Search results for: contextual targeting
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1032

Search results for: contextual targeting

972 Social Data-Based Users Profiles' Enrichment

Authors: Amel Hannech, Mehdi Adda, Hamid Mcheick

Abstract:

In this paper, we propose a generic model of user profile integrating several elements that may positively impact the research process. We exploit the classical behavior of users and integrate a delimitation process of their research activities into several research sessions enriched with contextual and temporal information, which allows reflecting the current interests of these users in every period of time and infer data freshness. We argue that the annotation of resources gives more transparency on users' needs. It also strengthens social links among resources and users, and can so increase the scope of the user profile. Based on this idea, we integrate the social tagging practice in order to exploit the social users' behavior to enrich their profiles. These profiles are then integrated into a recommendation system in order to predict the interesting personalized items of users allowing to assist them in their researches and further enrich their profiles. In this recommendation, we provide users new research experiences.

Keywords: user profiles, topical ontology, contextual information, folksonomies, tags' clusters, data freshness, association rules, data recommendation

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971 Designing and Formulating Action Plan for Development of Corporate Citizenship in Producing Units in Iran

Authors: Freyedon Ahmadi

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Corporate citizenship is considered as one of the most discussed topics in the developed countries, in which a citizen considers a Corporate just like a usual citizen with every civil right as respectful for corporate as for actual citizens, and in return citizens expect that corporate would pay a reciprocal respect to them. The current study’s purpose is to identify the impact of the current state of corporate citizenship along effective factors on its condition on industrial producing units, in order to find an accession plane for corporate citizenship development. In this study corporate citizenship is studied in four dimensions like legal corporate, economical corporate, ethical corporate and voluntary corporate. Moreover, effective factors’ impact on corporate citizenship is explored based on threefold dimensional model: behavioral, structural, and content factors, as well. In this study, 50 corporate of Food industry and of petrochemical industry, along with 200 selected individuals from directors’ board on Tehran province’s scale with stratified random sampling method, are chosen as actuarial sample. If based on functional goal and compilation methods, the present study is a description of correlation type; questionnaire is used for accumulation of initial Data. For Instrument Validity expert’s opinion is used and structural equations and its reliability is qualified by using Cronbach Alpha. The results of this study indicate that close to 70 percent of under survey corporate have not a good condition in corporate citizenship. And all of structural factors, behavioral factors, contextual factors, have a great deal of impression and impact on the advent corporate citizenship behavior in the producing Units. Among the behavioral factors, social responsibility; among structural factors, organic structure and human centered orientation, medium size, high organizational capacity; and among the contextual factors, the clientele’s positive viewpoints toward corporate had the utmost importance in impression on under survey Producing units.

Keywords: corporate citizenship, structural factors, behavioral factors, contextual factors, producing units

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970 Knowledge Reactor: A Contextual Computing Work in Progress for Eldercare

Authors: Scott N. Gerard, Aliza Heching, Susann M. Keohane, Samuel S. Adams

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The world-wide population of people over 60 years of age is growing rapidly. The explosion is placing increasingly onerous demands on individual families, multiple industries and entire countries. Current, human-intensive approaches to eldercare are not sustainable, but IoT and AI technologies can help. The Knowledge Reactor (KR) is a contextual, data fusion engine built to address this and other similar problems. It fuses and centralizes IoT and System of Record/Engagement data into a reactive knowledge graph. Cognitive applications and services are constructed with its multiagent architecture. The KR can scale-up and scaledown, because it exploits container-based, horizontally scalable services for graph store (JanusGraph) and pub-sub (Kafka) technologies. While the KR can be applied to many domains that require IoT and AI technologies, this paper describes how the KR specifically supports the challenging domain of cognitive eldercare. Rule- and machine learning-based analytics infer activities of daily living from IoT sensor readings. KR scalability, adaptability, flexibility and usability are demonstrated.

Keywords: ambient sensing, AI, artificial intelligence, eldercare, IoT, internet of things, knowledge graph

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969 Structured-Ness and Contextual Retrieval Underlie Language Comprehension

Authors: Yao-Ying Lai, Maria Pinango, Ashwini Deo

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While grammatical devices are essential to language processing, how comprehension utilizes cognitive mechanisms is less emphasized. This study addresses this issue by probing the complement coercion phenomenon: an entity-denoting complement following verbs like begin and finish receives an eventive interpretation. For example, (1) “The queen began the book” receives an agentive reading like (2) “The queen began [reading/writing/etc.…] the book.” Such sentences engender additional processing cost in real-time comprehension. The traditional account attributes this cost to an operation that coerces the entity-denoting complement to an event, assuming that these verbs require eventive complements. However, in closer examination, examples like “Chapter 1 began the book” undermine this assumption. An alternative, Structured Individual (SI) hypothesis, proposes that the complement following aspectual verbs (AspV; e.g. begin, finish) is conceptualized as a structured individual, construed as an axis along various dimensions (e.g. spatial, eventive, temporal, informational). The composition of an animate subject and an AspV such as (1) engenders an ambiguity between an agentive reading along the eventive dimension like (2), and a constitutive reading along the informational/spatial dimension like (3) “[The story of the queen] began the book,” in which the subject is interpreted as a subpart of the complement denotation. Comprehenders need to resolve the ambiguity by searching contextual information, resulting in additional cost. To evaluate the SI hypothesis, a questionnaire was employed. Method: Target AspV sentences such as “Shakespeare began the volume.” were preceded by one of the following types of context sentence: (A) Agentive-biasing, in which an event was mentioned (…writers often read…), (C) Constitutive-biasing, in which a constitutive meaning was hinted (Larry owns collections of Renaissance literature.), (N) Neutral context, which allowed both interpretations. Thirty-nine native speakers of English were asked to (i) rate each context-target sentence pair from a 1~5 scale (5=fully understandable), and (ii) choose possible interpretations for the target sentence given the context. The SI hypothesis predicts that comprehension is harder for the Neutral condition, as compared to the biasing conditions because no contextual information is provided to resolve an ambiguity. Also, comprehenders should obtain the specific interpretation corresponding to the context type. Results: (A) Agentive-biasing and (C) Constitutive-biasing were rated higher than (N) Neutral conditions (p< .001), while all conditions were within the acceptable range (> 3.5 on the 1~5 scale). This suggests that when lacking relevant contextual information, semantic ambiguity decreases comprehensibility. The interpretation task shows that the participants selected the biased agentive/constitutive reading for condition (A) and (C) respectively. For the Neutral condition, the agentive and constitutive readings were chosen equally often. Conclusion: These findings support the SI hypothesis: the meaning of AspV sentences is conceptualized as a parthood relation involving structured individuals. We argue that semantic representation makes reference to spatial structured-ness (abstracted axis). To obtain an appropriate interpretation, comprehenders utilize contextual information to enrich the conceptual representation of the sentence in question. This study connects semantic structure to human’s conceptual structure, and provides a processing model that incorporates contextual retrieval.

