Search results for: distant cellular interaction
3650 Coverage Probability Analysis of WiMAX Network under Additive White Gaussian Noise and Predicted Empirical Path Loss Model
Authors: Chaudhuri Manoj Kumar Swain, Susmita Das
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This paper explores a detailed procedure of predicting a path loss (PL) model and its application in estimating the coverage probability in a WiMAX network. For this a hybrid approach is followed in predicting an empirical PL model of a 2.65 GHz WiMAX network deployed in a suburban environment. Data collection, statistical analysis, and regression analysis are the phases of operations incorporated in this approach and the importance of each of these phases has been discussed properly. The procedure of collecting data such as received signal strength indicator (RSSI) through experimental set up is demonstrated. From the collected data set, empirical PL and RSSI models are predicted with regression technique. Furthermore, with the aid of the predicted PL model, essential parameters such as PL exponent as well as the coverage probability of the network are evaluated. This research work may assist in the process of deployment and optimisation of any cellular network significantly.Keywords: WiMAX, RSSI, path loss, coverage probability, regression analysis
Procedia PDF Downloads 1793649 Winkler Springs for Embedded Beams Subjected to S-Waves
Authors: Franco Primo Soffietti, Diego Fernando Turello, Federico Pinto
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Shear waves that propagate through the ground impose deformations that must be taken into account in the design and assessment of buried longitudinal structures such as tunnels, pipelines, and piles. Conventional engineering approaches for seismic evaluation often rely on a Euler-Bernoulli beam models supported by a Winkler foundation. This approach, however, falls short in capturing the distortions induced when the structure is subjected to shear waves. To overcome these limitations, in the present work an analytical solution is proposed considering a Timoshenko beam and including transverse and rotational springs. The present research proposes ground springs derived as closed-form analytical solutions of the equations of elasticity including the seismic wavelength. These proposed springs extend the applicability of previous plane-strain models. By considering variations in displacements along the longitudinal direction, the presented approach ensures the springs do not approach zero at low frequencies. This characteristic makes them suitable for assessing pseudo-static cases, which typically govern structural forces in kinematic interaction analyses. The results obtained, validated against existing literature and a 3D Finite Element model, reveal several key insights: i) the cutoff frequency significantly influences transverse and rotational springs; ii) neglecting displacement variations along the structure axis (i.e., assuming plane-strain deformation) results in unrealistically low transverse springs, particularly for wavelengths shorter than the structure length; iii) disregarding lateral displacement components in rotational springs and neglecting variations along the structure axis leads to inaccurately low spring values, misrepresenting interaction phenomena; iv) transverse springs exhibit a notable drop in resonance frequency, followed by increasing damping as frequency rises; v) rotational springs show minor frequency-dependent variations, with radiation damping occurring beyond resonance frequencies, starting from negative values. This comprehensive analysis sheds light on the complex behavior of embedded longitudinal structures when subjected to shear waves and provides valuable insights for the seismic assessment.Keywords: shear waves, Timoshenko beams, Winkler springs, sol-structure interaction
Procedia PDF Downloads 633648 Public Squares and Their Potential for Social Interactions: A Case Study of Historical Public Squares in Tehran
Authors: Asma Mehan
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Under the thrust of technological changes, population growth and vehicular traffic, Iranian historical squares have lost their significance and they are no longer the main social nodes of the society. This research focuses on how historical public squares can inspire designers to enhance social interactions among citizens in Iranian urban context. Moreover, the recent master plan of Tehran demonstrates the lack of public spaces designed for the purpose of people’s social gatherings. For filling this gap, first the current situation of 7 selected primary historical public squares in Tehran including Sabze Meydan, Arg, Topkhaneh, Baherstan, Mokhber-al-dole, Rah Ahan and Hassan Abad have been compared. Later, the influencing elements on social interactions of the public squares such as subjective factors (human relationships and memories) and objective factors (natural and built environment) have been investigated. As a conclusion, some strategies are proposed for improving social interactions in historical public squares like; holding cultural, national, athletic and religious events, defining different and new functions in public squares’ surrounding, increasing pedestrian routs, reviving the collective memory, demonstrating the historical importance of square, eliminating visual obstacles across the square, organization the natural elements of the square, appropriate pavement for social activities. Finally, it is argued that the combination of all influencing factors which are: human interactions, natural elements and built environment criteria will lead to enhance the historical public squares’ potential for social interaction.Keywords: historical square, Iranian public square, social interaction, Tehran
Procedia PDF Downloads 4063647 Use of RAPD and ISSR Markers in Detection of Genetic Variation among Colletotrichum falcatum Went Isolates from South Gujarat India
Authors: Prittesh Patel, Rushabh Shah, Krishnamurthy Ramar, Vakulbhushan Bhaskar
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The present research work aims at finding genetic differences in the genomes of sugarcane red rot isolates Colletotrichum falcatum Went using Random Amplified Polymorphic DNA (RAPD) and interspersed simple sequence repeat (ISSR) molecular markers. Ten isolates of C. falcatum isolated from different red rot infected sugarcane cultivars stalk were used in present study. The amplified bands were scored across the lanes obtained in 15 RAPD primes and 21 ISSR primes successfully. The data were analysed using NTSYSpc 2.2 software. The results showed 80.6% and 68.07% polymorphism in RPAD and ISSR analysis respectively. Based on the RAPD analysis, ten genotypes were grouped into two major clusters at a cut-off value of 0.75. Geographically distant C. falcatum isolate cfGAN from south Gujarat had a level of similarity with Coimbatore isolate cf8436 presented on separate clade of bootstrapped dendrograms. First and second cluster consisted of five and three isolates respectively, indicating the close relation among them. The 21 ISSR primers produced 119 distinct and scorable loci in that 38 were monomorphic. The number of scorable loci for each primer varied from 2 (ISSR822) to 8 (ISSR807, ISSR823 and ISSR15) with an average of 5.66 loci per primer. Primer ISSR835 amplified the highest number of bands (57), while only 16 bands were obtained by primers ISSR822. Four primers namely ISSR830, ISSR845, ISSR4 and ISSR15 showed the highest value of percentage of polymorphism (100%). The results indicated that both of the marker systems RAPD and ISSR, individually can be effectively used in determination of genetic relationship among C falcatum accessions collected from different parts of south Gujarat.Keywords: Colletotrichum falcatum, ISSR, RAPD, Red Rot
Procedia PDF Downloads 3633646 Experimental Investigation on the Efficiency of Expanded Polystyrene Geofoam Post and Beam System in Protecting Lifelines
Authors: Masood Abdollahi, Seyed Naser Moghaddas Tafreshi
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Expanded polystyrene (EPS) geofoam is a cellular geosynthetic material that can be used to protect lifelines (e.g. pipelines, electricity cables, etc.) below ground. Post and beam system is the most recent configuration of EPS blocks which can be implemented for this purpose. It provides a void space atop lifelines which allows settlement of the loading surface with imposing no pressure on the lifelines system. This paper investigates the efficiency of the configuration of post-beam system subjected to static loading. To evaluate the soil surface settlement, beam deformation and transferred pressure over the beam, laboratory tests using two different densities for EPS blocks are conducted. The effect of geogrid-reinforcing the cover soil on system response is also investigated. The experimental results show favorable performance of EPS post and beam configuration in protecting underground lifelines.Keywords: beam deformation, EPS block, laboratory test, post-Beam system, soil surface settlement
Procedia PDF Downloads 2383645 Can the Intervention of SCAMPER Bring about Changes of Neural Activation While Taking Creativity Tasks?
