical assays mainly HMF formation, fructoseamine, reduction of fructoseamine with NaBH4, carbonyl content estimation, lysine and arginine residues estimation, ANS binding property and thiol group estimation. This study find structural and biochemical changes in Amadori modified HSA with normal to hyperchronic range of glucose with respect to native HSA. When glucose concentration was increased from normal to chronic range biochemical and structural changes also increased. Highest alteration in secondary and tertiary structure and conformation in glycated HSA was observed at the hyperchronic concentration (75mM) of glucose. Although it has been found that Amadori modified proteins is also involved in secondary complications of diabetes as AGEs but very few studies have been done to analyze the conformational changes in Amadori modified proteins due to early glycation. Most of the studies were found on the structural changes in Amadori protein at a particular glucose concentration but no study was found to compare the biophysical and biochemical changes in HSA due to early glycation with a range of glucose concentration at a constant incubation time. So this study provide the information about the biochemical and biophysical changes occur in Amadori modified albumin at a range of glucose normal to chronic in diabetes. Although many implicates currently in use i.e. glycaemic control, insulin treatment and other chemical therapies that can control many aspects of diabetes. However, even with intensive use of current antidiabetic agents more than 50 % of diabetic patient’s type 2 suffers poor glycaemic control and 18 % develop serious complications within six years of diagnosis. Experimental evidence related to diabetes suggests that preventing the nonenzymatic glycation of relevant proteins or blocking their biological effects might beneficially influence the evolution of vascular complications in diabetic patients or quantization of amadori adduct of HSA by authentic antibodies against HSA-EGPs can be used as marker for early detection of the initiation/progression of secondary complications of diabetes. So this research work may be helpful for the same.Keywords: diabetes mellitus, glycation, albumin, amadori, biophysical and biochemical techniques
Procedia PDF Downloads 272268 Chrysin-Loaded PLGA-PEG Nanoparticles Designed for Enhanced Inhibitory Effect on the Breast Cancer Cell Line
Authors: Faraz Zarghami, Elham Anari, Nosratollah Zarghami, Yones Pilehvar-Soltanahmadi, Abolfazl Akbarzadeh, Sepideh Jalilzadeh-Tabrizi
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The development of nanotherapy has presented a new method of drug delivery targeted directly to the neoplasmic tissues, to maximize the action with fewer dose requirements. In the past two decades, poly(lactic-co-glycolic acid) (PLGA) has frequently been investigated by many researchers and is a popular polymeric candidate, due to its biocompatibility and biodegradability, exhibition of a wide range of erosion times, tunable mechanical properties, and most notably, because it is a FDA-approved polymer. Chrysin is a natural flavonoid which has been reported to have some significant biological effects on the processes of chemical defense, nitrogen fixation, inflammation, and oxidation. However, the low solubility in water decreases its bioavailability and consequently disrupts the biomedical benefits. Being loaded with PLGA-PEG increases chrysin solubility and drug tolerance, and decreases the discordant effects of the drug. The well-structured chrysin efficiently accumulates in the breast cancer cell line (T47D). In the present study, the structure and chrysin loading were delineated using proton nuclear magnetic resonance (HNMR), Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM), and the in vitro cytotoxicity of pure and nanochrysin was studied by the MTT assay. Next, the RNA was exploited and the cytotoxic effects of chrysin were studied by real-time PCR. In conclusion, the nanochrysin therapy developed is a novel method that could increase cytotoxicity to cancer cells without damaging the normal cells, and would be promising in breast cancer therapy.Keywords: MTT assay, chrysin, flavonoids, nanotherapy
Procedia PDF Downloads 250267 Role of Giardia lamblia Infection in the Pathogenesis of Gastritis in Patients with Dyspepsia
Authors: Aly Kassem, Eman A. Sabet, Hanaa A. El-Hady, Doha S. Mohamed, Abeer Sheneef, Mona Fattouh, Mamdouh M. Esmat
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Objective: Giardia lamblia parasite is the most common protozoal infection in human. Concomitant Helecobacter Pylori (H. pylori) and Giardia lamblia infection is common for their similar mode of transmission and strong correlation to socioeconomic levels. Only few reports had described gastric giardiasis. Our aim was to detect H. pylori and Giardia in gastric antral mucosal biopsies from patients with dyspepsia. The impact of both pathogens on clinical, endoscopic and histopathogical changes was studied. Methods: 48 patients with dyspepsia (group1) and 28 control patients (patients undergoing esophagogastroduodenoscopy EGD for reasons other than dyspepsia), (group 2) were studied. Endoscopic data were reported and gastric biopsy specimens were obtained for subsequent PCR assay for both organisms and for histopathological and electron microscopic examination. Results: Endoscopic antral gastritis and duodenal lesions were found in both groups, however, they were significantly more frequently in group 1 (p= 0.002 and P= 0.0005 respectively). Esophageal lesions, nodular antral gastritis, gastric ulcers and superficial corpal gastritis were found only in group 1. PCR detected H. pylori infection in 58% Vs 64 % for group 1 and group 2 respectively (P: NS). Giardia infection was present in 67 % Vs 42 % for group 1 and group 2 respectively (P=0.0003, Odd ratio=2.6). Co-infection with H. pylori and Giardia was present in 33% of group 1 Vs 36% for group 2 (P:NS). Abnormal histologic findings were found in both groups, however, intestinal metaplasia was found in group 1 only. Cellular abnormalities in the form of cytoplasmic vacuoles, mitochondrial destruction or nuclear abnormalities were found by Electron microscopic study in infected subjects of both groups. Conclusion: H. pylori is not the only gastric pathogen in our community, gastric giardiasis is another pathogen. Its contribution might be a factor in persistent dyspepsia after H. pylori eradication.Keywords: dyspepsia, gastritis, Giardia lamblia, H. pylori
Procedia PDF Downloads 305266 Appraisal of Trace Elements in Scalp Hair of School Children in Kandal Province, Cambodia
Authors: Alireza Yavar, Sukiman Sarmani, Kok Siong Khoo
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Trace element analysis of human hair has the potential to disclose retroactive information about an individual’s nutritional status and exposure. The residents of villages in Kandal province of Cambodia, due to dietary habits, lifestyle and ecological conditions, are unprotected from toxic elements particularly arsenic (As). The purpose of this research was to valuation levels of toxic and vital elements in scalp human hair. Scalp hair samples of 12-17 school children from three villages of Anglong Romiot (AR), Svay Romiot (SR) and Kampong Kong (KK) in the Kandal province of Cambodia were evaluated using k0- instrumental neutron activation method (k0-INAA). The samples were irradiated 6 hours in a Malaysian nuclear agency (MNA) research reactor and afterward, an HPGe detector was utilized to obtain gamma peaks of radionuclides in samples. We achieved profiles of 31 elements in human hair in our studied area, namely, As, Au, Br, Ca, Ce, Co, Dy, Eu152m, Hg197, Hg203, Ho, Ir, K, La, Lu, Mn, Na, Pa, Pt195m, Pt197, Sb, Sc46, Sc47, Sm, Sn117m, W181, W187, Yb169, Yb175, Zn and Zn69m. The precision of the method was assessed by evaluating ERM-DB001-human hair as certified reference materials (CRMs), and which experimental result of ERM-DB001 was consistent with certified values. Whereas Arsenic (As) pollution is major contamination in our studied area, correlation between the concentration of As and other elements were determined by Pearson’s correlation test that it may be useful as a database source for toxic and essential elements in the hair of teenage individuals in our studied areaKeywords: scalp human hair, toxic and essential elements, Kandal province of Cambodia, k₀- instrumental neutron activation method
