Search results for: scale inhibitor
6299 Elucidation of Dynamics of Murine Double Minute 2 Shed Light on the Anti-cancer Drug Development
Authors: Nigar Kantarci Carsibasi
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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.Keywords: cancer, drug design, elastic network model, MDM2
Procedia PDF Downloads 1286298 Design of Organic Inhibitors from Quantum Chemistry
Authors: Rahma Tibigui, Ikram Hadj Said, Rachid Belkada, Dalila Hammoutene
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The vulnerability of industrial facilities is highly concerned with multiple risks from corrosion. The commonly adopted solution is based on the use of organic inhibitors, which are gradually being replaced by environmentally friendly organic inhibitors. In our work, we carried out a quantum chemical study based on the Density Functional Theory (DFT) method at the B3LYP/6-311G (d,p) level of theory. The inhibitory performance of a derivative of the tetrazole molecule has been investigated and reported as a carbon steel-friendly corrosion inhibitor in hydrochloric acid (HCl) medium. The relationship is likely to exist between the molecular structure of this compound as well as its various global reactivity descriptors, and its corrosion inhibition efficiency, which was examined and then discussed. The results show low values of ΔE, which represent strong adsorption of the inhibitor on the steel surface. Moreover, the flat adsorption orientation confirmed the great ability to donate (accept) electrons to (from) steel, fabricating an anchored barrier to prevent steel from corrosion.Keywords: eco-friendly, corrosion inhibitors, tetrazole, DFT
Procedia PDF Downloads 2306297 A Density Functional Theory Computational Study on the Inhibiting Action of Some Derivatives of 1,8-Bis(Benzylideneamino)Naphthalene against Aluminum Corrosion
Authors: Taher S. Ababneh, Taghreed M. A. Jazzazi, Tareq M. A. Alshboul
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The inhibiting action against aluminum corrosion by three derivatives of 1,8-bis (benzylideneamino) naphthalene (BN) Schiff base has been investigated by means of DFT quantum chemical calculations at the B3LYP/6-31G(d) level of theory. The derivatives (CBN, NBN and MBN) were prepared from the condensation reaction of 1,8-diaminonaphthalene with substituted benzaldehyde (4-CN, 3-NO₂ and 3,4-(OMe)₂, respectively). Calculations were conducted to study the adsorption of each Schiff base on aluminum surface to evaluate its potential as a corrosion inhibitor. The computational structural features and electronic properties of each derivative such as relative energies and energies of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) have been reported. Thermodynamic functions and quantum chemical parameters such as the hardness of the inhibitor, the softness and the electrophilicity index were calculated to determine the derivative of the highest inhibition efficiency.Keywords: corrosion, aluminum, DFT calculation, 1, 8-diaminonaphthalene, benzaldehyde
Procedia PDF Downloads 3466296 Delamination of Scale in a Fe Carbon Steel Surface by Effect of Interface Roughness and Oxide Scale Thickness
Authors: J. M. Lee, W. R. Noh, C. Y. Kim, M. G. Lee
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Delamination of oxide scale has been often discovered at the interface between Fe carbon steel and oxide scale. Among several mechanisms of this delamination behavior, the normal tensile stress to the substrate-scale interface has been described as one of the main factors. The stress distribution at the interface is also known to be affected by thermal expansion mismatch between substrate and oxide scale, creep behavior during cooling and the geometry of the interface. In this study, stress states near the interface in a Fe carbon steel with oxide scale have been investigated using FE simulations. The thermal and mechanical properties of oxide scales are indicated in literature and Fe carbon steel is measured using tensile testing machine. In particular, the normal and shear stress components developed at the interface during bending are investigated. Preliminary numerical sensitivity analyses are provided to explain the effects of the interface geometry and oxide thickness on the delamination behavior.Keywords: oxide scale, delamination, Fe analysis, roughness, thickness, stress state
Procedia PDF Downloads 3436295 Application of Response Surface Methodology to Optimize the Factor Influencing the Wax Deposition of Malaysian Crude Oil
Authors: Basem Elarbe, Ibrahim Elganidi, Norida Ridzuan, Norhyati Abdullah
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Wax deposition in production pipelines and transportation tubing from offshore to onshore is critical in the oil and gas industry due to low-temperature conditions. It may lead to a reduction in production, shut-in, plugging of pipelines and increased fluid viscosity. The most significant popular approach to solve this issue is by injection of a wax inhibitor into the channel. This research aims to determine the amount of wax deposition of Malaysian crude oil by estimating the effective parameters using (Design-Expert version 7.1.6) by response surface methodology (RSM) method. Important parameters affecting wax deposition such as cold finger temperature, inhibitor concentration and experimental duration were investigated. It can be concluded that SA-co-BA copolymer had a higher capability of reducing wax in different conditions where the minimum point of wax reduction was found at 300 rpm, 14℃, 1h, 1200 ppmThe amount of waxes collected for each parameter were 0.12g. RSM approach was applied using rotatable central composite design (CCD) to minimize the wax deposit amount. The regression model’s variance (ANOVA) results revealed that the R2 value of 0.9906, indicating that the model can be clarified 99.06% of the data variation, and just 0.94% of the total variation were not clarified by the model. Therefore, it indicated that the model is extremely significant, confirming a close agreement between the experimental and the predicted values. In addition, the result has shown that the amount of wax deposit decreased significantly with the increase of temperature and the concentration of poly (stearyl acrylate-co-behenyl acrylate) (SABA), which were set at 14°C and 1200 ppm, respectively. The amount of wax deposit was successfully reduced to the minimum value of 0.01 g after the optimization.Keywords: wax deposition, SABA inhibitor, RSM, operation factors
