Search results for: personalized therapeutics
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 389

Search results for: personalized therapeutics

359 Cloning and Expression of Azurin: A Protein Having Antitumor and Cell Penetrating Ability

Authors: Mohsina Akhter

Abstract:

Cancer has become a wide spread disease around the globe and takes many lives every year. Different treatments are being practiced but all have potential side effects with somewhat less specificity towards target sites. Pseudomonas aeruginosa is known to secrete a protein azurin with special anti-cancer function. It has unique cell penetrating peptide comprising of 18 amino acids that have ability to enter cancer cells specifically. Reported function of Azurin is to stabilize p53 inside the tumor cells and induces apoptosis through Bax mediated cytochrome c release from mitochondria. At laboratory scale, we have made recombinant azurin through cloning rpTZ57R/T-azu vector into E.coli strain DH-5α and subcloning rpET28-azu vector into E.coli BL21-CodonPlus (DE3). High expression was ensured with IPTG induction at different concentrations then optimized high expression level at 1mM concentration of IPTG for 5 hours. Purification has been done by using Ni+2 affinity chromatography. We have concluded that azurin can be a remarkable improvement in cancer therapeutics if it produces on a large scale. Azurin does not enter into the normal cells so it will prove a safe and secure treatment for patients and prevent them from hazardous anomalies.

Keywords: azurin, pseudomonas aeruginosa, cancer, therapeutics

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358 3D Printing of Dual Tablets: Modified Multiple Release Profiles for Personalized Medicine

Authors: Veronika Lesáková, Silvia Slezáková, František Štěpánek

Abstract:

Additive manufacturing technologies producing drug dosage forms aimed at personalized medicine applications are promising strategies with several advantages over the conventional production methods. One of the emerging technologies is 3D printing which reduces manufacturing steps and thus allows a significant drop in expenses. A decrease in material consumption is also a highly impactful benefit as the tested drugs are frequently expensive substances. In addition, 3D printed dosage forms enable increased patient compliance and prevent misdosing as the dosage forms are carefully designed according to the patient’s needs. The incorporation of multiple drugs into a single dosage form further increases the degree of personalization. Our research focuses on the development of 3D printed tablets incorporating multiple drugs (candesartan, losartan) and thermoplastic polymers (e.g., KlucelTM HPC EF). The filaments, an essential feed material for 3D printing,wereproduced via hot-melt extrusion. Subsequently, the extruded filaments of various formulations were 3D printed into tablets using an FDM 3D printer. Then, we have assessed the influence of the internal structure of 3D printed tablets and formulation on dissolution behaviour by obtaining the dissolution profiles of drugs present in the 3D printed tablets. In conclusion, we have developed tablets containing multiple drugs providing modified release profiles. The 3D printing experiments demonstrate the high tunability of 3D printing as each tablet compartment is constructed with a different formulation. Overall, the results suggest that the 3D printing technology is a promising manufacturing approach to dual tablet preparation for personalized medicine.

Keywords: 3D printing, drug delivery, hot-melt extrusion, dissolution kinetics

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357 Predicting Potential Protein Therapeutic Candidates from the Gut Microbiome

Authors: Prasanna Ramachandran, Kareem Graham, Helena Kiefel, Sunit Jain, Todd DeSantis

Abstract:

Microbes that reside inside the mammalian GI tract, commonly referred to as the gut microbiome, have been shown to have therapeutic effects in animal models of disease. We hypothesize that specific proteins produced by these microbes are responsible for this activity and may be used directly as therapeutics. To speed up the discovery of these key proteins from the big-data metagenomics, we have applied machine learning techniques. Using amino acid sequences of known epitopes and their corresponding binding partners, protein interaction descriptors (PID) were calculated, making a positive interaction set. A negative interaction dataset was calculated using sequences of proteins known not to interact with these same binding partners. Using Random Forest and positive and negative PID, a machine learning model was trained and used to predict interacting versus non-interacting proteins. Furthermore, the continuous variable, cosine similarity in the interaction descriptors was used to rank bacterial therapeutic candidates. Laboratory binding assays were conducted to test the candidates for their potential as therapeutics. Results from binding assays reveal the accuracy of the machine learning prediction and are subsequently used to further improve the model.

Keywords: protein-interactions, machine-learning, metagenomics, microbiome

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356 Characterization of the Catalytic and Structural Roles of the Human Hexokinase 2 in Cancer Progression

Authors: Mir Hussain Nawaz, Lyudmila Nedyalkova, Haizhong Zhu, Wael M. Rabeh

Abstract:

In this study, we aim to biochemically and structurally characterize the interactions of human HK2 with the mitochondria in addition to the role of its N-terminal domain in catalysis and stability of the full-length enzyme. Here, we solved the crystal structure of human HK2 in complex with glucose and glucose-6-phosphate (PDB code: 2NZT), where it is a homodimer with catalytically active N- and C-terminal domains linked by a seven-turn α-helix. Different from the inactive N-terminal domains of isozymes 1 and 3, the N- domain of HK2 not only capable to catalyze a reaction but it is responsible for the thermodynamic stabilizes of the full-length enzyme. Deletion of first α-helix of the N-domain that binds to the mitochondria altered the stability and catalytic activity of the full-length HK2. In addition, we found the linker helix between the N- and C-terminal domains to play an important role in controlling the catalytic activity of the N-terminal domain. HK2 is a major step in the regulation of glucose metabolism in cancer making it an ideal target for the development of new anticancer therapeutics. Characterizing the structural and molecular mechanisms of human HK2 and its role in cancer metabolism will accelerate the design and development of new cancer therapeutics that are safe and cancer specific.

Keywords: cancer metabolism, enzymology, drug discovery, protein stability

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355 Prospects of Acellular Organ Scaffolds for Drug Discovery

Authors: Inna Kornienko, Svetlana Guryeva, Natalia Danilova, Elena Petersen

Abstract:

Drug toxicity often goes undetected until clinical trials, the most expensive and dangerous phase of drug development. Both human cell culture and animal studies have limitations that cannot be overcome by improvements in drug testing protocols. Tissue engineering is an emerging alternative approach to creating models of human malignant tumors for experimental oncology, personalized medicine, and drug discovery studies. This new generation of bioengineered tumors provides an opportunity to control and explore the role of every component of the model system including cell populations, supportive scaffolds, and signaling molecules. An area that could greatly benefit from these models is cancer research. Recent advances in tissue engineering demonstrated that decellularized tissue is an excellent scaffold for tissue engineering. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularized Organs preserve organ microenvironment, which is critical for cancer metastasis. Utilizing 3D tumor models results greater proximity of cell culture morphological characteristics in a model to its in vivo counterpart, allows more accurate simulation of the processes within a functioning tumor and its pathogenesis. 3D models allow study of migration processes and cell proliferation with higher reliability as well. Moreover, cancer cells in a 3D model bear closer resemblance to living conditions in terms of gene expression, cell surface receptor expression, and signaling. 2D cell monolayers do not provide the geometrical and mechanical cues of tissues in vivo and are, therefore, not suitable to accurately predict the responses of living organisms. 3D models can provide several levels of complexity from simple monocultures of cancer cell lines in liquid environment comprised of oxygen and nutrient gradients and cell-cell interaction to more advanced models, which include co-culturing with other cell types, such as endothelial and immune cells. Following this reasoning, spheroids cultivated from one or multiple patient-derived cell lines can be utilized to seed the matrix rather than monolayer cells. This approach furthers the progress towards personalized medicine. As an initial step to create a new ex vivo tissue engineered model of a cancer tumor, optimized protocols have been designed to obtain organ-specific acellular matrices and evaluate their potential as tissue engineered scaffolds for cultures of normal and tumor cells. Decellularized biomatrix was prepared from animals’ kidneys, urethra, lungs, heart, and liver by two decellularization methods: perfusion in a bioreactor system and immersion-agitation on an orbital shaker with the use of various detergents (SDS, Triton X-100) in different concentrations and freezing. Acellular scaffolds and tissue engineered constructs have been characterized and compared using morphological methods. Models using decellularized matrix have certain advantages, such as maintaining native extracellular matrix properties and biomimetic microenvironment for cancer cells; compatibility with multiple cell types for cell culture and drug screening; utilization to culture patient-derived cells in vitro to evaluate different anticancer therapeutics for developing personalized medicines.

Keywords: 3D models, decellularization, drug discovery, drug toxicity, scaffolds, spheroids, tissue engineering

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354 Prevalence of Cyp2d6 and Its Implications for Personalized Medicine in Saudi Arabs

Authors: Hamsa T. Tayeb, Mohammad A. Arafah, Dana M. Bakheet, Duaa M. Khalaf, Agnieszka Tarnoska, Nduna Dzimiri

Abstract:

Background: CYP2D6 is a member of the cytochrome P450 mixed-function oxidase system. The enzyme is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, especially in breast cancer and psychiatric therapy. Different phenotypes have been described displaying alleles that lead to a complete loss of enzyme activity, reduced function (poor metabolizers – PM), hyperfunctionality (ultrarapid metabolizers–UM) and therefore drug intoxication or loss of drug effect. The prevalence of these variants may vary among different ethnic groups. Furthermore, the xTAG system has been developed to categorized all patients into different groups based on their CYP2D6 substrate metabolization. Aim of the study: To determine the prevalence of the different CYP2D6 variants in our population, and to evaluate their clinical relevance in personalized medicine. Methodology: We used the Luminex xMAP genotyping system to sequence 305 Saudi individuals visiting the Blood Bank of our Institution and determine which polymorphisms of CYP2D6 gene are prevalent in our region. Results: xTAG genotyping showed that 36.72% (112 out of 305 individuals) carried the CYP2D6_*2. Out of the 112 individuals with the *2 SNP, 6.23% had multiple copies of *2 SNP (19 individuals out of 305 individuals), resulting in an UM phenotype. About 33.44% carried the CYP2D6_*41, which leads to decreased activity of the CYP2D6 enzyme. 19.67% had the wild-type alleles and thus had normal enzyme function. Furthermore, 15.74% carried the CYP2D6_*4, which is the most common nonfunctional form of the CYP2D6 enzyme worldwide. 6.56% carried the CYP2D6_*17, resulting in decreased enzyme activity. Approximately 5.73% carried the CYP2D6_*10, consequently decreasing the enzyme activity, resulting in a PM phenotype. 2.30% carried the CYP2D6_*29, leading to decreased metabolic activity of the enzyme, and 2.30% carried the CYP2D6_*35, resulting in an UM phenotype, 1.64% had a whole-gene deletion CYP2D6_*5, thus resulting in the loss of CYP2D6 enzyme production, 0.66% carried the CYP2D6_*6 variant. One individual carried the CYP2D6_*3(B), producing an inactive form of the enzyme, which leads to decrease of enzyme activity, resulting in a PM phenotype. Finally, one individual carried the CYP2D6_*9, which decreases the enzyme activity. Conclusions: Our study demonstrates that different CYP2D6 variants are highly prevalent in ethnic Saudi Arabs. This finding sets a basis for informed genotyping for these variants in personalized medicine. The study also suggests that xTAG is an appropriate procedure for genotyping the CYP2D6 variants in personalized medicine.

Keywords: CYP2D6, hormonal breast cancer, pharmacogenetics, polymorphism, psychiatric treatment, Saudi population

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353 Nitric Oxide: Role in Immunity and Therapeutics

Authors: Anusha Bhardwaj, Shekhar Shinde

Abstract:

Nitric oxide (NO•) has been documented in research papers as one of the most versatile player in the therapeutics. It is identified as a biological multifunctional messenger molecule which is synthesized by the action of nitric oxide synthase (NOS) enzyme from L-arginine. The protective and the toxic effect in conjunction form the complete picture of the biological function of nitric oxide in humans. The dual nature is because of various factors such as concentration of NO, the isoform of NOS involved, type of cells in which it is synthesized, reaction partners like proteins, reactive oxygen intermediates, prosthetic groups, thiols etc., availability of the substrate L-arginine, intracellular environment in which NO is produced and generation of guanosine 3, 5’- cyclic monophosphate (cGMP). Activation of NOS through infection or trauma leads to one or more systemic effects including enhanced immune activity against invading pathogens, vaso/bronchodilatation in the cardiovascular and respiratory systems and altered neurotransmission which can be protective or toxic. Hence, NO affects the balance between healthy signaling and neurodegeneration in the brain. In lungs, it has beneficial effects on the function of airways as a bronchodilator and acts as the neurotransmitter of bronchodilator nerves. Whereas, on the other hand, NO may have deleterious effects by amplifying the asthmatic inflammatory response and also act as a vasodilator in the airways by increasing plasma exudation. But NOS Inhibitors and NO donors hamper the signalling pathway and hence a therapeutic application of NO is compromised.

