Search results for: modified Krieger and Dougherty expression

Authors: Piotr J. Balwierz, Mikhail Pachkov, Phil Arnold, Andreas J. Gruber, Mihaela Zavolan, Erik van Nimwegen

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Understanding the key players and interactions in the regulatory networks that control gene expression and chromatin state across different cell types and tissues in metazoans remains one of the central challenges in systems biology. Our laboratory has pioneered a number of methods for automatically inferring core gene regulatory networks directly from high-throughput data by modeling gene expression (RNA-seq) and chromatin state (ChIP-seq) measurements in terms of genome-wide computational predictions of regulatory sites for hundreds of transcription factors and micro-RNAs. These methods have now been completely automated in an integrated webserver called ISMARA that allows researchers to analyze their own data by simply uploading RNA-seq or ChIP-seq data sets and provides results in an integrated web interface as well as in downloadable flat form. For any data set, ISMARA infers the key regulators in the system, their activities across the input samples, the genes and pathways they target, and the core interactions between the regulators. We believe that by empowering experimental researchers to apply cutting-edge computational systems biology tools to their data in a completely automated manner, ISMARA can play an important role in developing our understanding of regulatory networks across metazoans.

Keywords: gene expression analysis, high-throughput sequencing analysis, transcription factor activity, transcription regulation

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Authors: Chengcao Sun, Cuili Yang, Shujun Li, Ruilin Xue, Yongyong Xi, Liang Wang, Dejia Li

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Backgrounds: A few lines of evidence show that Sulforaphane (SFN) has anti-fibrosis effect in liver tissue via Nrf2-mediated inhibition of TGF-β/Smad signaling. However, its effects on muscular dystrophic fibrosis remain unknown. This work was undertaken to evaluate the effects of SFN on fibrosis in dystrophic muscle. Methods: 3-month-old male mdx mice were treated with SFN by gavage (2 mg/kg body weight per day) for 3 months. Gastrocnemius, tibial anterior and triceps brachii muscles were collected for related analysis. Fibrosis in skeletal muscles was analyzed by Sirius red staining. Histology and morphology of skeletal muscles were investigated by H&E staining. Moreover, the expressions of Nrf2, NQO1, HO-1, and TGF-β/Smad signaling pathway were detected by western blot, qRT-PCR, immunohistochemistry and immunofluorescence assays. Results: Our results demonstrated that SFN treatment significantly decreased and improved morphological features in mdx muscles. Moreover, SFN increased the expression of muscle phase II enzymes NQO1 and HO-1 and significantly decreased the expression of TGF-β1，p-smad2, p-smad3, α-SMA, fibronectin, collagen I, PAI-1, and TIMP-1 in Nrf2 dependent manner. Additionally, SFN significantly decreased the expression of CD45 and TNF-α. Conclusions: Collectively, these results show that SFN can ameliorate muscle fibrosis in mdx mice by Nrf2-induced inhibition of TGF-β/Smad signaling pathway, which indicate Nrf2 may be useful for the treatment of muscular dystrophy.

Keywords: sulforaphane, Nrf2, TGF-β/smad signaling, duchenne muscular dystrophy, fibrosis

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Authors: Soheila Afkar

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Mentha piperita is a medicinal plant that contains a large amount of secondary metabolite that has adverse effect on RNA extraction. Since high quality of RNA is the first step to real time-PCR, in this study optimization of total RNA isolation from leaf tissues of Mentha piperita was evaluated. From this point of view, we researched two different total RNA extraction methods on leaves of Mentha piperita to find the best one that contributes the high quality. The methods tested are RNX-plus, modified RNX-plus (1-5 numbers). RNA quality was analyzed by agarose gel 1.5%. The RNA integrity was also assessed by visualization of ribosomal RNA bands on 1.5% agarose gels. In the modified RNX-plus method (number 2), the integrity of 28S and 18S rRNA was highly satisfactory when analyzed in agarose denaturing gel, so this method is suitable for RNA isolation from Mentha piperita.

Keywords: Mentha piperita, polyphenol, polysaccharide, RNA extraction

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Authors: Laskri Yamina, Rehouma Abdel Hamid

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In this paper we present a new class named polar of monic orthogonal polynomials with respect to the area measure supported on G, where G is a bounded simply-connected domain in the complex planeℂ. We analyze some open questions and discuss some ideas properties related to solving asymptotic behavior of polar Bergman polynomials over domains with corners and asymptotic behavior of modified Bergman polynomials by affine transforms in variable and polar modified Bergman polynomials by affine transforms in variable. We show that uniform asymptotic of Bergman polynomials over domains with corners and by Pritsker's theorem imply uniform asymptotic for all their derivatives.

