Search results for: genes expression
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2505

Search results for: genes expression

615 Effects of Lateness Gene on Yield and Related Traits in Indica Rice

Authors: B. B. Rana, M. Yokota, Y. Shimizu, Y. Koide, I. Takamure, T. Kawano, M. Murai

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Various genes which control or affect heading time have been found in rice. Out of them, Se1 and E1 loci play important roles in determining heading time by controlling photosensitivity. An isogenic-line pair of late and early lines were developed from progenies of the F1 from Suweon 258 × 36U. A lateness gene tentatively designated as “Ex” was found to control the difference in heading time between the early and late lines mentioned above. The present study was conducted to examine the effect of Ex on yield and related traits. Indica-type variety Suweon 258 was crossed with 36U, which is an Ur1 (Undulate rachis-1) isogenic line of IR36. In the F2 population, comparatively early-heading, late-heading and intermediate-heading plants were segregated. Segregation similar to that by the three types of heading was observed in the F3 and later generations. A late-heading plant and an early-heading plant were selected in the F8 population from an intermediate-heading F7 plant, for developing L and E of the isogenic-line pair, respectively. Experiments for L and E were conducted by randomized block design with three replications. Transplanting was conducted on May 3 at a planting distance of 30 cm × 15 cm with two seedlings per hill to an experimental field of the Faculty of Agriculture, Kochi University. Chemical fertilizers containing N, P2O5 and K2O were applied at the nitrogen levels of 4 g/m2, 9 g/m2 and 18 g/m2 in total being denoted by "N4", "N9" and "N18", respectively. Yield, yield components and other traits were measured. Ex delayed 80%-heading by 17 or 18 days in L as compared with E. In total brown rice yield (g/m2), L was 635, 606 and 590, and E was 577, 548 and 501, respectively, at N18, N9 and N4, indicating that Ex increased this trait by 10% to 18%. Ex increased yield-1.5 mm sieve (g/m2) b 9% to 15% at the three fertilizer levels. Ex increased the spikelet number per panicle by 16% to 22%. As a result, the spikelet number per m2 was increased by 11% to 18% at the three fertilizer levels. Ex decreased 1000-grain weight (g) by 2 to 4%. L was not significantly different from E in ripened-grain percentage, fertilized-spikelet percentage and percentage of ripened grains to fertilized spikelets. Hence, it is inferred that Ex increased yield by increasing spikelet number per panicle. Hence, Ex could be utilized to develop high yielding varieties for warmer districts.

Keywords: heading time, lateness gene, photosensitivity, yield, yield components

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614 Obsession of Time and the New Musical Ontologies. The Concert for Saxophone, Daniel Kientzy and Orchestra by Myriam Marbe

Authors: Dutica Luminita

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For the music composer Myriam Marbe the musical time and memory represent 2 (complementary) phenomena with conclusive impact on the settlement of new musical ontologies. Summarizing the most important achievements of the contemporary techniques of composition, her vision on the microform presented in The Concert for Daniel Kientzy, saxophone and orchestra transcends the linear and unidirectional time in favour of a flexible, multi-vectorial speech with spiral developments, where the sound substance is auto(re)generated by analogy with the fundamental processes of the memory. The conceptual model is of an archetypal essence, the music composer being concerned with identifying the mechanisms of the creation process, especially of those specific to the collective creation (of oral tradition). Hence the spontaneity of expression, improvisation tint, free rhythm, micro-interval intonation, coloristic-timbral universe dominated by multiphonics and unique sound effects. Hence the atmosphere of ritual, however purged by the primary connotations and reprojected into a wonderful spectacular space. The Concert is a work of artistic maturity and enforces respect, among others, by the timbral diversity of the three species of saxophone required by the music composer (baritone, sopranino and alt), in Part III Daniel Kientzy shows the performance of playing two saxophones concomitantly. The score of the music composer Myriam Marbe contains a deeply spiritualized music, full or archetypal symbols, a music whose drama suggests a real cinematographic movement.

Keywords: archetype, chronogenesis, concert, multiphonics

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613 Uncertainty Assessment in Building Energy Performance

Authors: Fally Titikpina, Abderafi Charki, Antoine Caucheteux, David Bigaud

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The building sector is one of the largest energy consumer with about 40% of the final energy consumption in the European Union. Ensuring building energy performance is of scientific, technological and sociological matter. To assess a building energy performance, the consumption being predicted or estimated during the design stage is compared with the measured consumption when the building is operational. When valuing this performance, many buildings show significant differences between the calculated and measured consumption. In order to assess the performance accurately and ensure the thermal efficiency of the building, it is necessary to evaluate the uncertainties involved not only in measurement but also those induced by the propagation of dynamic and static input data in the model being used. The evaluation of measurement uncertainty is based on both the knowledge about the measurement process and the input quantities which influence the result of measurement. Measurement uncertainty can be evaluated within the framework of conventional statistics presented in the \textit{Guide to the Expression of Measurement Uncertainty (GUM)} as well as by Bayesian Statistical Theory (BST). Another choice is the use of numerical methods like Monte Carlo Simulation (MCS). In this paper, we proposed to evaluate the uncertainty associated to the use of a simplified model for the estimation of the energy consumption of a given building. A detailed review and discussion of these three approaches (GUM, MCS and BST) is given. Therefore, an office building has been monitored and multiple sensors have been mounted on candidate locations to get required data. The monitored zone is composed of six offices and has an overall surface of 102 $m^2$. Temperature data, electrical and heating consumption, windows opening and occupancy rate are the features for our research work.

Keywords: building energy performance, uncertainty evaluation, GUM, bayesian approach, monte carlo method

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612 Sequence Analysis and Molecular Cloning of PROTEOLYSIS 6 in Tomato