Procedia PDF Downloads 116265 Effect of Naphtha in Addition to a Cycle Steam Stimulation Process Reducing the Heavy Oil Viscosity Using a Two-Level Factorial Design
Authors: Nora A. Guerrero, Adan Leon, María I. Sandoval, Romel Perez, Samuel Munoz
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The addition of solvents in cyclic steam stimulation is a technique that has shown an impact on the improved recovery of heavy oils. In this technique, it is possible to reduce the steam/oil ratio in the last stages of the process, at which time this ratio increases significantly. The mobility of improved crude oil increases due to the structural changes of its components, which at the same time reflected in the decrease in density and viscosity. In the present work, the effect of the variables such as temperature, time, and weight percentage of naphtha was evaluated, using a factorial design of experiments 23. From the results of analysis of variance (ANOVA) and Pareto diagram, it was possible to identify the effect on viscosity reduction. The experimental representation of the crude-vapor-naphtha interaction was carried out in a batch reactor on a Colombian heavy oil of 12.8° API and 3500 cP. The conditions of temperature, reaction time, and percentage of naphtha were 270-300 °C, 48-66 hours, and 3-9% by weight, respectively. The results showed a decrease in density with values in the range of 0.9542 to 0.9414 g/cm³, while the viscosity decrease was in the order of 55 to 70%. On the other hand, simulated distillation results, according to ASTM 7169, revealed significant conversions of the 315°C+ fraction. From the spectroscopic techniques of nuclear magnetic resonance NMR, infrared FTIR and UV-VIS visible ultraviolet, it was determined that the increase in the performance of the light fractions in the improved crude is due to the breakdown of alkyl chains. The methodology for cyclic steam injection with naphtha and laboratory-scale characterization can be considered as a practical tool in improved recovery processes.Keywords: viscosity reduction, cyclic steam stimulation, factorial design, naphtha
Procedia PDF Downloads 175264 The Role of Cholesterol Oxidase of Mycobacterium tuberculosis in the Down-Regulation of TLR2-Signaling Pathway in Human Macrophages during Infection Process
Authors: Michal Kielbik, Izabela Szulc-Kielbik, Anna Brzostek, Jaroslaw Dziadek, Magdalena Klink
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The goal of many research groups in the world is to find new components that are important for survival of mycobacteria in the host cells. Mycobacterium tuberculosis (Mtb) possesses a number of enzymes degrading cholesterol that are considered to be an important factor for its survival and persistence in host macrophages. One of them - cholesterol oxidase (ChoD), although not being essential for cholesterol degradation, is discussed as a virulence compound, however its involvement in macrophages’ response to Mtb is still not sufficiently determined. The recognition of tubercle bacilli antigens by pathogen recognition receptors is crucial for the initiation of the host innate immune response. An important receptor that has been implicated in the recognition and/or uptake of Mtb is Toll-like receptor type 2 (TLR2). Engagement of TLR2 results in the activation and phosphorylation of intracellular signaling proteins including IRAK-1 and -4, TRAF-6, which in turn leads to the activation of target kinases and transcription factors responsible for bactericidal and pro-inflammatory response of macrophages. The aim of these studies was a detailed clarification of the role of Mtb cholesterol oxidase as a virulence factor affecting the TLR2 signaling pathway in human macrophages. As human macrophages the THP-1 differentiated cells were applied. The virulent wild-type Mtb strain (H37Rv), its mutant lacking a functional copy of gene encoding cholesterol oxidase (∆choD), as well as complimented strain (∆choD–choD) were used. We tested the impact of Mtb strains on the expression of TLR2-depended signaling proteins (mRNA level, cytosolic level and phosphorylation status). The cytokine and bactericidal response of THP-1 derived macrophages infected with Mtb strains in relation to TLR2 signaling pathway dependence was also determined. We found that during the 24-hours of infection process the wild-type and complemented Mtb significantly reduced the cytosolic level and phosphorylation status of IRAK-4 and TRAF-6 proteins in macrophages, that was not observed in the case of ΔchoD mutant. Decreasement of TLR2-dependent signaling proteins, induced by wild-type Mtb, was not dependent on the activity of proteasome. Blocking of TLR2 expression, before infection, effectively prevented the induced by wild-type strain reduction of cytosolic level and phosphorylation of IRAK-4. None of the strains affected the surface expression of TLR2. The mRNA level of IRAK-4 and TRAF-6 genes were significantly increased in macrophages 24 hours post-infection with either of tested strains. However, the impact of wild-type Mtb strain on both examined genes was significantly stronger than its ΔchoD mutant. We also found that wild-type strain stimulated macrophages to release high amount of immunosuppressive IL-10, accompanied by low amount of pro-inflammatory IL-8 and bactericidal nitric oxide in comparison to mutant lacking cholesterol oxidase. The influence of wild-type Mtb on this type of macrophages' response strongly dependent on fully active IRAK-1 and IRAK-4 signaling proteins. In conclusion, Mtb using cholesterol oxidase causes the over-activation of TLR2 signaling proteins leading to the reduction of their cytosolic level and activity resulting in the modulation of macrophages response to allow its intracellular survival. Supported by grant: 2014/15/B/NZ6/01565, National Science Center, PolandKeywords: Mycobacterium tuberculosis, cholesterol oxidase, macrophages, TLR2-dependent signaling pathway
Procedia PDF Downloads 419263 Quaternized PPO/PSF Anion Exchange Membranes Doped with ZnO-Nanoparticles for Fuel Cell Application
Authors: P. F. Msomi, P. T. Nonjola, P. G. Ndungu, J. Ramontja
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In view of the projected global energy demand and increasing levels of greenhouse gases and pollutants issues have inspired an intense search for alternative new energy technologies, which will provide clean, low cost and environmentally friendly solutions to meet the end user requirements. Alkaline anion exchange membrane fuel cells (AAEMFC) have been recognized as ideal candidates for the generation of such clean energy for future stationary and mobile applications due to their many advantages. The key component of the AAEMFC is the anion exchange membrane (AEM). In this report, a series of quaternized poly (2.6 dimethyl – 1.4 phenylene oxide)/ polysulfone (QPPO/PSF) blend anionic exchange membranes (AEM) were successfully fabricated and characterized for alkaline fuel cell application. Zinc Oxide (ZnO) nanoparticles were introduced in the polymer matrix to enhance the intrinsic properties of the AEM. The characteristic properties of the QPPO/PSF and QPPO/PSF-ZnO blend membrane were investigated with X-ray diffraction (XRD), thermogravimetric analysis (TGA) scanning electron microscope (SEM) and contact angle (CA). To confirm successful quaternisation, FT-IR spectroscopy and proton nuclear magnetic resonance (1H NMR) were used. Other properties such as ion exchange capacity (IEC), water uptake, contact angle and ion conductivity (IC) were also undertaken to check if the prepared nanocomposite materials are suitable for fuel cell application. The membrane intrinsic properties were found to be enhanced by the addition of ZnO nanoparticles. The addition of ZnO nanoparticles resulted to a highest IEC of 3.72 mmol/g and a 30-fold IC increase of the nanocomposite due to its lower methanol permeability. The above results indicate that QPPO/PSF-ZnO is a good candidate for AAEMFC application.Keywords: anion exchange membrane, fuel cell, zinc oxide nanoparticle, nanocomposite
Procedia PDF Downloads 427262 Recovery of Au and Other Metals from Old Electronic Components by Leaching and Liquid Extraction Process
Authors: Tomasz Smolinski, Irena Herdzik-Koniecko, Marta Pyszynska, M. Rogowski