Procedia PDF Downloads 2846294 CP-96345 Rregulates Hydrogen Sulphide Induced TLR4 Signaling Pathway Adhesion Molecules in Caerulein Treated Pancreatic Acinar Cells
Authors: Ramasamy Tamizhselvi, Leema George, Madhav Bhatia
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We have earlier shown that mouse pancreatic acinar cells produce hydrogen sulfide (H2S) and play a role in the pathogenesis of acute pancreatitis. This study is to determine the effect of H2S on TLR4 mediated innate immune signaling in acute pancreatitis via substance P (SP). Male Swiss mice were treated with hourly intraperitoneal injection of caerulein (50μg/kg) for 10 hour. DL-propargylglycine (PAG) (100 mg/kg i.p.), an inhibitor of H2S formation was administered 1h after the induction of acute pancreatitis. Pancreatic acinar cells from male Swiss mice were incubated with or without caerulein (10–7 M for 60 min) and CP-96345 (NK1R inhibitor). To better understand the effect of H2S in inflammation, acinar cells were stimulated with caerulein after addition of H2S donor, NaHS. In addition, caerulein treated pancreatic acinar cells were pretreated with PAG (30 µM), for 1h. H2S inhibitor, PAG, eliminated TLR4, IRAK4, TRAF6 and NF-kB levels in an in vitro and in vivo model of caerulein-induced acute pancreatitis. PPTA gene deletion reduced TLR4, MyD88, IRAK4, TRAF6, adhesion molecules and NF-kB in caerulein treated pancreatic acinar cells whereas administration of NaHS resulted in further rise in TLR4 and NF-kB levels in caerulein treated pancreatic acinar cells. In addition, acini isolated from mice and treated with PPTA gene receptor NK1R antagonist CP96345 did not exhibit further increase in TLR4, IRAK4, TRAF6, adhesion molecules and NF-kB levels after NaHS pretreatment. The present findings show for the first time that in acute pancreatitis, H2S up-regulates TLR4 pathway and NF-kB via substance P.Keywords: preprotachykinin-A gene, H2S, TLR4, acute pancreatitis
Procedia PDF Downloads 2756293 Development of the ‘Teacher’s Counselling Competence Self-Efficacy Scale’
Authors: Riin Seema
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Guidance and counseling as a whole-school responsibility is a global trend. Counseling is a specific competence, that consist of cognitive, emotional, attitudinal, and behavioral components. To authors best knowledge, there are no self-assessment scales for teachers in the whole world to measure teachers’ counseling competency. In 2016 an Estonian scale on teachers counseling competence was developed during an Interdisciplinary Project at Tallinn University. The team consisted of 10 interdisciplinary students (psychology, nursery school, special and adult education) and their supervisor. In 2017 another international Interdisciplinary Project was carried out for adapting the scale in English for international students. Firstly, the Estonian scale was translated by 2 professional translators, and then a group of international Erasmus students (again from psychology, nursery school, special and adult education) selected the most suitable translation for the scale. The developed ‘Teacher’s Counselling Competence Self-Efficacy Scale’ measures teacher’s self-efficacy beliefs in their own competence to perform different counseling tasks (creating a counseling relationship, using different reflection techniques, etc.). The scale consists of 47 questions in a 5-point numeric scale. The scale is created based on counseling theory and scale development and validation theory. The scale has been used as a teaching and learning material for counseling courses by 174 Estonian and 10 international student teachers. After filling out the scale, the students also reflected on the scale and their own counseling competencies. The study showed that the scale is unidimensional and has an excellent Cronbach alpha coefficient. Student’s qualitative feedback on the scale has been very positive, as the scale supports their self-reflection. In conclusion, the developed ‘Teacher’s Counselling Competence Self-Efficacy Scale’ is a useful tool for supporting student teachers’ learning.Keywords: competency, counseling, self-efficacy, teacher students
Procedia PDF Downloads 1456292 Experimental Investigation of Fluid Dynamic Effects on Crystallisation Scale Growth and Suppression in Agitation Tank
Authors: Prasanjit Das, M. M. K. Khan, M. G. Rasul, Jie Wu, I. Youn
