Search results for: solvent free synthesis

Authors: Mpho Agnes Mbeo, Patient Rambe

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The thirteenth year of the Central University of Technology, Free State’s (CUT) transition from a vocational and professional training orientation institution (i.e. a technikon) into a university with a strong research focus has neither been a smooth nor an easy one. At the heart of this transition was the need to transform the psychological faculties of academic and research staffs compliment who were accustomed to training graduates for industrial placement. The lack of a culture of research that fully embraces a strong ethos of conducting world-class research needed to be addressed. The induction and socialisation of academic staff into the development and execution of cutting-edge research also required the provision of research support and the creation of a conducive academic environment for research, both for emerging and non-research active academics. Drawing on ten cases, comprising four heads of departments, three prolific established researchers, and three emerging researchers, this study explores the challenges faced in establishing a strong research culture at the university. Furthermore, it gives an account of the extent to which the current research interventions have addressed the perceivably “missing research culture”, and the implications of these interventions for knowledge management. Evidence suggests that the endowment of an ideal institutional research environment (comprising strong internet networks, persistent connectivity on and off campus), research peer mentorship, and growing publication outputs should be matched by a coherent research incentive culture and strong research leadership. This is critical to building new knowledge and entrenching knowledge management founded on communities of practice and scholarly networking through the documentation and communication of research findings. The study concludes that the multiple policy documents set for the different domains of research may be creating pressure on researchers to engage research activities and increase output at the expense of research quality.

Keywords: Central University of Technology, performance, publication, research culture, university

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Authors: Marianna Ciaccia, Gennaro Agrimi, Isabella Pisano, Maurizio Bettiga, Silvia Rapacioli, Giulia Mensa, Monica Marzagalli

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Objective: Untargeted metabolomic analysis of extracellular metabolites is a powerful approach that focuses on comprehensively profiling in the extracellular space. In this study, we applied extracellular metabolomic analysis to investigate the metabolism of two probiotic microorganisms with health benefits that extend far beyond the digestive tract and the immune system. Methods: Analytical techniques employed in extracellular metabolomic analysis encompass various technologies, including mass spectrometry (MS), which enables the identification of metabolites present in the fermentation media, as well as the comparison of metabolic profiles under different experimental conditions. Multivariate statistical analysis techniques like principal component analysis (PCA) or partial least squares-discriminant analysis (PLS-DA) play a crucial role in uncovering metabolic signatures and understanding the dynamics of metabolic networks. Results: Different types of supernatants from fermentation processes, such as dairy-free, not dairy-free media and media with no cells or pasteurized, were subjected to metabolite profiling, which contained a complex mixture of metabolites, including substrates, intermediates, and end-products. This profiling provided insights into the metabolic activity of the microorganisms. The integration of advanced software tools has facilitated the identification and characterization of metabolites in different fermentation conditions and microorganism strains. Conclusions: In conclusion, untargeted extracellular metabolomic analysis, combined with software tools, allowed the study of the metabolites consumed and produced during the fermentation processes of probiotic microorganisms. Ongoing advancements in data analysis methods will further enhance the application of extracellular metabolomic analysis in fermentation research, leading to improved bioproduction and the advancement of sustainable manufacturing processes.

Keywords: biotechnology, metabolomics, lactic bacteria, probiotics, postbiotics

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

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

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

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Authors: J. A. N. Sandamali, R. P. Hewawasam, K. A. P. W. Jayatilaka, L. K. B. Mudduwa

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Introduction: Doxorubicin is widely used in the treatment of solid organ tumors and hematological malignancies, but the dose-dependent cardiotoxicity due to free radical formation compromises its clinical utility. Therapeutic strategies which enhance cellular endogenous defense systems have been identified as promising approaches to combat oxidative stress-associated conditions. Cinnamomum zeylanicum (Ceylon cinnamon) has a number antioxidant compounds, which can effectively scavenge reactive oxygen including superoxide anions, hydroxyl radicals and as well as other free radicals. Therefore, the objective of the study was to elucidate the most effective dose of Cinnamomum bark extract which ameliorates doxorubicin-induced cardiotoxicity. Materials and methods: Wistar rats were divided into seven groups of 10 animals in each. Group 1: normal control (distilled water, orally, for 14 days, 10 mL/kg saline, ip, after 16 hours fast on the 11th day); Group 2: doxorubicin control (distilled water, orally, for 14 days, 18 mg/kg doxorubicin, ip, after 16 hour fast on the 11th day); Groups 3-7: five doses of freeze dried aqueous bark extracts (0.125, 0.25, 0.5, 1.0, 2.0g/kg, orally, daily for 14 days, 18 mg/kg doxorubicin, ip, after 16 hours fast on the 11th day). Animals were sacrificed on the 15th day and blood was collected for the estimation of cardiac troponin I (cTnI), AST and LDH concentrations and myocardial tissues were collected for histopathological assessment of myocardial damage and irreversible changes were graded by developing a score. Results: cTnI concentration of groups 1-7 were 0, 161.9, 128.6, 95.9, 38, 19.41 & 12.36 pg/mL showing significant differences (p<0.05) between group 2 and groups 4-7. In groups 1-7, serum AST concentration were 26.82, 68.1, 37.18, 36.23, 26.8, 26.62 & 22.43U/L and LDH concentrations were 1166.13, 2428.84, 1658.35, 1474.34, 1277.58, 1110.21 & 974.40U/L and a significant difference (p<0.05) was observed between group 2 and groups 3-7. The maximum score for myocardial necrosis was observed in group 2. Parallel to the increase of the dosage of plant extract, a gradual reduction of the score for myocardial necrosis was observed in groups 3-7. Reversible histological changes such as vacuolation, congestion were observed in group 2 and all plant treated groups. Haemorrhages, inflammatory cell infiltrations, and interstitial oedema were observed in group 2, but absent in groups treated with higher doses of the plant extract. Discussion & Conclusion: According to the in vitro antioxidant assays performed, Cinnamomum zeylanicum (Ceylon cinnamon) bark possesses high amounts of polyphenolic substances and high antioxidant activity. The present study showed that Cinnamomum zeylanicum extract at 2.0 g/kg possesses the most significant cardioprotective effect against doxorubicin-induced cardiotoxicity. It can be postulated that pretreatment with Cinnamomum bark extract may replenish the cardiomyocytes with antioxidants that are needed for the defense against oxidative stress induced by doxorubicin.