Keywords: ambiguity resolution, contextual retrieval, spatial structured-ness, structured individual

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

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

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

Keywords: adhesion, interactome, precision, medicine

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967 Understanding the Experiences of School Teachers and Administrators Involved in a Multi-Sectoral Approach to the Creation of a Physical Literacy Enriched Community

Authors: M. Louise Humbert, Karen E. Chad, Natalie E. Houser, Marta E. Erlandson

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Physical literacy is the motivation, confidence, physical competence, knowledge, and understanding to value and takes responsibility for engagement in physical activities for life. In recent years, physical literacy has emerged as a determinant of health, promoting a positive lifelong physical activity trajectory. Physical literacy’s holistic approach and emphasis on the intrinsic valuation of movement provide an encouraging avenue for intervention among children to develop competent and confident movers. Although there is research on physical literacy interventions, no evidence exists on the outcomes of multi-sectoral interventions involving a combination of home, school, and community contexts. Since children interact with and in a wide range of contexts (home, school, community) daily, interventions designed to address a combination of these contexts are critical to the development of physical literacy. Working with school administrators and teachers, sports and recreation leaders, and community members, our team of university and community researchers conducted and evaluated one of the first multi-contextual and multi-sectoral physical literacy interventions in Canada. Schools played a critical role in this multi-sector intervention, and in this project, teachers and administrators focused their actions on developing physical literacy in students 10 to 14 years of age through the instruction of physical literacy-focused physical education lessons. Little is known about the experiences of educators when they work alongside an array of community representatives to develop physical literacy in school-aged children. Given the uniqueness of this intervention, we sought to answer the question, ‘What were the experiences of school-based educators involved in a multi-sectoral partnership focused on creating a physical literacy enriched community intervention?’ A thematic analysis approach was used to analyze data collected from interviews with educators and administrators, informal conversations, documents, and observations at workshops and meetings. Results indicated that schools and educators played the largest role in this multi-sector intervention. Educators initially reported a limited understanding of physical literacy and expressed a need for resources linked to the physical education curriculum. Some anxiety was expressed by the teachers as their students were measured, and educators noted they wanted to increase their understanding and become more involved in the assessment of physical literacy. Teachers reported that the intervention’s focus on physical literacy positively impacted the scheduling and their instruction of physical education. Administrators shared their desire for school and division-level actions targeting physical literacy development like the current focus on numeracy and literacy, treaty education, and safe schools. As this was one of the first multi-contextual and multi-sectoral physical literacy interventions, it was important to document creation and delivery experiences to encourage future growth in the area and develop suggested best practices.

Keywords: physical literacy, multi sector intervention, physical education, teachers

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966 A Qualitative Study Investigating the Relationship Between External Context and the Mechanism of Change for the Implementation of Goal-oriented Primary Care

Authors: Ine Huybrechts, Anja Declercq, Emily Verté, Peter Raeymaeckers, Sibyl Anthierens

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Goal-oriented care is a concept gaining increased interest as an approach to go towards more coordinated and integrated primary care. It places patients’ personal life goals at the core of health care support, hereby shifting the focus from “what’s the matter with this patient” to “what matters to this patient.” In Flanders/Belgium, various primary care providers, health and social care organizations and governmental bodies have picked up this concept and have initiated actions to facilitate this approach. The implementation of goal-oriented care not only happens on the micro-level, but it also requires efforts on the meso- and macro-level. Within implementation research, there is a growing recognition that the context in which an intervention takes place strongly relates to its implementation outcomes. However, when investigating contextual variables, the external context and its impact on implementation processes is often overlooked. This study aims to explore how we can better identify and understand the external context and how it relates to the mechanism of change within the implementation process of goal-oriented care in Flanders/Belgium. Results can be used to support and guide initiatives to introduce innovative approaches such as goal-oriented care inside an organization or in the broader primary care landscape. We have conducted qualitative research, performing in-depth interviews with n=23 respondents who have affinity with the implementation of goal-oriented care within their professional function. This lead to in-depth insights from a wide range of actors, with meso-level and/or macro-level perspectives on the implementation of goal-oriented care. This means that we have interviewed actors that are not only involved with initiatives to implement goal-oriented care, but also actors that actively give form to the external context in which goal-oriented care is implemented. Data were collected using a semi-structured interview guide, audio recorded, and analyzed first inductively and then deductively using various theories and concepts that derive from organizational research. Our preliminary findings suggest t Our findings can contribute to further define actions needed for sustainable implementation of goal-oriented primary care. It gives insights in the dynamics between contextual variables and implementation efforts, hereby indicating towards those contextual variables that can be further shaped to facilitate the implementation of an innovation such as goal-oriented care. hat organizational theories can help understand the mechanism of change of implementation processes with a macro-level perspective. Institutional theories, contingency theories, resources dependency theories and others can expose the mechanism of change for an innovation such as goal-oriented care. Our findings can contribute to further define actions needed for sustainable implementation of goal-oriented primary care. It gives insights in the dynamics between contextual variables and implementation efforts, hereby indicating towards those contextual variables that can be further shaped to facilitate the implementation of an innovation such as goal-oriented care.