Authors: Nurulhikma Md Isa, Intan Elya Suka, Nur Farhana Roslan, Chew Bee Lynn

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The evolutionarily conserved N-end rule pathway marks proteins for degradation by the Ubiquitin Proteosome System (UPS) based on the nature of their N-terminal residue. Proteins with a destabilizing N-terminal residue undergo a series of condition-dependent N-terminal modifications, resulting in their ubiquitination and degradation. Intensive research has been carried out in Arabidopsis previously. The group VII Ethylene Response Factor (ERFs) transcription factors are the first N-end rule pathway substrates found in Arabidopsis and their role in regulating oxygen sensing. ERFs also function as central hubs for the perception of gaseous signals in plants and control different plant developmental including germination, stomatal aperture, hypocotyl elongation and stress responses. However, nothing is known about the role of this pathway during fruit development and ripening aspect. The plant model system Arabidopsis cannot represent fleshy fruit model system therefore tomato is the best model plant to study. PROTEOLYSIS6 (PRT6) is an E3 ubiquitin ligase of the N-end rule pathway. Two homologs of PRT6 sequences have been identified in tomato genome database using the PRT6 protein sequence from model plant Arabidopsis thaliana. Homology search against Ensemble Plant database (tomato) showed Solyc09g010830.2 is the best hit with highest score of 1143, e-value of 0.0 and 61.3% identity compare to the second hit Solyc10g084760.1. Further homology search was done using NCBI Blast database to validate the data. The result showed best gene hit was XP_010325853.1 of uncharacterized protein LOC101255129 (Solanum lycopersicum) with highest score of 1601, e-value 0.0 and 48% identity. Both Solyc09g010830.2 and uncharacterized protein LOC101255129 were genes located at chromosome 9. Further validation was carried out using BLASTP program between these two sequences (Solyc09g010830.2 and uncharacterized protein LOC101255129) to investigate whether they were the same proteins represent PRT6 in tomato. Results showed that both proteins have 100 % identity, indicates that they were the same gene represents PRT6 in tomato. In addition, we used two different RNAi constructs that were driven under 35S and Polygalacturonase (PG) promoters to study the function of PRT6 during tomato developmental stages and ripening processes.

Keywords: ERFs, PRT6, tomato, ubiquitin

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611 Tool for Analysing the Sensitivity and Tolerance of Mechatronic Systems in Matlab GUI

Authors: Bohuslava Juhasova, Martin Juhas, Renata Masarova, Zuzana Sutova

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The article deals with the tool in Matlab GUI form that is designed to analyse a mechatronic system sensitivity and tolerance. In the analysed mechatronic system, a torque is transferred from the drive to the load through a coupling containing flexible elements. Different methods of control system design are used. The classic form of the feedback control is proposed using Naslin method, modulus optimum criterion and inverse dynamics method. The cascade form of the control is proposed based on combination of modulus optimum criterion and symmetric optimum criterion. The sensitivity is analysed on the basis of absolute and relative sensitivity of system function to the change of chosen parameter value of the mechatronic system, as well as the control subsystem. The tolerance is analysed in the form of determining the range of allowed relative changes of selected system parameters in the field of system stability. The tool allows to analyse an influence of torsion stiffness, torsion damping, inertia moments of the motor and the load and controller(s) parameters. The sensitivity and tolerance are monitored in terms of the impact of parameter change on the response in the form of system step response and system frequency-response logarithmic characteristics. The Symbolic Math Toolbox for expression of the final shape of analysed system functions was used. The sensitivity and tolerance are graphically represented as 2D graph of sensitivity or tolerance of the system function and 3D/2D static/interactive graph of step/frequency response.

Keywords: mechatronic systems, Matlab GUI, sensitivity, tolerance

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610 Effect of Genotype and Sex on Morphometric Traits of Turkey

Authors: I. O. Dudusola, I. Ogunjimi

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This study was carried out to determine the effect of sex and genotype on morphometric traits of turkey (Meleagris gallopavo) in a turkey population. Linear body measurements were taken on 150 turkeys. 70 exotic turkeys which include both males (20) and Females (50) and 80 locally adapted turkeys which include males (30) and females (50). The study was conducted at the Turkey Unit of the Teaching and Research Farm, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria. The linear body measurements taken and recorded were the beak length, head length, neck length, body length, keel length, wingspan, wing length, drumstick, Shank length, toe length, tail length and body girth all taken in centimetres (cm). The recorded variables were analyzed with SAS (2008). Duncan multiple range test was used to detect differences among means. Variation was noted between male and female turkeys in favour of the male turkeys as an expression of sexual dimorphism for all studied traits. The male is found to be significantly higher (p <0.05) than the females for all the morphometric traits measured both for the local and exotic type. The exotic type is found to be significantly higher (p <0.05) than the local type for all the morphometric traits measured. The interaction is higher significantly (p <0.05) in the exotic genotype and in the male sex in relation with the morphometric trait especially in the beak length, neck length, body length, keel length, drumstick, shank length and the toe length.

Keywords: exotic type, linear measurement, local type, morphometric traits, Meleagris gallopavo

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609 Igbo Art: A Reflection of the Igbo’s Visual Culture

Authors: David Osa-Egonwa

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Visual culture is the expression of the norms and social behavior of a society in visual images. A reflection simply shows you how you look when you stand before a mirror, a clear water or stream. The mirror does not alter, improve or distort your original appearance, neither does it show you a caricature of what stands before it, this is the case with visual images created by a tribe or society. The ‘uli’ is hand drawn body design done on Igbo women and speaks of a culture of body adornment which is a practice that is appreciated by that tribe. The use of pattern of the gliding python snake ‘ije eke’ or ‘ijeagwo’ for wall painting speaks of the Igbo culture as one that appreciates wall paintings based on these patterns. Modern life came and brought a lot of change to the Igbo-speaking people of Nigeria. Change cloaked in the garment of Westernization has influenced the culture of the Igbos. This has resulted in a problem which is a break in the cultural practice that has also affected art produced by the Igbos. Before the colonial masters arrived and changed the established culture practiced by the Igbos, visual images were created that retained the culture of this people. To bring this point to limelight, this paper has adopted a historical method. A large number of works produced during pre and post-colonial era which range from sculptural pieces, paintings and other artifacts, just to mention a few, were studied carefully and it was discovered that the visual images hold the culture or aspects of the culture of the Igbos in their renditions and can rightly serve as a mirror of the Igbo visual culture.

Keywords: artistic renditions, historical method, Igbo visual culture, changes

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608 Proteomics Application in Disease Diagnosis and Reproduction İmprovement in Cow

Authors: Abdollah Sobhani, Hossein Vaseghi-Dodaran

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Proteomics is defined as the study of the component of a cell, tissue and biological fluid. This technique has the potential to identify protein biomarkers of a disease states. In this study which was performed on bovine ovarian follicular cysts (BOFC), eight proteins are over expressed in BOFC that these proteins could be useful biomarkers for BOFC. The difference between serum proteome pattern cows affected by postpartum endometritis with healthy cows revealed that concentrations orosomucoid was decreased in endometritis. The comparison proteome of brucella abortus between laboratory adapted strains and clinical isolates could be useful to better understand this disease and vaccine development. Proteomics experiments identified new proteins and pathways that may be important in future hypothesis-driven studies of glucocorticoid-induced immunosuppression. Understanding the molecular mechanisms of effective parameters on male fertility is essential for obtaining high reproductive efficiency by decreasing cost and time. The investigations on proteome of high fertility spermatozoa indicated that expression of some proteins such as casein kinase 2 (CKII) prime poly peptide and tyrosine kinase in high fertility spermatozoa was higher compared to low fertility spermatozoa. Also, some evidence has indicated that variation in protein types and amounts in seminal fluid regulates fertility indexes in dairy bull. In conclusion, proteomics is a useful technique for discovering drugs, vaccine development, and diagnosis disease by biomarkers and improvement of reproduction efficiency.