Keywords: Bergman orthogonal polynomials, polar rthogonal polynomials, asymptotic behavior, Faber polynomials

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Authors: D. Adel, F. Giacomini, R. Gildenhaar, G. Berger, C. Gomes, U. Linow, M. Hardt, B. Peleskae, J. Günster, A. Houshmand, M. Stiller, A. Rack, K. Ghaffar, A. Gamal, M. El Mofty, C. Knabe

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The goal of this study was to develop 3D scaffolds from a silica containing calcium alkali orthophosphate utilizing two different fabrication processes, first a replica technique namely the Schwartzwalder Somers method (SSM), and second 3D printing, i.e. Rapid prototyping (RP). First, the mechanical and physical properties of the scaffolds (porosity, compressive strength, and solubility) was assessed and second their potential to facilitate homogenous colonization with osteogenic cells and extracellular bone matrix formation throughout the porous scaffold architecture. To this end murine and rat calavarie osteoblastic cells were dynamically seeded on both scaffold types under perfusion with concentrations of 3 million cells. The amount of cells and extracellular matrix as well as osteogenic marker expression was evaluated using hard tissue histology, immunohistochemistry, and histomorphometric analysis. Total porosities of both scaffolds were 86.9 % and 50% for SSM and RP respectively, Compressive strength values were 0.46 ± 0.2 MPa for SSM and 6.6± 0.8 MPa for RP. Regarding the cellular behavior, RP scaffolds displayed a higher cell and matrix percentage of 24.45%. Immunoscoring yielded strong osteocalcin expression of cells and matrix in RP scaffolds and a moderate expression in SSM scaffolds. 3D printed RP scaffolds displayed superior mechanical and biological properties compared to SSM. 3D printed scaffolds represent excellent candidates for bone tissue engineering.

Keywords: calcium alkali orthophosphate, extracellular matrix mineralization, osteoblast differentiation, rapid prototyping, scaffold

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Authors: Soheil Heydari, Ailar Hajimohammadi, Nasser Khalili

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Polystyrene, being made from a monomer called styrene, is a rigid and easy-to mould polymer that is widely used for many applications, from foam packaging to disposable containers. Considering that the degradation of waste polystyrene takes up to 500 years, there is an urgent need for a sustainable application for waste polystyrene. This study evaluates the application of waste polystyrene as an asphalt modifier. The inclusion of waste plastics in asphalt is either practised by the dry process or the wet process. In the dry process, plastics are added straight into the asphalt mixture and in the wet process, they are mixed and digested into bitumen. In this article, polystyrene was used as an asphalt modifier in a dry process. However, the mixing process is precisely designed to make sure that the polymer is melted and modified in the binder. It was expected that, due to the rigidity of polystyrene, it will have positive effects on the permanent deformation of the asphalt mixture. Therefore, different mixtures were manufactured with different contents of polystyrene and Marshall specimens were manufactured, and dynamic creep tests were conducted to evaluate the permanent deformation of the modification. This is a commonly repeated loading test conducted at different stress levels and temperatures. Loading cycles are applied to the AC specimen until failure occurs; with the amount of deformation constantly recorded the cumulative, permanent strain is determined and reported as a function of the number of cycles. Also, to our best knowledge, hybrid mixes of polystyrene with crumb rubber and low-density polyethylene were made and compared with a polystyrene-modified mixture. The test results of this study showed that the hybrid mix of polystyrene and low-density polyethylene has the highest resistance against permanent deformation. However, the polystyrene-modified mixture outperformed the hybrid mix of polystyrene and crumb rubber, and both demonstrated way lower permanent deformation than the unmodified specimen.

Keywords: permanent deformation, waste plastics, polystyrene, hybrid plastics, hybrid mix, hybrid modification, dry process

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Authors: Bin Liu

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Prokaryotic promoter, consisted of two short DNA sequences located at in -35 and -10 positions, is responsible for controlling the initiation and expression of gene expression. Different types of promoters have different functions, and their consensus sequences are similar. In addition, their consensus sequences may be different for the same type of promoter, which poses difficulties for promoter identification. Unfortunately, all existing computational methods treat promoter identification as a binary classification task and can only identify whether a query sequence belongs to a specific promoter type. It is desired to develop computational methods for effectively identifying promoters and their types. Here, a two-layer predictor is proposed to try to deal with the problem. The first layer is designed to predict whether a given sequence is a promoter and the second layer predicts the type of promoter that is judged as a promoter. Meanwhile, we also analyze the importance of feature and sequence conversation in two aspects: promoter identification and promoter type identification. To the best knowledge of ours, it is the first computational predictor to detect promoters and their types.

Keywords: promoter, promoter type, random forest, sequence information

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Authors: Ahmadreza Ashraf, Elias Saion, Elham Gharib Shahi, Chee Kong Yap, Mohd Suhaimi Hamzah

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Fifty-five core marine sediments from three locations at South China Sea and one location each at Sulu Sea and Sulawesi Sea of coastal East Malaysia was analyzed for heavy metals using Instrumental Neutron Activation Analysis and Inductively Coupled Plasma Mass Spectroscopy. The enrichment factor of As, Cd, Cr, Cu, Ni, Pb, and Zn varied from 0.42 to 4.26, 0.50 to 2.34, 0.31 to 0.82, 0.20 to 0.61, 0.91 to 1.92, 0.23 to 1.52, and 0.90 to 1.28 respectively, with the modified degree of contamination values below 0.6. Comparative data show that coastal East Malaysia is of low levels of contamination.