Keywords: cardioprotection, Cinnamomum zeylanicum, doxorubicin, free radicals

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Authors: Ratneev Kaur, Tajinder Kaur, Anupam Kaur

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Introduction: Polycystic Ovary Syndrome (PCOS) is a heterogenous disorder of endocrine system among women of reproductive age. PCOS is characterized by hyperandrogenism, anovulation, polycystic ovaries, hirsutism, obesity, and hyperinsulinemia. Several pathways are implicated in its etiology including the metabolic pathway of steroid hormone synthesis regulatory pathways. PCOS is an androgen excess disorder, genes operating in steroidogenesis may alter pathogenesis of PCOS. The cytochrome P450scc is a cholesterol side chain cleavage enzyme coded by CYP11A1 gene and catalyzes conversion of cholesterol to pregnenolone, the initial and rate-limiting step in steroid hormone synthesis. It is postulated that polymorphisms in this gene may play an important role in the regulation of CYP11A1 expression and leading to increased or decreased androgen production. The present study will be the first study from north India to best of our knowledge, to analyse the association of CYP11A1 (rs11632698) polymorphism in women suffering from PCOS. Methodology: The present study was approved by ethical committee of Guru Nanak Dev University in consistent with declaration of Helsinki. A total of 300 samples (150 PCOS cases and 150 controls) were recruited from Hartej hospital, for the present study. Venous blood sample (3ml) was withdrawn from women diagnosed with PCOS by doctor, according to Rotterdam 2003 criteria and from healthy age matched controls only after informed consent and detailed filled proforma. For molecular genetics analysis, blood was stored in EDTA vials. After DNA isolation by organic method, PCR-RFLP approach was used for genotyping and association analysis of rs11632698 polymorphism. Statistical analysis was done to check for significance of selected polymorphism with PCOS. Results: In 150 PCOS cases, the frequency of AA, AG and GG genotype was found to be 48%, 35%, and 13% compared to 62%, 27% and 8% in 150 controls. The major allele (A) and minor allele (G) frequency was 68% and 32% in cases and 78% and 22% in controls. Minor allele frequency was higher in cases as compared to controls, as well as the distribution of genotype was observed to be statistically significant (ᵡ²=6.525, p=0.038). Odds ratio in dominant, co-dominant and recessive models observed was 1.81 (p=0.013), 1.54 (p=0.012) and 1.77 (p=0.132) respectively. Conclusion: The present study showed statistically significant association of rs11632698 with PCOS (p=0.038) in North Indian women.

Keywords: polycystic ovary syndrome, CYP11A1, rs11632698, hyperandrogenism

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Authors: Jianwen Li, Hongfang Ma, Weixin Qian, Haitao Zhang, Weiyong Ying

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Methanol-to-propylene conversion was carried out in a continuous-flow fixed-bed reactor over nano-sized HZSM-5 zeolites. The HZSM-5 catalysts were synthesized with different Si/Al ratio and silicon sources, and treated with NaOH. The structural property, morphology, and acidity of catalysts were measured by XRD, N₂ adsorption, FE-SEM, TEM, and NH₃-TPD. The results indicate that the increment of Si/Al ratio decreased the acidity of catalysts and then improved propylene selectivity, while silicon sources had slight impact on the acidity but affected the product distribution. The desilication after alkali treatment could increase intracrystalline mesopores and enhance propylene selectivity.

Keywords: alkali treatment, HZSM-5, methanol-to-propylene, synthesis condition

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Authors: Mohamed M. A. Abumandour

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The red swamp freshwater crayfish breathe through three types of feather-like trichobranchiate gills; podobranchiae, arthrobranchiae and pleurobranchiae. All gills have the same general structure and appearance; plume-like with single broad setiferous, and single axis. The gill consists of axis with numerous finger-like filaments, having three morphological types; round, pointed and somewhat hooked shaped. The direction of filaments vary according their position; in middle region were nearly perpendicular to gill axis while in the apex were nearly parallel to axis. There were characteristic system of gill spines on; central axis (two types were distinguishable by presence of socket), basal plate, setobranch (long non-branched and short multidenticulate) and on the bilobed epipodal plate. There are four shape of spinated-like distal region of setobranch seta; two pointed processes (longitudinal arrangement and irregular arranged) and two broad processes (transverse triangular and multidenticulate). The bilobed epipodal plate devoid from any filaments and extended from outer side of podobranchiae as triangular basal part then extended between the gills as cord-like middle part then pass under the gill to lies against the thoracic body wall. By SEM, the apical part of bilobed epipodal plate have serrated free border and corrugated surface while the middle part have none serrated free border. There are two methods of gill cleaning mechanism in crayfish; passive and active method. The passive method occurred by; setae of setobranch, branchiostegite, bilobed epipodal plate, setiferous arthrodial lamellae and reversing the respiratory water through a narrow spaced branchial chamber.