Keywords: nitric oxide, multifunctional, dual nature, therapeutic applications

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352 Exploration of Probiotics and Anti-Microbial Agents in Fermented Milk from Pakistani Camel spp. Breeds

Authors: Deeba N. Baig, Ateeqa Ijaz, Saloome Rafiq

Abstract:

Camel is a religious and culturally significant animal in Asian and African regions. In Pakistan Dromedary and Bactrian are common camel breeds. Other than the transportation use, it is a pivotal source of milk and meat. The quality of its milk and meat is predominantly dependent on the geographical location and variety of vegetation available for the diet. Camel milk (CM) is highly nutritious because of its reduced cholesterol and sugar contents along with enhanced minerals and vitamins level. The absence of beta-lactoglobulin (like human milk), makes CM a safer alternative for infants and children having Cow Milk Allergy (CMA). In addition to this, it has a unique probiotic profile both in raw and fermented form. Number of Lactic acid bacteria (LAB) including lactococcus, lactobacillus, enterococcus, streptococcus, weissella, pediococcus and many other bacteria have been detected. From these LAB Lactobacilli, Bifidobacterium and Enterococcus are widely used commercially for fermentation purpose. CM has high therapeutic value as its effectiveness is known against various ailments like fever, arthritis, asthma, gastritis, hepatitis, Jaundice, constipation, postpartum care of women, anti-venom, dropsy etc. It also has anti-diabetic, anti-microbial, antitumor potential along with its robust efficacy in the treatment of auto-immune disorders. Recently, the role of CM has been explored in brain-gut axis for the therapeutics of neurodevelopmental disorders. In this connection, a lot of grey area was available to explore the probiotics and therapeutics latent in the CM available in Pakistan. Thus, current study was designed to explore the predominant probiotic flora and antimicrobial potential of CM from different local breeds of Pakistan. The probiotics have been identified through biochemical, physiological and ribo-typing methods. In addition to this, bacteriocins (antimicrobial-agents) were screened through PCR-based approach. Results of this study revealed that CM from different breeds of camel depicted a number of similar probiotic candidates along with the range of limited variability. However, the nucleotide sequence analysis of selected anti-listerial bacteriocins exposed least variability. As a conclusion, the CM has sufficient probiotic availability and significant anti-microbial potential.

Keywords: bacteriocins, camel milk, probiotics potential, therapeutics

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351 Randomized Controlled Trial for the Management of Pain and Anxiety Using Virtual Reality During the Care of Older Hospitalized Patients

Authors: Corbel Camille, Le Cerf Flora, Capriz Françoise, Vaillant-Ciszewicz Anne-Julie, Breaud Jean, Guerin Olivier, Corveleyn Xavier

Abstract:

Background: The medical environment can generate stressful and anxiety-provoking situations for patients, particularly during painful care procedures for the older population. These stressful environments have deleterious effects on the quality of care and can even put the patient at risk and set the care team up for failure. The search for a solution is, therefore, imperative. The development of new technologies, such as virtual reality (VR), seems to be an answer to this problem. Objectives: The objective of this study is to compare the effects of virtual reality on pain and anxiety when caring for older hospitalized people with the effects of usual care. More precisely, different individual factors (age, cognitive level, individual preferences, etc.) and different virtual reality universes (personalized or non-personalized) are studied to understand the role of these factors in reducing pain and anxiety during care procedures. The aim of this study is to improve the quality of life of patients and caregivers in their work environment. Method: This mono-centered, randomized, controlled study was conducted from September 2023 to September 2024 on 120 participants recruited from the geriatric departments of the Cimiez Hospital, Nice, France. Participants are randomized into three groups: a control group, a personalized VR group and a non-personalized VR group. Each participant is followed during a painful care session. Data are collected before, during and after the care, using measures of pain (Algoplus and numerical scale) and anxiety (Hospital anxiety scale and numerical scale). Physiological assessments with an oximeter are also performed to collect both heart and respiratory rate measurements. The implementation of the care will be assessed among healthcare providers to evaluate its effects on the difficulty and fatigue associated with the care. Additionally, a questionnaire (System Usability Scale) will be administered at the conclusion of the study to determine the willingness of healthcare providers to integrate VR into their daily care practices. Result: The preliminary results indicate significant effects on anxiety (p=.001) and pain (p=<.001) following the VR intervention during care, as compared to the control group. Conclusion: The preliminary results suggest that VRI appears to be a suitable and effective method for reducing anxiety and pain among older hospitalized individuals compared with standard care. Finally, the experiences of healthcare professionals involved will also be considered to assess the impact of these interventions on working conditions and patient support.

Keywords: anxiety, care, pain, older adults, virtual reality

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350 Evaluation of a Personalized Online Decision Aid for Colorectal Cancer Screening: A Randomized Controlled Trial

Authors: Linda P. M. Pluymen, Mariska M. G. Leeflang, I. Stegeman, Henock G. Yebyo, Anne E. M. Brabers, Patrick M. Bossuyt, E. Dekker, Anke J. Woudstra, Mirjam P. Fransen

Abstract:

Weighing the benefits and harms of colorectal cancer screening can be difficult for individuals. An existing online decision aid was expanded with a benefit-harm analysis to help people make an informed decision about participating in colorectal cancer screening. In a randomized controlled trial, we investigated whether those in the intervention group who used the decision aid with benefit-harm analysis were more certain about their decision than those in the control group who used the decision aid without benefit-harm analysis. Participants were 623 (39% of those invited) men and women aged 45 until 75 years old. Analyses were performed in those 386 participants (62%) who reported to have completed the entire decision aid. No statistically significant differences were observed between intervention and control group in decisional conflict score (mean difference 2.4, 95% CI -0.9, 5.6), clarity of values (mean difference 1.0, 95% CI -4.4, 6.6), deliberation score (mean difference 0.5, 95% CI -0.6, 1.7), anxiety score (mean difference 0.0, 95% CI -0.3, 0.3) and risk perception score (mean difference 0.1, -0.1, 0.3). Adding a benefit-harm analysis to an online decision aid did not improve informed decision making about participating in colorectal cancer screening.

Keywords: benefit-harm analysis, decision aid, informed decision making, personalized decision making

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349 Linking Excellence in Biomedical Knowledge and Computational Intelligence Research for Personalized Management of Cardiovascular Diseases within Personal Health Care

Authors: T. Rocha, P. Carvalho, S. Paredes, J. Henriques, A. Bianchi, V. Traver, A. Martinez

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The main goal of LINK project is to join competences in intelligent processing in order to create a research ecosystem to address two central scientific and technical challenges for personal health care (PHC) deployment: i) how to merge clinical evidence knowledge in computational decision support systems for PHC management and ii) how to provide achieve personalized services, i.e., solutions adapted to the specific user needs and characteristics. The final goal of one of the work packages (WP2), designated Sustainable Linking and Synergies for Excellence, is the definition, implementation and coordination of the necessary activities to create and to strengthen durable links between the LiNK partners. This work focuses on the strategy that has been followed to achieve the definition of the Research Tracks (RT), which will support a set of actions to be pursued along the LiNK project. These include common research activities, knowledge transfer among the researchers of the consortium, and PhD student and post-doc co-advisement. Moreover, the RTs will establish the basis for the definition of concepts and their evolution to project proposals.

