Search results for: self expression

Authors: Ankita Singh, Chandan Gorain, Amirul I. Mallick

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Successful adherence of the mucosal epithelial cells is the key early step for Campylobacter jejuni pathogenesis (C. jejuni). A set of Surface Exposed Colonization Proteins (SECPs) are among the major factors involved in host cell adherence and invasion of C. jejuni. Among them, constitutively expressed surface-exposed lipoprotein adhesin of C. jejuni, JlpA, interacts with intestinal heat shock protein 90 (hsp90α) and contributes in disease progression by triggering pro-inflammatory response via activation of NF-κB and p38 MAP kinase pathway. Together with its ability to express in the bacterial surface, higher sequence conservation and predicted predominance of several B cells epitopes, JlpA protein reserves its potential to become an effective vaccine candidate against wide range of Campylobacter sps including C. jejuni. Given that chickens are the primary sources for C. jejuni and persistent gut colonization remain as major cause for foodborne pathogenesis to humans, present study explicitly used chickens as model to test the immune-protective efficacy of JlpA protein. Taking into account that gastrointestinal tract is the focal site for C. jejuni colonization, to extrapolate the benefit of mucosal (intragastric) delivery of JlpA protein, a food grade Nisin inducible Lactic acid producing bacteria, Lactococcus lactis (L. lactis) was engineered to express recombinant JlpA protein (rJlpA) in the surface of the bacteria. Following evaluation of optimal surface expression and functionality of recombinant JlpA protein expressed by recombinant L. lactis (rL. lactis), the immune-protective role of intragastric administration of live rL. lactis was assessed in commercial broiler chickens. In addition to the significant elevation of antigen specific mucosal immune responses in the intestine of chickens that received three doses of rL. lactis, marked upregulation of Toll-like receptor 2 (TLR2) gene expression in association with mixed pro-inflammatory responses (both Th1 and Th17 type) was observed. Furthermore, intragastric delivery of rJlpA expressed by rL. lactis, but not the injectable form, resulted in a significant reduction in C. jejuni colonization in chickens suggesting that mucosal delivery of live rL. lactis expressing JlpA serves as a promising vaccine platform to induce strong immune-protective responses against C. jejuni in chickens.

Keywords: chickens, lipoprotein adhesion of Campylobacter jejuni, immuno-protection, Lactococcus lactis, mucosal delivery

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Authors: Mehdi Shekarzadeh, Pejman Taghipour Birgani

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In this paper, the effect of mass and height of tip on the flexural vibration modes of an atomic force microscope (AFM) rectangular cantilever is analyzed. A closed-form expression for the sensitivity of vibration modes is derived using the relationship between the resonant frequency and contact stiffness of cantilever and sample. Each mode has a different sensitivity to variations in surface stiffness. This sensitivity directly controls the image resolution. It is obtained an AFM cantilever is more sensitive when the mass of tip is lower and the first mode is the most sensitive mode. Also, the effect of changes of tip height on the flexural sensitivity is negligible.

Keywords: atomic force microscope, AFM, vibration analysis, flexural vibration, cantilever

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Authors: Enqing Chen, Jianbo Wang

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It is well known that the wavelet transform provides a very effective framework for multiscale edges analysis. However, wavelets are not very effective in representing images containing distributed discontinuities such as edges. In this paper, we propose a novel multiscale edge detection method in nonsubsampled contourlet transform (NSCT) domain, which is based on the dominant multiscale, multidirection edge expression and outstanding edge location of NSCT. Through real images experiments, simulation results demonstrate that the proposed method is better than other edge detection methods based on Canny operator, wavelet and contourlet. Additionally, the proposed method also works well for noisy images.

Keywords: edge detection, NSCT, shift invariant, modulus maxima

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Authors: W. R. Li, J. K. Xia, R. Q. Peng, Z. Y. Guo, L. Jiang

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According to 3D magnetic circuit of the transverse flux PM linear machine, distribution law is presented, and analytical expression of axial end flux leakage is derived using numerical method. Maxwell stress tensor is used to solve detent force of mover. A 3D finite element model of the transverse flux PM machine is built to analyze the flux distribution and detent force. Experimental results of the prototype verified the validity of axial end flux leakage and detent force theoretical derivation, the research on axial end flux leakage and detent force provides a valuable reference to other types of linear machine.