Authors: Yu-Chu Yeh, WeiChin Hsu, Chih-Yen Chang
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Substitution, combination, modification, putting to other uses, elimination, and rearrangement (SCAMPER) has been regarded as an effective technique that provides a structured way to help people to produce creative ideas and solutions. Although some neuroscience studies regarding creativity training have been conducted, no study has focused on SCAMPER. This study therefore aimed at examining whether the learning of SCAMPER through video tutorials would result in alternations of neural activation. Thirty college students were randomly assigned to the experimental group or the control group. The experimental group was requested to watch SCAMPER videos, whereas the control group was asked to watch natural-scene videos which were regarded as neutral stimulating materials. Each participant was brain scanned in a Functional magnetic resonance imaging (fMRI) machine while undertaking a creativity test before and after watching the videos. Furthermore, a two-way ANOVA was used to analyze the interaction between groups (the experimental group; the control group) and tasks (C task; M task; X task). The results revealed that the left precuneus significantly activated in the interaction of groups and tasks, as well as in the main effect of group. Furthermore, compared with the control group, the experimental group had greater activation in the default mode network (left precuneus and left inferior parietal cortex) and the motor network (left postcentral gyrus and left supplementary area). The findings suggest that the SCAMPER training may facilitate creativity through the stimulation of the default mode network and the motor network.Keywords: creativity, default mode network, neural activation, SCAMPER
Procedia PDF Downloads 1013644 Understanding the Multilingualism of the Mauritian Multilingual Primary School Learner and Translanguaging: A Linguistic Ethnographic Study
Authors: Yesha Devi Mahadeo-Doorgakant
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The Mauritian landscape is well-known for its multilingualism with the daily interaction of the number of languages that are used in the island; namely Kreol Morisien, the European languages (English and French) and the Oriental/Asian languages (Hindi, Arabic/Urdu, Tamil, Telegu, Marathi, Mandarin, etc.). However, within Mauritius’ multilingual educational system, English is the official medium of instruction while French is taught as compulsory subject till upper secondary and oriental languages are offered as optional languages at primary level. Usually, Mauritians choose one oriental language based on their ethnic/religious identity, when they start their primary schooling as an additional language to learn. In January 2012, Kreol Morisien, which is the considered the language of daily interaction of the majority of Mauritians, was introduced as an optional subject at primary level, taught at the same time as the oriental languages. The introduction of Kreol Morisien has spurred linguistic debates about the issue of multilingualism within the curriculum. Taking this into account, researchers have started pondering on the multilingual educational system of the country and questioning whether the current language curriculum caters for the complex everyday linguistic reality of the multilingual Mauritian learner, given most learners are embedded within an environment where the different languages interact with each other daily. This paper, therefore, proposes translanguaging as being a more befitting theoretical lens through which the multilingualism and the linguistic repertoire of Mauritian learners’ can best be understood.Keywords: multilingualism, translanguaging, multilingual learner, linguistic ethnography
Procedia PDF Downloads 1713643 Mobile Microscope for the Detection of Pathogenic Cells Using Image Processing
Authors: P. S. Surya Meghana, K. Lingeshwaran, C. Kannan, V. Raghavendran, C. Priya
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One of the most basic and powerful tools in all of science and medicine is the light microscope, the fundamental device for laboratory as well as research purposes. With the improving technology, the need for portable, economic and user-friendly instruments is in high demand. The conventional microscope fails to live up to the emerging trend. Also, adequate access to healthcare is not widely available, especially in developing countries. The most basic step towards the curing of a malady is the diagnosis of the disease itself. The main aim of this paper is to diagnose Malaria with the most common device, cell phones, which prove to be the immediate solution for most of the modern day needs with the development of wireless infrastructure allowing to compute and communicate on the move. This opened up the opportunity to develop novel imaging, sensing, and diagnostics platforms using mobile phones as an underlying platform to address the global demand for accurate, sensitive, cost-effective, and field-portable measurement devices for use in remote and resource-limited settings around the world.Keywords: cellular, hand-held, health care, image processing, malarial parasites, microscope
Procedia PDF Downloads 2673642 Fluid-Structure Interaction Study of Fluid Flow past Marine Turbine Blade Designed by Using Blade Element Theory and Momentum Theory
Authors: Abu Afree Andalib, M. Mezbah Uddin, M. Rafiur Rahman, M. Abir Hossain, Rajia Sultana Kamol
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This paper deals with the analysis of flow past the marine turbine blade which is designed by using the blade element theory and momentum theory for the purpose of using in the field of renewable energy. The designed blade is analyzed for various parameters using FSI module of Ansys. Computational Fluid Dynamics is used for the study of fluid flow past the blade and other fluidic phenomena such as lift, drag, pressure differentials, energy dissipation in water. Finite Element Analysis (FEA) module of Ansys was used to analyze the structural parameter such as stress and stress density, localization point, deflection, force propagation. Fine mesh is considered in every case for more accuracy in the result according to computational machine power. The relevance of design, search and optimization with respect to complex fluid flow and structural modeling is considered and analyzed. The relevancy of design and optimization with respect to complex fluid for minimum drag force using Ansys Adjoint Solver module is analyzed as well. The graphical comparison of the above-mentioned parameter using CFD and FEA and subsequently FSI technique is illustrated and found the significant conformity between both the results.Keywords: blade element theory, computational fluid dynamics, finite element analysis, fluid-structure interaction, momentum theory
Procedia PDF Downloads 3023641 Evaluation of Two Earliness Cotton Genotypes in Three Ecological Regions
Authors: Gholamhossein Hosseini
