Search results for: combined biomarker

Authors: Rasha Ahmadi

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Glioblastoma is one of the most frequent brain malignancies, having a high mortality rate and limited survival in individuals with this malignancy. Despite different treatments and surgery, recurrence of glioblastoma cancer stem cells may arise as a subsequent tumor. For this reason, it is crucial to research the markers associated with glioblastoma stem cells and specifically their microenvironment. In this study, using bioinformatics analysis, we analyzed and nominated genes in the microenvironment pathways of glioblastoma stem cells. In this study, an appropriate database was selected for analysis by referring to the GEO database. This dataset comprised gene expression patterns in stem cells derived from glioblastoma patients. Gene clusters were divided as high and low expression. Enrichment databases such as Enrichr, STRING, and GEPIA were utilized to analyze the data appropriately. Finally, we extracted the potential genes 2700 high-expression and 1100 low-expression genes are implicated in the metabolic pathways of glioblastoma cancer progression. Cellular senescence, MAPK, TNF, hypoxia, zimosterol biosynthesis, and phosphatidylinositol metabolism pathways were substantially expressed and the metabolic pathways were downregulated. After assessing the association between protein networks, MSMP, SOX2, FGD4 ,and CNTNAP3 genes with high expression and DMKN and SBSN genes with low were selected. All of these genes were observed in the survival curve, with a survival of fewer than 10 percent over around 15 months. hsa-mir-192-5p, hsa-mir-129-5p, hsa-mir-215-5p, hsa-mir-335-5p, and hsa-mir-340-5p played key function in glioblastoma cancer stem cells microenviroments. We introduced critical genes through integrated and regular bioinformatics studies by assessing the amount of gene expression profile data that can play an important role in targeting genes involved in the energy and microenvironment of glioblastoma cancer stem cells. Have. This study indicated that hsa-mir-192-5p, and hsa-mir-129-5p are appropriate candidates for this.

Keywords: Glioblastoma, Cancer Stem Cells, Biomarker Discovery, Gene Expression Profiles, Bioinformatics Analysis, Tumor Microenvironment

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Authors: Saoussen Dhib, Chris M. Mannaerts, Zoubeida Bargaoui, Ben H. P. Maathuis, Petra Budde

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In this study, a new method to delineate rain areas in northern Tunisia is presented. The proposed approach is based on the blending of the geostationary Meteosat Second Generation (MSG) infrared channel (IR) with the low-earth orbiting passive Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI). To blend this two products, we need to apply two main steps. Firstly, we have to identify the rainy pixels. This step is achieved based on a classification using MSG channel IR 10.8 and the water vapor WV 0.62, applying a threshold on the temperature difference of less than 11 Kelvin which is an approximation of the clouds that have a high likelihood of precipitation. The second step consists on fitting the relation between IR cloud top temperature with the TMI rain rates. The correlation coefficient of these two variables has a negative tendency, meaning that with decreasing temperature there is an increase in rainfall intensity. The fitting equation will be applied for the whole day of MSG 15 minutes interval images which will be summed. To validate this combined product, daily extreme rainfall events occurred during the period 2007-2009 were selected, using a threshold criterion for large rainfall depth (> 50 mm/day) occurring at least at one rainfall station. Inverse distance interpolation method was applied to generate rainfall maps for the drier summer season (from May to October) and the wet winter season (from November to April). The evaluation results of the estimated rainfall combining MSG and TMI was very encouraging where all the events were detected rainy and the correlation coefficients were much better than previous evaluated products over the study area such as MSGMPE and PERSIANN products. The combined product showed a better performance during wet season. We notice also an overestimation of the maximal estimated rain for many events.

Keywords: combination, extreme, rainfall, TMI-MSG, Tunisia

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Authors: Coriolano Salvini

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The increasing utilization of renewable energy sources for electric power production calls for the introduction of energy storage systems to match the electric demand along the time. Although many countries are pursuing as a final goal a “decarbonized” electrical system, in the next decades the traditional fossil fuel fed power plant still will play a relevant role in fulfilling the electric demand. Presently, such plants provide grid ancillary services (frequency control, grid balance, reserve, etc.) by adapting the output power to the grid requirements. An interesting option is represented by the possibility to use traditional plants to improve the grid storage capabilities. The present paper is addressed to small-medium size systems suited for distributed energy storage. The proposed Energy Storage System (ESS) is based on a Compressed Air Energy Storage (CAES) integrated into a Gas-Steam Combined Cycle (GSCC) or a Gas Turbine based CHP plants. The systems can be incorporated in an ex novo built plant or added to an already existing one. To avoid any geological restriction related to the availability of natural compressed air reservoirs, artificial storage is addressed. During the charging phase, electric power is absorbed from the grid by an electric driven intercooled/aftercooled compressor. In the course of the discharge phase, the compressed stored air is sent to a heat transfer device fed by hot gas taken upstream the Heat Recovery Steam Generator (HRSG) and subsequently expanded for power production. To maximize the output power, a staged reheated expansion process is adopted. The specific power production related to the kilogram per second of exhaust gas used to heat the stored air is two/three times larger than that achieved if the gas were used to produce steam in the HRSG. As a result, a relevant power augmentation is attained with respect to normal GSCC plant operations without additional use of fuel. Therefore, the excess of output power can be considered “fuel free” and the storage system can be compared to “pure” ESSs such as electrochemical, pumped hydro or adiabatic CAES. Representative cases featured by different power absorption, production capability, and storage capacity have been taken into consideration. For each case, a technical optimization aimed at maximizing the storage efficiency has been carried out. On the basis of the resulting storage pressure and volume, number of compression and expansion stages, air heater arrangement and process quantities found for each case, a cost estimation of the storage systems has been performed. Storage efficiencies from 0.6 to 0.7 have been assessed. Capital costs in the range of 400-800 €/kW and 500-1000 €/kWh have been estimated. Such figures are similar or lower to those featuring alternative storage technologies.

