Search results for: language signals
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4686

Search results for: language signals

876 Early Diagnosis of Myocardial Ischemia Based on Support Vector Machine and Gaussian Mixture Model by Using Features of ECG Recordings

Authors: Merve Begum Terzi, Orhan Arikan, Adnan Abaci, Mustafa Candemir

Abstract:

Acute myocardial infarction is a major cause of death in the world. Therefore, its fast and reliable diagnosis is a major clinical need. ECG is the most important diagnostic methodology which is used to make decisions about the management of the cardiovascular diseases. In patients with acute myocardial ischemia, temporary chest pains together with changes in ST segment and T wave of ECG occur shortly before the start of myocardial infarction. In this study, a technique which detects changes in ST/T sections of ECG is developed for the early diagnosis of acute myocardial ischemia. For this purpose, a database of real ECG recordings that contains a set of records from 75 patients presenting symptoms of chest pain who underwent elective percutaneous coronary intervention (PCI) is constituted. 12-lead ECG’s of the patients were recorded before and during the PCI procedure. Two ECG epochs, which are the pre-inflation ECG which is acquired before any catheter insertion and the occlusion ECG which is acquired during balloon inflation, are analyzed for each patient. By using pre-inflation and occlusion recordings, ECG features that are critical in the detection of acute myocardial ischemia are identified and the most discriminative features for the detection of acute myocardial ischemia are extracted. A classification technique based on support vector machine (SVM) approach operating with linear and radial basis function (RBF) kernels to detect ischemic events by using ST-T derived joint features from non-ischemic and ischemic states of the patients is developed. The dataset is randomly divided into training and testing sets and the training set is used to optimize SVM hyperparameters by using grid-search method and 10fold cross-validation. SVMs are designed specifically for each patient by tuning the kernel parameters in order to obtain the optimal classification performance results. As a result of implementing the developed classification technique to real ECG recordings, it is shown that the proposed technique provides highly reliable detections of the anomalies in ECG signals. Furthermore, to develop a detection technique that can be used in the absence of ECG recording obtained during healthy stage, the detection of acute myocardial ischemia based on ECG recordings of the patients obtained during ischemia is also investigated. For this purpose, a Gaussian mixture model (GMM) is used to represent the joint pdf of the most discriminating ECG features of myocardial ischemia. Then, a Neyman-Pearson type of approach is developed to provide detection of outliers that would correspond to acute myocardial ischemia. Neyman – Pearson decision strategy is used by computing the average log likelihood values of ECG segments and comparing them with a range of different threshold values. For different discrimination threshold values and number of ECG segments, probability of detection and probability of false alarm values are computed, and the corresponding ROC curves are obtained. The results indicate that increasing number of ECG segments provide higher performance for GMM based classification. Moreover, the comparison between the performances of SVM and GMM based classification showed that SVM provides higher classification performance results over ECG recordings of considerable number of patients.

Keywords: ECG classification, Gaussian mixture model, Neyman–Pearson approach, support vector machine

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875 Adapting Inclusive Residential Models to Match Universal Accessibility and Fire Protection

Authors: Patricia Huedo, Maria José Ruá, Raquel Agost-Felip

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Ensuring sustainable development of urban environments means guaranteeing adequate environmental conditions, being resilient and meeting conditions of safety and inclusion for all people, regardless of their condition. All existing buildings should meet basic safety conditions and be equipped with safe and accessible routes, along with visual, acoustic and tactile signals to protect their users or potential visitors, and regardless of whether they undergo rehabilitation or change of use processes. Moreover, from a social perspective, we consider the need to prioritize buildings occupied by the most vulnerable groups of people that currently do not have specific regulations tailored to their needs. Some residential models in operation are not only outside the scope of application of the regulations in force; they also lack a project or technical data that would allow knowing the fire behavior of the construction materials. However, the difficulty and cost involved in adapting the entire building stock to current regulations can never justify the lack of safety for people. Hence, this work develops a simplified model to assess compliance with the basic safety conditions in case of fire and its compatibility with the specific accessibility needs of each user. The purpose is to support the designer in decision making, as well as to contribute to the development of a basic fire safety certification tool to be applied in inclusive residential models. This work has developed a methodology to support designers in adapting Social Services Centers, usually intended to vulnerable people. It incorporates a checklist of 9 items and information from sources or standards that designers can use to justify compliance or propose solutions. For each item, the verification system is justified, and possible sources of consultation are provided, considering the possibility of lacking technical documentation of construction systems or building materials. The procedure is based on diagnosing the degree of compliance with fire conditions of residential models used by vulnerable groups, considering the special accessibility conditions required by each user group. Through visual inspection and site surveying, the verification model can serve as a support tool, significantly streamlining the diagnostic phase and reducing the number of tests to be requested by over 75%. This speeds up and simplifies the diagnostic phase. To illustrate the methodology, two different buildings in the Valencian Region (Spain) have been selected. One case study is a mental health facility for residential purposes, located in a rural area, on the outskirts of a small town; the other one, is a day care facility for individuals with intellectual disabilities, located in a medium-sized city. The comparison between the case studies allow to validate the model in distinct conditions. Verifying compliance with a basic security level can allow a quality seal and a public register of buildings adapted to fire regulations to be established, similarly to what is being done with other types of attributes such as energy performance.

Keywords: fire safety, inclusive housing, universal accessibility, vulnerable people

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874 Pedagogical Practices of a Teacher in Students' Experience Tellings: A Conversation Analytic Study

Authors: Derya Duran, Christine Jacknick

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This study explores post-task reflections in an English as a Medium of Instruction (EMI) setting, and it specifically focuses on how a teacher performs pedagogical practices such as reformulating, extending and evaluating following students’ spontaneous experience tellings in EMI classrooms. The data consist of 30 hours of video recordings from two EMI content classes, which were recorded for an academic term at a university in Turkey. The course, Guidance, is offered to fourth year undergraduate students as a compulsory course in the Department of Educational Sciences. The participants (n=78) study at the Faculty of Education, majoring in different educational departments (i.e., Computer Education and Instructional Technology, Elementary Education, Foreign Language Education). Using conversation analysis, we demonstrate that the teacher employs a variety of interactional resources to elicit (i.e., asking specific questions) and also provides (i.e., giving scientific information) as much content as possible, which also sheds light on the institutional fingerprints of the current research context. The study contributes to the existing research by unpacking articulation of personal experiences and cultivation of collaborativeness in classroom interaction. Moreover, describing the dialogic nature of these specific occasions, the study demonstrates how teacher and students address learning tasks together (collectivity), how they orient to each other turns interactionally (reciprocity), and how they keep the pedagogical focus in mind (purposefulness).

