Search results for: peptide designing

Authors: Fawzyah Albaldi

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Urinary tract infections (UTIs) are the most prevalent of infectious diseases and > 80% are caused by uropathogenic E. coli (UPEC). Infection occurs following adhesion to urothelial plaques on bladder epithelial cells, whose major protein constituent are the uroplakins (UPs). Two of the four uroplakins (UPIa and UPIb) are members of the tetraspanin superfamily. The UPEC adhesin FimH is known to interact directly with UPIa. Tetraspanins are a diverse family of transmembrane proteins that generally act as “molecular organizers” by binding different proteins and lipids to form tetraspanin enriched microdomains (TEMs). Previous work by our group has shown that TEMs are involved in the adhesion of many pathogenic bacteria to human cells. Adhesion can be blocked by tetraspanin-derived synthetic peptides, suggesting that tetraspanins may be valuable drug targets. In this study, we investigate the role of tetraspanins in UPEC adherence to bladder epithelial cells. Human bladder cancer cell lines (T24, 5637, RT4), commonly used as in-vitro models to investigate UPEC infection, along with primary human bladder cells, were used in this project. The aim was to establish a model for UPEC adhesion/infection with the objective of evaluating the impact of tetraspanin-derived reagents on this process. Such reagents could reduce the progression of UTI, particularly in patients with indwelling catheters. Tetraspanin expression on the bladder cells was investigated by q-PCR and flow cytometry, with CD9 and CD81 generally highly expressed. Interestingly, despite these cell lines being used by other groups to investigate FimH antagonists, uroplakin proteins (UPIa, UPIb and UPIII) were poorly expressed at the cell surface, although some were present intracellularly. Attempts were made to differentiate the cell lines, to induce cell surface expression of these UPs, but these were largely unsuccessful. Pre-treatment of bladder epithelial cells with anti-CD9 monoclonal antibody significantly decreased UPEC infection, whilst anti-CD81 had no effects. A short (15aa) synthetic peptide corresponding to the large extracellular region (EC2) of CD9 also significantly reduced UPEC adherence. Furthermore, we demonstrated specific binding of that fluorescently tagged peptide to the cells. CD9 is known to associate with a number of heparan sulphate proteoglycans (HSPGs) that have also been implicated in bacterial adhesion. Here, we demonstrated that unfractionated heparin (UFH)and heparin analogs significantly inhibited UPEC adhesion to RT4 cells, as did pre-treatment of the cells with heparinases. Pre-treatment with chondroitin sulphate (CS) and chondroitinase also significantly decreased UPEC adherence to RT4 cells. This study may shed light on a common pathogenicity mechanism involving the organisation of HSPGs by tetraspanins. In summary, although we determined that the bladder cell lines were not suitable to investigate the role of uroplakins in UPEC adhesion, we demonstrated roles for CD9 and cell surface proteoglycans in this interaction. Agents that target these may be useful in treating/preventing UTIs.

Keywords: UTIs, tspan, uroplakins, CD9

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Authors: Sozan H. Omar, Lina L. Al-Rewaili

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The current study aimed to measure the fifth Grade student skills of reading illustrates in physical and chemical chapter included in science textbook, as well as identity the tasks the dispersants related to designing these illustrates which obstruct the students to read them properly. The researcher applied the test instrument of open discuss questions to measure the skill of: recognizing, description, interpretation and assessment for a sample of this research consisted of (269) students who read three illustrates, and conduct an interview with sample of them (27) students to recognize the dispersants related to designing of these illustrates. The study results showed that there are poor levels in illustrated drawing reading skills: description, interpretation, and assessment. The most important dispersants which obstruct the students to read theses illustrates properly representing: Art impacts of these illustrates, there are some elements which don’t serve these illustrates. In the light of the above results, the researcher provided some recommendations such as training the students on using the images and illustrates properly in science textbooks, as well as create simple designs of illustrates and they should be free of crowded elements and impacts which don’t serve the illustrates.

