Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 248

Search results for: personalized therapeutics

248 Optimal Decisions for Personalized Products with Demand Information Updating and Limited Capacity

Authors: Meimei Zheng

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Product personalization could not only bring new profits to companies but also provide the direction of long-term development for companies. However, the characteristics of personalized product cause some new problems. This paper investigates how companies make decisions on the supply of personalized products when facing different customer attitudes to personalized product and service, constraints due to limited capacity and updates of personalized demand information. This study will provide optimal decisions for companies to develop personalized markets, resulting in promoting business transformation and improving business competitiveness.

Keywords: demand forecast updating, limited capacity, personalized products, optimization

Procedia PDF Downloads 153
247 User Modeling from the Perspective of Improvement in Search Results: A Survey of the State of the Art

Authors: Samira Karimi-Mansoub, Rahem Abri

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Currently, users expect high quality and personalized information from search results. To satisfy user’s needs, personalized approaches to web search have been proposed. These approaches can provide the most appropriate answer for user’s needs by using user context and incorporating information about query provided by combining search technologies. To carry out personalized web search, there is a need to make different techniques on whole of user search process. There are the number of possible deployment of personalized approaches such as personalized web search, personalized recommendation, personalized summarization and filtering systems and etc. but the common feature of all approaches in various domains is that user modeling is utilized to provide personalized information from the Web. So the most important work in personalized approaches is user model mining. User modeling applications and technologies can be used in various domains depending on how the user collected information may be extracted. In addition to, the used techniques to create user model is also different in each of these applications. Since in the previous studies, there was not a complete survey in this field, our purpose is to present a survey on applications and techniques of user modeling from the viewpoint of improvement in search results by considering the existing literature and researches.

Keywords: filtering systems, personalized web search, user modeling, user search behavior

Procedia PDF Downloads 151
246 Acoustic Performance and Application of Three Personalized Sound-Absorbing Materials

Authors: Fangying Wang, Zhang Sanming, Ni Qian

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In recent years, more and more personalized sound absorbing materials have entered the Chinese room acoustical decoration market. The acoustic performance of three kinds of personalized sound-absorbing materials: Flame-retardant Flax Fiber Sound-absorbing Cotton, Eco-Friendly Sand Acoustic Panel and Transparent Micro-perforated Panel (Film) are tested by Reverberation Room Method. The sound absorption characteristic curves show that their performance match for or even exceed the traditional sound absorbing material. Through the application in the actual projects, these personalized sound-absorbing materials also proved their sound absorption ability and unique decorative effect.

Keywords: acoustic performance, application prospect personalized sound-absorbing materials

Procedia PDF Downloads 78
245 A Next Generation Multi-Scale Modeling Theatre for in silico Oncology

Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

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Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

Procedia PDF Downloads 39
244 Tunable Control of Therapeutics Release from the Nanochannel Delivery System (nDS)

Authors: Thomas Geninatti, Bruno Giacomo, Alessandro Grattoni

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Nanofluidic devices have been investigated for over a decade as promising platforms for the controlled release of therapeutics. The nanochannel drug delivery system (nDS), a membrane fabricated with high precision silicon techniques, capable of zero-order release of drugs by exploiting diffusion transport at the nanoscale originated from the interactions between molecules with nanochannel surfaces, showed the flexibility of the sustained release in vitro and in vivo, over periods of time ranging from weeks to months. To improve the implantable bio nanotechnology, in order to create a system that possesses the key features for achieve the suitable release of therapeutics, the next generation of nDS has been created. Platinum electrodes are integrated by e-beam deposition onto both surfaces of the membrane allowing low voltage (<2 V) and active temporal control of drug release through modulation of electrostatic potentials at the inlet and outlet of the membrane’s fluidic channels. Hence, a tunable administration of drugs is ensured from the nanochannel drug delivery system. The membrane will be incorporated into a peek implantable capsule, which will include drug reservoir, control hardware and RF system to allow suitable therapeutic regimens in real-time. Therefore, this new nanotechnology offers tremendous potential solutions to manage chronic disease such as cancer, heart disease, circadian dysfunction, pain and stress.