Keywords: conversation analysis, English as a medium of instruction, higher education, post-task reflections

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873 Pragmatic Competence of Jordanian EFL Learners

Authors: Dina Mahmoud Hammouri

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The study investigates the Jordanian EFL learners’ pragmatic competence through their production of the speech acts of responding to requests, making suggestions, making threats and expressing farewells. The sample of the study consists of 130 Jordanian EFL learners and native speakers. 2600 responses were collected through a Discourse Completion Test (DCT). The findings of the study revealed that the tested students showed similarities and differences in performing the strategies of four speech acts. Differences in the students’ performances led to pragmatic failure instances. The pragmatic failure committed by students refers to a lack of linguistic competence (i.e., pragmalinguistic failure), sociocultural differences and pragmatic transfer (i.e., sociopragmatic failure). EFL learners employed many mechanisms to maintain their communicative competence; the analysis of the test on speech acts showed learners’ tendency towards using particular strategies, resorting to modify strategies and relating them to their grammatical competence, prefabrication, performing long forms, buffing and transfer. The results were also suggestive of the learners’ lack of pragmalinguistic and sociopragmatic knowledge. The implications of this study are for language teachers to teach interlanguage pragmatics explicitly in EFL contexts to draw learners’ attention to both pragmalinguistic and sociopragmatic features, pay more attention to these areas and allocate more time and practice to solve learners’ problems in these areas. The implication of this study is also for pedagogical material designers to provide sufficient and well-organized pragmatic input.

Keywords: pragmatic failure, Jordanian EFL learner, sociopragmatic competence, pragmalinguistic competence

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872 Wetting Characterization of High Aspect Ratio Nanostructures by Gigahertz Acoustic Reflectometry

Authors: C. Virgilio, J. Carlier, P. Campistron, M. Toubal, P. Garnier, L. Broussous, V. Thomy, B. Nongaillard

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Wetting efficiency of microstructures or nanostructures patterned on Si wafers is a real challenge in integrated circuits manufacturing. In fact, bad or non-uniform wetting during wet processes limits chemical reactions and can lead to non-complete etching or cleaning inside the patterns and device defectivity. This issue is more and more important with the transistors size shrinkage and concerns mainly high aspect ratio structures. Deep Trench Isolation (DTI) structures enabling pixels’ isolation in imaging devices are subject to this phenomenon. While low-frequency acoustic reflectometry principle is a well-known method for Non Destructive Test applications, we have recently shown that it is also well suited for nanostructures wetting characterization in a higher frequency range. In this paper, we present a high-frequency acoustic reflectometry characterization of DTI wetting through a confrontation of both experimental and modeling results. The acoustic method proposed is based on the evaluation of the reflection of a longitudinal acoustic wave generated by a 100 µm diameter ZnO piezoelectric transducer sputtered on the silicon wafer backside using MEMS technologies. The transducers have been fabricated to work at 5 GHz corresponding to a wavelength of 1.7 µm in silicon. The DTI studied structures, manufactured on the wafer frontside, are crossing trenches of 200 nm wide and 4 µm deep (aspect ratio of 20) etched into a Si wafer frontside. In that case, the acoustic signal reflection occurs at the bottom and at the top of the DTI enabling its characterization by monitoring the electrical reflection coefficient of the transducer. A Finite Difference Time Domain (FDTD) model has been developed to predict the behavior of the emitted wave. The model shows that the separation of the reflected echoes (top and bottom of the DTI) from different acoustic modes is possible at 5 Ghz. A good correspondence between experimental and theoretical signals is observed. The model enables the identification of the different acoustic modes. The evaluation of DTI wetting is then performed by focusing on the first reflected echo obtained through the reflection at Si bottom interface, where wetting efficiency is crucial. The reflection coefficient is measured with different water / ethanol mixtures (tunable surface tension) deposited on the wafer frontside. Two cases are studied: with and without PFTS hydrophobic treatment. In the untreated surface case, acoustic reflection coefficient values with water show that liquid imbibition is partial. In the treated surface case, the acoustic reflection is total with water (no liquid in DTI). The impalement of the liquid occurs for a specific surface tension but it is still partial for pure ethanol. DTI bottom shape and local pattern collapse of the trenches can explain these incomplete wetting phenomena. This high-frequency acoustic method sensitivity coupled with a FDTD propagative model thus enables the local determination of the wetting state of a liquid on real structures. Partial wetting states for non-hydrophobic surfaces or low surface tension liquids are then detectable with this method.

Keywords: wetting, acoustic reflectometry, gigahertz, semiconductor

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871 The Effects of Applying Linguistic Principles and Teaching Techniques in Teaching English at Secondary School in Thailand

Authors: Wannakarn Likitrattanaporn

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The purposes of this investigation were to investigate the effects of applying linguistic principles and teaching techniques in teaching English through experimenting the Adapted English Lessons and to determine the teachers’ opinions as well as students’ opinions towards the Adapted Lessons. The subjects of the study were 5 Thai teachers, who teach English, and 85 Grade 10 mixed-ability students at Triamudom Suksa Pattanakarn Ratchada School, Bangkok, Thailand. The research instruments included the Adapted English Lessons, questionnaires asking teachers’ and students’ opinions towards the Adapted Lessons and the informal interview. The data from the research instruments was collected and analyzed concerning the teachers’ and students’ opinions towards adapting linguistic principles and teaching techniques. Linguistic principles of minimal pair and articulatory phonetics and teaching techniques of mimicry-memorization; vocabulary substitution drills, language pattern drills, reading comprehension exercise, practicing listening, speaking and writing skill and communicative activities; informal talk and free writing are applied. The data was statistically compiled according to an arithmetic percentage. The results showed that the teachers and students have very highly positive opinions towards adapting linguistic principles for teaching and learning phonological accuracy. Teaching techniques provided in the Adapted English Lessons can be used efficiently in the classroom. The teachers and students have positive opinions towards them too.