Keywords: artificial air storage reservoir, compressed air energy storage (CAES), gas steam combined cycle (GSCC), techno-economic analysis

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Authors: Guillaume Lemahieu, Matthias Sentis, Giovanni Brambilla, Gérard Meunier

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Static Multiple Light Scattering (SMLS) has been shown to be a straightforward technique for the characterization of colloidal dispersions without dilution, as multiply scattered light in backscattered and transmitted mode is directly related to the concentration and size of scatterers present in the sample. In this view, the use of SMLS for stability measurement of various dispersion types has already been widely described in the literature. Indeed, starting from a homogeneous dispersion, the variation of backscattered or transmitted light can be attributed to destabilization phenomena, such as migration (sedimentation, creaming) or particle size variation (flocculation, aggregation). In a view to investigating more on the dispersibility of colloidal suspensions, an experimental set-up for “at the line” SMLS experiment has been developed to understand the impact of the formulation parameters on particle size and dispersibility. The SMLS experiment is performed with a high acquisition rate (up to 10 measurements per second), without dilution, and under direct agitation. Using such experimental device, SMLS detection can be combined with the Hansen approach to optimize the dispersing and stabilizing properties of TiO₂ particles. It appears that the dispersibility and the stability spheres generated are clearly separated, arguing that lower stability is not necessarily a consequence of poor dispersibility. Beyond this clarification, this combined SMLS-Hansen approach is a major step toward the optimization of dispersibility and stability of colloidal formulations by finding solvents having the best compromise between dispersing and stabilizing properties. Such study can be intended to find better dispersion media, greener and cheaper solvents to optimize particles suspensions, reduce the content of costly stabilizing additives or satisfy product regulatory requirements evolution in various industrial fields using suspensions (paints & inks, coatings, cosmetics, energy).

Keywords: dispersibility, stability, Hansen parameters, particles, solvents

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Authors: Nehal Adel Khalil, Amel Foad Ketat, Fairouz Elsayed Mohamed Ali, Nahla Abdelmoneim Hamid, Hazem Farag Manaa

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Background: Chronic myeloid leukemia (CML) represents 15% of adult leukemias. Imatinib Mesylate (IM) is the gold standard treatment for new cases of CML. Treatment with IM results in improvement of the majority of cases. However, about 25% of cases may develop resistance. Sensitive and specific early predictors of IM resistance in CML patients have not been established to date. Aim: To investigate the value of miR-451 in CML as an early predictor for IM resistance in Egyptian CML patients. Methods: The study employed Real time Polymerase Reaction (qPCR) technique to investigate the leucocytic expression of miR-451 in fifteen newly diagnosed CML patients (group I), fifteen IM responder CML patients (group II), fifteen IM resistant CML patients (group III) and fifteen healthy subjects of matched age and sex as a control group (group IV). The response to IM was defined as < 10% BCR-ABL transcript level after 3 months of therapy. The following parameters were assessed in subjects of all the studied groups: 1- Complete blood count (CBC). 2- Measurement of plasma level of miRNA 451 using real-time Polymerase Chain Reaction (qPCR). 3- Detection of BCR-ABL gene mutation in CML using qPCR. Results: The present study revealed that miR-451 was significantly down-regulated in leucocytes of newly diagnosed CML patients as compared to healthy subjects. IM responder CML patients showed an up-regulation of miR- 451 compared with IM resistant CML patients. Conclusion: According to the data from the present study, it can be concluded that leucocytic miR- 451 expression is a useful additional follow-up marker for the response to IM and a promising prognostic biomarker for CML.

Keywords: chronic myeloid leukemia, imatinib resistance, microRNA 451, Polymerase Chain Reaction

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Authors: Mahshid Hodjat, Maryam Baeeri, Mohammad Amin Rezvanfar, Mohammad Abdollahi

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Ethephon is one of the most widely used plant growth regulator in agriculture that its application has been increased in recent years. The toxicity of organophosphate compounds is mostly attributed to their potent inhibition of acetylcholinesterase and their involvement in neurodegenerative disease. Although there are few reports on butyrylcholinesterase inhibitory role of ethephon, still there is no evidence on neurotoxicity and genotoxicity of this compound. The aim of the current study is to assess the potential genotoxic effect of ethephon using two genotoxic endpoints; γH2AX expression and comet assay on embryonic murine fibroblast. γH2AX serves as an early and sensitive biomarker for evaluating the genotoxic effects of chemicals. Oxidative stress biomarkers, including intracellular reactive oxygen species, lipid peroxidation and antioxidant capacity were also examined. The results showed a significant increase in cell proliferation 24h post-treatment with 10, 40,160µg/ml ethephon. The γH2AX expression and γH2AX foci count per cell were increased at low concentration of ethephon that was concomitant with increased DNA damage break at 40 and 160 µg/ml as illustrated by increased comet tail moment. A significant increase in lipid peroxidation and ROS formation were observed at 160 µg/ml and higher doses. The results showed that low-dose of ethephon promoted cell proliferation while induce DNA damage, raising the possibility of ethephon mutagenicity. Ethephon-induced genotoxic effect of low dose might not related to oxidative damage. However, ethephon was found to increase oxidative stress at higher doses, lead to cellular cytotoxicity. Taken together, all data indicated that ethylene, deserves more attention as a plant regulator with potential genotoxicity for which appropriate control is needed to reduce its usage.

Keywords: ethephon, DNA damage, γH2AX, oxidative stress

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Authors: Sumera, Sanila Amber, Fatima Javed Mirza, Amjad Ali, Saadia Zahid

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Glioblastoma multiforme (GBM) is a widely spread and fatal primary brain tumor with an increased risk of relapse in spite of aggressive treatment. The current procedures for GBM diagnosis include invasive procedures i.e. resection or biopsy, to acquire tumor mass. Implementation of negligibly invasive tests as a potential diagnostic technique and biofluid-based monitoring of GBM stresses on discovering biomarkers in CSF and blood. Therefore, we performed a comprehensive in silico analysis to identify potential circulating biomarkers for GBM. Initially, six gene and protein databases were utilized to mine brain-specific proteins. The resulting proteins were filtered using a channel of five tools to predict the secretory proteins. Subsequently, the expression profile of the secreted proteins was verified in the brain and blood using two databases. Additional verification of the resulting proteins was done using Plasma Proteome Database (PPD) to confirm their presence in blood. The final set of proteins was searched in literature for their relationship with GBM, keeping a special emphasis on secretome proteome. 2145 proteins were firstly mined as brain-specific, out of which 69 proteins were identified as secretory in nature. Verification of expression profile in brain and blood eliminated 58 proteins from the 69 proteins, providing a final list of 11 proteins. Further verification of these 11 proteins further eliminated 2 proteins, giving a final set of nine secretory proteins i.e. OPCML, NPTX1, LGI1, CNTN2, LY6H, SLIT1, CREG2, GDF1 and SERPINI1. Out of these 9 proteins, 7 were found to be linked to GBM, whereas 2 proteins are not investigated in GBM so far. We propose that these secretory proteins can serve as potential circulating biomarker signatures of GBM and will facilitate the development of minimally invasive diagnostic methods and novel therapeutic interventions for GBM.