Keywords: reading illustrated drawings skills, fifth grade science, physical and chemical changes

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Authors: Waleed A. Basuliman, Khalid S. AlSaleh, Mohamed Z. Ramadan

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Applying the anthropometric dimensions is considered one of the important factors when designing any human-machine system. In this study, the estimation of anthropometric dimensions has been improved by developing artificial neural network that aims to predict the anthropometric measurements of the male in Saudi Arabia. A total of 1427 Saudi males from age 6 to 60 participated in measuring twenty anthropometric dimensions. These anthropometric measurements are important for designing the majority of work and life applications in Saudi Arabia. The data were collected during 8 months from different locations in Riyadh City. Five of these dimensions were used as predictors variables (inputs) of the model, and the remaining fifteen dimensions were set to be the measured variables (outcomes). The hidden layers have been varied during the structuring stage, and the best performance was achieved with the network structure 6-25-15. The results showed that the developed Neural Network model was significantly able to predict the body dimensions for the population of Saudi Arabia. The network mean absolute percentage error (MAPE) and the root mean squared error (RMSE) were found 0.0348 and 3.225 respectively. The accuracy of the developed neural network was evaluated by compare the predicted outcomes with a multiple regression model. The ANN model performed better and resulted excellent correlation coefficients between the predicted and actual dimensions.

Keywords: artificial neural network, anthropometric measurements, backpropagation, real anthropometric database

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Authors: Fatemeh Jannesarvatan, Ghazaal Parastooei, Jimmy frerejan, Saedeh Mokhtari, Peter Van Rosmalen

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Medical and dental education increasingly emphasizes the acquisition, integration, and coordination of complex knowledge, skills, and attitudes that can be applied in practical situations. Instructional design approaches have focused on using real-life tasks in order to facilitate complex learning in both real and simulated environments. The Four component instructional design (4C/ID) model has become a useful guideline for designing instructional materials that improve learning transfer, especially in health profession education. The objective of this study was to apply the 4C/ID model in the creation of virtual patients (VPs) that dental students can use to practice their clinical management and clinical reasoning skills. The study first explored the context and concept of complication factors and common errors for novices and how they can affect the design of a virtual patient program. The study then selected key dental information and considered the content needs of dental students. The design of virtual patients was based on the 4C/ID model's fundamental principles, which included: Designing learning tasks that reflect real patient scenarios and applying different levels of task complexity to challenge students to apply their knowledge and skills in different contexts. Creating varied learning materials that support students during the VP program and are closely integrated with the learning tasks and students' curricula. Cognitive feedback was provided at different levels of the program. Providing procedural information where students followed a step-by-step process from history taking to writing a comprehensive treatment plan. Four virtual patients were designed using the 4C/ID model's principles, and an experimental design was used to test the effectiveness of the principles in achieving the intended educational outcomes. The 4C/ID model provides an effective framework for designing engaging and successful virtual patients that support the transfer of knowledge and skills for dental students. However, there are some challenges and pitfalls that instructional designers should take into account when developing these educational tools.

Keywords: 4C/ID model, virtual patients, education, dental, instructional design

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Authors: Ehsan Sakhaei, Ali Taherabadi

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In this study, an aft sweep wing with specific characteristic feature was analysis with CFD method in Fluent software. In this analysis wings aerodynamic coefficient was calculated in different rake angle and wing lift curve slope to rake angle was achieved. Wing section was selected among NACA airfoils version 6. The sweep angle of wing is 15 degree, aspect ratio 8 and taper ratios 0.4. Designing and modeling this wing was done in CATIA software. This model was meshed in Gambit software and its three dimensional analysis was done in Fluent software. CFD methods used here were based on pressure base algorithm. SIMPLE technique was used for solving Navier-Stokes equation and Spalart-Allmaras model was utilized to simulate three dimensional wing in air. Roskam method is one of the common and most used methods for determining aerodynamics parameters in the field of airplane designing. In this study besides CFD analysis, an advanced aircraft analysis was used for calculating aerodynamic coefficient using Roskam method. The results of CFD were compared with measured data acquired from Roskam method and authenticity of relation was evaluated. The results and comparison showed that in linear region of lift curve there is a minor difference between aerodynamics parameter acquired from CFD to relation present by Roskam.