Keywords: goal-oriented care, implementation processes, organizational theories, person-centered care, implementation research

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965 Targeted Photoactivatable Multiagent Nanoconjugates for Imaging and Photodynamic Therapy

Authors: Shazia Bano

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Nanoconjugates that integrate photo-based therapeutics and diagnostics within a single platform promise great advances in revolutionizing cancer treatments. However, to achieve high therapeutic efficacy, designing functionally efficacious nanocarriers to tightly retain the drug, promoting selective drug localization and release, and the validation of the efficacy of these nanoconjugates is a great challenge. Here we have designed smart multiagent, liposome based targeted photoactivatable multiagent nanoconjugates, doped with a photoactivatable chromophore benzoporphyrin derivative (BPD) labelled with an active targeting ligand cetuximab to target the EGFR receptor (over expressed in various cancer cells) to deliver a combination of therapeutic agents. This study establishes a tunable nanoplatform for the delivery of the photoactivatable multiagent nanoconjugates for tumor-specific accumulation and targeted destruction of cancer cells in complex cancer model to enhance the therapeutic index of the administrated drugs.

Keywords: targeting, photodynamic therapy, photoactivatable, nanoconjugates

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964 Magnetic Single-Walled Carbon Nanotubes (SWCNTs) as Novel Theranostic Nanocarriers: Enhanced Targeting and Noninvasive MRI Tracking

Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

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Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

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963 Anticancer Effects of MicroRNA-1275 in Human Nasopharyngeal Carcinoma by Targeting HOXB5

Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

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Through analysis of a published micro-array-based high-throughput assessment, we discovered that miR-1275 was markedly down-regulated in nasopharyngeal carcinoma (NPC) tissues. However, little is known about its effect and mechanism involved in NPC development and progression. In this study, we investigated the role of miR-1275 on the development of NPC. The results indicated that miR-1275 was significantly down-regulated in primary NPC tissues, and very low levels were found in NPC cell lines. Ectopic expression of miR-1275 in NPC cell lines significantly suppressed cell growth as evidenced by cell viability assay and colony formation assay, through inhibition of HOXB5. In addition, miR-1275 suppresses G1/S transition through inhibition of HOXB5. Further, oncogene HOXB5 was revealed to be a putative target of miR-1275, which was inversely correlated with miR-1275 expression in NPC. Collectively, our study demonstrates that as a tumor suppressor, miR-1275 played a pivotal role on NPC through inhibiting cell proliferation, and suppressing G1/S transition by targeting oncogenic HOXB5.

Keywords: microRNA-1275 (miR-1275), HOXB5, nasopharyngeal carcinoma, proliferation

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962 Survey of the Role of Contextualism in the Designing of Cultural Constructions Based on Rapoport Views

Authors: E. Zarei, M. Bazaei, A. Seifi, A. Keshavarzi

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Amos Rapoport, based on his anthropology approach, believed that the space origins from the human body and influences on human body mutually. As a holistic approach in architecture, Contextualism describes a collection of views in philosophy which emphasize the context in which an action, utterance, or expression occurs, and argues that, in some important respect, the action, utterance, or expression can only be understood relative to that context. In this approach, the main goal – studying the role of cultural component in the Contextualism construction shaping up, based on Amos Rapoport’s anthropology approach- has being done by descriptive- analytic method. The results of the research indicate that in the field of Contextualism designing, referring to the cultural aspects are as necessary as the physical dimensions of a construction. Rapoport believes that the shape of a construction is influenced by cultural aspects and he suggests a kind of mutual interaction between human and environment that should be considered in housing. The mail goal of contextual architecture is to establish an interaction between environment, human and culture. According to this approach, a desirable design should be in harmony with this approach.

Keywords: Amos Rapoport, anthropology, contextual architecture, culture

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961 Topical Delivery of Griseofulvin via Lipid Nanoparticles

Authors: Yann Jean Tan, Hui Meng Er, Choy Sin Lee, Shew Fung Wong, Wen Huei Lim

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Griseofulvin is a long standing fungistatic agent against dermatophytosis. Nevertheless, it has several drawbacks such as poor and highly variable bio availability, long duration of treatment, systemic side effects and drug interactions. Targeted treatment for the superficial skin infection, dermatophytosis via topical route could be beneficial. Nevertheless, griseofulvin is only available in the form of oral preparation. Hence, it generates interest in developing a topical formulation for griseofulvin, by using lipid nano particle as the vehicle. Lipid nanoparticle is a submicron colloidal carrier with a core that is solid in nature (lipid). It has combined advantages of various traditional carriers and is a promising vehicle for topical delivery. The griseofulvin loaded lipid nano particles produced using high pressure homogenization method were characterized and investigated for its skin targeting effect in vitro. It has a mean particle size of 179.8±4.9 nm with polydispersity index of 0.306±0.011. Besides, it showed higher skin permeation and better skin targeting effect compared to the griseofulvin suspension.

Keywords: lipid nanoparticles, griseofulvin, topical, dermatophytosis

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960 Mathematical Modeling on Capturing of Magnetic Nanoparticles in an Implant Assisted Channel for Magnetic Drug Targeting

