Search results for: mRNA expression

Authors: Ryan D. Martinus

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Inflammation of the endothelium is an important process leading to diabetic atherosclerosis. However, the molecular mechanisms by which diabetes contributes to endothelial inflammation remain to be established. Using In-vitro cultured Human cells and Hsp60 specific ELISA assays, we show that Hsp60 is not only induced in Human monocyte cells under hyperglycaemic conditions but that the Hsp60 is also secreted from these cells. Furthermore, we also demonstrate that the Hsp60 secreted from these monocyte cells is also able to activate Toll-like receptor-4 (TLR4) from Human endothelial cells. This suggests that a potential link may exist between the hyperglycaemia-induced expression of Hsp60 in monocyte cells and vascular inflammation. Circulating levels of Hsp60 due to mitochondrial stress in diabetes patients could, therefore, be an important modulator of inflammation in endothelial cells and thus contribute to the increased incidences of atherosclerosis in diabetes mellitus.

Keywords: mitochondria, Hsp60, inflammation, diabetes mellitus

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Authors: Lugyi No

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This research delves into how students from two different backgrounds in a conflict-affected area, one group being internally displaced (IDP) and the other residing in permanent homes, express their emotions through art. Two experiments were conducted involving guided drawing to understand their emotional experiences. In the first experiment, where no specific instructions were given, both groups mostly used dark and dull colors, which suggests feelings of sadness and anxiety. Positive emotions were rarely depicted. In the second experiment, students were asked to express their emotions and provide reasons for their drawings. Here, we observed distinct variations: IDP students leaned towards vibrant colors, reflecting resilience, while town students tended to use monochromatic shades, likely due to their experiences with conflict. This abstract highlights the differing emotional expressions of these groups and the influence of instructions on their artwork.

Keywords: art therapy, conflict-affected areas, education in conflict zones, children's drawings

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Authors: Tianqi Yu, Yingnan Ding, Yina Zhang, Yulan Liu, Yahui Li, Jing Lei, Jiyong Zhou, Suquan Song, Boli Hu

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Circular RNAs (circRNAs) play critical roles in various diseases. However, whether and how circular RNA regulates influenza A virus (IAV) infection is unknown. Here, we studied the role of circular RNA GATA Zinc Finger Domain Containing 2A (circ-GATAD2A) in the replication of IAV H1N1 in A549 cells. Circ-GATAD2A was formed upon H1N1 infection. Knockdown of circ-GATAD2A in A549 cells enhanced autophagy and inhibited H1N1 replication. By contrast, overexpression of circ-GATAD2A impaired autophagy and promoted H1N1 replication. Similarly, knockout of vacuolar protein sorting 34 (VPS34) blocked autophagy and increased H1N1 replication. However, the expression of circ-GATAD2A could not further enhance H1N1 replication in VPS34 knockout cells. Collectively, these data indicated that circ-GATAD2A promotes the replication of H1N1 by inhibiting autophagy.

Keywords: autophagy, circ-GATAD2A, H1N1, replication

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Authors: D. R. Ambika, K. R. Radhika, D. Seshachalam

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Unconstrained authentication is an important component for personal automated systems and human-computer interfaces. Existing solutions mostly use face as the primary object of analysis. The performance of face-based systems is largely determined by the extent of deformation caused in the facial region and amount of useful information available in occluded face images. Periocular region is a useful portion of face with discriminative ability coupled with resistance to deformation. A reliable portion of periocular area is available for occluded images. The present work demonstrates that joint representation of periocular texture and periocular structure provides an effective expression and poses invariant representation. The proposed methodology provides an effective and compact description of periocular texture and shape. The method is tested over four benchmark datasets exhibiting varied acquisition conditions.

Keywords: periocular authentication, Zernike moments, LBP variance, shape and texture fusion

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Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

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This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

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Authors: Seyedeh Azadeh Johari

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For thousand years, the literature of the world has been mostly composed of men, and in all different forms of it, men have tried to propose their masculine desires, ideologies, and beliefs. What has been less written about or studied, however, was the role that female desire plays in the predominantly masculine society, and mostly the role of male desires was the key point in literature. Male writers have mostly shown their female characters either as stereotypes and void of dynamic characters, images of a meek person who bent to the will of her male superiors or as wicked or villains. The only exception was the kind of strong and courageous women who have mostly been masculinized by their authors, mostly male authors, as showing the valuable or important features of men, instead of women’s. These characters are transgendered by the author and have a gender identity or expression that differs from the sex to which they were assigned. This is the issue that is discussed in this project. We will refer to some examples of female characters who show masculine traits and characteristics.

Keywords: comparative literature, female, masculinized, transgendered

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Authors: Ouassila Labbani-Narsis, Christophe Nicolle

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Building formal ontologies remains a complex process for companies. In the literature, this process is based on the technical knowledge and expertise of domain experts, without further details on the used methodologies. Possible problems of disagreements between experts, expression of tacit knowledge related to high level know-how rarely verbalized, qualification of results by using cases, or simply adhesion of the group of experts, remain currently unsolved. This paper proposes a methodological approach based on knowledge elicitation for the conception of formal, consensual, and shared ontologies. The proposed approach is experimentally tested on industrial collaboration projects in the field of manufacturing (associating knowledge sources from multinational companies) and in the field of viticulture (associating explicit knowledge and implicit knowledge acquired through observation).