Keywords: LiNK Twin European Project, personal health care, cardiovascular diseases, research tracks

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348 Integrated Machine Learning Framework for At-Home Patients Personalized Risk Prediction Using Activities, Biometric, and Demographic Features

Authors: Claire Xu, Welton Wang, Manasvi Pinnaka, Anqi Pan, Michael Han

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Hospitalizations account for one-third of the total health care spending in the US. Early risk detection and intervention can reduce this high cost and increase the satisfaction of both patients and physicians. Due to the lack of awareness of the potential arising risks in home environment, the opportunities for patients to seek early actions of clinical visits are dramatically reduced. This research aims to offer a highly personalized remote patients monitoring and risk assessment AI framework to identify the potentially preventable hospitalization for both acute as well as chronic diseases. A hybrid-AI framework is trained with data from clinical setting, patients surveys, as well as online databases. 20+ risk factors are analyzed ranging from activities, biometric info, demographic info, socio-economic info, hospitalization history, medication info, lifestyle info, etc. The AI model yields high performance of 87% accuracy and 88 sensitivity with 20+ features. This hybrid-AI framework is proven to be effective in identifying the potentially preventable hospitalization. Further, the high indicative features are identified by the models which guide us to a healthy lifestyle and early intervention suggestions.

Keywords: hospitalization prevention, machine learning, remote patient monitoring, risk prediction

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347 Supply Chain Resource Optimization Model for E-Commerce Pure Players

Authors: Zair Firdaous, Fourka Mohamed, Elfelsoufi Zoubir

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The arrival of e-commerce has changed the supply chain management on the operational level as well as on the organization and strategic and even tactical decisions of the companies. The optimization of resources is an issue that is needed on the tactical and operational strategic plan. This work considers the allocation of resources in the case of pure players that have launched online sales. The aim is to improve the level of customer satisfaction and maintaining the benefits of e-retailer and of its cooperators and reducing costs and risks. We first modeled the B2C chain with all operations that integrates and possible scenarios since online retailers offer a wide selection of personalized service. The personalized services that online shopping companies offer to the clients can be embodied in many aspects, such as the customizations of payment, the distribution methods, and after-sales service choices. Every aspect of customized service has several modes. At that time, we analyzed the optimization problems of supply chain resource in customized online shopping service mode. Then, we realized an optimization model and algorithm for the development based on the analysis of the of the B2C supply chain resources. It is a multi-objective optimization that considers the collaboration of resources in operations, time and costs but also the risks and the quality of services as well as dynamic and uncertain characters related to the request.

Keywords: supply chain resource, e-commerce, pure-players, optimization

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346 Artificially Intelligent Context Aware Personal Computer Assistant (ACPCA)

Authors: Abdul Mannan Akhtar

Abstract:

In this paper a novel concept of a self learning smart personalized computer assistant (ACPCA) is established which is a context aware system. Based on user habits, moods, and other routines/situational reactions the system will manage various services and suggestions at appropriate times including what schedule to follow, what to watch, what software to be used, what should be deleted etc. This system will utilize a hybrid fuzzyNeural model to predict what the user will do next and support his actions. This will be done by establishing fuzzy sets of user activities, choices, preferences etc. and utilizing their combinations to predict his moods and immediate preferences. Various application of context aware systems exist separately e.g. on certain websites for music or multimedia suggestions but a personalized autonomous system that could adapt to user’s personality does not exist at present. Due to the novelty and massiveness of this concept, this paper will primarily focus on the problem establishment, product features and its functionality; however a small mini case is also implemented on MATLAB to demonstrate some of the aspects of ACPCA. The mini case involves prediction of user moods, activity, routine and food preference using a hybrid fuzzy-Neural soft computing technique.

Keywords: context aware systems, APCPCA, soft computing techniques, artificial intelligence, fuzzy logic, neural network, mood detection, face detection, activity detection

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345 Optimisation of B2C Supply Chain Resource Allocation

Authors: Firdaous Zair, Zoubir Elfelsoufi, Mohammed Fourka

Abstract:

The allocation of resources is an issue that is needed on the tactical and operational strategic plan. This work considers the allocation of resources in the case of pure players, manufacturers and Click & Mortars that have launched online sales. The aim is to improve the level of customer satisfaction and maintaining the benefits of e-retailer and of its cooperators and reducing costs and risks. Our contribution is a decision support system and tool for improving the allocation of resources in logistics chains e-commerce B2C context. We first modeled the B2C chain with all operations that integrates and possible scenarios since online retailers offer a wide selection of personalized service. The personalized services that online shopping companies offer to the clients can be embodied in many aspects, such as the customizations of payment, the distribution methods, and after-sales service choices. In addition, every aspect of customized service has several modes. At that time, we analyzed the optimization problems of supply chain resource allocation in customized online shopping service mode, which is different from the supply chain resource allocation under traditional manufacturing or service circumstances. Then we realized an optimization model and algorithm for the development based on the analysis of the allocation of the B2C supply chain resources. It is a multi-objective optimization that considers the collaboration of resources in operations, time and costs but also the risks and the quality of services as well as dynamic and uncertain characters related to the request.

Keywords: e-commerce, supply chain, B2C, optimisation, resource allocation

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344 Aza-Flavanones as Small Molecule Inhibitors of MicroRNA-10b in MDA-MB-231 Breast Cancer Cells

Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra

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MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.

Keywords: breast cancer, microRNA, metastasis, EMT

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343 Personalized Social Resource Recommender Systems on Interest-Based Social Networks

Authors: C. L. Huang, J. J. Sia

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The interest-based social networks, also known as social bookmark sharing systems, are useful platforms for people to conveniently read and collect internet resources. These platforms also providing function of social networks, and users can share and explore internet resources from the social networks. Providing personalized internet resources to users is an important issue on these platforms. This study uses two types of relationship on the social networks—following and follower and proposes a collaborative recommender system, consisting of two main steps. First, this study calculates the relationship strength between the target user and the target user's followings and followers to find top-N similar neighbors. Second, from the top-N similar neighbors, the articles (internet resources) that may interest the target user are recommended to the target user. In this system, users can efficiently obtain recent, related and diverse internet resources (knowledge) from the interest-based social network. This study collected the experimental dataset from Diigo, which is a famous bookmark sharing system. The experimental results show that the proposed recommendation model is more accurate than two traditional baseline recommendation models but slightly lower than the cosine model in accuracy. However, in the metrics of the diversity and executing time, our proposed model outperforms the cosine model.