Keywords: glioblastoma multiforme, secretory proteins, brain secretome, biomarkers

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Authors: Julia Zimmerman, Gaurav Savant

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This study aims to evaluate the efficacy of the U.S. Army Corp of Engineers’ River Analysis System (HEC-RAS) application to modeling the hydraulics of estuaries. HEC-RAS has been broadly used for a variety of riverine applications. However, it has not been widely applied to the study of circulation in estuaries. This report details the model development and validation of a combined 1D/2D unsteady flow hydraulic model using HEC-RAS for estuaries and they are associated with tidally influenced rivers. Two estuaries, Galveston Bay and Delaware Bay, were used as case studies. Galveston Bay, a bar-built, vertically mixed estuary, was modeled for the 2005 calendar year. Delaware Bay, a drowned river valley estuary, was modeled from October 22, 2019, to November 5, 2019. Water surface elevation was used to validate both models by comparing simulation results to NOAA’s Center for Operational Oceanographic Products and Services (CO-OPS) gauge data. Simulations were run using the Diffusion Wave Equations (DW), the Shallow Water Equations, Eulerian-Lagrangian Method (SWE-ELM), and the Shallow Water Equations Eulerian Method (SWE-EM) and compared for both accuracy and computational resources required. In general, the Diffusion Wave Equations results were found to be comparable to the two Shallow Water equations sets while requiring less computational power. The 1D/2D combined approach was valid for study areas within the 2D flow area, with the 1D flow serving mainly as an inflow boundary condition. Within the Delaware Bay estuary, the HEC-RAS DW model ran in 22 minutes and had an average R² value of 0.94 within the 2-D mesh. The Galveston Bay HEC-RAS DW ran in 6 hours and 47 minutes and had an average R² value of 0.83 within the 2-D mesh. The longer run time and lower R² for Galveston Bay can be attributed to the increased length of the time frame modeled and the greater complexity of the estuarine system. The models did not accurately capture tidal effects within the 1D flow area.

Keywords: Delaware bay, estuarine hydraulics, Galveston bay, HEC-RAS, one-dimensional modeling, two-dimensional modeling

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Authors: I-Yun Cheng, Min-Yu Chiang, Shwu-Jen Chang, San-Yuan Chen

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Osteoarthritis (OA) is among the most challenging joint diseases, and as far as we know, there is currently no exact and effective cure for it because it has low self-repair ability due to lack of blood vessels and low cell density in articular cartilage. So far, there have been several methods developed to treat cartilage disorder. The most common method is to treat the high molecular weight of hyaluronic acid (HA) injection, but it will degrade after a period of time, so the patients need to inject HA repeatedly. In recent years, self-healing hydrogel has drawn considerable attention because it can recover its initial mechanical properties after damaged and further increase the lifetime of the hydrogel. Here, we aim to develop a self-healable composite hydrogel combined with magnetic microspheres to trigger glutathione(GSH) release for promoting cartilage repair. We use HA-cyclodextrin (CD) as host polymer and poly(acrylic acid)-ferrocene (pAA-Fc) as guest polymer to form the self-healable HA-pAA hydrogel by host and guest interaction where various graft amount of pAA-Fc (pAA:Fc= 1:2, 1:1.5, 1:1, 2:1, 4:1) was conducted to develop different mechanical strength hydrogel. The rheology analysis showed that the 4:1 of pAA-Fc has higher mechanical strength than other formulations. On the other hand, iron oxide nanoparticle, poly(lactic-co-glycolic acid) (PLGA) and polyethyleneimine (PEI) were used to synthesize porous magnetic microspheres via double emulsification water-in-oil-in-water (W/O/W) to increase GSH loading which acted as a reductant to control the hydrogel crosslink density and promote hydrogel self-healing. The results show that the porous magnetic microspheres can be loaded with 70% of GSH and sustained release about 50% of GSH after 24 hours. More importantly, the HA-pAA composite hydrogel can self-heal rapidly within 24 hours when suffering external force destruction by releasing GSH from the magnetic microspheres. Therefore, the developed the HA-pAA composite hydrogel combined with GSH-loaded magnetic microspheres can be in-vivo guided to damaged OA surface for inducing the cartilage repair by controlling the crosslinking of self-healing hydrogel via GSH release.

Keywords: articular cartilage, magnetic microsphere, osteoarthritis, self-healing hydrogel

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Authors: Gurcharan Singh Buttar

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It has been discovered that although these two areas, statistics, and information theory, are independent in their nature, they can be combined to create applications in multidisciplinary mathematics. This is due to the fact that where in the field of statistics, statistical parameters (measures) play an essential role in reference to the population (distribution) under investigation. Information measure is crucial in the study of ambiguity, assortment, and unpredictability present in an array of phenomena. The following communication is a link between the two, and it has been demonstrated that the well-known conventional statistical measures can be used as a measure of information.

Keywords: probability distribution, entropy, concavity, symmetry, variance, central tendency

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Authors: Svetlana Guryeva, Inna Kornienko, Elena Petersen

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At present, translational medicine is a rapidly developing branch of biomedicine. The main idea of translational medicine is a practical application of fundamental research. One of the possible applications for translational medicine is researching therapies that improve human age-related organism condition. To fill the gap between experiments and clinical practice, it is necessary to create the standardized system for the investigation of different effects on cellular aging models. In this study, primary human fibroblasts derived from patients of different ages were used as a cellular aging model. The senescence-associated β-galactosidase activity, lipofuscin, γ-H2AX, the reactive oxygen species level, and cell death markers (annexin V/propidium iodide) were used as biomarkers of the cell functional state. The effects of damaging exposures (oxidative stress and heat shock), potential positive factors (metformin and acetaminophen), and their combinations were investigated using the described biomarkers. Oxidative stress and heat shock caused the increase in the levels of all biomarkers, and only the cells from young patients partly coped with stress 3 days after the exposures. Metformin improved the state of pretreatment cells from young and old patients. The acetaminophen did not show significant changes in the biomarker levels compare to the action of metformin. This study proved the opportunity to develop a standardized screening system based on biomarkers of the cell functional state to identify potential positive or negative effects of some physical and chemical exposures. Moreover, such a system can be useful for the aims of regenerative medicine to determine the effect of cell pretreatment before transplantation.