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Mineral scale formation is undoubtedly a more serious problem in the mineral industry than other process industries. To better understand scale growth and suppression, an experimental model is proposed in this study for supersaturated crystallised solutions commonly found in mineral process plants. In this experiment, surface crystallisation of potassium nitrate (KNO3) on the wall of the agitation tank and agitation effects on the scale growth and suppression are studied. The new quantitative scale suppression model predicts that at lower agitation speed, the scale growth rate is enhanced and at higher agitation speed, the scale suppression rate increases due to the increased flow erosion effect. A lab-scale agitation tank with and without baffles were used as a benchmark in this study. The fluid dynamic effects on scale growth and suppression in the agitation tank with three different size impellers (diameter 86, 114, 160 mm and model A310 with flow number 0.56) at various ranges of rotational speed (up to 700 rpm) and solution with different concentration (4.5, 4.75 and 5.25 mol/dm3) were investigated. For more elucidation, the effects of the different size of the impeller on wall surface scale growth and suppression rate as well as bottom settled scale accumulation rate are also discussed. Emphasis was placed on applications in the mineral industry, although results are also relevant to other industrial applications.Keywords: agitation tank, crystallisation, impeller speed, scale
Procedia PDF Downloads 2226291 The Development of the Self-concept Scale for Elders in Taiwan
Authors: Ting-Chia Lien, Tzu-Yin Yen, Szu-Fan Chen, Tai-chun Kuo, Hung-Tse Lin, Yi-Chen Chung, Hock-Sen Gwee
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The purpose of this study was to explore the result of the survey by developing “Self-Concept Scale for Elders”, which could provide community counseling and guidance institution for practical application. The sample of this study consisted of 332 elders in Taiwan (male: 33.4%; female: 66.6%). The mean age of participants was 65-98 years. The measurements applied in this study is “Self-Concept Scale for Elders”. After item and factor analyses, the preliminary version of the Self-Concept Scale for Elders was revised to the final version. The results were summarized as follows: 1) There were 10 items in Self-Concept Scale for Elders. 2) The variance explained for the scale accounted for 77.15%, with corrected item-total correlations Cronbach’s alpha=0.87. 3) The content validity, criterion validity and construct validity have been found to be satisfactory. Based on the findings, the implication and suggestions are offered for reference regarding counselor education and future research.Keywords: self-concept, elder, development scale, applied psychology
Procedia PDF Downloads 5696290 Oxidosqualene Cyclase: A Novel Inhibitor
Authors: Devadrita Dey Sarkar
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Oxidosqualene cyclase is a membrane bound enzyme in which helps in the formation of steroid scaffold in higher organisms. In a highly selective cyclization reaction oxidosqualene cyclase forms LANOSTEROL with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. In humans OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. The enzyme oxidosqualene: lanosterol cyclase (OSC) represents a novel target for the treatment of hypercholesterolemia. OSC catalyzes the cyclization of the linear 2,3-monoepoxysqualene to lanosterol, the initial four-ringed sterol intermediate in the cholesterol biosynthetic pathway. OSC also catalyzes the formation of 24(S), 25-epoxycholesterol, a ligand activator of the liver X receptor. Inhibition of OSC reduces cholesterol biosynthesis and selectively enhances 24(S),25-epoxycholesterol synthesis. Through this dual mechanism, OSC inhibition decreases plasma levels of low-density lipoprotein (LDL)-cholesterol and prevents cholesterol deposition within macrophages. The recent crystallization of OSC identifies the mechanism of action for this complex enzyme, setting the stage for the design of OSC inhibitors with improved pharmacological properties for cholesterol lowering and treatment of atherosclerosis. While studying and designing the inhibitor of oxidosqulene cyclase, I worked on the pdb id of 1w6k which was the most worked on pdb id and I used several methods, techniques and softwares to identify and validate the top most molecules which could be acting as an inhibitor for oxidosqualene cyclase. Thus, by partial blockage of this enzyme, both an inhibition of lanosterol and subsequently cholesterol formation as well as a concomitant effect on HMG-CoA reductase can be achieved. Both effects complement each other and lead to an effective control of cholesterol biosynthesis. It is therefore concluded that 2,3-oxidosqualene cyclase plays a crucial role in the regulation of intracellular cholesterol homeostasis. 2,3-Oxidosqualene cyclase inhibitors offer an attractive approach for novel lipid-lowering agents.Keywords: anticholesteraemic, crystallization, statins, homeostasis
Procedia PDF Downloads 3496289 Characterization of New Sources of Maize (Zea mays L.) Resistance to Sitophilus zeamais (Coleoptera: Curculionidae) Infestation in Stored Maize
Authors: L. C. Nwosu, C. O. Adedire, M. O. Ashamo, E. O. Ogunwolu
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The maize weevil, Sitophilus zeamais Motschulsky is a notorious pest of stored maize (Zea mays L.). The development of resistant maize varieties to manage weevils is a major breeding objective. The study investigated the parameters and mechanisms that confer resistance on a maize variety to S. zeamais infestation using twenty elite maize varieties. Detailed morphological, physical and chemical studies were conducted on whole-maize grain and the grain pericarp. Resistance was assessed at 33, 56, and 90 days post infestation using weevil mortality rate, weevil survival rate, percent grain damage, percent grain weight loss, weight of grain powder, oviposition rate and index of susceptibility as indices rated on a scale developed by the present study and on Dobie’s modified scale. Linear regression models that can predict maize grain damage in relation to the duration of storage were developed and applied. The resistant varieties identified