Keywords: crayfis, gill spines, setobranch, gill setae, cleaning mechanisms

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Authors: Khadse Saurabh, Talele Gokul, Surana Sanjay

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In an endeavor to find a new class of anti-inflammatory agents, a series of novel benzamides (ab1-ab16) were synthesized by utilizing some arylideneoxazolones (az1-az4) having 2-acetyloxyphenyl substitution on their second position. Structures of these synthesized compounds were confirmed by IR, 1H-NMR, 13C NMR, and HRMS. Among the tested benzamide compounds 3ab1, 3ab2, 3ab11, and 3ab16 showed promising anti-inflammatory activity with lessened propensity to cause gastro-intestinal hypermotility and ulceration when compared with standard Indomethacin. Virtual screening was performed by docking the designed compounds into the ATP binding site of COX-2 receptor to predict if these compounds have analogous binding mode to the COX-2 inhibitor.

Keywords: benzamides, anti-inflammatory, gastro-intestinal hypermotility, ulcerogenic activity, docking

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Authors: N. Chahmana, I. Zerroual

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The aim of our work is the contribution to the improvement of the performances of the positive plate of the lead acid battery. For that, we synthesized two varieties of PbO2 used in industry, alpha and beta PbO2 by electrochemical way starting from the not formed industrial plates. We studied the kinetics of reduction of the alpha varieties and PbO2 beta on electrode with microcavity in sulphuric medium. The electrochemical study of the powders of α and β-PbO2 was made by cyclic voltamperometry with sweeping of potential by using a traditional assembly with three electrodes. Values of the coefficient of diffusion of the proton in α and β-PbO2 are respectively equal to 0.498*10-8cm2 /s and 0.793*10-8 cm2 /s. During the cycling of the two varieties of PbO2, we obtain a clear increase in the capacity.

Keywords: lead accumulator, α and β - PbO2, synthesis, kinetics, cyclic voltametry, coefficient of diffusion

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Authors: Hui Tag, Jambey Tsering, Pallabi Kalita Hui, Baikuntha Jyoti Gogoi, Vijay Veer

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The food security issues and its relevance in High Mountain regions of the world have been often neglected. Wild edible plants have been playing a major role in livelihood security among the tribal Communities of East Himalayan Region of the world since time immemorial. The Eastern Himalayan Region of India is one of the mega diverse regions of world and rated as top 12th Global Biodiversity Hotspots by IUCN and recognized as one of the 200 significant eco-regions of the Globe. The region supports one of the world’s richest alpine floras and about one-third of them are endemic to the region. There are at least 7,500 flowering plants, 700 orchids, 58 bamboo species, 64 citrus species, 28 conifers, 500 mosses, 700 ferns and 728 lichens. The region is the home of more than three hundred different ethnic communities having diverse knowledge on traditional uses of flora and fauna as food, medicine and beverages. Monpa, Memba and Khamba are among the local communities residing in high altitude region of Eastern Himalaya with rich traditional knowledge related to utilization of wild edible plants. The Monpas, Memba and Khamba are the followers Mahayana sect of Himalayan Buddhism and they are mostly agrarian by primary occupation and also heavily relaying on wild edible plants for their livelihood security during famine since millennia. In the present study, we have reported traditional uses of 40 wild edible plant species and out of which 6 species were analysed at biochemical level for nutrients contents and free radical scavenging activities. The results have shown significant free radical scavenging (antioxidant) activity and nutritional potential of the selected 6 wild edible plants used by the local communities of Eastern Himalayan Region of India.

Keywords: East Himalaya, local community, wild edible plants, nutrition, food security

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Authors: Aditi Acharya

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Environmental pollution is threatening the environmental and human health in the most drastic way. This paper provides insight about the affects of environmental pollution in the perspective of water pollution. Sewage in drinking water, the increasing contamination of water bodies and water resources and the human beings are the major contributors, increasing the harsh activities of pollution. The research presents information about the sources of pollution, its impacts and control activities to be undertaken to make our environment free from water pollution.

Keywords: environmental pollution, water pollution, nanotechnology, nanomaterials

Procedia PDF Downloads 347

Authors: D. Zhigulskaya, V. Anisimov, A. Pikunov, K. Babanova, S. Zuev, A. Latyshkova, K. Сhernozatonskiy, A. Revazov

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Electrophysiology of information processing in reading is certainly a popular research topic. Natural reading, however, has been relatively poorly studied, despite having broad potential applications for learning and education. In the current study, we explore the relationship between text categories and spontaneous electroencephalogram (EEG) while reading. Thirty healthy volunteers (mean age 26,68 ± 1,84) participated in this study. 15 Russian-language texts were used as stimuli. The first text was used for practice and was excluded from the final analysis. The remaining 14 were opposite pairs of texts in one of 7 categories, the most important of which were: interesting/boring, fiction/non-fiction, free reading/reading with an instruction, reading a text/reading a pseudo text (consisting of strings of letters that formed meaningless words). Participants had to read the texts sequentially on an Apple iPad Pro. EEG was recorded from 12 electrodes simultaneously with eye movement data via ARKit Technology by Apple. EEG spectral amplitude was analyzed in Fz for theta-band (4-8 Hz) and in C3, C4, P3, and P4 for alpha-band (8-14 Hz) using the Friedman test. We found that reading an interesting text was accompanied by an increase in theta spectral amplitude in Fz compared to reading a boring text (3,87 µV ± 0,12 and 3,67 µV ± 0,11, respectively). When instructions are given for reading, we see less alpha activity than during free reading of the same text (3,34 µV ± 0,20 and 3,73 µV ± 0,28, respectively, for C4 as the most representative channel). The non-fiction text elicited less activity in the alpha band (C4: 3,60 µV ± 0,25) than the fiction text (C4: 3,66 µV ± 0,26). A significant difference in alpha spectral amplitude was also observed between the regular text (C4: 3,64 µV ± 0,29) and the pseudo text (C4: 3,38 µV ± 0,22). These results suggest that some brain activity we see on EEG is sensitive to particular features of the text. We propose that changes in theta and alpha bands during reading may serve as electrophysiological tools for assessing the reader’s cognitive state as well as his or her attitude to the text and the perceived information. These physiological markers have prospective practical value for developing technological solutions and biofeedback systems for reading in particular and for education in general.