Keywords: biomarkers, primary fibroblasts, regenerative medicine, senescence, test system, translational medicine

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Authors: Chen ChihYu, Tang Wen Tzu, Chen Kuang Hui

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Aim —To compare the dismount skill between Taiwanese and elite international gymnastics in parallel bars following the 2017-2020 code of points. Methods—The gymnasts who advanced to the parallel bars event finals of these four competitions including World Championships, Universiade, the National Games of Taiwan, and the National Intercollegiate Athletic Games of Taiwan both 2017 and 2019 were selected in this study. The dismount skill of parallel bars was analyzed, and the average difficulty score was compared by one-way ANOVA. Descriptive statistics were applied to present the type of dismount skill and the difficulty of each gymnast in these four competitions. The data from World Championships and Universiade were combined as the international group (INT), and data of Taiwanese National Games and National Intercollegiate Athletic Games were also combined as the national group (NAT). The differences between INT and NAT were analyzed by the Chi-square test. The statistical significance of this study was set at α= 0.05. Results— i) There was a significant difference in the mean parallel bars dismount skill in these four competitions analyzed by one-way ANOVA. Both dismount scores of World Championships and Universiade were significantly higher than in Taiwanese National Games and National Intercollegiate Athletic Games (0.58±0.08 & 0.56±0.08 > 0.42±0.06 & 40±0.06, p < 0.05). ii) Most of the gymnasts in World Championships and Universiade selected the 0.6-point skill as the parallel bars dismount element, and for the Taiwanese National Games and the National Intercollegiate Athletic Games, most of the gymnasts performed the 0.4-point dismount skill. iii) The result of the Chi-square test has shown that there was a significant difference in the selection of parallel bars dismount skill. The INT group used the E or E+ difficulty element as the dismount skill, and the NAT group selected the D or D- difficulty element. Conclusion— The level of parallel bars dismount in Taiwanese gymnastics is inferior to elite international gymnastics. It is suggested that Taiwanese gymnastics must try to practice the F difficulty dismount (double salto forward tucked with half twist) in the future.

Keywords: Artistic Gymnastics World Championships, dismount, difficulty score, element

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Authors: Sofia G. Meirinho, Luis G. Dias, António M. Peres, Lígia R. Rodrigues

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The emerging development of electrochemical aptasen sors has enabled the easy and fast detection of protein biomarkers in standard and real samples. Biomarkers are produced by body organs or tumours and provide a measure of antigens on cell surfaces. When detected in high amounts in blood, they can be suggestive of tumour activity. These biomarkers are more often used to evaluate treatment effects or to assess the potential for metastatic disease in patients with established disease. Osteopontin (OPN) is a protein found in all body fluids and constitutes a possible biomarker because its overexpression has been related with breast cancer evolution and metastasis. Currently, biomarkers are commonly used for the development of diagnostic methods, allowing the detection of the disease in its initial stages. A previously described RNA aptamer was used in the current work to develop a simple and sensitive electrochemical aptasensor with high affinity for human OPN. The RNA aptamer was biotinylated and immobilized on a gold electrode by avidin-biotin interaction. The electrochemical signal generated from the aptamer–target molecule interaction was monitored electrochemically using cyclic voltammetry in the presence of [Fe (CN) 6]−3/− as a redox probe. The signal observed showed a current decrease due to the binding of OPN. The preliminary results showed that this aptasensor enables the detection of OPN in standard solutions, showing good selectivity towards the target in the presence of others interfering proteins such as bovine OPN and bovine serum albumin. The results gathered in the current work suggest that the proposed electrochemical aptasensor is a simple and sensitive detection tool for human OPN and so, may have future applications in cancer disease monitoring.

Keywords: osteopontin, aptamer, aptasensor, screen-printed electrode, cyclic voltammetry

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Authors: Bhalke D. G., Bormane D. S., Kharate G. K.

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This paper presents classification of musical instrument using machine learning techniques. The classification has been carried out using temporal, spectral, cepstral and wavelet features. Detail feature analysis is carried out using separate and combined features. Further, instrument model has been developed using K-Nearest Neighbor and Support Vector Machine (SVM). Benchmarked McGill university database has been used to test the performance of the system. Experimental result shows that SVM performs better as compared to KNN classifier.

Keywords: feature extraction, SVM, KNN, musical instruments

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Authors: Shu Hwang Ang, Choo Yee Yu, Geik Yong Ang, Yean Yean Chan, Yatimah Binti Alias, And Sook Mei Khor

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With the high prevalence of Type 2 diabetes mellitus across the world, the morbidities and mortalities associated with Type 2 diabetes have significant impact on the production line for a nation. With routine scheduled clinical visits to manage Type 2 diabetes, diabetic patients with hectic lifestyles can have low clinical compliance. Hence, it often decreases the effectiveness of diabetic management personalized for each diabetic patient. Here, we report a useful developed point-of-care (POC) device that detect glycated hemoglobin (HbA1c, biomarker for long-term Type 2 diabetic management). In fact, the established POC devices certified to be used in clinical setting are not only expensive ($ 8 to $10 per test), they also require skillful practitioners to perform sampling and interpretation. As a paper-based biosensor, the developed HbA1c biosensor utilized lateral flow principle to offer an alternative for cost-effective (approximately $2 per test) and end-user friendly device for household testing. Requiring as little as 2 L of finger-picked blood, the test can be performed at the household with just simple dilution and washings. With visual interpretation of numbers of test lines shown on the developed biosensor, it can be interpreted as easy as a urine pregnancy test, aided with scale of intensity provided. In summary, the developed HbA1c immunosensor has been tested to have high selectivity towards HbA1c, and is stable with reasonably good performance in clinical testing. Therefore, our developed HbA1c immunosensor has high potential to be an effective diabetic management tool to increase patient compliance and thus contain the progression of the diabetes.