Keywords: applying linguistic principles and teaching techniques, teachers’ and students’ opinions, teaching English, the adapted English lessons

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870 The Analgesic Effect of Electroacupuncture in a Murine Fibromyalgia Model

Authors: Bernice Jeanne Lottering, Yi-Wen Lin

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Introduction: Chronic pain has a definitive lack of objective parameters in the measurement and treatment efficacy of diseases such as Fibromyalgia (FM). Persistent widespread pain and generalized tenderness are the characteristic symptoms affecting a large majority of the global population, particularly females. This disease has indicated a refractory tendency to conventional treatment ventures, largely resultant from a lack of etiological and pathogenic understanding of the disease development. Emerging evidence indicates that the central nervous system (CNS) plays a critical role in the amplification of pain signals and the neurotransmitters associated therewith. Various stimuli have been found to activate the channels existent on nociceptor terminals, thereby actuating nociceptive impulses along the pain pathways. The transient receptor potential vanalloid 1 (TRPV1) channel functions as a molecular integrator for numerous sensory inputs, such as nociception, and was explored in the current study. Current intervention approaches face a multitude challenges, ranging from effective therapeutic interventions to the limitation of pathognomonic criteria resultant from incomplete understanding and partial evidence on the mechanisms of action of FM. It remains unclear whether electroacupuncture (EA) plays an integral role in the functioning of the TRPV1 pathway, and whether or not it can reduce the chronic pain induced by FM. Aims: The aim of this study was to explore the mechanisms underlying the activation and modulation of the TRPV1 channel pathway in a cold stress model of FM applied to a murine model. Furthermore, the effect of EA in the treatment of mechanical and thermal pain, as expressed in FM was also to be investigated. Methods: 18 C57BL/6 wild type and 6 TRPV1 knockout (KO) mice, aged 8-12 weeks, were exposed to an intermittent cold stress-induced fibromyalgia-like pain model, with or without EA treatment at ZusanLi ST36 (2Hz/20min) on day 3 to 5. Von Frey and Hargreaves behaviour tests were implemented in order to analyze the mechanical and thermal pain thresholds on day 0, 3 and 5 in control group (C), FM group (FM), FM mice with EA treated group (FM + EA) and FM in KO group. Results: An increase in mechanical and thermal hyperalgesia was observed in the FM, EA and KO groups when compared to the control group. This initial increase was reduced in the EA group, which directs focus at the treatment efficacy of EA in nociceptive sensitization, and the analgesic effect EA has attenuating FM associated pain. Discussion: An increase in the nociceptive sensitization was observed through higher withdrawal thresholds in the von Frey mechanical test and the Hargreaves thermal test. TRPV1 function in mice has been scientifically associated with these nociceptive conduits, and the increased behaviour test results suggest that TRPV1 upregulation is central to the FM induced hyperalgesia. This data was supported by the decrease in sensitivity observed in results of the TRPV1 KO group. Moreover, the treatment of EA showed a decrease in this FM induced nociceptive sensitization, suggesting TRPV1 upregulation and overexpression can be attenuated by EA at bilateral ST36. This evidence compellingly implies that the analgesic effect of EA is associated with TRPV1 downregulation.

Keywords: fibromyalgia, electroacupuncture, TRPV1, nociception

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869 Prevalence Rate and Types of the Domestic Violence Against Deaf in Iran

Authors: Hadi Farahani, Mahsa Tahzibi, Laleh Golamrej Eliasi, Mohammad Torkashvand

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Iranian deafs are an under-researched population. The lack of research comes from the fact that if none, there are very few researchers capable of speaking sign language. The exclusion of this minority group from mainstream society often distorts the general understanding of prevalent issues of the deaf in Iran. The topic of this research was co-created through preliminary discussions with the Iranian deaf. Domestic violence then was picked up as an infrastructural issue impacting other dimensions of deaf lives such as work, education, and outside family relationships. For this purpose, we systematically searched the literature seeking a comprehensive questionnaire. We came across a 46-item standardized questionnaire measuring domestic violence in Iran. To adapt this questionnaire, we followed standard procedures reflected in another article. The inclusion criteria of the current research were married (had experienced living with a partner before) and +18-year-old deaf. Sampling was random and recruitment of the participants was through governmental or voluntary organizations for the deaf. 390 questionnaires then were analyzed through SPSS version 27. Analysis showed that the prevalence rate of domestic violence was 26% in general that emotional violence with 29% was the most prevalent type. Findings suggested that the more educated, and economically independent were the participants, the lower the probability of encountering domestic violence. Domestic violence within families where all members were deaf proved to be less usual than in families in which only the participant was deaf. Further interventional research is needed to assess how to empower the Iranian deaf regarding domestic violence.

Keywords: deaf, domestic violence, economic violence, emotional violence, physical violence, sexual violence

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868 Community Interpreting in the Process of Asylum Seeking in Brazil

Authors: Fernanda Garcia

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With the recent growth of refugees in the world, there has been an exponential increase in requests for asylum seeking in Brazil. When asylum seekers arrive in the country, the government initiates a process to evaluate the case, which will serve as grounds to determine the refugee status of the asylum seekers. During this process, an interview where the migrant has the chance to tell their story takes place. The aim of this article is to analyse how community interpreting is conducted in Brazil with regard to asylum seeking, as well as to analyse the role of the interpreter in the context of these official interviews to request refuge in Brazil. We investigate how the presence of an interpreter influences this interview, but more specifically, we study some of the linguistic techniques used by the interpreter in order to make the interaction more effective, as well as the challenges and difficulties they encounter during the interview. To do so, surveys with the interpreters took place, in addition to on-site observations. The interpreters involved in this research are volunteers as part of an extra-curricular extension programme from the University of Brasilia, in Brazil. Community Interpreting is a somewhat new field in Brazil, still facing several obstacles, such as the lack of professional community interpreters. This research illustrates some of these issues and, thus, has the potential to foster Brazilian literature in the matter as well as help understand the role of the interpreter in the interview to seek asylum in Brazil. The refugees’ situation in the world is certainly a pressing matter, and the language barrier is an issue of great importance. Hence, translation and interpretation studies have a fundamental role in this area, when it comes to contributing to a more inclusive world to those in need.

Keywords: asylum seeking, community interpreting, interviews, refugees

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867 Collocation Errors Made by Saudi Learners of English

Authors: Pakenam Shiha, Nadine Lacsina

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Systematic and in-depth analysis of ESL learners’ lexical errors, in general, and of collocation errors, in particular, are relatively rare. Analysis as such proves crucial in understanding how ESL learners construct and use these fixed expressions. Collocational competence of ESL learners is necessary for achieving a native-like proficiency level, which is one of the objectives of foundation programs. This study aims to examine the collocational competence of 50 Saudi foundation program students and identify the collocation errors that they often make. Furthermore, using a questionnaire, the challenges that students encounter in learning collocations and the ways in which their L1 affects their ability to recognize these expressions are identified. To identify the lexical errors and the collocational competence of the students a collocation test was administered. The 150-item lexical collocation test consists of verb-noun and adjective-noun structures. Results of the study reveal that there is a significant difference between the scores of students in the verb-noun and adjective-noun structures. The majority of errors were recorded in the adjective-noun structures due to the students’ L1 influence on the English collocations and the inability to distinguish between synonyms. Moreover, some challenges that students encountered were problems in translation, non-exposure to certain collocations, and degree of L1-L2 difference. All in all, the findings of this study can be interpreted in relation to the student's proficiency level and L2 instruction. Other findings of the study provide insights into language pedagogy—specifically strategies to help students learn collocations more effectively.