Keywords: coastal East Malaysia, core marine sediments, enrichment factor, heavy metals, INAA and ICP method, modified degree of contamination

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Authors: K. B. Ghazaryan, R. A. Ghazaryan

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Based on the constitutive model and anti-plane equations of anisotropic elastic body of monoclinic symmetry we consider the problem of shear wave propagation in multi-layered disordered composite structure with point defect. Using transfer matrix method the analytic expression is obtained providing solutions of shear Floquet wave propagation in periodic disordered anisotropic structure. The usefulness of the obtained analytical expression was discussed also in reflection and refraction problems from multi-layered reflector as well as in vibration problem of multi-layered waveguides. Numerical results are presented highlighting the effects arising in disordered periodic structure due to defects of multi-layered structure.

Keywords: shear elastic waves, monoclinic anisotropic media, periodic structure, disordered multilayer laminae, multi-layered waveguide

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Authors: Niroshan K. Walgama Wellalage, Tieling Zhang, Richard Dwight

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State-based Markov deterioration models (SMDM) sometimes fail to find accurate transition probability matrix (TPM) values, and hence lead to invalid future condition prediction or incorrect average deterioration rates mainly due to drawbacks of existing nonlinear optimization-based algorithms and/or subjective function types used for regression analysis. Furthermore, a set of separate functions for each condition state with age cannot be directly derived by using Markov model for a given bridge element group, which however is of interest to industrial partners. This paper presents a new approach for generating Homogeneous SMDM model output, namely, the Modified Weibull approach, which consists of a set of appropriate functions to describe the percentage condition prediction of bridge elements in each state. These functions are combined with Bayesian approach and Metropolis Hasting Algorithm (MHA) based Markov Chain Monte Carlo (MCMC) simulation technique for quantifying the uncertainty in model parameter estimates. In this study, factors contributing to rail bridge deterioration were identified. The inspection data for 1,000 Australian railway bridges over 15 years were reviewed and filtered accordingly based on the real operational experience. Network level deterioration model for a typical bridge element group was developed using the proposed Modified Weibull approach. The condition state predictions obtained from this method were validated using statistical hypothesis tests with a test data set. Results show that the proposed model is able to not only predict the conditions in network-level accurately but also capture the model uncertainties with given confidence interval.

Keywords: bridge deterioration modelling, modified weibull approach, MCMC, metropolis-hasting algorithm, bayesian approach, Markov deterioration models

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Authors: Mookyada Mankrut, Manit Nithitanakul

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An increase in the amount of atmospheric carbon dioxide (CO2) resulting from anthropogenic CO2 emission has been a concerned problem so far. Adsorption using porous materials is feasible way to reduce the content of CO2 emission into the atmosphere due to several advantages: low energy consumption in regeneration process, low-cost raw materials and, high CO2 adsorption capacity. In this work, the porous poly(divinylbenzene) (poly(DVB)) support was synthesized under high internal phase emulsion (HIPE) polymerization then modified with polyethyleneimine (PEI) by using solution plasma process. These porous polymers were then used as adsorbents for CO2 adsorption study. All samples were characterized by some techniques: Fourier transform infrared spectroscopy (FT-IR), scanning electron spectroscopy (SEM), water contact angle measurement and, surface area analyzer. The results of FT-IR and a decrease in contact angle, pore volume and, surface area of PEI-loaded materials demonstrated that surface of poly(DVB) support was modified. In other words, amine groups were introduced to poly(DVB) surface. In addition, not only the outer surface of poly(DVB) adsorbent was modified, but also the inner structure as shown by FT-IR study. As a result, PEI-loaded materials exhibited higher adsorption capacity, comparing with those of the unmodified poly(DVB) support.

Keywords: polyHIPEs, CO2 adsorption, solution plasma process, high internal phase emulsion

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Authors: Lucian Mocan, Flaviu Tabaran, Teodora Mocan, Cristian Matea, Cornel Iancu

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We present method of Gold Nanoparticle enhanced laser thermal ablation of HepG2 cells (Human hepatocellular liver carcinoma cell line), based on a simple gold nanoparticle carrier system, such as serum albumin (BSA), and demonstrate its selective therapeutic efficacy. Hyperspectral, contrast phase, and confocal microscopy combined immunochemical staining were used to demonstrate the selective internalization of HSA-GNPs via Gp60 receptors and the caveolin-mediated endocytosis inside HepG2 cells. We examined the ability of laser-activated carbon nanotubes to induce Hsp70 expression using confocal microscopy. Hep G2 cells heat-shocked (laser activated BSA-GNPs) to 42°C demonstrated an up-regulation of Hsp70 compared with control cells (BSA-GNPs treated cells without laser), which showed no detectable constitutive expression of Hsp70. We observed a time-dependent induction in Hsp70 expression in Hep G2 treated with BSA-GNPs and LASER irradiated. The post-irradiation apoptotic rate of HepG2 cells treated with HSA-GNPs ranged from 88.24% (for 50 mg/L) at 60 seconds, while at 30 minute the rate increased to 92.34% (50 mg/L). These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.

