Search results for: psoriasis mechanism of action
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Paper Count: 5296

Search results for: psoriasis mechanism of action

4996 The 5-HT1A Receptor Biased Agonists, NLX-101 and NLX-204, Elicit Rapid-Acting Antidepressant Activity in Rat Similar to Ketamine and via GABAergic Mechanisms

Authors: A. Newman-Tancredi, R. Depoortère, P. Gruca, E. Litwa, M. Lason, M. Papp

Abstract:

The N-methyl-D-aspartic acid (NMDA) receptor antagonist, ketamine, can elicit rapid-acting antidepressant (RAAD) effects in treatment-resistant patients, but it requires parenteral co-administration with a classical antidepressant under medical supervision. In addition, ketamine can also produce serious side effects that limit its long-term use, and there is much interest in identifying RAADs based on ketamine’s mechanism of action but with safer profiles. Ketamine elicits GABAergic interneuron inhibition, glutamatergic neuron stimulation, and, notably, activation of serotonin 5-HT1A receptors in the prefrontal cortex (PFC). Direct activation of the latter receptor subpopulation with selective ‘biased agonists’ may therefore be a promising strategy to identify novel RAADs and, consistent with this hypothesis, the prototypical cortical biased agonist, NLX-101, exhibited robust RAAD-like activity in the chronic mild stress model of depression (CMS). The present study compared the effects of a novel, selective 5-HT1A receptor-biased agonist, NLX-204, with those of ketamine and NLX-101. Materials and methods: CMS procedure was conducted on Wistar rats; drugs were administered either intraperitoneally (i.p.) or by bilateral intracortical microinjection. Ketamine: 10 mg/kg i.p. or 10 µg/side in PFC; NLX-204 and NLX-101: 0.08 and 0.16 mg/kg i.p. or 16 µg/side in PFC. In addition, interaction studies were carried out with systemic NLX-204 or NLX-101 (each at 0.16 mg/kg i.p.) in combination with intracortical WAY-100635 (selective 5-HT1A receptor antagonist; 2 µg/side) or muscimol (GABA-A receptor agonist, 12.5 ng/side). Anhedonia was assessed by CMS-induced decrease in sucrose solution consumption; anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), and cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Results: A single administration of NLX-204 was sufficient to reverse the CMS-induced deficit in sucrose consumption, similarly to ketamine and NLX-101. NLX-204 also reduced CMS-induced anxiety in the EPM and abolished CMS-induced NOR deficits. These effects were maintained (EPM and NOR) or enhanced (sucrose consumption) over a subsequent 2-week period of treatment. The anti-anhedonic response of the drugs was also maintained for several weeks Following treatment discontinuation, suggesting that they had sustained effects on neuronal networks. A single PFC administration of NLX-204 reversed deficient sucrose consumption, similarly to ketamine and NLX-101. Moreover, the anti-anhedonic activities of systemic NLX-204 and NLX 101 were abolished by coadministration with intracortical WAY-100635 or muscimol. Conclusions: (i) The antidepressant-like activity of NLX-204 in the rat CMS model was as rapid as that of ketamine or NLX-101, supporting targeting cortical 5-HT1A receptors with selective, biased agonists to achieve RAAD effects. (ii)The anti-anhedonic activity of systemic NLX-204 was mimicked by local administration of the compound in the PFC, confirming the involvement of cortical circuits in its RAAD-like effects. (iii) Notably, the effects of systemic NLX-204 and NLX-101 were abolished by PFC administration of muscimol, indicating that they act by (indirectly) eliciting a reduction in cortical GABAergic neurotransmission. This is consistent with ketamine’s mechanism of action and suggests that there are converging NMDA and 5-HT1A receptor signaling cascades in PFC underlying the RAAD-like activities of ketamine and NLX-204. Acknowledgements: The study was financially supported by NCN grant no. 2019/35/B/NZ7/00787.

Keywords: depression, ketamine, serotonin, 5-HT1A receptor, chronic mild stress

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4995 Women's Parliamentary Representation in Uganda: A Relative Analysis of the Pathways of Women on the Open vs. Affirmative Action Seat

Authors: Doreen Chemutai

Abstract:

While women's parliamentary representation has increased over the years, most women contest the affirmative action seat (A.A). There is a lack of knowledge on why women prefer the affirmative seat vis- a- vis the open seat. This study argues that comparing women's path on the reserved and open seat to parliamentary representation enables us to pass judgment on why this trend continues. This paper provides a narrative analysis of women members of parliament's (MPs) trajectory in the open seat and Affirmative Action seat to parliamentary representation. Purposive sampling was used to select participants from the Northern Uganda districts of Kitgum, Pader, Oyam, Agago, and Gulu. The eight women MPs chosen for the study completed in-depth interviews exploring their qualifications, careers, and experiences before joining the political office, their party affiliation, and the kind of seat they currently occupy in the 10th parliament. Findings revealed similarities between women on the open and reserved to include; women generally irrespective of the seat they choose to contest for find it difficult to win elections because voters doubt women's effectiveness as leaders. All women as incumbents find it difficult to be re-elected because their evaluation is harsher than that for men. Findings also revealed that women representatives are motivated by their personal lived experiences, community work, educational leadership, and local leadership. The study establishes that the popularity of the party in a given geographical location and the opponents' quality will determine the success of the parliamentary candidate in question irrespective of whether one is contesting on the open or Affirmative seat. However, the study revealed differences between MPs' experiences in the quest for the parliamentary seat, females on the open seat are subjected to gender discrimination in elections by party leadership, stereotyped, and are victims of propaganda in the initial contesting stages. Women who win elections in the open seat have to be superior to their male opponents. In other circumstances where a woman emerges successful, she may be voted for due to other reasons beyond capability, such as physical appearance or sociability. On the other hand, MPs' revelations on affirmative action seats show that the political terrain is smoother despite larger constituencies. Findings show that women on the Affirmative Action seat do not move to the open seat because of the comfort associated with the seat and maintain consistency, since the constituencies doubt the motives of representatives who change from one seat to another. The study concludes that women MPs who contest on the open seat are likely to suffer structural barriers such as gender discrimination and political recruitment bias instead of women on the affirmative seat. This explains why the majority of women contest on the affirmative seat.