Keywords: blood, glycated hemoglobin (HbA1c), lateral flow, type 2 diabetes mellitus

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Authors: Devinder Kaur Sugga, Ekamdeep Kaur, Jaspreet Kaur, C. Rajesh, Preeti Rajesh, Harsimran Kaur

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Withanolides are steroidal lactones and are highly oxygenated phytoconstituents that can be developed as potential anti-carcinogenic agents. The two main withanolides, namely Withaferin A and Withanolides D, have been extensively studied for their pharmacological activities. Both these withanolides are present in the Withania somnifera (WS) leaves belonging to the family Solanaceae, also known as “Indian ginseng .”In this study effects of WS leaf extract on the MCF7 breast cancer cell line were investigated by performing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects and in vitro wound-healing assay to study the effect on cancer cell migration. Our data suggest WS extracts have cytotoxic effects and are effective anti-migrating agents and thus can be a source of potential candidates for the development of potential agents against metastasis. Thus, it can be a source of potential candidates for the development of potential agents against metastasis. Insight into these results, the in-silico approach to identify the possible protein targets interacting with withanolides was taken. Protein kinase C alpha (PKCα) was among the selected 5 top-ranked target proteins identified by the Swiss Target Prediction tool. PKCα is known to promote the growth and invasion of cancer cells and is being evaluated as a prognostic biomarker and therapeutic target in clinically aggressive tumors. Molecular docking of Withaferin A and Withanolides D was performed using AutoDock Vina. Both the bioactive compounds interacted with PKCα. The targets predicted using this approach will serve as leads for the possible therapeutic potential of withanolides, the bioactive ingredients of WS extracts, as anti-cancer drugs.

Keywords: withania somnifera, withaferin A, withanolides D, PKCα

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Authors: Mojtaba Ghodsi, Morteza Mohammadzaheri, Payam Soltani

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This research aims to the characterisation of LTC3588 as a low-power energy storage model. A simple architecture of its internal circuit was presented. The effect of the storage capacitor (Cᵢₙ) and output capacitor (Cₒᵤₜ) on the output voltage (Vₒᵤₜ) when the vibration frequency was fixed at 3.2 Hz was investigated. The dependency of the rise time of the output voltage on the LTC3588's input and output capacitors was highlighted. It was found that by increasing the input capacitance from 1μF to 220μF, lower oscillation in the output voltage combined with a lower rate in the input voltage can be detected. Additionally, the smaller Cₒᵤₜ causes fewer jumps to meet the final output value (i.e., 3.2 V).

Keywords: LTC3588, modeling, zener diode, LED

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Authors: Xiaowei Zhang, Min Xu, Saeid Habibi, Fengjun Yan, Ryan Ahmed

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Recently, Electric Vehicles (EVs) have received extensive consideration since they offer a more sustainable and greener transportation alternative compared to fossil-fuel propelled vehicles. Lithium-Ion (Li-ion) batteries are increasingly being deployed in EVs because of their high energy density, high cell-level voltage, and low rate of self-discharge. Since Li-ion batteries represent the most expensive component in the EV powertrain, accurate monitoring and control strategies must be executed to ensure their prolonged lifespan. The Battery Management System (BMS) has to accurately estimate parameters such as the battery State-of-Charge (SOC), State-of-Health (SOH), and Remaining Useful Life (RUL). In order for the BMS to estimate these parameters, an accurate and control-oriented battery model has to work collaboratively with a robust state and parameter estimation strategy. Since battery physical parameters, such as the internal resistance and diffusion coefficient change depending on the battery state-of-life (SOL), the BMS has to be adaptive to accommodate for this change. In this paper, an extensive battery aging study has been conducted over 12-months period on 5.4 Ah, 3.7 V Lithium polymer cells. Instead of using fixed charging/discharging aging cycles at fixed C-rate, a set of real-world driving scenarios have been used to age the cells. The test has been interrupted every 5% capacity degradation by a set of reference performance tests to assess the battery degradation and track model parameters. As battery ages, the combined model parameters are optimized and tracked in an offline mode over the entire batteries lifespan. Based on the optimized model, a state and parameter estimation strategy based on the Extended Kalman Filter (EKF) and the relatively new Smooth Variable Structure Filter (SVSF) have been applied to estimate the SOC at various states of life.

Keywords: lithium-ion batteries, genetic algorithm optimization, battery aging test, parameter identification

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Authors: Kristina Jansen, Maximilian Lennartz, Patrick Lebok, Guido Sauter, Ronald Simon, David Dum, Stefan Steurer

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DOG1 (Discovered on GIST1) is a voltage-gated calcium-activated chloride and bicarbonate channel that is highly expressed in interstitial cells of Cajal and in gastrointestinal stromal tumors (GIST) derived from Cajal cells. To systematically determine in what tumor entities and normal tissue types DOG1 may be further expressed, a tissue microarray (TMA) containing 15,965 samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. DOG1 immunostaining was found in 67 tumor types, including GIST (95.7%), esophageal squamous cell carcinoma (31.9%), pancreatic ductal adenocarcinoma (33.6%), adenocarcinoma of the Papilla Vateri (20%), squamous cell carcinoma of the vulva (15.8%) and the oral cavity (15.3%), mucinous ovarian cancer (15.3%), esophageal adenocarcinoma (12.5%), endometrioid endometrial cancer (12.1%), neuroendocrine carcinoma of the colon (11.1%) and diffuse gastric adenocarcinoma (11%). Low level-DOG1 immunostaining was seen in 17 additional tumor entities. DOG1 expression was unrelated to histopathological parameters of tumor aggressiveness and/or patient prognosis in cancers of the breast (n=1,002), urinary bladder (975), ovary (469), endometrium (173), stomach (233), and thyroid gland (512). High DOG1 expression was linked to estrogen receptor expression in breast cancer (p<0.0001) and the absence of HPV infection in squamous cell carcinomas (p=0.0008). In conclusion, our data identify several tumor entities that can show DOG1 expression levels at similar levels as in GIST. Although DOG1 is tightly linked to a diagnosis of GIST in spindle cell tumors, the differential diagnosis is much broader in DOG1 positive epithelioid neoplasms.