Keywords: EEG, natural reading, reader's cognitive state, theta-rhythm, alpha-rhythm

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Authors: Simont Toussi

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Cameroon and the Central African Republic arebound by the provisions of many regional and international charters, which condemn the manipulation of information, obstacles to access reliable information, or the limitation of freedoms of expression and opinion. These two countries also have constitutional guarantees for free speech and access to true and liable information. However, they are yet to define specific policies and regulations for access to information, disinformation, or misinformation. Yet, certain countries’ laws and regulations related to information and communication technologies, to criminal procedures, to terrorism, or intelligence services contain provisions that rather hider human rights by condemning false information. Like many other African countries, Cameroon and the Central African Republic face a profound democratic regression, and governments use multiple methods to stifle online discourse and digital rights. Despite the increased uptake of digital tools for political participation, there is a lack of interactivity and adoption of these tools. This enables a scarcity of information and creates room for the spreading of disinformation in the public space, hamperingdemocracy and the respect for human rights. This research aims to analyse the adequacy of stakeholders’ responses to disinformation in Cameroon and the Central African Republic in periods of political contestation, such as elections and anti-government protests, to highlight the nature, perpetrators, strategies, and channels of disinformation, as well as its effects on democratic actors, including civil society, bloggers, government critics, activists, and other human rights defenders. The study follows a qualitative method with literature review, content analysis, andkey informant’sinterviews with stakeholders’ representatives, emphasized crowdsourcing as a data and information collecting method in the two countries.

Keywords: disinformation, democracy, political manipulation, social media, media, fake news, central Africa, cameroon, misinformation, free speech

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Authors: Yong Min You

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The study on the torque ripple of Permanent Magnet Synchronous Motors (PMSMs) has been rapidly progressed, which effects on the noise and vibration of the electric vehicle. There are several ways to reduce torque ripple, which are the increase in the number of slots and poles, the notch of the rotor and stator teeth, and the skew of the rotor and stator. However, the conventional methods have the disadvantage in terms of material cost and productivity. The demagnetization characteristic of PMSMs must be attained for electric vehicle application. Due to rare earth supply issue, the demand for Dy-free permanent magnet has been increasing, which can be applied to PMSMs for the electric vehicle. Dy-free permanent magnet has lower the coercivity; the demagnetization characteristic has become more significant. To improve the torque ripple as well as the demagnetization characteristics, which are significant parameters for electric vehicle application, an unequal air-gap model is proposed for a PMSM. A shape optimization is performed to optimize the design variables of an unequal air-gap model. Optimal design variables are the shape of an unequal air-gap and the angle between V-shape magnets. An optimization process is performed by Latin Hypercube Sampling (LHS), Kriging Method, and Genetic Algorithm (GA). Finite element analysis (FEA) is also utilized to analyze the torque and demagnetization characteristics. The torque ripple and the demagnetization temperature of the initial model of 45kW PMSM with unequal air-gap are 10 % and 146.8 degrees, respectively, which are reaching a critical level for electric vehicle application. Therefore, the unequal air-gap model is proposed, and then an optimization process is conducted. Compared to the initial model, the torque ripple of the optimized unequal air-gap model was reduced by 7.7 %. In addition, the demagnetization temperature of the optimized model was also increased by 1.8 % while maintaining the efficiency. From these results, a shape optimized unequal air-gap PMSM has shown the usefulness of an improvement in the torque ripple and demagnetization temperature for the electric vehicle.

Keywords: permanent magnet synchronous motor, optimal design, finite element method, torque ripple

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Authors: U. Arjun, K. Brinda, M. Padmanabhan, R. Nath

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Polycrystalline samples of rare-earth oxy-carbonates Ln2O2CO3 (Ln = Nd, Sm, and Dy) are synthesized, and their structural and magnetic properties are investigated. All of them crystallize in a hexagonal structure with space group P6_3/mmc. They form a double layered structure with frustrated triangular arrangement of rare-earth magnetic ions. An antiferromagnetic transition is observed at TN ≈ 1.25 K, 0.61 K, and 1.21 K for Nd2O2CO3, Sm2O2CO3, and Dy2O2CO3, respectively. From the analysis of magnetic susceptibility, the value of the Curie-Weiss temperature θ_CW is obtained to be ≈ 21.7 K, 18 K, and 10.6 K for Nd2O2CO3, Sm2O2CO3, and Dy2O2CO3, respectively. The magnetic frustration parameter f ( = |θ_CW|/T_N) is calculated to be ≈ 17.4, 31, and 8.8 for Nd2O2CO3, Sm2O2CO3, and Dy2O2CO3, respectively which indicates that Sm2O2CO3 is strongly frustrated compared to its Nd and Dy analogues.