Keywords: recommender systems, social networks, tagging, bookmark sharing systems, collaborative recommender systems, knowledge management

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342 Behavioral Analysis of Anomalies in Intertemporal Choices Through the Concept of Impatience and Customized Strategies for Four Behavioral Investor Profiles With an Application of the Analytic Hierarchy Process: A Case Study

Authors: Roberta Martino, Viviana Ventre

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The Discounted Utility Model is the essential reference for calculating the utility of intertemporal prospects. According to this model, the value assigned to an outcome is the smaller the greater the distance between the moment in which the choice is made and the instant in which the outcome is perceived. This diminution determines the intertemporal preferences of the individual, the psychological significance of which is encapsulated in the discount rate. The classic model provides a discount rate of linear or exponential nature, necessary for temporally consistent preferences. Empirical evidence, however, has proven that individuals apply discount rates with a hyperbolic nature generating the phenomenon of intemporal inconsistency. What this means is that individuals have difficulty managing their money and future. Behavioral finance, which analyzes the investor's attitude through cognitive psychology, has made it possible to understand that beyond individual financial competence, there are factors that condition choices because they alter the decision-making process: behavioral bias. Since such cognitive biases are inevitable, to improve the quality of choices, research has focused on a personalized approach to strategies that combines behavioral finance with personality theory. From the considerations, it emerges the need to find a procedure to construct the personalized strategies that consider the personal characteristics of the client, such as age or gender, and his personality. The work is developed in three parts. The first part discusses and investigates the weight of the degree of impatience and impatience decrease in the anomalies of the discounted utility model. Specifically, the degree of decrease in impatience quantifies the impact that emotional factors generated by haste and financial market agitation have on decision making. The second part considers the relationship between decision making and personality theory. Specifically, four behavioral categories associated with four categories of behavioral investors are considered. This association allows us to interpret intertemporal choice as a combination of bias and temperament. The third part of the paper presents a method for constructing personalized strategies using Analytic Hierarchy Process. Briefly: the first level of the analytic hierarchy process considers the goal of the strategic plan; the second level considers the four temperaments; the third level compares the temperaments with the anomalies of the discounted utility model; and the fourth level contains the different possible alternatives to be selected. The weights of the hierarchy between level 2 and level 3 are constructed considering the degrees of decrease in impatience derived for each temperament with an experimental phase. The results obtained confirm the relationship between temperaments and anomalies through the degree of decrease in impatience and highlight that the actual impact of emotions in decision making. Moreover, it proposes an original and useful way to improve financial advice. Inclusion of additional levels in the Analytic Hierarchy Process can further improve strategic personalization.

Keywords: analytic hierarchy process, behavioral finance anomalies, intertemporal choice, personalized strategies

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341 Mannose-Functionalized Lipopolysaccharide Nanoparticles for Macrophage-Targeted Dual Delivery of Rifampicin and Isoniazid

Authors: Mumuni Sumaila, Viness Pillay, Yahya E. Choonara, Pradeep Kumar, Pierre P. Kondiah

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Tuberculosis (TB) remains a serious challenge to public health globally, despite every effort put together to curb the disease. Current TB therapeutics available have proven to be inefficient due to a multitude of drawbacks that range from serious adverse effects/drug toxicity to inconsistent bioavailability, which ultimately contributes to the emergence of drug-resistant TB. An effective ‘cargo’ system designed to cleverly deliver therapeutic doses of anti-TB drugs to infection sites and in a sustained-release manner may provide a better therapeutic choice towards winning the war against TB. In the current study, we investigated mannose-functionalized lipopolysaccharide hybrid nanoparticles for safety and efficacy towards macrophage-targeted simultaneous delivery of the two first-line anti-TB drugs, rifampicin (RF) and isoniazid (IS). RF-IS-loaded lipopolysaccharide hybrid nanoparticles were fabricated using the solvent injection technique (SIT), incorporating soy lecithin (SL) and low molecular weight chitosan (CS) as the lipid and polysaccharide components, respectively. Surface-functionalized nanoparticles were obtained through the reaction of the aldehyde group of mannose with free amine functionality present at the surface of the nanoparticles. The functionalized nanocarriers were spherical with average particle size and surface charge of 107.83 nm and +21.77 mV, respectively, and entrapment efficiencies (EE) were 53.52% and 69.80% for RF and IS, respectively. FTIR spectrum revealed high-intensity bands between 1663 cm⁻¹ and 1408 cm⁻¹ wavenumbers (absent in non-functionalized nanoparticles), which could be attributed to the C=N stretching vibration produced by the formation of Schiff’s base (–N=CH–) during the mannosylation reaction. In vitro release studies showed a sustained-release profile for RF and IS, with less than half of the total payload released over a 48-hour period. The nanocarriers were biocompatible and safe, with more than 80% cell viability achieved when incubated with RAW 264.7 cells at concentrations 30 to 500 μg/mL over a 24-hour period. Cellular uptake studies (after a 24-hour incubation period with the murine macrophage cells, RAW 264.7) revealed a 13- and a 9-fold increase in intracellular accumulation of RF and IS, respectively, when compared with the unformulated RF+IS solution. A 6- and a 3-fold increase in intracellular accumulation of RF and IS, respectively, were observed when compared with the non-functionalized nanoparticles. Furthermore, fluorescent microscopy images showed nanoparticle internalization and accumulation within the RAW 264.7 cells, which was more significant in the mannose-functionalized system compared to the non-functionalized nanoparticles. The overall results suggested that the fabricated mannose-functionalized lipopolysaccharide nanoparticles are a safe and promising platform for macrophage-targeted delivery of anti-TB therapeutics. However, in vivo pharmacokinetic/pharmacodynamics studies are required to further substantiate the therapeutic efficacy of the nanosystem.

Keywords: anti-tuberculosis therapeutics, hybrid nanosystem, lipopolysaccharide nanoparticles, macrophage-targeted delivery

Procedia PDF Downloads 132
340 Transforming Healthcare with Immersive Visualization: An Analysis of Virtual and Holographic Health Information Platforms

Authors: Hossein Miri, Zhou YongQi, Chan Bormei-Suy

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The development of advanced technologies and innovative solutions has opened up exciting new possibilities for revolutionizing healthcare systems. One such emerging concept is the use of virtual and holographic health information platforms that aim to provide interactive and personalized medical information to users. This paper provides a review of notable virtual and holographic health information platforms. It begins by highlighting the need for information visualization and 3D representation in healthcare. It then proceeds to provide background knowledge on information visualization and historical developments in 3D visualization technology. Additional domain knowledge concerning holography, holographic computing, and mixed reality is then introduced, followed by highlighting some of their common applications and use cases. After setting the scene and defining the context, the need and importance of virtual and holographic visualization in medicine are discussed. Subsequently, some of the current research areas and applications of digital holography and holographic technology are explored, alongside the importance and role of virtual and holographic visualization in genetics and genomics. An analysis of the key principles and concepts underlying virtual and holographic health information systems is presented, as well as their potential implications for healthcare are pointed out. The paper concludes by examining the most notable existing mixed-reality applications and systems that help doctors visualize diagnostic and genetic data and assist in patient education and communication. This paper is intended to be a valuable resource for researchers, developers, and healthcare professionals who are interested in the use of virtual and holographic technologies to improve healthcare.