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Two earliness cotton genotypes I and II, which had been developed by hybridization and backcross methods between sindise-80 as an early maturing gene parent and two other lines i.e. Red leaf and Bulgare-557 as a second parent, are subjected to different environmental conditions. The early maturing genotypes with coded names of I and II were compared with four native cotton cultivars in randomized complete block design (RCBD) with four replications in three ecological regions of Iran from 2016-2017. Two early maturing genotypes along with four native cultivars viz. Varamin, Oltan, Sahel and Arya were planted in Agricultural Research Station of Varamin, Moghan and Kashmar for evaluation. Earliness data were collected for six treatments during two years in the three regions except missing data for the second year of Kashmar. Therefore, missed data were estimated and imputed. For testing the homogeneity of error variances, each experiment at a given location or year is analyzed separately using Hartley and Bartlett’s Chi-square tests and both tests confirmed homogeneity of variance. Combined analysis of variance showed that genotypes I and II were superior in Varamin, Moghan and Kashmar regions. Earliness means and their interaction effects were compared with Duncan’s multiple range tests. Finally combined analysis of variance showed that genotypes I and II were superior in Varamin, Moghan and Kashmar regions. Earliness means and their interaction effects are compared with Duncan’s multiple range tests.Keywords: cotton, combined, analysis, earliness
Procedia PDF Downloads 1433640 The Factors Constitute the Interaction between Teachers and Students: An Empirical Study at the Notion of Framing
Authors: Tien-Hui Chiang
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The code theory, proposed by Basil Bernstein, indicates that framing can be viewed as the core element in constituting the phenomenon of cultural reproduction because it is able to regulate the transmission of pedagogical information. Strong framing increases the social relation boundary between a teacher and pupils, which obstructs information transmission, so that in order to improve underachieving students’ academic performances, teachers need to reduce to strength of framing. Weak framing enables them to transform academic knowledge into commonsense knowledge in daily life language. This study posits that most teachers would deliver strong framing due to their belief mainly confined within the aspect of instrumental rationality that deprives their critical minds. This situation could make them view the normal distribution bell curve of students’ academic performances as a natural outcome. In order to examine the interplay between framing, instrumental rationality and pedagogical action, questionnaires were completed by over 5,000 primary school teachers in Henan province, China, who were stratified sample. The statistical results show that most teachers employed psychological concepts to measure students’ academic performances and, in turn, educational inequity was legitimatized as a natural outcome in the efficiency-led approach. Such efficiency-led minds made them perform as the agent practicing the mechanism of social control and in turn sustaining the phenomenon of cultural reproduction.Keywords: code, cultural reproduction, framing, instrumental rationality, social relation and interaction
Procedia PDF Downloads 1533639 Biosynthesis of Titanium Dioxide Nanoparticles and Their Antibacterial Property
Authors: Prachi Singh
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This paper presents a low-cost, eco-friendly and reproducible microbe mediated biosynthesis of TiO2 nanoparticles. TiO2 nanoparticles synthesized using the bacterium, Bacillus subtilis, from titanium as a precursor, were confirmed by TEM analysis. The morphological characteristics state spherical shape, with the size of individual or aggregate nanoparticles, around 30-40 nm. Microbial resistance represents a challenge for the scientific community to develop new bioactive compounds. Here, the antibacterial effect of TiO2 nanoparticles on Escherichia coli was investigated, which was confirmed by CFU (Colony-forming unit). Further, growth curve study of E. coli Hb101 in the presence and absence of TiO2 nanoparticles was done. Optical density decrease was observed with the increase in the concentration of TiO2. It could be attributed to the inactivation of cellular enzymes and DNA by binding to electron-donating groups such as carboxylates, amides, indoles, hydroxyls, thiols, etc. which cause little pores in bacterial cell walls, leading to increased permeability and cell death. This justifies that TiO2 nanoparticles have efficient antibacterial effect and have potential to be used as an antibacterial agent for different purposes.Keywords: antibacterial effect, CFU, Escherichia coli Hb101, growth curve, TEM, TiO2 nanoparticle, Toxicity, UV-Vis
Procedia PDF Downloads 2963638 Identification and Characterization of Small Peptides Encoded by Small Open Reading Frames using Mass Spectrometry and Bioinformatics
Authors: Su Mon Saw, Joe Rothnagel
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Short open reading frames (sORFs) located in 5’UTR of mRNAs are known as uORFs. Characterization of uORF-encoded peptides (uPEPs) i.e., a subset of short open reading frame encoded peptides (sPEPs) and their translation regulation lead to understanding of causes of genetic disease, proteome complexity and development of treatments. Existence of uORFs within cellular proteome could be detected by LC-MS/MS. The ability of uORF to be translated into uPEP and achievement of uPEP identification will allow uPEP’s characterization, structures, functions, subcellular localization, evolutionary maintenance (conservation in human and other species) and abundance in cells. It is hypothesized that a subset of sORFs are translatable and that their encoded sPEPs are functional and are endogenously expressed contributing to the eukaryotic cellular proteome complexity. This project aimed to investigate whether sORFs encode functional peptides. Liquid chromatography-mass spectrometry (LC-MS) and bioinformatics were thus employed. Due to probable low abundance of sPEPs and small in sizes, the need for efficient peptide enrichment strategies for enriching small proteins and depleting the sub-proteome of large and abundant proteins is crucial for identifying sPEPs. Low molecular weight proteins were extracted using SDS-PAGE from Human Embryonic Kidney (HEK293) cells and Strong Cation Exchange Chromatography (SCX) from secreted HEK293 cells. Extracted proteins were digested by trypsin to peptides, which were detected by LC-MS/MS. The MS/MS data obtained was searched against Swiss-Prot using MASCOT version 2.4 to filter out known proteins, and all unmatched spectra were re-searched against human RefSeq database. ProteinPilot v5.0.1 was used to identify sPEPs by searching against human RefSeq, Vanderperre and Human Alternative Open Reading Frame (HaltORF) databases. Potential sPEPs were analyzed by bioinformatics. Since SDS PAGE electrophoresis could not separate proteins <20kDa, this could not identify sPEPs. All MASCOT-identified peptide fragments were parts of main open reading frame (mORF) by ORF Finder search and blastp search. No sPEP was detected and existence of sPEPs could not be identified in this study. 