Keywords: affirmative action seats, open seats, parliamentary representation, pathways

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4994 Routing Protocol in Ship Dynamic Positioning Based on WSN Clustering Data Fusion System

Authors: Zhou Mo, Dennis Chow

Abstract:

In the dynamic positioning system (DPS) for vessels, the reliable information transmission between each note basically relies on the wireless protocols. From the perspective of cluster-based routing protocols for wireless sensor networks, the data fusion technology based on the sleep scheduling mechanism and remaining energy in network layer is proposed, which applies the sleep scheduling mechanism to the routing protocols, considering the remaining energy of node and location information when selecting cluster-head. The problem of uneven distribution of nodes in each cluster is solved by the Equilibrium. At the same time, Classified Forwarding Mechanism as well as Redelivery Policy strategy is adopted to avoid congestion in the transmission of huge amount of data, reduce the delay in data delivery and enhance the real-time response. In this paper, a simulation test is conducted to improve the routing protocols, which turn out to reduce the energy consumption of nodes and increase the efficiency of data delivery.

Keywords: DPS for vessel, wireless sensor network, data fusion, routing protocols

Procedia PDF Downloads 514
4993 Sustainable Antimicrobial Biopolymeric Food & Biomedical Film Engineering Using Bioactive AMP-Ag+ Formulations

Authors: Eduardo Lanzagorta Garcia, Chaitra Venkatesh, Romina Pezzoli, Laura Gabriela Rodriguez Barroso, Declan Devine, Margaret E. Brennan Fournet

Abstract:

New antimicrobial interventions are urgently required to combat rising global health and medical infection challenges. Here, an innovative antimicrobial technology, providing price competitive alternatives to antibiotics and readily integratable with currently technological systems is presented. Two cutting edge antimicrobial materials, antimicrobial peptides (AMPs) and uncompromised sustained Ag+ action from triangular silver nanoplates (TSNPs) reservoirs, are merged for versatile effective antimicrobial action where current approaches fail. Antimicrobial peptides (AMPs) exist widely in nature and have recently been demonstrated for broad spectrum of activity against bacteria, viruses, and fungi. TSNP’s are highly discrete, homogenous and readily functionisable Ag+ nanoreseviors that have a proven amenability for operation within in a wide range of bio-based settings. In a design for advanced antimicrobial sustainable plastics, antimicrobial TSNPs are formulated for processing within biodegradable biopolymers. Histone H5 AMP was selected for its reported strong antimicrobial action and functionalized with the TSNP (AMP-TSNP) in a similar fashion to previously reported TSNP biofunctionalisation methods. A synergy between the propensity of biopolymers for degradation and Ag+ release combined with AMP activity provides a novel mechanism for the sustained antimicrobial action of biopolymeric thin films. Nanoplates are transferred from aqueous phase to an organic solvent in order to facilitate integration within hydrophobic polymers. Extrusion is used in combination with calendering rolls to create thin polymerc film where the nanoplates are embedded onto the surface. The resultant antibacterial functional films are suitable to be adapted for food packing and biomedical applications. TSNP synthesis were synthesized by adapting a previously reported seed mediated approach. TSNP synthesis was scaled up for litre scale batch production and subsequently concentrated to 43 ppm using thermally controlled H2O removal. Nanoplates were transferred from aqueous phase to an organic solvent in order to facilitate integration within hydrophobic polymers. This was acomplised by functionalizing the TSNP with thiol terminated polyethylene glycol and using centrifugal force to transfer them to chloroform. Polycaprolactone (PCL) and Polylactic acid (PLA) were individually processed through extrusion, TSNP and AMP-TSNP solutions were sprayed onto the polymer immediately after exiting the dye. Calendering rolls were used to disperse and incorporate TSNP and TSNP-AMP onto the surface of the extruded films. Observation of the characteristic blue colour confirms the integrity of the TSNP within the films. Antimicrobial tests were performed by incubating Gram + and Gram – strains with treated and non-treated films, to evaluate if bacterial growth was reduced due to the presence of the TSNP. The resulting films successfully incorporated TSNP and AMP-TSNP. Reduced bacterial growth was observed for both Gram + and Gram – strains for both TSNP and AMP-TSNP compared with untreated films indicating antimicrobial action. The largest growth reduction was observed for AMP-TSNP treated films demonstrating the additional antimicrobial activity due to the presence of the AMPs. The potential of this technology to impede bacterial activity in food industry and medical surfaces will forge new confidence in the battle against antibiotic resistant bacteria, serving to greatly inhibit infections and facilitate patient recovery.

Keywords: antimicrobial, biodegradable, peptide, polymer, nanoparticle

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4992 Sugar-Induced Stabilization Effect of Protein Structure

Authors: Mitsuhiro Hirai, Satoshi Ajito, Nobutaka Shimizu, Noriyuki Igarashi, Hiroki Iwase, Shinichi Takata

Abstract:

Sugars and polyols are known to be bioprotectants preventing such as protein denaturation and enzyme deactivation and widely used as a nontoxic additive in various industrial and medical products. The mechanism of their protective actions has been explained by specific bindings between biological components and additives, changes in solvent viscosities, and surface tension and free energy changes upon transfer of those components into additive solutions. On the other hand, some organisms having tolerances against extreme environment produce stress proteins and/or accumulate sugars in cells, which is called cryptobiosis. In particular, trehalose has been drawing attention relevant to cryptobiosis under external stress such as high or low temperature, drying, osmotic pressure, and so on. The function of cryptobiosis by trehalose has been explained relevant to the restriction of the intra-and/or-inter-molecular movement by vitrification or from the replacement of water molecule by trehalose. Previous results suggest that the structure and interaction between sugar and water are a key determinant for understanding cryptobiosis. Recently, we have shown direct evidence that the protein hydration (solvation) and structural stability against chemical and thermal denaturation significantly depend on sugar species and glycerol. Sugar and glycerol molecules tend to be preferentially or weakly excluded from the protein surface and preserved the native protein hydration shell. Due to the protective action of the protein hydration shell by those molecules, the protein structure is stabilized against chemical (guanidinium chloride) and thermal denaturation. The protective action depends on sugar species. To understand the above trend and difference in detail, it is essentially important to clarify the characteristics of solutions containing those additives. In this study, by using wide-angle X-ray scattering technique covering a wide spatial region (~3-120 Å), we have clarified structures of sugar solutions with the concentration from 5% w/w to 65% w/w. The sugars measured in the present study were monosaccharides (glucose, fructose, mannose) and disaccharides (sucrose, trehalose, maltose). Due to observed scattering data with a wide spatial resolution, we have succeeded in obtaining information on the internal structure of individual sugar molecules and on the correlation between them. Every sugar gradually shortened the average inter-molecular distance as the concentration increased. The inter-molecular interaction between sugar molecules was essentially showed an exclusive tendency for every sugar, which appeared as the presence of a repulsive correlation hole. This trend was more weakly seen for trehalose compared to other sugars. The intermolecular distance and spread of individual molecule clearly showed the dependence of sugar species. We will discuss the relation between the characteristic of sugar solution and its protective action of biological materials.