Authors: Shashi Sharma, V. K. Katiyar, Uaday Singh

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The ability to manipulate magnetic particles in fluid flows by means of inhomogeneous magnetic fields is used in a wide range of biomedical applications including magnetic drug targeting (MDT). In MDT, magnetic carrier particles bounded with drug molecules are injected into the vascular system up-stream from the malignant tissue and attracted or retained at the specific region in the body with the help of an external magnetic field. Although the concept of MDT has been around for many years, however, wide spread acceptance of the technique is still looming despite the fact that it has shown some promise in both in vivo and clinical studies. This is because traditional MDT has some inherent limitations. Typically, the magnetic force is not very strong and it is also very short ranged. Since the magnetic force must overcome rather large hydrodynamic forces in the body, MDT applications have been limited to sites located close to the surface of the skin. Even in this most favorable situation, studies have shown that it is difficult to collect appreciable amounts of the MDCPs at the target site. To overcome these limitations of the traditional MDT approach, Ritter and co-workers reported the implant assisted magnetic drug targeting (IA-MDT). In IA-MDT, the magnetic implants are placed strategically at the target site to greatly and locally increase the magnetic force on MDCPs and help to attract and retain the MDCPs at the targeted region. In the present work, we develop a mathematical model to study the capturing of magnetic nanoparticles flowing in a fluid in an implant assisted cylindrical channel under the magnetic field. A coil of ferromagnetic SS 430 has been implanted inside the cylindrical channel to enhance the capturing of magnetic nanoparticles under the magnetic field. The dominant magnetic and drag forces, which significantly affect the capturing of nanoparticles, are incorporated in the model. It is observed through model results that capture efficiency increases from 23 to 51 % as we increase the magnetic field from 0.1 to 0.5 T, respectively. The increase in capture efficiency by increase in magnetic field is because as the magnetic field increases, the magnetization force, which is attractive in nature and responsible to attract or capture the magnetic particles, increases and results the capturing of large number of magnetic particles due to high strength of attractive magnetic force.

Keywords: capture efficiency, implant assisted-magnetic drug targeting (IA-MDT), magnetic nanoparticles, modelling

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959 Site-Specific Delivery of Hybrid Upconversion Nanoparticles for Photo-Activated Multimodal Therapies of Glioblastoma

Authors: Yuan-Chung Tsai, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu

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In order to enhance the photodynamic/photothermal therapeutic efficacy on glioblastoma, the functionized upconversion nanoparticles with the capability of converting the deep tissue penetrating near-infrared light into visible wavelength for activating photochemical reaction were developed. The drug-loaded nanoparticles (NPs) were obtained from the self-assembly of oleic acid-coated upconversion nanoparticles along with maleimide-conjugated poly(ethylene glycol)-cholesterol (Mal-PEG-Chol), as the NP stabilizer, and hydrophobic photosensitizers, IR-780 (for photothermal therapy, PTT) and mTHPC (for photodynamic therapy, PDT), in aqueous phase. Both the IR-780 and mTHPC were loaded into the hydrophobic domains within NPs via hydrophobic association. The peptide targeting ligand, angiopep-2, was further conjugated with the maleimide groups at the end of PEG adducts on the NP surfaces, enabling the affinity coupling with the low-density lipoprotein receptor-related protein-1 of tumor endothelial cells and malignant astrocytes. The drug-loaded NPs with the size of ca 80 nm in diameter exhibit a good colloidal stability in physiological conditions. The in vitro data demonstrate the successful targeting delivery of drug-loaded NPs toward the ALTS1C1 cells (murine astrocytoma cells) and the pronounced cytotoxicity elicited by combinational effect of PDT and PTT. The in vivo results show the promising brain orthotopic tumor targeting of drug-loaded NPs and sound efficacy for brain tumor dual-modality treatment. This work shows great potential for improving photodynamic/photothermal therapeutic efficacy of brain cancer.

Keywords: drug delivery, orthotopic brain tumor, photodynamic/photothermal therapies, upconversion nanoparticles

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958 Corpus-Based Analysis on the Translatability of Conceptual Vagueness in Traditional Chinese Medicine Classics Huang Di Nei Jing

Authors: Yan Yue

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Huang Di Nei Jing (HDNJ) is one of the significant traditional Chinese medicine (TCM) classics which lays the foundation of TCM theory and practice. It is an important work for the world to study the ancient civilizations and medical history of China. Language in HDNJ is highly concise and vague, and notably challenging to translate. This paper investigates the translatability of one particular vagueness in HDNJ: the conceptual vagueness which carries the Chinese philosophical and cultural connotations. The corpora tool Sketch Engine is used to provide potential online contexts and word behaviors. Selected two English translations of HDNJ by TCM practitioner and non-practitioner are used to examine frequency and distribution of linguistic features of the translation. It was found the hypothesis about the universals of translated language (explicitation, normalisation) is true in one translation, but it is on the sacrifice of some original contextual connotations. Transliteration is purposefully used in the second translation to retain the original flavor, which is argued as a violation of the principle of relevance in communication because it yields little contextual effects and demands more processing effort of the reader. The translatability of conceptual vagueness in HDNJ is constrained by source language context and the reader’s cognitive environment.

Keywords: corpus-based translation, translatability, TCM classics, vague language

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957 Targeting Violent Extremist Narratives: Applying Network Targeting Techniques to the Communication Functions of Terrorist Groups

Authors: John Hardy

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Over the last decade, the increasing utility of extremist narratives to the operational effectiveness of terrorist organizations has been evidenced by the proliferation of inspired or affiliated attacks across the world. Famous examples such as regional al-Qaeda affiliates and the self-styled “Islamic State” demonstrate the effectiveness of leveraging communication technologies to disseminate propaganda, recruit members, and orchestrate attacks. Terrorist organizations with the capacity to harness the communicative power offered by digital communication technologies and effective political narratives have held an advantage over their targets in recent years. Terrorists have leveraged the perceived legitimacy of grass-roots actors to appeal to a global audience of potential supporters and enemies alike, and have wielded a proficiency in profile-raising which remains unmatched by counter terrorism narratives around the world. In contrast, many attempts at propagating official counter-narratives have been received by target audiences as illegitimate, top-down and impersonally bureaucratic. However, the benefits provided by widespread communication and extremist narratives have come at an operational cost. Terrorist organizations now face a significant challenge in protecting their access to communications technologies and authority over the content they create and endorse. The dissemination of effective narratives has emerged as a core function of terrorist organizations with international reach via inspired or affiliated attacks. As such, it has become a critical function which can be targeted by intelligence and security forces. This study applies network targeting principles which have been used by coalition forces against a range of non-state actors in the Middle East and South Asia to the communicative function of terrorist organizations. This illustrates both a conceptual link between functional targeting and operational disruption in the abstract and a tangible impact on the operational effectiveness of terrorists by degrading communicative ability and legitimacy. Two case studies highlight the utility of applying functional targeting against terrorist organizations. The first case is the targeted killing of Anwar al-Awlaki, an al-Qaeda propagandist who crafted a permissive narrative and effective propaganda videos to attract recruits who committed inspired terrorist attacks in the US and overseas. The second is a series of operations against Islamic State propagandists in Syria, including the capture or deaths of a cadre of high profile Islamic State members, including Junaid Hussain, Abu Mohammad al-Adnani, Neil Prakash, and Rachid Kassim. The group of Islamic State propagandists were linked to a significant rise in affiliated and enabled terrorist attacks and were subsequently targeted by law enforcement and military agencies. In both cases, the disruption of communication between the terrorist organization and recruits degraded both communicative and operational functions. Effective functional targeting on member recruitment and operational tempo suggests that narratives are a critical function which can be leveraged against terrorist organizations. Further application of network targeting methods to terrorist narratives may enhance the efficacy of a range of counter terrorism techniques employed by security and intelligence agencies.

