Search results for: cell free supernatant

Authors: Zh. Saffari, A. Naeimi, M. S. Ekrami-Kakhki, F. Hamidi

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Fe3O4 is one of the important magnetic oxides with spinel structure; it has exhibited unique electric and magnetic properties based on the electron transfer between Fe2+ and Fe3+ in the octahedral sites. Fe3O4 has received considerable attention in various areas such as cancer therapy, drug targeting, enzyme immobilization catalysis, magnetic cell separation, magnetic refrigeration systems and super-paramagnetic materials Fe3O4–TiO2 nanostructures were synthesized by simple, effective and new co-precipitation method assisted by ultrasonic reaction at room temperatures with organic surfactant. The effect of various parameters such as temperature, time, and power on the size and morphology of the product was investigated. Alternating gradient force magnetometer shows that Fe3O4 nanoparticles exhibit super-paramagnetic behaviour at room temperature. For preparation of nanocomposite, 1 g of TiO2 nanostructures were dispersed in 100 mL of ethanol. 0.25 g of Fe(NO3)2 and 2 mL of octanoic acid was added to the solution as a surfactant. Then, NaOH solution (1.5 M) was slowly added into the solution until the pH of the mixture was 7–8. After complete precipitation, the solution placed under the ultrasonic irradiation for 30 min. The product was centrifuged, washed with distilled water and dried in an oven at 100 °C for 3 h. The resulting red powder was calcinated at 800 °C for 3 h to remove any organic residue. The photocatalytic behaviour of Fe3O4–TiO2 nanoparticles was evaluated using the degradation of a Methyl Violet (MV) aqueous solution under ultraviolet light irradiation. As time increased, more and more MV was adsorbed on the nanoparticles catalyst, until the absorption peak vanish. The MV concentration decreased rapidly with increasing UV-irradiation time

Keywords: magnetic, methyl violet, nanocomposite, photocatalytic

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Authors: H. Li, W. Qin, Ben Ye

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Friction Push Plug Welding (FPPW) is a solid phase welding suitable for repairing defective welds and filling self-reacting weld keyholes in Friction Stir Welds. In FPPW process, a tapered shaped plug is rotated at high speed and forced into a tapered hole in the substrate. The plug and substrate metal is softened by the increasing temperature generated by friction and material plastic deformation. This paper aims to investigate the effect of process parameters on the quality of the weld. Orthogonal design methods were employed to reduce the amount of experiment. Three values were selected for each process parameter, rotation speed (1500r/min, 2000r/min, 2500r/min), plunge depth (2mm, 3mm, 4mm) and plunge speed (60mm/min, 90mm/min, 120r/min). AA6061aluminum alloy plug and substrate plate was used in the experiment. In a trial test with the plunge depth of 1mm, a noticeable defect appeared due to the short plunge time and insufficient temperature. From the recorded temperature profiles, it was found that the peak temperature increased with the increase of the rotation speed, plunge speed and plunge depth. In the initial stage, the plunge speed was the main factor affecting heat generation, while in the steady state welding stage, the rotation speed played a more important role. The FPPW weld defect includes flash and incomplete penetration in the upper, middle and bottom interface with the substrate. To obtain defect free weld, the higher rotation speed and proper plunge depth were recommended.

Keywords: friction push plug welding, process parameter, weld defect, orthogonal design

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Authors: Gyula I. Tóth, Shaho Abdalla

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Even though numerical simulations indeed have a significant precursory/supportive role in exploring the disordered phase displaying no long-range order in pattern formation models, studying the stability properties of this phase and determining the order of the ordered-disordered phase transition in these models necessitate an analytical description of the disordered phase. First, we will present the results of a comprehensive statistical analysis of a large number (1,000-10,000) of numerical simulations in the Swift-Hohenberg model, where the bulk disordered (or amorphous) phase is stable. We will show that the average free energy density (over configurations) converges, while the variance of the energy density vanishes with increasing system size in numerical simulations, which suggest that the disordered phase is a thermodynamic phase (i.e., its properties are independent of the configuration in the macroscopic limit). Furthermore, the structural analysis of this phase in the Fourier space suggests that the phase can be modeled by a colored isotropic Gaussian noise, where any instant of the noise describes a possible configuration. Based on these results, we developed the general mathematical framework of finding a pool of solutions to partial differential equations in the sense of continuous probability measure, which we will present briefly. Applying the general idea to the Swift-Hohenberg model we show, that the amorphous phase can be found, and its properties can be determined analytically. As the general mathematical framework is not restricted to continuum theories, we hope that the proposed methodology will open a new chapter in studying disordered phases.

Keywords: fundamental theory, mathematical physics, continuum models, analytical description

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Authors: Saja M. Nabat Al-Ajrash, Charles Browning, Rose Eckerle, Li Cao

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A process that utilizes a combination of additive manufacturing (AM), a preceramic polymer, and a chopped carbon fiber precursorto fabricate Silicon Carbon/ Carbon fibers (SiC/C) composites have been developed. The study has shown a promising, cost-effective, and efficient route to fabricate complex SiC/C composites using additive manufacturing. A key part of this effort was the mapping of the material’s microstructure through the thickness of the composite. Microstructural features in the pyrolyzed composites through the successive AM layers, such as defects, crystal size and their distribution, interatomic spacing, chemical bonds, were investigated using high-resolution scanning and transmission electron microscopy. As a result, the microstructure developed in SiC/C composites after printing, cure, and pyrolysis has been successfully mapped through the thickness of the derived composites. Dense and nearly defect-free parts after polymer to ceramic conversion were observed. The ceramic matrix composite displayed three coexisting phases, including silicon carbide, silicon oxycarbide, and turbostratic carbon. Lattice fringes imaging and X-Ray Diffraction analysis showed well-defined SiC and turbostratic carbon features. The cross-sectional mapping of the printed-then-pyrolyzed structures has confirmed consistent structural and chemical features within the internal layers of the AM parts. Noteworthy, however, is that a crust-like area with high crystallinity has been observed in the first and last external layers. Not only do these crust-like regions have structural characteristics distinct from the internal layers, but they also have elemental distributions different than the internal layers.