Keywords: hydration, protein, sugar, X-ray scattering

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4991 Research on Routing Protocol in Ship Dynamic Positioning Based on WSN Clustering Data Fusion System

Authors: Zhou Mo, Dennis Chow

Abstract:

In the dynamic positioning system (DPS) for vessels, the reliable information transmission between each note basically relies on the wireless protocols. From the perspective of cluster-based routing pro-tocols for wireless sensor networks, the data fusion technology based on the sleep scheduling mechanism and remaining energy in network layer is proposed, which applies the sleep scheduling mechanism to the routing protocols, considering the remaining energy of node and location information when selecting cluster-head. The problem of uneven distribution of nodes in each cluster is solved by the Equilibrium. At the same time, Classified Forwarding Mechanism as well as Redelivery Policy strategy is adopted to avoid congestion in the transmission of huge amount of data, reduce the delay in data delivery and enhance the real-time response. In this paper, a simulation test is conducted to improve the routing protocols, which turns out to reduce the energy consumption of nodes and increase the efficiency of data delivery.

Keywords: DPS for vessel, wireless sensor network, data fusion, routing protocols

Procedia PDF Downloads 442
4990 Ethylene Sensitivity in Orchids and Its Control Using 1-MCP: A Review

Authors: Parviz Almasi

Abstract:

Ethylene is produced as a gaseous growth regulator in all plants and their constructive parts such as roots, stems, leaves, flowers and fruits. It is considered a multifunctional phytohormone that regulates both growths including flowering, fruit ripening, inhibition of root growth, and senescence such as senescence of leaves and flowers and etc. In addition, exposure to external ethylene is caused some changes that are often undesirable and harmful. Some flowers are more sensitive to others and when exposed to ethylene; their aging process is hastened. 1-MCP is an exogenous and endogenous ethylene action inhibitor, which binds to the ethylene receptors in the plants and prevents ethylene-dependent reactions. The binding affinity of 1- MCP for the receptors is about 10 times more than ethylene. Hence, 1-MCP can be a potential candidate for controlling of ethylene injury in horticultural crops. This review integrates knowledge of ethylene biosynthesis in the plants and also a mode of action of 1-MCP in preventing of ethylene injury.

Keywords: ethylene injury, biosynthesis, ethylene sensitivity, 1-MCP

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4989 Collaborative Reflexive/Reflective Teaching and Action Research in TESL

Authors: O. F. Elkommos

Abstract:

Teaching English as a Second Language (TESL) has become a very rich area of research. Practitioners or teachers of English as a foreign or a second language are now promoting both collaborative learning and collaborative teaching. Students learning a language collaboratively and cooperatively are learning in a better environment of team work where they learn from each other. Further, teaching English collaboratively also creates an enriching environment that is also very enriching to students’ and teachers’ experiences of learning and teaching. Moreover, action research stems from actual teacher concerns and students’ needs. Reflection in turn, on the experience of the material taught and the delivery of material is becoming an integral part of the teaching and learning experience self- evaluation and self-development. In this case, the concern of the research field in the area of TESL will be the development of teaching delivery, material and quality of learning. In the present research, the TESL module taught to year two students in the Faculty of Arts and Humanities, British University in Egypt (BUE) will be evaluated reflexively by the students and teachers. The module was taught to students in two different specialisms. It was taught and delivered through collaborative teaching and was evaluated by both teachers and students as very successful and enjoyable. The reflections of both teachers and students as well as student results confirm that it was a success.

Keywords: action research, addressing differentiation, collaborative teaching, reflective teaching and learning, reflexive learning, reflexive teaching, self-development, self-evaluation, TESL

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4988 An Improved Tie Force Method for Progressive Collapse Resistance Design of Precast Concrete Cross Wall Structures

Authors: M. Tohidi, J. Yang, C. Baniotopoulos

Abstract:

Progressive collapse of buildings typically occurs when abnormal loading conditions cause local damages, which leads to a chain reaction of failure and ultimately catastrophic collapse. The tie force (TF) method is one of the main design approaches for progressive collapse. As the TF method is a simplified method, further investigations on the reliability of the method is necessary. This study aims to develop an improved TF method to design the cross wall structures for progressive collapse. To this end, the pullout behavior of strands in grout was firstly analyzed; and then, by considering the tie force-slip relationship in the friction stage together with the catenary action mechanism, a comprehensive analytical method was developed. The reliability of this approach is verified by the experimental results of concrete block pullout tests and full scale floor-to-floor joints tests undertaken by Portland Cement Association (PCA). Discrepancies in the tie force between the analytical results and codified specifications have suggested the deficiency of TF method, hence an improved model based on the analytical results has been proposed to address this concern.

Keywords: cross wall, progressive collapse, ties force method, catenary, analytical

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4987 The Effect of Action Potential Duration and Conduction Velocity on Cardiac Pumping Efficacy: Simulation Study

Authors: Ana Rahma Yuniarti, Ki Moo Lim

Abstract:

Slowed myocardial conduction velocity (CV) and shortened action potential duration (APD) due to some reason are associated with an increased risk of re-entrant excitation, predisposing to cardiac arrhythmia. That is because both of CV reduction and APD shortening induces shortening of wavelength. In this study, we investigated quantitatively the cardiac mechanical responses under various CV and APD using multi-scale computational model of the heart. The model consisted of electrical model coupled with the mechanical contraction model together with a lumped model of the circulatory system. The electrical model consisted of 149.344 numbers of nodes and 183.993 numbers of elements of tetrahedral mesh, whereas the mechanical model consisted of 356 numbers of nodes and 172 numbers of elements of hexahedral mesh with hermite basis. We performed the electrical simulation with two scenarios: 1) by varying the CV values with constant APD and 2) by varying the APD values with constant CV. Then, we compared the electrical and mechanical responses for both scenarios. Our simulation showed that faster CV and longer APD induced largest resultants wavelength and generated better cardiac pumping efficacy by increasing the cardiac output and consuming less energy. This is due to the long wave propagation and faster conduction generated more synchronous contraction of whole ventricle.