Keywords: nanochannel membrane, drug delivery, tunable release, personalized administration, nanoscale transport, biomems

Procedia PDF Downloads 191
243 A Framework for Internet Education: Personalised Approach

Authors: Zoe Wong

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The purpose of this paper is to develop a framework for internet education. This framework uses the personalized learning approach for everyone who can freely develop their qualifications & careers. The key components of the framework includes students, teachers, assessments and infrastructure. It allows remove the challenges and limitations of the current educational system and allows learners' to cope with progressing learning materials.

Keywords: internet education, personalized approach, information technology, framework

Procedia PDF Downloads 224
242 Morphology of Cartographic Words: A Perspective from Chinese Characters

Authors: Xinyu Gong, Zhilin Li, Xintao Liu

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Maps are a means of communication. Cartographic language involves established theories of natural language for understanding maps. “Cartographic words’, or “map symbols”, are crucial elements of cartographic language. Personalized mapping is increasingly popular, with growing demands for customized map-making by the general public. Automated symbol-making and customization play a key role in personalized mapping. However, formal representations for the automated construction of map symbols are still lacking. In natural language, the process of word and sentence construction can be formalized. Through the analogy between natural language and graphical language, formal representations of natural language construction can be used as a reference for constructing cartographic language. We selected Chinese character structures (i.e., S

Keywords: personalized mapping, Chinese character, cartographic language, map symbols

Procedia PDF Downloads 36
241 Assessment of Barriers to the Clinical Adoption of Cell-Based Therapeutics

Authors: David Pettitt, Benjamin Davies, Georg Holländer, David Brindley

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Cellular based therapies, whose origins can be traced from the intertwined concepts of tissue engineering and regenerative medicine, have the potential to transform the current medical landscape and offer an approach to managing what were once considered untreatable diseases. However, despite a large increase in basic science activity in the cell therapy arena alongside a growing portfolio of cell therapy trials, the number of industry products available for widespread clinical use correlates poorly with such a magnitude of activity, with the number of cell-based therapeutics in mainstream use remaining comparatively low. This research serves to quantitatively assess the barriers to the clinical adoption of cell-based therapeutics through identification of unique barriers, specific challenges and opportunities facing the development and adoption of such therapies.

Keywords: cell therapy, clinical adoption, commercialization, translation

Procedia PDF Downloads 228
240 Personalized Learning: An Analysis Using Item Response Theory

Authors: A. Yacob, N. Hj. Ali, M. H. Yusoff, M. Y. MohdSaman, W. M. A. F. W. Hamzah

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Personalized learning becomes increasingly popular which not is restricted by time, place or any other barriers. This study proposes an analysis of Personalized Learning using Item Response Theory which considers course material difficulty and learner ability. The study investigates twenty undergraduate students at TATI University College, who are taking programming subject. By using the IRT, it was found that, finding the most appropriate problem levels to each student include high and low level test items together is not a problem. Thus, the student abilities can be asses more accurately and fairly. Learners who experience more anxiety will affect a heavier cognitive load and receive lower test scores. Instructors are encouraged to provide a supportive learning environment to enhance learning effectiveness because Cognitive Load Theory concerns the limited capacity of the brain to absorb new information.

Keywords: assessment, item response theory, cognitive load theory, learning, motivation, performance

Procedia PDF Downloads 194
239 An Analysis of a Canadian Personalized Learning Curriculum

