Search results for: genes expression

Authors: Tanima Chatterjee, Maitree Bhattacharyya

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The global challenge of type 2 diabetes mellitus is a major health concern in this millennium, and researchers are continuously exploring new targets to develop a novel therapeutic strategy. Type 2 diabetes mellitus (T2DM) is often coupled with dyslipidemia increasing the risks for cardiovascular (CVD) complications. Enhanced oxidative and nitrosative stresses appear to be the major risk factors underlying insulin resistance, dyslipidemia, β-cell dysfunction, and T2DM pathogenesis. Autophagy emerges to be a promising defense mechanism against stress-mediated cell damage regulating tissue homeostasis, cellular quality control, and energy production, promoting cell survival. In this study, we have attempted to explore the pivotal role of autophagy in T2DM subjects with or without dyslipidemia in peripheral blood mononuclear cells and insulin-resistant HepG2 cells utilizing flow cytometric platform, confocal microscopy, and molecular biology techniques like western blotting, immunofluorescence, and real-time polymerase chain reaction. In the case of T2DM with dyslipidemia higher population of autophagy, positive cells were detected compared to patients with the only T2DM, which might have resulted due to higher stress. Autophagy was observed to be triggered both by oxidative and nitrosative stress revealing a novel finding of our research. LC3 puncta was observed in peripheral blood mononuclear cells and periphery of HepG2 cells in the case of the diabetic and diabetic-dyslipidemic conditions. Increased expression of ATG5, LC3B, and Beclin supports the autophagic pathway in both PBMC and insulin-resistant Hep G2 cells. Upon blocking autophagy by 3-methyl adenine (3MA), the apoptotic cell population increased significantly, as observed by caspase‐3 cleavage and reduced expression of Bcl2. Autophagy has also been evidenced to control oxidative stress-mediated up-regulation of inflammatory markers like IL-6 and TNF-α. To conclude, this study elucidates autophagy to play a protective role in the case of diabetes mellitus with dyslipidemia. In the present scenario, this study demands to have a significant impact on developing a new therapeutic strategy for diabetic dyslipidemic subjects by enhancing autophagic activity.

Keywords: autophagy, apoptosis, dyslipidemia, reactive oxygen species, reactive nitrogen species, Type 2 diabetes

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Authors: Aleksander Mendoza

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Glushkov's construction has many interesting properties, and they become even more evident when applied to transducers. This article strives to show the vast range of possible extensions and optimisations for this algorithm. Special flavour of regular expressions is introduced, which can be efficiently converted to e-free functional subsequential weighted finite state transducers. Produced automata are very compact, as they contain only one state for each symbol (from input alphabet) of original expression and only one transition for each range of symbols, no matter how large. Such compactified ranges of transitions allow for efficient binary search lookup during automaton evaluation. All the methods and algorithms presented here were used to implement open-source compiler of regular expressions for multitape transducers.

Keywords: weighted automata, transducers, Glushkov, follow automata, regular expressions

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Authors: Kyujin Shim

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This study explores how individual motivations in political psychology will lead to political expression and online discourse, and how those online political discourses result in individuals’ exposure to extreme/ personally-entertaining/ disinhibiting content. This study argues that a new framework beyond the conventional paradigm (e.g., selective exposure based on partisanship/ ideology) is needed for better grasp of non-ideological/ anarchic, and/or of nonpartisan yet anonymity-/ extremity-/ disinhibition-related online behaviors regarding political conversations. Further, this study proposes a new definition of ‘selective exposure,’ with special attention to online efficacy and psychological motivations/gratifications sought in the online sphere.