Keywords: collaborative ontology engineering, knowledge elicitation, knowledge engineering, knowledge management

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Authors: Tahraoui Boualem

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The International Labor Organization is one of the specialized agencies of the United Nations, and it is the only organization within the United Nations system that is distinguished by its tripartite legitimacy and which simultaneously includes governments, workers' and employers' organizations of its member states in a joint effort to set standards and policies Work to promote decent work in various parts of the world, and the expression of international labor standards basically means two types of documents, namely international labor agreements and international labor recommendations, and so far its general conference, which is held annually, has set a number of standards, the number of which has reached 184 agreements and 192 recommendations so far. For this reason, it is decided to clarify the International Labor Organization and the formulation of international labor standards within two sections. In the first topic, the researcher discusses the concept of the International Labor Organization, and in the second topic, it highlights the legal basis for the authority of the International Labor Organization in protecting the rights of workers.

Keywords: international labor, international labor standards, rights of workers, nation’s system

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Authors: Kai Chen, Shuguang Cui, Feng Yin

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Gaussian process (GP) with spectral mixture (SM) kernel demonstrates flexible non-parametric Bayesian learning ability in modeling unknown function. In this work a novel time-varying and non-stationary convolution spectral mixture (TN-CSM) kernel with a significant enhancing of interpretability by using process convolution is introduced. A way decomposing the SM component into an auto-convolution of base SM component and parameterizing it to be input dependent is outlined. Smoothly, performing a convolution between two base SM component yields a novel structure of non-stationary SM component with much better generalized expression and interpretation. The TN-CSM perfectly allows compatibility with the stationary SM kernel in terms of kernel form and spectral base ignored and confused by previous non-stationary kernels. On synthetic and real-world datatsets, experiments show the time-varying characteristics of hyper-parameters in TN-CSM and compare the learning performance of TN-CSM with popular and representative non-stationary GP.

Keywords: Gaussian process, spectral mixture, non-stationary, convolution

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Authors: Kim Hyekyoung, Au Yunkyung

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As media plays an increasingly important role in our lives, the age at which media usage begins is getting younger worldwide. Particularly, young children are exposed to media at an early age, making early childhood media literacy education an essential task. However, most existing early childhood media literacy education programs focus solely on teaching children how to use media, and practical implementation and application are challenging. Therefore, this study aims to develop a play-based early childhood media literacy education program utilizing topic-based media content and explore the potential application and impact of this program on young children's media literacy learning. Based on theoretical and literature review on media literacy education, analysis of existing educational programs, and a survey on the current status and teacher perceptions of media literacy education for preschool children, this study developed a media literacy education program for preschool children, considering the components of media literacy (understanding media characteristics, self-regulation, self-expression, critical understanding, ethical norms, and social communication). To verify the effectiveness of the program, 20 preschool children aged 5 from C City M Kindergarten were chosen as participants, and the program was implemented from March 28th to July 4th, 2022, once a week for a total of 7 sessions. The program was developed based on Gallenstain's (2003) iterative learning model (participation-exploration-explanation-extension-evaluation). To explore the quantitative changes before and after the program, a repeated measures analysis of variance was conducted, and qualitative analysis was employed to examine the observed process changes. It was found that after the application of the education program, media literacy levels such as understanding media characteristics, self-regulation, self-expression, critical understanding, ethical norms, and social communication significantly improved. The recursive learning-based early childhood media literacy education program developed in this study can be effectively applied to young children's media literacy education and help enhance their media literacy levels. In terms of observed process changes, it was confirmed that children learned about various topics, expressed their thoughts, and improved their ability to communicate with others using media content. These findings emphasize the importance of developing and implementing media literacy education programs and can contribute to empowering young children to safely and effectively utilize media in their media environment. The results of this study, exploring the potential application and impact of the recursive learning-based early childhood media literacy education program on young children's media literacy learning, demonstrated positive changes in young children's media literacy levels. These results go beyond teaching children how to use media and can help foster their ability to safely and effectively utilize media in their media environment. Additionally, to enhance young children's media literacy levels and create a safe media environment, diverse content and methodologies are needed, and the continuous development and evaluation of education programs should be conducted.

Keywords: young children, media literacy, recursive learning, education program

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Authors: Li Shuping, Shu Huaping, Yi Chaofan, Tao Jiang

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Equestrian practice is often considered having a unique effect on improving symptoms in children with autism. This study evaluated and measured the changes in daily behavior, morphological, physical function, and fitness indexes of two group children with autism by means of 12 weeks of equestrian and basketball exercises. 19 clinically diagnosed children with moderate/mild autism were randomly divided into equestrian group (9 children, age=10.11±1.90y) and basketball group (10 children, age=10.70±2.16y). Both the equestrian and basketball groups practiced twice a week for 45 to 60 minutes each time. Three scales, the Autism Behavior Checklist (ABC), the Childhood Autism Rating Scale (CARS) and the Clancy Autism Behavior Scale (CABS) were used to assess their human behavior and psychology. Four morphological, seven physical function and fitness indicators were measured to evaluate the effects of the two exercises on the children’s body. The evaluations were taken by every four weeks ( pre-exercise, the 4th week, the 8th week and 12th week (post exercise). The result showed that the total scores of ABC, CARS and CABS, the dimension scores of ABC on the somatic motor, language and life self-care obtained after exercise were significantly lower than those obtained before 12 week exercises in both groups. The ABC feeling dimension scores of equestrian group and ABC communication dimension score of basketball group were significantly lower,and The upper arm circumference, sitting forward flexion, 40 second sit-up, 15s lateral jump, vital capacity, and single foot standing of both groups were significantly higher than that of before exercise.. The BMI of equestrian group was significantly reduced. The handgrip strength of basketball group was significantly increased. In conclusion, both types of exercises could improve daily behavior, morphological, physical function, and fitness indexes of the children with autism. However, the behavioral psychological scores, body morphology and function indicators and time points were different in the middle and back of the two interventions.But the indicators and the timing of the improvement were different. To the group of equestrian, the improvement of the flexibility occurred at week 4, the improvement of the sensory perception, control and use their own body, and promote the development of core strength endurance, coordination and cardiopulmonary function occurred at week 8，and the improvement of core strength endurance, coordination and cardiopulmonary function occurred at week 12. To the group of basketball, the improvement of the hand strength, balance, flexibility and cardiopulmonary function occurred at week 4, the improvement of the self-care ability and language expression ability, and core strength endurance and coordination occurred at week 8, the improvement of the control and use of their own body and social interaction ability occurred at week 12. In comparison of the exercise effects, the equestrian exercise improved the physical control and application ability appeared earlier than that of basketball group. Basketball exercise improved the language expression ability, self-care ability, balance ability and cardiopulmonary function of autistic children appeared earlier than that of equestrian group.