Keywords: SiC, preceramic polymer, additive manufacturing, ceramic

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Authors: Himanshi Rathore, Shalinee Prasad, Satyawati Sharma, Ajay Singh Yadav

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Medicinal mushrooms are acceptable all over the world not only because they have a unique flavour and texture but also due to the presence of great nutritional, nutraceutical and functional properties. High content of physiologically active substances like ergosterol, vitamin D, phenolic compounds, triterpenoids and steroids make these medicinal mushrooms a key source of nutraceuticals. Calocybe indica is a popular medicinal mushroom of India which is known to possess high amount of secondary metabolites including ergosterol (vitamin D2). The ergosterol gets converted to vitamin D in the presence of UV rays by a photochemical reaction. In lieu of the above facts the present study was undertaken to investigate the effect of UV-B light treatment on the vitamin D2 concentration, phenolic content and non volatile compounds in Calocybe indica. For this study, UV-B light source of intensity 5.3w/m2 was used to expose mushrooms for the time period of 0min, 30min, 60min and 90 min. It was found that the vitamin D2 concentration increased with the time duration i.e. 85±0.15 (0 min), 182±1.6 (30 min), 187±0.4 (60 min) and 182 ±0.8 (90 min) μg/g (dry weight). Highest concentration of vitamin D2 was found at 60 min duration. No discoloration in sliced mushrooms was observed during the exposure time. The results revealed that the exposure of mushrooms for a minimum of 30 min duration under UVB source can be a novel, convenient and cheapest way to increase the vitamin D content in mushrooms. This can be one of richest source to fulfil the recommended dietary allowances of vitamin D in our daily diets. The paper provides information on the enhancement of vitamin D content by UV lights and its effects on the non volatile (soluble sugars, free amino acids, 5′-nucleotides and phenolics) compounds will also be presented.

Keywords: Calocybe indica, ergosterol, nutraceutical, phenolics

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Authors: Khalid Mehmood, Riaz Hussain, Rao Z. Abbas, Tariq Abbas, Abdul Ghaffar, Ahmad J. Sabir

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Blood born diseases such as trypanosomiasis have negative impacts on health, production and working efficiency of camels in different camel-rearing areas of the world including Pakistan. In present study blood samples were collected from camels kept at the desert condition of cholistan to estimate the prevalence of trypanosomiasis and hemato-biochemical changes in naturally infected cases. Results showed an overall 9.31% prevalence of trypanosomiasis in camels. Various clinical signs such as pyrexia, occasional shivering, inappetence, urticaria, swelling, lethargy, going down in condition and edema of pads were observed in few cases. The statistical analysis did not show significant association of age and sex with trypanosomiasis. However, results revealed significantly decreased values of total erythrocyte counts, packed cell volume, hemoglobin concentration, mean corpuscular hemoglobin concentration, serum total proteins and albumin while increased values of mean corpuscular volume was recorded in infected animals as compared to healthy. A significant (P<0.01) increased values of total leukocyte count, monocyte, lymphocyte, neutrophils, and eosinophils was recorded in infected animals. Moreover, microscopic examination of blood films obtained from naturally infected cases showed the presence of parasite and various morphological changes in cells such as stomatocyte, hyperchromasia, and polychromasia. Significantly increased values of different hepatic enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were also recorded.

Keywords: camel, hematological indices, serum enzymes, Trypanosomiasis

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Authors: Shadia Al-Bahlani, Khadija Al-Bulushi, Zuweina Al-Hadidi, Buthaina Al-Dhahl, Nadia Al-Abri

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Breast cancer is the most common cancer in women worldwide. Triple-Negative Breast Cancer (TNBC) is an aggressive type of breast cancer, which is defined by the absence of Estrogen (ER), Progesterone (PR) and human epidermal growth factor (Her-2) receptors. The calpain system plays an important role in many cellular processes including apoptosis, necrosis, cell signaling and proliferation. However, the role of calpain in cisplatin (CDDP)-induced apoptosis in TNBC cells is not fully understood. Here, TNBC (MDA-MB231) cells were treated with different concentration of CDDP (0, 20 & 40 µM) and calpain activation and apoptosis were measured by western blot and Hoechst Stain respectively. In addition, calpain modulation by either activation and/or inhibition and its effect on CDDP-induced apoptosis were assessed by the same above approaches. Our findings showed that CDDP induced endoplasmic reticulum stress and thus Calcium release and subsequently activate calpain α-fodrin cleavage indicated by the increase in GRP78 and Calmodulin protein expression and respectively in MDA-MB231 cells. It also induced apoptosis as measured by Hoechst stain and caspase-12 cleavage. Calpain activation by both Cyclopiazonic acid and Thapsigargin showed similar effect and enhanced the sensitivity of these cells to CDDP treatment. On the other hand, calpain inhibition by either specific siRNA and/or exogenous inhibitor (Calpeptin) had an adverse effect where it attenuated calpain activation and thus CDDP- induced apoptosis in these cells. Altogether, these findings suggested that calpain activation play an essential role in sensitizing the TNBC cells to CDDP-induced apoptosis. This might lead to the discovery of novel treatment to over this aggressive type of breast cancer.

Keywords: calpain, cisplatin, apoptosis, breast cancer

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Authors: F. Yılmaz, Y. Saylan, A. Derazshamshir, S. Atay, A. Denizli

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Quartz crystal microbalance (QCM), high-resolution mass-sensing technique, measures changes in mass on oscillating quartz crystal surface by measuring changes in oscillation frequency of crystal in real time. Protein adsorption techniques via hydrophobic interaction between protein and solid support, called hydrophobic interaction chromatography (HIC), can be favorable in many cases. Some nanoparticles can be effectively applied for HIC. HIC takes advantage of the hydrophobicity of proteins by promoting its separation on the basis of hydrophobic interactions between immobilized hydrophobic ligands and nonpolar regions on the surface of the proteins. Lysozyme is found in a variety of vertebrate cells and secretions, such as spleen, milk, tears, and egg white. Its common applications are as a cell-disrupting agent for extraction of bacterial intracellular products, as an antibacterial agent in ophthalmologic preparations, as a food additive in milk products and as a drug for treatment of ulcers and infections. Lysozyme has also been used in cancer chemotherapy. The aim of this study is the synthesis of hydrophobic nanoparticles for Lysozyme detection. For this purpose, methacryoyl-L-phenylalanine was chosen as a hydrophobic matrix. The hydrophobic nanoparticles were synthesized by micro-emulsion polymerization method. Then, hydrophobic QCM nanosensor was characterized by Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, atomic force microscopy (AFM) and zeta size analysis. Hydrophobic QCM nanosensor was tested for real-time detection of Lysozyme from aqueous solution. The kinetic and affinity studies were determined by using Lysozyme solutions with different concentrations. The responses related to a mass (Δm) and frequency (Δf) shifts were used to evaluate adsorption properties.