Keywords: countering violent extremism, counter terrorism, intelligence, terrorism, violent extremism

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956 Immunoliposomes Conjugated with CD133 Antibody for Targeting Melanoma Cancer Stem Cells

Authors: Chuan Yin

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Cancer stem cells (CSCs) represent a subpopulation of cancer cells that possess the characteristics associated with normal stem cells. CD133 is a phenotype of melanoma CSCs responsible for melanoma metastasis and drug resistance. Although adriamycin (ADR) is commonly used drug in melanoma therapy, but it is ineffective in the treatment of melanoma CSCs. In this study, we constructed CD133 antibody conjugated ADR immunoliposomes (ADR-Lip-CD133) to target CD133+ melanoma CSCs. The results showed that the immunoliposomes possessed a small particle size (~150 nm), high drug encapsulation efficiency (~90%). After 72 hr treatment on the WM266-4 melanoma tumorspheres, the IC50 values of the drug formulated in ADR-Lip-CD133, ADR-Lip (ADR liposomes) and ADR are found to be 24.42, 57.13 and 59.98 ng/ml respectively, suggesting that ADR-Lip-CD133 was more effective than ADR-Lip and ADR. Significantly, ADR-Lip-CD133 could almost completely abolish the tumorigenic ability of WM266-4 tumorspheres in vivo, and showed the best therapeutic effect in WM266-4 melanoma xenograft mice. It is noteworthy that ADR-Lip-CD133 could selectively kill CD133+ melanoma CSCs of WM266-4 cells both in vitro and in vivo. ADR-Lip-CD133 represent a potential approach in targeting and killing CD133+ melanoma CSCs.

Keywords: cancer stem cells, melanoma, immunoliposomes, CD133

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955 Hsa-miR-139-5p Acts as a Tumor Suppressor by Targeting C-Met in Non-Small Cell Lung Cancer

Authors: Chengcao Sun, Shujun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, Dejia Li

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Hsa-miRNA-139-5p (miR-139-5p) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-139-5p on lung cancer is still ambiguous. In this study, we investigated the role of miR-139-5p on development of lung cancer. Results indicated miR-139-5p was significantly down-regulated in primary tumor tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-139-5p in NSCLC cell lines significantly suppressed cell growth through inhibition of cyclin D1 and up-regulation of p57(Kip2). In addition, miR-139-5p induced apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-139-5p inhibited cellular metastasis through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene c-Met was revealed to be a putative target of miR-139-5p, which was inversely correlated with miR-139-5p expression. Taken together, our results demonstrated that miR-139-5p plays a pivotal role in lung cancer through inhibiting cell proliferation, metastasis, and promoting apoptosis by targeting oncogenic c-Met.

Keywords: hsa-miRNA-139-5p (miR-139-5p), c-Met, non-small cell lung cancer (NSCLC), proliferation, apoptosis

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954 A Study on Explicitation Strategies Employed in Persian Subtitling of English Crime Movies

Authors: Hossein Heidari Tabrizi, Azizeh Chalak, Hossein Enayat

Abstract:

The present study seeks to investigate the application of expansion strategy in Persian subtitles of English crime movies. More precisely, this study aims at classifying the different types of expansion used in subtitles as well as investigating the appropriateness or inappropriateness of the application of each type. To achieve this end, three English movies; namely, The Net (1995), Contact (1997) and Mission Impossible 2 (2000), available with Persian subtitles, were selected for the study. To collect the data, the above mentioned movies were watched and those parts of the Persian subtitles in which expansion had been used were identified and extracted along with their English dialogs. Then, the extracted Persian subtitles were classified based on the reason that led to expansion in each case. Next, the appropriateness or inappropriateness of using expansion in the extracted Persian subtitles was descriptively investigated. Finally, an equivalent not containing any expansion was proposed for those cases in which the meaning could be fully transferred without this strategy. The findings of the study indicated that the reasons range from explicitation (explicitation of visual, co-textual and contextual information), mistranslation and paraphrasing to the preferences of subtitlers. Furthermore, it was found that the employment of expansion strategy was inappropriate in all cases except for those caused by explicitation of contextual information since correct and shorter equivalents which were equally capable of conveying the intended meaning could be posited for the original dialogs.