Keywords: selective exposure, fear of isolation, political psychology, online discourse

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Authors: H. Yousefnia, MS. Mousavi-Daramoroudi, S. Zolghadri, F. Abbasi-Davani

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High expression of somatostatin receptors on a wide range of human tumours makes them as potential targets for peptide receptor radionuclide tomography. A series of octreotide analogues were synthesized while [DOTA-DPhe1, Tyr3]octreotide (DOTATOC) indicated advantageous properties in tumour models. In this study, 177Lu-DOTATOC was prepared with the radiochemical purity of higher than 99% in 30 min at the optimized condition. Biological behavior of the complex was studied after intravenous injection into the Syrian rats. Major difference uptake was observed compared to 177LuCl3 solution especially in somatostatin receptor-positive tissues such as pancreas and adrenal.

Keywords: Biodistribution, 177Lu, Octreotide, Syrian rats

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Authors: Marinka K. Baghdasaryan, Siranush M. Muradyan, Avgen A. Gasparyan

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Based on the experimental data, the impact of resistance and reactance of the winding, as well as the magnetic permeability of the magnetic circuit steel material on the value of the electromotive force of the induction converter is investigated. The obtained results allow to estimate the main technological spreads and determine the maximum level of the electromotive force change. By the method of experiment planning, the expression of a polynomial for the electromotive force which can be used to estimate the adequacy of mathematical models to be used at the investigation and design of induction converters is obtained.

Keywords: induction converter, electromotive force, expectation, technological spread, deviation, planning an experiment, polynomial, confidence level

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Authors: D. Beckwith

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This research explored sexual identity for women with physical disability, both congenital and acquired. It also explored whether exposure to violence or negative risk-taking had played a role in their intimate relationships. This phenomenological research used semi-structured interviews and photo elicitation with the researcher’s insider knowledge adding experiential substance and understanding to the discussion. Findings confirm sexuality for women with physical disability is marginalised and de-gendered making it less of a priority for professionals and policy makers and emphasising the need to more effectively support women with disability in relation to their sexuality, sexual expression and violence.

Keywords: lived-experience, identity, PhotoVoice, sexuality, violence, women with physical disability

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Authors: Pei Luen Jiang

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Oysters (Ostreidae) and hard clams (Meretrix lusoria) are important shallow sea-cultured shellfish in Taiwan, and are mainly farmed in Changhua, Yunlin, Chiayi and Tainan. As these shellfish are fed primarily on natural plankton, the artificial feed is not required, leading to high economic value in aquatic farming. However, in recent years, though mariculture production areas have expanded steadily, large-scale deaths of farmed shellfish have also become increasingly common due to climate change and human factors. Through studies over the past few years, our research team has determined the impact of nitrogen deprivation on growth and morphological variations in algae and sea anemones (Actiniaria) and identified the target genes affected by adverse environmental factors. In mariculture, high-density farming is commonly adopted, which results in elevated concentrations of nitrogenous waste in the water. In addition, excessive carbon dioxide from the atmosphere also dissolves in seawater, causing a steady decrease in the pH of seawater, leading to acidification. This study to observe the impact of high concentrations of nitrogen sources and carbon dioxide on algae.

Keywords: algae, shellfish, nitrogen, acidification

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Authors: Dalal Alghawas, Jetty Lee, Kaisa Poutanen, Hani El-Nezami