Keywords: biomarker, DOG1, immunohistochemistry, tissue microarray

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Authors: J. DeBoard, R. Dietrich, J. Hughes, K. Yurko, G. Harms

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Alzheimer’s disease (AD) is a predominant type of dementia and is likely a major cause of neural network impairment. The pathogenesis of this neurodegenerative disorder has yet to be fully elucidated. There are currently no known cures for the disease, and the best hope is to be able to detect it early enough to impede its progress. Beyond age and genetics, another prevalent risk factor for AD might be traumatic brain injury (TBI), which has similar neurodegenerative hallmarks. Our research focuses on obtaining information and methods to be able to predict when neurodegenerative effects might occur at a clinical level by observation of events at a cellular and molecular level in model mice. First, we wish to introduce our evidence that brain damage can be observed via brain imaging prior to the noticeable loss of neuromuscular control in model mice of AD. We then show our evidence that some blood biomarkers might be able to be early predictors of AD in the same model mice. Thus, we were interested to see if we might be able to predict which mice might show long-term neurodegenerative effects due to differing degrees of TBI and what level of TBI causes further damage and earlier death to the AD model mice. Upon application of TBIs via an apparatus to effectively induce extremely mild to mild TBIs, wild-type (WT) mice and AD mouse models were tested for cognition, neuromuscular control, olfactory ability, blood biomarkers, and brain imaging. Experiments are currently still in process, and more results are therefore forthcoming. Preliminary data suggest that neuromotor control diminishes as well as olfactory function for both AD and WT mice after the administration of five consecutive mild TBIs. Also, seizure activity increases significantly for both AD and WT after the administration of the five TBI treatment. If future data supports these findings, important implications about the effect of TBI on those at risk for AD might be possible.

Keywords: Alzheimer's disease, blood biomarker, neurodegeneration, neuromuscular control, olfaction, traumatic brain injury

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Authors: Sung-mo Seo, Chang-u Chae

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The Product Carbon Footprint Labeling has been run for more than four years by the Ministry of Environment and there are number of products labeled by KEITI, as for declaring products with their carbon emission during life cycle stages. There are several categories for certifying products by the characteristics of usage. Building products which are applied to a building as combined components. In this paper, current status of PCF labeling has been compared with LCI DB for data composition. By this comparative analysis, we suggest carbon labeling development.

Keywords: carbon labeling, LCI DB, building materials, life cycle assessment

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Authors: Mohammed Alasel, Michael Keusgen

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Gold is a noble metal; in its nano-scale level (e.g. spherical nanoparticles), the conduction electrons are triggered to collectively oscillate with a resonant frequency when certain wavelengths of electromagnetic radiation interact with its surface; this phenomenon is known as surface plasmon resonance (SPR). SPR is responsible for giving the gold nanoparticles its intense red color depending mainly on its size, shape and distance between nanoparticles. A decreased distance between gold nanoparticles results in aggregation of them causing a change in color from red to blue. This aggregation enables gold nanoparticles to serve as a sensitive biosensoric indicator. In the proposed work, gold nanoparticles were modified with two proteins: i) Borrelia antigen, variable lipoprotein surface-exposed protein (VlsE), and ii) protein A. VlsE antigen induces a strong antibody response against Lyme disease and can be detected from early to late phase during the disease in humans infected with Borrelia. In addition, it shows low cross-reaction with the other non-pathogenic Borrelia strains. The high specificity of VlsE antigen to anti-Borrelia antibodies, combined simultaneously with the high specificity of protein A to the Fc region of all IgG human antibodies, was utilized to develop a rapid test for serological point of care diagnosis of borreliosis in human serum. Only in the presence of anti-Borrelia antibodies in the serum probe, an aggregation of gold nanoparticles can be observed, which is visible by a concentration-dependent colour shift from red (low IgG) to blue (high IgG). Experiments showed it is clearly possible to distinguish between positive and negative sera samples using a simple suspension of the two-protein modified gold nanoparticles in a very short time (30 minutes). The proposed work showed the potential of using such modified gold nanoparticles generally for serological diagnosis. Improved specificity and reduced assay time can be archived in applying increased salt concentrations combined with decreased pH values (pH 5).

Keywords: gold nanoparticles, gold aggregation, serological diagnosis, protein A, lyme borreliosis

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Authors: P. M. G. Pathiraja, P. Egodawatta, A. Goonetilleke, V. S. J. Te'o

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The production and use of Polychlorinated biphenyls (PCBs), a group of synthetic halogenated hydrocarbons have been restricted worldwide due to its toxicity and categorized as one of the twelve priority persistent organic pollutants (POP) by the Stockholm Convention. Low reactivity and high chemical stability of PCBs have made them highly persistent in the environment and bio-concentration and bio-magnification along the food chain contribute to multiple health impacts in humans and animals. Remediating environments contaminated with PCBs is a challenging task for decades. Use of microorganisms for remediation of PCB contaminated soils and sediments have been widely investigated due to the potential of breakdown these complex contaminants with minimum environmental impacts. To achieve an effective bioremediation of polychlorinated biphenyls (PCBs) contaminated environments, microbes were sourced from environmental samples and tested for their ability to hydrolyze PCBs under different conditions. Comparison of PCB degradation efficiencies of four naturally occurring facultative bacterial cultures isolated through selective enrichment under aerobic and anaerobic conditions were simultaneously investigated in minimal salt medium using 50 mg/L Aroclor 1260, a commonly used commercial PCB mixture as the sole source of carbon. The results of a six-week study demonstrated that all the tested facultative Achromobacter, Ochrobactrum, Lysinibacillus and Pseudomonas strains are capable of degrading PCBs under both anaerobic and aerobic conditions while assisting hydrophobic PCBs to make solubilize in the aqueous minimal medium. Overall, the results suggest that some facultative bacteria are capable of effective in degrading PCBs under anaerobic conditions through reductive dechlorination and under aerobic conditions through oxidation. Therefore, use of suitable facultative microorganisms under combined anaerobic-aerobic conditions and combination of such strains capable of solubilization and breakdown of PCBs has high potential in achieving higher PCB removal rates.