Keywords: audiovisual translation, English crime movies, expansion strategies, Persian subtitles

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953 An Experimental Study on the Variability of Nonnative and Native Inference of Word Meanings in Timed and Untimed Conditions

Authors: Swathi M. Vanniarajan

Abstract:

Reading research suggests that online contextual vocabulary comprehension while reading is an interactive and integrative process. One’s success in it depends on a variety of factors including the amount and the nature of available linguistic and nonlinguistic cues, his/her analytical and integrative skills, schema memory (content familiarity), and processing speed characterized along the continuum of controlled to automatic processing. The experiment reported here, conducted with 30 native speakers as one group and 30 nonnative speakers as another group (all graduate students), hypothesized that while working on (24) tasks which required them to comprehend an unfamiliar word in real time without backtracking, due to the differences in the nature of their respective reading processes, the nonnative subjects would be less able to construct the meanings of the unknown words by integrating the multiple but sufficient contextual cues provided in the text but the native subjects would be able to. The results indicated that there were significant inter-group as well as intra-group differences in terms of the quality of definitions given. However, when given additional time, while the nonnative speakers could significantly improve the quality of their definitions, the native speakers in general would not, suggesting that all things being equal, time is a significant factor for success in nonnative vocabulary and reading comprehension processes and that accuracy precedes automaticity in the development of nonnative reading processes also.

Keywords: reading, second language processing, vocabulary comprehension

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952 Integration of Natural Hazard Governance: A Historical Analysis in a Swiss Alpine Region

Authors: Nicole Hiltbrand, Simone Quatrini, Eva Lieberherr

Abstract:

This research delves into the evolution of natural hazard management policy in Switzerland through the lens of policy integration, a crucial concept for addressing complex, cross-cutting issues like natural hazards. Through a descriptive case study approach focussing on the Canton of Grisons, the research explores how policy integration has evolved between 1870 and 2020 alongside with specific contextual conditions characterizing the complex relation between humans and nature in Alpine areas subject to natural hazards with high damage potential, such as landslides, avalanches and floods. The primary objective of the research is to evaluate the changes in policy integration that can be observed across the study period and discern the key drivers behind these transformations. Employing a mixed-method qualitative approach, the research begins with a semi-systematic literature and document review, examining the legislative context in a historical perspective. Subsequently, policy integration is analysed using an established conceptual framework that distinguishes between four crucial dimensions: policy frames, subsystem involvement, policy goals, and policy instruments. Lastly, expert interviews were conducted to validate and enrich the findings from the analysis. The study reveals a discernible increase in policy integration across all dimensions analysed. Among the drivers of such change, the study highlights key factors that can be categorized as follows: (i) socio-political factors, (ii) advancements in technical and scientific knowledge, (iii) federal legislation and guidelines, as well as (iv) natural events. This study – conducted as part of a Master’s programme in the Department of Environmental Systems Science of the Swiss Federal Institute of Technology (ETH) in Zurich – contributes to policy integration research by offering valuable insights into the evolving landscape of policy integration and the pivotal role played by contextual conditions. By casting light on the interconnectedness between policy evolution and contextual factors, this study offers insightful perspectives on how natural hazard management policy can adapt and respond to dynamic socio-political, technical, and environmental challenges.

Keywords: natural hazard management, policy integration, policy coherence, alpine region

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951 Target Drug Delivery of Pamidronate Nanoparticles for Enhancing Osteoblastic Activity in Osteoporosis

Authors: Purnima Rawat, Divya Vohora, Sarika Gupta, Farhan J. Ahmad, Sushama Talegaonkar

Abstract:

Nanoparticles (NPs) that target bone tissue were developed using PLGA–mPEG (poly(lactic-co-glycolic-acid)–polyethylene glycol) diblock copolymers by using pamidronate as a bone-targeting moieties. These NPs are expected to enable the transport of hydrophilic drugs. The NP was prepared by in situ polymerization method, and their in- vitro characteristics were evaluated using dynamic light scattering, transmission electron microscopy (TEM) and in phosphate-buffered solution. The bone targeting potential of the NP was also evaluated on in-vitro pre-osteoblast MCT3E1 cell line using ALP activity, degree of mineralization and RT-PCR assay. The average particle size of the NP was 101.6 ± 3.7nm, zeta potential values were negative (-25±0.34mV) of the formulations and the entrapment efficiency was 93± 3.1 % obtained. The moiety of the PLGA–mPEG–pamidronate NPs exhibited the best apatite mineral binding ability in-vitro MCT3E1 pre-osteoblast cell line. Our results suggested that the developed nanoparticles may use as a delivery system for Pamidronate in bone repair and regeneration, warranting further evaluation of the treatment of bone disease.

Keywords: nanoparticle, pamidronate, in-situ polymerization, osteoblast

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950 The Impact of Social Support on Anxiety and Depression under the Context of COVID-19 Pandemic: A Scoping Review and Meta-Analysis

Authors: Meng Wu, Atif Rahman, Eng Gee, Lim, Jeong Jin Yu, Rong Yan

Abstract:

Context: The COVID-19 pandemic has had a profound impact on mental health, with increased rates of anxiety and depression observed. Social support, a critical factor in mental well-being, has also undergone significant changes during the pandemic. This study aims to explore the relationship between social support, anxiety, and depression during COVID-19, taking into account various demographic and contextual factors. Research Aim: The main objective of this study is to conduct a comprehensive systematic review and meta-analysis to examine the impact of social support on anxiety and depression during the COVID-19 pandemic. The study aims to determine the consistency of these relationships across different age groups, occupations, regions, and research paradigms. Methodology: A scoping review and meta-analytic approach were employed in this study. A search was conducted across six databases from 2020 to 2022 to identify relevant studies. The selected studies were then subjected to random effects models, with pooled correlations (r and ρ) estimated. Homogeneity was assessed using Q and I² tests. Subgroup analyses were conducted to explore variations across different demographic and contextual factors. Findings: The meta-analysis of both cross-sectional and longitudinal studies revealed significant correlations between social support, anxiety, and depression during COVID-19. The pooled correlations (ρ) indicated a negative relationship between social support and anxiety (ρ = -0.30, 95% CI = [-0.333, -0.255]) as well as depression (ρ = -0.27, 95% CI = [-0.370, -0.281]). However, further investigation is required to validate these results across different age groups, occupations, and regions. Theoretical Importance: This study emphasizes the multifaceted role of social support in mental health during the COVID-19 pandemic. It highlights the need to reevaluate and expand our understanding of social support's impact on anxiety and depression. The findings contribute to the existing literature by shedding light on the associations and complexities involved in these relationships. Data Collection and Analysis Procedures: The data collection involved an extensive search across six databases to identify relevant studies. The selected studies were then subjected to rigorous analysis using random effects models and subgroup analyses. Pooled correlations were estimated, and homogeneity was assessed using Q and I² tests. Question Addressed: This study aimed to address the question of the impact of social support on anxiety and depression during the COVID-19 pandemic. It sought to determine the consistency of these relationships across different demographic and contextual factors. Conclusion: The findings of this study highlight the significant association between social support, anxiety, and depression during the COVID-19 pandemic. However, further research is needed to validate these findings across different age groups, occupations, and regions. The study emphasizes the need for a comprehensive understanding of social support's multifaceted role in mental health and the importance of considering various contextual and demographic factors in future investigations.