Keywords: virtual, holographic, health information platform, personalized interactive medical information

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339 Triazenes: Unearthing Their Hidden Arsenal Against Malaria and Microbial Menace

Authors: Frans J. Smit, Wisdom A. Munzeiwa, Hermanus C. M. Vosloo, Lyn-Marie Birkholtz, Richard K. Haynes

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Malaria and antimicrobial infections remain significant global health concerns, necessitating the continuous search for novel therapeutic approaches. This abstract presents an overview of the potential use of triazenes as effective agents against malaria and various antimicrobial pathogens. Triazenes are a class of compounds characterized by a linear arrangement of three nitrogen atoms, rendering them structurally distinct from their cyclic counterparts. This study investigates the efficacy of triazenes against malaria and explores their antimicrobial activity. Preliminary results revealed significant antimalarial activity of the triazenes, as evidenced by in vitro screening against P. falciparum, the causative agent of malaria. Furthermore, the compounds exhibited broad-spectrum antimicrobial activity, indicating their potential as effective antimicrobial agents. These compounds have shown inhibitory effects on various essential enzymes and processes involved in parasite survival, replication, and transmission. The mechanism of action of triazenes against malaria involves interactions with critical molecular targets, such as enzymes involved in the parasite's metabolic pathways and proteins responsible for host cell invasion. The antimicrobial activity of the triazenes against bacteria and fungi was investigated through disc diffusion screening. The antimicrobial efficacy of triazenes has been observed against both Gram-positive and Gram-negative bacteria, as well as multidrug-resistant strains, making them potential candidates for combating drug-resistant infections. Furthermore, triazenes possess favourable physicochemical properties, such as good stability, solubility, and low toxicity, which are essential for drug development. The structural versatility of triazenes allows for the modification of their chemical composition to enhance their potency, selectivity, and pharmacokinetic properties. These modifications can be tailored to target specific pathogens, increasing the potential for personalized treatment strategies. In conclusion, this study highlights the potential of triazenes as promising candidates for the development of novel antimalarial and antimicrobial therapeutics. Further investigations are necessary to determine the structure-activity relationships and optimize the pharmacological properties of these compounds. The results warrant additional research, including MIC studies, to further explore the antimicrobial activity of the triazenes. Ultimately, these findings contribute to the development of more effective strategies for combating malaria and microbial infections.

Keywords: malaria, anti-microbials, triazene, resistance

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338 Tip60 Histone Acetyltransferase Activators as Neuroepigenetic Therapeutic Modulators for Alzheimer’s Disease

Authors: Akanksha Bhatnagar, Sandhya Kortegare, Felice Elefant

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Context: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive cognitive decline and memory loss. The cause of AD is not fully understood, but it is thought to be caused by a combination of genetic, environmental, and lifestyle factors. One of the hallmarks of AD is the loss of neurons in the hippocampus, a brain region that is important for memory and learning. This loss of neurons is thought to be caused by a decrease in histone acetylation, which is a process that regulates gene expression. Research Aim: The research aim of the study was to develop mall molecule compounds that can enhance the activity of Tip60, a histone acetyltransferase that is important for memory and learning. Methodology/Analysis: The researchers used in silico structural modeling and a pharmacophore-based virtual screening approach to design and synthesize small molecule compounds strongly predicted to target and enhance Tip60’s HAT activity. The compounds were then tested in vitro and in vivo to assess their ability to enhance Tip60 activity and rescue cognitive deficits in AD models. Findings: The researchers found that several of the compounds were able to enhance Tip60 activity and rescue cognitive deficits in AD models. The compounds were also developed to cross the blood-brain barrier, which is an important factor for the development of potential AD therapeutics. Theoretical Importance: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Data Collection: The study collected data from a variety of sources, including in vitro assays and animal models. The in vitro assays assessed the ability of compounds to enhance Tip60 activity using histone acetyltransferase (HAT) enzyme assays and chromatin immunoprecipitation assays. Animal models were used to assess the ability of the compounds to rescue cognitive deficits in AD models using a variety of behavioral tests, including locomotor ability, sensory learning, and recognition tasks. The human clinical trials will be used to assess the safety and efficacy of the compounds in humans. Questions: The question addressed by this study was whether Tip60 HAT activators could be developed as therapeutic agents for AD. Conclusions: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Further research is needed to confirm the safety and efficacy of these compounds in humans.

Keywords: Alzheimer's disease, cognition, neuroepigenetics, drug discovery

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337 Ethicality of Algorithmic Pricing and Consumers’ Resistance

Authors: Zainab Atia, Hongwei He, Panagiotis Sarantopoulos

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Over the past few years, firms have witnessed a massive increase in sophisticated algorithmic deployment, which has become quite pervasive in today’s modern society. With the wide availability of data for retailers, the ability to track consumers using algorithmic pricing has become an integral option in online platforms. As more companies are transforming their businesses and relying more on massive technological advancement, pricing algorithmic systems have brought attention and given rise to its wide adoption, with many accompanying benefits and challenges to be found within its usage. With the overall aim of increasing profits by organizations, algorithmic pricing is becoming a sound option by enabling suppliers to cut costs, allowing better services, improving efficiency and product availability, and enhancing overall consumer experiences. The adoption of algorithms in retail has been pioneered and widely used in literature across varied fields, including marketing, computer science, engineering, economics, and public policy. However, what is more, alarming today is the comprehensive understanding and focus of this technology and its associated ethical influence on consumers’ perceptions and behaviours. Indeed, due to algorithmic ethical concerns, consumers are found to be reluctant in some instances to share their personal data with retailers, which reduces their retention and leads to negative consumer outcomes in some instances. This, in its turn, raises the question of whether firms can still manifest the acceptance of such technologies by consumers while minimizing the ethical transgressions accompanied by their deployment. As recent modest research within the area of marketing and consumer behavior, the current research advances the literature on algorithmic pricing, pricing ethics, consumers’ perceptions, and price fairness literature. With its empirical focus, this paper aims to contribute to the literature by applying the distinction of the two common types of algorithmic pricing, dynamic and personalized, while measuring their relative effect on consumers’ behavioural outcomes. From a managerial perspective, this research offers significant implications that pertain to providing a better human-machine interactive environment (whether online or offline) to improve both businesses’ overall performance and consumers’ wellbeing. Therefore, by allowing more transparent pricing systems, businesses can harness their generated ethical strategies, which fosters consumers’ loyalty and extend their post-purchase behaviour. Thus, by defining the correct balance of pricing and right measures, whether using dynamic or personalized (or both), managers can hence approach consumers more ethically while taking their expectations and responses at a critical stance.