13 translated sORFs in HEK293 cells by mass spectrometry in previous studies were characterized by bioinformatics. Identified sPEPs from previous studies were <100 amino acids and <15 kDa. Bioinformatics results showed that sORFs are translated to sPEPs and contribute to proteome complexity. uPEP translated from uORF of SLC35A4 was strongly conserved in human and mouse while uPEP translated from uORF of MKKS was strongly conserved in human and Rhesus monkey. Cross-species conserved uORFs in association with protein translation strongly suggest evolutionary maintenance of coding sequence and indicate probable functional expression of peptides encoded within these uORFs. Translation of sORFs was confirmed by mass spectrometry and sPEPs were characterized with bioinformatics.Keywords: bioinformatics, HEK293 cells, liquid chromatography-mass spectrometry, ProteinPilot, Strong Cation Exchange Chromatography, SDS-PAGE, sPEPs
Procedia PDF Downloads 1883637 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
Procedia PDF Downloads 1053636 The Human Rights Code: Fundamental Rights as the Basis of Human-Robot Coexistence
Authors: Gergely G. Karacsony
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Fundamental rights are the result of thousand years’ progress of legislation, adjudication and legal practice. They serve as the framework of peaceful cohabitation of people, protecting the individual from any abuse by the government or violation by other people. Artificial intelligence, however, is the development of the very recent past, being one of the most important prospects to the future. Artificial intelligence is now capable of communicating and performing actions the same way as humans; such acts are sometimes impossible to tell from actions performed by flesh-and-blood people. In a world, where human-robot interactions are more and more common, a new framework of peaceful cohabitation is to be found. Artificial intelligence, being able to take part in almost any kind of interaction where personal presence is not necessary without being recognized as a non-human actor, is now able to break the law, violate people’s rights, and disturb social peace in many other ways. Therefore, a code of peaceful coexistence is to be found or created. We should consider the issue, whether human rights can serve as the code of ethical and rightful conduct in the new era of artificial intelligence and human coexistence. In this paper, we will examine the applicability of fundamental rights to human-robot interactions as well as to the actions of artificial intelligence performed without human interaction whatsoever. Robot ethics has been a topic of discussion and debate of philosophy, ethics, computing, legal sciences and science fiction writing long before the first functional artificial intelligence has been introduced. Legal science and legislation have approached artificial intelligence from different angles, regulating different areas (e.g. data protection, telecommunications, copyright issues), but they are only chipping away at the mountain of legal issues concerning robotics. For a widely acceptable and permanent solution, a more general set of rules would be preferred to the detailed regulation of specific issues. We argue that human rights as recognized worldwide are able to be adapted to serve as a guideline and a common basis of coexistence of robots and humans. This solution has many virtues: people don’t need to adjust to a completely unknown set of standards, the system has proved itself to withstand the trials of time, legislation is easier, and the actions of non-human entities are more easily adjudicated within their own framework. In this paper we will examine the system of fundamental rights (as defined in the most widely accepted source, the 1966 UN Convention on Human Rights), and try to adapt each individual right to the actions of artificial intelligence actors; in each case we will examine the possible effects on the legal system and the society of such an approach, finally we also examine its effect on the IT industry.Keywords: human rights, robot ethics, artificial intelligence and law, human-robot interaction
Procedia PDF Downloads 2443635 Effects of Clozapine and Risperidone Antipsychotic Drugs on the Expression of CACNA1C and Behavioral Changes in Rat ‘Ketamine Model of Schizophrenia
Authors: Mehrnoosh Azimi Sanavi, Hamed Ghazvini, Mehryar Zargari, Hossein Ghalehnoei, Zahra Hosseini-khah
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Objectives: Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C) is one of the most important genes associated with schizophrenia. Methods: 45 male Wistar rats were divided into 5 groups: saline, control, ketamine, clozapine, and risperidone. Animals in ketamine, risperidone, and clozapine groups received ketamine (30 mg/ kg-i.p.) for 10 days. After the last injection of ketamine, we started injecting clozapine (7.5 mg/kg-i.p.) risperidone (1 mg/kg-i.p.) for up to 28 days. Twenty-four hours after the last injection, open field, social interaction, and elevated plus-maze tests, and gene expression in the hippocampus were performed. Results: The results of the social interaction test revealed a significant decrease in cumulative time with ketamine compared with the saline group and an increase with clozapine and risperidone compared with the ketamine group. Moreover, results from the elevated plus-maze test demonstrated a critical decrease in open-arm time and an increase in close-arm time with ketamine compared with saline, as well as an increase in open-arm time with risperidone compared with ketamine. Further results revealed a significant increase in rearing and grooming with ketamine compared to saline, as well as a decrease with risperidone and clozapine compared to ketamine. There were no significant differences in CACNA1C gene expression between groups in the rat hippocampus. In brief, the results of this study indicated that clozapine and risperidone could partially improve cognitive impairments in the rat. However, our findings demonstrated that this treatment is not related to CACNA1C gene expression.Keywords: schizophrenia, ketamine, clozapine, risperidone
Procedia PDF Downloads 633634 The Interaction between Blood-Brain Barrier and the Cerebral Lymphatics Proposes Therapeutic Method for Alzheimer’S Disease
Authors: M. Klimova, O. Semyachkina-Glushkovskaya, J. Kurts, E. Zinchenko, N. Navolokin, A. Shirokov, A. Dubrovsky, A. Abdurashitov, A. Terskov, A. Mamedova, I. Agranovich, T. Antonova, I. Blokhina