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Old electronic components can be easily found nowadays. Significant quantities of valuable metals such as gold, silver or copper are used for the production of advanced electronic devices. Old useless electronic device slowly became a new source of precious metals, very often more efficient than natural. For example, it is possible to recover more gold from 1-ton personal computers than seventeen tons of gold ore. It makes urban mining industry very profitable and necessary for sustainable development. For the recovery of metals from waste of electronic equipment, various treatment options based on conventional physical, hydrometallurgical and pyrometallurgical processes are available. In this group hydrometallurgy processes with their relatively low capital cost, low environmental impact, potential for high metal recoveries and suitability for small scale applications, are very promising options. Institute of Nuclear Chemistry and Technology has great experience in hydrometallurgy processes especially focused on recovery metals from industrial and agricultural wastes. At the moment, urban mining project is carried out. The method of effective recovery of valuable metals from central processing units (CPU) components has been developed. The principal processes such as acidic leaching and solvent extraction were used for precious metals recovery from old processors and graphic cards. Electronic components were treated by acidic solution at various conditions. Optimal acid concentration, time of the process and temperature were selected. Precious metals have been extracted to the aqueous phase. At the next step, metals were selectively extracted by organic solvents such as oximes or tributyl phosphate (TBP) etc. Multistage mixer-settler equipment was used. The process was optimized.Keywords: electronic waste, leaching, hydrometallurgy, metal recovery, solvent extraction
Procedia PDF Downloads 137261 Plasma Ion Implantation Study: A Comparison between Tungsten and Tantalum as Plasma Facing Components
Authors: Tahreem Yousaf, Michael P. Bradley, Jerzy A. Szpunar
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Currently, nuclear fusion is considered one of the most favorable options for future energy generation, due both to its abundant fuel and lack of emissions. For fusion power reactors, a major problem will be a suitable material choice for the Plasma Facing Components (PFCs) which will constitute the reactor first wall. Tungsten (W) has advantages as a PFC material because of its high melting point, low vapour pressure, high thermal conductivity and low retention of hydrogen isotopes. However, several adverse effects such as embrittlement, melting and morphological evolution have been observed in W when it is bombarded by low-energy and high-fluence helium (He) and deuterium (D) ions, as a simulation conditions adjacent to a fusion plasma. Recently, tantalum (Ta) also investigate as PFC and show better reluctance to nanostructure fuzz as compared to W under simulated fusion plasma conditions. But retention of D ions found high in Ta than W. Preparatory to plasma-based ion implantation studies, the effect of D and He ion impact on W and Ta is predicted by using the stopping and range of ions in the matter (SRIM) code. SRIM provided some theoretical results regarding projected range, ion concentration (at. %) and displacement damage (dpa) in W and Ta. The projected range for W under Irradiation of He and D ions with an energy of 3-keV and 1×fluence is determined 75Å and 135 Å and for Ta 85Å and 155Å, respectively. For both W and Ta samples, the maximum implanted peak for helium is predicted ~ 5.3 at. % at 12 nm and for De ions concentration peak is located near 3.1 at. % at 25 nm. For the same parameters, the displacement damage for He ions is observed in W ~ 0.65 dpa and Ta ~ 0.35 dpa at 5 nm. For D ions the displacement damage for W ~ 0.20 dpa at 8 nm and Ta ~ 0.175 dpa at 7 nm. The mean implantation depth is same for W and Ta, i.e. for He ions ~ 40 nm and D ions ~ 70 nm. From these results, we conclude that retention of D is high than He ions, but damage is low for Ta as compared to W. Further investigation still in progress regarding W and T.Keywords: helium and deuterium ion impact, plasma facing components, SRIM simulation, tungsten, tantalum
Procedia PDF Downloads 131260 Understanding Chromosome Movement in Starfish Oocytes
Authors: Bryony Davies
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Many cell and tissue culture practices ignore the effects of gravity on cell biology, and little is known about how cell components may move in response to gravitational forces. Starfish oocytes provide an excellent model for interrogating the movement of cell components due to their unusually large size, ease of handling, and high transparency. Chromosomes from starfish oocytes can be visualised by microinjection of the histone-H2B-mCherry plasmid into the oocytes. The movement of the chromosomes can then be tracked by live-cell fluorescence microscopy. The results from experiments using these methods suggest that there is a replicable downward movement of centrally located chromosomes at a median velocity of 0.39 μm/min. Chromosomes nearer the nuclear boundary showed more restricted movement. Chromosome density and shape could also be altered by microinjection of restriction enzymes, primarily Alu1, before imaging. This was found to alter the speed of chromosome movement, with chromosomes from Alu1-injected nuclei showing a median downward velocity of 0.60 μm/min. Overall, these results suggest that there is a non-negligible movement of chromosomes in response to gravitational forces and that this movement can be altered by enzyme activity. Future directions based on these results could interrogate if this observed downward movement extends to other cell components and to other cell types. Additionally, it may be important to understand whether gravitational orientation and vertical positioning of cell components alter cell behaviour. The findings here may have implications for current cell culture practices, which do not replicate cell orientations or external forces experienced in vivo. It is possible that a failure to account for gravitational forces in 2D cell culture alters experimental results and the accuracy of conclusions drawn from them. Understanding possible behavioural changes in cells due to the effects of gravity would therefore be beneficial.Keywords: starfish, oocytes, live-cell imaging, microinjection, chromosome dynamics
Procedia PDF Downloads 104259 Economic Evaluation of Varying Scenarios to Fulfill the Regional Electricity Demand in Pakistan
Authors: Muhammad Shahid, Kafait Ullah, Kashif Imran, Arshad Mahmood, Maarten Arentsen
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Poor planning and governance in the power sector of Pakistan have generated several issues ranging from gradual reliance on thermal-based expensive energy mix, supply shortages, unrestricted demand, subsidization, inefficiencies at different levels of the value chain and resultantly, the circular debt. This situation in the power sector has also hampered the growth of allied economic sectors. This study uses the Long-range Energy Alternative Planning (LEAP) system for electricity modelling of Pakistan from the period of 2016 to 2040. The study has first time in Pakistan forecasted the electricity demand at the provincial level. At the supply side, five scenarios Business as Usual Scenario (BAUS), Coal Scenario (CS), Gas Scenario (GS), Nuclear Scenario (NS) and Renewable Scenario (RS) have been analyzed based on the techno-economic and environmental parameters. The study has also included environmental externality costs for evaluating the actual costs and benefits of different scenarios. Contrary to the expectations, RS has a lower output than even BAUS. The study has concluded that the generation from RS has five times lesser costs than BAUS, CS, and GS. NS can also be an alternative for the sustainable future of Pakistan. Generation from imported coal is not a good option, however, indigenous coal with clean coal technologies should be promoted. This paper proposes energy planners of the country to devise incentives for the utilization of indigenous energy resources including renewables on priority and then clean coal to reduce the energy crises of Pakistan.Keywords: economic evaluation, externality cost, penetration of renewable energy, regional electricity supply-demand planning
Procedia PDF Downloads 116258 Obesity and Physical Inactivity: Contributing Factors to Hypertension in Early Adults
Authors: Sadaf Ambreen, Ayesha Bibi, Sara Rafiq