Authors: Ruthanne Tobin

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The shift to a personalized learning (PL) curriculum in Canada represents an innovative approach to teaching and learning that is also evident in various initiatives across the 32-nation OECD. The premise behind PL is that empowering individual learners to have more input into how they access and construct knowledge, and express their understanding of it, will result in more meaningful school experiences and academic success. In this paper presentation, the author reports on a document analysis of the new curriculum in the province of British Columbia. Three theoretical frameworks are used to analyze the new curriculum. Framework 1 focuses on five dominant aspects (FDA) of PL at the classroom level. Framework 2 focuses on conceptualizing and enacting personalized learning (CEPL) within three spheres of influence. Framework 3 focuses on the integration of three types of knowledge (content, technological, and pedagogical). Analysis is ongoing, but preliminary findings suggest that the new curriculum addresses framework 1 quite well, which identifies five areas of personalized learning: 1) assessment for learning; 2) effective teaching and learning; 3) curriculum entitlement (choice); 4) school organization; and 5) “beyond the classroom walls” (learning in the community). Framework 2 appears to be less well developed in the new curriculum. This framework speaks to the dynamics of PL within three spheres of interaction: 1) nested agency, comprised of overarching constraints [and enablers] from policy makers, school administrators and community; 2) relational agency, which refers to a capacity for professionals to develop a network of expertise to serve shared goals; and 3) students’ personalized learning experience, which integrates differentiation with self-regulation strategies. Framework 3 appears to be well executed in the new PL curriculum, as it employs the theoretical model of technological, pedagogical content knowledge (TPACK) in which there are three interdependent bodies of knowledge. Notable within this framework is the emphasis on the pairing of technologies with excellent pedagogies to significantly assist students and teachers. This work will be of high relevance to educators interested in innovative school reform.

Keywords: curriculum reform, K-12 school change, innovations in education, personalized learning

Procedia PDF Downloads 177
238 A Semantic E-Learning and E-Assessment System of Learners

Authors: Wiem Ben Khalifa, Dalila Souilem, Mahmoud Neji

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The evolutions of Social Web and Semantic Web lead us to ask ourselves about the way of supporting the personalization of learning by means of intelligent filtering of educational resources published in the digital networks. We recommend personalized courses of learning articulated around a first educational course defined upstream. Resuming the context and the stakes in the personalization, we also suggest anchoring the personalization of learning in a community of interest within a group of learners enrolled in the same training. This reflection is supported by the display of an active and semantic system of learning dedicated to the constitution of personalized to measure courses and in the due time.

Keywords: Semantic Web, semantic system, ontology, evaluation, e-learning

Procedia PDF Downloads 183
237 Personalize E-Learning System Based on Clustering and Sequence Pattern Mining Approach

Authors: H. S. Saini, K. Vijayalakshmi, Rishi Sayal

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Network-based education has been growing rapidly in size and quality. Knowledge clustering becomes more important in personalized information retrieval for web-learning. A personalized-Learning service after the learners’ knowledge has been classified with clustering. Through automatic analysis of learners’ behaviors, their partition with similar data level and interests may be discovered so as to produce learners with contents that best match educational needs for collaborative learning. We present a specific mining tool and a recommender engine that we have integrated in the online learning in order to help the teacher to carry out the whole e-learning process. We propose to use sequential pattern mining algorithms to discover the most used path by the students and from this information can recommend links to the new students automatically meanwhile they browse in the course. We have Developed a specific author tool in order to help the teacher to apply all the data mining process. We tend to report on many experiments with real knowledge so as to indicate the quality of using both clustering and sequential pattern mining algorithms together for discovering personalized e-learning systems.

Keywords: e-learning, cluster, personalization, sequence, pattern

Procedia PDF Downloads 333
236 A Reading Light That Can Adjust Indoor Light Intensity According to the Activity and Person for Improve Indoor Visual Comfort of Occupants and Tested using Post-occupancy Evaluation Techniques for Sri Lankan Population