particularly 2000 SYNEE-WSTR and TZBRELD3C5 with very high degree of resistance should be used singly or best in an integrated pest management system for the control of S. zeamais infestation in stored maize. Though increases in the physical properties of grain hardness, weight, length, and width increased varietal resistance, it was found that the bases of resistance were increased chemical attributes of phenolic acid, trypsin inhibitor and crude fibre while the bases of susceptibility were increased protein, starch, magnesium, calcium, sodium, phosphorus, manganese, iron, cobalt and zinc, the role of potassium requiring further investigation. Characters that conferred resistance on the test varieties were found distributed in the pericarp and the endosperm of the grains. Increases in grain phenolic acid, crude fibre, and trypsin inhibitor adversely and significantly affected the bionomics of the weevil on further assessment. The flat side of a maize grain at the point of penetration was significantly preferred by the weevil. Why the south area of the flattened side of a maize grain was significantly preferred by the weevil is clearly unknown, even though grain-face-type seemed to be a contributor in the study. The preference shown to the south area of the grain flat side has implications for seed viability. The study identified antibiosis, preference, antixenosis, and host evasion as the mechanisms of maize post harvest resistance to Sitophilus zeamais infestation.Keywords: maize weevil, resistant, parameters, mechanisms, preference
Procedia PDF Downloads 3076288 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 1226287 Aza-Flavanones as Small Molecule Inhibitors of MicroRNA-10b in MDA-MB-231 Breast Cancer Cells
Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra
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MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.Keywords: breast cancer, microRNA, metastasis, EMT
Procedia PDF Downloads 5646286 Grating Scale Thermal Expansion Error Compensation for Large Machine Tools Based on Multiple Temperature Detection
Authors: Wenlong Feng, Zhenchun Du, Jianguo Yang
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To decrease the grating scale thermal expansion error, a novel method which based on multiple temperature detections is proposed. Several temperature sensors are installed on the grating scale and the temperatures of these sensors are recorded. The temperatures of every point on the grating scale are calculated by interpolating between adjacent sensors. According to the thermal expansion principle, the grating scale thermal expansion error model can be established by doing the integral for the variations of position and temperature. A novel compensation method is proposed in this paper. By applying the established error model, the grating scale thermal expansion error is decreased by 90% compared with no compensation. The residual positioning error of the grating scale is less than 15um/10m and the accuracy of the machine tool is significant improved.Keywords: thermal expansion error of grating scale, error compensation, machine tools, integral method
Procedia PDF Downloads 3646285 Developing New Media Credibility Scale: A Multidimensional Perspective
Authors: Hanaa Farouk Saleh
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The main purposes of this study are to develop a scale that reflects emerging theoretical understandings of new media credibility, based on the evolution of credibility studies in western researches, identification of the determinants of credibility in the media and its components by comparing traditional and new media credibility scales and building accumulative scale to test new media credibility. This approach was built on western researches using conceptualizations of media credibility, which focuses on four principal components: Source (journalist), message (article), medium (newspaper, radio, TV, web, etc.), and organization (owner of the medium), and adding user and cultural context as key components to assess new media credibility in particular. This study’s value lies in its contribution to the conceptualization and development of new media credibility through the creation of a theoretical measurement tool. Future studies should explore this scale to test new media credibility, which represents a promising new approach in the efforts to define and measure credibility of all media types.Keywords: credibility scale, media credibility components, new media credibility scale, scale development
Procedia PDF Downloads 3206284 Design, Molecular Modeling, Synthesize, and Biological Evaluation of Some Dual Inhibitors of Soluble Epoxide Hydrolase (sEH) and Cyclooxygenase 2 (COX-2)
Authors: Elham Rezaee, Sayyed Abbas Tabatabai
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Dual inhibition of COX-2 and sEH enzymes represents one of the distinct pharmaceutical approaches for the treatment of inflammation, pain, cancers, and other diseases. The discovery of these inhibitors for treatment is a great deal of attention because of some advantages such as increased efficacy, a promising safety profile, ease of formulation, and better target engagement. In this research, based on the structure-activity relationship of COX-2 and sEH inhibitors, some amide derivatives with oxadiazole and dihydropyrimidinone rings against sEH and COX-2 enzymes were developed. The designed compounds showed high affinity to the active site of both enzymes in docking studies and were synthesized in good yield and characterized by IR, Mass, 1HNMR, and 13CNMR. All of the novel compounds exhibited considerable in-vitro sEH and COX-2 inhibitory activities in comparison with 12-(3-Adamantan-1-yl-ureido)- dodecanoic acid and celecoxib (a potent urea-based sEH inhibitor and selective nonsteroidal anti-inflammatory drug, respectively). Ethyl 6-methyl-4-(4-(4-(methylsulfonyl)benzamido)phenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate was found to be the most selective COX-2 inhibitor (COX-2/COX-1 ratio: 683) with IC50 value of 2.1 nM targeting sEH enzyme.Keywords: COX-2, dual inhibitors, sEH, synthesis