Keywords: axial end flux leakage, detent force, flux distribution, transverse flux PM linear machine

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Authors: Indu Gaur, Neha Bhadauria, Shilpi Shilpi, Susmita Goswami, Prem D. Sharma, Prabir K. Paul

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The concept of organic agriculture has been accepted as novelty in Indian society, but there is no data available on the human pathogens colonizing plant parts due to such practices. Also, the pattern and mechanism of their colonization need to be understood in order to devise possible strategies for their prevention. In the present study, human pathogenic bacteria were isolated from organically grown tomato plants and five of them were identified as Klebsiella pneumoniae, Enterobacter ludwigii, Serratia fonticola, Stenotrophomonas maltophilia and Chryseobacterium jejuense. Tomato plants were grown in controlled aseptic conditions with 25±1˚C, 70% humidity and 12 hour L/D photoperiod. Six weeks old plants were divided into 6 groups of 25 plants each and treated as follows: Group 1: K. pneumonia, Group 2: E. ludwigii, Group 3: S. fonticola, Group 4: S. maltophilia, Group 5: C. jejuense, Group 6: Sterile distilled water (control). The inoculums for all treatments were prepared by overnight growth with uniform concentration of 108 cells/ml. Leaf samples from above groups were collected at 0.5, 2, 4, 6 and 24 hours post inoculation for the colony forming unit counts (CFU/cm2 of leaf area) of individual pathogens using leaf impression method. These CFU counts were used for the in vivo colonization assay and adherence assay of individual pathogens. Also, resistance of these pathogens to at least 12 antibiotics was studied. Based on these findings S. fonticola was found to be most prominently colonizing the phylloplane of tomato and was further studied. Tomato plants grown in controlled aseptic conditions same as mentioned above were divided into 2 groups of 25 plants each and treated as follows: Group 1: S. fonticola, Group 2: Sterile distilled water (control). Leaf samples from above groups were collected at 0, 24, 48, 72 and 96 hours post inoculation and homogenized in suitable buffers for surface and cell wall protein isolation. Protein samples thus obtained were subjected to isocratic SDS-gel electrophoresis and analyzed. It was observed that presence of S. fonticola could induce the expression of at least 3 additional cell wall proteins at different time intervals. Surface proteins also showed variation in the expression pattern at different sampling intervals. Further identification of these proteins by MALDI-MS and bioinformatics tools revealed the gene(s) involved in the interaction of S. fonticola with tomato phylloplane.

Keywords: cell wall proteins, human pathogenic bacteria, phylloplane, solanum lycopersicum

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Authors: Mohammad Hamzah Alshehab

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Metaphor is a substitute expression in everyday life in languages, thoughts and actions. It has an original value in language use with different conceptual, grammatical and properties. In addition, it is a central concept in literary studies. The present paper aims at investigating metaphor’s types imbedded in some Holy Verses (HV). For achieving the objectives of this paper, two English versions were chosen , the first is the Translation of the Meanings of the Noble Qura’n in the English Language by Mohammad AlHilali and Mohammad Khan, and the second version is the English Translation of the Holy Qura’n by Mohammad Ali were used. The researcher selected (20) Holy Verses include metaphors to be analyzed and investigated. Metaphor types were categorized by an assessment of the two translations followed by a discussion between the two versions of translation.

Keywords: metaphor, metaphor’s types, Holy Qura’n, Holy Verses

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Authors: Alan Ruiz-Padilla, Brando Villalobos-Villalobos, Yeniley Ruiz-Noa, Claudia Mendoza-Macías, Claudia Palafox-Sánchez, Miguel Marín-Rosales, Álvaro Cruz, Rubén Rangel-Salazar

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Introduction: In patients with rheumatoid arthritis, resistance or poor response to disease modifying antirheumatic drugs (DMARD) may be a reflection of the increase in g-P. The expression of g-P may be important in mediating the effluence of DMARD from the cell. In addition, P-glycoprotein is involved in the transport of cytokines, IL-1, IL-2 and IL-4, from normal lymphocytes activated to the surrounding extracellular matrix, thus influencing the activity of RA. The involvement of P-glycoprotein in the transmembrane transport of cytokines can serve as a modulator of the efficacy of DMARD. It was shown that a number of lymphocytes with glycoprotein P activity is increased in patients with RA; therefore, P-glycoprotein expression could be related to the activity of RA and could be a predictor of poor response to therapy. Objective: To evaluate in RA patients, if the G2677T/A MDR1 polymorphisms is associated with differences in the rate of therapeutic response to disease-modifying antirheumatic agents in patients with rheumatoid arthritis. Material and Methods: A prospective cohort study was conducted. Fifty seven patients with RA were included. They had an active disease according to DAS-28 (score >3.2). We excluded patients receiving biological agents. All the patients were followed during 6 months in order to identify the rate of therapeutic response according to the American College of Rheumatology (ACR) criteria. At the baseline peripheral blood samples were taken in order to identify the G2677T/A MDR1 polymorphisms using PCR- Specific allele. The fragment was identified by electrophoresis in polyacrylamide gels stained with ethidium bromide. For statistical analysis, the genotypic and allelic frequencies of MDR1 gene polymorphism between responders and non-responders were determined. Chi-square tests as well as, relative risks with 95% confidence intervals (95%CI) were computed to identify differences in the risk for achieving therapeutic response. Results: RA patients had a mean age of 47.33 ± 12.52 years, 87.7% were women with a mean for DAS-28 score of 6.45 ± 1.12. At the 6 months, the rate of therapeutic response was 68.7 %. The observed genotype frequencies were: for G/G 40%, T/T 32%, A/A 19%, G/T 7% and for A/A genotype 2%. Patients with G allele developed at 6 months of treatment, higher rate for therapeutic response assessed by ACR20 compared to patients with others alleles (p=0.039). Conclusions: Patients with G allele of the - G2677T/A MDR1 polymorphisms had a higher rate of therapeutic response at 6 months with DMARD. These preliminary data support the requirement for a deep evaluation of these and other genotypes as factors that may influence the therapeutic response in RA.