Keywords: gold nanoparticles, liver cancer, albumin, laser irradiation

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Authors: Mailin Misson, Bo Jin, Sheng Dai, Hu Zhang

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Advances in biotechnology have witnessed a growing interest in enzyme applications for the development of green and sustainable bio processes. While known as powerful bio catalysts, enzymes are no longer of economic value when extended to large commercialization. Alternatively, immobilization technology allows enzyme recovery and continuous reuse which subsequently compensates high operating costs. Employment of enzymes on nano structured materials has been recognized as a promising approach to enhance enzyme catalytic performances. High porosity, inter connectivity and self-assembling behaviors endow nano fibers as exciting candidate for enzyme carrier in bio reactor systems. In this study, nano fibers were successfully fabricated via electro spinning system by optimizing the polymer concentration (10-30 %, w/v), applied voltage (10-30 kV) and discharge distance (11-26 cm). Microscopic images have confirmed the quality as homogeneous and good fiber alignment. The nano fibers surface was modified using strong oxidizing agent to facilitate bio molecule binding. Bovine serum albumin and β-galactosidase enzyme were employed as model bio catalysts and immobilized onto the oxidized surfaces through covalent binding. Maximum enzyme adsorption capacity of the modified nano fibers was 3000 mg/g, 3-fold higher than the unmodified counterpart (1000 mg/g). The highest immobilization yield was 80% and reached the saturation point at 2 mg/ml of enzyme concentration. The results indicate a significant increase of activity retention by the enzyme-bound modified nano fibers (80%) as compared to the nascent one (60%), signifying excellent enzyme-nano carrier bio compatibility. The immobilized enzyme was further used for the bio conversion of dairy wastes into value-added products. This study demonstrates great potential of acid-modified electrospun polystyrene nano fibers as enzyme carriers.

Keywords: immobilization, enzyme, nanocarrier, nanofibers

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Authors: Hassan Sabo

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Language is a system of conventionally spoken, manual and written symbols by human beings that members of a certain social group and participants in its culture express themselves. Communication, expression of identity and imaginative expression are among the functions of language. Dialect is a form of language, or a regional variety of language that is spoken in a particular geographical setting by a particular group of people. Hausa is one of the major languages in Africa, in terms of large number of people for whom it is the first language. Hausa is one of the western Chadic groups of languages. It constitutes one of the five or six branches of Afro-Asiatic family. The predominant Hausa speakers are in Nigeria and they live in different geographical locations which resulted to variety of dialects within the Hausa language apart of the standard Hausa language, the Hausa language has a variety of dialect that distinguish from one another by such features as phonology, grammar and vocabulary. This study intends to examine such features that serve as means of identification among Hausa speakers who are set off from others, geographically or socially.

Keywords: dialect, features, geographical location, Hausa language

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Authors: Ala’a H. Al-Muhtaseb, Farrukh Jamil, Sandeep K. Saxena

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The fast growth rate of energy consumption along with world population expected to demand 50% more energy by 2030 than nowadays. At present, the energy demand is mostly provided by limited fossil fuel sources such as oil, natural gas, and coal that are resulting in dramatic increase in CO2 emissions from combustion of fossil fuels. The growth of the biodiesel industry over the last decade has resulted in a price drop because glycerol is obtained as a by-product during transesterification of vegetable oil or animal fats, which accounts for one tenth of every gallon of biodiesel produced. The production of oxygenates from glycerol gains much importance due to the excellent diesel-blending property of the oxygenates that not only improve the quality of the fuel but also increases the overall yield of the biodiesel in helping to meet the target for energy production from renewable sources for transport in the energy utilization directives. The reaction of bio-glycerol with bio-acetone was carried out in a magnetically stirred two necked round bottom flaskS. Condensation of bio-glycerol with acetone in the presence of various modified forms of beta zeolite has been done for synthesizing solketal (AB-2 modified with nitric acid, AB-3 modified with oxalic acid). Among all modified forms of beta zeolite, AB-2 showed the best performance for maximum glycerol conversion 94.26 % with 94.21 % solketal selectivity and minimum acetal formation 0.05 %. The physiochemical properties of parent beta zeolite and all its modified forms were analyzed by XRD, SEM, TEM, BET, FTIR and TPD. It has been revealed that AB-2 catalysts with high pore volume and surface area gave high glycerol conversion with maximum solketal selectivity. Despite this, the crystallinity of AB-3 was lower than AB-2 which helps to provide the shorter path length for reactants and product but due high pore volume AB-2 was preferred which gave maximum bio-glycerol conversion. Temperature does matter the glycerol conversion and selectivity of solketal, as it increases from 40 ºC to 60 ºC the conversion of glycerol rises from 80.04 % to 94.26 % and selectivity of solketal from 80.0 % to 94.21 % but further increase in temperature to 100 ºC glycerol conversion reduced to 93.06 % and solketal selectivity to 92.08 %. AB-2 was found to be highly stable as up to 4 repeated experimental runs there was less than 10% decrease in its activity. This process offers an attractive route for converting bio-glycerol, the main by-product of biodiesel to solketal with bio-acetone; a value-added green product with potential industrial applications as a valuable green fuel additive or combustion promoter for gasoline/diesel engines.