Keywords: proteomics, reproduction, biomarker, immunity

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607 ScRNA-Seq RNA Sequencing-Based Program-Polygenic Risk Scores Associated with Pancreatic Cancer Risks in the UK Biobank Cohort

Authors: Yelin Zhao, Xinxiu Li, Martin Smelik, Oleg Sysoev, Firoj Mahmud, Dina Mansour Aly, Mikael Benson

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Background: Early diagnosis of pancreatic cancer is clinically challenging due to vague, or no symptoms, and lack of biomarkers. Polygenic risk score (PRS) scores may provide a valuable tool to assess increased or decreased risk of PC. This study aimed to develop such PRS by filtering genetic variants identified by GWAS using transcriptional programs identified by single-cell RNA sequencing (scRNA-seq). Methods: ScRNA-seq data from 24 pancreatic ductal adenocarcinoma (PDAC) tumor samples and 11 normal pancreases were analyzed to identify differentially expressed genes (DEGs) in in tumor and microenvironment cell types compared to healthy tissues. Pathway analysis showed that the DEGs were enriched for hundreds of significant pathways. These were clustered into 40 “programs” based on gene similarity, using the Jaccard index. Published genetic variants associated with PDAC were mapped to each program to generate program PRSs (pPRSs). These pPRSs, along with five previously published PRSs (PGS000083, PGS000725, PGS000663, PGS000159, and PGS002264), were evaluated in a European-origin population from the UK Biobank, consisting of 1,310 PDAC participants and 407,473 non-pancreatic cancer participants. Stepwise Cox regression analysis was performed to determine associations between pPRSs with the development of PC, with adjustments of sex and principal components of genetic ancestry. Results: The PDAC genetic variants were mapped to 23 programs and were used to generate pPRSs for these programs. Four distinct pPRSs (P1, P6, P11, and P16) and two published PRSs (PGS000663 and PGS002264) were significantly associated with an increased risk of developing PC. Among these, P6 exhibited the greatest hazard ratio (adjusted HR[95% CI] = 1.67[1.14-2.45], p = 0.008). In contrast, P10 and P4 were associated with lower risk of developing PC (adjusted HR[95% CI] = 0.58[0.42-0.81], p = 0.001, and adjusted HR[95% CI] = 0.75[0.59-0.96], p = 0.019). By comparison, two of the five published PRS exhibited an association with PDAC onset with HR (PGS000663: adjusted HR[95% CI] = 1.24[1.14-1.35], p < 0.001 and PGS002264: adjusted HR[95% CI] = 1.14[1.07-1.22], p < 0.001). Conclusion: Compared to published PRSs, scRNA-seq-based pPRSs may be used not only to assess increased but also decreased risk of PDAC.

Keywords: cox regression, pancreatic cancer, polygenic risk score, scRNA-seq, UK biobank

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606 Deciphering Orangutan Drawing Behavior Using Artificial Intelligence

Authors: Benjamin Beltzung, Marie Pelé, Julien P. Renoult, Cédric Sueur

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To this day, it is not known if drawing is specifically human behavior or if this behavior finds its origins in ancestor species. An interesting window to enlighten this question is to analyze the drawing behavior in genetically close to human species, such as non-human primate species. A good candidate for this approach is the orangutan, who shares 97% of our genes and exhibits multiple human-like behaviors. Focusing on figurative aspects may not be suitable for orangutans’ drawings, which may appear as scribbles but may have meaning. A manual feature selection would lead to an anthropocentric bias, as the features selected by humans may not match with those relevant for orangutans. In the present study, we used deep learning to analyze the drawings of a female orangutan named Molly († in 2011), who has produced 1,299 drawings in her last five years as part of a behavioral enrichment program at the Tama Zoo in Japan. We investigate multiple ways to decipher Molly’s drawings. First, we demonstrate the existence of differences between seasons by training a deep learning model to classify Molly’s drawings according to the seasons. Then, to understand and interpret these seasonal differences, we analyze how the information spreads within the network, from shallow to deep layers, where early layers encode simple local features and deep layers encode more complex and global information. More precisely, we investigate the impact of feature complexity on classification accuracy through features extraction fed to a Support Vector Machine. Last, we leverage style transfer to dissociate features associated with drawing style from those describing the representational content and analyze the relative importance of these two types of features in explaining seasonal variation. Content features were relevant for the classification, showing the presence of meaning in these non-figurative drawings and the ability of deep learning to decipher these differences. The style of the drawings was also relevant, as style features encoded enough information to have a classification better than random. The accuracy of style features was higher for deeper layers, demonstrating and highlighting the variation of style between seasons in Molly’s drawings. Through this study, we demonstrate how deep learning can help at finding meanings in non-figurative drawings and interpret these differences.

Keywords: cognition, deep learning, drawing behavior, interpretability

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605 Interaction between Kazal-Type Serine Proteinase Inhibitor SPIPm2 and Cyclophilin A from the Black Tiger Shrimp Penaeus monodon

Authors: Sirikwan Ponprateep, Anchalee Tassanakajon, Vichien Rimphanitchayakit

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A Kazal-type serine proteinase inhibitor, SPIPm2, was abundantly expressed in the hemocytes and secreted into shrimp plasma has anti-viral property against white spot syndrome virus (WSSV). To discover the molecular mechanism of antiviral activity, the binding assay showed that SPIPm2 bind to the components of viral particle and shrimp hemocyte. From our previous report, viral target protein of SPIPm2 was identified, namely WSV477 using yeast two-hybrid screening. WSV477 is an early gene product of WSSV and involved in viral propagation. In this study, the co-immunoprecipitation technique and Tandem Mass Spectrometry (LC-MS/MS) was used to identify the target protein of SPIPm2 from shrimp hemocyte. The target protein of SPIPm2 was cyclophilin A. In vertebrate, cyclophilin A or peptidylprolyl isomerase A was reported to be the immune suppressor interacted with cyclosporin A involved in immune defense response. The recombinant cyclophilin A from Penaeus monodon (rPmCypA) was produced in E.coli system and purified using Ni-NTA column to confirm the protein-protein interaction. In vitro pull-down assay showed the interaction between rSPIPm2 and rPmCypA. To study the biological function of these proteins, the expression analysis of immune gene in shrimp defense pathways will be investigated after rPmCypA administration.