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Oat β-glucan a water soluble non starch linear polysaccharide has been approved as a cholesterol lowering agent by various food safety administrations and is commonly used to reduce the risk of heart disease. The molecular weight of oat β-glucan can vary depending on the extraction and fractionation methods. It is not clear whether the molecular weight has a significant impact at reducing the acceleration of atherosclerosis. The aim of this study was to investigate three different oat β-glucan fractionations on the development of atherosclerosis in vivo. With special focus on plaque stability and the intestinal barrier function. To test this, ApoE-/- female mice were fed a high fat diet supplemented with oat bran, high molecular weight (HMW) oat β-glucan fractionate and low molecular weight (LMW) oat β-glucan fractionate for 16 weeks. Atherosclerosis risk markers were measured in the plasma, heart and aortic tree. Plaque size was measured in the aortic root and aortic tree. ICAM-1, VCAM-1, E-Selectin, P-Selectin, protein levels were assessed from the aortic tree to determine plaque stability at 16 weeks. The expression of p22phox at the aortic root was evaluated to study the NADPH oxidase complex involved in nitric oxide bioavailability and vascular elasticity. The tight junction proteins E-cadherin and beta-catenin from western blot analyses were analysed as an intestinal barrier function test. Plasma LPS, intestinal D-lactate levels and hepatic FMO gene expression were carried out to confirm whether the compromised intestinal barrier lead to endotoxemia. The oat bran and HMW oat β-glucan diet groups were more effective than the LMW β-glucan diet group at reducing the plaque size and showed marked improvements in plaque stability. The intestinal barrier was compromised for all the experimental groups however the endotoxemia levels were higher in the LMW β-glucan diet group. The oat bran and HMW oat β-glucan diet groups were more effective at attenuating the development of atherosclerosis. Reasons for this could be due to the LMW oat β-glucan diet group’s low viscosity in the gut and the inability to block the reabsorption of cholesterol. Furthermore the low viscosity may allow more bacterial endotoxin translocation through the impaired intestinal barrier. In future food technologists should carefully consider how to incorporate LMW oat β-glucan as a health promoting food.

Keywords: Atherosclerosis, beta glucan, endotoxemia, intestinal barrier function

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Authors: Vesna Kirandziska, Nevena Ackovska, Ana Madevska Bogdanova

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The problem of emotion recognition is a challenging problem. It is still an open problem from the aspect of both intelligent systems and psychology. In this paper, both voice features and facial features are used for building an emotion recognition system. A Support Vector Machine classifiers are built by using raw data from video recordings. In this paper, the results obtained for the emotion recognition are given, and a discussion about the validity and the expressiveness of different emotions is presented. A comparison between the classifiers build from facial data only, voice data only and from the combination of both data is made here. The need for a better combination of the information from facial expression and voice data is argued.

Keywords: emotion recognition, facial recognition, signal processing, machine learning

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Authors: Yu-Chen Hu

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Gene editing by CRISPR and gene regulation by microRNA or CRISPR activation have dramatically changed the way to manipulate cellular gene expression and cell fate. In recent years, various gene editing and gene manipulation technologies have been applied to control stem cell differentiation to enhance tissue regeneration. This research will focus on how to develop CRISPR, CRISPR activation (CRISPRa), CRISPR inhibition (CRISPRi), as well as bi-directional CRISPR-AI gene regulation technologies to control cell differentiation and bone regeneration. Moreover, in this study, CRISPR/Cas13d-mediated RNA editng for miRNA editing and bone regeneration will be discussed.

Keywords: gene therapy, bone regeneration, stem cell, CRISPR, gene regulation

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Authors: Saurav Sharma, Deepshikha Sharma, Pratibha Sharma

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This paper includes fast fashion verses sustainable fashion or slow fashion Indian based consumers. The expression ‘Fast fashion’ is generally referred to low-cost clothing collections that considered first hand copy of luxury brands, sometime interchangeably used with ‘mass fashion’. Whereas slow fashion or limited fashion which are consider to be more organic or eco-friendly. "Sustainable fashion is ethical fashion and here the consumer is just not design conscious but also social-environment conscious". Paper will deal with desire of young Indian consumer towards such luxury brands present in India, and their understanding of sustainable fashion, how to maintain the equilibrium between never newer fashion, style, and fashion sustainability.

Keywords: fast fashion, sustainable fashion, sustainability, India

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Authors: Yifeng Shi, Xingping Wang