Keywords: chemical synthesis, exchange and superexchange, heat capacity, magnetically ordered materials

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Authors: Neha Singh

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Background: Nowadays, the nanoparticle is gaining unexceptional attention in targeted drug delivery. But before proceeding to this episode of accomplishment, the journey and closure of these nanoparticles inside the cells should be disentangle. Being foreign for the cells, nanoparticles will easily getcleared off without any effective outcome. As the cancer cells withhold these nanoparticles for a longer period of time, more will be the drug’s effect. Chlorpromazine is a cationic amphiphilic drug which is believed to inhibit clathrin-coated pit formation by a reversible translocation of clathrin and its adapter proteins from the plasma membrane to intracellular vesicles. Chlorpromazine has a role in increasing the retention of nanoparticles in cancer cells. The mechanism of action how this small molecule increases the retention of nanoparticles is still uncovered. Method: Polymeric nanoparticle (PLGA) with Cyanine3.5 dye were synthesized by solvent evaporation method and characterized for size and zeta potential. FTIR was also done. Pulse and chase studies with and without inhibitor were done to check the retention of nanoparticle using fluorescence microscopy. Mean fluorescence intensity was measured by ImageJ software. Results: Increased retention of nanoparticle with inhibitor was observed in both pulse and chase studies. Conclusion: Our results demonstrate that by repurposing these small molecule inhibitor, we can increase the retention of nanoparticle at the targeted site.

Keywords: nanoparticle, endocytosis, clathrin inhibitor, cancer cell

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Authors: Fatemeh Benakashani, Hossein Tavakoli, Elias Soltani

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To ensure the sustainability of crop cultivation and rural economies, it is imperative that we focus on cultivating resilient crops capable of withstanding salt stress. However, the effective management of weeds in salt-affected soils remains a significant challenge. This study investigates the impact of living mulches, specifically Berseem clover (Trifolium alexandrinum) and Barley (Hordeum vulgare), on weed control, as well as the quality and yield of Black cumin (Nigella sativa) in salt-affected soil. In our research, we employed a two-fold mowing strategy for the living mulches: once following crop establishment and once before the flowering stage. Notably, the weed-free plots demonstrated Black cumin's seed yield, and oil content (31.1% to 34.3%), consistent with previous studies, highlighting its potential for the reclamation and utilization of salt-affected lands. However, Black cumin exhibited limited competitiveness against prevalent weeds in the field, such as Amaranthus retroflexus, Chenopodium album, and Portulaca oleracea, which significantly diminished both the 1000 grain mass in plots where weeds were present. Interestingly, the introduction of living mulches led to improvements in seed yield and seed oil content when compared to both weed-free and weed-infested plots. Notably, Berseem clover exhibited greater biomass than Barley, indicating its heightened competitiveness against weeds. Nevertheless, it's worth noting that in the long term, Berseem clover also competed with the main crop, thereby limiting overall productivity. Consequently, we recommend relocating the Berseem clover living mulch following the establishment of Black cumin as a strategy for weed management in Black cumin fields situated in salt-affected soils.

Keywords: weed management, competition, clover, barley, medicinal plant

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Authors: Sidra Pervez, Afsheen Aman, Shah Ali Ul Qader

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The importance of attaining an optimum performance of an enzyme is often a question of devising an effective method for its immobilization. Cross-linked enzyme aggregate (CLEAs) is a new approach for immobilization of enzymes using carrier free strategy. This method is exquisitely simple (involving precipitation of the enzyme from aqueous buffer followed by cross-linking of the resulting physical aggregates of enzyme molecules) and amenable to rapid optimization. Among many industrial enzymes, amyloglucosidase is an important amylolytic enzyme that hydrolyzes alpha (1→4) and alpha (1→6) glycosidic bonds in starch molecule and produce glucose as a sole end product. Glucose liberated by amyloglucosidase can be used for the production of ethanol and glucose syrups. Besides this amyloglucosidase can be widely used in various food and pharmaceuticals industries. For production of amyloglucosidase on commercial scale, filamentous fungi of genera Aspergillus are mostly used because they secrete large amount of enzymes extracellularly. The current investigation was based on isolation and identification of filamentous fungi from genus Aspergillus for the production of amyloglucosidase in submerged fermentation and optimization of cultivation parameters for starch saccharification. Natural isolates were identified as Aspergillus niger KIBGE-IB36, Aspergillus fumigatus KIBGE-IB33, Aspergillus flavus KIBGE-IB34 and Aspergillus terreus KIBGE-IB35 on taxonomical basis and 18S rDNA analysis and their sequence were submitted to GenBank. Among them, Aspergillus fumigatus KIBGE-IB33 was selected on the basis of maximum enzyme production. After optimization of fermentation conditions enzyme was immobilized on CLEA. Different parameters were optimized for maximum immobilization of amyloglucosidase. Data of enzyme stability (thermal and Storage) and reusability suggested the applicability of immobilized amyloglucosidase for continuous saccharification of starch in industrial processes.

Keywords: aspergillus, immobilization, industrial processes, starch saccharification

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Authors: Merouani Nawel, Belhattab Rachid

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Aristolochia longa L. (Aristolochiacea) is a native plant of Algeria used in traditional medicine. This study was devoted to the determination of polyphenols, flavonoids, and condensed tannins contents of Aristolochia longa L. after their extraction by using various solvents with different polarities (methanol, acetone and distilled water). These extracts were prepared from stem, leaves, fruits and rhizome. The antioxidant activity was determined using three in vitro assays methods: scavenging effect on DPPH, the reducing power assay and ẞ-carotene bleaching inhibition (CBI). The results obtained indicate that the acetone extracts from the aerial parts presented the highest contents of polyphenols. The results of The antioxidant activity showed that all extracts of Aristolochia longa L., prepared using different solvent, have diverse antioxidant capacities. However, the aerial parts methanol extract exhibited the highest antioxidant capacity of DPPH and reducing power (Respectively 55,04ug/ml±1,29 and 0,2 mg/ml±0,019 ). Nevertheless, the aerial parts acetone extract showed the highest antioxidant capacity in the test of ẞ-carotene bleaching inhibition with 57%. These preliminary results could be used to justify the traditional use of this plant and their bioactive substances could be exploited for therapeutic purposes such as antioxidant and antimicrobial.