Keywords: cyclophilin A, protein-protein interaction, Kazal-type serine proteinase inhibitor, Penaeus monodon

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604 Fashion Performing/Fashioning Performances: Catwalks as Communication Tools between Market, Branding and Performing Art

Authors: V. Linfante

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Catwalks are one of the key moments in fashion: the first and most relevant display where brands stage their collections, products, ideas, and style. The garment is 'the star' of the catwalk and must show itself not just as a product but as a result of a design process endured for several months. All contents developed within this process become ingredients for connecting scenography, music, lights, and direction into a unique fashion narrative. According to the spirit of different ages, fashion shows have been transformed and shaped into peculiar formats: from Pandoras to presentations organized by Parisian couturiers, across the 'marathons' typical of the beginning of modern fashion system, coming up to the present structure of fashion weeks, with their complex organization and related creative and technical businesses. The paper intends to introduce the evolution of the fashion system through its unique process of seasonally staging and showing its production. The paper intends to analyse the evolution of the fashion shows from the intimacy of ballrooms at the beginning of the 20th century, passing through the enthusiasm attitude typical from the '70s and the '80s, to finally depict our present. In this last scenario, catwalks are not anymore a standard collections presentation but become one of the most exciting expression of contemporary culture (and sub-cultures), going from sophisticated performances (as Karl Lagerfeld's Chanel shows) to real artistic happenings (as the events of Victor&Rolf, Alexander McQueen, OFF_WHITE, Vetements, and Martin Margiela), often involving contemporary architecture, digital world, technology, social media, performing art and artists.

Keywords: branding, communication, fashion, new media, performing art

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603 The Culture of Journal Writing among Manobo Senior High School Students

Authors: Jessevel Montes

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This study explored on the culture of journal writing among the Senior High School Manobo students. The purpose of this qualitative morpho-semantic and syntactic study was to discover the morphological, semantic, and syntactic features of the written output through morphological, semantic, and syntactic categories present in their journal writings. Also, beliefs and practices embedded in the norms, values, and ideologies were identified. The study was conducted among the Manobo students in the Senior High Schools of Central Mindanao, particularly in the Division of North Cotabato. Findings revealed that morphologically, the features that flourished are the following: subject-verb concordance, tenses, pronouns, prepositions, articles, and the use of adjectives. Semantically, the features are the following: word choice, idiomatic expression, borrowing, and vernacular. Syntactically, the features are the types of sentences according to structure and function; and the dominance of code switching and run-on sentences. Lastly, as to the beliefs and practices embedded in the norms, values, and ideologies of their journal writing, the major themes are: valuing education, family, and friends as treasure, preservation of culture, and emancipation from the bondage of poverty. This study has shed light on the writing capabilities and weaknesses of the Manobo students when it comes to English language. Further, such an insight into language learning problems is useful to teachers because it provides information on common trouble-spots in language learning, which can be used in the preparation of effective teaching materials.

Keywords: applied linguistics, culture, morpho-semantic and syntactic analysis, Manobo Senior High School, Philippines

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602 The Environmental Influence on Slow Learners' Learning Achievement

Authors: Niphattha Hannapha

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This paper examines how the classroom environment influences slow learners’ learning achievement; it focuses on how seating patterns affect students’ behaviours and which patterns best contribute to students’ learning performance. The researcher studied how slow learners’ characteristics and seating patterns influenced their behaviours and performance at Ban Hin Lad School. As a nonparticipant observation, the target groups included 15 slow learners from Prathomsueksa (Grades) 4 and 5. Students’ behaviours were recorded during their learning activities in order to minimize their reading and written expression disorder in Thai language tutorials. The result showed four seating patterns and two behaviors which obstructed students’ learning. The average of both behaviours mostly occurred when students were seated with patterns 1 (the seat facing the door, with the corridor alongside) and 3 (the seat alongside the door, facing the aisle) respectively. Seating patterns 1 and 3 demonstrated visibility (the front and side) of a walking path with two-way movement. However, seating patterns 2 (seating with the door alongside and the aisle at the back) and 4 (sitting with the door at the back and the aisle alongside) demonstrated visibility (the side) of a walking path with one-way movement. In Summary, environmental design is important to enhance concentration in slow learners who have reading and writing disabilities. This study suggests that students should be seated where they can have the least visibility of movement to help them increase continuous learning. That means they can have a better chance of developing reading and writing abilities in comparison with other patterns of seating.

Keywords: slow learning, interior design, interior environment, classroom

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601 Modified Acetamidobenzoxazolone Based Biomarker for Translocator Protein Mapping during Neuroinflammation

Authors: Anjani Kumar Tiwari, Neelam Kumari, Anil Mishra

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The 18-kDa translocator protein (TSPO) previously called as peripheral benzodiazepine receptor, is proven biomarker for variety of neuroinflammation. TSPO is tryptophane rich five transmembranal protein found on outer mitochondrial membrane of steroid synthesising and immunomodulatory cells. In case of neuronal damage or inflammation the expression level of TSPO get upregulated as an immunomodulatory response. By utilizing Benzoxazolone as a basic scaffold, series of TSPO ligands have been designed followed by their screening through in silico studies. Synthesis has been planned by employing convergent methodology in six high yielding steps. For the synthesized ligands the ‘in vitro’ assay was performed to determine the binding affinity in term of Ki. On ischemic rat brain, autoradiography studies were also carried to check the specificity and affinity of the designed radiolabelled ligand for TSPO.Screening was performed on the basis of GScore of CADD based schrodinger software. All the modified and better prospective compound were successfully carried out and characterized by spectroscopic techniques (FTIR, NMR and HRMS). In vitro binding assay showed best binding affinity Ki = 6.1+ 0.3 for TSPO over central benzodiazepine receptor (CBR) Ki > 200. ARG studies indicated higher uptake of two analogues on the lesion side compared with that on the non-lesion side of ischemic rat brains. Displacement experiments with unlabelled ligand had minimized the difference in uptake between the two sides which indicates the specificity of the ligand towards TSPO receptor.