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The Soviet Union-style of urban planning has produced a broad and profound influence on China’s urban planning system. The study on extendibility and development experience of Soviet planning in China helps to change the current embarrassing situation 'one-hand planning practice, second-hand planning theory', and also beneficial to facilitate the establishment of China's domestic urban planning theory from the planning source, especially the overseas cooperation parks rich in 'Chinese characteristics'. In practice, as the world’s major infrastructure country, China is exporting to the world especially countries along 'the Belt and Road' a development model featuring cooperation parks as Chinese characteristics. This is of great significance to evaluate and summarize the experiences of Soviet Union-style of planning for China's development objectively and rationally, from removing ideological factors and extracting positive factors to carry them forward in overseas cooperation parks. This article briefly reviews the Soviet influence on urban planning after the founding of China and divided the influences stages into 'guidance, internalization and absorption, selective learning, decline' four periods. The impact includes production-oriented planning and planning concepts continue to be implemented, the establishment of the regional planning, master planning, detailed planning of the basic framework of urban planning, and homogenized cellular structure of the space, as well as planning techniques, professional training, planning techniques and so on. China and even most socialist countries now still carry such planning genes. At present, in the process of implementing 'the Belt and Road' strategy, the planning and construction of China’s overseas cooperation parks generally encounter many problems as lack of strategic planning and systematic planning, lack of top-level design, uncoordinated planning and layout in parks, and redundant construction in some areas. After sublating the planning genes of the Soviet Union-style of urban planning for the development of the socialist countries, especially the industrial planning system, this paper puts forward some views as follows to realize the overseas output and development of China's planning model and technology. Firstly the future development of overseas cooperation park should be from a rational planning point of view. Secondly the government should not only rigidly and equitably allocate the resources of the parks but also closely integrate the national economic plans or economic development strategies. Lastly management department should frame the threshold of development rationally, give full play to the pragmatic planning style in accordance with the local land system and planning system. It has an important guiding and reference role for the development of China's overseas cooperation park under the 'go global' strategy, after objectively evaluating the impact of the Soviet Union-style urban planning and absorbing the beneficial components on China. However, we should also recognize that the cooperation parks and the urban industrial system behind it are only part of urban development. More attention should be payed on the design of the local and the general rules of urban development to take the lead effect of cooperation parks suitable. Foundation item: Under the auspices of the Specific Plan for Strategic International Cooperation in Scientific and Technological Innovation, the National Key Research and Development Plan 'Research Cooperation and Exemplary Application in Planning of Development of Overseas Industrial Parks' (No 2016YFE0201000).

Keywords: China cooperative parks, history of urban planning, output mode, The Soviet Union

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Authors: Andrea Trimarchi

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This paper is designed to provide a comprehensive overview on the EU Regulation No. 868/2004 concerning protection against subsidisation and unfair pricing practices regarding non-EU carriers and causing injury to Community air carriers. The analysis will focus, at first, on the exegetical scrutiny of the legal categories encompassed by the Regulation. In addition to that, while considering the peculiarities of such legal instrument, the attention will be addressed on the assessment on its effectiveness. The Regulation, indeed, having received lots of criticism, is in need of a profound revision. In this context, the present work will try to take into account the policy alternatives. In light of the failure of Regulation 868, which is to be seen as the expression of a unilateral and regional approach, there would seem to be the necessity for the aviation sector to reconsider the topic of subsidisation and unfair pricing practices in a more international oriented manner.

Keywords: non-EU airlines, aviation, subisidisation, unfair

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Authors: Constantius Tri Handoko

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Tattoos on the body of Christian youths seemed interesting as the majority of Christian look at tattoo and tattooing activity are prohibited. This research besides to understand the motivation behind why Christian youth in Surabaya and Sidoarjo, Indonesia being tattooed also focus on the regard to what functions and meanings of the tattoos are. By using visual discourse analysis, the tattoos had relation to the informants’ social lives dimension, such as the Christian symbol tattoos expressed their spiritual life journey, a faith symbol to God, as personal symbols (identity), art expression, as well as fashion. On the other hands, tattoos also became a hatred symbol to Jesus and the Christian faith, since the tattoo wearers who were a former Christians felt disappointed to God as they thought God never help them to survive in their lives.