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The direction for research of Alzheimer's disease is to find an effective non-invasive and non-pharmacological way of treatment. Here we tested our hypothesis that the opening of the blood-brain barrier (BBB) induces activation of lymphatic drainage and clearing functions that can be used as a method for non-invasive stimulation of clearance of beta-amyloid and therapy of Alzheimer’s disease (AD). To test our hypothesis, in this study on healthy male mice we analyzed the interaction between BBB opening by repeated loud music (100-10000 Hz, 100 dB, duration 2 h: 60 sec – sound; 60 sec - pause) and functional changes in the meningeal lymphatic vessels (MLVs). We demonstrate clearance of dextran 70 kDa (i.v. injection), fluorescent beta-amyloid (intrahippocampal injection) and gold nanorods (intracortical injection) via MLV that significantly increased after the opening of BBB. Our studies also demonstrate that the BBB opening was associated with the improvement of neurocognitive status in mice with AD. Thus, we uncover therapeutic effects of BBB opening by loud music, such as non-invasive stimulation of lymphatic clearance of beta-amyloid in mice with AD, accompanied by improvement of their neurocognitive status. Our data are consistent with other results suggesting the therapeutic effect of BBB opening by focused ultrasound without drugs for patients with AD. This research was supported by a grant from RSF 18-75-10033Keywords: Alzheimer's disease, beta-amyloid, blood-brain barrier, meningeal lymphatic vessels, repeated loud music
Procedia PDF Downloads 1423633 A Conceptual Model of the 'Driver – Highly Automated Vehicle' System
Authors: V. A. Dubovsky, V. V. Savchenko, A. A. Baryskevich
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The current trend in the automotive industry towards automatic vehicles is creating new challenges related to human factors. This occurs due to the fact that the driver is increasingly relieved of the need to be constantly involved in driving the vehicle, which can negatively impact his/her situation awareness when manual control is required, and decrease driving skills and abilities. These new problems need to be studied in order to provide road safety during the transition towards self-driving vehicles. For this purpose, it is important to develop an appropriate conceptual model of the interaction between the driver and the automated vehicle, which could serve as a theoretical basis for the development of mathematical and simulation models to explore different aspects of driver behaviour in different road situations. Well-known driver behaviour models describe the impact of different stages of the driver's cognitive process on driving performance but do not describe how the driver controls and adjusts his actions. A more complete description of the driver's cognitive process, including the evaluation of the results of his/her actions, will make it possible to more accurately model various aspects of the human factor in different road situations. This paper presents a conceptual model of the 'driver – highly automated vehicle' system based on the P.K. Anokhin's theory of functional systems, which is a theoretical framework for describing internal processes in purposeful living systems based on such notions as goal, desired and actual results of the purposeful activity. A central feature of the proposed model is a dynamic coupling mechanism between the decision-making of a driver to perform a particular action and changes of road conditions due to driver’s actions. This mechanism is based on the stage by stage evaluation of the deviations of the actual values of the driver’s action results parameters from the expected values. The overall functional structure of the highly automated vehicle in the proposed model includes a driver/vehicle/environment state analyzer to coordinate the interaction between driver and vehicle. The proposed conceptual model can be used as a framework to investigate different aspects of human factors in transitions between automated and manual driving for future improvements in driving safety, and for understanding how driver-vehicle interface must be designed for comfort and safety. A major finding of this study is the demonstration that the theory of functional systems is promising and has the potential to describe the interaction of the driver with the vehicle and the environment.Keywords: automated vehicle, driver behavior, human factors, human-machine system
Procedia PDF Downloads 1473632 Three Dimensional Large Eddy Simulation of Blood Flow and Deformation in an Elastic Constricted Artery
Authors: Xi Gu, Guan Heng Yeoh, Victoria Timchenko
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In the current work, a three-dimensional geometry of a 75% stenosed blood vessel is analysed. Large eddy simulation (LES) with the help of a dynamic subgrid scale Smagorinsky model is applied to model the turbulent pulsatile flow. The geometry, the transmural pressure and the properties of the blood and the elastic boundary were based on clinical measurement data. For the flexible wall model, a thin solid region is constructed around the 75% stenosed blood vessel. The deformation of this solid region was modelled as a deforming boundary to reduce the computational cost of the solid model. Fluid-structure interaction is realised via a two-way coupling between the blood flow modelled via LES and the deforming vessel. The information of the flow pressure and the wall motion was exchanged continually during the cycle by an arbitrary lagrangian-eulerian method. The boundary condition of current time step depended on previous solutions. The fluctuation of the velocity in the post-stenotic region was analysed in the study. The axial velocity at normalised position Z=0.5 shows a negative value near the vessel wall. The displacement of the elastic boundary was concerned in this study. In particular, the wall displacement at the systole and the diastole were compared. The negative displacement at the stenosis indicates a collapse at the maximum velocity and the deceleration phase.Keywords: Large Eddy Simulation, Fluid Structural Interaction, constricted artery, Computational Fluid Dynamics
Procedia PDF Downloads 2953631 Access to the Forest Ecosystem Services: Understanding the Interaction between Livelihood Capitals and Access
Authors: Abu S. M. G. Kibria, Alison M. Behie, Robert Costanza, Colin Groves, Tracy Farrell