Keywords: beta-zeolite, bio-glycerol, catalyst, solketal

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Authors: Amine Ez-Zoubi, Abdellah Farah

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Because of their effectiveness and environmental safety, many essential oils have been investigated as biopesticides. Nevertheless, the encapsulation process is necessary to improve its physical, chemical, and biological properties. Therefore, the purpose of this paper was to study the physicochemical characteristics, and antifungal activity of the Artemisia Herba-Alba essential oil (HAEO) encapsulated in succinic acid modified β-CD (SACD). A yellowish oil was obtained from plant A. Herba-Alba using hydrodistillation and GC-MS was used to identify the chemical composition, in which α-Thujone (65.0%) was the main component in HAEO. The succinic acid has been esterified via the hydroxyl groups in β-CD to produce SACD. In addition, the inclusion complex formation of HAEO and SACD was generated according to the co-precipitation method and was analyzed by several techniques. The antifungal activity in vitro was examined against Botrytis cinerea by direct contact with a potato dextrose agar culture medium. At a 0.1 % concentration, the HAEO in encapsulated form showed higher potential for the control of B. cinerea when compared to the EO in free form (38.34 to 12%). Thus, these results produced evidence that the encapsulation of EOs in SACD can be useful for the development of B.cinerea inhibitors and a promising alternative biopesticide.

Keywords: Artemisia Herba-Alba essential oil, succinic acid modified β-cyclodextrin, inclusion complex, co-precipitation, Botrytis cinerea, direct contact

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Authors: D. Önen, N. Kızılcan, B. Yıldız, A. Akar

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In situ modified cyclohexanone-formaldehyde resins were prepared by addition of alendronic acid during resin preparation. Clay nanocomposites in ketonic resins were achieved by adding clay into the flask at the beginning of the resin preparation. The prepared resins were used for the synthesis of fire resistant polyurethanes foam. Both phosphorous containing modifier compound alendronic acid and nanoclay increases fire resistance of the cyclohexanone-formaldehyde resin thus polyurethane produced from these resins. The effect of the concentrations of alendronic acid and clay on the fire resistance and physical properties of polyurethanes was studied.

Keywords: alendronic acid, clay, ketonic resin, polyurethane

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Authors: Hend K. Moosa, Eman A. Rashwan, Ezzat M. Hassan, Amany A. Ghazy, Amel G. Sheredy

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The stability of microRNA (miR) in the circulation can show a great progress toward the discovery of non-invasive diagnostic and prognostic biomarkers in many diseases. In the present study, circulatory miR-122 and miR-130a were analysed in chronic hepatitis C Egyptian patients in predicting the clinical outcome of interferon treatment. In addition, their expression levels were correlated to viral RNA levels, necro-inflammatory markers (AST, ALT) and to each other. This study was conducted on 51 subjects where 36 were chronic HCV patients in which they were divided into naive and interferon treated HCV patients (responders and non-responders) and 15 matched healthy controls. Serum quantification of miR-122 and miR-130a were performed by quantitative Real-time Polymerase Chain Reaction (qRT-PCR). The results showed a significant upregulation of miR-122 in non-responder patients (P=0.049). By receiver operating characteristic analysis curve, miR-122 revealed 65% sensitivity and 92.3% specificity in predicting non-responsiveness of patients to IFN treatment, while miR-130a showed a sensitivity of 100% and specificity of 53.85%. Remarkably, there was a significant positive correlation between miR-122 and miR-130a in naive HCV patients (r=0.714, p=0.003). However, there was no significant correlation between serum miR-122, miR-130a expression levels and necro-inflammatory markers (AST, ALT). To conclude, miR-122 and miR-130a have a significant association with viral RNA levels and accordingly, they may have a synergistic power in promoting viral replication. Interestingly, miR-122 and miR-130a have a predictive power in predicting clinical outcome of IFN treatment which can be further studied in currently used drugs in order to reduce the socio-economic burden of potentially non-responders.

Keywords: hepatitis C, microRNA, miR-122, miR-130a

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Authors: Metin Kömsöken, Ayşe Güneş Tanır, Onur Karaman

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Usage of high energy charged particles for diagnosis and treatment has been widespread in medicine. The main purpose is to investigate that Bremsstrahlung which occurs by tissue interactions with charged particles should not be neglected. Nuclear stopping power (Bremsstrahlung) was calculated for lung, brain, skin, muscle, bone (cortical) and water targets for the energies of electrons obtained from LINAC used in radiotherapy and of β+ sources used in positron emission tomography (PET). These calculations were done by using the four different analytical functions including classical Bethe-Bloch, Tsoulfanidis, modified Bethe-Bloch and modified Tsoulfanidis equations. It was concluded that obtained results were compatible with that of National Institute of Standards and Technology (NIST-ESTAR).