Keywords: aft sweep wing, CFD method, fluent, Roskam, Spalart-Allmaras model

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Authors: Huda Alyami

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The present study aims to measure the effectiveness of an "Interactive eBook" in order to develop skills of designing and employing webquests for female intern teachers. The study uses descriptive analytical methodology as well as quasi-experimental methodology. The sample of the study consists of (30) female intern teachers from the Department of Special Education (in the tracks of Gifted Education and Learning Difficulties), during the first semester of the academic year 2015, at King Abdul-Aziz University in Jeddah city. The sample is divided into (15) female intern teachers for the experimental group, and (15) female intern teachers for the control group. A set of qualitative and quantitative tools have been prepared and verified for the study, embodied in: a list of the designing webquests' skills, a list of the employing webquests' skills, a webquests' knowledge achievement test, a product rating card, an observation card, and an interactive ebook. The study concludes the following results: 1. After pre-control, there are statistically significant differences, at the significance level of (α ≤ 0.05), between the mean scores of the experimental and the control groups in the post measurement of the webquests' knowledge achievement test, in favor of the experimental group. 2. There are statistically significant differences, at the significance level of (α ≤ 0.05), between the mean scores of experimental and control groups in the post measurement of the product rating card in favor of the experimental group. 3. There are statistically significant differences, at the significance level of (α ≤ 0.05), between the mean scores of experimental and control groups in the post measurement of the observation card for the experimental group. In the light of the previous findings, the study recommends the following: taking advantage of interactive ebooks when teaching all educational courses for various disciplines at the university level, creating educational participative platforms to share educational interactive ebooks for various disciplines at the local and regional levels. The study suggests conducting further qualitative studies on the effectiveness of interactive ebooks, in addition to conducting studies on the use of (Web 2.0) in webquests.

Keywords: interactive eBook, webquest, design, employing, develop skills

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Authors: Jayantha Withanaarachchi, Sujeeva Setunge, Sara Moridpour

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Gaps in strategic thinking and planning lead to critical transport infrastructure resilience. These gaps in strategic transport and land use development planning have an impact on communities and cities. Natural and man-induced disasters can be catastrophic to communities. After a disaster, many types of critical infrastructure, including transport infrastructure gets un-usable or gets damaged. This paper examines strategic thinking behind the resilience and protection of Critical Transport Infrastructure (CI) within transport networks by investigating the impact of disasters such as bushfires, hurricanes and earthquakes. A detailed analysis of three case studies have been conducted to identify the gaps in strategic transport planning and strategic decision making processes required to mitigate the impacts of disasters. Case studies will be analysed to identify existing gaps in road design, transport planning and decision making. This paper examines the effect of road designing, transport corridors and decision making during transport planning stages and how it impacts transport infrastructure as well as community resilience. A set of recommendations to overcome the shortcomings of existing strategic planning and designing process are presented. This research paper reviews transport infrastructure planning issues and presents the common approach suitable for future strategic thinking and planning which could be adopted in practices.

Keywords: community resilience, decision making , infrastructure resilience, strategic transport planning, transport infrastructure

Procedia PDF Downloads 254

Authors: Waleed Basuliman

Abstract:

Anthropometric dimensions are considered one of the important factors when designing human-machine systems. In this study, the estimation of anthropometric dimensions has been improved by using Artificial Neural Network (ANN) model that is able to predict the anthropometric measurements of Saudi males in Riyadh City. A total of 1427 Saudi males aged 6 to 60 years participated in measuring 20 anthropometric dimensions. These anthropometric measurements are considered important for designing the work and life applications in Saudi Arabia. The data were collected during eight months from different locations in Riyadh City. Five of these dimensions were used as predictors variables (inputs) of the model, and the remaining 15 dimensions were set to be the measured variables (Model’s outcomes). The hidden layers varied during the structuring stage, and the best performance was achieved with the network structure 6-25-15. The results showed that the developed Neural Network model was able to estimate the body dimensions of Saudi male population in Riyadh City. The network's mean absolute percentage error (MAPE) and the root mean squared error (RMSE) were found to be 0.0348 and 3.225, respectively. These results were found less, and then better, than the errors found in the literature. Finally, the accuracy of the developed neural network was evaluated by comparing the predicted outcomes with regression model. The ANN model showed higher coefficient of determination (R2) between the predicted and actual dimensions than the regression model.