Keywords: aristolochia longa l., polyphenols, flavonoids, condensed tannins, antioxidant activity

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Authors: Md. Kabir Azaharul Islam

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Background: The purpose of this interventions was to describe the source and extent to increase health seeking rights and uptake of quality integrated maternal health, family planning and HIV information, clinical-non clinical services, and commodities amongst young people age 10-24 among brothel based Female Sex Worker’s in Bangladesh. Such Knowledge will equip with information to develop more appropriate and effective interventions that address the problem of HIV/AIDS and SRHR within the brothel based female sex worker’s community. Methods: Before start the intervention we observed situation in brothel and identify lack of knowledge about health issues, modern health facility, sexual harassment and violence & health rights. To enable access to the intervention obtained permission from a series of stakeholders within the brothel system. This intervention to the most vulnerable young key people during January 2014 to December, 2015, it designed an intervention that focuses on using peer education and sensitization meeting with self help group leader’s, pimbs, swardarni, house owner, local leaders, law enforcement agencies and target young key people (YKPs) through peer educator’s distributed BCC materials and conducted one to one and group session issues of HIV/AIDS, life skill education, maternal health, sexual reproductive health & rights, gender based violence, STD/STI and drug users in the community. Set up community based satellite clinic to provided clinical-non clinical services and commodities for SRH, FP and HIV including general health among brothel based FSWs. Peer educator frequently move and informed target beneficiaries’ age 10-24 YKPs about satellite clinic as well as time & date in the community. Results: This intervention highly promotes of brothel based FSW utilization of local facility based health providers private and public health facilities.2400 FSWs age 10-24 received information on SRHR, FP and HIV as well as existing health facilities, most of FSWs to received service from traditional healer before intervention. More than 1080 FSWs received clinical-non clinical services and commodities from satellite clinic including 12 ANC, 12 PNC and 25 MR. Most of young FSW age 10-24 are treated bonded girls under swardarni, house owner and pimbs, they have no rights to free movement as per need. As a result, they have no rights for free movement. However the brothel self help group (SHG) has become sensitized flowing this intervention. Conclusions: The majority of female sex workers well being regarding information on SRHR, FP and HIV as well as local health facilities now they feel free to go outside facilities for better health service. not only increased FSWs’ vulnerability to HIV infection and sexual reproductive health rights but also had huge implications for their human rights. This means that even when some clients impinged FSW’s rights (for example avoiding payment for services under the pretext of dissatisfaction), they might not be able to seek redress for fear of being ejected from the brothel. They raise voice national & local level different forum.

Keywords: ANC, HIV, PNC, SRHR

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Authors: Weixiang Liu, Yukun Qin, Song Liu, Pengcheng Li

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Plant diseases can cause the death of crops with great economic losses. Particularly, those diseases are usually caused by pathogenic fungi. Metal fungicides are a type of pesticide that has advantages of a low-cost, broad antimicrobial spectrum and strong sterilization effect. However, the frequent and wide application of traditional metal fungicides has caused serious problems such as environmental pollution, the outbreak of mites and phytotoxicity. Therefore, it is critically necessary to discover new organic metal fungicides alternatives that have a low metal content, low toxicity, and little influence on mites. Chitosan, the second most abundant natural polysaccharide next to cellulose, was proved to have broad-spectrum antifungal activity against a variety of fungi. However, the use of chitosan was limited due to its poor solubility and weaker antifungal activity compared with commercial fungicide. Therefore, in order to improve the water solubility and antifungal activity, many researchers grafted the active groups onto chitosan. The present work was to combine free metal ions with chitosan, to prepare more potent antifungal chitosan derivatives, thus, based on condensation reaction, chitosan derivative bearing amino pyridine group was prepared and subsequently followed by coordination with cupric ions, zinc ions and nickel ions to synthesize chitosan metal complexes. The calculations by density functional theory (DFT) show that the copper ions and nickel ions underwent dsp2 hybridization, the zinc ions underwent sp3 hybridization, and all of them are coordinated by the carbon atom in the p-π conjugate group and the oxygen atoms in the acetate ion. The antifungal properties of chitosan metal complexes against Phytophthora capsici (P. capsici), Gibberella zeae (G. zeae), Fusarium oxysporum (F. oxysporum) and Botrytis cinerea (B. cinerea) were also assayed. In addition, a plant toxicity experiment was carried out. The experiments indicated that the derivatives have significantly enhanced antifungal activity after metal ions complexation compared with the original chitosan. It was shown that 0.20 mg/mL of O-CSPX-Cu can 100% inhibit the growth of P. capsici and 0.20 mg/mL of O-CSPX-Ni can 87.5% inhibit the growth of B. cinerea. In general, their activities are better than the positive control oligosaccharides. The combination of the pyridine formyl groups seems to favor biological activity. Additionally, the ligand fashion was precisely analyzed, and the results revealed that the copper ions and nickel ions underwent dsp2 hybridization, the zinc ions underwent sp3 hybridization, and the carbon atoms of the p-π conjugate group and the oxygen atoms of acetate ion are involved in the coordination of metal ions. The phytotoxicity assay of O-CSPX-M was also conducted, unlike the traditional metal fungicides, the metal complexes were not significantly toxic to the leaves of wheat. O-CSPX-Zn can even increase chlorophyll content in wheat leaves at 0.40 mg/mL. This is mainly because chitosan itself promotes plant growth and counteracts the phytotoxicity of metal ions. The chitosan derivative described here may lend themselves to future applicative studies in crop protection.