Keywords: nanosensor, HIC, lysozyme, QCM

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Authors: Achim Kampker, Heiner Hans Heimes, Nemanja Sarovic, Jan-Philip Ganser, Saskia Wessel, Christoph Lienemann

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The electrification of the power train is a fundamental technical transition in the automotive industry and poses a major challenge for established car companies. Providing the traction energy, requiring an ever greater amount of space within the car and having a high share of value-add the lithium-ion battery is a central component of the electric power train and a completely new component to car manufacturers at the same time. Being relatively new to the automotive industry, the current design of the product architecture and production process (including manufacturing and assembling processes) of lithium-ion battery modules do not allow for an easy and cost-efficient disassembly or product design change. Yet these two requirements will increase in importance with rising sales volumes of electric cars in the near future and need to be addressed for the electric car to be competitive with conventional power train systems. This paper focuses on the current product architecture and production process of common automotive battery modules from prismatic lithium-ion battery cells to derive impacts for a remanufacturing concept. The information necessary for this purpose were gathered by literature research, patent inquiries, industry expert interviews and first-hand experiences of the authors. On the basis of these results, the underlying causes for the design´s lack of remanufacturability and flexibility with regards to product design changes are examined. In all, this paper gives an extensive and detailed overview of the state of the art of the product architecture and production process of lithium-ion battery modules from prismatic battery cells, identifies its deficiencies and derives improvement measures.

Keywords: battery module, prismatic lithium-ion battery cell, product architecture, production process, remanufacturing, flexibility

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Authors: Weiyao Zhu, Qian Qi, Ming Yue, Dongxu Ma

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Due to the nano-micro pore structures and the massive multi-stage multi-cluster hydraulic fracturing in shale gas reservoirs, the multi-scale seepage flows are much more complicated than in most other conventional reservoirs, and are crucial for the economic development of shale gas. In this study, a new multi-scale non-linear flow model was established and simplified, based on different diffusion and slip correction coefficients. Due to the fact that different flow laws existed between the fracture network and matrix zone, a three-zone composite model was proposed. Then, according to the conformal transformation combined with the law of equivalent percolation resistance, the productivity equation of a horizontal fractured well, with consideration given to diffusion, slip, desorption, and absorption, was built. Also, an analytic solution was derived, and the interference of the multi-cluster fractures was analyzed. The results indicated that the diffusion of the shale gas was mainly in the transition and Fick diffusion regions. The matrix permeability was found to be influenced by slippage and diffusion, which was determined by the pore pressure and diameter according to the Knudsen number. It was determined that, with the increased half-lengths of the fracture clusters, flow conductivity of the fractures, and permeability of the fracture network, the productivity of the fractured well also increased. Meanwhile, with the increased number of fractures, the distance between the fractures decreased, and the productivity slowly increased due to the mutual interference of the fractures. In regard to the fractured horizontal wells, the free gas was found to majorly contribute to the productivity, while the contribution of the desorption increased with the increased pressure differences.

Keywords: multi-scale, fracture network, composite model, productivity

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Authors: Larisa Gheber

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Mitosis is an essential process by which duplicated genetic information is transmitted from mother to daughter cells. Incorrect chromosome segregation during mitosis can lead to genetic diseases, chromosome instability and cancer. This process is mediated by a dynamic microtubule-based intracellular structure, the mitotic spindle. One of the major factors that govern the mitotic spindle dynamics are the kinesin-5 biological nano motors that were believed to move unidirectionally on the microtubule filaments, using ATP hydrolysis, thus performing essential functions in mitotic spindle dynamics. Surprisingly, several reports from our and other laboratories have demonstrated that some kinesin-5 motors are bi-directional: they move in minus-end direction on the microtubules as single-molecules and can switch directionality under a number of conditions. These findings broke a twenty-five-years old dogma regarding kinesin directionality (1, 2). The mechanism of this bi-directional motility and its physiological significance remain unclear. To address this unresolved problem, we apply an interdisciplinary approach combining live cell imaging, biophysical single molecule, and structural experiments to examine the activity of these motors and their mutated variants in vivo and in vitro. Our data shows that factors such as protein phosphorylation (3, 4), motor clustering on the microtubules (5, 6) and structural elements (7, 8) regulate the bi-directional motility of kinesin motors. We also show, using Cryo-EM, that bi-directional kinesin motors obtain non-canonical microtubule binding, which is essential to their special motile properties and intracellular functions. We will discuss the implication of these findings to mechanism bi-directional motility and physiological roles in mitosis.

Keywords: mitosis, cancer, kinesin, microtubules, biochemistry, biophysics

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Authors: Abdul Azarrudin M. A., Pothiraj K., Kandasamy Satish

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In the current automobile scenario, there comes a demand on more sophistication and comfort drive feel on passenger segments. The clutch pedal effort is one such customer touch feels in manual transmission vehicles, where the driver continuous to operate the clutch pedal in his entire the driving maneuvers. Hence optimum pedal efforts at green condition and over mileage to be ensured for fatigue free the driving. As friction is one the predominant factor and its tendency to challenge the technicality by causing the function degradation. One such semi-hydraulic systems shows load efficiency of about 70-75% over lifetime only due to the increase in friction which leads to the increase in pedal effort and cause fatigue to the vehicle driver. This work deals with the study of friction with different interfaces and its influence in the fulcrum points over mileage, with the objective of understanding the trend over mileage and determining the alternative ways of resolving it. In that one way of methodology is the reduction of friction by experimental investigation of various friction reduction interfaces like metal-to-metal interface and it has been tried out and is detailed further. Also, the specific attention has been put up considering the fulcrum load and its contact interfaces to move on with this study. The main results of the experimental data with the influence of three different contact interfaces are being presented with an ultimate intention of ending up into less fatigue with longer consistent pedal effort, thus smoothens the operation of the end user. The Experimental validation also has been done through rig-level test setup to depict the performance at static condition and in-parallel vehicle level test has also been performed to record the additional influences if any.