Keywords: tattoo, representation, identity, belief, Christian

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Authors: Jacek Kabzinski, Karolina Przybylowska, Lukasz Dziki, Adam Dziki, Ireneusz Majsterek

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The incidence of colorectal cancer (CRC) is increasing from year to year. Despite intensive research CRC etiology remains unknown. Studies suggest that at the basis of the process of carcinogenesis can lie reduced efficiency of DNA repair mechanisms, often caused by polymorphisms in DNA repair genes. The aim of the study was to determine the relationship between gene polymorphisms Pro242Arg of PolB gene and Arg780His of Lig3 gene and modulation of the risk of colorectal cancer in the Polish population. Determination of the molecular basis of carcinogenesis process and predicting increased risk will allow qualifying patients to increased risk group and including them in preventive program. We used blood collected from 110 patients diagnosed with colorectal cancer. The control group consisted of equal number of healthy people. Genotyping was performed by TaqMan method. The obtained results indicate that the genotype 780Arg/His of Lig3 gene is associated with an increased risk of colorectal cancer. On the basis of these results, we conclude that Lig3 gene polymorphism Arg780His may be associated with an increased risk of colorectal cancer.

Keywords: BER, colorectal cancer, PolB, Lig3, polymorphisms

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Authors: Jae Woong Sull

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Lipid levels are related to the risk of cardiovascular diseases. Cholesterol ester transfer protein (CETP) gene is one of the candidate genes of cardiovascular diseases. A total of 2,304 persons were chosen from a Hospital (N=4,294) in South Korea. Female subjects with the CG/GG genotype had a 2.03 -fold (p=0.0001) higher risk of having abnormal HDL cholesterol levels (<40 mg/dL) than subjects with the CC genotype. Male subjects with the CG/GG genotype had a 1.34 -fold (p=0.0019) higher risk than subjects with the CC genotype. When analyzed by body mass index, the association with CETP was much stronger in male subjects with BMI>=25.69 (OR=1.55, 95% CI: 1.15-2.07, P=0.0037) than in male lean subjects. When analyzed by family history of diabetes, the association with CETP was much stronger in male subjects with positive family history of low physical activity (OR=4.82, 95% CI: 1.86-12.5, P=0.0012) than in male subjects with negative family history of diabetes. This study clearly demonstrates that genetic variants in CETP influence HDL cholesterol levels in Korean adults.

Keywords: CETP, diabetes, obesity, polymorphisms

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Authors: S. Pradhan, D. Pradhan, G. Tripathy

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Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

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Authors: Ashutosh Mishra, Nikhil Goyal

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A 3D facial emotion recognition model based on deep learning is proposed in this paper. Two convolution layers and a pooling layer are employed in the deep learning architecture. After the convolution process, the pooling is finished. The probabilities for various classes of human faces are calculated using the sigmoid activation function. To verify the efficiency of deep learning-based systems, a set of faces. The Kaggle dataset is used to verify the accuracy of a deep learning-based face recognition model. The model's accuracy is about 65 percent, which is lower than that of other facial expression recognition techniques. Despite significant gains in representation precision due to the nonlinearity of profound image representations.

Keywords: facial recognition, computational intelligence, convolutional neural network, depth map

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Authors: Shreya Bokare, Sanjay Pawar, Shika Nema

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Growth in cloud applications is generating the tremendous amount of data, building load on traditional storage management systems. Software Defined Storage (SDS) is a new storage management concept becoming popular to handle this large amount of data. CoprHD is one of the open source SDS controller, available for experimentation and development in the storage industry. In this paper, the storage management techniques provided by CoprHD to manage heterogeneous storage platforms are experimented and analyzed. Various storage management parameters such as time to provision, storage capacity measurement, and heterogeneity are experimentally evaluated along with the theoretical expression to prove the completeness of CoprHD controller for storage management.

Keywords: software defined storage, SDS, CoprHD, open source, SMI-S simulator, clarion, Symmetrix

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Authors: Aliya Ashraf, Mehreen Sirshar, Fatima Akhtar, Farwa Kazmi, Jawaria Wazir

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Vision, the basis for performing navigational tasks, is absent or greatly reduced in visually impaired people due to which they face many hurdles. For increasing the navigational capabilities of visually impaired people a desktop application ODAPTA is presented in this paper. The application uses camera to capture video from surroundings, apply various image processing algorithms to get information about path and obstacles, tracks them and delivers that information to user through voice commands. Experimental results show that the application works effectively for straight paths in daylight.