Keywords: coordination, chitosan, metal complex, antifungal properties

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Authors: Ahmed El Naggar, Homyan Saleh

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Dams are crucial for flood control, water supply, and the creation of hydroelectric power. Every dam has a water conveyance system, such as a spillway, providing the safe discharge of catastrophic floods when necessary. Spillway design has historically been investigated in laboratory research owing to the absence of suitable full-scale flow monitoring equipment and safety problems. Prototype measurements of aerated flows are urgently needed to quantify projected scale effects and provide missing validation data for design guidelines and numerical simulations. In this work, an image-based investigation of free-surface flows on a tiered spillway was undertaken at the laboratory (fixed camera installation) and prototype size (drone video) (drone footage) (drone footage). The drone videos were generated using data from citizen science. Analyses permitted the measurement of the free-surface aeration inception point, air-water surface velocities, fluctuations, and residual energy at the chute's downstream end from a remote site. The prototype observations offered full-scale proof of concept, while laboratory results were efficiently confirmed against invasive phase-detection probe data. This paper stresses the efficacy of image-based analyses at prototype spillways. It highlights how citizen science data may enable academics better understand real-world air-water flow dynamics and offers a framework for a small collection of long-missing prototype data.

Keywords: remote sensing, aerated flows, large dams, proof of concept, dam spillways, air-water flows, prototype operation, remote sensing, inception point, optical flow, turbulence, residual energy

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

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

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

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Authors: Acacia A. Salomão, Willian L. Gomes da Silva, Gustavo G. Shimamoto, Matthieu Tubino

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Biodiesel physical and chemical properties depend on the raw material composition used in its synthesis. Saturated fatty acid esters confer high oxidative stability, while unsaturated fatty acid esters improve the cold flow properties. In this study, an alternative vegetal source - the macauba kernel oil - was used in the biodiesel synthesis instead of conventional sources. Macauba can be collected from native palm trees and is found in several regions in Brazil. Its oil is a promising source when compared to several other oils commonly obtained from food products, such as soybean, corn or canola oil, due to its specific characteristics. However, the usage of biodiesel made from macauba oil alone is not recommended due to the difficulty of producing macauba in large quantities. For this reason, this project proposes the usage of blends of the macauba oil with conventional oils. These blends were prepared by mixing the macauba biodiesel with biodiesels obtained from soybean, corn, and from residual frying oil, in the following proportions: 20:80, 50:50 e 80:20 (w/w). Three parameters were evaluated, using the standard methods, in order to check the quality of the produced biofuel and its blends: oxidative stability, cold filter plugging point (CFPP), and iodine value. The induction period (IP) expresses the oxidative stability of the biodiesel, the CFPP expresses the lowest temperature in which the biodiesel flows through a filter without plugging the system and the iodine value is a measure of the number of double bonds in a sample. The biodiesels obtained from soybean, residual frying oil and corn presented iodine values higher than 110 g/100 g, low oxidative stability and low CFPP. The IP values obtained from these biodiesels were lower than 8 h, which is below the recommended standard value. On the other hand, the CFPP value was found within the allowed limit (5 ºC is the maximum). Regarding the macauba biodiesel, a low iodine value was observed (31.6 g/100 g), which indicates the presence of high content of saturated fatty acid esters. The presence of saturated fatty acid esters should imply in a high oxidative stability (which was found accordingly, with IP = 64 h), and high CFPP, but curiously the latter was not observed (-3 ºC). This behavior can be explained by looking at the size of the carbon chains, as 65% of this biodiesel is composed by short chain saturated fatty acid esters (less than 14 carbons). The high oxidative stability and the low CFPP of macauba biodiesel are what make this biofuel a promising source. The soybean, corn and residual frying oil biodiesels also have low CFPP, but low oxidative stability. Therefore the blends proposed in this work, if compared to the common biodiesels, maintain the flow properties but present enhanced oxidative stability.

Keywords: biodiesel, blends, macauba kernel oil, stability oxidative

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Authors: Behrooz Ghasemi, Bahram Sharijian

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Al2O3/Mo nanocomposite powders were successfully synthesized by mechanical milling through mechanochemical reaction between MoO3 and Al. The structural evolutions of powder particles during mechanical milling were studied by X-ray diffractometry (XRD), energy dispersive X-ray spectroscopy(EDX) and scanning electron microscopy (SEM). Results show that Al2O3-Mo was completely obtained after 5 hr of milling. The crystallite sizes of Al2O3 and Mo after milling for 20 hr were about 45 nm and 23 nm, respectively. With longer milling time, the intensities of Al2O3 and Mo peaks decreased and became broad due to the decrease in crystallite size. Morphological features of powders were influenced by the milling time. The resulting Al2O3- Mo nanocomposite powder exhibited an average particle size of 200 nm after 20 hr of milling. Also nanocomposite powder after 10 hr milling had relatively equiaxed shape with uniformly distributed Mo phase in Al2O3 matrix.

Keywords: Al2O3/Mo, nanocomposites, mechanochemical, mechanical milling

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Authors: Victor Chinecherem Ejeke, Raphael Eze Nnam

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The main objective of this research is to produce biodiesel from waste vegetable oil using activated eggshell waste as solid catalysts. A transesterification reaction was performed for the conversion to biodiesel. Waste eggshells were calcined at 700°C, 800°C and 900°C for a time period of 3hrs for the preparation of the renewable catalyst. The calcined waste eggshell catalyst was characterized using X-Ray Florescence (XRF) Spectroscopy, which revealed CaO as the major constituent (90.86%); this was further confirmed by X-Ray Diffraction (XRD) and Fourier Transform Infrared (FTIR) analyses. The prepared catalyst was used for transesterification reaction and the effects of calcination temperature (700 to 900°C), Deep Eutectic Solvent DES loading (3 to 18 wt. %), Waste Egg Shell (WES) catalyst loading (6 to 14 wt. %) on the conversion to biodiesel were studied. The yield of biodiesel using a waste eggshell catalyst (91%) is comparable to conventional catalyst like sodium hydroxide with a yield of 80-90%. The maximum biodiesel production yield was obtained at a specific oil-to methanol molar ratio of 1:10, a temperature of 65°C and a catalyst loading of 14g-wt%. The biodiesel produced was characterized as being composed of methyl Tetradecanoate (C₁₄H₂₈O₂) 30.92% using the Gas Chromatographic (GC-MS) analysis. The fuel properties of the biodiesel (Flashpoint 138ᵒC) were comparable to commercial diesel, and hence it can be used in compression-ignition engines. The results indicated that the catalysts derived from waste eggshell had high potential to be used as biodiesel production catalysts in transesterification of waste vegetable oil with the advantage of reusability and also not requiring water washing steps.