Keywords: intervention, children with autism, equestrain, basketball

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Authors: Robert Birkholc

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One of the basic issues related to the creation of characters in media, such as literature and film, is the representation of the characters' thoughts, emotions, and perceptions. This paper is devoted to the social perspective (or the focalization) expressed in film narration. The aim of the paper is to show how social point of view of the hero –conditioned by his origin and the environment from which he comes– can be created by using non-verbal, purely audiovisual means of expression. The issue will be considered on the example of the little-known polish movie The Dancing Hawk (1977) by Grzegorz Królikiewicz, based on the novel by Julian Kawalec. The thesis of the paper is that the polish director uses a narrative figure, which is somewhat analogous to literary form of free indirect discourse. In literature, free indirect discourse is formally ‘spoken’ by the external narrator, but the narration is clearly filtered through the language and thoughts of the character. According to some scholars (such as Roy Pascal), the narrator in this form of speech does not cite the character's words, but uses his way of thinking and imitates his perspective – sometimes with a deep irony. Free indirect discourse is frequently used in Julian Kawalec’s novel. Through the linguistic stylization, the author tries to convey the socially determined perspective of a peasant who migrates to the big city after the Second World War. Grzegorz Królikiewicz expresses the same social experience by pure cinematic form in the adaptation of the book. Both Kawalec and Królikiewicz show the consequences of so-called ‘social advancement’ in Poland after 1945, when the communist party took over political power. On the example of the fate of the main character, Michał Toporny, the director presents the experience of peasants who left their villages and had to adapt to new, urban space. However, the paper is not focused on the historical topic itself, but on the audiovisual form of the movie. Although Królikiewicz doesn’t use frequently POV shots, the narration of The Dancing Hawk is filtered through the sensations of the main character, who feels uprooted and alienated in the new social space. The director captures the hero's feelings through very complex audiovisual procedures – high or low points of view (representing the ‘social position’), grotesque soundtrack, expressionist scenery, and associative editing. In this way, he manages to create the world from the perspective of a socially maladjusted and internally split subject. The Dancing Hawk is a successful attempt to adapt the subjective narration of the book to the ‘language’ of the cinema. Mieke Bal’s notion of focalization helps to describe ‘free indirect discourse’ as a transmedial figure of representing of the characters’ perceptions. However, the polysemiotic medium of the film also significantly transforms this figure of representation. The paper shows both the similarities and differences between literary and cinematic ‘free indirect discourse.’

Keywords: film and literature, free indirect discourse, social experience, subjective narration

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Authors: Nouredine Benouzza, Ahmed Hamida Boudinar, Azeddine Bendiabdellah

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An algorithm for Eccentricity Fault Detection (EFD) applied to a squirrel cage induction machine is proposed in this paper. This algorithm employs the behavior of the stator current spectral analysis and the localization of the Rotor Slot Harmonic (RSH) frequency to detect eccentricity faults in three phase induction machine. The RHS frequency once obtained is used as a key parameter into a simple developed expression to directly compute the eccentricity fault frequencies in the induction machine. Experimental tests performed for both a healthy motor and a faulty motor with different eccentricity fault severities illustrate the effectiveness and merits of the proposed EFD algorithm.

Keywords: squirrel cage motor, diagnosis, eccentricity faults, current spectral analysis, rotor slot harmonic

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Authors: Dina Sabirova, Madina Moldagali

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The rapid development of new media, especially the Internet, has led to major changes in folk culture. The net space is increasingly becoming a creation of the ‘folk’ imagination, saturated with multimedia stories with collective authorship, like traditional folklore. Moreover, the Internet picks up and changes old folklore traditions, such as the form of publication, the way of storytelling, or gave a new morality to the ‘old tales’. In this article, the similarities and differences between Internet folklore/ cyber-folklore/ digital folklore and oral folk art were examined by using the material of modern Kazakh authors. The relationship between tradition and innovation was studied in order to interpret the sequence of the authors' research taking into account the realities. The material of the article was the prose texts of Kazakh writers published in internet magazines and social networks. An immanent and intertextual analysis of the text was carried out. Thus, the new forms of Internet folklore lead to new forms of expression and social morality in society

Keywords: internet literature, modern Kazakhstani authors, net folklore, oral folk art

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Authors: Thea Silayro, Isabella Tan, Carlo Manuel, Denisse Abellon

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Romantic love is highly universal and exists in most cultures. The current study explored its definition for people in different relationship durations and explored how this definition influences their expression of love and their conflict resolutions. Gender‟s influence on the definitions was explored, as well. Nine couples from different relationship durations (2-3 years, 7-10 years and more than 25 years) were interviewed. Transcripts of the interviews underwent thematic analysis. The results of the study suggest that 2-3 years in the relationship is the courting stage, 7-10 years in the relationship is the settling down stage and more than 25 years, the most stable stage. Men and women have similar ways of expressing love and resolving conflicts, but differ in such a way that men highlight actions and women highlight emotions when talking about love; changes in definitions arise internally in men and externally in females. Generally, romantic love is expressed through service. Communication is essential among all couples, and they become more secure with time.