Keywords: collocations, ESL, applied linguistics, lexical collocations

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866 Women Retelling the Iranian Revolution: A Comparative Study of Novelists Maryam Madjidi and Negar Djavadi

Authors: Alessandro Giardino

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The Iranian Revolution has been the object of numberless historical and semi-fictional accounts, often providing a monolithic perspective on the events, due to the westerner positioning of those recounting them. Against this tradition, two contemporary French-Iranian novels "Disoriental" (2016) by Negar Djavadi and "Marx and The Doll" (2017) by Maryam Madjidi have offered readers a female-oriented and interestingly layered representation of the Iranian Revolution, hence addressing the responsibilities and misconceptions of Western countries. Furthermore, these two women writers have shed light on the disenchantment of the Iranian intellectual class vis-à-vis the foundation of the Islamic Republic, by particularly focusing on the deterioration of women’s rights, as well as the repression of political, ethnical, religious and sexual minorities. By a psycholinguistic and semasiological analysis of the two novels by Djavadi and Madjidi, this essay will focus on alternative accounts of the revolution in order to reflect upon the role of intersectional literature to the understanding of history. More specifically, as both women, refugees, and bi-cultural writers, Djavadi and Madjidi unearthed moments and figures of the revolution which had disappeared from the prevalent narrative. In doing so, however, these two writers resorted to entirely opposite styles of writing that, it will be argued, stem from different types of female resistance. In defining these two approaches as a "narrative resistance" and a "photographic resistance," the essay will elucidate the dependence of these writers’ language on generational and psychological factors, but it will also stir a reflection on their different communicative strategies.

Keywords: Iranian revolution, French-Iranian, intersectionality, literature, women writers

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865 Interpreting Chopin’s Music Today: Mythologization of Art: Kitsch

Authors: Ilona Bala

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The subject of this abstract is related to the notion of 'popular music', a notion that should be treated with extreme care, particularly when applied to Frederic Chopin, one of the greatest composers of Romanticism. By ‘popular music’, we mean a category of everyday music, set against the more intellectual kind, referred to as ‘classical’. We only need to look back to the culture of the nineteenth century to realize that this ‘popular music’ refers to the ‘music of the low’. It can be studied from a sociological viewpoint, or as sociological aesthetics. However, we cannot ignore the fact that, very quickly, this music spread to the wealthiest strata of the European society of the nineteenth century, while likewise the lowest classes often listen to the intellectual classical music, so pleasant to listen to. Further, we can observe that a sort of ‘sacralisation of kitsch’ occurs at the intersection between the classical and popular music. This process is the topic of this contribution. We will start by investigating the notion of kitsch through the study of Chopin’s popular compositions. However, before considering the popularisation of this music in today’s culture, we will have to focus on the use of the word kitsch in Chopin’s times, through his own musical aesthetics. Finally, the objective here will be to negate the theory that art is simply the intellectual definition of aesthetics. A kitsch can, obviously, only work on the emotivity of the masses, as it represents one of the features of culture-language (the words which the masses identify with). All art is transformed, becoming something outdated or even outmoded. Here, we are truly within a process of mythologization of art, through the study of the aesthetic reception of the musical work.

Keywords: F. Chopin, kitsch, musical work, mythologization of art, popular music, romantic music

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864 Effect of Early Therapeutic Intervention for the Children With Autism Spectrum Disorders: A Quasi Experimental Design

Authors: Sultana Razia

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The number of children whose social, communication and behavior pattern is affected due to mental and developmental conditions is on the rise. Most of these conditions develop to uncontrollable levels because of ignorance and unaware about their child’s condition. The many myths surrounding mental or developmental conditions are a major cause of families of affected children to develop bitterness and to shy off from seeking appropriate help in time. Several early intervention programs have been put in place, and the number of beneficiaries of these programs is increasing by the day. This research seeks to look into early intervention programs and their effectiveness. The purpose of this study was to investigate the effect of early therapeutic intervention for the children with autism spectrum disorder. Participants were 140 children with autism spectrum disorder from Autism Corner in a selected rehabilitation center of Bangladesh. This study included children who are at age of 18-month to 36-month and who were taking occupational therapy and speech and language therapy from the autism center. They were primarily screened using M-CHAT; however, children with other physical disability or medical conditions excluded. 3-months interventions of 6 sessions per week are a minimum of 45-minutes long per session, one to one interaction followed by parent-led structured home-based therapy were provided. The results indicated that early intensive therapeutic intervention improve understanding, social skills and sensory skills. It can be concluded that therapeutic early intervention a positive effect on diminishing symptoms of Autism Spectrum Disorder.

Keywords: M-CHAT, ASD, sensory cheeklist, OT

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863 Educating the Education Student: Technology as the Link between Theory and Praxis

Authors: Rochelle Botha-Marais

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When lecturing future educators in South Africa, praxis is an indispensable aspect that is often neglected. Without properly understanding how the theory taught in lecture halls relates to their future position as educators, we can not expect these students to be fully equipped future teachers. To enable education students at the Vaal Campus of the North West University - who have the Afrikaans language as major - to discover the link between theory and practice, the author created an assignment on phonetics in which the use of technology was incorporated. In the past, students had to submit an assignment or worksheet and they did not get the opportunity to apply their newly found knowledge in a practical manner. For potential future teachers, this application is essential. This paper will demonstrate how technology is used in the second year Afrikaans education module to promote student engagement and self-directed learning. Students were introduced to innovative new technologies alongside more familiar applications to shape a 21st century learning environment where students can think, communicate, solve problems, collaborate and take responsibility for their own teaching and learning. The paper will also reflect on student feedback pertaining the use and efficiency of technology in the Afrikaans module and the possible impact thereof on their own teaching and learning landscape. The aim of this paper is to showcase how technology can be used to maximize the students learning experience and equip future education students with the tools and knowledge to introduce technology-enhanced learning in their own teaching practice.

Keywords: education students, theory and practice, self-directed learning, student engagement, technology

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862 Relation of Cad/Cam Zirconia Dental Implant Abutments with Periodontal Health and Final Aesthetic Aspects; A Systematic Review

Authors: Amin Davoudi

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Aim: New approaches have been introduced to improve soft tissue indices of the dental implants. This systematic review aimed to investigate the effect of computer-aided design and computer-assisted manufacture (CAD/CAM) zirconia (Zr) implant abutments on periodontal aspects. Materials and Methods: Five electronic databases were searched thoroughly based on prior defined MeSH and non-MeSH keywords. Clinical studies were collected via hand searches in English language journals up to September 2020. Interproximal papilla stability, papilla recession, pink and white esthetic score (PES, WES), bone and gingival margin levels, color, and contour of soft tissue were reviewed. Results: The initial literature search yielded 412 articles. After the evaluation of abstracts and full texts, six studies were eligible to be screened. The study design of the included studies was a prospective cohort (n=3) and randomized clinical trial (n=3). The outcome was found to be significantly better for Zr than titanium abutments, however, the studies did not show significant differences between stock and CAD/CAM abutments. Conclusion: Papilla fill, WES, PES, and the distance from the contact point to dental crest bone of adjacent tooth and inter-tooth–implant distance were not significantly different between Zr CAD/CAM and Zr stock abutments. However, soft tissue stability and recession index were better in Zr CAD/CAM abutments.