Keywords: automobile, clutch, friction, fork

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Authors: Vadim Makarov, Stewart T.Cole

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PBTZ169 is novel drug candidate with high efficacy in animals models, and its combination treatment of PBTZ169 with BDQ and pyrazinamide was shown to be more efficacious than the standard treatment for tuberculosis in a mouse model. The target of PBTZ169 is famous DprE1, an essential enzyme in cell wall biosynthesis. The crystal structure of the DprE1-PBTZ169 complex reveals formation of a semimercaptal adduct with Cys387 in the active site and explains the irreversible inactivation of the enzyme. Furthermore, this drug candidate demonstrated during preclinical research ‘drug like’ properties what made it an attractive drug candidate to treat tuberculosis in humans. During first clinical trials several cohorts of the healthy volunteers were treated by the single doses of PBTZ169 as well as two weeks repeated treatment was chosen for two maximal doses. As expected PBTZ169 was well tolerated, and no significant toxicity effects were observed during the trials. The study of the metabolism shown that human metabolism of PBTZ169 is very different from microbial or animals compound transformation. So main pathway of microbial, mice and less rats metabolism connected with reduction processes, but human metabolism mainly connected with oxidation processes. Due to this difference we observed several metabolites of PBTZ169 in humans with antitubercular activity, and now we can conclude that animal antituberculosis activity of PBTZ169 is a result not only activity of the drug itself, but it is a result of the sum activity of the drug and its metabolites. Direct antimicrobial plasma activity was studied, and such activity was observed for 24 hours after human treatment for some doses. This data gets high chance for good efficacy of PBTZ169 in human for treatment TB infection. Second phase of clinical trials was started summer of 2017 and continues to the present day. Available data will be presented.

Keywords: clinical trials, DprE1, PBTZ169, metabolism

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Authors: Elizabeth Bourgeois

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During social distancing, fashion and self-expression have been pushed further into virtual environments. In VR spaces, identities can be curated easily, untethered from the necessities of life and work. Personal styles reach a wider audience and follow new rules. Digital platforms leave some, but not all, 'real world' clothing constraints behind. Virtual aesthetics are set by the user and the software. Gen Z is a native user, applying face filters on Instagram and Snapchat and styling outfits and skins in apps like Gacha Life, Roblox, and Fortnite. These games cultivate space for community and personal style. Loosely tied to human forms, each app has physical aesthetics, with clear vernacular dress defining it. There are ecosystems of makers, consumers, and critics. Designer-modelers create original assets, brands, and luxury items. Fashion and beauty are ephemeral but always reflect the idealization of form and self. Online communities have already established new beauty ideals that impact live fashion trends. Fashion houses develop AR filters, gaming hairstyles challenge real-world colorists, and musicians perform virtual concerts in their avatar forms. In these times, social media and gaming communities promote the expression of public identity. The online dress is no longer tied to 'real' bodies or cloth. In virtual worlds, there are still tribes, status symbols, gender identities, and roles, but free of fabric, form, and static social structure, there is room for fantastic invention.

Keywords: virtual reality, fashion, Gen Z, social media, gaming

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Authors: Amritanshu Sandilya, M. V. Shah

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Collapsible soils such as loess are a common geotechnical challenge due to their potential to undergo sudden and severe settlement under certain loading conditions. The need for filling engineering to increase developing land has grown significantly in recent years, which has created several difficulties in managing soil strength and stability during compaction. Numerous engineering problems, such as roadbed subsidence and pavement cracking, have been brought about by insufficient fill strength. Therefore, strict control of compaction parameters is essential to reduce these distresses. Accurately measuring the degree of compaction, which is often represented by compactness is an important component of compaction control. For credible predictions of how collapsible soils will behave under complicated loading situations, the accuracy of laboratory studies is essential. Therefore, this study aims to investigate the energy transfer in collapsible soils during laboratory Proctor compaction tests to provide insights into how energy transfer can be optimized to achieve more accurate and reliable results in compaction testing. The compaction characteristics in terms of energy of loess soil have been studied at moisture content corresponding to dry of optimum, at the optimum and wet side of optimum and at different compaction energy levels. The hammer impact force (E0) and soil bottom force (E) were measured using an impact load cell mounted at the bottom of the compaction mould. The variation in energy consumption ratio (E/ E0) was observed and compared with the compaction curve of the soil. The results indicate that the plot of energy consumption ratio versus moisture content can serve as a reliable indicator of the compaction characteristics of the soil in terms of energy.

Keywords: soil compaction, proctor compaction test, collapsible soil, energy transfer

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Authors: Yi-Hui Lai, Chih-Hsiang Yang, Li-Chung Hsu

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The inflammasome is a protein complex that modulates caspase-1 activity, resulting in proteolytic cleavage of proinflammatory cytokines such as IL-1β and IL-18, into their bioactive forms. It has been shown that the inflammasomes play a crucial role in the clearance of pathogenic infection and tissue repair. However, dysregulated inflammasome activation contributes to a wide range of human diseases such as cancers and auto-inflammatory diseases. Yet, regulation of NLRP3 inflammasome activation remains largely unknown. We discovered a novel DEAD box protein, whose biological function has not been reported, not only negatively regulates NLRP3 inflammasome activation by interfering NLRP3 inflammasome assembly and cellular localization but also mitigate pyroptosis upon pathogen evasion. The DEAD-box protein is the first DEAD-box protein gets involved in modulation of the inflammasome activation. In our study, we found that caspase-1 activation and mature IL-1β production were largely enhanced upon LPS challenge in the DEAD box-containing protein- deleted THP-1 macrophages and bone marrow-derived macrophages (BMDMs). In addition, this DEAD box-containing protein migrates from the nucleus to the cytoplasm upon LPS stimulation, which is required for its inhibitory role in NLRP3 inflammasome activation. The DEAD box-containing protein specifically interacted with the LRR motif of NLRP3 via its DEAD domain. Furthermore, due to the crucial role of the NLRP3 LRR domain in the recruitment of NLRP3 to mitochondria and binding to its adaptor ASC, we found that the interaction of NLRP3 and ASC was downregulated in the presence of the DEAD box-containing protein. In addition to the mechanical study, we also found that this DEAD box protein protects host cells from inflammasome-triggered cell death in response to broad-ranging pathogens such as Candida albicans, Streptococcus pneumoniae, etc., involved in nosocomial infections and severe fever shock. Collectively, our results suggest that this novel DEAD box molecule might be a key therapeutic strategy for various infectious diseases.