Keywords: conduction velocity, action potential duration, mechanical contraction model, circulatory model

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4986 Cognition of Driving Context for Driving Assistance

Authors: Manolo Dulva Hina, Clement Thierry, Assia Soukane, Amar Ramdane-Cherif

Abstract:

In this paper, we presented our innovative way of determining the driving context for a driving assistance system. We invoke the fusion of all parameters that describe the context of the environment, the vehicle and the driver to obtain the driving context. We created a training set that stores driving situation patterns and from which the system consults to determine the driving situation. A machine-learning algorithm predicts the driving situation. The driving situation is an input to the fission process that yields the action that must be implemented when the driver needs to be informed or assisted from the given the driving situation. The action may be directed towards the driver, the vehicle or both. This is an ongoing work whose goal is to offer an alternative driving assistance system for safe driving, green driving and comfortable driving. Here, ontologies are used for knowledge representation.

Keywords: cognitive driving, intelligent transportation system, multimodal system, ontology, machine learning

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4985 Calycosin Ameliorates Osteoarthritis by Regulating the Imbalance Between Chondrocyte Synthesis and Catabolism

Authors: Hong Su, Qiuju Yan, Wei Du, En Hu, Zhaoyu Yang, Wei Zhang, Yusheng Li, Tao Tang, Wang yang, Shushan Zhao

Abstract:

Osteoarthritis (OA) is a severe chronic inflammatory disease. As the main active component of Astragalus mongholicus Bunge, a classic traditional ethnic herb, calycosin exhibits anti-inflammatory action and its mechanism of exact targets for OA have yet to be determined. In this study, we established an anterior cruciate ligament transection (ACLT) mouse model. Mice were randomized to sham, OA, and calycosin groups. Cartilage synthesis markers type II collagen (Col-2) and SRY-Box Transcription Factor 9 (Sox-9) increased significantly after calycosin gavage. While cartilage matrix degradation index cyclooxygenase-2 (COX-2), phosphor-epidermal growth factor receptor (p-EGFR), and matrix metalloproteinase-9 (MMP9) expression were decreased. With the help of network pharmacology and molecular docking, these results were confirmed in chondrocyte ATDC5 cells. Our results indicated that the calycosin treatment significantly improved cartilage damage, this was probably attributed to reversing the imbalance between chondrocyte synthesis and catabolism.

Keywords: calycosin, osteoarthritis, network pharmacology, molecular docking, inflammatory, cyclooxygenase 2

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4984 Collapse Capacity and Energy Absorption Mechanism of High Rise Steel Moment Frame Considering Aftershock Effects

Authors: Mohammadmehdi Torfehnejad, Serhan Sensoy

Abstract:

Many structures sustain damage during a mainshock earthquake but undergo severe damage under aftershocks following the mainshock. Past researches have studied aftershock effects through different methodologies, but few structural systems have been evaluated for these effects. Collapse capacity and energy absorption mechanism of the Special Steel Moment Frame (SSMF) system is evaluated in this study, under aftershock earthquakes when prior damage is caused by the mainshock. A twenty-story building is considered in assessing the residual collapse capacity and energy absorption mechanism under aftershock excitation. In addition, various levels of mainshock damage are considered and reflected through two different response parameters. Aftershock collapse capacity is estimated using incremental dynamic analysis (IDA) applied following the mainshock. The study results reveal that the collapse capacity of high-rise structures undergoes a remarkable reduction for high level of mainshock damage. The energy absorption in the columns is decreased by increasing the level of mainshock damage.

Keywords: seismic collapse, mainshock-aftershock effect, incremental dynamic analysis, energy absorption

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4983 Examining the Role of Farmer-Centered Participatory Action Learning in Building Sustainable Communities in Rural Haiti

Authors: Charles St. Geste, Michael Neumann, Catherine Twohig

Abstract:

Our primary aim is to examine farmer-centered participatory action learning as a tool to improve agricultural production, build resilience to climate shocks and, more broadly, advance community-driven solutions for sustainable development in rural communities across Haiti. For over six years, sixty plus farmers from Deslandes, Haiti, organized in three traditional work groups called konbits, have designed and tested low-input agroecology techniques as part of the Konbit Vanyan Kapab Pwoje Agroekoloji. The project utilizes a participatory action learning approach, emphasizing social inclusion, building on local knowledge, experiential learning, active farmer participation in trial design and evaluation, and cross-community sharing. Mixed methods were used to evaluate changes in knowledge and adoption of agroecology techniques, confidence in advancing agroecology locally, and innovation among Konbit Vanyan Kapab farmers. While skill and knowledge in application of agroecology techniques varied among individual farmers, a majority of farmers successfully adopted techniques outside of the trial farms. The use of agroecology techniques on trial and individual farms has doubled crop production in many cases. Farm income has also increased, and farmers report less damage to crops and property caused by extreme weather events. Furthermore, participatory action strategies have led to greater local self-determination and greater capacity for sustainable community development. With increased self-confidence and the knowledge and skills acquired from participating in the project, farmers prioritized sharing their successful techniques with other farmers and have developed a farmer-to-farmer training program that incorporates participatory action learning. Using adult education methods, farmers, trained as agroecology educators, are currently providing training in sustainable farming practices to farmers from five villages in three departments across Haiti. Konbit Vanyan Kapab farmers have also begun testing production of value-added food products, including a dried soup mix and tea. Key factors for success include: opportunities for farmers to actively participate in all phases of the project, group diversity, resources for application of agroecology techniques, focus on group processes and overcoming local barriers to inclusive decision-making.