Keywords: zirconia, CADCAM, periodental, implant

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861 Efficacy of Sparganium stoloniferum–Derived Compound in the Treatment of Acne Vulgaris: A Pilot Study

Authors: Wanvipa Thongborisute, Punyaphat Sirithanabadeekul, Pichit Suvanprakorn, Anan Jiraviroon

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Background: Acne vulgaris is one of the most common dermatologic problems, and can have a significant psychological and physical effect on patients. Propionibacterium acnes' roles in acne vulgaris involve the activation of toll-like receptor 4 (TLR4), and toll-like receptor 2 (TLR2) pathways. By activating these pathways, inflammatory events of acne lesions, comedogenesis and sebaceous lipogenesis can occur. Currently, there are several topical agents commonly use in treating acne vulgaris that are known to have an effect on TLRs, such as retinoic acid and adapalene, but these drugs still have some irritating effects. At present, there is an alarming increase in rate of bacterial resistance due to irrational used of antibiotics both orally and topically. For this reason, acne treatments should contain bioactive molecules targeting at the site of action for the most effective therapeutic effect with the least side effects. Sparganium stoloniferumis a Chinese aquatic herb containing a compound called Sparstolonin B (SsnB), which has been reported to selectively blocks Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4)-mediated inflammatory signals. Therefore, this topical TLR2 and TLR4 antagonist, in a form of Sparganium stoloniferum-derived compound containing SsnB, should give a benefit in reducing inflammation of acne vulgaris lesions and providing an alternative treatments for patients with this condition. Materials and Methods: The objectives of this randomized double blinded split faced placebo controlled trial is to study the safety and efficacy of the Sparganium stoloniferum-derived compound. 32 volunteered patients with mild to moderate degree of acne vulgaris according to global acne grading system were included in the study. After being informed and consented the subjects were given 2 topical treatments for acne vulgaris, one being topical 2.40% Sparganium stoloniferum extraction (containing Sparstolonin B) and the other, placebo. The subjects were asked to apply each treatment to either half of the face daily morning and night by randomization for 8 weeks, and come in for a weekly follow up. For each visit, the patients went through a procedure of lesion counting, including comedones, papules, nodules, pustules, and cystic lesions. Results: During 8 weeks of experimentation, the result shows a reduction in total lesions number between the placebo and the treatment side show statistical significance starting at week 4, where the 95% confidence interval begin to no longer overlap, and shows a trend of continuing to be further apart. The decrease in the amount of total lesions between week 0 and week 8 of the placebo side shows no statistical significant at P value >0.05. While the decrease in the amount of total lesions of acne vulgaris of the treatment side comparing between week 0 and week 8 shows statistical significant at P value <0.001. Conclusion: The data demonstrates that 2.40% Sparganium stoloniferum extraction (containing Sparstolonin B) is more effective in treating acne vulgaris comparing to topical placebo in treating acne vulgaris, by showing significant reduction in the total numbers of acne lesions. Therefore, this topical Sparganium stoloniferum extraction could become a potential alternative treatment for acne vulgaris.

Keywords: acne vulgaris, sparganium stoloniferum, sparstolonin B, toll-like receptor 2, toll-like receptor 4

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860 Flashsonar or Echolocation Education: Expanding the Function of Hearing and Changing the Meaning of Blindness

Authors: Thomas, Daniel Tajo, Kish

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Sight is primarily associated with the function of gathering and processing near and extended spatial information which is largely used to support self-determined interaction with the environment through self-directed movement and navigation. By contrast, hearing is primarily associated with the function of gathering and processing sequential information which may typically be used to support self-determined communication through the self-directed use of music and language. Blindness or the lack of vision is traditionally characterized by a lack of capacity to access spatial information which, in turn, is presumed to result in a lack of capacity for self-determined interaction with the environment due to limitations in self-directed movement and navigation. However, through a specific protocol of FlashSonar education developed by World Access for the Blind, the function of hearing can be expanded in blind people to carry out some of the functions normally associated with sight, that is to access and process near and extended spatial information to construct three-dimensional acoustic images of the environment. This perceptual education protocol results in a significant restoration in blind people of self-determined environmental interaction, movement, and navigational capacities normally attributed to vision - a new way to see. Thus, by expanding the function of hearing to process spatial information to restore self-determined movement, we are not only changing the meaning of blindness, and what it means to be blind, but we are also recasting the meaning of vision and what it is to see.

Keywords: echolocation, changing, sensory, function

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859 Wolof Voice Response Recognition System: A Deep Learning Model for Wolof Audio Classification

Authors: Krishna Mohan Bathula, Fatou Bintou Loucoubar, FNU Kaleemunnisa, Christelle Scharff, Mark Anthony De Castro

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Voice recognition algorithms such as automatic speech recognition and text-to-speech systems with African languages can play an important role in bridging the digital divide of Artificial Intelligence in Africa, contributing to the establishment of a fully inclusive information society. This paper proposes a Deep Learning model that can classify the user responses as inputs for an interactive voice response system. A dataset with Wolof language words ‘yes’ and ‘no’ is collected as audio recordings. A two stage Data Augmentation approach is adopted for enhancing the dataset size required by the deep neural network. Data preprocessing and feature engineering with Mel-Frequency Cepstral Coefficients are implemented. Convolutional Neural Networks (CNNs) have proven to be very powerful in image classification and are promising for audio processing when sounds are transformed into spectra. For performing voice response classification, the recordings are transformed into sound frequency feature spectra and then applied image classification methodology using a deep CNN model. The inference model of this trained and reusable Wolof voice response recognition system can be integrated with many applications associated with both web and mobile platforms.