Keywords: waste vegetable oil, catalyst , biodiesel , waste egg shell

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Authors: Xiang Zheng, Zhaoping Zhong

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In this study, Aspen Plus was used to simulate the whole process of biomass conversion to liquid fuel in different ways, and the main results of material and energy flow were obtained. The process optimization and evaluation were carried out on the four routes of cellulosic biomass pyrolysis gasification low-carbon olefin synthesis olefin oligomerization, biomass water pyrolysis and polymerization to jet fuel, biomass fermentation to ethanol, and biomass pyrolysis to liquid fuel. The environmental impacts of three biomass species (poplar wood, corn stover, and rice husk) were compared by the gasification synthesis pathway. The global warming potential, acidification potential, and eutrophication potential of the three biomasses were the same as those of rice husk > poplar wood > corn stover. In terms of human health hazard potential and solid waste potential, the results were poplar > rice husk > corn stover. In the popular pathway, 100 kg of poplar biomass was input to obtain 11.9 kg of aviation coal fraction and 6.3 kg of gasoline fraction. The energy conversion rate of the system was 31.6% when the output product energy included only the aviation coal product. In the basic process of hydrothermal depolymerization process, 14.41 kg aviation kerosene was produced per 100 kg biomass. The energy conversion rate of the basic process was 33.09%, which can be increased to 38.47% after the optimal utilization of lignin gasification and steam reforming for hydrogen production. The total exergy efficiency of the system increased from 30.48% to 34.43% after optimization, and the exergy loss mainly came from the concentration of precursor dilute solution. Global warming potential in environmental impact is mostly affected by the production process. Poplar wood was used as raw material in the process of ethanol production from cellulosic biomass. The simulation results showed that 827.4 kg of pretreatment mixture, 450.6 kg of fermentation broth, and 24.8 kg of ethanol were produced per 100 kg of biomass. The power output of boiler combustion reached 94.1 MJ, the unit power consumption in the process was 174.9 MJ, and the energy conversion rate was 33.5%. The environmental impact was mainly concentrated in the production process and agricultural processes. On the basis of the original biomass pyrolysis to liquid fuel, the enzymatic hydrolysis lignin residue produced by cellulose fermentation to produce ethanol was used as the pyrolysis raw material, and the fermentation and pyrolysis processes were coupled. In the coupled process, 24.8 kg ethanol and 4.78 kg upgraded liquid fuel were produced per 100 kg biomass with an energy conversion rate of 35.13%.

Keywords: biomass conversion, biofuel, process optimization, life cycle assessment

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Authors: Fatih Sonmez

Abstract:

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and it is the most common form of dementia that affects aged people. Acetylcholinesterase is a hydrolase involved in the termination of impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter ACh in the central and peripheral nervous system. Carvacrol (5-iso-propyl-2-methyl-phenol) is a main bioactive monoterpene isolated from many medicinal herbs, such as Thymus vulgaris, Monarda punctate and Origanum vulgare spp. It is known that carvacrol has been widely used as an active anti-inflammatory ingredient, which can inhibit the isoproterenol induced inflammation in myocardial infarcted rats. In this paper, a series of 12 carvacrol substituted carbamate derivatives (2a-l) was synthesized and their inhibitory activities on AChE and BuChE were evaluated. Among them, 2d exhibited the strongest inhibition against AChE with an IC50 value of 2.22 µM, which was 130-fold more than that of carvacrol (IC50 = 288.26 µM).

Keywords: Acetylcholinesterase, Butyrylcholinesterase, Carbamate, Carvacrol

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Authors: K. Menad, A. Faddeg

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Zeolites are a family of mineral compounds. With special properties that have led to several important industrial applications. Ion exchange has enabled the first industrial application in the field of water treatment. The exchange by aqueous pathway is the method most used in the case of such microporous materials and this technique will be used in this work. The objective of this work is to find performance materials for the recovery of heavy metals such as cadmium. The study is to compare the properties of different ion exchange zeolite Na-X, Na-A, their physical mixture and the composite A (LTA) / X (FAU). After the synthesis of various zeolites X and A, it was designed a model Core-Shell to form a composite zeolite A on zeolite X. Finally, ion exchange studies were performed on these zeolite materials. The cation is exclusively tested for cadmium, a toxic element and is harmful to health and the environment.

Keywords: zeolite A, zeolite X, ion exchange, water treatment

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Authors: Aicha Bensouici, Assia Mili, Naouel Rdjem, Nacera Baali

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Copper oxide decorated reduced graphene oxide (GO) was obtained successfully using two steps route synthesis was used. Firstly, graphene oxide was obtained using a modified Hummers method by excluding sodium nitrate from starting materials. After washing-centrifugation routine pristine GO was decorated by copper oxide using a refluxation technique at 120°C during 2h, and an equal amount of GO and copper acetate was used. Three CuO-rGO nanocomposite samples types were obtained at 30min, 24h, and 7 day stirring time. TAC results show dose dependent behavior of CuO-rGO and confirm no influence of stirring time on antioxidant properties, 30min is considered as an optimal stirring condition.

Keywords: copper oxide, reduced graphene oxide, TAC, GO

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