Keywords: inflammasome, inflammation, innate immunity, pyroptosis

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Authors: Gyati Shilakari Asthana, Abhay Asthana, Dharm Veer Kohli, Suresh Prasad Vyas

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Purpose: The therapeutic potential of oligonucleotide (ODN) is primarily dependent upon its safe and efficient delivery to specific cells overcoming degradation and maximizing cellular uptake in vivo. The present study is focused to design low molecular weight chitosan nanoconstructs to meet the requirements of safe and effectual delivery of ODNs. LMW-chitosan is a biodegradable, water soluble, biocompatible polymer and is useful as a non-viral vector for gene delivery due to its better stability in water. Methods: LMW chitosan ODN nanoparticles (CHODN NPs) were formulated by self-assembled method using various N/P ratios (moles ratio of amine groups of CH to phosphate moieties of ODNs; 0.5:1, 1:1, 3:1, 5:1, and 7:1) of CH to ODN. The developed CHODN NPs were evaluated with respect to gel retardation assay, particle size, zeta potential and cytotoxicity and transfection efficiency. Results: Complete complexation of CH/ODN was achieved at the charge ratio of 0.5:1 or above and CHODN NPs displayed resistance against DNase I. On increasing the N/P ratio of CH/ODN, the particle size of the NPs decreased whereas zeta potential (ZV) value increased. No significant toxicity was observed at all CH concentrations. The transfection efficiency was increased on increasing N/P ratio from 1:1 to 3:1, whereas it was decreased with further increment in N/P ratio upto 7:1. Maximum transfection of CHODN NPs with both the cell lines (Raw 267.4 cells and Hela cells) was achieved at N/P ratio of 3:1. The results suggest that transfection efficiency of CHODN NPs is dependent on N/P ratio. Conclusion: Thus the present study states that LMW chitosan nanoparticulate carriers would be acceptable choice to improve transfection efficiency in vitro as well as in vivo delivery of oligonucleotide.

Keywords: LMW-chitosan, chitosan nanoparticles, biocompatibility, cytotoxicity study, transfection efficiency, oligonucleotide

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Authors: Juliet Udoudom

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Inappropriate complement selection constitutes one of the major features of non-standard complementation in the Nigerian users of English output of sentence construction. This paper investigates complement clause choice in Written Educated Nigerian English (ENE) and offers some results. It aims at determining preferred and dispreferred patterns of complement clause selection in respect of verb heads in English by selected Nigerian users of English. The complementation data analyzed in this investigation were obtained from experimental tasks designed to elicit complement categories of Verb – Noun -, Adjective – and Prepositional – heads in English. Insights from the Government – Binding relations were employed in analyzing data, which comprised responses obtained from one hundred subjects to a picture elicitation exercise, a grammaticality judgement test, and a free composition task. The findings indicate a general tendency for clausal complements (CPs) introduced by the complementizer that to be preferred by the subjects studied. Of the 235 tokens of clausal complements which occurred in our corpus, 128 of them representing 54.46% were CPs headed by that, while whether – and if-clauses recorded 31.07% and 8.94%, respectively. The complement clause-type which recorded the lowest incidence of choice was the CP headed by the Complementiser, for with a 5.53% incident of occurrence. Further findings from the study indicate that semantic features of relevant embedding verb heads were not taken into consideration in the choice of complementisers which introduce the respective complement clauses, hence the that-clause was chosen to complement verbs like prefer. In addition, the dispreferred choice of the for-clause is explicable in terms of the fact that the respondents studied regard ‘for’ as a preposition, and not a complementiser.

Keywords: complement, complement clause complement selection, complementisers, government-binding

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Authors: P. G. Romeo

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A Lie group is a highly sophisticated structure which is a smooth manifold whose underlying set of elements is equipped with the structure of a group such that the group multiplication and inverse-assigning functions are smooth. This structure was introduced by the Norwegian mathematician So- phus Lie who founded the theory of continuous groups. The Lie groups are well developed and have wide applications in areas including Mathematical Physics. There are several advances and generalizations for Lie groups and Lie groupoids is one such which is termed as a "many-object generalization" of Lie groups. A groupoid is a category whose morphisms are all invertible, obviously, every group is a groupoid but not conversely. Definition 1. A Lie groupoid G ⇒ M is a groupoid G on a base M together with smooth structures on G and M such that the maps α, β: G → M are surjective submertions, the object inclusion map x '→ 1x, M → G is smooth, and the partial multiplication G ∗ G → G is smooth. A bundle is a triple (E, p, B) where E, B are topological spaces p: E → B is a map. Space B is called the base space and space E is called total space and map p is the projection of the bundle. For each b ∈ B, the space p−1(b) is called the fibre of the bundle over b ∈ B. Intuitively a bundle is regarded as a union of fibres p−1(b) for b ∈ B parametrized by B and ’glued together’ by the topology of the space E. A cross-section of a bundle (E, p, B) is a map s: B → E such that ps = 1B. Example 1. Given any space B, a product bundle over B with fibre F is (B × F, p, B) where p is the projection on the first factor. Definition 2. A principal bundle P (M, G, π) consists of a manifold P, a Lie group G, and a free right action of G on P denoted (u, g) '→ ug, such that the orbits of the action coincide with the fibres of the surjective submersion π : P → M, and such that M is covered by the domains of local sections σ: U → P, U ⊆ M, of π. Definition 3. A Lie group bundle, or LGB, is a smooth fibre bundle (K, q, M ) in which each fibre (Km = q−1(m), and the fibre type G, has a Lie group structure, and for which there is an atlas {ψi: Ui × G → KUi } such that each {ψi,m : G → Km}, is an isomorphism of Lie groups. A morphism of LGB from (K, q, M ) to (K′, q′, M′) is a morphism (F, f ) of fibre bundles such that each Fm: Km → K′ is a morphism of Lie groups. In this paper, we will be discussing the Lie groupoid bundles. Here it is seen that to a Lie groupoid Ω on base B there is associated a collection of principal bundles Ωx(B, Ωx), all of which are mutually isomorphic and conversely, associated to any principal bundle P (B, G, p) there is a groupoid called the Ehresmann groupoid which is easily seen to be Lie. Further, some interesting properties of the category of Lie groupoids and bundles will be explored.