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Hypertension is a medical condition in which blood pressure in the arteries is elevated than the normal, having systolic blood pressure more than 120mmHg and diastolic blood pressure more than 80 mmHg. It leads to health complications and increase the risk of diseases such as stroke, heart failure, heart attack, and even death. The aim of the current study was to evaluate nutritional status and activity level among hypertensive early adults in District Mardan Data was collected from the subjects of Public Hospital, Mardan Medical Complex, through questionnaire. A complete information about individual sociodemographic, anthropometry and health status were collected, and physical activity was assessed by using IPAQ questionnaire. A total of 150 individuals were included in the study, in which 90% were females, and 10% were males. Data was analyzed through SPSS Version 22. Majority of the study subjects, 88%, were married, 70% having nuclear living system, 43% were having elementary education, and 43% were working as laborer. Body mass index and waist circumference in female counterpart were found to be positively associated with hypertension and was found statistically significant P=<0.01. Results showed that majority of females were fall in hypertension crisis category with mild activity, and males were having hypertension stage 1 with moderate activity. Our study concluded that non-optimal nutritional status and physical inactivity resulted in elevated blood pressure in females, therefore, lifestyle change such as optimal nutritional status and physical activity may play key role in reducing risk of hypertension.Keywords: obesity/overwight, body mass index, waist circumference, early adulthood
Procedia PDF Downloads 148257 Synthesis and Anticancer Evaluation of Substituted 2-(3,4-Dimethoxyphenyl) Benzazoles
Authors: Cigdem Karaaslan, Yalcin Duydu, Aylin Ustundag, Can Ozgur Yalcın, Hakan Goker
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Benzazole nucleus is found in the structure of many compounds as anticancer agents. Bendamustine (Alkylating agent), Nocodazole (Mitotic inhibitor), Veliparib (PARP inhibitor), Glasdegib (SMO inhibitor) are clinically used as anticancer therapeutics which bearing benzimidazole moiety. Based on the principle of bioisosterism in the present work, 23 compounds belonging to 2-(3,4-dimethoxy-phenyl) benzazoles and imidazopyridine series were synthesized and evaluated for their anticancer activities. N-(5-Chloro-2-hydroxyphenyl)-3,4-dimethoxybenzamide, was obtained by the amidation of 2-hydroxy-5-chloroaniline with 3,4-dimethoxybenzoic acid by using 1,1'-carbonyldiimidazole. Cyclization of benzamide derivative to benzoxazole, was achieved by p-toluenesulfonic acid. Other 1H-benz (or pyrido) azoles were prepared by the reaction between 2-aminothiophenol, o-phenylenediamine, o-pyridinediamine with sodium metabisulfite adduct of 3,4-dimethoxybenzaldehyde. The NMR assignments of the dimethoxy groups were established by the Nuclear Overhauser Effect Spectroscopy. A compound named, 5(4),7(6)-Dichloro-2-(3,4-dimethoxy) phenyl-1H-benzimidazole, bearing two chlorine atoms at the 5(4) and 7(6) positions of the benzene moiety of benzimidazole was found the most potent analogue, against A549 cells with the GI50 value of 1.5 µg/mL. In addition, 2-(3,4-Dimethoxyphenyl)-5,6-dimethyl-1H-benzimi-dazole showed remarkable cell growth inhibition against MCF-7 and HeLa cells with the GI₅₀ values of 7 and 5.5 µg/mL, respectively. It could be concluded that introduction of di-chloro atoms at the phenyl ring of 2-(3,4-dimethoxyphenyl)-1H-benzimidazoles increase significant cytotoxicity to selected human tumor cell lines in comparison to other all benzazoles synthesized in this study. Unsubstituted 2-(3,4-dimethoxyphenyl) imidazopyridines also gave the good inhibitory profile against A549 and HeLa cells.Keywords: 3, 4-Dimethoxyphenyl, 1H-benzimidazole, benzazole, imidazopyridine
Procedia PDF Downloads 122256 World Peace and Conflict Resolution: A Solution from a Buddhist Point of View
Authors: Samitharathana R. Wadigala
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The peace will not be established until the self-consciousness would reveal in the human beings. In this nuclear age, the establishment of a lasting peace on the earth represents the primary condition for the preservation of human civilization and survival of human beings. Nothing perhaps is so important and indispensable as the achievement and maintenance of peace in the modern world today. Peace in today’s world implies much more than the mere absence of war and violence. In the interdependent world of today the United Nations needs to be representative of the modern world and democratic in its functioning because it came into existence to save the generations from the scourge of war and conflict. Buddhism is the religion of peaceful co-existence and philosophy of enlightenment. Violence and conflict from the perspective of the Buddhist theory of interdependent origination (Paṭiccasamuppāda) are same with everything else in the world a product of causes and conditions. Buddhism is totally compatible with the congenial and peaceful global order. The canonical literature, doctrines, and philosophy of Buddhism are the best suited for inter-faith dialogue, harmony, and universal peace. Even today Buddhism can resurrect the universal brotherhood, peaceful co-existence and harmonious surroundings in the comity of nations. With its increasing vitality in regions around the world, many people today turn to Buddhism for relief and guidance at the time when peace seems to be a deferred dream more than ever. From a Buddhist point of view the roots of all unwholesome actions (Conflict) i. e. greed, hatred and delusion are viewed as the root cause of all human conflicts. Conflict often emanates from attachment to material things: pleasures, property, territory, wealth, economic dominance or political superiority. Buddhism has some particularly rich resources for deployment in dissolving conflict. Buddhism addresses the Buddhist perspective on the causes of conflict and ways to resolve conflict to realize world peace. The world has enough to satisfy every body’s needs but not every body’s greed.Keywords: Buddhism, conflict-violence, peace, self-consciousness
Procedia PDF Downloads 208255 Rice Serine/Threonine Kinase 1 Is Required for the Stimulation of OsNug2 GTPase Activity
Authors: Jae Bok Heo, Yun Mi Lee, Hee Rang Yun
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Several GTPases are required for ribosome biogenesis and assembly. We recently characterized rice (Oryza sativa) nuclear/nucleolar GTPase 2 (OsNug2), belonging to the YlqF/YawG family of GTPases, as playing a role in pre-60S ribosomal subunit maturation. To investigate the potential factors involved in regulating the function of OsNug2, yeast two-hybrid screens were carried out using OsNug2 as bait. Rice serine/threonine kinase 1 (OsSTK1) was identified as a potential interacting protein candidate. In vitro pull down and bimolecular fluorescence complementation assays confirmed the interaction between OsNug2 and OsSTK1, and like green fluorescent protein-tagged OsNug2, green fluorescent protein-tagged OsSTK1 was targeted to the nucleus of Arabidopsis protoplasts. OsSTK1 was not found to affect the GTP-binding activity of OsNug2; however, when recombinant OsSTK1 was included in OsNug2 assay reaction mixtures, OsSTK1 increased the GTPase activity of OsNug2. To test whether OsSTK1 phosphorylates OsNug2 in vitro, a kinase assay was performed. OsSTK1 was found to have weak autophosphorylation activity and strongly phosphorylated serine 209 of OsNug2. Yeast complementation testing resulted in a GAL::OsNug2(S209N) mutant-harboring yeast strain exhibiting a growth-defective phenotype on galactose medium at 39°C, divergent from that of a yeast strain harboring GAL::OsNug2. The intrinsic GTPase activity of mutant OsNug2(S209N) was found to be similar to that of OsNug2, was not fully enhanced upon weak binding of OsSTK1. Our findings reported here indicate that OsSTK1 functions as a positive regulator protein of OsNug2 by enhancing the GTPase activity of OsNug2, and that the phosphorylation of serine 209 of OsNug2 is essential for the complete function of OsNug2 in ribosome biogenesis.Keywords: OsSTK1, OsNug2, GTPase activity, GTP binding activity, phosphorylation