Procedia PDF Downloads 506283 Impacts of Financial Development and Operational Scale on Bank Efficiencies in Taiwan
Authors: Ying-Hsiu Chen, Pao-Peng Hsu
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This paper adopts a two-stage data envelopment analysis to explore the impacts of financial development and bank operational scale on bank efficiencies. The sample comprises of unbalanced panel data of 32 Taiwanese enlisted in domestic commercial banks over the period 1998 to 2013. Empirical results show that technical efficiency is positively related to financial development, whereas the effect of financial development on scale efficiency is insignificant. The effect of operational scale exerts a significantly positive effect on bank efficiencies, but the gain of efficiency is decreased gradually when operational scale increases. Furthermore, increase in capital adequacy ratio and market power of banks leads to a growth of bank efficiencies.Keywords: financial development, operational scale, efficiency, DEA
Procedia PDF Downloads 5246282 The Impact of Co-Administration of Phosphodiesterase-5 Inhibitor and Sodium Selenite on Ischemia/Reperfusion Injury in a Rat Ovary Model: Biochemical and Histopathologic Evaluation
Authors: Waleed Aly Sayed Ahmed, Eman Kishk, Tahani Shams
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Aim: To study the effects of co-administration of phosphodiesterase-5 inhibitor (PDE-5) and sodium selenite against the damage induced by ovarian ischemia-reperfusion in rats. Materials and Methods: A total of forty-two sexually mature, virgin, female rats were divided randomly into six groups of seven each: sham group (C), ischemia group (I), ischemia/reperfusion group (I/R), ischemia/reperfusion plus 1.4mg/kg sildenafil (I/R+S) group, ischemia/reperfusion plus 0.2mg/kg selenium (I/R+Se) group and ischemia/reperfusion plus combination of sildenafil and selenium (I/R+S+Se) group. In ischemia group (I), rats were exposed to ischemia for 3 hours (h). In ischemia/reperfusion group (I/R), rats were exposed to ischemia for 3 h followed by 6 h of reperfusion. Treated groups received 1.4mg/kg sildenafil or 0.2 mg/kg selenium or both 30 min before reperfusion. Both ovaries were surgically removed carefully. One ovary was examined for histopathological changes and the other was subject to biochemical analysis including malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx). Results: Assessment of ovarian tissue damage using a scoring system showed marked vascular congestion, interstitial edema, leukocyte infiltration, hemorrhage, and follicular degeneration in ischemia and ischemia/reperfusion groups. Tissue damage score for I, IR and all treated groups were significantly higher than those of the sham group (p<0.001), while tissue damage score decreased significantly in I/R+S and I/R+Se groups compared to I/R group (p<0.05), and notably, the difference was highly significant in I/R+S+Se group (p<0.001). There was significant increase in MDA levels and reduction in activities of CAT and GPx in I/R group compared to the sham group (p < 0.05). In I/R+S and I/R+Se groups, MDA was significantly decreased compared to the I/R group (p<0.05) and the difference was highly significant with co-administration of sildenafil and selenium (p<0.001). CAT and GPx were higher in all treated groups compared to I/R group (p<0.05). Conclusion: The co-administration of sildenafil citrate and selenium are highly protective against damage induced by ovarian ischemia/reperfusion in rats.Keywords: phosphodiesterase-5 inhibitor, sildenafil, antioxidant, selenium, ovarian ischemia
Procedia PDF Downloads 3116281 Pancreatic Lipase and Cholesterol Esterase Inhibitors from Thai Medicinal Plants
Authors: Kwanchai Ratanamanee, Pattra Ahmadi Pirshahid, Yaowaluk Khamphan, Sirinan Thubthimthad
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Obesity is a main global health problem. The obesity rated has continued to be higher and higher. It causes to serious systems, diabetes, coronary artery disease, stroke, and some types of cancer. Oristat is one of the best drugs worldwide used as a pancreatic lipase inhibitor. To develop the new therapeutic drugs from medicinal plant always explored. In this study, 24 medicinal plants were investigated for their pancreatic lipase and cholesterol esterase inhibitory effects with Fluorometer assay and oristat as a positive control. It showed that the ethanolic extract of pods of Acacia concinna (Willd.) D.C., possess pancreatic lipase and cholesterol esterase inhibitory activities of IC50 at 2.73 and 3.77 mg/ml respectively as well as oral acute toxicity of the extract (LD50) was 6,300 mg/kg body weight. The extract of A.concinna should be further investigated in animal testing. The results of pancreatic lipase and cholesterol esterase inhibitor of the extracts will lead us to utilize A.concinna for developing as obesity dietary supplement from a medicinal plant.Keywords: Acacia concinna (Willd.) D. C., cholesterol esterase, obesity, pancreatic lipase
Procedia PDF Downloads 4776280 Prediction of Fire Growth of the Office by Real-Scale Fire Experiment
Authors: Kweon Oh-Sang, Kim Heung-Youl