Keywords: automatic speech recognition, interactive voice response, voice response recognition, wolof word classification

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858 A Novel PWM/PFM Controller for PSR Fly-Back Converter Using a New Peak Sensing Technique

Authors: Sanguk Nam, Van Ha Nguyen, Hanjung Song

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For low-power applications such as adapters for portable devices and USB chargers, the primary side regulation (PSR) fly-back converter is widely used in lieu of the conventional fly-back converter using opto-coupler because of its simpler structure and lower cost. In the literature, there has been studies focusing on the design of PSR circuit; however, the conventional sensing method in PSR circuit using RC delay has a lower accuracy as compared to the conventional fly-back converter using opto-coupler. In this paper, we propose a novel PWM/PFM controller using new sensing technique for the PSR fly-back converter which can control an accurate output voltage. The conventional PSR circuit can sense the output voltage information from the auxiliary winding to regulate the duty cycle of the clock that control the output voltage. In the sensing signal waveform, there has two transient points at time the voltage equals to Vout+VD and Vout, respectively. In other to sense the output voltage, the PSR circuit must detect the time at which the current of the diode at the output equals to zero. In the conventional PSR flyback-converter, the sensing signal at this time has a non-sharp-negative slope that might cause a difficulty in detecting the output voltage information since a delay of sensing signal or switching clock may exist which brings out an unstable operation of PSR fly-back converter. In this paper instead of detecting output voltage at a non-sharp-negative slope, a sharp-positive slope is used to sense the proper information of the output voltage. The proposed PRS circuit consists of a saw-tooth generator, a summing circuit, a sample and hold circuit and a peak detector. Besides, there is also the start-up circuit which protects the chip from high surge current when the converter is turned on. Additionally, to reduce the standby power loss, a second mode which operates in a low frequency is designed beside the main mode at high frequency. In general, the operation of the proposed PSR circuit can be summarized as following: At the time the output information is sensed from the auxiliary winding, a saw-tooth signal from the saw-tooth generator is generated. Then, both of these signals are summed using a summing circuit. After this process, the slope of the peak of the sensing signal at the time diode current is zero becomes positive and sharp that make the peak easy to detect. The output of the summing circuit then is fed into a peak detector and the sample and hold circuit; hence, the output voltage can be properly sensed. By this way, we can sense more accurate output voltage information and extend margin even circuit is delayed or even there is the existence of noise by using only a simple circuit structure as compared with conventional circuits while the performance can be sufficiently enhanced. Circuit verification was carried out using 0.35μm 700V Magnachip process. The simulation result of sensing signal shows a maximum error of 5mV under various load and line conditions which means the operation of the converter is stable. As compared to the conventional circuit, we achieved very small error only used analog circuits compare with conventional circuits. In this paper, a PWM/PFM controller using a simple and effective sensing method for PSR fly-back converter has been presented in this paper. The circuit structure is simple as compared with the conventional designs. The gained results from simulation confirmed the idea of the design

Keywords: primary side regulation, PSR, sensing technique, peak detector, PWM/PFM control, fly-back converter

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857 Commuters Trip Purpose Decision Tree Based Model of Makurdi Metropolis, Nigeria and Strategic Digital City Project

Authors: Emmanuel Okechukwu Nwafor, Folake Olubunmi Akintayo, Denis Alcides Rezende

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Decision tree models are versatile and interpretable machine learning algorithms widely used for both classification and regression tasks, which can be related to cities, whether physical or digital. The aim of this research is to assess how well decision tree algorithms can predict trip purposes in Makurdi, Nigeria, while also exploring their connection to the strategic digital city initiative. The research methodology involves formalizing household demographic and trips information datasets obtained from extensive survey process. Modelling and Prediction were achieved using Python Programming Language and the evaluation metrics like R-squared and mean absolute error were used to assess the decision tree algorithm's performance. The results indicate that the model performed well, with accuracies of 84% and 68%, and low MAE values of 0.188 and 0.314, on training and validation data, respectively. This suggests the model can be relied upon for future prediction. The conclusion reiterates that This model will assist decision-makers, including urban planners, transportation engineers, government officials, and commuters, in making informed decisions on transportation planning and management within the framework of a strategic digital city. Its application will enhance the efficiency, sustainability, and overall quality of transportation services in Makurdi, Nigeria.

Keywords: decision tree algorithm, trip purpose, intelligent transport, strategic digital city, travel pattern, sustainable transport

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856 Challenges in Early Diagnosis of Enlarged Vestibular Aqueduct (EVA) in Pediatric Population: A Single Case Report

Authors: Asha Manoharan, Sooraj A. O, Anju K. G

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Enlarged vestibular aqueduct (EVA) refers to the presence of congenital sensorineural hearing loss with an enlarged vestibular aqueduct. The Audiological symptoms of EVA are fluctuating and progressive in nature and the diagnosis of EVAS can be confirmed only with radiological evaluation. Hence it is difficult to differentiate EVA from conditions like Meniere’s disease, semi-circular dehiscence, etc based on audiological findings alone. EVA in adults is easy to identify due to distinct vestibular symptoms. In children, EVA can remain either unidentified or misdiagnosed until the vestibular symptoms are evident. Motor developmental delay, especially the ones involving a change of body alignment, has been reported in the pediatric population with EVA. So, it should be made mandatory to recommend radiological evaluation in young children with fluctuating hearing loss reporting with motor developmental delay. This single case study of a baby with Enlarged Vestibular Aqueduct (EVA) primarily aimed to address the following: a) Challenges while diagnosing young patients with EVA and fluctuating hearing loss, b) Importance of radiological evaluation in audiological diagnosis in the pediatric population, c) Need for regular monitoring of hearing, hearing aid performance, and cochlear implant mapping closely for potential fluctuations in such populations, d) Importance of reviewing developmental, language milestones in very young children with fluctuating hearing loss.

Keywords: enlarged vestibular aqueduct (EVA), motor delay, radiological evaluation, fluctuating hearing loss, cochlear implant

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855 Preservice EFL Teachers in a Blended Professional Development Program: Learning to Teach Speech Acts

Authors: Mei-Hui Liu

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This study examines the effectiveness of a blended professional development program on preservice EFL (English as a foreign language) teachers’ learning to teach speech acts with the advent of Information and Communication Technology, researchers and scholars underscore the significance of integrating online and face-to-face learning opportunities in the teacher education field. Yet, a paucity of evidence has been documented to investigate the extent to which such a blended professional learning model may impact real classroom practice and student learning outcome. This yearlong project involves various stakeholders, including 25 preservice teachers, 5 English professionals, and 45 secondary school students. Multiple data sources collected are surveys, interviews, reflection journals, online discussion messages, artifacts, and discourse completion tests. Relying on the theoretical lenses of Community of Inquiry, data analysis depicts the nature and process of preservice teachers’ professional development in this blended learning community, which triggers and fosters both face-to-face and synchronous/asynchronous online interactions among preservice teachers and English professionals (i.e., university faculty and in-service teachers). Also included is the student learning outcome after preservice teachers put what they learn from the support community into instructional practice. Pedagogical implications and research suggestions are further provided based on the research findings and limitations.