Procedia PDF Downloads 371254 Acanthopanax koreanum and Major Ingredient, Impressic Acid, Possess Matrix Metalloproteinase-13 Down-Regulating Capacity and Protect Cartilage Destruction
Authors: Hyun Lim, Dong Sook Min, Han Eul Yun, Kil Tae Kim, Ya Nan Sun, Young Ho Kim, Hyun Pyo Kim
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Matrix metalloproteinase (MMP)-13 has an important role for degrading cartilage materials under inflammatory conditions such as arthritis. Since the 70% ethanol extract of Acanthopanax koreanum inhibited MMP-13 expression in IL-1β-treated human chondrocyte cell line, SW1353, two major constituents including acanthoic acid and impressic acid were initially isolated from the same plant materials and their MMP-13 down-regulating capacity was examined. In IL-1β-treated SW1353 cells, acanthoic acid and impressic acid significantly and concentration-dependently inhibited MMP-13 expression at 10 – 100 μM and 0.5 – 10 μM, respectively. The potent one, impressic acid, was found to inhibit MMP-13 expression by blocking the phosphorylation of signal transducer and activator of transcription-1/-2 (STAT-1/-2) and activation of c-Jun and c-Fos among cellular signaling pathway involved, but did not affect the activation of mitogen-activated protein kinases (MAPKs) and nuclear transcription factor-κB (NF-κB). Further, impressic acid was also found to inhibit the expression of MMP-13 mRNA (47.7% inhibition at 10 μM), the glycosaminoglycan release (42.2% reduction at 10 μM) and proteoglycan loss in IL-1-treated rabbit cartilage explants culture. For a further study, 21 impressic acid derivatives were isolated from the same plant materials and their suppressive activities against MMP-13 expression were examined. Among the derivatives, 3α-hydroxy-lup-20(29)-en-23-oxo,28-oic acid, (20R)-3α-hydroxy-29-dimethoxylupan-23,28-dioic acid, acankoreoside F and acantrifoside A clearly down-regulated MMP-13 expression, but impressic acid being most potent. All these results suggest that impressic acid, 3α-hydroxy-lup-20(29)-en-23-oxo,28-oic acid, (20R)-3α-hydroxy-29-dimethoxylupan-23,28-dioic acid, acankoreoside F, acantrifoside A and A. koreanum may have a potential for therapeutic agents to prevent cartilage degradation possibly by inhibiting matrix protein degradation.Keywords: acanthoic acid, Acanthopanax koreanum, cartilage, impressic acid, matrix metalloproteinase
Procedia PDF Downloads 361253 Analysis of the Behavior of the Structure Under Internal Anfo Explosion
Authors: Seung-Min Ko, Seung-Jai Choi, Gun Jung, Jang-Ho Jay Kim
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Although extensive explosion-related research has been performed in the past several decades, almost no research has focused on internal blasts. However, internal blast research is needed to understand about the behavior of a containment structure or building under internal blast loading, as in the case of the Chornobyl and Fukushima nuclear accidents. Therefore, the internal blast study concentrated on RC and PSC structures is performed. The test data obtained from reinforced concrete (RC) and prestressed concrete (PSC) tubular structures applied with an internal explosion using ammonium nitrate/fuel oil (ANFO) charge are used to assess their deformation resistance and ultimate failure load based on the structural stiffness change under various charge weight. For the internal blast charge weight, ANFO explosive charge weights of 15.88, 20.41, 22.68 and 24.95 kg were selected for the RC tubular structures, and 22.68, 24.95, 27.22, 29.48, and 31.75 kg were selected for PSC tubular structures, which were detonated at the center of cross section at the mid-span with a standoff distance of 1,000mm to the inner wall surface. Then, the test data were used to predict the internal charge weight required to fail a real scale reinforced concrete containment vessels (RCCV) and prestressed concrete containment vessel (PCCV). Then, the analytical results based on the experimental data were derived using the simple assumptions of the models, and another approach using the stiffness, deformation and explosion weight relationship was used to formulate a general method for analyzing internal blasted tubular structures. A model of the internal explosion of a steel tube was used as an example for validation. The proposed method can be used generically, using factors according to the material characteristics of the target structures. The results of the study are discussed in detail in the paper.Keywords: internal blast, reinforced concrete, RCCV, PCCV, stiffness, blast safety
Procedia PDF Downloads 79252 Comparison of FNTD and OSLD Detectors' Responses to Light Ion Beams Using Monte Carlo Simulations and Exprimental Data
Authors: M. R. Akbari, H. Yousefnia, A. Ghasemi
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Al2O3:C,Mg fluorescent nuclear track detector (FNTD) and Al2O3:C optically stimulated luminescence detector (OSLD) are becoming two of the applied detectors in ion dosimetry. Therefore, the response of these detectors to hadron beams is highly of interest in radiation therapy (RT) using ion beams. In this study, these detectors' responses to proton and Helium-4 ion beams were compared using Monte Carlo simulations. The calculated data for proton beams were compared with Markus ionization chamber (IC) measurement (in water phantom) from M.D. Anderson proton therapy center. Monte Carlo simulations were performed via the FLUKA code (version 2011.2-17). The detectors were modeled in cylindrical shape at various depths of the water phantom without shading each other for obtaining relative depth dose in the phantom. Mono-energetic parallel ion beams in different incident energies (100 MeV/n to 250 MeV/n) were collided perpendicularly on the phantom surface. For proton beams, the results showed that the simulated detectors have over response relative to IC measurements in water phantom. In all cases, there were good agreements between simulated ion ranges in the water with calculated and experimental results reported by the literature. For proton, maximum peak to entrance dose ratio in the simulated water phantom was 4.3 compared with about 3 obtained from IC measurements. For He-4 ion beams, maximum peak to entrance ratio calculated by both detectors was less than 3.6 in all energies. Generally, it can be said that FLUKA is a good tool to calculate Al2O3:C,Mg FNTD and Al2O3:C OSLD detectors responses to therapeutic proton and He-4 ion beams. It can also calculate proton and He-4 ion ranges with a reasonable accuracy.Keywords: comparison, FNTD and OSLD detectors response, light ion beams, Monte Carlo simulations
Procedia PDF Downloads 343251 Numerical Analysis of Laminar Reflux Condensation from Gas-Vapour Mixtures in Vertical Parallel Plate Channels
Authors: Foad Hassaninejadafarahani, Scott Ormiston
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Reflux condensation occurs in a vertical channels and tubes when there is an upward core flow of vapor (or gas-vapor mixture) and a downward flow of the liquid film. The understanding of this condensation configuration is crucial in the design of reflux condensers, distillation columns, and in loss-of-coolant safety analyses in nuclear power plant steam generators. The unique feature of this flow is the upward flow of the vapor-gas mixture (or pure vapor) that retards the liquid flow via shear at the liquid-mixture interface. The present model solves the full, elliptic governing equations in both the film and the gas-vapor core flow. The computational mesh is non-orthogonal and adapts dynamically the phase interface, thus produces sharp and accurate interface. Shear forces and heat and mass transfer at the interface are accounted for fundamentally. This modeling is a big step ahead of current capabilities by removing the limitations of previous reflux condensation models which inherently cannot account for the detailed local balances of shear, mass, and heat transfer at the interface. Discretisation has been done based on a finite volume method and a co-located variable storage scheme. An in-house computer code was developed to implement the numerical solution scheme. Detailed results are presented for laminar reflux condensation from steam-air mixtures flowing in vertical parallel plate channels. The results include velocity and pressure profiles, as well as axial variations of film thickness, Nusselt number and interface gas mass fraction.Keywords: Reflux, Condensation, CFD-Two Phase, Nusselt number