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Estimating the engineering properties of fires is important to be prepared for the complex and various fire risks of large-scale structures such as super-tall buildings, large stadiums, and multi-purpose structures. In this study, a mock-up of a compartment which was 2.4(L) x 3.6 (W) x 2.4 (H) meter in dimensions was fabricated at the 10MW LSC (Large Scale Calorimeter) and combustible office supplies were placed in the compartment for a real-scale fire test. Maximum heat release rate was 4.1 MW and total energy release obtained through the application of t2 fire growth rate was 6705.9 MJ.Keywords: fire growth, fire experiment, t2 curve, large scale calorimeter
Procedia PDF Downloads 3366279 Quantum Chemical Calculations Synthesis and Corrosion Inhibition Efficiency of Nonionic Surfactants on API X65 Steel Surface under H2s Environment
Authors: E. G. Zaki, M. A. Migahed, A. M. Al-Sabagh, E. A. Khamis
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Inhibition effect of four novel nonionic surfactants based on sulphonamide, of linear alkyl benzene sulphonic acid (LABS), was reacted with 1 mole triethylenetetramine, tetraethylenepentamine then Ethoxylation of amide X 65 type carbon steel in oil wells formation water under H2S environment was investigated by electrochemical measurements. Scanning electron microscopy (SEM) and energy dispersion X-ray (EDX) were used to characterize the steel surface. The results showed that these surfactants act as a corrosion inhibitor in and their inhibition efficiencies depend on the ethylene oxide content in the system. The obtained results showed that the percentage inhibition efficiency (η%) was increased by increasing the inhibitor concentration until the critical micelle concentration (CMC) reached The quantum chemistry calculations were carried out to study the molecular geometry and electronic structure of obtained derivatives. The energy gap between the highest occupied molecular orbital and lowest unoccupied molecular orbital has been calculated using the theoretical computations to reflect the chemical reactivity and kinetic stability of compounds.Keywords: corrosion, surfactants, steel surface, quantum
Procedia PDF Downloads 3766278 Pilot Scale Deproteinization Study on Fish Scale Using Response Surface Methodology
Authors: Fatima Bellali, Mariem Kharroubi
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Fish scale wastes are one of the main sources of production of value-added products such as collagen. The main aim of this study is to investigate the optimization conditions of the sardine scale deproteinization using response surface methodology (RSM) on a pilot scale. In order to look for the optimal conditions, a Box–Behnken-based design of experiment (DOE) method was carried out. The model predicted values of product coal ash content were in good agreement with the experiment values (R2 = 0.9813). Finally, model-based optimization was carried out to identify the operating parameters (reaction time=4h and the solid-liquid ratio= 1/10) and to obtain the lowest collagen content.Keywords: pilot scale, Plackett and Burman design, fish waste, deproteinization
Procedia PDF Downloads 1596277 Rationally Designed Dual PARP-HDAC Inhibitor Elicits Striking Anti-leukemic Effects
Authors: Amandeep Thakur, Yi-Hsuan Chu, Chun-Hsu Pan, Kunal Nepali
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The transfer of ADP-ribose residues onto target substrates from nicotinamide adenine dinucleotide (NAD) (PARylation) is catalyzed by Poly (ADP-ribose) polymerases (PARPs). Amongst the PARP family members, the DNA damage response in cancer is majorly regulated by PARP1 and PARP2. The blockade of DNA repair by PARP inhibitors leads to the progression of DNA single-strand breaks (induced by some triggering factors) to double-strand breaks. Notably, PARP inhibitors are remarkably effective in cancers with defective homologous recombination repair (HRR). In particular, cancer cells with BRCA mutations are responsive to therapy with PARP inhibitors. The aforementioned requirement for PARP inhibitors to be effective confers a narrow activity spectrum to PARP inhibitors, which hinders their clinical applicability. Thus, the quest to expand the application horizons of PARP inhibitors beyond BRCA mutations is the need of the hour. Literature precedents reveal that HDAC inhibition induces BRCAness in cancer cells and can broaden the therapeutic scope of PARP inhibitors. Driven by such disclosures, dual inhibitors targeting both PARP and HDAC enzymes were designed by our research group to extend the efficacy of PARP inhibitors beyond BRCA-mutated cancers to cancers with induced BRCAness. The design strategy involved the installation of Veliparib, an investigational PARP inhibitor, as a surface recognition part in the HDAC inhibitor pharmacophore model. The chemical architecture of veliparib was deemed appropriate as a starting point for the generation of dual inhibitors by virtue of its size and structural flexibility. A validatory docking study was conducted at the outset to predict the binding mode of the designed dual modulatory chemical architectures. Subsequently, the designed chemical architectures were synthesized via a multistep synthetic route and evaluated for antitumor efficacy. Delightfully, one compound manifested impressive anti-leukemic effects (HL-60 cell lines) mediated via dual inhibition of PARP and class I HDACs. The outcome of the western blot analysis revealed that the compound could downregulate the expression levels of PARP1 and PARP2 and the HDAC isoforms (HDAC1, 2, and 3). Also, the dual PARP-HDAC inhibitor upregulated the protein expression of the acetyl histone H3, confirming its abrogation potential for class I HDACs. In addition, the dual modulator could arrest the cell cycle at the G0/G1 phase and induce autophagy. Further, polymer-based nanoformulation of the dual inhibitor was furnished to afford targeted delivery of the dual inhibitor at the cancer site. Transmission electron microscopy (TEM) results indicate that the nanoparticles were monodispersed and spherical. Moreover, the polymeric nanoformulation exhibited an appropriate particle size. Delightfully, pH-sensitive behavior was manifested by the polymeric nanoformulation that led to selective antitumor effects towards the HL-60 cell lines. In light of the magnificent anti-leukemic profile of the identified dual PARP-HDAC inhibitor, in-vivo studies (pharmacokinetics and pharmacodynamics) are currently being conducted. Notably, the optimistic findings of the aforementioned study have spurred our research group to initiate several medicinal chemistry campaigns to create bifunctional small molecule inhibitors addressing PARP as the primary target.Keywords: PARP inhibitors, HDAC inhibitors, BRCA mutations, leukemia