Keywords: β- emitting source, bremsstrahlung, therapeutic radionuclides, LINAC

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Authors: Eitan Yefenof

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Glucocorticoid (GC) hormones, e.g. Dexamethasone and Prednisone, are widely used in the therapy of leukemia and lymphoma owing to their apoptogenic effect on lymphoid cells. However, the emergence of GC resistant cells during therapy is a major cause for treatment failure, urging the need for novel strategies that maintain leukemia sensitivity to the pro-apoptotic activity of GCs. GCs act by binding to the GC receptor (GR), which, in its inactive state, is sequestered in the cytosol by a multi-subunit complex of heat shock proteins. Upon ligand binding, the complex dissociates, allowing GR activation and translocation to the nucleus, where it regulates transcription of multiple genes. We demonstrated that in addition to gene expression, GR also regulates microRNA (miR) expression. Deep-sequencing analysis revealed 14 miRs that are regulated in GC-sensitive but resistant leukemias upon treatment with GC. GC up-regulates miR-103, miR-15~16 and miR-30e/d, while down-regulates miR-17, mir-18a, miR-19a, miR-19b, miR-20a and miR-92a (members of the miR-17∼92a multi-cistron). Upon transfection, miR-103 confers GC apoptotic sensitivity to otherwise GC-resistant cell. Furthermore, knocking down miR-103 expression reduces the GC apoptotic response of sensitive cells. miR-103 abrogates c-Myc expression, an oncogenic transcription factor which is deregulated in many cancers. In addition, miR-103 up-regulates Bim, a pro-apoptotic protein crucial for GC-induced death. Activated glycogen synthase kinase 3 (GSK3) is also crucial for GC-induced apoptosis. GSK3 is active in GC-sensitive but not in GC-resistant cells. We found that GSK3 associates with the GR multi-subunit complex. Upon GC exposure, it dissociates from the GR and interacts with Bim to enable activation of the mitochondrial apoptosis pathway. miR-103 mediated c-Myc ablation is followed by down-regulation of the multi-cistron miR-17~92a, in particular miR-18a and miR-20a. miR-18a targets GR for degradation whereas miR-20a targets Bim degradation. Hence, miR-103 acts, in concert with Bim and GR, as a "tumor suppressor" that leads to reduced proliferation, cell-cycle arrest and cell death. We suggest that miR-103 can provide a diagnostic tool that predicts the sensitivity of leukemia to GC based therapy. Furthermore, exosomal delivery of miR-103 or up-regulation of the endogenous miR-103 could confer apoptotic sensitivity to resistant cells at the outset, thus becoming a useful therapeutic tool combined with GCs.

Keywords: apoptosis, leukemia, micro-RNA, steroids

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Authors: Helder Shelton Abel Manguene, Giovanna Buonocore, Herminio Francisco Muiambo

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Paved roads are designed for 10-15 years of life. However, many asphalted roads suffer degradation before reaching their lifetime due to aging caused by load conditions and climatic factors. Oxidation is the main asphalt aging mechanism, which leads to a reduced bond between aggregate particles, increasing the potential for stripping and moisture damage, decreasing fatigue lifetime and reducing resistance to thermal cracking. To improve the performance of asphalt and mitigate these problems, modifiers such as polymers, oils and certain residues have been used. This work aims to study the influence of the addition of high-density polyethylene (HDPE) and engine oil on the thermal stability of asphalt in an oxidizing atmosphere. For the study, compositions containing asphalt, motor oil and HDPE were prepared, varying the concentration of the motor oil by 2.5%, 5%, 7.5% and 10% and keeping the HDPE concentration fixed at 5%. The results show that the pure asphalt sample is degraded in a single step that starts at approximately 311 ºC; All samples of modified asphalt except the one that contains 5% of motor oil have three degradation steps that start below the starting temperature of degradation of pure asphalt (about 250-300 ºC); The temperature of onset of degradation of the modified asphalt is shown to decrease as the concentration of the motor oil increases, suggesting a slight loss of thermal stability of the asphalt as the quantity of the motor oil increases.

Keywords: Asphalt, DTG, engine oil, HDPE, TGA

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Authors: Pattanapon Kayansamruaj, Ha Thanh Dong, Nopadon Pirarat, Channarong Rodkhum

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Streptococcus iniae (SI) is a devastating pathogenic bacteria causing heavy mortality in farmed fish. The application of commercialized bacterin vaccine has been reported failures as the outbreaks of the new serotype of SI were emerged in farms after vaccination and subsequently caused severe losses. In the present study, we attempted to develop effective DNA vaccines against SI infection using Nile tilapia (Oreochromis niloticus) as an animal model. Two monovalent DNA vaccines were constructed by the insertion of coding sequences of cell wall-associated virulence factors-encoding genes, comprised of eno (α-enolase) and mtsB (hydrophobic membrane protein), into cytomegalovirus expression vector (pCI-neo). In the animal trial, 30-g Nile tilapia were injected intramuscularly with 15 µg of each vaccine (mock vaccine group was injected by naked pCI-neo) and maintained for 35 days prior challenging with pathogenic SI at the dosage of 107 CFU/fish. At 13 days post-challenge, the relative percent survival of pEno, pMtsB and mock vaccine were 57%, 45% and 27%, respectively. The expression levels of immune responses-associated genes, namely, IL1β, TNF-α, TGF-β, COX2, IL-6, IL-12 and IL-13, were investigated from the spleen of experimental animal at 7 days post-vaccination (PV) and 7 days post-challenge (PC) using quantitative RT-PCR technique. Generally, at 7 days PV, the pEno vaccinated group exhibited highest level of up-regulation (1.7 to 2.9 folds) of every gene, but TGF-β, comparing to pMtsB and mock vaccine groups. However, at 7 days PC, pEno group showed significant up-regulation (1.4 to 8.5 folds) of immune-related genes as similar as mock vaccine group, while pMtsB group had lowest level of up-regulation (0.7 to 3.3 folds). Summarily, this study indicated that the pEno and pMtsB vaccines could elicit the immune responses of the fish and the magnitude of gene expression at 7 days PV was also consistent with the protection level conferred by the vaccine.