Keywords: relationship duration, love, expressions of love, relationships

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Authors: Yuriko Takayama, Norihiro Kato

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Quorum sensing (QS) is a cell-to-cell communication system in bacteria to regulate expression of target genes. In gram-negative bacteria, activation on QS is controlled by a concentration increase of N-acylhomoserine lactone (AHL), which can diffuse in and out of the cell. Effective control of QS is expected to avoid virulence factor production in infectious pathogens, biofilm formation, and antibiotic production because various cell functions in gram-negative bacteria are controlled by AHL-mediated QS. In this research, we applied cyclodextrins (CDs) as artificial hosts for the AHL signal to reduce the AHL concentration in the culture broth below its threshold for QS activation. The AHL-receptor complex induced under the high AHL concentration activates transcription of the QS-target gene. Accordingly, artificial reduction of the AHL concentration is one of the effective strategies to inhibit the QS. A hydrophobic cavity of the CD can interact with the acyl-chain of the AHL due to hydrophobic interaction in aqueous media. We studied N-hexanoylhomoserine lactone (C6HSL)-mediated QS in Serratia marcescens; accumulation of C6HSL is responsible for regulation of the expression of pig cluster. Inhibitory effects of added CDs on QS were demonstrated by determination of prodigiosin amount inside cells after reaching stationary phase, because production of prodigiosin depends on the C6HSL-mediated QS. By adding approximately 6 wt% hydroxypropyl-β-CD (HP-β-CD) in Luria-Bertani (LB) medium prior to inoculation of S. maecescens AS-1, the intracellularly accumulated prodigiosin was drastically reduced to 7-10%, which was determined after the extraction of prodigiosin in acidified ethanol. The AHL retention ability of HP-β-CD was also demonstrated by Chromobacterium violacuem CV026 bioassay. The CV026 strain is an AHL-synthase defective mutant that activates QS solely by adding AHLs from outside of cells. A purple pigment violacein is induced by activation of the AHL-mediated QS. We demonstrated that the violacein production was effectively suppressed when the C6HSL standard solution was spotted on a LB agar plate dispersing CV026 cells and HP-β-CD. Physico-chemical analysis was performed to study the affinity between the immobilized CD and added C6HSL using a quartz crystal microbalance (QCM) sensor. The COOH-terminated self-assembled monolayer was prepared on a gold electrode of 27-MHz AT-cut quartz crystal. Mono(6-deoxy-6-N, N-diethylamino)-β-CD was immobilized on the electrode using water-soluble carbodiimide. The C6HSL interaction with the β-CD cavity was studied by injecting the C6HSL solution to a cup-type sensor cell filled with buffer solution. A decrement of resonant frequency (ΔFs) clearly showed the effective C6HSL complexation with immobilized β-CD and its stability constant for MBP-SpnR-C6HSL complex was on the order of 102 M-1. The CD has high potential for engineered control of QS because it is safe for human use.

Keywords: acylhomoserine lactone, cyclodextrin, intracellular signaling, quorum sensing

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Authors: Iñaki Milton-Laskibar, Leixuri Aguirre, Maria P. Portillo

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Introduction: Energy restriction is an effective approach in preventing liver steatosis. However, due to social and economic reasons among others, compliance with this treatment protocol is often very poor, especially in the long term. Resveratrol, a natural polyphenolic compound that belongs to stilbene group, has been widely reported to imitate the effects of energy restriction. Objective: To analyze the effects of resveratrol under normoenergetic feeding conditions and under a mild energy restriction on liver fat accumulation and hepatic fatty acid oxidation. Methods: 36 male six-week-old rats were fed a high-fat high-sucrose diet for 6 weeks in order to induce steatosis. Then, rats were divided into four groups and fed a standard diet for 6 additional weeks: control group (C), resveratrol group (RSV, resveratrol 30 mg/kg/d), restricted group (R, 15 % energy restriction) and combined group (RR, 15 % energy restriction and resveratrol 30 mg/kg/d). Liver triacylglycerols (TG) and total cholesterol contents were measured by using commercial kits. Carnitine palmitoyl transferase 1a (CPT 1a) and citrate synthase (CS) activities were measured spectrophotometrically. TFAM (mitochondrial transcription factor A) and peroxisome proliferator-activator receptor alpha (PPARα) protein contents, as well as the ratio acetylated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)/Total PGC1α were analyzed by Western blot. Statistical analysis was performed by using one way ANOVA and Newman-Keuls as post-hoc test. Results: No differences were observed among the four groups regarding liver weight and cholesterol content, but the three treated groups showed reduced TG when compared to the control group, being the restricted groups the ones showing the lowest values (with no differences between them). Higher CPT 1a and CS activities were observed in the groups supplemented with resveratrol (RSV and RR), with no difference between them. The acetylated PGC1α /total PGC1α ratio was lower in the treated groups (RSV, R and RR) than in the control group, with no differences among them. As far as TFAM protein expression is concerned, only the RR group reached a higher value. Finally, no changes were observed in PPARα protein expression. Conclusions: Resveratrol administration is an effective intervention for liver triacylglycerol content reduction, but a mild energy restriction is even more effective. The mechanisms of action of these two strategies are different. Thus resveratrol, but not energy restriction, seems to act by increasing fatty acid oxidation, although mitochondriogenesis seems not to be induced. When both treatments (resveratrol administration and a mild energy restriction) were combined, no additive or synergic effects were appreciated. Acknowledgements: MINECO-FEDER (AGL2015-65719-R), Basque Government (IT-572-13), University of the Basque Country (ELDUNANOTEK UFI11/32), Institut of Health Carlos III (CIBERobn). Iñaki Milton is a fellowship from the Basque Government.