Procedia PDF Downloads 363250 Synergistic Effect of Curcumin and Insulin on GLUT4 Translocation in C2C12 Cell
Authors: Javad Mohiti-Ardekani, Shabodin Asadii, Ali Moradi
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Introduction: Curcumin, the yellow pigment in turmeric, has been shown as an anti-diabetic agent for centuries but only in recent few years, its mechanism of action has been under investigation. Some studies showed that curcumin might exert its anti-diabetic effect via increasing glucose transporter isotype-4 (GLUT4) gene and glycoprotein contents in cells. To investigate this possibility, we investigate the effects of extract and commercial curcumin with and without insulin on GLUT4 translocation from intracellular compartments of nuclear or endoplasmic reticulum membranes (N/ER) into the cytoplasmic membrane (CM). Methods and Material: C2C12 myoblastic cell line were seeded in DMEM plus 20 % FBS and differentiated to myotubes using 2 % horse serum. After myotubes formation, 40 µmolar Extract and Commercial curcumin, with or without insulin as intervention, and as control 1 % DMSO were added for 3 h. Cells were washed and homogenized followed by ultracentrifuge fractionation, protein separation by SDS-PAGE and GLUT4 detection using semi-quantitative Western blotting. Data analysis was done by two independent samples t-test for comparison of mean ± SD of GLUT4 percent in categories. GLUT4 contents were higher in CM groups curcumin and curcumin with insulin in comparison to 1 % DMSO-treated myotubes control group. Results: As our results have shown extract and commercial curcumin induces GLUT4 translocation from intra-cell into cell surface. The results have also shown synergic effect of curcumin on translocation of GLUT4 from intra-cell into cell surface in the presence of 100 nm insulin. Discussion: We conclude that curcumin may be a choice of type-2 diabetes mellitus treatment because its extract and commercial enhances GLUT4 contents in CM where it facilitates glucose entrance into the cell. However, it is necessary to trace the signaling pathways which are activated by curcumin.Keywords: Curcumin, insulin, Diabetes type-2, GLUT4
Procedia PDF Downloads 243249 Assessment of Cardioprotective Effect of Deferiprone on Doxorubicin-Induced Cardiac Toxicity in a Rat Model
Authors: Sadaf Kalhori
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Introduction: Doxorubicin (DOX)-induced cardiotoxicity is widely known as the most severe complication of anthracycline-based chemotherapy in patients with cancer. It is unknown whether Deferiprone (DFP), could reduce the severity of DOX-induced cardiotoxicity by inhibiting free radical reactions. Thus, this study was performed to assess the protective effect of Deferiprone on DOX-induced cardiotoxicity in a rat model. Methods: The rats were divided into five groups. Group one was a control group. Group 2 was DOX (2 mg/kg/day, every other day for 12 days), and Group three to five which receiving DOX as in group 2 and DFP 75,100 and 150 mg/kg/day, for 19 days, respectively. DFP was starting 5 days prior to the first DOX injection and two days after the last DOX injection throughout the study. Electrocardiographic and hemodynamic studies, along with histopathological examination, were conducted. In addition, serum sample was taken and total cholesterol, Malone dialdehyde, triglyceride, albumin, AST, ALT, total protein, lactate dehydrogenase, total anti-oxidant and creatine kinase were assessed. Result: Our results showed the normal structure of endocardial, myocardial and pericardial in the control group. Pathologic data such as edema, hyperemia, bleeding, endocarditis, myocarditis and pericarditis, hyaline degeneration, cardiomyocyte necrosis, myofilament degeneration and nuclear chromatin changes were assessed in all groups. In the DOX group, all pathologic data was seen with mean grade of 2±1.25. In the DFP group with a dose of 75 and 100 mg, the mean grade was 1.41± 0.31 and 1±.23, respectively. In DFP group with a dose of 150, the pathologic data showed a milder change in comparison with other groups with e mean grade of 0.45 ±0.19. Most pathologic data in DFP groups showed significant changes in comparison with the DOX group (p < 0.001). Discussion: The results also showed that DFP treatment significantly improved DOX-induced heart damage, structural changes in the myocardium, and ventricular function. Our data confirm that DFP is protective against cardiovascular-related disorders induced by DOX. Clinical studies are needed to be involved to examine these findings in humans.Keywords: cardiomyopathy, deferiprone, doxorubicin, rat
Procedia PDF Downloads 142248 Experimental Study of Hydrogen and Water Vapor Extraction from Helium with Zeolite Membranes for Tritium Processes
Authors: Rodrigo Antunes, Olga Borisevich, David Demange
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The Tritium Laboratory Karlsruhe (TLK) has identified zeolite membranes as most promising for tritium processes in the future fusion reactors. Tritium diluted in purge gases or gaseous effluents, and present in both molecular and oxidized forms, can be pre-concentrated by a stage of zeolite membranes followed by a main downstream recovery stage (e.g., catalytic membrane reactor). Since 2011 several membrane zeolite samples have been tested to measure the membrane performances in the separation of hydrogen and water vapor from helium streams. These experiments were carried out in the ZIMT (Zeolite Inorganic Membranes for Tritium) facility where mass spectrometry and cold traps were used to measure the membranes’ performances. The membranes were tested at temperatures ranging from 25 °C up to 130 °C, at feed pressures between 1 and 3 bar, and typical feed flows of 2 l/min. During this experimental campaign, several zeolite-type membranes were studied: a hollow-fiber MFI nanocomposite membrane purchased from IRCELYON (France), and tubular MFI-ZSM5, NaA and H-SOD membranes purchased from Institute for Ceramic Technologies and Systems (IKTS, Germany). Among these membranes, only the MFI-based showed relevant performances for the H2/He separation, with rather high permeances (~0.5 – 0.7 μmol/sm2Pa for H2 at 25 °C for MFI-ZSM5), however with a limited ideal selectivity of around 2 for H2/He regardless of the feed concentration. Both MFI and NaA showed higher separation performances when water vapor was used instead; for example, at 30 °C, the separation factor for MFI-ZSM5 is approximately 10 and 38 for 0.2% and 10% H2O/He, respectively. The H-SOD evidenced to be considerably defective and therefore not considered for further experiments. In this contribution, a comprehensive analysis of the experimental methods and results obtained for the separation performance of different zeolite membranes during the past four years in inactive environment is given. These results are encouraging for the experimental campaign with molecular and oxidized tritium that will follow in 2017.Keywords: gas separation, nuclear fusion, tritium processes, zeolite membranes
Procedia PDF Downloads 248247 Comparative in silico and in vitro Study of N-(1-Methyl-2-Oxo-2-N-Methyl Anilino-Ethyl) Benzene Sulfonamide and Its Analogues as an Anticancer Agent
Authors: Pamita Awasthi, Kirna, Shilpa Dogra, Manu Vatsal, Ritu Barthwal
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Doxorubicin, also known as adriamycin, is an anthracycline class of drug used in cancer chemotherapy. It is used in the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute leukemias, breast cancer, lung cancer, endometrium cancer and ovary cancers. It functions via intercalating DNA and ultimately killing cancer cells. The major side effects of doxorubicin are hair loss, myelosuppression, nausea & vomiting, oesophagitis, diarrhoea, heart damage and liver dysfunction. The minor modifications in the structure of compound exhibit large variation in the biological activity, has prompted us to carry out the synthesis of sulfonamide derivatives. Sulfonamide is an important feature with broad spectrum of biological activity such as antiviral, antifungal, diuretics, anti-inflammatory, antibacterial and anticancer activities. Structure of the synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilino-ethyl)benzene sulfonamide confirmed by proton nuclear magnetic resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools to assure the position of all protons and hence stereochemistry of the molecule. Further we have reported the binding potential of synthesized sulfonamide analogues in comparison to doxorubicin drug using Auto Dock 4.2 software. Computational binding energy (B.E.) and inhibitory constant (Ki) has been evaluated for the synthesized compound in comparison of doxorubicin against Poly (dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences. The in vitro cytotoxic study against human breast cancer cell lines confirms the better anticancer activity of the synthesized compound over currently in use anticancer drug doxorubicin. The IC50 value of the synthesized compound is 7.12 µM where as for doxorubicin is 7.2 µ.Keywords: Doxorubicin, auto dock, in silco, in vitro