Keywords: blended professional development, preservice EFL teachers, speech act instruction, student learning outcome

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854 PaSA: A Dataset for Patent Sentiment Analysis to Highlight Patent Paragraphs

Authors: Renukswamy Chikkamath, Vishvapalsinhji Ramsinh Parmar, Christoph Hewel, Markus Endres

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Given a patent document, identifying distinct semantic annotations is an interesting research aspect. Text annotation helps the patent practitioners such as examiners and patent attorneys to quickly identify the key arguments of any invention, successively providing a timely marking of a patent text. In the process of manual patent analysis, to attain better readability, recognising the semantic information by marking paragraphs is in practice. This semantic annotation process is laborious and time-consuming. To alleviate such a problem, we proposed a dataset to train machine learning algorithms to automate the highlighting process. The contributions of this work are: i) we developed a multi-class dataset of size 150k samples by traversing USPTO patents over a decade, ii) articulated statistics and distributions of data using imperative exploratory data analysis, iii) baseline Machine Learning models are developed to utilize the dataset to address patent paragraph highlighting task, and iv) future path to extend this work using Deep Learning and domain-specific pre-trained language models to develop a tool to highlight is provided. This work assists patent practitioners in highlighting semantic information automatically and aids in creating a sustainable and efficient patent analysis using the aptitude of machine learning.

Keywords: machine learning, patents, patent sentiment analysis, patent information retrieval

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853 Cultural-Creative Design with Language Figures of Speech

Authors: Wei Chen Chang, Ming Yu Hsiao

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The commodity takes one kind of mark, the designer how to construction and interpretation the user how to use the process and effectively convey message in design education has always been an important issue. Cultural-creative design refers to signifying cultural heritage for product design. In terms of Peirce’s Semiotic Triangle: signifying elements-object-interpretant, signifying elements are the outcomes of design, the object is cultural heritage, and the interpretant is the positioning and description of product design. How to elaborate the positioning, design, and development of a product is a narrative issue of the interpretant, and how to shape the signifying elements of a product by modifying and adapting styles is a rhetoric matter. This study investigated the rhetoric of elements signifying products to develop a rhetoric model with cultural style. Figures of speech are a rhetoric method in narrative. By adapting figures of speech to the interpretant, this study developed the rhetoric context of cultural context by narrative means. In this two-phase study, phase I defines figures of speech and phase II analyzes existing cultural-creative products in terms of figures of speech to develop a rhetoric of style model. We expect it can reference for the future development of Cultural-creative design.

Keywords: cultural-creative design, cultural-creative products, figures of speech, Peirce’s semiotic triangle, rhetoric of style model

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852 Perceiving Casual Speech: A Gating Experiment with French Listeners of L2 English

Authors: Naouel Zoghlami

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Spoken-word recognition involves the simultaneous activation of potential word candidates which compete with each other for final correct recognition. In continuous speech, the activation-competition process gets more complicated due to speech reductions existing at word boundaries. Lexical processing is more difficult in L2 than in L1 because L2 listeners often lack phonetic, lexico-semantic, syntactic, and prosodic knowledge in the target language. In this study, we investigate the on-line lexical segmentation hypotheses that French listeners of L2 English form and then revise as subsequent perceptual evidence is revealed. Our purpose is to shed further light on the processes of L2 spoken-word recognition in context and better understand L2 listening difficulties through a comparison of skilled and unskilled reactions at the point where their working hypothesis is rejected. We use a variant of the gating experiment in which subjects transcribe an English sentence presented in increments of progressively greater duration. The spoken sentence was “And this amazing athlete has just broken another world record”, chosen mainly because it included common reductions and phonetic features in English, such as elision and assimilation. Our preliminary results show that there is an important difference in the manner in which proficient and less-proficient L2 listeners handle connected speech. Less-proficient listeners delay recognition of words as they wait for lexical and syntactic evidence to appear in the gates. Further statistical results are currently being undertaken.

Keywords: gating paradigm, spoken word recognition, online lexical segmentation, L2 listening

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851 Expression of Stance in Lower- and Upper- Level Students’ Writing in Business Administration at English-Medium University in Burundi

Authors: Clement Ndoricimpa

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The expression of stance is highly expected in writing at tertiary level. Through a selection of linguistic and rhetorical elements, writers express commitment, critical distance and build a critically discerning reader in texts. Despite many studies on patterns of stance in students’ academic writing, little may not be known about how English as a Foreign Language students learns to build a critically discerning reader in their texts. Therefore, this study examines patterns of stance in essays written by students majoring in business administration at English-medium University in Burundi as part of classroom assignments. It draws on systemic functional linguistics to analyze qualitatively and quantitatively the data. The quantitative analysis is used to identify the differences in frequency of stance patterns in the essays. The results show a significant difference in the use of boosters by lower- and upper-level students. Lower-level students’ writing contains more boosters and many idiosyncratic sentence structures than do upper-level students’ writing, and upper-level students’ essays contain more hedging and few grammatical mistakes than do lower-level students’ essays. No significant difference in the use of attitude markers and concessive and contrastive expressions. Students in lower- and upper-level do not use attitude markers and disclaimer markers appropriately and accurately. These findings suggest that students should be taught the use of stance patterns in academic writing.

Keywords: academic writing, metadiscourse, stance, student corpora

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850 Improving Technical Translation Ability of the Iranian Students of Translation Through Multimedia: An Empirical Study

Authors: Dina Zakeri, Ali Aminzad

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Multimedia-assisted teaching results in eliminating traditional training barriers, facilitating the cognition process and upgrading learning outcomes. This study attempted to examine the effects of implementing multimedia on teaching technical translation model and on the technical text translation ability of Iranian students of translation. To fulfill the purpose of the study, a total of forty-six learners were selected out of fifty-seven participants in a higher education center in Tehran based on their scores in Preliminary English Test (PET) and were divided randomly into the experimental and control groups. Prior to the treatment, a technical text translation questionnaire was devised and then approved and validated by three assistant professors of technical fields and three assistant professors of Teaching English as a Foreign Language (TEFL) at the university. This questionnaire was administered as a pretest to both groups. Control and experimental groups were trained for five successive weeks using identical course books but with a different lesson plan that allowed employing multimedia for the experimental group only. The devised and approved questionnaire was administered as a posttest to both groups at the end of the instruction. A multivariate ANOVA was run to compare the two groups’ means on the PET, pretest and posttest. The results showed the rejection of all null hypotheses of the study and revealed that multimedia significantly improved technical text translation ability of the learners.