Keywords: gene expression, DNA vaccine, Nile tilapia, Streptococcus iniae

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Authors: Abdelrahman Elsehsah, Hany Madkour, Khalid Farah

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This article presents a 3-D modified non-linear elastic model in the strain space. The Helmholtz free energy function is introduced with the existence of a dissipation potential surface in the space of thermodynamic conjugate forces. The constitutive equation and the damage evolution were derived as well. The modified damage has been examined to model the nonlinear behavior of reinforced concrete (RC) slabs with an opening. A parametric study with RC was carried out to investigate the impact of different factors on the behavior of RC slabs. These factors are the opening area, the opening shape, the place of opening, and the thickness of the slabs. And the numerical results have been compared with the experimental data from literature. Finally, the model showed its ability to be applied to the structural analysis of RC slabs.

Keywords: damage mechanics, 3-D numerical analysis, RC, slab with opening

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Authors: Roxane A. Legaie, Kjiana E. Schwab, Caroline E. Gargett

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Studies looking at the changes in gene expression from RNAseq data often make use of linear models. It is also common practice to focus on a subset of data for a comparison of interest, leaving aside the samples not involved in this particular comparison. This work shows the importance of including all observations in the modeling process to better estimate variance parameters, even when the samples included are not directly used in the comparison under test. The human endometrium is a dynamic tissue, which undergoes cycles of growth and regression with each menstrual cycle. The mesenchymal stem cells (MSCs) present in the endometrium are likely responsible for this remarkable regenerative capacity. However recent studies suggest that MSCs also plays a role in the pathogenesis of endometriosis, one of the most common medical conditions affecting the lower abdomen in women in which the endometrial tissue grows outside the womb. In this study we compared gene expression profiles between MSCs and non-stem cell counterparts (‘non-MSC’) obtained from women with (‘E’) or without (‘noE’) endometriosis from RNAseq. Raw read counts were used for differential expression analysis using a linear model with the limma-voom R package, including either all samples in the study or only the samples belonging to the subset of interest (e.g. for the comparison ‘E vs noE in MSC cells’, including only MSC samples from E and noE patients but not the non-MSC ones). Using the full dataset we identified about 100 differentially expressed (DE) genes between E and noE samples in MSC samples (adj.p-val < 0.05 and |logFC|>1) while only 9 DE genes were identified when using only the subset of data (MSC samples only). Important genes known to be involved in endometriosis such as KLF9 and RND3 were missed in the latter case. When looking at the MSC vs non-MSC cells comparison, the linear model including all samples identified 260 genes for noE samples (including the stem cell marker SUSD2) while the subset analysis did not identify any DE genes. When looking at E samples, 12 genes were identified with the first approach and only 1 with the subset approach. Although the stem cell marker RGS5 was found in both cases, the subset test missed important genes involved in stem cell differentiation such as NOTCH3 and other potentially related genes to be used for further investigation and pathway analysis.

Keywords: differential expression, endometriosis, linear model, RNAseq

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Authors: Ksheeraj Sai Vepuri, Nada Attar

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We as humans use words with accompanying visual and facial cues to communicate effectively. Classifying facial emotion using computer vision methodologies has been an active research area in the computer vision field. In this paper, we propose a simple method for facial expression recognition that enhances accuracy. We tested our method on the FER-2013 dataset that contains static images. Instead of using Histogram equalization to preprocess the dataset, we used Unsharp Mask to emphasize texture and details and sharpened the edges. We also used ImageDataGenerator from Keras library for data augmentation. Then we used Convolutional Neural Networks (CNN) model to classify the images into 7 different facial expressions, yielding an accuracy of 69.46% on the test set. Our results show that using image preprocessing such as the sharpening technique for a CNN model can improve the performance, even when the CNN model is relatively simple.

Keywords: facial expression recognittion, image preprocessing, deep learning, CNN

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Authors: H. G. C. P. Dinesh, G. Tharshini, M. P. B. Ekanayake, G. M. R. I. Godaliyadda

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This paper presents a new spatial feature extraction method based on principle component analysis (PCA) and Fisher Discernment Analysis (FDA) for facial expression recognition. It not only extracts reliable features for classification, but also reduces the feature space dimensions of pattern samples. In this method, first each gray scale image is considered in its entirety as the measurement matrix. Then, principle components (PCs) of row vectors of this matrix and variance of these row vectors along PCs are estimated. Therefore, this method would ensure the preservation of spatial information of the facial image. Afterwards, by incorporating the spectral information of the eigen-filters derived from the PCs, a feature vector was constructed, for a given image. Finally, FDA was used to define a set of basis in a reduced dimension subspace such that the optimal clustering is achieved. The method of FDA defines an inter-class scatter matrix and intra-class scatter matrix to enhance the compactness of each cluster while maximizing the distance between cluster marginal points. In order to matching the test image with the training set, a cosine similarity based Bayesian classification was used. The proposed method was tested on the Cohn-Kanade database and JAFFE database. It was observed that the proposed method which incorporates spatial information to construct an optimal feature space outperforms the standard PCA and FDA based methods.