Authors: R.T.P. De Silva, T. K. Wijayasiriwardhane, B. Jayawardena

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Most people nowadays spend their time indoor environment. Because of that, a quality indoor environment needs for them. This study was conducted to identify how to improve indoor visual comfort using a personalized light system. Light intensity, light color, glare, and contrast are the main facts that affect visual comfort. The light intensity which needs to perform a task is changed according to the task. Using necessary light intensity and we can improve the visual comfort of occupants. The hue can affect the emotions of occupants. The preferred light colors and intensity change according to the occupant's age and gender. The research was conducted to identify is there any relationship between personalization and visual comfort. To validate this designed an Internet of Things-based reading light. This light can work according to the standard light levels and personalized light levels. It also can measure the current light intensity of the environment and maintain continuous light levels according to the task. The test was conducted by using 25 undergraduates, and 5school students, and 5 adults. The feedbacks are gathered using Post-occupancy evaluation (POE) techniques. Feedbacks are gathered in three steps, It was done without any light control, with standard light level, and with personalized light level Users had to spend 10 minutes under each condition. After finishing each step, collected their feedbacks. According to the result gathered, 94% of participants rated a personalized light system as comfort for them. The feedbacks show stay under continuous light level help to keep their concentrate. Future research can be conducted on how the color of indoor light can affect for indoor visual comfort of occupants using a personalized light system. Further proposed IoT based can improve to change the light colors according to the user's preference.

Keywords: indoor environment quality, internet of things based light system, post occupancy evaluation, visual comfort

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235 The Analysis of Personalized Low-Dose Computed Tomography Protocol Based on Cumulative Effective Radiation Dose and Cumulative Organ Dose for Patients with Breast Cancer with Regular Chest Computed Tomography Follow up

Authors: Okhee Woo

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Purpose: The aim of this study is to evaluate 2-year cumulative effective radiation dose and cumulative organ dose on regular follow-up computed tomography (CT) scans in patients with breast cancer and to establish personalized low-dose CT protocol. Methods and Materials: A retrospective study was performed on the patients with breast cancer who were diagnosed and managed consistently on the basis of routine breast cancer follow-up protocol between 2012-01 and 2016-06. Based on ICRP (International Commission on Radiological Protection) 103, the cumulative effective radiation doses of each patient for 2-year follow-up were analyzed using the commercial radiation management software (Radimetrics, Bayer healthcare). The personalized effective doses on each organ were analyzed in detail by the software-providing Monte Carlo simulation. Results: A total of 3822 CT scans on 490 patients was evaluated (age: 52.32±10.69). The mean scan number for each patient was 7.8±4.54. Each patient was exposed 95.54±63.24 mSv of radiation for 2 years. The cumulative CT radiation dose was significantly higher in patients with lymph node metastasis (p = 0.00). The HER-2 positive patients were more exposed to radiation compared to estrogen or progesterone receptor positive patient (p = 0.00). There was no difference in the cumulative effective radiation dose with different age groups. Conclusion: To acknowledge how much radiation exposed to a patient is a starting point of management of radiation exposure for patients with long-term CT follow-up. The precise and personalized protocol, as well as iterative reconstruction, may reduce hazard from unnecessary radiation exposure.

Keywords: computed tomography, breast cancer, effective radiation dose, cumulative organ dose

Procedia PDF Downloads 66
234 The Effect of Heat Stress on the Gastro-Intestinal Microbiota of Pigs

Authors: Yadnyavalkya Patil, Ravi Gooneratne, Xiang-Hong Ju

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Heat stress (HS) negatively affects the physiology of pigs. In this study, 6 pigs will be subjected to temperatures of 35 ± 2℃ for 12 hrs/day for a duration of 21 days. The changes in the gastrointestinal tract (GIT) microbiota will be observed by analyzing the freshly collected faeces on days 1, 3, 7, 14 and 21. The changes will be compared to faeces from a set of 6 control pigs kept simultaneously at temperatures of 26 ± 2℃ for the same duration of 21 days. Different types of stresses such a weaning have a detrimental effect on GIT microflora. Similarly, HS is expected to have a harmful effect on the microbial diversity of the GIT. How these changes affect the immune system of the pigs will be studied and therapeutics to reduce the negative effects of HS will be developed.