Keywords: TSPO, PET, imaging, Acetamidobenzoxazolone

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600 Characteristics of Serum Exosomes after Burn Injury and Dermal Fibroblast Regulation by Exosomes in Vitro

Authors: Jie Ding, Yingying Pan, Shammy Raj, Lindy Schaffrick, Jolene Wong, Antoinette Nguyen, Sharada Manchikanti, Larry Unsworth, Peter Kwan, Edward E. Tredget

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Background: Exosomes (EXOs) have been considered a new target that is thought to be involved in and treat wound healing. More research is needed to fully understand the EXO characteristics and mechanisms of EXO-mediated wound healing, especially wound healing after burn injury. Methods: Total EXOs were isolated from 85 serum samples of 29 burn patients and 13 healthy individuals. We characterized the EXOs for morphology and density, serum concentration, protein level, marker expression, size distribution, and cytokine content. After confirmation of EXO uptake by dermal fibroblasts, we also explored functional regulation of primary human normal skin and hypertrophic scar fibroblast cell lines by the EXOs in vitro, including cell proliferation and apoptosis. Results: EXOs dynamically changed their morphology, density, size, and cytokine level during wound healing in burn patients, which were correlated with burn severity and the stages of wound healing. EXOs from both burn patients and healthy individuals stimulated dermal fibroblast proliferation and apoptosis. Conclusion: EXO features may be important signals that influence wound healing after burn injury; however, to understand the mechanisms by which EXOs regulated the fibroblasts in healing wounds, further studies will be required in the future.

Keywords: exosome, burn, wound healing, hypertrophic scarring, cytokines

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599 Identification of Potential Small Molecule Regulators of PERK Kinase

Authors: Ireneusz Majsterek, Dariusz Pytel, J. Alan Diehl

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PKR-like ER kinase (PERK) is serine/threonie endoplasmic reticulum (ER) transmembrane kinase activated during ER-stress. PERK can activate signaling pathways known as unfolded protein response (UPR). Attenuation of translation is mediated by PERK via phosphorylation of eukaryotic initiation factor 2α (eIF2α), which is necessary for translation initiation. PERK activation also directly contributes to activation of Nrf2 which regulates expression of anti-oxidant enzymes. An increased phosphorylation of eIF2α has been reported in Alzheimer disease (AD) patient hippocampus, indicating that PERK is activated in this disease. Recent data have revealed activation of PERK signaling in non-Hodgkins lymphomas. Results also revealed that loss of PERK limits mammary tumor cell growth in vitro and in vivo. Consistent with these observations, activation of UPR in vitro increases levels of the amyloid precursor protein (APP), the peptide from which beta-amyloid plaques (AB) fragments are derived. Finally, proteolytic processing of APP, including the cleavages that produce AB, largely occurs in the ER, and localization coincident with PERK activity. Thus, we expect that PERK-dependent signaling is critical for progression of many types of diseases (human cancer, neurodegenerative disease and other). Therefore, modulation of PERK activity may be a useful therapeutic target in the treatment of different diseases that fail to respond to traditional chemotherapeutic strategies, including Alzheimer’s disease. Our goal will be to developed therapeutic modalities targeting PERK activity.

Keywords: PERK kinase, small molecule inhibitor, neurodegenerative disease, Alzheimer’s disease

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598 Evaluation of Developmental Toxicity and Teratogenicity of Perfluoroalkyl Compounds Using FETAX

Authors: Hyun-Kyung Lee, Jehyung Oh, Young Eun Jeong, Hyun-Shik Lee

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Perfluoroalkyl compounds (PFCs) are environmental toxicants that persistently accumulate in the human blood. Their widespread detection and accumulation in the environment raise concerns about whether these chemicals might be developmental toxicants and teratogens in the ecosystem. We evaluated and compared the toxicity of PFCs of containing various numbers of carbon atoms (C8-11 carbons) on vertebrate embryogenesis. We assessed the developmental toxicity and teratogenicity of various PFCs. The toxic effects on Xenopus embryos were evaluated using different methods. We measured teratogenic indices (TIs) and investigated the mechanisms underlying developmental toxicity and teratogenicity by measuring the expression of organ-specific biomarkers such as xPTB (liver), Nkx2.5 (heart), and Cyl18 (intestine). All PFCs that we tested were found to be developmental toxicants and teratogens. Their toxic effects were strengthened with increasing length of the fluorinated carbon chain. Furthermore, we produced evidence showing that perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFuDA) are more potent developmental toxicants and teratogens in an animal model compared to the other PFCs we evaluated [perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA)]. In particular, severe defects resulting from PFDA and PFuDA exposure were observed in the liver and heart, respectively, using the whole mount in situ hybridization, real-time PCR, pathologic analysis of the heart, and dissection of the liver. Our studies suggest that most PFCs are developmental toxicants and teratogens, however, compounds that have higher numbers of carbons (i.e., PFDA and PFuDA) exert more potent effects.

Keywords: PFC, xenopus, fetax, development

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597 A Critical Discourse Analysis of Jamaican and Trinidadian News Articles about D/Deafness

Authors: Melissa Angus Baboun

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Utilizing a Critical Discourse Analysis (CDA) methodology and a theoretical framework based on disability studies, how Jamaican and Trinidadian newspapers discussed issues relating to the Deaf community were examined. The term deaf was inputted into the search engine tool of the online website for the Jamaica Observer and the Trinidad & Tobago Guardian. All 27 articles that contained the term deaf in its content and were written between August 1, 2017 and November 15, 2017 were chosen for the study. The data analysis was divided into three steps: (1) listing and analysis instances of metaphorical deafness (e.g. fall on deaf ears), (2) categorization of the content of the articles into the models of disability discourse (the medical, socio-cultural, and superscrip models of disability narratives), and (3) the analysis of any additional data found. A total of 42% of the articles pulled for this study did not deal with the Deaf community in any capacity, but rather instances of the use of idiomatic expressions that use deafness as a metaphor for a non-physical, undesirable trait. The most common idiomatic expression found was fall on deaf ears. Regarding the models of disability discourse, eight articles were found to follow the socio-cultural model, two were found to follow the medical model, and two were found to follow the superscrip model. The additional data found in these articles include two instances of the term deaf and mute, an overwhelming use of lower case d for the term deaf, and the misuse of the term translator (to mean interpreter).