Keywords: agroecology, participatory action learning, rural Haiti, sustainable community development

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4982 Effect of Serine/Threonine Kinases on Autophagy Mechanism

Authors: Ozlem Oral, Seval Kilic, Ozlem Yedier, Serap Dokmeci, Devrim Gozuacik

Abstract:

Autophagy is a degradation pathway, activating under stress conditions. It digests macromolecules, such as abnormal proteins and long-lived organelles by engulfing them and by subsequent delivery of the cargo to lysosomes. The members of the phospholipid-dependent serine/threonine kinases, involved in many signaling pathways, which are necessary for the regulation of cellular metabolic activation. Previous studies implicate that, serine/threonine kinases have crucial roles in the mechanism of many diseases depend on the activated and/or inactivated signaling pathway. Data indicates, the signaling pathways activated by serine/threonine kinases are also involved in activation of autophagy mechanism. However, the information about the effect of serine/threonine kinases on autophagy mechanism and the roles of these effects in disease formation is limited. In this study, we investigated the effect of activated serine/threonine kinases on autophagic pathway. We performed a commonly used autophagy technique, GFP-LC3 dot formation and by using microscopy analyses, we evaluated promotion and/or inhibition of autophagy in serine/threonine kinase-overexpressed fibroblasts as well as cancer cells. In addition, we carried out confocal microscopy analyses and examined autophagic flux by utilizing the differential pH sensitivities of RFP and GFP in mRFP-GFP-LC3 probe. Based on the shRNA-library based screening, we identified autophagy-related proteins affected by serine/threonine kinases. We further studied the involvement of serine/threonine kinases on the molecular mechanism of newly identified autophagy proteins and found that, autophagic pathway is indirectly controlled by serine/threonine kinases via specific autophagic proteins. Our data indicate the molecular connection between two critical cellular mechanisms, which have important roles in the formation of many disease pathologies, particularly cancer. This project is supported by TUBITAK-1001-Scientific and Technological Research Projects Funding Program, Project No: 114Z836.

Keywords: autophagy, GFP-LC3 dot formation assay, serine/threonine kinases, shRNA-library screening

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4981 Locally Crafted Sustainability: A Scoping Review for Nesting Social-Ecological and Socio-Technical Systems Towards Action Research in Agriculture

Authors: Marcia Figueira

Abstract:

Context: Positivist transformations in agriculture were responsible for top-down – often coercive – mechanisms of uniformed modernization that weathered local diversities and agency. New development pathways need to now shift according to comprehensive integrations of knowledge - scientific, indigenous, and local, and to be sustained on political interventions, bottom-up change, and social learning if climate goals are to be met – both in mitigation and adaptation. Objectives The objectives of this research are to understand how social-ecological and socio-technical systems characterisation can be nested to bridge scientific research/knowledge into a local context and knowledge system; and, with it, stem sustainable innovation. Methods To do so, we conducted a scoping review to explore theoretical and empirical works linked to Ostrom’s Social-Ecological Systems framework and Geels’ multi-level perspective of socio-technical systems transformations in the context of agriculture. Results As a result, we were able to identify key variables and connections to 1- understand the rules in use and the community attributes influencing resource management; and 2- how they are and have been shaped and shaping systems innovations. Conclusion Based on these results, we discuss how to leverage action research for mutual learning toward a replicable but highly place-based agriculture transformation frame.

Keywords: agriculture systems innovations, social-ecological systems, socio-technical systems, action research

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4980 The Research on Decentralization Supervision Mechanism of Town and Village Culture Based On Authenticity Evaluation

Authors: Chao Ma

Abstract:

In this paper, the evaluation criteria of authenticity evaluation system model are taken as the foundation so as to discuss the establishment problems about decentralization supervision system and mechanism of historical cultural town and village. The filtration of fitting towns and village's authenticity is conducted from the level, characteristic index and authentic assessment of evaluation model, thereby, supervising subject -interest related- coordinate organization can be taken as the venation in the management level, thus supervision mechanism of town and village's cultural inheritance can be combed, and the cultural inheritance management system and mechanism which is suitable to historical and cultural Chinese town and village will be provided. As the settlement with strong self-organizing characteristic, town and village don't recognize the management system as deeply as city. Therefore, it is necessary to establish town and village cultural evaluation system based on authenticity evaluation criteria. In this paper, authenticity evaluation system is established by taking this village's value evaluation criteria and protection as the cores, and the classification of participating options is beneficial to distribute local limited resources, protect hierarchically and accord with the local characters of town and village, build the evaluation system to run through the whole process of cultural inheritance, moreover, provide abundant information resources and make sure the value judgment criteria, thus supervision and management can be strengthened to effectively guard risk. By the above judgement and filtration of participating options, the management object with clear functions and supervision and coordination organization are established, thereby, the managerial logic of interest-related persons' decentralization can be clarified, evaluation system can be established, and the more targeted decentralization supervision system and mechanism of historical and cultural village will be built ultimately. Taking this method as a fundamental in cultural protection of town and village, not only can it be carried forward in the mass media, but also can cultivate the identity sense of indigenous people to come back historical and cultural villages, and resist the replacement of city culture.

Keywords: authenticity, rural culture, inheritance, supervision

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4979 Frames as Interests and Goals: The Case of MedTech Entrepreneurs' Capital Raising Strategies in Australia

Authors: Joelle Hawa, Michael Gilding

Abstract:

The role of interest as a driver of action has been an on-going debate in the sociological sciences. This paper shows evidence as to how economic actors frame their environment in terms of interests and goals to take action. It introduces the concept of 'dynamic actor compass', a cognitive tool that is socially contingent and allows economic actors to navigate their environment, evaluate the level of alignment of interests and goals with other players, and decide whether or not they are willing to rely on, collaborate or partner with others in the field. The paper builds on Kaplan’s model of framing contests and integrates Max Weber’s interests, and ideas construct as well as Beckert’s concept of fictional expectations. The author illustrates this conceptual framework in the case of MedTech entrepreneurs’ capital raising activities in Australia. The study adopts a grounded theory methodology, running in-depth interviews with 24 MedTech entrepreneurs in order to examine their decision-making processes and actions to finance their innovation trajectory. The findings show that participants take into account material and ideal interests and goals that they impose adapt or negotiate with other actors in their environment. These interactions affect the way MedTech entrepreneurs perceive other funders in the field, influencing their capital raising strategies.