Keywords: GIT microbiota, heat stress, immune system, therapeutics

Procedia PDF Downloads 50
233 Conceptualizing Personalized Learning: Review of Literature 2007-2017

Authors: Ruthanne Tobin

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As our data-driven, cloud-based, knowledge-centric lives become ever more global, mobile, and digital, educational systems everywhere are struggling to keep pace. Schools need to prepare students to become critical-thinking, tech-savvy, life-long learners who are engaged and adaptable enough to find their unique calling in a post-industrial world of work. Recognizing that no nation can afford poor achievement or high dropout rates without jeopardizing its social and economic future, the thirty-two nations of the OECD are launching initiatives to redesign schools, generally under the banner of Personalized Learning or 21st Century Learning. Their intention is to transform education by situating students as co-enquirers and co-contributors with their teachers of what, when, and how learning happens for each individual. In this focused review of the 2007-2017 literature on personalized learning, the author sought answers to two main questions: “What are the theoretical frameworks that guide personalized learning?” and “What is the conceptual understanding of the model?” Ultimately, the review reveals that, although the research area is overly theorized and under-substantiated, it does provide a significant body of knowledge about this potentially transformative educational restructuring. For example, it addresses the following questions: a) What components comprise a PL model? b) How are teachers facilitating agency (voice & choice) in their students? c) What kinds of systems, processes and procedures are being used to guide the innovation? d) How is learning organized, monitored and assessed? e) What role do inquiry based models play? f) How do teachers integrate the three types of knowledge: Content, pedagogical and technological? g) Which kinds of forces enable, and which impede, personalizing learning? h) What is the nature of the collaboration among teachers? i) How do teachers co-regulate differentiated tasks? One finding of the review shows that while technology can dramatically expand access to information, expectations of its impact on teaching and learning are often disappointing unless the technologies are paired with excellent pedagogies in order to address students’ needs, interests and aspirations. This literature review fills a significant gap in this emerging field of research, as it serves to increase conceptual clarity that has hampered both the theorizing and the classroom implementation of a personalized learning model.

Keywords: curriculum change, educational innovation, personalized learning, school reform

Procedia PDF Downloads 127
232 An Integrative Computational Pipeline for Detection of Tumor Epitopes in Cancer Patients

Authors: Tanushree Jaitly, Shailendra Gupta, Leila Taher, Gerold Schuler, Julio Vera

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Genomics-based personalized medicine is a promising approach to fight aggressive tumors based on patient's specific tumor mutation and expression profiles. A remarkable case is, dendritic cell-based immunotherapy, in which tumor epitopes targeting patient's specific mutations are used to design a vaccine that helps in stimulating cytotoxic T cell mediated anticancer immunity. Here we present a computational pipeline for epitope-based personalized cancer vaccines using patient-specific haplotype and cancer mutation profiles. In the workflow proposed, we analyze Whole Exome Sequencing and RNA Sequencing patient data to detect patient-specific mutations and their expression level. Epitopes including the tumor mutations are computationally predicted using patient's haplotype and filtered based on their expression level, binding affinity, and immunogenicity. We calculate binding energy for each filtered major histocompatibility complex (MHC)-peptide complex using docking studies, and use this feature to select good epitope candidates further.

Keywords: cancer immunotherapy, epitope prediction, NGS data, personalized medicine

Procedia PDF Downloads 156
231 Methodology of Personalizing Interior Spaces in Public Libraries

Authors: Baharak Mousapour

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Creating public spaces which are tailored for the specific demands of the individuals is one of the challenges for the contemporary interior designers. Improving the general knowledge as well as providing a forum for all walks of life to exploit is one of the objectives of a public library. In this regard, interior design in consistent with the demands of the individuals is of paramount importance. Seemingly, study spaces, in particular, those in close relation to the personalized sector, have proven to be challenging, according to the literature. To address this challenge, attributes of individuals, namely, perception of people from public spaces and their interactions with the so-called spaces, should be analyzed to provide interior designers with something to work on. This paper follows the analytic-descriptive research methodology by outlining case study libraries which have personalized public libraries with the investigation of the type of personalization as its primary objective and (I) recognition of physical schedule and the know-how of the spatial connection in indoor design of a library and (II) analysis of each personalized space in relation to other spaces of the library as its secondary objectives. The significance of the current research lies in the concept of personalization as one of the most recent methods of attracting people to libraries. Previous research exists in this regard, but the lack of data concerning personalization makes this topic worth investigating. Hence, this study aims to put forward approaches through real-case studies for the designers to deal with this concept.