Keywords: energy restriction, fat, liver, oxidation, resveratrol

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Authors: Vinaya Kambappa, Chinnadurai Mani, Komaraiah Palle

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Non-small cell-lung cancer (NSCLC) cells have increased expression of EGFR, which makes them a potential target for cancer therapy. Based on molecular docking and previous reports, we designed and synthesized quinazoline derivatives as potent EGFR inhibitors. Among the derivatives, three compounds showed good antiproliferative activity against A-549 and H-1299 cells. Furthermore, these compounds inhibited EGFR signaling exhibiting diminishing p-EGFR and its downstream proteins like p-Akt, p-Erk1/2, and p-mTOR; however, it did not alter the levels of EGFR, Akt, Erk1/2 and mTOR proteins. Flow cytometric analysis indicated the accumulation of cells at G1 phase suggesting induction of apoptosis, which was further confirmed by annexin V/propidium iodide staining. Our study suggested that quinazoline scaffold can be developed as novel EGFR kinase inhibitors for cancer therapy.

Keywords: apoptosis, non-small cell-lung cancer cells, EGFR, quinazoline

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Authors: Juliana Chiarini Balbino Fernandes

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This article aims to investigate the Spanish didactic book, entitled ‘El Calculo y La Medida en El Primer Grado de La Escuela Decroly’, written by Dr. O. Decroly and A. Hamaide, published in Madrid, in the year 1934. In addition to analyzing how mathematical knowledge is present in the proposed Centers of Interest. The textbooks, in addition to pedagogical tools, reflect a certain moment in society and allow the analysis of the theoretical-methodological proposal that can be implemented by the teacher. The study proposed here will be carried out by the lens of Cultural History, supported by Roger Chartier (1991) and by the concepts on textbooks, based on Alain Choppin (2004). The textbook selected for this study exposes a program of ideas associated with the method of Centers of Interest and arithmetic is linked to these interests. In the first courses (six to eight years), most centers can be considered to correspond to occasional calls, as they take advantage of events that arise spontaneously to work with observation, measurement, association and expression exercises. The program of ideas associated with Centers of Interest addresses the biological and social aspects of children, as long as they can express their needs for activities and games, satisfying the natural curiosity. Still, the program of associated ideas offers occasions for problems whose data are taken in observation exercises and concrete expressions (manuals, drawings). In the method applied at the school of L'Ermitage, school created by Decroly in Belgium in 1907, observation, is the basis of each center of interest. It offers the chance to compare and measure. To observe is more than to perceive; it is also to establish relations between the graded aspects of the same object, to seek relations between different intensities; is to verify successions, special and temporary relationships; is to make comparisons, to notice differences and similarities in block or datable (analysis), is to establish a bridge between the world and the thought. To make the observation more precise, it is important to compare, measure, and resort to considered objects as natural units of measure. Measurement and calculation are, therefore, quite naturally subject to observation. Thus, it is possible to make the child enter into the interest in the calculation, linking it to the observation. It was observed that the Centers of Interest, according to Decroly, should respond to the concerns and attend to the motivations of the students and the teaching of arithmetical must obey a logical seriation, considering the interest and the experience of the children. The teaching of arithmetical should not be limited to the schedule, it should cover every quantitative aspect that arises in the other disciplines. The feeling of unity is established in observation, association and expression, which coordinate a whole program of cultural activities, concentrating it around a central idea.

Keywords: didactic book, centers of interest, mathematical knowledge, primary education

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Authors: Manduth Ramchander

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Evaluating expressions involving multiplication and division can give rise to the fallacy that brackets can be arbitrarily inserted into expressions involving multiplication and division. The aim of this article was to draw upon mathematical theory to prove that brackets cannot be arbitrarily inserted into expressions involving multiplication and division and in particular in expressions where division precedes multiplication. In doing so, it demonstrates that the notion that two different answers are possible, when evaluating expressions involving multiplication and division, is indeed a false one. Searches conducted in a number of scholarly databases unearthed the rules to be applied when removing brackets from expressions, which revealed that consideration needs to be given to sign changes when brackets are removed. The rule pertaining to expressions involving multiplication and division was then extended upon, in its reverse format, to prove that brackets cannot be arbitrarily inserted into expressions involving multiplication and division. The application of the rule demonstrates that an expression involving multiplication and division can have only one correct answer. It is recommended that both the rule and its reverse be included in the curriculum, preferably at the juncture when manipulation with brackets is introduced.