Keywords: algorithmic pricing, dynamic pricing, personalized pricing, price ethicality

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336 Research on Construction of Subject Knowledge Base Based on Literature Knowledge Extraction

Authors: Yumeng Ma, Fang Wang, Jinxia Huang

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Researchers put forward higher requirements for efficient acquisition and utilization of domain knowledge in the big data era. As literature is an effective way for researchers to quickly and accurately understand the research situation in their field, the knowledge discovery based on literature has become a new research method. As a tool to organize and manage knowledge in a specific domain, the subject knowledge base can be used to mine and present the knowledge behind the literature to meet the users' personalized needs. This study designs the construction route of the subject knowledge base for specific research problems. Information extraction method based on knowledge engineering is adopted. Firstly, the subject knowledge model is built through the abstraction of the research elements. Then under the guidance of the knowledge model, extraction rules of knowledge points are compiled to analyze, extract and correlate entities, relations, and attributes in literature. Finally, a database platform based on this structured knowledge is developed that can provide a variety of services such as knowledge retrieval, knowledge browsing, knowledge q&a, and visualization correlation. Taking the construction practices in the field of activating blood circulation and removing stasis as an example, this study analyzes how to construct subject knowledge base based on literature knowledge extraction. As the system functional test shows, this subject knowledge base can realize the expected service scenarios such as a quick query of knowledge, related discovery of knowledge and literature, knowledge organization. As this study enables subject knowledge base to help researchers locate and acquire deep domain knowledge quickly and accurately, it provides a transformation mode of knowledge resource construction and personalized precision knowledge services in the data-intensive research environment.

Keywords: knowledge model, literature knowledge extraction, precision knowledge services, subject knowledge base

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335 A Study of EFL Learners with Different Goal Orientations in Response to Cognitive Diagnostic Reading Feedback

Authors: Yuxuan Tang

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Cognitive diagnostic assessment has received much attention in second language education, and assessment for it can provide pedagogically useful feedback for language learners. However, there is a lack of research on how students interpret and use cognitive diagnostic feedback. Thus the present study aims to adopt a mixed-method approach mainly to explore the relationship between the goal-orientation and students' response to cognitive diagnostic feedback. Almost 200 Chinese undergraduates from two universities in Xi'an, China, will be invited to do a cognitive diagnostic reading test, and each student will receive specialized cognitive diagnostic feedback, comprising of students' reading attributes mastery level generated by applying a well-selected cognitive diagnostic model, students' perceived reading ability assessed by a self-assessing questionnaire and students’ level position in the whole class. And a goal-orientation questionnaire and a self-generated questionnaire on the perception of feedback will be given to students the moment they receive feedback. In addition, interviews of students will be conducted on their future plans to see whether they have awareness of carrying out studying plans. The study aims to find a new perspective towards how students use and interpret cognitive diagnostic feedback in terms of their different goal-orientation (self-based, task-based, and other-based goals) by applying the newest goal orientation model, which is an important construct of motivation in psychology, seldom researched under language learning area. And the study is expected to provide evidence on how diagnostic feedback promotes students' learning under the educational belief of assessment for learning. Practically speaking, according to the personalized diagnostic feedback, students can take remedial self-learning more purposefully, and teachers can target students' weaknesses to adjust teaching methods and carry out tailored teaching.

Keywords: assessment for learning, cognitive diagnostic assessment, goal-orientation, personalized feedback

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334 E-Learning Recommender System Based on Collaborative Filtering and Ontology

Authors: John Tarus, Zhendong Niu, Bakhti Khadidja

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In recent years, e-learning recommender systems has attracted great attention as a solution towards addressing the problem of information overload in e-learning environments and providing relevant recommendations to online learners. E-learning recommenders continue to play an increasing educational role in aiding learners to find appropriate learning materials to support the achievement of their learning goals. Although general recommender systems have recorded significant success in solving the problem of information overload in e-commerce domains and providing accurate recommendations, e-learning recommender systems on the other hand still face some issues arising from differences in learner characteristics such as learning style, skill level and study level. Conventional recommendation techniques such as collaborative filtering and content-based deal with only two types of entities namely users and items with their ratings. These conventional recommender systems do not take into account the learner characteristics in their recommendation process. Therefore, conventional recommendation techniques cannot make accurate and personalized recommendations in e-learning environment. In this paper, we propose a recommendation technique combining collaborative filtering and ontology to recommend personalized learning materials to online learners. Ontology is used to incorporate the learner characteristics into the recommendation process alongside the ratings while collaborate filtering predicts ratings and generate recommendations. Furthermore, ontological knowledge is used by the recommender system at the initial stages in the absence of ratings to alleviate the cold-start problem. Evaluation results show that our proposed recommendation technique outperforms collaborative filtering on its own in terms of personalization and recommendation accuracy.

Keywords: collaborative filtering, e-learning, ontology, recommender system

Procedia PDF Downloads 319
333 Personalized Climate Change Advertising: The Role of Augmented Reality (A.R.) Technology in Encouraging Users for Climate Change Action

Authors: Mokhlisur Rahman

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The growing consensus among scientists and world leaders indicates that immediate action should be considered regarding the climate change phenomenon. However, climate change is no more a global issue but a personal one. Thus, individual participation is necessary to address such a significant issue. Studies show that individuals who perceive climate change as a personal issue are more likely to act toward it. This abstract presents augmented reality (A.R.) technology in the social media platform Facebook video advertising. The idea involves creating a video advertisement that enables users to interact with the video by navigating its features and experiencing the result uniquely and engagingly. This advertisement uses A.R. to bring changes, such as people making changes in real-life scenarios by simple clicks on the video and hearing an instant rewarding fact about their choices. The video shows three options: room, lawn, and driveway. Users select one option and engage in interaction based on while holding the camera in their personal spaces: Suppose users select the first option, room, and hold their camera toward spots such as by the windows, balcony, corners, and even walls. In that case, the A.R. offers users different plants appropriate for those unoccupied spaces in the room. Users can change the options of the plants and see which space at their house deserves a plant that makes it more natural. When a user adds a natural element to the video, the video content explains a piece of beneficiary information about how the user contributes to the world more to be livable and why it is necessary. With the help of A.R., if users select the second option, lawn, and hold their camera toward their lawn, the options are various small trees for their lawn to make it more environmentally friendly and decorative. The video plays a beneficiary explanation here too. Suppose users select the third option, driveway, and hold their camera toward their driveway. In that case, the A.R. video option offers unique recycle bin designs using A.I. measurement of spaces. The video plays audio information on anthropogenic contribution to greenhouse gas emission. IoT embeds tracking code in the video ad on Facebook, which stores the exact number of views in the cloud for data analysis. An online survey at the end collects short qualitative answers. This study helps understand the number of users involved and willing to change their behavior; It makes personalized advertising in social media. Considering the current state of climate change, the urgency for action is increasing. This ad increases the chance to make direct connections with individuals and gives a sense of personal responsibility for climate change to act