Keywords: expectations, financing innovation, frames, goals, interest-oriented action, managerial cognition

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4978 Biomimetic Systems to Reveal the Action Mode of Epigallocatechin-3-Gallate in Lipid Membrane

Authors: F. Pires, V. Geraldo, O. N. Oliveira Jr., M. Raposo

Abstract:

Catechins are powerful antioxidants which have attractive properties useful for tumor therapy. Considering their antioxidant activity, these molecules can act as a scavenger of the reactive oxygen species (ROS), alleviating the damage of cell membrane induced by oxidative stress. The complexity and dynamic nature of the cell membrane compromise the analysis of the biophysical interactions between drug and cell membrane and restricts the transport or uptake of the drug by intracellular targets. To avoid the cell membrane complexity, we used biomimetic systems as liposomes and Langmuir monolayers to study the interaction between catechin and membranes at the molecular level. Liposomes were formed after the dispersion of anionic 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)(sodium salt) (DPPG) phospholipids in an aqueous solution, which mimic the arrangement of lipids in natural cell membranes and allows the entrapment of catechins. Langmuir monolayers were formed after dropping amphiphilic molecules, DPPG phospholipids, dissolved in an organic solvent onto the water surface. In this work, we mixed epigallocatechin-3-gallate (EGCG) with DPPG liposomes and exposed them to ultra-violet radiation in order to evaluate the antioxidant potential of these molecules against oxidative stress induced by radiation. The presence of EGCG in the mixture decreased the rate of lipid peroxidation, proving that EGCG protects membranes through the quenching of the reactive oxygen species. Considering the high amount of hydroxyl groups (OH groups) on structure of EGCG, a possible mechanism to these molecules interact with membrane is through hydrogen bonding. We also investigated the effect of EGCG at various concentrations on DPPG Langmuir monolayers. The surface pressure isotherms and infrared reflection-absorption spectroscopy (PM-IRRAS) results corroborate with absorbance results preformed on liposome-model, showing that EGCG interacts with polar heads of the monolayers. This study elucidates the physiological action of EGCG which can be incorporated in lipid membrane. These results are also relevant for the improvement of the current protocols used to incorporate catechins in drug delivery systems.

Keywords: catechins, lipid membrane, anticancer agent, molecular interactions

Procedia PDF Downloads 223
4977 Kinetics and Mechanism of Oxidation of Some Amino Acids by Peroxodisulphate

Authors: Abdelmahmod Saad

Abstract:

In this study two amino acids were chosen (DL.alanine,DL.serine) to determine their effect on dissociation of S2O8-2 ino. As the reaction was very slow, Ag+ ino was used as a catalyst. The kinetics measurement showed that the reactions in both cases were found in the first order with respect to S2O8-2, half order with respect to Ag+ and zero order with respect to substrates. Mechanisms were proposed for these reactions according to the determined orders. The energy of activation (AE) was determined for each reaction, and was found to by 30.50 k JmoI-1 in case of DL. Serine and 24.40 k JmoI-1 in case of DL.alanine.

Keywords: mechanism, oxidation, amino acids, peroxodisulphate

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4976 Approximate Spring Balancing for Swimming Pool Lift Mechanism to Reduce Actuator Torque

Authors: Apurva Patil, Sujatha Srinivasan

Abstract:

Reducing actuator loads is important for applications in which human effort is required for actuation. The potential benefit of applying spring balancing to rehabilitation devices which work against gravity on a nonhorizontal plane is well recognized, but practical applications have been elusive. Although existing methods provide exact spring balance, they require additional masses or auxiliary links, or all the springs used originate from the ground, which makes the resulting device bulky and space-inefficient. This paper uses a method of static balancing of mechanisms with conservative loads such as gravity and spring loads using non-zero-free-length springs and no auxiliary links. Application of this method to a manually operated swimming pool lift mechanism which lowers and raises the physically challenged users into or out of the swimming pool is presented here. Various possible configurations using extension and compression springs as well as gas spring in the mechanism are compared. This work involves approximate spring balancing of the mechanism using minimization of potential energy variance. It uses the approach of flattening the potential energy distribution over the workspace and fuses it with numerical optimization. The results show the considerable reduction in actuator torque requirement with practical spring design and arrangement. Although the method provides only an approximate balancing, it is versatile, flexible in choosing appropriate control variables that are relevant to the design problem and easy to implement. The true potential of this technique lies in the fact that it uses a very simple optimization to find the spring constant, free length of the spring and the optimal attachment points subject to the optimization constraints. Also, it uses physically realizable non-zero-free-length springs directly, thereby reducing the complexity involved in simulating zero-free-length springs from non-zero-free-length springs. This method allows springs to be attached inside the mechanism, which makes the implementation of spring balancing practical. Because auxiliary linkages can be avoided, the resultant swimming pool lift mechanism is compact. The cost benefits and reduced complexity can be significant advantages in the development of this user-actuated swimming pool lift for developing countries.

Keywords: gas spring, rehabilitation device, spring balancing, swimming pool lift

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4975 Design of a Satellite Solar Panel Deployment Mechanism Using the Brushed DC Motor as Rotational Speed Damper

Authors: Hossein Ramezani Ali-Akbari

Abstract:

This paper presents an innovative method to control the rotational speed of a satellite solar panel during its deployment phase. A brushed DC motor has been utilized in the passive spring driven deployment mechanism to reduce the deployment speed. In order to use the DC motor as a damper, its connector terminals have been connected with an external resistance in a closed circuit. It means that, in this approach, there is no external power supply in the circuit. The working principle of this method is based on the back electromotive force (or back EMF) of the DC motor when an external torque (here the torque produced by the torsional springs) is coupled to the DC motor’s shaft. In fact, the DC motor converts to an electric generator and the current flows into the circuit and then produces the back EMF. Based on Lenz’s law, the generated current produced a torque which acts opposite to the applied external torque, and as a result, the deployment speed of the solar panel decreases. The main advantage of this method is to set an intended damping coefficient to the system via changing the external resistance. To produce the sufficient current, a gearbox has been assembled to the DC motor which magnifies the number of turns experienced by the DC motor. The coupled electro-mechanical equations of the system have been derived and solved, then, the obtained results have been presented. A full-scale prototype of the deployment mechanism has been built and tested. The potential application of brushed DC motors as a rotational speed damper has been successfully demonstrated.