Keywords: groupoid, lie group, lie groupoid, bundle

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Authors: Gajanan M. Sonwane

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The computational studies on 2-phenazinamines with their protein targets have been carried out to design compounds with potential anticancer activity. This strategy of designing compounds possessing selectivity over specific tyrosine kinase has been achieved through G-QSAR and molecular docking studies. The objective of this research has been to design newer 2-phenazinamine derivatives as Bcr-Abl tyrosine kinase inhibitors by G-QSAR, molecular docking studies followed by wet-lab studies along with evaluation of their anticancer potential. Computational chemistry was done by using VLife MDS 4.3 and Autodock 4.2 followed by wet-lab experiments for synthesizing 2-phenazinamine derivatives. The chemical structures of ligands in 2D were drawn by employing Chemdraw 2D Ultra 8.0 and were converted into 3D. These were optimized by using a semi-empirical method called MOPAC. The protein structure was retrieved from RCSC protein data bank as a PDB file. The binding interactions of protein and ligands were done by using PYMOL. The molecular properties of the designed compounds were predicted in silico by using Osiris property explorer. The parent compound 2-phenazinamine was synthesized by reduction of 2, 4-dinitro-N-phenyl-benzenamine in the presence of tin chloride followed by cyclization in the presence of nitrobenzene and magnesium sulfate. The derivatization at the amino function of 2-phenazinamine was performed by treating parent compound with various aldehydes in the presence of dicyclohexylcarbodiimide (DCC) and urea to afford 2-(2-chlorophenyl)-3-(phenazine-2-yl) thiazolidine-4-one. Synthesized 39 novel derivatives of 2-phenazinamine and performed antioxidant activity, anti antiproliferative on the bulb of onion and anticancer activity on cell line showing significant competition with marked blockbuster drug imatinib.

Keywords: computer-aided drug design, tyrosin kinases, anticancer, docking

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Authors: Tannaz Alimardani, Amirhossein Moghanian, Morteza Elsa

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Bioactive glasses (BGs) are a group of surface-reactive biomaterials used in clinical applications as implants or filler materials in the human body to repair and replace diseased or damaged bone. Sol-gel technique was employed to prepare a SiO₂-CaO-P₂O₅ glass with a nominal composition of 58S BG with the addition of Sr and Li modifiers which imparts special properties to the BG. The effect of simultaneous addition of Sr and Li on bioactivity and biocompatibility, proliferation, alkaline phosphatase (ALP) activity of osteoblast cell line MC3T3-E1 and antibacterial property against methicillin-resistant Staphylococcus aureus (MRSA) bacteria were examined. BGs were characterized by X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy before and after soaking the samples in the simulated body fluid (SBF) for different time intervals to characterize the formation of hydroxyapatite (HA) formed on the surface of BGs. Structural characterization indicated that the simultaneous presence of 5% Sr and 5% Li in 58S-BG composition not only did not retard HA formation because of the opposite effect of Sr and Li of the dissolution of BG in the SBF, but also stimulated the differentiation and proliferation of MC3T3-E1s. Moreover, the presence of Sr and Li on the dissolution of the ions resulted in an increase in the mean number of DAPI-labeled nuclei which was in good agreement with the live/dead assay. The result of antibacterial tests revealed that Sr and Li-substituted 58S bioactive glass exhibited a potential antibacterial effect against MRSA bacteria. Because of optimal proliferation and ALP activity of MC3T3-E1cells, proper bioactivity and high antibacterial potential against MRSA, BG-5/5 is suggested as a multifunctional candidate for bone tissue engineering.

Keywords: alkaline, alkaline earth, bioglass, co-doping, ion release

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Authors: Moquan Gong

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In recent years, with the rapid development of deep learning, pre-training technology for natural language processing has made great progress. The early field of natural language processing has long used word vector methods such as Word2Vec to encode text. These word vector methods can also be regarded as static pre-training techniques. However, this context-free text representation brings very limited improvement to subsequent natural language processing tasks and cannot solve the problem of word polysemy. ELMo proposes a context-sensitive text representation method that can effectively handle polysemy problems. Since then, pre-training language models such as GPT and BERT have been proposed one after another. Among them, the BERT model has significantly improved its performance on many typical downstream tasks, greatly promoting the technological development in the field of natural language processing, and has since entered the field of natural language processing. The era of dynamic pre-training technology. Since then, a large number of pre-trained language models based on BERT and XLNet have continued to emerge, and pre-training technology has become an indispensable mainstream technology in the field of natural language processing. This article first gives an overview of pre-training technology and its development history, and introduces in detail the classic pre-training technology in the field of natural language processing, including early static pre-training technology and classic dynamic pre-training technology; and then briefly sorts out a series of enlightening technologies. Pre-training technology, including improved models based on BERT and XLNet; on this basis, analyze the problems faced by current pre-training technology research; finally, look forward to the future development trend of pre-training technology.