Keywords: social support, anxiety, depression, COVID-19, meta-analysis

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949 Synthesis of Highly Stable Multi-Functional Iron Oxide Nanoparticles for Active Mitochondrial Targeting in Immunotherapy

Authors: Masome Moeni, Roya Abedizadeh, Elham Aram, Hamid Sadeghi-Abandansari, Davood Sabour, Robert Menzel, Ali Hassanpour

Abstract:

Mitochondria- targeting immunogenic cell death inducers (MT-ICD) have been designed to trigger intrinsic apoptosis signalling pathway in malignant cells and revive the antitumour immune system. MT-ICD inducers have considered to be non-specific, which can deteriorate the ability to initiate mitochondria-selective oxidative stress, causing high toxicity. Iron oxide nanoparticles (IONPs) can be an ideal candidate as vehicles for utilizing in immunotherapy due to their biocompatibility, modifiable surface chemistry, magnetic characteristics and multi-functional applications in single platform. These types of NPs can facilitate a real time imaging which can provide an effective strategy to analyse pharmacokinetic parameters of nano-formula, including blood circulation time, targeted and controlled release at tumour microenvironment. To our knowledge, the conjugation of IONPs with MT-ICD and oxaliplatin (a chemotherapeutic agent used for the treatment of colorectal cancer) for immunotherapy have not been investigated. Herein, IONPs were generated via co-precipitation reaction at high temperatures, followed by coating the colloidal suspension with tetraethyl orthosilicate and 3-aminopropyltriethoxysilane to optimize their bio-compatibility, preventing aggregation and maintaining stability at physiological pH, then functionalized with (3-carboxypropyl) triphenyl phosphonium bromide for mitochondrial delivery. Analytical results demonstrated the successful process of IONPs functionalization. In particular, the colloidal particles of doped IONPs exhibited an excellent stability and dispersibility. The resultant particles were also successfully loaded with the oxaliplatin for an active mitochondrial targeting in immunotherapy, resulting in well-maintained super-paramagnetic characteristics and stable structure of the functionalized IONPs with nanoscale particle sizes.

Keywords: Immunotherapy, mitochondria, cancer, iron oxide nanoparticle

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948 Reviewing the Effect of Healing Design on Mental Health Establishments in the Context of India

Authors: Aratrika Sarkar, Jayita Guha Niyogi

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This paper focuses on the application of general healing design theories to modulate them into case-specific and contextual design considerations. Existing literature focuses on the relationship between architecture and mental health. Primary case studies are selected in India to focus on the effect of a specific location on design considerations. They are qualitatively analysed to further contextualise the inferences from the literature study. An academic project is cited as an example to apply the learnings from the study and understand the influence of various parameters on the design process for further conclusion. Literature studies, case studies and hypothetical design applications helped in finding the different ways of achieving the similar goal of a sensitive approach toward mental health. Along with salutogenic parameters, category of establishment, age group, location of the site and user preference plays a crucial role in the design process. Design of mental health establishments, especially in India, has to involve transparency between stakeholders and users. Owing to different climatic zones and diverse sociocultural traditions, the approach toward healing should adapt accordingly. It should be an effort towards striking a balance between contradictory elements of healing design and resolving the dilemmas with sensitivity and consensus. Lastly, the design should not force a person towards communication or companionship but rather let the person realise that naturally through the healing process.

Keywords: contextual healing design, deinstitutionalisation, Indian mental healthcare establishments, environmental psychology, salutogenesis, therapeutic design

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947 Girls’ Education Policy and Practices in Three Selected Countries of Africa: Feminism, Educational Reform and Cultural Inflections in View

Authors: Endalew Fufa Kufi

Abstract:

One of the major concerns in educational provision and success determination is access to available opportunities. In that, girls’ access to education has been a point of concern, and more emphasis has come to be at the forefront regarding success. Researches have mostly been held on extremes such as equal access and success, but only a few works deal with process issues related to home and school interplay, issues of progress from lower to higher levels, and spatial conditions related to girls’ education. Hence, this survey assessed experiences in three countries of Africa: Ethiopia, Ghana, and Botswana regarding girls’ education in policy and practice as related to contextual matters in girls’ education. Contextual discourse analysis of qualitative design was used to materialize the study. From each country, five research works held 2010 onwards were purposively selected through criterion-sampling. On the policy aspect, workable documents were looked into. The findings denoted that educational access was of more stretch and generic nature, and the narration was dominated by institutional expectations, not identifying which group should benefit what. The researches largely dealt with either subject-specific dealings or access alone at large. Success studies, by far, dealt with a comparison of girls with boys rather than determinant-related projections. Moreover, the cultural representation of girls’ education had a very minimal part in both policy and researches. From that, it could be found that in-depth scrutiny on the individual, institutional, and leadership determinants of girls’ education would be necessary.