Keywords: back electromotive force, brushed DC motor, rotational speed damper, satellite solar panel deployment mechanism

Procedia PDF Downloads 317
4974 Glucose Uptake Rate of Insulin-Resistant Human Liver Carcinoma Cells (IR/HepG2) by Flavonoids from Enicostema littorale via IR/IRS1/AKT Pathway

Authors: Priyanka Mokashi, Aparna Khanna, Nancy Pandita

Abstract:

Diabetes mellitus is a chronic metabolic disorder which will be the 7th leading cause of death by 2030. The current line of treatment for the diabetes mellitus is oral antidiabetic drugs (biguanides, sulfonylureas, meglitinides, thiazolidinediones and alpha-glycosidase inhibitors) and insulin therapy depending upon the type 1 or type 2 diabetes mellitus. But, these treatments have their disadvantages, ranging from the developing of resistance to the drugs and adverse effects caused by them. Alternative to these synthetic agents, natural products provides a new insight for the development of more efficient and safe drugs due to their therapeutic values. Enicostema littorale blume (A. Raynal) is a traditional Indian plant belongs to the Gentianaceae family. It is widely distributed in Asia, Africa, and South America. There are few reports on Swrtiamarin, major component of this plant for its antidiabetic activity. However, the antidiabetic activity of flavonoids from E. littorale and their mechanism of action have not yet been elucidated. Flavonoids have a positive relationship with disease prevention and can act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, adipocytes, hepatocytes and skeletal myofibers. They may exert beneficial effects in diabetes by (i) improving hyperglycemia through regulation of glucose metabolism in hepatocytes; (ii) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells; (iii) increasing glucose uptake in hepatocytes, skeletal muscle and white adipose tissue (iv) reducing insulin resistance, inflammation and oxidative stress. Therefore, we have isolated four flavonoid rich fractions, Fraction A (FA), Fraction B (FB), Fraction C (FC), Fraction D (FD) from crude alcoholic hot (AH) extract from E. littorale, identified by LC/MS. Total eight flavonoids were identified on the basis of fragmentation pattern. Flavonoid FA showed the presence of swertisin, isovitexin, and saponarin; FB showed genkwanin, quercetin, isovitexin, FC showed apigenin, swertisin, quercetin, 5-O-glucosylswertisin and 5-O-glucosylisoswertisin whereas FD showed the presence of swertisin. Further, these fractions were assessed for their antidiabetic activity on stimulating glucose uptake in insulin-resistant HepG2 cell line model (IR/HepG2). The results showed that FD containing C-glycoside Swertisin has significantly increased the glucose uptake rate of IR/HepG2 cells at the concentration of 10 µg/ml as compared to positive control Metformin (0.5mM) which was determined by glucose oxidase- peroxidase method. It has been reported that enhancement of glucose uptake of cells occurs due the translocation of Glut4 vesicles to cell membrane through IR/IRS1/AKT pathway. Therefore, we have studied expressions of three genes IRS1, AKT and Glut4 by real-time PCR to evaluate whether they follow the same pathway or not. It was seen that the glucose uptake rate has increased in FD treated IR/HepG2 cells due to the activation of insulin receptor substrate-1 (IRS1) followed by protein kinase B (AKT) through phosphoinositide 3-kinase (PI3K) leading to translocation of Glut 4 vesicles to cell membrane, thereby enhancing glucose uptake and insulin sensitivity of insulin resistant HepG2 cells. Hence, the up-regulation indicated the mechanism of action through which FD (Swertisin) acts as antidiabetic candidate in the treatment of type 2 diabetes mellitus.

Keywords: E. littorale, glucose transporter, glucose uptake rate, insulin resistance

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4973 Participatory Action Research for Sustainability with Special Focus on Student Initiatives

Authors: Soni T. L.

Abstract:

Sustainable environmental stress is a major concern which needs immediate attention. This paper is an attempt to present participatory action research for sustainable agriculture. Being first and best culture, agriculture protects and improves the natural environment, the social and economic conditions of people, and safeguards the health and welfare of all groups. During course of time agriculture turned to agribusiness, then the values are not safeguarded. Moreover, in today’s busy life many are not taking efforts to take part in agriculture production. Then children are not getting the opportunity to understand agriculture and farming practices. So student initiatives are vital to make them aware. Here the programmes structured by the researcher come under the auspicious of National Service Scheme, a student-centered educational programme, organized by Ministry of Youth Affairs, Government of India. The twin objectives of the study are to examine the role of student initiatives for sustainable agriculture and the role of participatory action research in student initiatives. SWOT analysis is made to study strengths, weaknesses, threats and opportunities. The Methodology adopted is Participatory Action Research. The method is participatory in a sense there is collaboration through participation. The method is action, there is lab land experiences which is real. The method is research that there is documented lessons and creation of new knowledge. Plan of action cover measures adopted and strategies taken i.e., bhavana – kalpana – yojana – sadhana. Through the team effort, the team was successful in converting more than 10 hectares of barren land into cultivable land within and outside the campus. Team efforts of students saved a huge amount of labour cost and produced a huge quantity of organic output and the team was also successful in creating 1000 rain pits in the premises of College for rainwater harvesting. The findings include conveyance of the Message: Food Production is superior to Food donation. Moreover, the study fostered good work ethic and social responsibility among students. Students undertake innovative programmes underlying social and environmental issues and participants got increased opportunities to interact with local and less privileged and acquired increased awareness about real-life experiences which make them confident to interact with people and it resulted in the strengthening of social capital- cooperation, team spirit, social commitment among students. Participants promoted sustainable domestic efforts and ultimately environmental protection is ensured. Finally, there is recognition to the team, institution and the researcher at the university level, state level and at the national level. The learned lessons are, if the approach is good, the response is good and success generates success. Participatory action research is empowering experience for practitioners, focusing the combined time, energy and creativity of a committed group we should lead so many programmes which makes the institution centre of excellence. Authorities should take necessary steps for the Inclusion of community development activities in the curriculum. Action research is problem, client and action centered. So, we must adapt and adopt, coordinates and correlates measures which preserve and conserve the environment.

Keywords: participatory action research, student initiatives, sustainable development, sustainability

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4972 Shaking Force Balancing of Mechanisms: An Overview

Authors: Vigen Arakelian

Abstract:

The balancing of mechanisms is a well-known problem in the field of mechanical engineering because the variable dynamic loads cause vibrations, as well as noise, wear and fatigue of the machines. A mechanical system with unbalance shaking force and shaking moment transmits substantial vibration to the frame. Therefore, the objective of the balancing is to cancel or reduce the variable dynamic reactions transmitted to the frame. The resolution of this problem consists in the balancing of the shaking force and shaking moment. It can be fully or partially, by internal mass redistribution via adding counterweights or by modification of the mechanism's architecture via adding auxiliary structures. The balancing problems are of continue interest to researchers. Several laboratories around the world are very active in this area and new results are published regularly. However, despite its ancient history, mechanism balancing theory continues to be developed and new approaches and solutions are constantly being reported. Various surveys have been published that disclose particularities of balancing methods. The author believes that this is an appropriate moment to present a state of the art of the shaking force balancing studies completed by new research results. This paper presents an overview of methods devoted to the shaking force balancing of mechanisms, as well as the historical aspects of the origins and the evolution of the balancing theory of mechanisms.