Keywords: brackets, multiplications and division, operations, order

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Authors: Kênio Angelo Dantas Freitas Estrela

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Traditionally meaning holism is a theory that is related to the meaning attributed to words and their relationships to other words in a language. This theory can be more specifically defined as a defense of the mutual interdependence of all items of linguistic knowledge, so that, for example, to understand the meaning of a given expression, it is necessary to understand a large sector of the language in question or, even the complete language. The aim of this paper is to present a moderate version of meaning holism, which argues that, among other things, meaning holism does not imply the thesis of instability - if there is the change of belief about an object, there is a change of meaning - and, in this way, it is possible to attribute meanings to objects admitting changes of opinions and then beliefs. It will be shown how this version of holism gives an account of the main criticisms made of meaning holism in the last decades and also show how this theory can justify linguistic phenomena (like vagueness and polysemy) that are often treated as problems of language. Finally, it will also be argued that these linguistic phenomena are intrinsic to languages and that the moderate version of meaning holism can justify the occurrence of these phenomena.

Keywords: linguistics, meaning holism, philosophy of language, semantics

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Authors: Fawzyah Albaldi

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Urinary tract infections (UTIs) are the most prevalent of infectious diseases and > 80% are caused by uropathogenic E. coli (UPEC). Infection occurs following adhesion to urothelial plaques on bladder epithelial cells, whose major protein constituent are the uroplakins (UPs). Two of the four uroplakins (UPIa and UPIb) are members of the tetraspanin superfamily. The UPEC adhesin FimH is known to interact directly with UPIa. Tetraspanins are a diverse family of transmembrane proteins that generally act as “molecular organizers” by binding different proteins and lipids to form tetraspanin enriched microdomains (TEMs). Previous work by our group has shown that TEMs are involved in the adhesion of many pathogenic bacteria to human cells. Adhesion can be blocked by tetraspanin-derived synthetic peptides, suggesting that tetraspanins may be valuable drug targets. In this study, we investigate the role of tetraspanins in UPEC adherence to bladder epithelial cells. Human bladder cancer cell lines (T24, 5637, RT4), commonly used as in-vitro models to investigate UPEC infection, along with primary human bladder cells, were used in this project. The aim was to establish a model for UPEC adhesion/infection with the objective of evaluating the impact of tetraspanin-derived reagents on this process. Such reagents could reduce the progression of UTI, particularly in patients with indwelling catheters. Tetraspanin expression on the bladder cells was investigated by q-PCR and flow cytometry, with CD9 and CD81 generally highly expressed. Interestingly, despite these cell lines being used by other groups to investigate FimH antagonists, uroplakin proteins (UPIa, UPIb and UPIII) were poorly expressed at the cell surface, although some were present intracellularly. Attempts were made to differentiate the cell lines, to induce cell surface expression of these UPs, but these were largely unsuccessful. Pre-treatment of bladder epithelial cells with anti-CD9 monoclonal antibody significantly decreased UPEC infection, whilst anti-CD81 had no effects. A short (15aa) synthetic peptide corresponding to the large extracellular region (EC2) of CD9 also significantly reduced UPEC adherence. Furthermore, we demonstrated specific binding of that fluorescently tagged peptide to the cells. CD9 is known to associate with a number of heparan sulphate proteoglycans (HSPGs) that have also been implicated in bacterial adhesion. Here, we demonstrated that unfractionated heparin (UFH)and heparin analogs significantly inhibited UPEC adhesion to RT4 cells, as did pre-treatment of the cells with heparinases. Pre-treatment with chondroitin sulphate (CS) and chondroitinase also significantly decreased UPEC adherence to RT4 cells. This study may shed light on a common pathogenicity mechanism involving the organisation of HSPGs by tetraspanins. In summary, although we determined that the bladder cell lines were not suitable to investigate the role of uroplakins in UPEC adhesion, we demonstrated roles for CD9 and cell surface proteoglycans in this interaction. Agents that target these may be useful in treating/preventing UTIs.

Keywords: UTIs, tspan, uroplakins, CD9

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Authors: Saleh Abu Dabous, Khaled Hamad, Rami Al-Ruzouq

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Bridge condition assessment and rating provide essential information needed for bridge management. This paper reviews bridge inspection and condition rating practices and introduces a defect-based urgency index. The index is estimated at the element-level based on the extent and severity of the different defects typical to the bridge element. The urgency index approach has the following advantages: (1) It facilitates judgment submission, i.e. instead of rating the bridge element with a specific linguistic overall expression (which can be subjective and used differently by different people), the approach is based on assessing the defects; (2) It captures multiple defects that can be present within a deteriorated element; and (3) It reflects how critical the element is through quantifying critical defects and their severity. The approach can be further developed and validated. It is expected to be useful for practical purposes as an early-warning system for critical bridge elements.

Keywords: condition rating, deterioration, inspection, maintenance

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Authors: Anna Trusek-Holownia, Andrzej Noworyta

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Using an enzyme of known specificity the hydrolysis of protein was carried out in a controlled manner. The aim was to obtain oligopeptides being the so-called active peptides or their direct precursors. An original way of expression of the protein hydrolysis kinetics was introduced. Peptide bonds contained in the protein were recognized as a diverse-quality substrate for hydrolysis by the applied protease. This assumption was positively verified taking as an example the hydrolysis of albumin by thermolysin. Peptide linkages for this system should be divided into at least four groups. One of them is a group of bonds non-hydrolyzable by this enzyme. These that are broken are hydrolyzed at a rate that differs even by tens of thousands of times. Designated kinetic constants were k'F = 10991.4 L/g.h, k'M = 14.83L/g.h, k'S about 10-1 L/g.h for fast, medium and slow bonds, respectively. Moreover, a procedure for unfolding of the protein, conducive to the improved susceptibility to enzymatic hydrolysis (approximately three-fold increase in the rate) was proposed.