Keywords: pharmacogenetics, MDR1, P-glycoprotein, therapeutic response, rheumatoid arthritis

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Authors: Likith Reddy Pinninti, Fredrik Ribsskog Staven, Leslie Robert Noble, Jorge Manuel de Oliveira Fernandes, Deepti Manjari Patel, Torstein Kristensen

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Understanding fish behavior is essential to improve animal welfare in aquaculture research. Behavioral traits can have a strong influence on fish health and habituation. To identify the genes and biological pathways responsible for lumpfish behavior, we performed an experiment to understand the interspecies relationship (mutualism) between the lumpfish and salmon. Also, we tested the correlation between the gene expression data vs. observational/physiological data to know the essential genes that trigger stress and swimming behavior in lumpfish. After the de novo assembly of the brain transcriptome, all the samples were individually mapped to the available lumpfish (Cyclopterus lumpus L.) primary genome assembly (fCycLum1.pri, GCF_009769545.1). Out of ~16749 genes expressed in brain samples, we found 267 genes to be statistically significant (P > 0.05) found only in odor and control (1), model and control (41) and salmon and control (225) groups. However, genes with |LogFC| ≥0.5 were found to be only eight; these are considered as differentially expressed genes (DEG’s). Though, we are unable to find the differential genes related to the behavioral traits from RNA-Seq data analysis. From the correlation analysis, between the gene expression data vs. observational/physiological data (serotonin (5HT), dopamine (DA), 3,4-Dihydroxyphenylacetic acid (DOPAC), 5-hydroxy indole acetic acid (5-HIAA), Noradrenaline (NORAD)). We found 2495 genes found to be significant (P > 0.05) and among these, 1587 genes are positively correlated with the Noradrenaline (NORAD) hormone group. This suggests that Noradrenaline is triggering the change in pigmentation and skin color in lumpfish. Genes related to behavioral traits like rhythmic, locomotory, feeding, visual, pigmentation, stress, response to other organisms, taxis, dopamine synthesis and other neurotransmitter synthesis-related genes were obtained from the correlation analysis. In KEGG pathway enrichment analysis, we find important pathways, like the calcium signaling pathway and adrenergic signaling in cardiomyocytes, both involved in cell signaling, behavior, emotion, and stress. Calcium is an essential signaling molecule in the brain cells; it could affect the behavior of fish. Our results suggest that changes in calcium homeostasis and adrenergic receptor binding activity lead to changes in fish behavior during stress.

Keywords: behavior, De novo, lumpfish, salmon

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Authors: Claude Tadonki

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We address the issues related to the computation of the covariance matrix. This matrix is likely to be ill conditioned following its canonical expression, thus consequently raises serious numerical issues. The underlying linear system, which therefore should be solved by means of iterative approaches, becomes computationally challenging. A huge number of iterations is expected in order to reach an acceptable level of convergence, necessary to meet the required accuracy of the computation. In addition, this linear system needs to be solved at each iteration following the general form of the covariance matrix. Putting all together, its comes that we need to compute as fast as possible the associated matrix-vector product. This is our purpose in the work, where we consider and discuss skillful formulations of the problem, then propose a parallel implementation of the matrix-vector product involved. Numerical and performance oriented discussions are provided based on experimental evaluations.

Keywords: covariance-matrix, multicore, numerical computing, parallel computing

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Authors: Seok Woo Chang, Kee Yeon Kum, Kwang Shik Bae, WooCheol Lee

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Aim: The objective of this study was to compare the biocompatibilities and mineralization potential of ProRoot MTA and newly developed calcium phosphate based cement, Capseal. Materials and Methods: The biocompatibilities and mineralization-related gene expressions (Bone sialoprotein (BSP) and osteocalcin (OCN)) of ProRoot MTA and Capseal were also compared by a methylthiazol tetrazolium (MTT) assay and reverse transcription-polymerization chain reaction (RT-PCR) analysis on 1, 3, and 7 days, respectively. Empty rings were used as control group. The results were statistically analyzed by Kruskal-Wallis test with a Bonferroni correction. P-value of < 0.05 was considered significant. Results: The biocompatibilities of ProRoot MTA and Capseal were equally favorable. ProRoot MTA and Capseal affected the messenger RNA expression of osteocalcin and osteonectin. Conclusions: Based on the results, both ProRoot MTA and Capseal could be a useful biomaterial in clinical endodontics.