Procedia PDF Downloads 419246 Wind Energy Status in Turkey
Authors: Mustafa Engin Başoğlu, Bekir Çakir
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Since large part of electricity generation is provided by using fossil based resources, energy is an important agenda for countries. Depletion of fossil resources, increasing awareness of climate change and global warming concerns are the major reasons for turning to alternative energy resources. Solar, wind and hydropower energy are the main renewable energy sources. Among of them, wind energy is promising for Turkey whose installed power capacity increases approximately eight times between 2008 - seventh month of 2014. Signing of Kyoto Protocol can be accepted as a milestone for Turkey's energy policy. Turkish government has announced 2023 Vision (2023 targets) in 2010-2014 Strategic Plan prepared by Ministry of Energy and Natural Resources (MENR). 2023 Energy targets can be summarized as follows: Share of renewable energy sources in electricity generation is 30% of total electricity generation by 2023. Installed capacity of wind energy will be 20 GW by 2023. Other renewable energy sources such as solar, hydropower and geothermal are encouraged with new incentive mechanisms. Share of nuclear power plants in electricity generation will be 10% of total electricity generation by 2023. Dependence on foreign energy is reduced for sustainability and energy security. As of seventh month of 2014, total installed capacity of wind power plants is 3.42 GW and a lot of wind power plants are under construction with capacity 1.16 GW. Turkish government also encourages the locally manufactured equipments. MILRES is an important project aimed to promote the use of renewable sources in electricity generation. A 500 kW wind turbine will be produced in the first phase of project. Then 2.5 MW wind turbine will be manufactured domestically within this projectKeywords: wind energy, wind speed, 2023 vision, MILRES, wind energy potential in TURKEY
Procedia PDF Downloads 545245 Targeting TACI Signaling Enhances Immune Function and Halts Chronic Lymphocytic Leukemia Progression
Authors: Yong H Sheng, Beatriz Garcillán, Eden Whitlock, Yukli Freedman, SiLing Yang, M Arifur Rahman, Nicholas Weber, Fabienne Mackay
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Chronic lymphocytic leukemia (CLL) is closely associated with immune dysfunction, yet the mechanisms underlying this immune deficiency remain poorly understood. Transmembrane Activator and CAML Interactor (TACI), a receptor known for its role in IL-10 regulation and autoimmunity, to the best of our knowledge has not been investigated in the context of anti-tumor immunity or its impact on CLL progression. This study addresses the gap by exploring the role of TACI in regulating CLL cells within the tumor microenvironment and its broader effects on disease progression and immune competence. We utilized the Eµ-TCL1 mouse model to generate CLL mice deficient in TACI and examined the consequences of TACI loss in adoptive transfer models over a five-week period. Comprehensive transcriptomic analysis, including RNA sequencing and microarray, was employed to determine TACI’s influence on the CLL gene expression profile. Additionally, we studied TACI’s direct role in CLL cell migration and immune modulation using patient-derived CLL cells in culture and Patient-Derived Xenograph (PDX) models. Our findings demonstrate that TACI signaling plays a pivotal role in promoting CLL progression and immune suppression. Loss of TACI signaling significantly inhibited CLL development and enhanced immune functionality. When TACI+/+ or TACI-/- TCL1 CLL cells were transferred into wild-type recipient mice, those receiving TACI-deficient cells showed reduced disease progression and lower incidence of CLL. Mice with TACI-/- CLL cells exhibited normalized serum levels of pro-inflammatory cytokines IL-6 and IL-10, restored proportions of T-cell subsets, and improved immune compartment function compared to counterparts with TACI+/+ CLL cells. Mechanistically, TACI-deficient CLL cells expressed significantly lower levels of IL-10, TNF, and inhibitory receptors such as PD-L1 and PD-L2. These cells also display restored circulating immunoglobulin levels and responses to T cell-dependent antigens, highlighting a recovery of immune competence. Further mechanistic studies revealed that TACI signaling drives CLL cell migration and homing to the spleen, where these cells actively establish an immunosuppressive microenvironment that supports immune evasion and tumor growth. Patient-derived CLL cells and PDX models confirmed TACI’s direct role in enhancing CLL cell migration and fostering immune suppression, emphasizing its critical function in the tumor microenvironment. By disrupting TACI signaling, we observed a reduction in CLL-associated immune suppression and tumor progression, offering a promising therapeutic avenue. This study establishes, for the first time, that targeting TACI disrupts key mechanisms underlying CLL progression while preserving vital immune functions. Unlike existing treatments that often impair immunity and lead to infection-related complications, TACI inhibition offers the dual benefit of controlling disease and maintaining immune homeostasis. These findings provide a strong rationale for developing therapeutic strategies that inhibit TACI as a means to improve outcomes in CLL patients. Beyond its implications for CLL, this research underscores the broader importance of TACI in regulating immune-tumor interactions, paving the way for future studies into its role in other malignancies.Keywords: chronic lymphocytic leukemia, TACI, IL-10, immune suppression
Procedia PDF Downloads 1244 Applying Resilience Engineering to improve Safety Management in a Construction Site: Design and Validation of a Questionnaire
Authors: M. C. Pardo-Ferreira, J. C. Rubio-Romero, M. Martínez-Rojas
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Resilience Engineering is a new paradigm of safety management that proposes to change the way of managing the safety to focus on the things that go well instead of the things that go wrong. Many complex and high-risk sectors such as air traffic control, health care, nuclear power plants, railways or emergencies, have applied this new vision of safety and have obtained very positive results. In the construction sector, safety management continues to be a problem as indicated by the statistics of occupational injuries worldwide. Therefore, it is important to improve safety management in this sector. For this reason, it is proposed to apply Resilience Engineering to the construction sector. The Construction Phase Health and Safety Plan emerges as a key element for the planning of safety management. One of the key tools of Resilience Engineering is the Resilience Assessment Grid that allows measuring the four essential abilities (respond, monitor, learn and anticipate) for resilient performance. The purpose of this paper is to develop a questionnaire based on the Resilience Assessment Grid, specifically on the ability to learn, to assess whether a Construction Phase Health and Safety Plans helps companies in a construction site to implement this ability. The research process was divided into four stages: (i) initial design of a questionnaire, (ii) validation of the content of the questionnaire, (iii) redesign of the questionnaire and (iii) application of the Delphi method. The questionnaire obtained could be used as a tool to help construction companies to evolve from Safety-I to Safety-II. In this way, companies could begin to develop the ability to learn, which will serve as a basis for the development of the other abilities necessary for resilient performance. The following steps in this research are intended to develop other questions that allow evaluating the rest of abilities for resilient performance such as monitoring, learning and anticipating.Keywords: resilience engineering, construction sector, resilience assessment grid, construction phase health and safety plan