Keywords: peptide bond hydrolysis, kinetics, enzyme specificity, biologically active peptides

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Authors: Luca Martignoni, Joseph Nserat, Eric Arand, Marvin Braun

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The increasing application of conversational agents in healthcare and the demand for applications that enable patients to take informed decisions is changing the way patients access healthcare and take decisions. Promising results related to the acceptance of CAs in healthcare have been accomplished. In that regard, understanding how to design CAs in a way that patients trust their recommendations and decisions constitutes an important area of research. Our study examines self-disclosure and transparency as drivers of trust to enhance the medical assistance of CAs for patients. Accordingly, we examined the effects of self-disclosure and transparency on patients trust and service satisfaction by conducting an online experiment with 136 participants. Our results show that the expression of both self-disclosure and conversational agents transparency leads to an increased perception of trust but does not necessarily improve the service satisfaction. Therefore, developers should implement self-disclosure and transparency to create a trustworthy environment.

Keywords: conversational agent, transparency, self-disclosure, healthcare

Procedia PDF Downloads 127

Authors: Jingjing Li, Shifu Wang

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After the irreversible consequences of the traditional renewal mode of ‘function first and then beautification’, such as the constructive destruction, social differentiation, and cultural, ecological imbalance, the renewal of the historical urban area began to pay attention to the excavation of cultural connotation, and entered a new stage from the pursuit of ‘quantity’ growth to the promotion of ‘quality’, expecting to rejuvenate the old city through the intervention of public art. This paper interprets the cases at home and abroad, summarizes the different forms of expression and application strategies of public art in the renewal of historical urban areas, and combs the limitations of the existing practice in Guangzhou through observation. Finally, it puts forward suggestions from three aspects of the system, implementation strategy, and implementation path, respectively, and explores the path of simultaneous rejuvenation of material space and cultural space in historical urban areas under the intervention of public art.

Keywords: public art, historic city, public space, renewal activation

Procedia PDF Downloads 124

Authors: Shaista Suhail

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As cancer populations is increasing sharply, the incidence of oral squamous cell carcinoma (OSCC) has also been expected to increase. Oral carcinogenesis is a highly complex, multistep process which involves accumulation of genetic alterations that lead to the induction of proteins promoting cell growth (encoded by oncogenes), increased enzymatic (telomerase) activity promoting cancer cell proliferation. The global increase in frequency and mortality, as well as the poor prognosis of oral squamous cell carcinoma, has intensified current research efforts in the field of prevention and early detection of this disease. The advances in the understanding of the molecular basis of oral cancer should help in the identification of new markers. The study of the carcinogenic process of the oral cancer, including continued analysis of new genetic alterations, along with their temporal sequencing during initiation, promotion and progression, will allow us to identify new diagnostic and prognostic factors, which will provide a promising basis for the application of more rational and efficient treatments. Telomerase activity has been readily found in most cancer biopsies, in premalignant lesions or germ cells. Activity of telomerase is generally absent in normal tissues. It is known to be induced upon immortalization or malignant transformation of human cells such as in oral cancer cells. Maintenance of telomeres plays an essential role during transformation of precancer to malignant stage. Mammalian telomeres, a specialized nucleoprotein structures are composed of large conctamers of the guanine-rich sequence 5_-TTAGGG-3_. The roles of telomeres in regulating both stability of genome and replicative immortality seem to contribute in essential ways in cancer initiation and progression. It is concluded that activity of telomerase can be used as a biomarker for diagnosis of malignant oral cancer and a target for inactivation in chemotherapy or gene therapy. Its expression will also prove to be an important diagnostic tool as well as a novel target for cancer therapy. The activation of telomerase may be an important step in tumorgenesis which can be controlled by inactivating its activity during chemotherapy. The expression and activity of telomerase are indispensable for cancer development. There are no drugs which can effect extremely to treat oral cancers. There is a general call for new emerging drugs or methods that are highly effective towards cancer treatment, possess low toxicity, and have a minor environment impact. Some novel natural products also offer opportunities for innovation in drug discovery. Natural compounds isolated from medicinal plants, as rich sources of novel anticancer drugs, have been of increasing interest with some enzyme (telomerase) blockage property. The alarming reports of cancer cases increase the awareness amongst the clinicians and researchers pertaining to investigate newer drug with low toxicity.