Keywords: facial expression recognition, principle component analysis (PCA), fisher discernment analysis (FDA), eigen-filter, cosine similarity, bayesian classifier, f-measure

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Authors: Rameshwar Singh Seema

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In today’s world where diabetes has become an epidemic, our aim was to potentiate the effect of probiotics by integrating probiotics with cereals to formulate composite foods using Lactobacillus rhamnosus GG (LGG) and Lactobacillus casei NCDC19 against type 2 diabetes. After optimizing the product by Response Surface Methodology, it was studied for their effect on induction and progression of type 2 diabetes in HFD-fed Wistar rats. After 9 weeks study, best results were shown by the group fed with oat and milk based product fermented with LGG and L. casei NCDC19 which resulted in a significant decrease in blood glucose, HBA1c, improved OGTT, oxidative stress, cholesterol and triglycerides level during progression study of type 2 diabetes. During induction study also, there was significant reduction in blood glucose level, oxidative stress, cholesterol level and triglycerides level but slightly less as compared to progression study. Real time PCR gene expression studies were done for 5 genes (GLUT-4, IRS-2, ppar-γ, TNF-α, IL-6) whose expression is directly related to type 2 diabetes. The relative fold change expression was increased in case of GLUT-4, IRS-2, ppar-γ and decreased in case of TNF-α and IL-6 during both induction and progression study of diabetes but more significantly during progression study. Hence it was concluded that oat and milk based probiotic fermented product showed the synergistic effect of probiotics and oats especially in case of progression of type 2 diabetes. The benefits of these probiotic formulations may be further validated by clinical trials.

Keywords: type 2 diabetes, LGG, L.casei NCDC19, food science

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Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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Authors: Shabnam Abdi, Behzad Toosi

Abstract:

Background: Melanoma is the most lethal type of malignant skin cancer in humans and dogs since it spreads rapidly throughout the body. Despite significant advances in treatment, cancer at an advanced stage has a poor prognosis. Hence, more effective treatments are needed to enhance outcomes with fewer side effects. Erythropoietin-producing hepatocellular receptors are the largest family of receptor tyrosine kinases and are divided into two subfamilies, EphA and EphB, both of which play a significant role in disease, especially cancer. Due to their association with proliferation and invasion in many aggressive types of cancer, Eph receptor tyrosine kinases (Eph RTKs) are promising cancer therapy molecules. Because these receptors have not been studied in canine melanoma, we investigated how EphA2 influences survival and tumorigenicity of melanoma cells. Methods: Expression of EphA2 protein in canine melanoma cell lines and human melanoma cell line was evaluated by Western blot. Melanoma cells were transduced with lentiviral particles encoding Eph-targeting shRNAs or non-silencing shRNAs (control) for silencing the expression of EphA2 receptor, and silencing was confirmed by Western blotting and immunofluorescence. The effect of siRNA treatment on cellular proliferation, colony formation, tumorsphere assay, invasion was analyzed by Resazurin assay Matrigel invasion assay, respectively. Results: Expression of EphA2 was detected in canine and human melanoma cell lines. Moreover, stably silencing EphA2 by specific shRNAs significantly and consistently decreased the expression of EphA2 protein in both human and canine melanoma cells. Proliferation, colony formation, tumorsphere and invasion of melanoma cells were significantly decreased in EphA2 siRNA-treated cells compared to control. Conclusion: Our data provide the first functional evidence that the EphA2 receptor plays a critical role in the malignant cellular behavior of melanoma in both human and dogs.

Keywords: ephA2, targeting, melanoma, human, canine

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Authors: Alaa M. M. Badr Eldin, Marwa I. Ezzat, Mohammed S. Sedeek, Manal S. Afifi, Omar M. Sabry

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Cytotoxic activity of the total methanol extract against breast cancer cell line MCF-7 was amazing IC50 at 54 ug/ml. 130 polyphenolic compounds were tentatively identified in pomegranate peel (Punica granatum L.) methanol extract using HPLC-MS/MS technique. The antiestrogenic activity of the polyphenolic constituents found in pomegranate extract was confirmed experimentally in-vitro and by the in-silico molecular docking using gallagic acid, ellagic acid, and Punicalagin as these are considered model compounds confirmed in pomegranate peel extract. The methanolic extract was found to suppress ER, TGF-β, and NF-kB in-vitro gene expression strongly, and that was verified by qPCR and Western Blot gel electrophoresis techniques.

Keywords: HPLC-MS/MS, pomegranate, breast cancer, ovarian cancer, ER, TGF-β, NF-kB

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