Procedia PDF Downloads 137243 Effect of Temperature on Corrosion Fatigue Cracking Behavior of Inconel 625 in Steam and Supercritical Water
Authors: Hasan Izhar Khan, Naiqiang Zhang, Hong Xu, Zhongliang Zhu, Dongfang Jiang
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Inconel 625 is a nickel-based alloy having outstanding corrosion resistance and developed for use at service temperatures ranging from cryogenic to 980°C. It got a wide range of applications in nuclear, petrochemical, chemical, marine, aeronautical, and aerospace industries. Currently, it is one of the candidate materials to be used as a structural material in ultra-supercritical (USC) power plants. In the high-temperature corrosive medium environment, metallic materials are susceptible to corrosion fatigue (CF). CF is an interaction between cyclic stress and corrosive medium environment that acts on a susceptible material and results in initiation and propagation of cracks. For the application of Inconel 625 as a structural material in USC power plants, CF behavior must be evaluated in steam and supercritical water (SCW) environment. Fatigue crack growth rate (FCGR) curves obtained from CF experiments are required to predict residual life of metallic materials used in power plants. In this study, FCGR tests of Inconel 625 were obtained by using compact tension specimen at 550-650 °C in steam (8 MPa) and SCW (25 MPa). The dissolved oxygen level was kept constant at 8000 ppb for the test conducted in steam and SCW. The tests were performed under sine wave loading waveform, 1 Hz loading frequency, stress ratio of 0.6 and maximum stress intensity factor of 32 MPa√m. Crack growth rate (CGR) was detected by using direct current potential drop technique. Results showed that CGR increased with an increase in temperature in the tested environmental conditions. The mechanism concerning the influence of temperature on FCGR are further discussed.Keywords: corrosion fatigue, crack growth rate, nickel-based alloy, temperature
Procedia PDF Downloads 131242 Apoptosis Inducing Potential of Onosma Bracteata Wall. in Mg-63 Human Osteosarcoma Cells via cdk2/Cyclin E Pathway
Authors: Ajay Kumar, Satwinderjeet Kaur
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Onosma bracteata Wall. (Boraginaceae), is known to be a medicinal plant, useful in the treatment of body swellings, abdominal pain and urinary calculi, etc. The present study focused on the radical scavenging and cancer growth inhibitory properties of isolates from O. bracteata. Obea fraction demonstrated noticeable free radical scavenging ability along with antiproliferative activity in human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung cancer A549 cell lines using MTT assay with GI50 values of 88.56, 101.61 and 112.7 μg/ml, respectively. The scanning electron and confocal microscopy studies showed morphological alterations including nuclear condensation and formation of apoptotic bodies in osteosarcoma MG-63 cells. Obea fraction in osteosarcoma MG-63 cells augmented the reactive oxygen species (ROS) level and decreased the mitochondrial membrane potential. Flow cytometry analysis revealed the Obea treated cells to be arrested in the G0/G1 phase in a dose dependent manner supported by the observed increase in the early apoptotic cell population. Western blotting analysis showed that the expression of p-NF-kB, COX-2, p-Akt, and Bcl-xL decreased whereas, the expression of GSK-3β, p53, caspase-3 and caspase-9 proteins increased. The downregulation of Bcl-2, Cyclin E, CDK2 and mortalin gene expression and upregulation of p53 genes was unfolded in RT-qPCR studies. The presence of catechin, kaempferol, Onosmin A and epicatechin, as revealed in high-performance liquid chromatography (HPLC) studies, contributes towards the chemopreventive potential of O. bracteata which can be tapped for chemotherapeutic use.Keywords: apoptosis, confocal microscopy, HPLC, mitochondria membrane potential, reactive oxygen species
Procedia PDF Downloads 136241 Beta-Carotene Attenuates Cognitive and Hepatic Impairment in Thioacetamide-Induced Rat Model of Hepatic Encephalopathy via Mitigation of MAPK/NF-κB Signaling Pathway
Authors: Marawan Abd Elbaset Mohamed, Hanan A. Ogaly, Rehab F. Abdel-Rahman, Ahmed-Farid O.A., Marwa S. Khattab, Reham M. Abd-Elsalam
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Liver fibrosis is a severe worldwide health concern due to various chronic liver disorders. Hepatic encephalopathy (HE) is one of its most common complications affecting liver and brain cognitive function. Beta-Carotene (B-Car) is an organic, strongly colored red-orange pigment abundant in fungi, plants, and fruits. The study attempted to know B-Car neuroprotective potential against thioacetamide (TAA)-induced neurotoxicity and cognitive decline in HE in rats. Hepatic encephalopathy was induced by TAA (100 mg/kg, i.p.) three times per week for two weeks. B-Car was given orally (10 or 20 mg/kg) daily for two weeks after TAA injections. Organ body weight ratio, Serum transaminase activities, liver’s antioxidant parameters, ammonia, and liver histopathology were assessed. Also, the brain’s mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), antioxidant parameters, adenosine triphosphate (ATP), adenosine monophosphate (AMP), norepinephrine (NE), dopamine (DA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) cAMP response element-binding protein (CREB) expression and B-cell lymphoma 2 (Bcl-2) expression were measured. The brain’s cognitive functions (Spontaneous locomotor activity, Rotarod performance test, Object recognition test) were assessed. B-Car prevented alteration of the brain’s cognitive function in a dose-dependent manner. The histopathological outcomes supported these biochemical evidences. Based on these results, it could be established that B-Car could be assigned to treat the brain’s neurotoxicity consequences of HE via downregualtion of MAPK/NF-κB signaling pathways.Keywords: beta-carotene, liver injury, MAPK, NF-κB, rat, thioacetamide
Procedia PDF Downloads 154240 Insights into Insect Vectors: Liberibacter Interactions
Authors: Murad Ghanim
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The citrus greening disease, also known as Huanglongbing, caused by the phloem-limited bacterium Candidatus Liberibacter asiaticus (CLas) has resulted in tremendous losses and the death of millions of citrus trees worldwide. CLas is transmitted by the Asian citrus psyllid (ACP) Diaphorina citri. The closely-related bacterium Candidatus Liberibacter solanacearum (CLso), which is associated with vegetative disorders in carrots and the zebra chips disease in potatoes, is transmitted by other psyllid species including Bactericera trigonica in carrots and B. ckockerelli in potatoes. Chemical sprays are currently the prevailing method for managing these diseases for limiting psyllid populations; however, they are limited in their effectiveness. A promising approach to prevent the transmission of these pathogens is to interfere with the vector-pathogen interactions, but our understanding of these processes is very limited. CLas induces changes in the nuclear architecture in the midgut of ACP and activates programmed cell death (apoptosis) in this organ. Strikingly, CLso displayed an opposite effect in the gut of B. trigonica, showing limited apoptosis, but widespread necrosis. Electron and fluorescent microscopy further showed that CLas induced the formation of Endoplasmic reticulum (ER) inclusion- and replication-like bodies, in which it increases and multiplies. ER involvement in bacterial replication is hypothesized to be the first stage of an immune response leading to the apoptotic and necrotic responses. ER exploitation and the subsequent events that lead to these cellular and stress responses might activate a cascade of molecular responses ending up with apoptosis and necrosis. Understanding the molecular interactions that underlay the necrotic/apoptotic responses to the bacteria will increase our knowledge of ACP-CLas, and BT-CLso interactions, and will set the foundation for developing novel, and efficient strategies to disturb these interactions and inhibit the transmission.Keywords: Liberibacter, psyllid, transmission, apoptosis, necrosis
Procedia PDF Downloads 146