Keywords: deafness, disability, news coverage, Caribbean newspapers

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596 Computerized Analysis of Phonological Structure of 10,400 Brazilian Sign Language Signs

Authors: Wanessa G. Oliveira, Fernando C. Capovilla

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Capovilla and Raphael’s Libras Dictionary documents a corpus of 4,200 Brazilian Sign Language (Libras) signs. Duduchi and Capovilla’s software SignTracking permits users to retrieve signs even when ignoring the gloss corresponding to it and to discover the meaning of all 4,200 signs sign simply by clicking on graphic menus of the sign characteristics (phonemes). Duduchi and Capovilla have discovered that the ease with which any given sign can be retrieved is an inverse function of the average popularity of its component phonemes. Thus, signs composed of rare (distinct) phonemes are easier to retrieve than are those composed of common phonemes. SignTracking offers a means of computing the average popularity of the phonemes that make up each one of 4,200 signs. It provides a precise measure of the degree of ease with which signs can be retrieved, and sign meanings can be discovered. Duduchi and Capovilla’s logarithmic model proved valid: The degree with which any given sign can be retrieved is an inverse function of the arithmetic mean of the logarithm of the popularity of each component phoneme. Capovilla, Raphael and Mauricio’s New Libras Dictionary documents a corpus of 10,400 Libras signs. The present analysis revealed Libras DNA structure by mapping the incidence of 501 sign phonemes resulting from the layered distribution of five parameters: 163 handshape phonemes (CherEmes-ManusIculi); 34 finger shape phonemes (DactilEmes-DigitumIculi); 55 hand placement phonemes (ArtrotoToposEmes-ArticulatiLocusIculi); 173 movement dimension phonemes (CinesEmes-MotusIculi) pertaining to direction, frequency, and type; and 76 Facial Expression phonemes (MascarEmes-PersonalIculi).

Keywords: Brazilian sign language, lexical retrieval, libras sign, sign phonology

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595 Exhaled Breath Condensate in Lung Cancer: A Non-Invasive Sample for Easier Mutations Detection by Next Generation Sequencing

Authors: Omar Youssef, Aija Knuuttila, Paivi Piirilä, Virinder Sarhadi, Sakari Knuutila

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Exhaled breath condensate (EBC) is a unique sample that allows studying different genetic changes in lung carcinoma through a non-invasive way. With the aid of next generation sequencing (NGS) technology, analysis of genetic mutations has been more efficient with increased sensitivity for detection of genetic variants. In order to investigate the possibility of applying this method for cancer diagnostics, mutations in EBC DNA from lung cancer patients and healthy individuals were studied by using NGS. The key aim is to assess the feasibility of using this approach to detect clinically important mutations in EBC. EBC was collected from 20 healthy individuals and 9 lung cancer patients (four lung adenocarcinomas, four 8 squamous cell carcinoma, and one case of mesothelioma). Mutations in hotpot regions of 22 genes were studied by using Ampliseq Colon and Lung cancer panel and sequenced on Ion PGM. Results demonstrated that all nine patients showed a total of 19 cosmic mutations in APC, BRAF, EGFR, ERBB4, FBXW7, FGFR1, KRAS, MAP2K1, NRAS, PIK3CA, PTEN, RET, SMAD4, and TP53. In controls, 15 individuals showed 35 cosmic mutations in BRAF, CTNNB1, DDR2, EGFR, ERBB2, FBXW7, FGFR3, KRAS, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, and TP53. Additionally, 45 novel mutations not reported previously were also seen in patients’ samples, and 106 novel mutations were seen in controls’ specimens. KRAS exon 2 mutations G12D was identified in one control specimen with mutant allele fraction of 6.8%, while KRAS G13D mutation seen in one patient sample showed mutant allele fraction of 17%. These findings illustrate that hotspot mutations are present in DNA from EBC of both cancer patients and healthy controls. As some of the cosmic mutations were seen in controls too, no firm conclusion can be drawn on the clinical importance of cosmic mutations in patients. Mutations reported in controls could represent early neoplastic changes or normal homeostatic process of apoptosis occurring in lung tissue to get rid of mutant cells. At the same time, mutations detected in patients might represent a non-invasive easily accessible way for early cancer detection. Follow up of individuals with important cancer mutations is necessary to clarify the significance of these mutations in both healthy individuals and cancer patients.

Keywords: exhaled breath condensate, lung cancer, mutations, next generation sequencing

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594 The Discussions of Love, Determinism, and Providence in Ibn Sina (Avicenna) and al-Kirmani

Authors: Maria De Cillis

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This paper addresses the subject of love in two of the most prominent Islamic philosophers: Ibn Sīnā (known in the Latin World as Avicenna d. 1037) Avicenna and al-Kirmānī (DC 1021). By surveying the connection that the concept of love entertains with the notions of divine providence and determinism in the luminaries’ theoretical systems, the present paper highlights differences and similarities in their respective approaches to the subjects. Through a thorough analysis of primary and secondary literature, it will be shown that Avicenna’s thought, which is mainly informed by the Aristotelian and Farābīan metaphysical and cosmological stances, is also integrated with mystical underpinnings. Particularly, in Avicenna’s Risāla fī’l-ʿishq love becomes the expression of the divine providence which operates through the intellectual striving the souls undertake in their desire to return to their First Cause. Love is also portrayed as an instrument helping the divine decree to remain unadulterated by way of keeping existing beings within their species and genera as well as an instrument which is employed by God to know and be known. This paper also discusses that if on the one hand, al-Kirmānī speaks of love as the Aristotelian and Farābian motive-force spurring existents to achieve perfection and as a tool which facilitates the status quo of divine creation, on the other hand, he remains steadily positioned within Ismā‘īlī and Neoplatonic paradigms: the return of all loving-beings to their Source is interrupted at the level of the first Intellect, whilst God remains inaccessible and ineffable. By investigating his opus magnum, the Rāḥat al-ʿaql, we shall highlight how al-Kirmānī also emphasizes the notion of divine providence which allows humans to attain their ultimate completeness by following the teachings of the Imams, repositories of the knowledge necessary to serve the unreachable deity.

Keywords: Avicenna, determinism, love, al-Kirmani, Ismaili philosophy

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593 A Precision Medicine Approach to Sickle Cell Disease by Targeting the Adhesion Interactome

Authors: Anthara Vivek, Manisha Shukla, Mahesh Narayan, Prakash Narayan

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Sickle cell disease disproportionately affects sub-Saharan Africa and certain tribal populaces in India and has consequently drawn little intertest from Pharma. In sickle cell patients, adhesion of erythrocytes or reticulocytes to one another and the vessel wall results in painful ischemic episodes with few, if any, effective treatments for vaso-occlusive crises. Identification of disease-associated adhesion markers on erythrocytes or reticulocytes might inform the use of more effective therapies against vaso-occlusive crises. Increased expression of one or more of bcam, itga4, cd44, cd47, rap1a, vcam1, or icam4 has been reported in sickle cell subjects. Using the miRNet ontology knowledgebase, peripheral blood interactomes were generated by seeding various combinations of the afore-referenced mRNA. These interactomes yielded an array of miR targets. As examples, targeting hsa-miR-155-5p can potentially neutralize the rap1a-bcam-cd44-itga4-vcam1 erythrocyte/reticulocyte adhesion interactome whereas targeting hsa-miRs-103a-3p or 107 can potentially neutralize adhesion in cells overexpressing icam4-cd47-bcam-itga4-cd36. AM3380 (MIRacle™) is an off-the shelf hsa-miR-155-5p agomiR that can potentially neutralize the rap1a-bcam-cd44-itga4-vcam1 signaling axis. Phlebotomy coupled with transcriptomics represents a potentially feasible and effective precision medicine strategy to mitigate vaso-occlusive crises in sickle cell patients.