Keywords: visually impaired, ODAPTA, Region of Interest (ROI), driver fatigue, face detection, expression recognition, CCD camera, artificial intelligence

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Authors: Rim Sghiri, Samia Al Shouli, Hana Benhassine, Nejla Elamri, Zahid Shakoor, Foued Slama, Adel Almogren, Hala Zeglaoui, Elyes Bouajina, Ramzi Zemni

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Objectives: Little is known about genes predisposing to systemic bone loss (SBL) in rheumatoid arthritis (RA). Therefore, we examined the association between SBL and a variant of CD40 gene, which is known to play a critical role in both immune response and bone homeostasis among patients with RA. Methods: CD40 rs48104850 was genotyped in 176 adult RA patients. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). Results: Low BMD was observed in 116 (65.9%) patients. Among them, 60 (34.1%) had low femoral neck (FN) Z score, 72 (40.9%) had low total femur (TF) Z score, and 105 (59.6%) had low lumbar spine (LS) Z score. CD40 rs4810485 was found to be associated with reduced TF Z score with the CD40 rs4810485 T allele protecting against reduced TF Z score (OR = 0.40, 95% CI = 0.23-0.68, p = 0.0005). This association was confirmed in the multivariate logistic regression analysis (OR=0.31, 95% CI= 0.16-0.59, p=3.84 x 10₋₄). Moreover, median FN BMD was reduced among RA patients with CD40 rs4810485 GG genotype compared to RA patients harbouring CD40 rs4810485 TT and GT genotypes (0.788± 0.136 versus 0.826± 0.146g/cm², p=0.001). Conclusion: This study, for the first time ever, demonstrated an association between a CD40 genetic variant and SBL among patients with RA.

Keywords: rheumatoid arthritis, CD40 gene, bone mineral density, systemic bone loss, rs48104850

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Authors: Ibrahim Ilker Ozyigit, Ertugrul Filiz, Ilhan Dogan

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An in silico analysis of Brachypodium distachyon, Triticum aestivum, Festuca arundinacea, Lolium perenne, Hordeum vulgare subsp. vulgare of the Pooideaea was performed based on complete chloroplast genomes including rbcL coding and trnH-psbA intergenic spacer regions alone to compare phylogenetic resolving power. Neighbor-joining, Minimum Evolution, and Unweighted Pair Group Method with arithmetic mean methods were used to reconstruct phylogenies with the highest bootstrap supported the obtained data from whole chloroplast genome sequence. The highest and lowest values from nucleotide diversity (π) analysis were found to be 0.315813 and 0.043495 in rbcL coding region in chloroplast genome and complete chloroplast genome, respectively. The highest transition/transversion bias (R) value was recorded as 1.384 in complete chloroplast genomes. F. arudinacea-L. perenne clade was uncovered in all phylogenies. Sequences of rbcL and trnH-psbA regions were not able to resolve the Pooideae phylogenies due to lack of genetic variation.

Keywords: chloroplast DNA, Pooideae, phylogenetic analysis, rbcL, trnH-psbA

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Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi

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Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.

Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis

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Authors: Natalia Fontes De Oliveira

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The Canadian author Margaret Atwood deconstructs the tainted dichotomies between women and men by embracing the disorder throughout her dystopias. In Atwood’s The Testaments, nature can be seen as a background to the story as well as a metaphorical expression of the characters’ state of mind, nevertheless, the protagonists’ nature writing portrays conveys a curiosity to the pre-established sanctions of a docile garden, viewing nature as an autonomous entity, especially when they are away from the confinements of Gilead’s regime. The three narrating protagonists, Agnes, Aunt Lydia, and Nicole, use nature writing subversively as a form of rebellion. This paper investigates how the three protagonists narrate nature through an intimist point of view, with sensibility to observe the multiple relationships among humanity, nature, and the impositions of a theocratic ultra conservative patriarchal society.