Keywords: natural language processing, pre-training, language model, word vectors

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Authors: Anish Shah, Steve A. Wakelin, Derrick Moot, Aurélie Laugraud, Hayley J. Ridgway

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A mixed pasture system of ryegrass-clover is used in New Zealand, where clovers are generally inoculated with commercially available strains of rhizobia. The community of rhizobia living in the soil and the way in which they interact with the plant are affected by different biotic and abiotic factors. In general, bacterial richness and diversity in soil varies by soil pH. pH also affects cell physiology and acts as a master variable that controls the wider soil physiochemical conditions such as P availability, Al release and micronutrient availability. As such, pH can have both primary and secondary effects on soil biology and processes. The aim of this work was to investigate the effect of soil pH on the genetic diversity and metabolic profile of Rhizobium leguminosarum strains nodulating clover. Soils were collected from 12 farms across New Zealand which had a pH(water) range of between 4.9 and 7.5, with four acidic (pH 4.9 – 5.5), four ‘neutral’ (5.8 – 6.1) and four alkaline (6.5 – 7.5) soils. Bacteria were recovered from nodules of Trifolium repens (white clover) and T. subterraneum (subterranean clover) grown in the soils. The strains were cultured and screened against a range of pH-amended media to demonstrate whether they were adapted to pH levels similar to their native soils. The strains which showed high relative growth at a given pH (~20% of those isolated) were selected for metabolic and taxonomic profiling. The Omnilog (Biolog Inc., Hayward, CA) phenotype array was used to perform assays on carbon (C) utilisation for selected strains. DNA was extracted from the strains which had differing C utilisation profiles and PCR products for both forward and reverse primers were sequenced for the following genes: 16S rRNA, recA, nodC, nodD and nifH (symbiotic).

Keywords: bacterial diversity, clover, metabolic and taxonomic profiling, pH adaptation, rhizobia

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Authors: Dukali Abujnah, Mokhtar Blgacem Halbuda

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Water is one of the world's natural resources. It is an essential source for the maintenance of human, animal, and plant life. It has a significant impact on the country's economy and all human activities. Over the past twenty years, pressure on water resources has increased due to population and industrial growth and increasing demand for agricultural and household products, which has become a major concern of the international community. The aim of this study is the physical and bacteriological analysis of drinking water in the city of Value. The study covered different locations in the city. Thirty-six groundwater samples were taken from wells and various tanks owned by the State and private wells, and the Ain Thalia spring and other samples were taken from underground water tanks. It fills up with rainwater during the rainy season. These samples were analyzed for their physical, chemical, and biological status and the results were compared to Libyan and World Health Organization drinking water specifications to assess the quality of drinking water in the city of Value. Physical and chemical analysis of water samples showed acceptable values for acidity and electrical conductivity, and turbidity was found in water samples collected from underground reservoirs compared to Libyan and World Health Organization standards. The highest levels of electrical conductivity and alkalinity, TDS, and water hardness in the samples collected were below the maximum acceptable levels for drinking water as recommended by Libyan and World Health Organization specifications. The biological test results also showed that the water samples were free of intestinal bacteria.

Keywords: quality, agriculture, region, reservoir, evaluation

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Authors: I. D. Laryushin, V. A. Kostin, A. A. Silaev, N. V. Vvedenskii

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Generation of broadband intense terahertz (THz) radiation attracts reasonable interest due to various applications, such as the THz time-domain spectroscopy, the probing and control of various ultrafast processes, the THz imaging with subwavelength resolution, and many others. One of the most promising methods for generating powerful and broadband terahertz pulses is based on focusing two-color femtosecond ionizing laser pulses in gases, including ambient air. For this method, the amplitudes of terahertz pulses are determined by the free-electron current density remaining in a formed plasma after the passage of the laser pulse. The excitation of this residual current density can be treated as multi-wave mixing: Аn effective generation of terahertz radiation is possible only when the frequency ratio of one-color components in the two-color pulse is close to irreducible rational fraction a/b with small odd sum a + b. This work focuses on the optimal parameters (polarizations and intensities) of laser components for the strongest THz generation. The optimal values of parameters are found numerically and analytically with the use of semiclassical approach for calculating the residual current density. For frequency ratios close to a/(a ± 1) with natural a, the strongest THz generation is shown to take place when the both laser components have circular polarizations and equal intensities. For this optimal case, an analytical formula for the residual current density was derived. For the frequency ratios such as 2/5, the two-color ionizing pulses with circularly polarized components practically do not excite the residual current density. However, the optimal parameters correspond generally to specific elliptical (not linear) polarizations of the components and intensity ratios close to unity.

Keywords: broadband terahertz radiation, ionization, laser plasma, ultrashort two-color pulses

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Authors: Radoslav Stojchevski, Leonid Poretsky, Dimiter Avtanski

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Proinflammatory cytokines play an important role in cancer initiation and progression by mediating the intracellular communication between the cancer cells and tumor microenvironment. Increased tumor growth causing reduced oxygen concentration and oxygen pressure commonly result in hypoxia. Mechanistically, hypoxia is characterized by stabilization and nuclear translocation of hypoxia-inducible factor 1 alpha (HIF-1α) followed by propagation of molecular pathway cascade involving multiple downstream targets. Cobalt(II) chloride (CoCl₂) is commonly used to mimic hypoxia in experimental conditions since it directly induces the expression of HIF-1α. The aim of the present study was to investigate the in vitro effects and the molecular mechanisms by which hypoxia regulates the cytokine secretory profile of breast cancer cells. As a model for this study, we used several breast cancer cell lines bearing various molecular characteristics and metastatic potential (MDA-MB-231 (clauding low, ER-/PR-/HER²⁻), MCF-7 (luminal A, ER⁺/PR⁺/HER²⁻), and BT-474 (liminal B, ER⁺/PR⁺/HER²⁺)). We demonstrated that breast cancer cells secrete numerous cytokines and cytokine ligands, including interleukins, chemokines, and growth factors. Treatment with CoCl₂significantly modulated the breast cancer cells' cytokine expression in a concentration- and time-dependent manner. These effects were mediated via activation of several signaling pathways (JNK/SAPK1, NF-κB, STAT5A/B, and Erk/MAPK1/2). Taken together, the present data define some of the molecular mechanisms by which hypoxia affects the breast cancer cells' cytokine secretory profile, thus contributing to the development of novel therapies for metastatic breast cancer.