Keywords: adhesion, interactome, precision, medicine

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592 Phage Capsid for Efficient Delivery of Cytotoxic Drugs

Authors: Simona Dostalova, Dita Munzova, Ana Maria Jimenez Jimenez, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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The boom of nanomedicine in recent years has led to the development of numerous new nanomaterials that can be used as nanocarriers in the drug delivery. These nanocarriers can either be synthetic or natural-based. The disadvantage of many synthetic nanocarriers is their toxicity in patient’s body. Protein cages that can naturally be found in human body do not exhibit such disadvantage. However, the release of cargo from some protein cages in target cells can be problematic. As a special type of protein cages can serve the capsid of many viruses, including phage. Phages infect bacterial cells; therefore they are not harmful to human cells. The targeting of phage particles to cancer cells can be solved by producing of empty phage capsids during which the targeting moieties (e.g. peptides) can be cloned into genes of phage capsid to decorate its surface. Moreover, the produced capsids do not contain viral nucleic acid and are therefore not infectious to beneficial bacteria in the patient’s body. The protein cage composed of viral capsid is larger than other frequently used apoferritin cage but its size is still small enough to benefit from passive targeting by Enhanced Permeability and Retention effect. In this work, bacteriophage λ was used, both whole and its empty capsid for delivery of different cytotoxic drugs (cisplatin, carboplatin, oxaliplatin, etoposide and doxorubicin). Large quantities of phage λ were obtained from phage λ-producing strain of E. coli cultivated in medium with 0.2 % maltose. After killing of E. coli with chloroform and its removal by centrifugation, the phage was concentrated by ultracentrifugation at 130 000 g and 4 °C for 3 h. The encapsulation of the drugs was performed by infusion method and four different concentrations of the drugs were encapsulated (200; 100; 50; 25 µg/ml). Free molecules of drugs were removed by dialysis. The encapsulation was verified using spectrophotometric and electrochemical methods. The amount of encapsulated drug linearly increased with the amount of applied drug (determination coefficient R2=0.8013). 76% of applied drug was encapsulated in phage λ particles (concentration of 10 µg/ml), even with the highest applied concentration of drugs, 200 µg/ml. Only 1% of encapsulated drug was detected in phage DNA. Similar results were obtained with encapsulation in phage empty capsid. Therefore, it can be concluded that the encapsulation of drugs into phage particles is efficient and mostly occurs by interaction of drugs with protein capsid.

Keywords: cytostatics, drug delivery, nanocarriers, phage capsid

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591 Developing Oral Communication Competence in a Second Language: The Communicative Approach

Authors: Ikechi Gilbert

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Oral communication is the transmission of ideas or messages through the speech process. Acquiring competence in this area which, by its volatile nature, is prone to errors and inaccuracies would require the adoption of a well-suited teaching methodology. Efficient oral communication facilitates exchange of ideas and easy accomplishment of day-to-day tasks, by means of a demonstrated mastery of oral expression and the making of fine presentations to audiences or individuals while recognizing verbal signals and body language of others and interpreting them correctly. In Anglophone states such as Nigeria, Ghana, etc., the French language, for instance, is studied as a foreign language, being used majorly in teaching learners who have their own mother tongue different from French. The same applies to Francophone states where English is studied as a foreign language by people whose official language or mother tongue is different from English. The ideal approach would be to teach these languages in these environments through a pedagogical approach that properly takes care of the oral perspective for effective understanding and application by the learners. In this article, we are examining the communicative approach as a methodology for teaching oral communication in a foreign language. This method is a direct response to the communicative needs of the learner involving the use of appropriate materials and teaching techniques that meet those needs. It is also a vivid improvement to the traditional grammatical and audio-visual adaptations. Our contribution will focus on the pedagogical component of oral communication improvement, highlighting its merits and also proposing diverse techniques including aspects of information and communication technology that would assist the second language learner communicate better orally.

Keywords: communication, competence, methodology, pedagogical component

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590 Efficient Reuse of Exome Sequencing Data for Copy Number Variation Callings

Authors: Chen Wang, Jared Evans, Yan Asmann

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With the quick evolvement of next-generation sequencing techniques, whole-exome or exome-panel data have become a cost-effective way for detection of small exonic mutations, but there has been a growing desire to accurately detect copy number variations (CNVs) as well. In order to address this research and clinical needs, we developed a sequencing coverage pattern-based method not only for copy number detections, data integrity checks, CNV calling, and visualization reports. The developed methodologies include complete automation to increase usability, genome content-coverage bias correction, CNV segmentation, data quality reports, and publication quality images. Automatic identification and removal of poor quality outlier samples were made automatically. Multiple experimental batches were routinely detected and further reduced for a clean subset of samples before analysis. Algorithm improvements were also made to improve somatic CNV detection as well as germline CNV detection in trio family. Additionally, a set of utilities was included to facilitate users for producing CNV plots in focused genes of interest. We demonstrate the somatic CNV enhancements by accurately detecting CNVs in whole exome-wide data from the cancer genome atlas cancer samples and a lymphoma case study with paired tumor and normal samples. We also showed our efficient reuses of existing exome sequencing data, for improved germline CNV calling in a family of the trio from the phase-III study of 1000 Genome to detect CNVs with various modes of inheritance. The performance of the developed method is evaluated by comparing CNV calling results with results from other orthogonal copy number platforms. Through our case studies, reuses of exome sequencing data for calling CNVs have several noticeable functionalities, including a better quality control for exome sequencing data, improved joint analysis with single nucleotide variant calls, and novel genomic discovery of under-utilized existing whole exome and custom exome panel data.