Procedia PDF Downloads 236276 Analysis of Efficiency Production of Grass Black Jelly (Mesona palustris) in Double Scale
Authors: Irvan Adhin Cholilie, Susinggih Wijana, Yusron Sugiarto
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The aim of this research is to compare the results of black grass jelly produced using laboratory scale and double scale. In this research, the production from the laboratory scale is using ingredients of 1 kg black grass jelly added with 5 liters of water, while the double scale is using 5 kg black grass jelly and 75 liters of water. The results of organoleptic tests performed by 30 panelists (general) to the sample gels of grass black powder produced from both of laboratory and double scale are not different significantly in color, odor, flavor, and texture. Proximate test results conducted in both of grass black jelly powder produced in laboratory scale and double scale also have no significant differences in all parameters. Grass black jelly powder from double scale contains water, carbohydrate, crude fiber, and yield in the amount of 12,25 %; 43,7 %; 5,89 %; and 16,28 % respectively. The results of the energy efficiency analysis by boiling, draining, evaporation, drying, and milling processes are 85,11 %; 76,97 %; 99,64 %; 99,99% and 99,39% respectively. The utility needs including water needs for each batch amounted 0.1 m3 and cost Rp 220,5 per batch, the electricity needs for each batch is 20.01 kWh and cost Rp 18569.28 per batch, and LPG needs for each batch is 30 kg costed Rp 234,000.00 so that the total cost spent for the process is Rp 252,789.78 .Keywords: black grass jelly, powder, mass balance, energy balance, cost
Procedia PDF Downloads 3846275 Comparative Study of Isothermal and Cyclic Oxidation on Titanium Alloys
Authors: Poonam Yadav, Dong Bok Lee
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Isothermal oxidation at 800°C for 50h and Cyclic oxidation at 600°C and 800°C for 40h of Pure Ti and Ti64 were performed in a muffle furnace. In Cyclic oxidation, massive scale spallation occurred, and the oxide scale cracks and peels off were observed at high temperature, it represents oxide scale that formed during cyclic oxidation was spalled out owing to stresses due to thermal shock generated during repetitive oxidation and subsequent cooling. The thickness of scale is larger in cyclic oxidation than the isothermal case. This is due to inward diffusion of oxygen through oxide scales and/or pores and cracks in cyclic oxidation.Keywords: cyclic, diffusion, isothermal, cyclic
Procedia PDF Downloads 9186274 Adjustment and Scale-Up Strategy of Pilot Liquid Fermentation Process of Azotobacter sp.
Authors: G. Quiroga-Cubides, A. Díaz, M. Gómez
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The genus Azotobacter has been widely used as bio-fertilizer due to its significant effects on the stimulation and promotion of plant growth in various agricultural species of commercial interest. In order to obtain significantly viable cellular concentration, a scale-up strategy for a liquid fermentation process (SmF) with two strains of A. chroococcum (named Ac1 and Ac10) was validated and adjusted at laboratory and pilot scale. A batch fermentation process under previously defined conditions was carried out on a biorreactor Infors®, model Minifors of 3.5 L, which served as a baseline for this research. For the purpose of increasing process efficiency, the effect of the reduction of stirring speed was evaluated in combination with a fed-batch-type fermentation laboratory scale. To reproduce the efficiency parameters obtained, a scale-up strategy with geometric and fluid dynamic behavior similarities was evaluated. According to the analysis of variance, this scale-up strategy did not have significant effect on cellular concentration and in laboratory and pilot fermentations (Tukey, p > 0.05). Regarding air consumption, fermentation process at pilot scale showed a reduction of 23% versus the baseline. The percentage of reduction related to energy consumption reduction under laboratory and pilot scale conditions was 96.9% compared with baseline.Keywords: Azotobacter chroococcum, scale-up, liquid fermentation, fed-batch process
Procedia PDF Downloads 4396273 Scaling-Down an Agricultural Waste Biogas Plant Fermenter
Authors: Matheus Pessoa, Matthias Kraume
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Scale-Down rules in process engineering help us to improve and develop Industrial scale parameters into lab scale. Several scale-down rules available in the literature like Impeller Power Number, Agitation device Power Input, Substrate Tip Speed, Reynolds Number and Cavern Development were investigated in order to stipulate the rotational speed to operate an 11 L working volume lab-scale bioreactor within industrial process parameters. Herein, xanthan gum was used as a fluid with a representative viscosity of a hypothetical biogas plant, with H/D = 1 and central agitation, fermentation broth using sewage sludge and sugar beet pulp as substrate. The results showed that the cavern development strategy was the best method for establishing a rotational speed for the bioreactor operation, while the other rules presented values out of reality for this article proposes.Keywords: anaerobic digestion, cavern development, scale down rules, xanthan gum