Keywords: multimedia, multimedia-mediated teaching, technical translation model, technical text, translation ability

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849 The Discursive Construction of Emotions in the Headlines of French Newspapers on Seismic Disasters

Authors: Mirela-Gabriela Bratu

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The main objective of this study is to highlight the way in which emotions are constructed discursively in the French written press, more particularly in the titles of informative articles. To achieve this objective, we will begin the study with the theoretical part, which aims to capture the characteristics of journalistic discourse, to which we will add clues of emotions that we will identify in the titles of the articles. The approach is based on the empirical results from the analysis of the articles published on the earthquake that took place on August 24, 2016, in Italy, as described by two French national daily newspapers: Le Monde and Le Point. The corpus submitted to the analysis contains thirty-seven titles, published between August 24, 2016, and August 24, 2017. If the textual content of the speech offers information respecting the grammatical standards and following the presentation conventions, the choice of words can touch the reader, so the journalist must add other means than mastering of the language to create emotion. This study aims to highlight the strategies, such as rhetorical figures, the tenses, or factual data, used by journalists to create emotions for the readers. We also try, thanks to the study of the articles which were published for several days relating to the same event, to emphasize whether we can speak or not of the dissipation of emotion and the catastrophic side as the event fades away in time. The theoretical framework is offered by works on rhetorical strategies (Perelman, 1992; Amossi, 2000; Charaudeau, 2000) and on the study of emotions (Plantin, 1997, 1998, 2004; Tetu, 2004).

Keywords: disaster, earthquake, emotion, feeling

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848 Ectopic Osteoinduction of Porous Composite Scaffolds Reinforced with Graphene Oxide and Hydroxyapatite Gradient Density

Authors: G. M. Vlasceanu, H. Iovu, E. Vasile, M. Ionita

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Herein, the synthesis and characterization of chitosan-gelatin highly porous scaffold reinforced with graphene oxide, and hydroxyapatite (HAp), crosslinked with genipin was targeted. In tissue engineering, chitosan and gelatin are two of the most robust biopolymers with wide applicability due to intrinsic biocompatibility, biodegradability, low antigenicity properties, affordability, and ease of processing. HAp, per its exceptional activity in tuning cell-matrix interactions, is acknowledged for its capability of sustaining cellular proliferation by promoting bone-like native micro-media for cell adjustment. Genipin is regarded as a top class cross-linker, while graphene oxide (GO) is viewed as one of the most performant and versatile fillers. The composites with natural bone HAp/biopolymer ratio were obtained by cascading sonochemical treatments, followed by uncomplicated casting methods and by freeze-drying. Their structure was characterized by Fourier Transform Infrared Spectroscopy and X-ray Diffraction, while overall morphology was investigated by Scanning Electron Microscopy (SEM) and micro-Computer Tomography (µ-CT). Ensuing that, in vitro enzyme degradation was performed to detect the most promising compositions for the development of in vivo assays. Suitable GO dispersion was ascertained within the biopolymer mix as nanolayers specific signals lack in both FTIR and XRD spectra, and the specific spectral features of the polymers persisted with GO load enhancement. Overall, correlations between the GO induced material structuration, crystallinity variations, and chemical interaction of the compounds can be correlated with the physical features and bioactivity of each composite formulation. Moreover, the HAp distribution within follows an auspicious density gradient tuned for hybrid osseous/cartilage matter architectures, which were mirrored in the mice model tests. Hence, the synthesis route of a natural polymer blend/hydroxyapatite-graphene oxide composite material is anticipated to emerge as influential formulation in bone tissue engineering. Acknowledgement: This work was supported by the project 'Work-based learning systems using entrepreneurship grants for doctoral and post-doctoral students' (Sisteme de invatare bazate pe munca prin burse antreprenor pentru doctoranzi si postdoctoranzi) - SIMBA, SMIS code 124705 and by a grant of the National Authority for Scientific Research and Innovation, Operational Program Competitiveness Axis 1 - Section E, Program co-financed from European Regional Development Fund 'Investments for your future' under the project number 154/25.11.2016, P_37_221/2015. The nano-CT experiments were possible due to European Regional Development Fund through Competitiveness Operational Program 2014-2020, Priority axis 1, ID P_36_611, MySMIS code 107066, INOVABIOMED.

Keywords: biopolymer blend, ectopic osteoinduction, graphene oxide composite, hydroxyapatite

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847 Single Pass Design of Genetic Circuits Using Absolute Binding Free Energy Measurements and Dimensionless Analysis

Authors: Iman Farasat, Howard M. Salis

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Engineered genetic circuits reprogram cellular behavior to act as living computers with applications in detecting cancer, creating self-controlling artificial tissues, and dynamically regulating metabolic pathways. Phenemenological models are often used to simulate and design genetic circuit behavior towards a desired behavior. While such models assume that each circuit component’s function is modular and independent, even small changes in a circuit (e.g. a new promoter, a change in transcription factor expression level, or even a new media) can have significant effects on the circuit’s function. Here, we use statistical thermodynamics to account for the several factors that control transcriptional regulation in bacteria, and experimentally demonstrate the model’s accuracy across 825 measurements in several genetic contexts and hosts. We then employ our first principles model to design, experimentally construct, and characterize a family of signal amplifying genetic circuits (genetic OpAmps) that expand the dynamic range of cell sensors. To develop these models, we needed a new approach to measuring the in vivo binding free energies of transcription factors (TFs), a key ingredient of statistical thermodynamic models of gene regulation. We developed a new high-throughput assay to measure RNA polymerase and TF binding free energies, requiring the construction and characterization of only a few constructs and data analysis (Figure 1A). We experimentally verified the assay on 6 TetR-homolog repressors and a CRISPR/dCas9 guide RNA. We found that our binding free energy measurements quantitatively explains why changing TF expression levels alters circuit function. Altogether, by combining these measurements with our biophysical model of translation (the RBS Calculator) as well as other measurements (Figure 1B), our model can account for changes in TF binding sites, TF expression levels, circuit copy number, host genome size, and host growth rate (Figure 1C). Model predictions correctly accounted for how these 8 factors control a promoter’s transcription rate (Figure 1D). Using the model, we developed a design framework for engineering multi-promoter genetic circuits that greatly reduces the number of degrees of freedom (8 factors per promoter) to a single dimensionless unit. We propose the Ptashne (Pt) number to encapsulate the 8 co-dependent factors that control transcriptional regulation into a single number. Therefore, a single number controls a promoter’s output rather than these 8 co-dependent factors, and designing a genetic circuit with N promoters requires specification of only N Pt numbers. We demonstrate how to design genetic circuits in Pt number space by constructing and characterizing 15 2-repressor OpAmp circuits that act as signal amplifiers when within an optimal Pt region. We experimentally show that OpAmp circuits using different TFs and TF expression levels will only amplify the dynamic range of input signals when their corresponding Pt numbers are within the optimal region. Thus, the use of the Pt number greatly simplifies the genetic circuit design, particularly important as circuits employ more TFs to perform increasingly complex functions.

Keywords: transcription factor, synthetic biology, genetic circuit, biophysical model, binding energy measurement

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