Keywords: breast cancer, cytokines, cobalt(II) chloride (CoCl₂), hypoxia

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Authors: Khaled Igbaria

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Laila Al-Othman is a well-known feminist writer in Kuwait and the entire Arab world. She was born in 1943 in Kuwait to a large and wealthy family. The author has written several short stories, as well as novels, such as The Woman and the Cat (1985) and Wasumayya Comes out of the Sea (1986), which was chosen as one of the best 100 Arab novels of the 21st century. Another prominent novel of hers is Ṣamt al-Farāshāt [Silence of the Butterflies] (2007), which was highly controversial in her native Kuwait upon publication. For this study, her engagement in feminism was achieved by exploring the different ways in which her novel, Ṣamt al-Farāshāt [Silence of the Butterflies], addresses several feminist issues, mainly forced marriage, rape and sexual abuse, gender-based physical, sexual violence, and enforced silence. This paper focuses on demonstrating social obstacles and continuous trauma caused by a sequence of pain experienced by Arab females in their patriarchal society. This study argues that the novel reveals a sustained effort to raise the banner of feminism and a strong desire to liberate Arab women from patriarchal domination. Al-Othman successfully and uniquely represents women as gender-based traumatic victims of sexual and physical violence, forced silence, and general oppression in the patriarchal Arab society, as those needing help, support, protection, and liberation. They are not represented as independent or free. Methodologically, the study employs a qualitative literary analysis method in addition to trauma theory psychoanalysis, concentrating on feminist issues highlighted in the novel.

Keywords: Al-Othman, Arab women pain, trauma within narration., Silence of the Butterflies

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Authors: Mohammed T. Shabeer

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Hoary moorlands of Tibet bear bundle of religious traditions. Vajrayana tradition of Tibetan Buddhism is one of the deep rooted religious orders of the area. It demands the homage to a variety of gods and diverse worships, especially to manifestations like the Dalai Lamas. This divine diversity has been conceptualized by remoteness of the area and transcontinental intrusion of Asiatic philosophies like Indian Buddhism, Mongolian Shamanism and Hindu Tantrism. This study reveals the role of Hindu Tantrism in conceptualizing the manifestations in Vajrayana Tradition of Tibetan Buddhism in a comparative way. Nowadays, the academic explorations and researches in the field of ‘Tibetology’ are widely tolerable in east and west alike. International community concerns such studies supportive of the restless campaigns for ‘free Tibet’. Moreover, the scientific sources on the topic are rarest and precious in the field of comparative religion. This study reveals a clear account of god concept of Vajrayana tradition and insists that the god concept of the tradition is conceptualized from the amalgamation of Indian Hindu Tantrism, Mongolian Shamanism, and Indian Buddhism. Primly, it sheds the light upon the mysterious similarities between Indian and Tibetan concepts of manifestation of gods. The scientific examination of this problem lasts in the conclusion that the transcontinental transmission of Hindu Tantrism in the special occasion of Buddhist Diaspora of 12th century in consequence of the invasion of Muslim Ghorid Sultanate had paved a vital role in shaping the Vajrayana tradition especially conceptualizing the manifestation of Tibetan gods.

Keywords: Buddhist diaspora, Hindu tantrism, manifestation of god, Vajrayana tradition of Tibetan Buddhism

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Authors: V. Nigam, V. Nambiar

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Aegle Marmelos leaf has been used as a remedy for various gastrointestinal infections and lowering blood sugar level in traditional system of medicine in India due to the presence of various constituents such as flavonoids, tannins and alkaloids (eg. Aegelin, Marmelosin, Luvangetin).The objective of the present study was to evaluate the total antioxidant activity, total and individual phenol content of the wild and cultivated variety of Aegle marmelos leaves to assess the role of this plant in ethanomedicine in India. The methanolic extracts of the leaves were screened for total antioxidant capacity through Ferric Reducing Antioxidant Potential (FRAP) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay; Total Phenol content (TPC) through spectrophotometric technique based on Folin Ciocalteau assay and for qualitative estimation of phenols, High performance Liquid Chromatography was used. The TPC of wild and cultivated variety was 7.6% and 6.5% respectively whereas HPLC analysis for quantification of individual polyphenol revealed the presence of gallic acid, chlorogenic acid and Ferullic acid in wild variety whereas gallic acid, Ferullic acid and pyrocatechol in cultivated variety. FRAP values and IC 50 value (DPPH) for wild and cultivated variety was 14.65 μmol/l and 11.80μmol/l; 437 μg/ml and 620μg/ml respectively and thus it can be used as potential inhibitor of free radicals. The wild variety was having more antioxidant capacity than the cultivated one it can be exploited further for its therapeutic application. As Aegle marmelos is rich in antioxidant, it can be used as food additives to delay the oxidative deterioration of foods and as nutraceutical in medicinal formulation against degenerative diseases like diabetes.

Keywords: antioxidant activity, aegle marmelos, antidiabetic, nutraceutical

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Authors: Majda El Moufarej

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Higher education plays a central role in socio-economic development. However, with the wave of change mainly due to the extensive use of technology in the workplace, the rate of unemployment among graduates rises because they lack the appropriate competencies and skills currently required in professional life. This situation has led higher education institutions worldwide to reconsider their missions, strategic planning, and curricula, among other elements to redress the image of the university as expected. When it comes to practice, there are many obstacles that hinder the achievement of the expected objectives, especially in public universities with free access, as in the case of Morocco. Nevertheless, huge efforts have been made by educational managers to improve the quality of education by focusing on the issue of pedagogical approaches, where university teachers assume more responsibility to save the situation. In this paper, the focus will be placed on the issue of pedagogical approaches to be adopted, depending on the nature of the subject, the size of the class, the available equipment, the students’ level and degree of motivation. Before elaborating on this idea, it may be more insightful to begin by addressing another variable, which concerns the new role of university teachers and their qualification in pedagogical competence. Then, the discussion will revolve around five pedagogical approaches currently adopted in western universities and the focus will be exclusively placed on the one which is called “the Systematic Approach to course Design”, due to its crucial relevance in the teaching of subjects in the schools of humanities, as it can guide the teacher in the development of an explicit program for purposeful teaching and learning. The study is based on a qualitative method, and the findings will be analyzed and followed by some recommendations about how to overcome difficulties in teaching large groups, while transmitting the relevant knowledge and skills on demand in the workplace.

Keywords: higher education, public universities, pedagogical approaches, pedagogical competence

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