Keywords: bioremediation, combined anaerobic-aerobic degradation, facultative microorganisms, polychlorinated biphenyls

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Authors: Nurul Hamirah Kamsani, Mohd Hamim Rajikin, Nor Ashikin Mohamed Noor Khan, Sharaniza Abdul Rahim

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Cytoskeletal structures, in particular actin and tubulin, provide a fundamental framework in all cells, including embryos. Under influence of nicotine, the cytoskeletal organization may be subjected to oxidative stress (OS) insult and cause alteration. Tocotrienol-rich fraction (TRF) is proven to enhance fertility better than the other sub-group of Vitamin E, tocopherols (TCPs). The objective of this study was to evaluate the effects of TRF on 1) actin and tubulin of 2- and 8-cell murine embryos and 2) the regulation of reactive oxygen species (ROS)-scavenging enzymes; induced by nicotine. Twenty four female Balb/C were subjected to either subcutaneous (sc) injection of 0.9% NaCl; sc injection of 3.0 mg/kg bw/day nicotine; sc injection of 3.0 mg/kg bw/day nicotine + oral gavage (OG) of 60 mg/kg bw/day TRF; or OG of 60 mg/kg bw/day TRF for 7 consecutive days. After superovulation and mating, animals were euthanized. 2-cell developing embryos were retrieved. 50% of the retrieved embryos were visualized under confocal laser staining microscopy (CLSM) for alterations of actin and tubulin. The remaining amount of embryos was cultured in vitro until 8-cell stage followed by CLSM visualization. Blood plasma was subjected to OS assays. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined and analysed accordingly. At both 2- and 8-cell developing stages, actin intensities were significantly reduced in the nicotine group (p<0.001). After the intervention, actin intensity was significantly increased compared to that of the nicotine group (p<0.001). The same trend was seen in tubulin at both cell stages. TRF has minimized the deleterious effects of nicotine in actin and tubulin of both 2- and 8-cell developmental stages during pre-implantation embryonic development in mice in vitro. Levels of endogenous anti-oxidative enzymes were sustained close to control accompanied by decreased levels of OS biomarker.

Keywords: actin, nicotine, pre-implantation embryos, tocotrienol rich fraction, tubulin

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Authors: Mohammad Alkhatatbeh, Nehad Ayoub, Nizar Mhaidat, Nesreen Saadeh, Lisa Lincz

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CD36 is involved in the development of atherosclerosis by enhancing macrophage endocytosis of oxidized-low density lipoproteins and foam cell formation. Soluble CD36 (sCD36) was found to be elevated in type 2 diabetic patients and was supposed to act as a marker of insulin resistance and atherosclerosis. In young subjects, sCD36 was associated with cardiovascular risk factors including obesity and hypertriglyceridemia. This study was conducted to further investigate the relationship between plasma sCD36 and cardiovascular risk factors among middle-aged patients with metabolic syndrome (MetS) and healthy controls. SCD36 concentrations were determined by enzyme-linked immunosorbent assays (ELISA) for 41 patients with MetS and 36 healthy controls. Data for other variables were obtained from patients' medical records. SCD36 concentrations were relatively low compared to most other studies and were not significantly different between the MetS group and controls (P-value=0.17). SCD36 was also not correlated with age, body mass index, glucose, lipid profile, serum electrolytes and blood counts. SCD36 was not significantly different between subjects with obesity, hyperglycemia, dyslipidemia, hypertension or cardiovascular disease and those without these abnormalities (P-value > 0.05). The inconsistency between results reported in this study and other studies may be unique to the study population or be a result of the lack of a reliable standardized method for determining absolute sCD36 concentrations. However, further investigations are required to assess CD36 tissue expression in the study population and to assess the accuracy of various commercially available sCD36 ELISA kits. Thus, the availability of a standardized simple sCD36 ELISA that could be performed in any basic laboratory would be more favorable to the specialized flow cytometry methods that detect CD36+ microparticles if it was to be used as a biomarker.

Keywords: metabolic syndrome, CD36, cardiovascular risk, obesity, type 2 diabetes mellitus

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Authors: Shagufta Tazin Shathy, Mohammad Imam Hasan Reza

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Fragmentation due to urbanization and agricultural expansion has become the main reason for destruction of forest area and loss of biodiversity particularly in the developing world. At present, the world is experiencing the largest wave of urban growth in human history, and it is estimated that this influx will be mainly taking place in developing world. Therefore, study on urban fragmentation is vital for a sustainable urban development. Landscape fragmentation is one of the most important conservation issues in the last few decades. Habitat fragmentation due to landscape alteration has caused habitat isolation, destruction in ecosystem pattern and processes. Thus, this research analyses the spatial and temporal extent of urban fragmentation using landscape indices in the Kuala Lumpur (KL) – the capital and most populous city in Malaysia. The objective of this study is to examine the urban fragmentation index in KL city. Fragmentation metrics used in the study are: a) Urban landscape ratio (the ratio of urban landscape area and build up area), b) Infill (development that occurred within urbanized open space), and c) Extension (development of exterior open space). After analyzing all three metrics, these are calculated for the combined urban fragmentation index (UFI). In this combined index, all three metrics are given an equal weight. Land cover/ land use maps of the year 1996 and 2005 have been developed from the Landsat TM 30 m resolution satellite image. The year 1996 is taken as a reference year to analyze the changes. The UFI calculated for the year of 1996 and2005 found that the KL city has undergone rapid landscape changes destructing forest ecosystem adversely. Increasing UFI for the year of 1996 compared to 2005 indicates that the developmental activities have been occupying open spaces and fragmenting natural lands and forest. This index can be implemented in other unplanned and rapidly urbanizing Asian cities for example Dhaka and Delhi to calculate the urban fragmentation rate. The findings from the study will help the stakeholders and urban planners for a sustainable urban management planning in this region.

Keywords: GIS, index, sustainable urban management, urbanization

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Authors: Diego Alejandro Espíndola-Fernández, Ana María Posada-Cano, Dagnóvar Aristizábal-Ocampo, Jaime Alberto Gallo-Villegas

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Background: With the increase in life expectancy, aging has been subject of frequent research, and therefore multiple strategies have been proposed to quantify the advance of the years based on the known physiology of human senescence. For several decades, attempts have been made to characterize these changes through the concept of biological age, which aims to integrate, in a measure of time, structural or functional variation through biomarkers in comparison with simple chronological age. The objective of this scoping review is to deepen the updated concept of measuring biological age composed of biomarkers in the general population and to summarize recent evidence to identify gaps and priorities for future research. Methods: A scoping review was conducted according to the five-phase methodology developed by Arksey and O'Malley through a search of five bibliographic databases to February 2021. Original articles were included with no time or language limit that described the biological age composed of at least two biomarkers in those over 18 years of age. Results: 674 articles were identified, of which 105 were evaluated for eligibility and 65 were included with information on the measurement of biological age composed of biomarkers. Articles from 1974 of 15 nationalities were found, most observational studies, in which clinical or paraclinical biomarkers were used, and 11 different methods described for the calculation of the composite biological age were informed. The outcomes reported were the relationship with the same measured biomarkers, specified risk factors, comorbidities, physical or cognitive functionality, and mortality. Conclusions: The concept of biological age composed of biomarkers has evolved since the 1970s and multiple methods of its quantification have been described through the combination of different clinical and paraclinical variables from observational studies. Future research should consider the population characteristics, and the choice of biomarkers against the proposed outcomes to improve the understanding of aging variables to direct effective strategies for a proper approach.