Keywords: inertial forces, shaking forces, balancing, dynamics, mechanism design

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4971 Proposing an Architecture for Drug Response Prediction by Integrating Multiomics Data and Utilizing Graph Transformers

Authors: Nishank Raisinghani

Abstract:

Efficiently predicting drug response remains a challenge in the realm of drug discovery. To address this issue, we propose four model architectures that combine graphical representation with varying positions of multiheaded self-attention mechanisms. By leveraging two types of multi-omics data, transcriptomics and genomics, we create a comprehensive representation of target cells and enable drug response prediction in precision medicine. A majority of our architectures utilize multiple transformer models, one with a graph attention mechanism and the other with a multiheaded self-attention mechanism, to generate latent representations of both drug and omics data, respectively. Our model architectures apply an attention mechanism to both drug and multiomics data, with the goal of procuring more comprehensive latent representations. The latent representations are then concatenated and input into a fully connected network to predict the IC-50 score, a measure of cell drug response. We experiment with all four of these architectures and extract results from all of them. Our study greatly contributes to the future of drug discovery and precision medicine by looking to optimize the time and accuracy of drug response prediction.

Keywords: drug discovery, transformers, graph neural networks, multiomics

Procedia PDF Downloads 136
4970 Transnational Higher Education: Developing a Transnational Student Success Signature for Clinical Medical Students an Action Research Project

Authors: Wendy Maddison

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This paper describes an Action Research project which was undertaken to inform professional practice in order to develop a newly created Centre for Student Success in the specific context of transnational medical and nursing education in the Middle East. The objectives were to enhance the academic performance, persistence, integration and personal and professional development of a multinational study body, in particular in relation to preclinical medical students, and to establish a comfortable, friendly and student-driven environment within an Irish medical university recently established in Bahrain. Expatriating a new part of itself into a corner of the world and within a context which could be perceived as the antithesis of itself, in particular in terms of traditional cultural and organisational values, the university has had to innovate in the range of services, programmes and other offerings which engages and supports the academic success of medical and nursing students as they “encounter the world in the classroom” in the context of an Arab Islamic culture but within a European institution of transnational education, engaging with a global learning environment locally. The outcomes of the project resulted in the development of a specific student success ‘signature’ for this particular transnational higher education context.

Keywords: transnational higher education, medical education, action research, student success, Middle Eastern context, student persistence in the global-local, student support mechanisms

Procedia PDF Downloads 690
4969 Mechanism of Performance of Soil-Cement Columns under Shallow Foundations in Liquefiable Soil

Authors: Zaheer Ahmed Almani, Agha Faisal Habib Pathan, Aneel Kumar Hindu

Abstract:

In this study, the effects of ground reinforcement with stiff soil-cement columns on liquefiable ground and on the shallow foundation of structure were investigated. The modelling and analysis of shallow foundation of the structure founded on the composite reinforced ground were carried out with finite difference FLAC commercial software. The results showed that stiff columns were not effective to the redistribute the shear stresses in the composite ground, thus, were not effective to reduce shear stress and shear strain on the soil between the columns. The excessive pore pressure increase which is dependent on volumetric strain (contractive) tendency of loose sand upon shearing, was not reduced to a significant level that liquefaction potential could be remediated. Thus, mechanism of performance with reduction of pore pressure and consequent liquefaction was not predicted in numerical analysis. Nonetheless, the columns were effective to resist the load of structure in compression and reduced the liquefaction-induced large settlements of structure to tolerable limits when provided adjacent and beneath the pad of shallow foundation.

Keywords: earthquake, liquefaction, mechanism, soil-cement columns

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4968 An Analysis of Privacy and Security for Internet of Things Applications

Authors: Dhananjay Singh, M. Abdullah-Al-Wadud

Abstract:

The Internet of Things is a concept of a large scale ecosystem of wireless actuators. The actuators are defined as things in the IoT, those which contribute or produces some data to the ecosystem. However, ubiquitous data collection, data security, privacy preserving, large volume data processing, and intelligent analytics are some of the key challenges into the IoT technologies. In order to solve the security requirements, challenges and threats in the IoT, we have discussed a message authentication mechanism for IoT applications. Finally, we have discussed data encryption mechanism for messages authentication before propagating into IoT networks.

Keywords: Internet of Things (IoT), message authentication, privacy, security

Procedia PDF Downloads 371
4967 A Comparison of the Adsorption Mechanism of Arsenic on Iron-Modified Nanoclays

Authors: Michael Leo L. Dela Cruz, Khryslyn G. Arano, Eden May B. Dela Pena, Leslie Joy Diaz

Abstract:

Arsenic adsorbents were continuously being researched to ease the detrimental impact of arsenic to human health. A comparative study on the adsorption mechanism of arsenic on iron modified nanoclays was undertaken. Iron intercalated montmorillonite (Fe-MMT) and montmorillonite supported zero-valent iron (ZVI-MMT) were the adsorbents investigated in this study. Fe-MMT was produced through ion-exchange by replacing the sodium intercalated ions in montmorillonite with iron (III) ions. The iron (III) in Fe-MMT was later reduced to zero valent iron producing ZVI-MMT. Adsorption study was performed by batch technique. Obtained data were fitted to intra-particle diffusion, pseudo-first order, and pseudo-second-order models and the Elovich equation to determine the kinetics of adsorption. The adsorption of arsenic on Fe-MMT followed the intra-particle diffusion model with intra-particle rate constant of 0.27 mg/g-min0.5. Arsenic was found to be chemically bound on ZVI-MMT as suggested by the pseudo-second order and Elovich equation. The derived pseudo-second order rate constant was 0.0027 g/mg-min with initial adsorption rate computed from the Elovich equation was 113 mg/g-min.

Keywords: adsorption mechanism, arsenic, montmorillonite, zero valent iron

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