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This study is aimed to understand the level of access and the influence of livelihood capitals in maintaining access and control of ecosystem services (ESS) in the Sundarbans, Bangladesh. Besides the villagers, we consider other stakeholders including the forest department, coast guard, police, merchants, pirates and villagers who ‘controlled’ or ‘maintained’ access to ESS (crab catching, shrimp fry, honey, shrimp, mixed fish, fuel wood) in this region. Villagers used human, physical, natural and social capitals to gain access to ESS. The highest level of access was observed in crab catching and the lowest was found in honey collection, both of which were done when balancing the costs and benefits of accessing one ESS against another. The outcomes of these ongoing access negotiations were determined by livelihood capitals of the households. In addition, it was often found that the certain variables could have a positive effect on one ESS and a negative effect on another. For instance, human, social and natural capitals (eldest daughter’s education and No. of livelihood group membership and) had significant positive effects on honey collection while two components of human and social capitals including ‘eldest son’s education’ and ‘severity of pirate problem’ had exactly the opposite impact. These complex interactions were also observed in access to other ESS. It thus seems that access to ESS is not anything which is provided, but rather it is achieved by using livelihood capitals. Protecting any ecosystem from over exploitation and improve wellbeing can be achieved by properly balancing the livelihood capital-access nexus.Keywords: provisioning services, access level, livelihood capital, interaction, access gain
Procedia PDF Downloads 2833630 Visualisation in Health Communication: Taking Weibo Interaction in COVD19 as the Example
Authors: Zicheng Zhang, Linli Zhang
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As China's biggest social media platform, Weibo has taken on essential health communication responsibilities during the pandemic. This research takes 105 posters in 15 health-related official Weibo accounts as the analysis objects to explore COVID19 health information communication and visualisation. First, the interaction between the audiences and Weibo, including forwarding, comments, and likes, is statistically analysed. The comments about the information design are extracted manually, and then the sentiment analysis is carried out to verdict audiences' views about the poster's design. The forwarding and comments are quantified as the attention index for a reference to the degree of likes. In addition, this study also designed an evaluation scale based on the standards of Health Literacy Resource by the Centers for Medicare& Medicaid Services (US). Then designers scored all selected posters one by one. Finally, combining the data of the two parts, concluded that: 1. To a certain extent, people think that the posters do not deliver substantive and practical information; 2. Non-knowledge posters(i.e., cartoon posters) gained more Forwarding and Likes, such as Go, Wuhan poster; 3. The analysis of COVID posters is still mainly picture-oriented, mainly about encouraging people to overcome difficulties; 4. Posters for pandemic prevention usually contain more text and fewer illustrations and do not clearly show cultural differences. In conclusion, health communication usually involves a lot of professional knowledge, so visualising that knowledge in an accessible way for the general public is challenging. The relevant posters still have the problems of lack of effective communication, superficial design, and insufficient content accessibility.Keywords: weibo, visualisation, covid posters, poster design
Procedia PDF Downloads 1293629 Web-Based Cognitive Writing Instruction (WeCWI): A Theoretical-and-Pedagogical e-Framework for Language Development
Authors: Boon Yih Mah
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Web-based Cognitive Writing Instruction (WeCWI)’s contribution towards language development can be divided into linguistic and non-linguistic perspectives. In linguistic perspective, WeCWI focuses on the literacy and language discoveries, while the cognitive and psychological discoveries are the hubs in non-linguistic perspective. In linguistic perspective, WeCWI draws attention to free reading and enterprises, which are supported by the language acquisition theories. Besides, the adoption of process genre approach as a hybrid guided writing approach fosters literacy development. Literacy and language developments are interconnected in the communication process; hence, WeCWI encourages meaningful discussion based on the interactionist theory that involves input, negotiation, output, and interactional feedback. Rooted in the e-learning interaction-based model, WeCWI promotes online discussion via synchronous and asynchronous communications, which allows interactions happened among the learners, instructor, and digital content. In non-linguistic perspective, WeCWI highlights on the contribution of reading, discussion, and writing towards cognitive development. Based on the inquiry models, learners’ critical thinking is fostered during information exploration process through interaction and questioning. Lastly, to lower writing anxiety, WeCWI develops the instructional tool with supportive features to facilitate the writing process. To bring a positive user experience to the learner, WeCWI aims to create the instructional tool with different interface designs based on two different types of perceptual learning style.Keywords: WeCWI, literacy discovery, language discovery, cognitive discovery, psychological discovery
Procedia PDF Downloads 5623628 Text Emotion Recognition by Multi-Head Attention based Bidirectional LSTM Utilizing Multi-Level Classification
Authors: Vishwanath Pethri Kamath, Jayantha Gowda Sarapanahalli, Vishal Mishra, Siddhesh Balwant Bandgar
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Recognition of emotional information is essential in any form of communication. Growing HCI (Human-Computer Interaction) in recent times indicates the importance of understanding of emotions expressed and becomes crucial for improving the system or the interaction itself. In this research work, textual data for emotion recognition is used. The text being the least expressive amongst the multimodal resources poses various challenges such as contextual information and also sequential nature of the language construction. In this research work, the proposal is made for a neural architecture to resolve not less than 8 emotions from textual data sources derived from multiple datasets using google pre-trained word2vec word embeddings and a Multi-head attention-based bidirectional LSTM model with a one-vs-all Multi-Level Classification. The emotions targeted in this research are Anger, Disgust, Fear, Guilt, Joy, Sadness, Shame, and Surprise. Textual data from multiple datasets were used for this research work such as ISEAR, Go Emotions, Affect datasets for creating the emotions’ dataset. Data samples overlap or conflicts were considered with careful preprocessing. Our results show a significant improvement with the modeling architecture and as good as 10 points improvement in recognizing some emotions.Keywords: text emotion recognition, bidirectional LSTM, multi-head attention, multi-level classification, google word2vec word embeddings
Procedia PDF Downloads 1743627 Presence, Distribution and Form of Calcium Oxalate Crystals in Relation to Age of Actinidia Deliciosa Leaves and Petioles
Authors: Muccifora S., Rinallo C., Bellani L.