Keywords: biological age, biological aging, aging, senescence, biomarker

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Authors: Ali Jibran

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China was considered as a revisionist state by the countries of East Asia during Maoist era; but China’s role changed from a revisionist state to a constructive member of East Asian Community in post-Maoist era. This research will mainly investigate the two phenomena: what were reasons of behavioral change of China in East Asia and what role has China played to promote regionalism in East Asia since Open Door Policy of Deng Xiaoping. To understand these two phenomena, this study applies the international relations theory of Uneven and Combined Development (U&CD). The central finding of this study is that ‘whip of external necessity’ posed by the Western dominance during the Chinese ‘century of ignominy’ resulted in a Maoist regime in China in 1948 which was hostile to its neighbors due to ideological tensions. Maoist regime in China could not solve the challenges posed by the ‘international’; therefore after Mao’s death, a new economic approach was introduced in China to deal with the challenges postured by the ‘international’. Due to Deng Xiaoping’s 'Open Door Policy' era, China used its ‘privilege of historic backwardness’ and witnessed unprecedented economic growth. As the societies are multiple and exist in real time, therefore interaction among societies is pertinent. Export oriented domestic policy pushed China to concentrate less on class struggle and improve its relations with its neighbors in East Asia. As China soon become a global hub of trade after market oriented reforms, therefore friendly relations with the states of East Asia was pertinent. This study will investigate Chinese role in regionalism in East Asia in three area: Chinese role in promoting regionalism in East Asia, China’s role in economic integration in East Asia and China’s role in combatting terrorism in East Asia. This study will be divided in two section. The first section will deal with the transformation in Chinese behavior in East Asia in post Maoist era, and the second section will analyze China’s role in East Asia by looking at Chinese role in institutional mechanism, economic integration and combatting terrorism in East Asia.

Keywords: East Asia, regionalism, institutionlism, economic integration

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Authors: Ahmed Nouainia, Mohamed Hajji, Taoufik Aguili

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In this paper, an electromagnetic analysis is presented for describing the influence of shielding in a rectangular waveguide. A hybridization based on the method of moments combined to the generalized equivalent circuit MoM-GEC is used to model the problem. This is validated by applying the MoM-GEC hybridization to investigate a diffraction structure. It consists of electromagnetic diffraction by an iris in a rectangular waveguide. Numerical results are shown and discussed and a comparison with FEM and Marcuvitz methods is achieved.

Keywords: method MoM-GEC, waveguide, shielding, equivalent circuit

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Authors: Wang Hong, Liu Chang Kui, Zhao Bing Jing, Hu Min

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Objection We observed the repairment effection of canine mandibular defect with meshy Ti6Al4V scaffold fabricated by electron beam melting (EBM) combined with bone marrow mesenchymal stem cells (BMMSCs) encapsulated in chitosan hydrogel. Method Meshy titanium scaffolds were prepared by EBM of commercial Ti6Al4V power. The length of scaffolds was 24 mm, the width was 5 mm and height was 8mm. The pore size and porosity were evaluated by scanning electron microscopy (SEM). Chitosan /Bio-Oss hydrogel was prepared by chitosan, β- sodium glycerophosphate and Bio-Oss power. BMMSCs were harvested from canine iliac crests. BMMSCs were seeded in titanium scaffolds and encapsulated in Chitosan /Bio-Oss hydrogel. The validity of BMMSCs was evaluated by cell count kit-8 (CCK-8). The osteogenic differentiation ability was evaluated by alkaline phosphatase (ALP) activity and gene expression of OC, OPN and CoⅠ. Combination were performed by injecting BMMSCs/ Chitosan /Bio-Oss hydrogel into the meshy Ti6Al4V scaffolds and solidified. 24 mm long box-shaped bone defects were made at the mid-portion of mandible of adult beagles. The defects were randomly filled with BMMSCs/ Chitosan/Bio-Oss + titanium, Chitosan /Bio-Oss+titanium, titanium alone. Autogenous iliac crests graft as control group in 3 beagles. Radionuclide bone imaging was used to monitor the new bone tissue at 2, 4, 8 and 12 weeks after surgery. CT examination was made on the surgery day and 4 weeks, 12 weeks and 24 weeks after surgery. The animals were sacrificed in 4, 12 and 24 weeks after surgery. The bone formation were evaluated by histology and micro-CT. Results: The pores of the scaffolds was interconnected, the pore size was about 1 mm, the average porosity was about 76%. The pore size of the hydrogel was 50-200μm and the average porosity was approximately 90%. The hydrogel were solidified under the condition of 37℃in 10 minutes. The validity and the osteogenic differentiation ability of BMSCs were not affected by titanium scaffolds and hydrogel. Radionuclide bone imaging shown an increasing tendency of the revascularization and bone regeneration was observed in all the groups at 2, 4, 8 weeks after operation, and there were no changes at 12weeks.The tendency was more obvious in the BMMSCs/ Chitosan/Bio-Oss +titanium group and autogenous group. CT, Micro-CT and histology shown that new bone formed increasingly with the time extend. There were more new bone regenerated in BMMSCs/ Chitosan /Bio-Oss + titanium group and autogenous group than the other two groups. At 24 weeks, the autogenous group was achieved bone union. The BMSCs/ Chitosan /Bio-Oss group was seen extensive new bone formed around the scaffolds and more new bone inside of the central pores of scaffolds than Chitosan /Bio-Oss + titanium group and titanium group. The difference was significantly. Conclusion: The titanium scaffolds fabricated by EBM had controlled porous structure, good bone conduction and biocompatibility. Chitosan /Bio-Oss hydrogel had injectable plasticity, thermosensitive property and good biocompatibility. The meshy Ti6Al4V scaffold produced by EBM combined BMSCs encapsulated in chitosan hydrogel had good capacity on mandibular bone defect repair.

Keywords: mandibular reconstruction, tissue engineering, electron beam melting, titanium alloy

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