Keywords: oral carcinoma, telomere, telomerase, blockage

Procedia PDF Downloads 163

Authors: Razieh Karimi Aghcheh, Christian Kubicek, Joseph Strauss, Gerhard Braus

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Filamentous fungi are of considerable economic and social significance for human health, nutrition and in white biotechnology. These organisms are dominant producers of a range of primary metabolites such as citric acid, microbial lipids (biodiesel) and higher unsaturated fatty acids (HUFAs). In particular, they produce also important but structurally complex secondary metabolites with enormous therapeutic applications in pharmaceutical industry, for example: cephalosporin, penicillin, taxol, zeranol and ergot alkaloids. Several fungal secondary metabolites, which are significantly relevant to human health do not only include antibiotics, but also e.g. lovastatin, a well-known antihypercholesterolemic agent produced by Aspergillus. terreus, or aflatoxin, a carcinogen produced by A. flavus. In addition to their roles for human health and agriculture, some fungi are industrially and commercially important: Species of the ascomycete genus Hypocrea spp. (teleomorph of Trichoderma) have been demonstrated as efficient producer of highly active cellulolytic enzymes. This trait makes them effective in disrupting and depolymerization of lignocellulosic materials and thus applicable tools in number of biotechnological areas as diverse as clothes-washing detergent, animal feed, and pulp and fuel productions. Fungal LaeA/LAE1 (Loss of aflR Expression A) homologs their gene products act at the interphase between secondary metabolisms, cellulase production and development. Lack of the corresponding genes results in significant physiological changes including loss of secondary metabolite and lignocellulose degrading enzymes production. At the molecular level, the encoded proteins are presumably methyltransferases or demethylases which act directly or indirectly at heterochromatin and interact with velvet domain proteins. Velvet proteins bind to DNA and affect expression of secondary metabolites (SMs) genes and cellulases. The dynamic interplay between LaeA/LAE1, velvet proteins and additional interaction partners is the key for an understanding of the coordination of metabolic and morphological functions of fungi and is required for a biotechnological control of the formation of desired bioactive products. Aspergilli and Trichoderma represent different biotechnologically significant species with significant differences in the LaeA/LAE1-Velvet protein machinery and their target proteins. We, therefore, performed a comparative study of the interaction partners of this machinery and the dynamics of the various protein-protein interactions using our robust proteomic and mass spectrometry techniques. This enhances our knowledge about the fungal coordination of secondary metabolism, cellulase production and development and thereby will certainly improve recombinant fungal strain construction for the production of industrial secondary metabolite or lignocellulose hydrolytic enzymes.

Keywords: cellulases, LaeA/1, proteomics, secondary metabolites

Procedia PDF Downloads 262

Authors: Edwin Foo, Woei Wen, Lui, Meijun Zhao, Shigeru Kuchii, Chin Sai Wong, Chung Sern Goh, Yi Hao He

Abstract:

This presentation presents an elderly care and assistive social robot development work. We named this robot JOS and he is restricted to table top operation. JOS is designed to have a maximum volume of 3600 cm3 with its base restricted to 250 mm and his mission is to provide companion, assist and help the elderly. In order for JOS to accomplish his mission, he will be equipped with perception, reaction and cognition capability. His appearance will be not human like but more towards cute and approachable type. JOS will also be designed to be neutral gender. However, the robot will still have eyes, eyelid and a mouth. For his eyes and eyelids, they will be built entirely with Robotis Dynamixel AX18 motor. To realize this complex task, JOS will be also be equipped with micro-phone array, vision camera and Intel i5 NUC computer and a powered by a 12 V lithium battery that will be self-charging. His face is constructed using 1 motor each for the eyelid, 2 motors for the eyeballs, 3 motors for the neck mechanism and 1 motor for the lips movement. The vision senor will be house on JOS forehead and the microphone array will be somewhere below the mouth. For the vision system, Omron latest OKAO vision sensor is used. It is a compact and versatile sensor that is only 60mm by 40mm in size and operates with only 5V supply. In addition, OKAO vision sensor is capable of identifying the user and recognizing the expression of the user. With these functions, JOS is able to track and identify the user. If he cannot recognize the user, JOS will ask the user if he would want him to remember the user. If yes, JOS will store the user information together with the capture face image into a database. This will allow JOS to recognize the user the next time the user is with JOS. In addition, JOS is also able to interpret the mood of the user through the facial expression of the user. This will allow the robot to understand the user mood and behavior and react according. Machine learning will be later incorporated to learn the behavior of the user so as to understand the mood of the user and requirement better. For the speech system, Microsoft speech and grammar engine is used for the speech recognition. In order to use the speech engine, we need to build up a speech grammar database that captures the commonly used words by the elderly. This database is built from research journals and literature on elderly speech and also interviewing elderly what do they want to robot to assist them with. Using the result from the interview and research from journal, we are able to derive a set of common words the elderly frequently used to request for the help. It is from this set that we build up our grammar database. In situation where there is more than one person near JOS, he is able to identify the person who is talking to him through an in-house developed microphone array structure. In order to make the robot more interacting, we have also included the capability for the robot to express his emotion to the user through the facial expressions by changing the position and movement of the eyelids and mouth. All robot emotions will be in response to the user mood and request. Lastly, we are expecting to complete this phase of project and test it with elderly and also delirium patient by Feb 2015.

Keywords: social robot, vision, elderly care, machine learning

Procedia PDF Downloads 435

Authors: Jamal Takhchi

Abstract:

The understanding of vibration propagation in complex structures such as automotive body in white remains a challenging issue in car design regarding NVH performances. The current analysis is limited to the low frequency range where modal concepts are dominant. Higher frequencies, between 200 and 1000 Hz, will become critical With the rise of electrification. EVs annoying sounds are mostly whines created by either Gears or e-motors between 300 Hz and 2 kHz. Structural intensity analysis was Experienced a few years ago on finite element models. The application was promising but limited by the fact that the propagating 3D intensity vector field is masked by a rotational Intensity field. This rotational field should be filtered using a differential operator. The expression of this operator in the framework of finite element modeling is not yet known. The aim of the proposed work is to implement this operator in the current dynamic solver (NASTRAN) of Stellantis and develop the Expected methodology for the mid-frequency structural analysis of electrified vehicles.

Keywords: structural intensity, NVH, body in white, irrotatational intensity

Procedia PDF Downloads 145