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Calcium (Ca²+) is an element essential to the plant being involved in plant growth and development. At high concentrations, it is toxic and can influence every stage, process and cellular activity of plant life. Given its toxicity, cells implement mechanisms to compartmentalize calcium in a vacuole, endoplasmic reticulum, mitochondria, plastids and cell wall. One of the most effective mechanisms to reduce the excess of calcium, thus avoiding cellular damage, is its complexation with oxalic acid to form calcium oxalate crystals that are no longer osmotically or physiologically active. However, the sequestered calcium can be mobilized when the plant needs it. Calcium crystals can be accumulated in the vacuole of specialized sink-cells called idioblasts, with different crystalline forms (druse, raphyde and styloid) of diverse physiological meanings. Actinidia deliciosa cv. Hayward presents raphydes and styloid localized in idioblasts in cells of photosynthetic and non-photosynthetic tissues. The purpose of this work was to understand if there is a relationship between the age of Actinidia leaves and the presence, distribution, dimension and shape of oxalate crystals by means of light, fluorescent, polarized and transmission electron microscopy. Three vines from female plants were chosen at the beginning of the season and used throughout the study. The leaves with petioles were collected at various stages of development from the bottom to the shoot of the plants monthly from April to July. The samples were taken in corresponding areas of the central and lateral parts of the leaves and of the basal portion of the petiole. The results showed that in the leaves, the number of raphyde idioblasts decreased with the progress of the growing season, while the styloid idioblasts increased progressively, becoming very numerous in the upper nodes of July. In June and in July samples, in the vacuoles of the highest nodes, a portion regular in shape strongly stained with rubeanic acid was present. Moreover, the chlortetracycline (CTC) staining for localization of free calcium marked the wall of the idioblasts and the wall of the cells near vascular bundles. In April petiole samples, moving towards the youngest nodes, the raphydes idioblast decreased in number and in the length of the single raphydes. Besides, crystals stained with rubeanic acid appeared in the vacuoles of some cells. In June samples, numerous raphyde idioblasts oriented parallel to vascular bundles were evident. Under the electron microscope, numerous idioblasts presented not homogeneous electrondense aggregates of material, in which a few crystals (styloids) in the form of regular holes were scattered. In July samples, an increase in the number of styloid idioblasts in the youngest nodes and little masses stained with CTC near styloids were observed. Peculiar cells stained with rubeanic acid were detected and hypothesized to be involved in the formation of the idioblasts. In conclusion, in Actinidia leaves and petioles, it seems to confirm the hypothesis that the formation of styloid idioblasts can be correlated to increasing calcium levels in growing tissues.Keywords: calcium oxalate crystals, actinidia deliciosa, light and electron microscopy, idioblasts
Procedia PDF Downloads 843626 Building on Previous Microvalving Approaches for Highly Reliable Actuation in Centrifugal Microfluidic Platforms
Authors: Ivan Maguire, Ciprian Briciu, Alan Barrett, Dara Kervick, Jens Ducrèe, Fiona Regan
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With the ever-increasing myriad of applications of which microfluidic devices are capable, reliable fluidic actuation development has remained fundamental to the success of these microfluidic platforms. There are a number of approaches which can be taken in order to integrate liquid actuation on microfluidic platforms, which can usually be split into two primary categories; active microvalves and passive microvalves. Active microvalves are microfluidic valves which require a physical parameter change by external, or separate interaction, for actuation to occur. Passive microvalves are microfluidic valves which don’t require external interaction for actuation due to the valve’s natural physical parameters, which can be overcome through sample interaction. The purpose of this paper is to illustrate how further improvements to past microvalve solutions can largely enhance systematic reliability and performance, with both novel active and passive microvalves demonstrated. Covered within this scope will be two alternative and novel microvalve solutions for centrifugal microfluidic platforms; a revamped pneumatic-dissolvable film active microvalve (PAM) strategy and a spray-on Sol-Gel based hydrophobic passive microvalve (HPM) approach. Both the PAM and the HPM mechanisms were demonstrated on a centrifugal microfluidic platform consisting of alternating layers of 1.5 mm poly(methyl methacrylate) (PMMA) (for reagent storage) sheets and ~150 μm pressure sensitive adhesive (PSA) (for microchannel fabrication) sheets. The PAM approach differs from previous SOLUBON™ dissolvable film methods by introducing a more reliable and predictable liquid delivery mechanism to microvalve site, thus significantly reducing premature activation. This approach has also shown excellent synchronicity when performed in a multiplexed form. The HPM method utilises a new spray-on and low curing temperature (70°C) sol-gel material. The resultant double layer coating comprises a PMMA adherent sol-gel as the bottom layer and an ultra hydrophobic silica nano-particles (SNPs) film as the top layer. The optimal coating was integrated to microfluidic channels with varying cross-sectional area for assessing microvalve burst frequencies consistency. It is hoped that these microvalving solutions, which can be easily added to centrifugal microfluidic platforms, will significantly improve automation reliability.Keywords: centrifugal microfluidics, hydrophobic microvalves, lab-on-a-disc, pneumatic microvalves
Procedia PDF Downloads 1893625 The Expression of a Novel Gene Encoding an Ankyrin-Repeat Protein, DRA1, Is Regulated by Drought-Responsive Alternative Splicing
Authors: H. Sakamoto, Y. Nakagawara, S. Oguri
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Drought stress is a critical environmental factor that adversely affects crop productivity and quality. Because of their immobile nature, plants have evolved mechanisms to sense and respond to drought stress. We identified a novel locus of Arabidopsis, designated DRA1 (drought responsive ankyrin 1), whose disruption leads to increased drought stress tolerance. DRA1 encodes a transmembrane protein with an ankyrin repeat motif that has been implicated in diverse cellular processes such as signal transduction. RT-PCR analysis revealed that there were at least two splicing variants of DRA1 transcripts in wild type plants. In response to drought stress, the levels of DRA1 transcripts retaining second and third introns were increased, whereas these introns were removed under unstressed conditions. These results suggest that DRA1 protein may negatively regulate plant drought tolerance and that the expression of DRA1 is regulated in response to drought stress by alternative splicing.Keywords: alternative splicing, ankyrin repeat, Arabidopsis, drought tolerance