Keywords: biocompatibility, calcium silicate cement, MTT, RT-PCR

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Authors: Xiaoqian Zhang, Ping Zou, Pengcheng Li

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Salt stress is one of the most serious abiotic stresses, and it can lead to the reduction of agricultural productivity. High salt concentration makes it more difficult for roots to absorb water and disturbs the homeostasis of cellular ions resulting in osmotic stress, ion toxicity and generation of reactive oxygen species (ROS). Compared with the normal physiological conditions, salt stress could inhibit the photosynthesis, break metabolic balance and damage cellular structures, and ultimately results in the reduction of crop yield. Therefore it is vital to develop practical methods for improving the salt tolerance of plants. Chitooligomers (COS) is partially depolymerized products of chitosan, which is consisted of D-glucosamine and N-acetyl-D-glucosamine. In agriculture, COS has the ability to promote plant growth and induce plant innate immunity. The bioactivity of COS closely related to its degree of polymerization (DP) and acetylation (DA). However, most of the previous reports fail to mention the function of COS with different DP and DAs in improving the capacity of plants against salt stress. Accordingly, in this study, chitooligomers (COS) with different degrees of DAs were used to test wheat seedlings response to salt stress. In addition, the determined degrees of polymerization (DPs) COS(DP 4-12) and a heterogeneous COS mixture were applied to explore the relationship between the DP of COSs and its effect on the growth of wheat seedlings in response to salt stress. It showed that COSs, the exogenous elicitor, could promote the growth of wheat seedling, reduce the malondialdehyde (MDA) concentration, and increase the activities of antioxidant enzymes. The results of mRNA expression level test for salt stress-responsive genes indicated that COS keep plants away from being hurt by the salt stress via the regulation of the concentration and the increased antioxidant enzymes activities. Moreover, it was found that the activities of COS was closely related to its Das and COS (DA: 50%) displayed the best salt resistance activity to wheat seedlings. The results also showed that COS with different DP could promote the growth of wheat seedlings under salt stress. COS with a DP (6-8) showed better activities than the other tested samples, implied its activity had a close relationship with its DP. After treatment with chitohexaose, chitoheptaose, and chitooctaose, the photosynthetic parameters were improved obviously. The soluble sugar and proline contents were improved by 26.7%-53.3% and 43.6.0%-70.2%, respectively, while the concentration of malondialdehyde (MDA) was reduced by 36.8% - 49.6%. In addition, the antioxidant enzymes activities were clearly activated. At the molecular level, the results revealed that they could obviously induce the expression of Na+/H+ antiporter genes. In general, these results were fundamental to the study of action mechanism of COS on promoting plant growth under salt stress and the preparation of plant growth regulator.

Keywords: chitooligomers (COS), degree of polymerization (DP), degree of acetylation (DA), salt stress

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Authors: Senol Dogan, Gunay Karli

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Identification of relevant publications based on a Medline query is time-consuming and error-prone. An all based process has the potential to solve this problem without any manual work. To the best of our knowledge, our study is the first to investigate the ability of machine learning to identify relevant articles accurately. 5 different machine learning algorithms were tested using 23 predictors based on several metadata fields attached to publications. We find that the Boosted model is the best-performing algorithm and its overall accuracy is 96%. In addition, specificity and sensitivity of the algorithm is 97 and 93%, respectively. As a result of the work, we understood that we can apply the same procedure to understand cancer gene expression big data.

Keywords: prediction of publications, machine learning, algorithms, bariatric surgery, comparison of algorithms, boosted, tree, logistic regression, ANN model

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Authors: Fakhrosadat Sajjadian

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The majority of deaths in cancer patients are caused by distant metastasis. Breast cancer shows a unique spread pattern, often affecting bone, liver, lung, and brain. Breast cancer can be categorized into various subtypes according to gene expression patterns, and these subtypes exhibit specific preferences for organs where metastasis occurs. Breast tumors with luminal characteristics have a preference for spreading to the bone, whereas basal-like breast cancer (BLBC) shows a tendency to metastasize to the lungs. Still, the mechanisms behind this particular pattern of metastasis in organs have yet to be fully understood. In this evaluation, we will outline the latest progress in molecular signaling pathways and treatment methods for breast cancer lung metastasis.

Keywords: lung cancer, liver cancer, diagnosis, BLBC, metastasis

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Authors: Fadi Saleh, Çığdem Sezer Zhmurov