Keywords: bioinformatics, computational genetics, copy number variations, data reuse, exome sequencing, next generation sequencing

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589 Proposed Intervention to the Attention of Harassment at a Public University

Authors: R. Echeverría Echeverría, C. Carrillo Trujillo, N. Evia Alamilla

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Today, bullying is an expression of violence. It is a present problem in different contexts. Bullying and harassment have become subject matter of professional psychology , anthropology and other social sciences and related areas. However, most research on bullying have focused on peer violence and basic education. There is little attention to harassment in higher education. It also has little generation of research and interventions in universities, undergraduate and postgraduate level. The aim of this paper is to present a proposal for intervention to the attention of college students who have had an experience of harassment and / or bullying in a Public University of Merida, Yucatan, Mexico. The methodology was qualitative phenomenological. Semiestructura interview techniques and focus groups were used. 6 students participated who have lived harassment or bullying. Also they are participating teachers and university leaders who play an important role in the presence of such cases. The purpose is to analyze the presence of policies for the prevention, treatment and punishment of those problems. The qualitative data analysis will be based on the general proposal of Rodriguez Gomez Gil Flores and García Jiménez (1999). The results show the need to create a body entrusted to provide timely attention to cases of bullying or harassment that are reported. It is important to take legal and psychological support of the University authorities. It is proposed to create a mechanism to ensure timely care and not victimized who has had the experience; in addition to the punishment of those who exercised to ensure that violence. In discussing the successes and failures of the proposal are highlighted. And the processes that have been facilitated or hampered progress for the project.

Keywords: bullying, harassment, intervention, public university

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588 Determining the Efficacy of Phenol, Sodium Hypochlorite and Ethanol for Inactivation of Carbapenem-Resistant Strain of Acinetobacter baumannii

Authors: Deepika Biswas

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Acinetobacter baumannii, a hospital-acquired pathogen, causes nosocomial infections including pneumonia, urinary tract infection, and secondary meningitis. Carbapenem is most effective antibiotics against it. Its increased resistance to carbapenems has been a rising global concern. Antibiotics such as carbapenem are unable to use on hospital setups to eradicate A. baumannii, hence different concentrations of disinfectants including phenol; sodium hypochlorite and ethanol are increasingly being used. The objective of the present study is to find an effective concentration of above disinfectants against carbapenem-resistant strain RS307 of A. baumannii. Growth kinetics of RS307 has been determined using UV-Vis spectrophotometer in the presence and absence of disinfectants in triplicate and its standard deviation has also been calculated which make the results more reliable. Differential growth curves were plotted, which showed the effective concentration among all the concentrations of phenol, sodium hypochlorite and ethanol. On disc diffusion assay, antimicrobial effect was observed by comparing all the concentrations of disinfectants to check its synergy with imipenem, most effective carbapenem. All the results collectively revealed that 0.5% phenol, 0.5% sodium hypochlorite, and 70% ethanol could preferably be used as disinfectant for hospital setup against the carbapenem-resistant strain of A. baumannii. SDS PAGE analysis showed differential expression in the protein profile of A. baumannii after treatment. The present study highlighted that few disinfectants even in low concentration had shown better antimicrobial activity hence may be recommended for regular use in the hospitals, which will be cost effective and less harmful.

Keywords: Acenatobacter bomunii, phenol, sodium hypoclirite, ethanol, carbapenem resistance, disinfectant

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587 Sergei Prokofiev and Ukraine: The Influence of the Ukrainian Musical Tradition

Authors: Khrystyna Zai

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This research delves into the profound impact of Ukrainian musical traditions on the life and works of the renowned composer Sergei Prokofiev. Sergei Prokofiev's formative years in Ukraine, particularly in Sontsivka(Eastern Ukraine), allowed him to immerse himself in the local music. He encountered Ukrainian folk songs and dances, which left an indelible mark on his musical sensibilities. With a focus on the early 20th century, a period of significant cultural transformation in both Ukraine and Europe, this study examines how Prokofiev's exposure to Ukrainian folk music, its melodic motifs, and rhythmic patterns influenced his compositions. Prokofiev’s works showcase his deliberate efforts to fuse Ukrainian elements with his distinctive modernist style. This study analyzes Prokofiev's engagement with Ukrainian themes in his music, such as the "Semen Kotko”, “The Love of Three Oranges”, “On the Dnieper”, “Scythian Suite”, “Sinfonia Concertante" for cello and orchestra, "Sonata No. 9,", “Partisans in the steppes of Ukraine” (where Prokofiev uses texts in Ukrainian). The scientific work mentions his interactions and collaborations with Ukrainian musicians and cultural figures during Prokofiev’s career. Notably, his association with Ukrainian pianist Sviatoslav Richter and conductor Kirill Karabits led to interpretations of his compositions with a Ukrainian perspective. This research illuminates the nuances of cross-cultural influences in Prokofiev's oeuvre, contributing to a deeper understanding of the interplay between national identities and artistic expression during a pivotal period in history, based on the fact that the composer himself considered Ukraine to be his homeland, calling himself “steppe boy”.

Keywords: florida atlantic university, ukrainian music, ukrainian composer, sergei prokofiev

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586 Effect of Leptin Gene Methylation on Colorectal Cancer Chemoresistance

Authors: Wissem Abdaoui, Nizar M. Mhaidat, Ilhem Mokhtari, Adel Gouri

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Colorectal cancer (CRC) is one of the most common tumors all over the world. Obesity, considered a risk factor of CRC, is characterized by a high level of secreted cytokines from adipose tissue. Among these inflammatory molecules, leptin is considered the key mediator for CRC cancer development and progression by activation of mitogenic and anti apoptotic signaling pathways. Gene expression can be significantly modulated by alterations in DNA methylation patterns. The aim of this study is to investigate the impact of leptin gene methylation on CRC prognosis and sensitivity to chemotherapy. The study involved 70 CRC tissue samples collected from King Abdullah University Hospital (KAUH) from which only 53 was analyzed because of bisulfate fragmentation and low yield of DNA extracted from FFPE tissues. A total of 22 blood samples were collected from healthy volunteers and enrolled as a control group. Leptin promoter methylation was analyzed by methylation specific PCR after bisulfate conversion. Results revealed that the incidence of leptin gene methylation was significantly higher in CRC patients in comparison to that of controls (P < 0.05). The correlation between patient’s demographics and leptin gene methylation was not significant (P < 0.05). However, a significant correlation between leptin gene methylation status and early cancer stages (I, II and III) was found in male but not in female (p < 0.05). Moreover, a significant correlation was found between leptin promoter methylation and early tumor localization T1-2 (p < 0.05). The correlation between epigenetic regulation of leptin and chemosensitivity was not significant. Taken together, these results suggest the possibility to use leptin gene methylation as a biomarker for the evaluation of CRC prognosis and metastasis.

Keywords: colorectal cancer, obesity, leptin, DNA methylation, disease prognosis, bisulfate conversion, chemoresistance

Procedia PDF Downloads 348