Procedia PDF Downloads 3263624 Study on the Effects of Indigenous Biological Face Treatment
Authors: Saron Adisu Gezahegn
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Commercial cosmetic has been affecting human health due to their contents and dosage composition. Chemical base cosmetics exposes users to unnecessary health problems and financial cost. Some of the cosmetics' interaction with the environment has negative impacts on health such as burning, cracking, coloring, and so on. The users are looking for a temporary service without evaluating the side effects of cosmetics that contain chemical compositions that result in irritation, burning, allergies, cracking, and the nature of the face. Every cosmetic contains a heavy metal such as lead, zinc, cadmium, silicon, and other heavy cosmetics materials. The users may expose at the end of the day to untreatable diseases like cancer. The objective of the research is to study the effects of indigenous biological face treatment without any additives like chemicals. In ancient times this thought was highly tremendous in the world but things were changing bit by bit and reached chemical base cosmetics to maintain the beauty of hair, skin, and faces. The side effects of the treatment on the face were minimum and the side effects with the interaction of the environment were almost nil. But this thought is changed and replaces the indigenous substances with chemical substances by adding additives like heavy chemical lead and cadmium in the sense of preservation, pigments, dye, and shining. Various studies indicated that cosmetics have dangerous side effects that expose users to health problems and expensive financial loss. This study focuses on a local indigenous plant called Kulkual. Kulkual is available everywhere in a study area and sustainable products can harvest to use as indigenous face treatment materials.25 men and 25 women were selected as a sample population randomly to conduct the study effectively.The plant is harvested from the guard in the productive season. The plant was exposed to the sun dry for a week. Then the peel was removed from the plant fruit and the peels were taken to a bath filled with water to soak for three days. Then the flesh of the peel was avoided from the fruit and ready to use as a face treatment. The fleshy peel was smeared on each sample for almost a week and continued for a week. The result indicated that the effects of the treatment were a positive response with minimum cost and minimum side effects due to the environment. The beauty shines, smoothness, and color are better than chemical base cosmetics. Finally, the study is recommended that all users prefer a biological method of treatment with minimum cost and minimums side effects on health with the interaction of the environment.Keywords: cosmetic, indigneous, heavymetals, toxic
Procedia PDF Downloads 1093623 An In-Depth Conceptual Framework for the Development of Prosthetic Hands: Emphasizing Transradial Prostheses
Authors: Touil Issam, Bouraghda Skander
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The human hand is a vital yet intricate organ, essential for tasks ranging from grasping to executing fine motor skills. It serves as the most advanced and natural interface for interaction between humans and their surroundings. Upper-limb deficiencies, caused by conditions such as illness, accidents, or congenital factors, are prevalent worldwide. These deficiencies are categorized into seven types: partial hand, wrist disarticulation, transradial, elbow disarticulation, transhumeral, shoulder disarticulation, and forequarter, with transradial amputations being the most common and often well-suited for prosthetic hands. Advancements in technology and healthcare services have amplified the need for affordable, user-friendly, and functional prosthetic hands capable of restoring essential hand and finger functions. As a critical subset of medical robotics, prosthetic hands have seen notable design and development progress. However, challenges remain in achieving widespread user acceptance and satisfaction, highlighting the need for a holistic approach to their design and implementation. This study aims to consolidate the various factors involved in the development of prosthetic hands, focusing particularly on transradial prosthetics. It considers all types of prosthetic hands, whether actively powered, passively powered, or nonpowered. By presenting a comprehensive concept map, we aim to integrate these factors into a cohesive framework, guiding the development of prosthetic hands that offer enhanced functionality, improved user acceptance, and better alignment with user.Keywords: prosthetic hands, user-centeren design, human machine interaction design, assistive technologies, meical robotics
Procedia PDF Downloads 43622 A Human Centered Design of an Exoskeleton Using Multibody Simulation
Authors: Sebastian Kölbl, Thomas Reitmaier, Mathias Hartmann
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Trial and error approaches to adapt wearable support structures to human physiology are time consuming and elaborate. However, during preliminary design, the focus lies on understanding the interaction between exoskeleton and the human body in terms of forces and moments, namely body mechanics. For the study at hand, a multi-body simulation approach has been enhanced to evaluate actual forces and moments in a human dummy model with and without a digital mock-up of an active exoskeleton. Therefore, different motion data have been gathered and processed to perform a musculosceletal analysis. The motion data are ground reaction forces, electromyography data (EMG) and human motion data recorded with a marker-based motion capture system. Based on the experimental data, the response of the human dummy model has been calibrated. Subsequently, the scalable human dummy model, in conjunction with the motion data, is connected with the exoskeleton structure. The results of the human-machine interaction (HMI) simulation platform are in particular resulting contact forces and human joint forces to compare with admissible values with regard to the human physiology. Furthermore, it provides feedback for the sizing of the exoskeleton structure in terms of resulting interface forces (stress justification) and the effect of its compliance. A stepwise approach for the setup and validation of the modeling strategy is presented and the potential for a more time and cost-effective development of wearable support structures is outlined.Keywords: assistive devices, ergonomic design, inverse dynamics, inverse kinematics, multibody simulation
Procedia PDF Downloads 1643621 Defective Autophagy Disturbs Neural Migration and Network Activity in hiPSC-Derived Cockayne Syndrome B Disease Models
Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche
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It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells
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