Keywords: contemporary literature, dystopias, feminism, women’s writing

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Authors: Triloki Nath, R. K. Gupta, L. P. Singh

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The aim of this paper is to find the new exact solution of the blast wave problem in one-dimensional unsteady adiabatic flow for generalized geometry in a compressible, inviscid ideal gas with dust particles. The density of the undisturbed region is assumed to vary according to a power law of the distance from the point of explosion. The exact solution of the problem in form of a power in the distance and the time is obtained. Further, the behaviour of the total energy carried out by the blast wave for planar, cylindrically symmetric and spherically symmetric flow corresponding to different Mach number of the fluid flow in dusty gas is presented. It is observed that the presence of dust particles in the gas yields more complex expression as compared to the ordinary Gasdynamics.

Keywords: shock wave, blast wave, dusty gas, strong shock

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Authors: Sibel Özkan

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This study aims to set forth the perception of young people in Turkey about “Gezi Parkı Actions” which has been represented by different views on social and traditional media. In-depth interview method was carried out with all of the participants who consisted of high school students. All interviews has been conducted in areas where the actions take place and the numbers of participants who are using and not using social media were equal. There are minor differences between young people who are using and not using social media. Participants who are not using social media had an opinion only about saving nature aspect of Gezi Parkı Actions. On the other hand, people who are using social media had another reasons such as freedom of expression, respect to the lifestyles etc. to join Gezi Parkı Actions. It was found that young people do not completely trust traditional media anymore.

Keywords: Gezi Parkı, resistance, social media, hegemony

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Authors: Michal Almagor, Rivka Tuval-Mashiach

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This presentation will explore the main processes identified in women writing group, as an interdisciplinary field with personal and social effects. It is based on the initial findings of a Ph.D. research focus on the intersection of group processes with the element of writing, in the context of gender. Writing as a therapeutic mean has been recognized and found to be highly effective. Additionally, a substantial amount of research reveals the psychological impact of group processes. However, the combination of writing and groups as a therapeutic tool was hardly investigated; this is the contribution of this research. In the following qualitative-phenomenological study, the experiences of eight women participating in a 10-sessions structured writing group were investigated. We used the meetings transcripts, semi-structured interviews, and the texts to analyze and understand the experience of participating in the group. The two significant findings revealed were spiral intersubjectivity and archaic level of semiotic language. We realized that the content and the process are interwoven; participants are writing, reading and discussing their texts in a group setting that enhanced self-dialogue between the participants and their own narratives and texts, as well as dialogue with others. This process includes working through otherness within and between while discovering and creating a multiplicity of narratives. A movement of increasing shared circles from the personal to the group and to the social-cultural environment was identified, forming what we termed as spiral intersubjectivity. An additional layer of findings was revealed while we listened to the resonance of the group-texts, and discourse; during this process, we could trace the semiotic level in addition to the symbolic one. We were witness to the dominant presence of the body, and primal sensuality, expressed by rhythm, sound and movements, signs of pre-verbal language. Those findings led us to a new understanding of the semiotic function as a way to express the fullness of women experience and the enabling role of writing in reviving what was repressed. The poetic language serves as a bridge between the symbolic and the semiotic. Re-reading the group materials, exposed another layer of expression, an old-new language. This approach suggests a feminine expression of subjective experience with personal and social importance. It is a subversive move, encouraging women to write themselves, as a craft that every woman can use, giving voice to the silent and hidden, and experiencing the power of performing 'my story'. We suggest that women writing group is an efficient, powerful yet welcoming way to raise the awareness of researchers and clinicians, and more importantly of the participants, to the uniqueness of the feminine experience, and to gender-sensitive curative approaches.

Keywords: group, intersubjectivity, semiotic, writing

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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

Abstract:

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

Abstract:

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

Procedia PDF Downloads 476