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Biopharmaceuticals represent one of the wildest developing fields within biotechnology, and the biological macromolecules being produced inside cells have a variety of applications for therapies. In the past, mammalian cells, especially CHO cells, have been employed in the production of biopharmaceuticals. This is because these cells can achieve human-like completion of PTM. These systems, however, carry apparent disadvantages like high production costs, vulnerability to contamination, and limitations in scalability. This research is focused on the utilization of microalgae as a bioreactor system for the synthesis of biopharmaceutical glycoproteins in relation to PTMs, particularly N-glycosylation. The research points to a growing interest in microalgae as a potential substitute for more conventional expression systems. A number of advantages exist in the use of microalgae, including rapid growth rates, the lack of common human pathogens, controlled scalability in bioreactors, and the ability of some PTMs to take place. Thus, the potential of microalgae to produce recombinant proteins with favorable characteristics makes this a promising platform in order to produce biopharmaceuticals. The study focuses on the examination of the N-glycosylation pathways across different species of microalgae. This investigation is important as N-glycosylation—the process by which carbohydrate groups are linked to proteins—profoundly influences the stability, activity, and general performance of glycoproteins. Additionally, bioinformatics methodologies are employed to explain the genetic pathways implicated in N-glycosylation within microalgae, with the intention of modifying these organisms to produce glycoproteins suitable for human consumption. In this way, the present comparative analysis of the N-glycosylation pathway in humans and microalgae can be used to bridge both systems in order to produce biopharmaceuticals with humanized glycosylation profiles within the microalgal organisms. The results of the research underline microalgae's potential to help improve some of the limitations associated with traditional biopharmaceutical production systems. The study may help in the creation of a cost-effective and scale-up means of producing quality biopharmaceuticals by modifying microalgae genetically to produce glycoproteins with N-glycosylation that is compatible with humans. Improvements in effectiveness will benefit biopharmaceutical production and the biopharmaceutical sector with this novel, green, and efficient expression platform. This thesis, therefore, is thorough research into the viability of microalgae as an efficient platform for producing biopharmaceutical glycoproteins. Based on the in-depth bioinformatic analysis of microalgal N-glycosylation pathways, a platform for their engineering to produce human-compatible glycoproteins is set out in this work. The findings obtained in this research will have significant implications for the biopharmaceutical industry by opening up a new way of developing safer, more efficient, and economically more feasible biopharmaceutical manufacturing platforms.

Keywords: microalgae, glycoproteins, post-translational modification, genome

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Authors: Peter Williams

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Mobile digital technology, in the form of smart phones, tablets, laptops and their accompanying functionality/apps etc., is becoming ever more used by people with Learning Disabilities (LD) - for entertainment, to communicate and socialize, and enjoy self-expression. Despite this, there has been very little research into the experiences of such technology by this cohort, it’s role in articulating personal identity and self-advocacy and the barriers encountered in negotiating technology in everyday life. The proposed talk describes research funded by the British Academy addressing these issues. It aims to explore: i) the experiences of people with LD in using mobile technology in their everyday lives – the benefits, in terms of entertainment, self-expression and socialising, and possible greater autonomy; and the barriers, such as accessibility or usability issues, privacy or vulnerability concerns etc. ii) how the technology, and in particular the software/apps and interfaces, can be improved to enable the greater access to entertainment, information, communication and other benefits it can offer. It is also hoped that results will inform parents, carers and other supporters regarding how they can use the technology with their charges. Rather than the project simply following the standard research procedure of gathering and analysing ‘data’ to which individual ‘research subjects’ have no access, people with Learning Disabilities (and their supporters) will help co-produce an accessible, annotated and hyperlinked living e-archive of their experiences. Involving people with LD as informants, contributors and, in effect, co-researchers will facilitate digital inclusion and empowerment. The project is working with approximately 80 adults of all ages who have ‘mild’ learning disabilities (people who are able to read basic texts and write simple sentences). A variety of methods is being used. Small groups of participants have engaged in simple discussions or storytelling about some aspect of technology (such as ‘when my phone saved me’ or ‘my digital photos’ etc.). Some individuals have been ‘interviewed’ at a PC, laptop or with a mobile device etc., and asked to demonstrate their usage and interests. Social media users have shown their Facebook pages, Pinterest uploads or other material – giving them an additional focus they have used to discuss their ‘digital’ lives. During these sessions, participants have recorded (or employed the researcher to record) their observations on to the e-archive. Parents, carers and other supporters are also being interviewed to explore their experiences of using mobile technology with the cohort, including any difficulties they have observed their charges having. The archive is supplemented with these observations. The presentation will outline the methods described above, highlighting some of the special considerations required when working inclusively with people with LD. It will describe some of the preliminary findings and demonstrate the e-archive with a commentary on the pages shown.

Keywords: inclusive research, learning disabilities, methods, technology

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Authors: Huai-Feng Wang, Meng-Lin Lou, Ru-Lin Zhang

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One good analysis method in seismic response analysis is direct time integration, which widely adopts Rayleigh damping. An approach is presented for selection of Rayleigh damping coefficients to be used in seismic analyses to produce a response that is consistent with Modal damping response. In the presented approach, the expression of the error of peak response, acquired through complete quadratic combination method, and Rayleigh damping coefficients was set up and then the coefficients were produced by minimizing the error. Two finite element modes of soil layers, excited by 28 seismic waves, were used to demonstrate the feasibility and validity.