Keywords: determinants, girls, education, feminism

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946 Design of the Intelligent Virtual Learning Coach. A Contextual Learning Approach to Digital Literacy of Senior Learners in the Context of Electronic Health Record (EHR)

Authors: Ilona Buchem, Carolin Gellner

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The call for the support of senior learners in the development of digital literacy has become prevalent in recent years, especially in view of the aging societies paired with advances in digitalization in all spheres of life, including e-health. The goal has been to create opportunities for learning that incorporate the use of context in a reflective and dialogical way. Contextual learning has focused on developing skills through the application of authentic problems. While major research efforts in supporting senior learners in developing digital literacy have been invested so far in e-learning, focusing on knowledge acquisition and cognitive tasks, little research exists in reflective mentoring and coaching with the help of pedagogical agents and addressing the contextual dimensions of learning. This paper describes an approach to creating opportunities for senior learners to improve their digital literacy in the authentic context of the electronic health record (EHR) with the support of an intelligent virtual learning coach. The paper focuses on the design of the virtual coach as part of an e-learning system, which was developed in the EPA-Coach project founded by the German Ministry of Education and Research. The paper starts with the theoretical underpinnings of contextual learning and the related design considerations for a virtual learning coach based on previous studies. Since previous research in the area was mostly designed to cater to the needs of younger audiences, the results had to be adapted to the specific needs of senior learners. Next, the paper outlines the stages in the design of the virtual coach, which included the adaptation of the design requirements, the iterative development of the prototypes, the results of the two evaluation studies and how these results were used to improve the design of the virtual coach. The paper then presents the four prototypes of a senior-friendly virtual learning coach, which were designed to represent different preferences related to the visual appearance, the communication and social interaction styles, and the pedagogical roles. The first evaluation of the virtual coach design was an exploratory, qualitative study, which was carried out in October 2020 with eight seniors aged 64 to 78 and included a range of questions about the preferences of senior learners related to the visual design, gender, age, communication and role. Based on the results of the first evaluation, the design was adapted to the preferences of the senior learners and the new versions of prototypes were created to represent two male and two female options of the virtual coach. The second evaluation followed a quantitative approach with an online questionnaire and was conducted in May 2021 with 41 seniors aged 66 to 93 years. Following three research questions, the survey asked about (1) the intention to use, (2) the perceived characteristics, and (3) the preferred communication/interaction style of the virtual coach, i. e. task-oriented, relationship-oriented, or a mix. This paper follows with the discussion of the results of the design process and ends with conclusions and next steps in the development of the virtual coach including recommendations for further research.

Keywords: virtual learning coach, virtual mentor, pedagogical agent, senior learners, digital literacy, electronic health records

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945 Development of Ketorolac Tromethamine Encapsulated Stealth Liposomes: Pharmacokinetics and Bio Distribution

Authors: Yasmin Begum Mohammed

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Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

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944 Role of Endonuclease G in Exogenous DNA Stability in HeLa Cells

Authors: Vanja Misic, Mohamed El-Mogy, Yousef Haj-Ahmad

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Endonuclease G (EndoG) is a well conserved mitochondrio-nuclear nuclease with dual lethal and vital roles in the cell. The aim of our study was to examine whether EndoG exerts its nuclease activity on exogenous DNA substrates such as plasmid DNA (pDNA), considering their importance in gene therapy applications. The effects of EndoG knockdown on pDNA stability and levels of encoded reporter gene expression were evaluated in the cervical carcinoma HeLa cells. Transfection of pDNA vectors encoding short-hairpin RNAs (shRNAs) reduced levels of EndoG mRNA and nuclease activity in HeLa cells. In physiological circumstances, EndoG knockdown did not have an effect on the stability of pDNA or the levels of encoded transgene expression as measured over a four day time-course. However, when endogenous expression of EndoG was induced by an extrinsic stimulus, targeting of EndoG by shRNA improved the perceived stability and transgene expression of pDNA vectors. Therefore, EndoG is not a mediator of exogenous DNA clearance, but in non-physiological circumstances it may non-specifically cleave intracellular DNA regardless of its origin. These findings make it unlikely that targeting of EndoG is a viable strategy for improving the duration and level of transgene expression from non-viral DNA vectors in gene therapy efforts.

Keywords: EndoG, silencing, exogenous DNA stability, HeLa cells

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943 Targeting the EphA2 Receptor Tyrosine Kinases in Melanoma Cancer, both in Humans and Dogs

Authors: Shabnam Abdi, Behzad Toosi

Abstract:

Background: Melanoma is the most lethal type of malignant skin cancer in humans and dogs since it spreads rapidly throughout the body. Despite significant advances in treatment, cancer at an advanced stage has a poor prognosis. Hence, more effective treatments are needed to enhance outcomes with fewer side effects. Erythropoietin-producing hepatocellular receptors are the largest family of receptor tyrosine kinases and are divided into two subfamilies, EphA and EphB, both of which play a significant role in disease, especially cancer. Due to their association with proliferation and invasion in many aggressive types of cancer, Eph receptor tyrosine kinases (Eph RTKs) are promising cancer therapy molecules. Because these receptors have not been studied in canine melanoma, we investigated how EphA2 influences survival and tumorigenicity of melanoma cells. Methods: Expression of EphA2 protein in canine melanoma cell lines and human melanoma cell line was evaluated by Western blot. Melanoma cells were transduced with lentiviral particles encoding Eph-targeting shRNAs or non-silencing shRNAs (control) for silencing the expression of EphA2 receptor, and silencing was confirmed by Western blotting and immunofluorescence. The effect of siRNA treatment on cellular proliferation, colony formation, tumorsphere assay, invasion was analyzed by Resazurin assay Matrigel invasion assay, respectively. Results: Expression of EphA2 was detected in canine and human melanoma cell lines. Moreover, stably silencing EphA2 by specific shRNAs significantly and consistently decreased the expression of EphA2 protein in both human and canine melanoma cells. Proliferation, colony formation, tumorsphere and invasion of melanoma cells were significantly decreased in EphA2 siRNA-treated cells compared to control. Conclusion: Our data provide the first functional evidence that the EphA2 receptor plays a critical role in the malignant cellular behavior of melanoma in both human and dogs.

Keywords: ephA2, targeting, melanoma, human, canine

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