Procedia PDF Downloads 4926272 Understanding the Role of Nitric Oxide Synthase 1 in Low-Density Lipoprotein Uptake by Macrophages and Implication in Atherosclerosis Progression
Authors: Anjali Roy, Mirza S. Baig
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Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid rich plaque enriched with necrotic core, modified lipid accumulation, smooth muscle cells, endothelial cells, leucocytes and macrophages. Macrophage foam cells play a critical role in the occurrence and development of inflammatory atherosclerotic plaque. Foam cells are the fat-laden macrophages in the initial stage atherosclerotic lesion formation. Foam cells are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening. The mechanisms that drive atherosclerotic plaque progression remain largely unknown. Dissecting the molecular mechanism involved in process of macrophage foam cell formation will help to develop therapeutic interventions for atherosclerosis. To investigate the mechanism, we studied the role of nitric oxide synthase 1(NOS1)-mediated nitric oxide (NO) on low-density lipoprotein (LDL) uptake by bone marrow derived macrophages (BMDM). Using confocal microscopy, we found that incubation of macrophages with NOS1 inhibitor, TRIM (1-(2-Trifluoromethylphenyl) imidazole) or L-NAME (N omega-nitro-L-arginine methyl ester) prior to LDL treatment significantly reduces the LDL uptake by BMDM. Further, addition of NO donor (DEA NONOate) in NOS1 inhibitor treated macrophages recovers the LDL uptake. Our data strongly suggest that NOS1 derived NO regulates LDL uptake by macrophages and foam cell formation. Moreover, we also checked proinflammatory cytokine mRNA expression through real time PCR in BMDM treated with LDL and copper oxidized LDL (OxLDL) in presences and absences of inhibitor. Normal LDL does not evoke cytokine expression whereas OxLDL induced proinflammatory cytokine expression which significantly reduced in presences of NOS1 inhibitor. Rapid NOS-1-derived NO and its stable derivative formation act as signaling agents for inducible NOS-2 expression in endothelial cells, leading to endothelial vascular wall lining disruption and dysfunctioning. This study highlights the role of NOS1 as critical players of foam cell formation and would reveal much about the key molecular proteins involved in atherosclerosis. Thus, targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages at early stage of disease and hence dampening the atherosclerosis progression.Keywords: atherosclerosis, NOS1, inflammation, oxidized LDL
Procedia PDF Downloads 1276271 A Comparative Performance of Polyaspartic Acid and Sodium Polyacrylate on Silicate Scale Inhibition
Authors: Ismail Bin Mohd Saaid, Abubakar Abubakar Umar
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Despite the successes recorded by Alkaline/Surfactant/Polymer (ASP) flooding as an effective chemical EOR technique, the combination CEOR is not unassociated with stern glitches, one of which is the scaling of downhole equipment. One of the major issues inside the oil industry is how to control scale formation, regardless of whether it is in the wellhead equipment, down-hole pipelines or even the actual field formation. The best approach to handle the challenge associated with oilfield scale formation is the application of scale inhibitors to avert the scale formation. Chemical inhibitors have been employed in doing such. But due to environmental regulations, the industry have focused on using green scale inhibitors to mitigate the formation of scales. This paper compares the scale inhibition performance of Polyaspartic acid and sodium polyacrylic acid, both commercial green scale inhibitors, in mitigating silicate scales formed during Alkaline/Surfactant/polymer flooding under static conditions. Both PASP and TH5000 are non-threshold inhibitors, therefore their efficiency was only seeing in delaying the deposition of the silicate scales.Keywords: alkaline/surfactant/polymer flooding (ASP), polyaspartic acid (PASP), sodium polyacrylate (SPA)
Procedia PDF Downloads 3506270 Effects of Employees’ Training Program on the Performance of Small Scale Enterprises in Oyo State
Authors: Itiola Kehinde Adeniran
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The study examined the effect of employees’ training on the performance of small scale enterprises in Oyo State. A structured questionnaire was used to collect data from 150 respondents through purposive sampling method. Linear regression was used with the aid of statistical package for social science (SPSS) version 20 to analyze the data collected in order to examine the effect of independent variable, employees’ training on dependent variable, performance (profit) of small scale enterprises. The result revealed that employees’ training has a significant effect on the performance of small scale enterprises. It was concluded that predictor variable namely (training) is 55.5% variance of enterprises performance (profitability). Therefore, the paper recommended that all small scale enterprises in Nigeria should embrace manpower training and development in order to improve employees’ performance leading to organizational profitability.Keywords: training, employee performance, small scale enterprise, organizational profitability
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