Keywords: motivations, climate, iot, personalized-advertising, action

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332 Periplasmic Expression of Anti-RoxP Antibody Fragments in Escherichia Coli.

Authors: Caspar S. Carson, Gabriel W. Prather, Nicholas E. Wong, Jeffery R. Anton, William H. McCoy

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Cutibacterium acnes is a commensal bacterium found on human skin that has been linked to acne. C. acnes can also be an opportunistic pathogen when it infiltrates the body during surgery. This pathogen can cause dangerous infections of medical implants, such as shoulder replacements, leading to life-threatening blood infections. Compounding this issue, C. acnes resistance to many antibiotics has become an increasing problem worldwide, creating a need for special forms of treatment. C. acnes expresses the protein RoxP, and it requires this protein to colonize human skin. Though this protein is required for C. acnes skin colonization, its function is not yet understood. Inhibition of RoxP function might be an effective treatment for C. acnes infections. To develop such reagents, the McCoy Laboratory generated four unique anti-RoxP antibodies. Preliminary studies in the McCoy Lab have established that each antibody binds a distinct site on RoxP. To assess the potential of these antibodies as therapeutics, it is necessary to specifically characterize these antibody epitopes and evaluate them in assays that assess their ability to inhibit RoxP-dependent C. acnes growth. To provide material for these studies, an antibody expression construct, Fv-clasp(v2), was adapted to encode anti-RoxP antibody sequences. The author hypothesizes that this expression strategy can produce sufficient amounts of >95% pure antibody fragments for further characterization of these antibodies. Four anti-RoxP Fv-clasp(v2) expression constructs (pET vector-based) were transformed into E. coli BL21-Gold(DE3) cells and a small-scale expression and purification trial was performed for each construct to evaluate anti-RoxP Fv-clasp(v2) yield and purity. Successful expression and purification of these antibody constructs will allow for their use in structural studies, such as protein crystallography and cryogenic electron microscopy. Such studies would help to define the antibody binding sites on RoxP, which could then be leveraged in the development of certain methods to treat C. acnes infection through RoxP inhibition.

Keywords: structural biology, protein expression, infectious disease, antibody, therapeutics, E. coli

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331 Unlocking the Future of Grocery Shopping: Graph Neural Network-Based Cold Start Item Recommendations with Reverse Next Item Period Recommendation (RNPR)

Authors: Tesfaye Fenta Boka, Niu Zhendong

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Recommender systems play a crucial role in connecting individuals with the items they require, as is particularly evident in the rapid growth of online grocery shopping platforms. These systems predominantly rely on user-centered recommendations, where items are suggested based on individual preferences, garnering considerable attention and adoption. However, our focus lies on the item-centered recommendation task within the grocery shopping context. In the reverse next item period recommendation (RNPR) task, we are presented with a specific item and challenged to identify potential users who are likely to consume it in the upcoming period. Despite the ever-expanding inventory of products on online grocery platforms, the cold start item problem persists, posing a substantial hurdle in delivering personalized and accurate recommendations for new or niche grocery items. To address this challenge, we propose a Graph Neural Network (GNN)-based approach. By capitalizing on the inherent relationships among grocery items and leveraging users' historical interactions, our model aims to provide reliable and context-aware recommendations for cold-start items. This integration of GNN technology holds the promise of enhancing recommendation accuracy and catering to users' individual preferences. This research contributes to the advancement of personalized recommendations in the online grocery shopping domain. By harnessing the potential of GNNs and exploring item-centered recommendation strategies, we aim to improve the overall shopping experience and satisfaction of users on these platforms.

Keywords: recommender systems, cold start item recommendations, online grocery shopping platforms, graph neural networks

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330 Improved Thermal Comfort and Sensation with Occupant Control of Ceiling Personalized Ventilation System: A Lab Study

Authors: Walid Chakroun, Sorour Alotaibi, Nesreen Ghaddar, Kamel Ghali

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This study aims at determining the extent to which occupant control of microenvironment influences, improves thermal sensation and comfort, and saves energy in spaces equipped with ceiling personalized ventilation (CPV) system assisted by chair fans (CF) and desk fans (DF) in 2 experiments in a climatic chamber equipped with two-station CPV systems, one that allows control of fan flow rate and the other is set to the fan speed of the selected participant in control. Each experiment included two participants each entering the cooled space from transitional environment at a conventional mixed ventilation (MV) at 24 °C. For CPV diffuser, fresh air was delivered at a rate of 20 Cubic feet per minute (CFM) and a temperature of 16 °C while the recirculated air was delivered at the same temperature but at a flow rate 150 CFM. The macroclimate air of the space was at 26 °C. The full speed flow rates for both the CFs and DFs were at 5 CFM and 20 CFM, respectively. Occupant 1 was allowed to operate the CFs or the DFs at (1/3 of the full speed, 2/3 of the full speed, and the full speed) while occupant 2 had no control on the fan speed and their fan speed was selected by occupant 1. Furthermore, a parametric study was conducted to study the effect of increasing the fresh air flow rate on the occupants’ thermal comfort and whole body sensations. The results showed that most occupants in the CPV+CFs, who did not control the CF flow rate, felt comfortable 6 minutes. The participants, who controlled the CF speeds, felt comfortable in around 24 minutes because they were preoccupied with the CFs. For the DF speed control experiments, most participants who did not control the DFs felt comfortable within the first 8 minutes. Similarly to the CPV+CFs, the participants who controlled the DF flow rates felt comfortable at around 26 minutes. When the CPV system was either supported by CFs or DFs, 93% of participants in both cases reached thermal comfort. Participants in the parametric study felt more comfortable when the fresh air flow rate was low, and felt cold when as the flow rate increased.

Keywords: PMV, thermal comfort, thermal environment, thermal sensation

Procedia PDF Downloads 217