Keywords: interior design, library, library design, personalization

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230 Pharmacokinetic Model of Warfarin and Its Application in Personalized Medicine

Authors: Vijay Kumar Kutala, Addepalli Pavani, M. Amresh Rao, Naushad Sm

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In this study, we evaluated the impact of CYP2C9*2 and CYP2C9*3 variants on binding and hydroxylation of warfarin. In silico data revealed that warfarin forms two hydrogen bonds with protein backbone i.e. I205 and S209, one hydrogen bond with protein side chain i.e. T301 and stacking interaction with F100 in CYP2C9*1. In CYP2C9*2 and CYP2C9*3 variants, two hydrogen bonds with protein backbone are disrupted. In double variant, all the hydrogen bonds are disrupted. The distances between C7 of S-warfarin and Fe-O in CYP2C9*1, CYP2C9*2, CYP2C9*3 and CYP2C9*2/*3 were 5.81A°, 7.02A°, 7.43° and 10.07°, respectively. The glide scores (Kcal/mol) were -7.698, -7.380, -6.821 and -6.986, respectively. Increase in warfarin/7-hydroxy warfarin ratio was observed with increase in variant alleles. To conclude, CYP2C9*2 and CYP2C9*3 variants result in disruption of hydrogen bonding interactions with warfarin and longer distance between C7 and Fe-O thus impairing warfarin 7-hydroxylation due to lower binding affinity of warfarin.

Keywords: warfarin, CYP2C9 polymorphism, personalized medicine, in Silico

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229 Anti-Fibrillation Propensity of a Flavonoid Baicalein against the Fibrils of Hen Egg White Lysozyme: Potential Therapeutics for Lysozyme Amyloidosis

Authors: Naveed Ahmad Fazili

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More than 20 human diseases involve the fibrillation of a specific protein/peptide which forms pathological deposits at various sites. Hereditary lysozyme amyloidosis is a systemic disorder which mostly affects liver, spleen and kidney. This conformational disorder is featured by lysozyme fibril formation. In vivo lysozyme fibrillation was simulated under in vitro conditions using a strong denaturant GdHCl at 3M concentration. Sharp decline in the ANS fluorescence intensity compared to the partially unfolded states, almost 20 fold increase in ThT fluorescence intensity, increase in absorbance at 450 nm suggesting turbidity, negative ellipticity peak in the far-UVCD at 217 nm, red shift of 50 nm compared to the native state in congo red assay and appearance of a network of long rope like fibrils in TEM analysis suggested HEWL fibrillation. Anti-fibrillation potency of baicalein against the preformed fibrils of HEWL was investigated following ThT assay in which there was a dose dependent decrease in ThT fluorescence intensity compared to the fibrillar state of HEWL with the maximum effect observed at 150 μM baicalein concentration, loss of negative ellipticity peak in the far-UVCD region, dip in the Rayleigh scattering intensity and absorbance at 350 nm and 450 nm respectively together with a reduction in the density of fibrillar structure in TEM imaging. Thus, it could be suggested that baicalein could prove to be a positive therapeutics for hereditary human lysozyme amyloidosis.

Keywords: amyloid fibrils, baicalein, congo red, negative ellipticity, therapeutics

Procedia PDF Downloads 212
228 3D Printing of Dual Tablets: Modified Multiple Release Profiles for Personalized Medicine

Authors: Veronika Lesáková, Silvia Slezáková, František Štěpánek

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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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227 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

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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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226 Prospects of Acellular Organ Scaffolds for Drug Discovery

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

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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

Procedia PDF Downloads 219
225 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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224 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

Abstract:

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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223 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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222 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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221 Supply Chain Resource Optimization Model for E-Commerce Pure Players

Authors: Zair Firdaous, Fourka Mohamed, Elfelsoufi Zoubir

Abstract:

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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220 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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219 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

Procedia PDF Downloads 357