Keywords: Rayleigh damping, modal damping, damping coefficients, seismic response analysis

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Authors: Xi Chen, King-Yip Cheng

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Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

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Authors: Paulo Da Silva Quadros

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This work aims to point out comparative parameters between the artistic production of two exponents of the contemporary popular culture scene: Caetano Veloso (Brazil) and David Bowie (England). Both Caetano Veloso and David Bowie were pioneers in establishing an aesthetic game between various artistic expressions at the service of the music-visual scene, that is, the conceptual interconnections between several forms of aesthetic processes, such as fine arts, theatre, cinema, poetry, and literature. There are also correlations in their expressive attitudes of art, especially regarding the dialogue between the fields of art and politics (concern with respect to human rights, human dignity, racial issues, tolerance, gender issues, and sexuality, among others); the constant tension and cunning game between market, free expression and critical sense; the sophisticated, playful mechanisms of metalanguage and aesthetic metacritique. Fact is that both of them almost came to cooperate with each other in the 1970s when Caetano was in exile in England, and when both had at the same time the same music producer, who tried to bring them closer, noticing similar aesthetic qualities in both artistic works, which was later glimpsed by some music critics. Among many of the most influential issues in Caetano's and Bowie's game of artistic-aesthetic expression are, for example, the ideas advocated by the sensation of strangeness (Albert Camus), art as transcendence (Friedrich Nietzsche), the deconstruction and reconstruction of auratic reconfiguration of artistic signs (Walter Benjamin and Andy Warhol). For deepen more theoretical issues, the following authors will be used as supportive interpretative references: Hans-Georg Gadamer, Immanuel Kant, Friedrich Schiller, Johan Huizinga. In addition to the aesthetic meanings of Ars Ludens characteristics of the two artists, the following supporting references will be also added: the question of technique (Martin Heidegger), the logic of sense (Gilles Deleuze), art as an event and the sense of the gesture of art ( Maria Teresa Cruz), the society of spectacle (Guy Debord), Verarbeitung and Durcharbeitung (Sigmund Freud), the poetics of interpretation and the sign of relation (Cremilda Medina). The purpose of such interpretative references is to seek to understand, from a cultural reading perspective (cultural semiology), some significant elements in the dynamics of aesthetic and media interconnections of both artists, which made them as some of the most influential interlocutors in contemporary music aesthetic thought, as a playful vivid experience of life and art.

Keywords: Caetano Veloso, David Bowie, music aesthetics, symbolic playfulness, cultural reading

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Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay

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Background: Cervical cancer is the third major cause of cancer in women and the second most frequent cause of cancer related deaths causing 300,000 deaths annually worldwide. Evasion of immune response by Human Papilloma Virus (HPV), the key contributing factor behind cancer and pre-cancerous lesions of the uterine cervix, makes immunotherapy a necessity to treat this disease. Objective: A Heat killed fraction of Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium has been shown to exhibit cytotoxic effects on different cancer cells, including human cervical carcinoma cell line HeLa. However, the underlying mechanisms remain unknown. The aim of this study is to decipher the mechanism of MIP induced HeLa cell death. Methods: The cytotoxicity of Mycobacterium indicus pranii against HeLa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and Propidium iodide (PI) staining. The assessment of reactive oxygen species (ROS) generation and cell cycle analysis were measured by flow cytometry. The expression of apoptosis associated genes was analyzed by real time PCR. Result: MIP could inhibit the proliferation of HeLa cell in a time and dose dependent manner but caused minor damage to normal cells. The induction of apoptosis was confirmed by the cell surface presentation of phosphatidyl serine, DNA fragmentation, and mitochondrial damage. MIP caused very early (as early as 30 minutes) transcriptional activation of p53, followed by a higher activation (32 fold) at 24 hours suggesting prime importance of p53 in MIP-induced apoptosis in HeLa cell. The up regulation of p53 dependent pro-apoptotic genes Bax, Bak, PUMA, and Noxa followed a lag phase that was required for the transcriptional p53 program. MIP also caused the transcriptional up regulation of Toll like receptor 2 and 4 after 30 minutes of MIP treatment suggesting recognition of MIP by toll like receptors. Moreover, MIP caused the inhibition of expression of HPV anti apoptotic gene E6, which is known to interfere with p53/PUMA/Bax apoptotic cascade. This inhibition might have played a role in transcriptional up regulation of PUMA and subsequently apoptosis. ROS was generated transiently which was concomitant with the highest transcription activation of p53 suggesting a plausible feedback loop network of p53 and ROS in the apoptosis of HeLa cells. Scavenger of ROS, such as N-acetyl-L-cysteine, decreased apoptosis suggesting ROS is an important effector of MIP induced apoptosis. Conclusion: Taken together, MIP possesses full potential to be a novel therapeutic agent in the clinical treatment of cervical cancer.

Keywords: cancer, mycobacterium, immunity, immunotherapy.

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Authors: Hosein Maghsoudi

Abstract:

Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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Authors: Y. R. Adullayev, О. О. Karimzada

Abstract:

Analytical expressions for inductances, current, ampere-turns, excitation winding, maximum width, coordinates of the levitation screen (LS) are derived for the calculation of electromagnetic devices based on tracking systems with levitation elements (TS with LS). Taking into account the expression of the complex magnetic resistance of the screen, the dependence of the screen width on the heating temperature of the physical and technical characteristics of the screen material and the relationship of the geometric dimensions of the magnetic circuit is established. Analytic expressions for a number of functional dependencies characterizing complex parameter relationships in explicit form are obtained and analyzed.

Keywords: tracking systems, levitation screens, electromagnetic levitation, excitation windings, magnetic cores, defining converter, receiving converter, electromagnetic force, electrical and magnetic resistance

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Authors: L. K. Akila

Abstract:

Art activities can fund as a clinical support tool (CST) between interventions in Art Therapy to direct the client back towards better outcome goals. In the present study, during free art sessions, researcher examined the possibilities of motivating the adolescent group to involve in art making process by reflecting upon art intervention administered. Results show that adolescents’ reflecting upon their art works generated during the intervention; could change their perceptions and cognitions to improve their positive approach by restructuring their art expressions. Consequently, such reflections triggered and improved their emotions, feelings and ideas, and produced secure attachment between family, peers and teachers. By the end of interference, transformations experienced were effective more upon depression, self-image, and self-efficacy, and to a certain extent on aggressive patterns represented.

Keywords: adolescent, adolescent psychology, aggression, art, art therapy, cognition, depression, emotion, self-image

Procedia PDF Downloads 259

Authors: Mesfin Angaw Tesfay

Abstract:

Uridine-5’-diphosphate (UDP)-glucose is one of the most versatile building blocks within the metabolism of prokaryotes and eukaryotes, serving as an activated sugar donor during the glycosylation of natural products. It is formed by the enzyme UDP-glucose pyrophosphorylase (UGPase) using uridine-5′-triphosphate (UTP) and α-d-glucose 1-phosphate as a substrate. Herein, two UGPase genes from Lactobacillus kefiranofaciens ZW3 (LkUGPase) and Rhodococcus wratislaviensis IFP 2016 (RwUGPase) were identified through genome mining approaches. The LkUGPase and RwUGPase have 299 and 306 amino acids, respectively. Both UGPase has the conserved UTP binding site (G-X-G-T-R-X-L-P) and the glucose -1-phosphate binding site (V-E-K-P). The LkUGPase and RwUGPase were cloned in E. coli, and SDS-PAGE analysis showed the expression of both enzymes forming about 36 KDa of protein band after induction. LkUGPase and RwUGPase have an activity of 1549.95 and 671.53 U/mg, respectively. Currently, their kinetic properties are under investigation.

Keywords: UGPase, LkUGPase, RwUGPase, UDP-glucose, glycosylation

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Authors: Xiaochen Mu

Abstract:

Whether in common law countries that adhere to the "commercial copyright theory" or in civil law countries that center around "author's rights," the standards for judging originality have undergone continuous adjustments in response to the development of information technology. The adherence to originality standards does not arbitrarily dictate that all types of works be judged according to a single standard of originality, nor does it rigidly ignore the changes in creative methods and dissemination models brought about by technology. Adjustments and interpretations should be allowed based on the different forms of expression of works. Appropriate adjustments and interpretations are our response to technological advancements. However, what should be upheld are the principles and bottom lines of these adjustments and interpretations, namely the legislative intent and purpose of copyright law, which are to encourage the creation and dissemination of outstanding cultural works and to promote the flourishing of culture.

Keywords: generative artificial intelligence, originality, works, copyright

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Authors: Zuzana Komrsková

Abstract:

This paper shows the connection between emoticons and politeness in written computer-mediated communication. It studies if there are some differences in the use of emoticon between Czech and English written tweets. My assumptions about the use of emoticons were based on the use of greetings and thanks in real, face to face situations. The first assumption, that welcome greeting phrase would be accompanied by positive emoticon was correct. But for the farewell greeting both positive and negative emoticons are possible. My results show lower frequency of negative emoticons in this context. I also found quite often both positive and negative emoticon in the same tweet. The expression of gratitude is associated with positive emotions. The results show that emoticons accompany polite phrases of greeting and thanks very often both in Czech and English. The use of emoticons with studied polite phrases shows that emoticons have become an integral part of these phrases.

Keywords: Czech, emoticon, english, politeness, twitter

Procedia PDF Downloads 403

Authors: Carmela Nardelli, Laura Iaffaldano, Valentina Capobianco, Antonietta Tafuto, Maddalena Ferrigno, Angela Capone, Giuseppe Maria Maruotti, Maddalena Raia, Rosa Di Noto, Luigi Del Vecchio, Pasquale Martinelli, Lucio Pastore, Lucia Sacchetti

Abstract:

Maternal obesity and nutrient excess in utero increase the risk of future metabolic diseases in the adult life. The mechanisms underlying this process are probably based on genetic, epigenetic alterations and changes in foetal nutrient supply. In mammals, the placenta is the main interface between foetus and mother, it regulates intrauterine development, modulates adaptive responses to sub optimal in uterus conditions and it is also an important source of human amniotic mesenchymal stem cells (hA-MSCs). We previously highlighted a specific microRNA (miRNA) profiling in amnion from obese (Ob) pregnant women, here we compared the miRNA expression profile of hA-MSCs isolated from (Ob) and control (Co) women, aimed to search for any alterations in metabolic pathways that could predispose the new-born to the obese phenotype. Methods: We isolated, at delivery, hA-MSCs from amnion of 16 Ob- and 7 Co-women with pre-pregnancy body mass index (mean/SEM) 40.3/1.8 and 22.4/1.0 kg/m2, respectively. hA-MSCs were phenotyped by flow cytometry. Globally, 384 miRNAs were evaluated by the TaqMan Array Human MicroRNA Panel v 1.0 (Applied Biosystems). By the TargetScan program we selected the target genes of the miRNAs differently expressed in Ob- vs Co-hA-MSCs; further, by KEGG database, we selected the statistical significant biological pathways. Results: The immunophenotype characterization confirmed the mesenchymal origin of the isolated hA-MSCs. A large percentage of the tested miRNAs, about 61.4% (232/378), was expressed in hA-MSCs, whereas 38.6% (146/378) was not. Most of the expressed miRNAs (89.2%, 207/232) did not differ between Ob- and Co-hA-MSCs and were not further investigated. Conversely, 4.8% of miRNAs (11/232) was higher and 6.0% (14/232) was lower in Ob- vs Co-hA-MSCs. Interestingly, 7/232 miRNAs were obesity-specific, being expressed only in hA-MSCs isolated from obese women. Bioinformatics showed that these miRNAs significantly regulated (P<0.001) genes belonging to several metabolic pathways, i.e. MAPK signalling, actin cytoskeleton, focal adhesion, axon guidance, insulin signaling, etc. Conclusions: Our preliminary data highlight an altered miRNA profile in Ob- vs Co-hA-MSCs and suggest that an epigenetic miRNA-based mechanism of gene regulation could affect pathways involved in placental growth and function, thereby potentially increasing the newborn’s risk of metabolic diseases in the adult life.

Keywords: hA-MSCs, obesity, miRNA, biosystem

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Authors: S. Aizikovich, L. Krenev, Y. Tokovyy, Y. C. Wang

Abstract:

An approximate analytical-numerical solution to the axisymmetric problem on thermo-mechanical indentation of a flat cylindrical punch into an arbitrarily non-homogeneous elastic half-space is constructed by making use of the bilateral asymptotic method. The key point of this method lies in evaluation of the ker¬nels in the obtained integral equations by making use of a numerical technique. Once the structure of the kernel is defined, it then is approximated by an analytical expression of special kind so that the solution of the integral equation can be achieved analytically. This fact allows for construction of the solution in an analytical form, which is convenient for analysis of the mechanical effects concerned with arbitrarily presumed non-homogeneity of the material.

Keywords: contact problem, circular punch, arbitrarily-nonhomogeneous halfspace

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Authors: Muhammad Sohail Khan, Rehan Ali Shah

Abstract:

The present paper applies the optimal homotopy perturbation method (OHPM) and the optimal homotopy asymptotic method (OHAM) introduced recently to obtain analytic approximations of the non-linear equations modeling the flow of polymer in case of wire coating of a corotational Maxwell fluid. Expression for the velocity field is obtained in non-dimensional form. Comparison of the results obtained by the two methods at different values of non-dimensional parameter l₁₀, reveal that the OHPM is more effective and easy to use. The OHPM solution can be improved even working in the same order of approximation depends on the choices of the auxiliary functions.

Keywords: corotational Maxwell model, optimal homotopy asymptotic method, optimal homotopy perturbation method, wire coating die

Procedia PDF Downloads 335

Authors: Yahia Massinissa, Melakhessou Med Akram, Mezahdia Mehdi, Marref Salah Eddine

Abstract:

Cytokines are natural proteins which act as true intercellular communication signals in immune and inflammatory responses. Reverse signaling pathways that activate cytokines help to regulate different functions at the target cell, causing its activation, its proliferation, the differentiation, its survival or death. It was shown that malfunctioning of the cytokine regulation, particularly over-expression, contributes to the onset and development of certain serious diseases such as chronic rheumatoid arthritis, Crohn's disease, psoriasis, lupus. The action mode of Kinoid® technology is based on the principle vaccine: The patient's immune system is activated so that it neutralizes itself and the factor responsible for the disease. When applied specifically to autoimmune diseases, therapeutic vaccination allows the body to neutralize cytokines (proteins) overproduced through a highly targeted stimulation of the immune system.

Keywords: cytokines, Kinoid tech, auto-immune diseases, vaccination

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Authors: Chukwuma Anya, Mekwa Eme

Abstract:

The term ‘’FORM’’ in design could be referred to as the combination of various shapes of different sizes and assembling them in appropriate positions to achieve a unique figure of high aesthetic value. A deduction from this definition is that forms contribute immensely to the actualization of aesthetics in a building. When these various shapes and figures are properly assembled, it may give rise to a concept in design. However some architects and other designers either misuse or abuse the use of these shapes, hence resulting to a design imbalance, lack of uniformity and expression. This academic work is designed to educate the public on the proper usage of some regular shapes like circles, rectangles, pentagons, hexagons, triangles etc, to achieve a unique form in design. By the end of this work, one should be able to assemble different shapes to express different emotions of the mind, such as peace, love, confusion, war, and unity. Some elements of design, such as balance, stability, functionality and aesthetics, will also be achieved even as the building maintains its unique form.

Keywords: aesthetics, form, balance, stability

Procedia PDF Downloads 83