Keywords: artificial neural network, anthropometric measurements, back-propagation

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Authors: Yoonjung An, Yongtae Park

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Offering a Product-Service System (PSS) is a well-accepted strategy that companies may adopt to provide a set of systemic solutions to customers. PSSs were initially provided in a simple form but now take diversified and complex forms involving multiple services, products and technologies. With the growing interest in the PSS, frameworks for the PSS development have been introduced by many researchers. However, most of the existing frameworks fail to examine various relations existing in a complex PSS. Since designing a complex PSS involves full integration of multiple products and services, it is essential to identify not only product-service relations but also product-product/ service-service relations. It is also equally important to specify how they are related for better understanding of the system. Moreover, as customers tend to view their purchase from a more holistic perspective, a PSS should be developed based on the whole system’s requirements, rather than focusing only on the product requirements or service requirements. Thus, we propose a framework to develop a complex PSS that is coordinated fully with the requirements of both worlds. Specifically, our approach adopts a multi-domain matrix (MDM). A MDM identifies not only inter-domain relations but also intra-domain relations so that it helps to design a PSS that includes highly desired and closely related core functions/ features. Also, various dependency types and rating schemes proposed in our approach would help the integration process.

Keywords: inter-domain relations, intra-domain relations, multi-domain matrix, product-service system design

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Authors: Siddharth Soni, Gourav Kumar Pandey, Sneha Kumari, Dev Mani Pandey, Koel Mukherjee

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The silkworm Bombyx mori is a commercially important insect, but a major roadblock in silk production are silkworm diseases. Flacherie is one of the diseases of the silkworm, that affects the midgut of the 4th and 5th instar larvae and eventually makes them lethargic, stop feeding and finally result in their death. The concerned disease is a result of bacterial and viral infection and in some instances a combination of both. The present study aims to identify and study the expression level of genes in the flacherie condition. For the said work, total RNA was isolated from the infected larvae at their most probable infectious instar and cDNA was synthesized using Reverse Transcriptase PCR (RT-PCR). This cDNA was then used to amplify disease relalted genes whose expression levels were checked using quantitaive PCR (qPCR) using the double delta Ct method. Cry toxin receptors like APN and BtR-175, ROS mediator Dual Oxidase are few proteins whose genes were overexpressed. Interestingly, pattern recognition receptors (PRRs) C-type lectins' genes were found to be downregulated. The results explain about the strong expression of genes that can distinguish the concerned protein in the midgut of diseased silkworm and thereby aiding knowledge in the field of inhibitor designing research.

Keywords: Bombyx mori, flacherie disease, inhibitor designing, up and down regulation

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Authors: Fengmei Li, Li Xu, Guoliang Xia

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Lysozyme is a catalytic enzyme that performs bacterial cell lysis by cleaving the β-1,4-glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine of peptidoglycan in cell walls. In the present study, an invertebrate-type (i-type) lysozyme gene was cloned from Chinese mitten crab Eriocheir sinensis (designated as EsLysozyme) based on PCR-based rapid amplification of cDNA ends (RACE) technology. The full-length cDNA of EsLysozyme was of 831 bp. SMART and SIGNALP 3.0 program analysis revealed that EsLysozyme contained a signal peptide and a destabilase domain. The five amino acid residues (Tyr63, Trp64, Tyr91, His110, Pro114) and the conserved motif GSLSCG(P/Y)FQI and CL(E/L/R/H)C(I/M)C in i-type lysozymes were also found in EsLysozyme. The high similarity of EsLysozyme with L. vannamei lysozymes and phylogenetic analysis suggested that EsLysozyme should be a new member of i-type lysozyme family.

Keywords: i-type lysozyme, Eriocheir sinensis, cloning, characterization

Procedia PDF Downloads 263

Authors: M. Abdel-Hamid, P. Saporito, R. V. Mateiu, A. Osman, E. Romeih, H. Jenssen

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Camel milk whey (CMW) was hydrolyzed with papain from Carica papaya and fractionated by size exclusion chromatography (SEC). The antibacterial and anti-biofilm activity of the CMW, Camel milk whey hydrolysate (CMWH) and the obtained SEC-fractions was assessed against Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA). SEC-F2 (fraction 2) exhibited antibacterial effectiveness against MRSA and P. aeruginosa with the minimum inhibitory concentration of 0.31 and 0.156 mg/ml, respectively. Furthermore, SEC-F2 significantly decreased biofilm biomass by 71% and 83 % for MRSA and P. aeruginosa in a crystal violet microplate assay. Scanning electron microscopy showed that the SEC-F2 caused changes in the treated bacterial cells. Additionally, LC/MS analysis was used to characterize the peptides of SEC-F2. Two major peptides were detected in SEC-F2 having masses of 414.05 Da and 456.06 Da. In conclusion, this study has demonstrated that hydrolysis of CMW with papain generates small and extremely potent antibacterial and anti-biofilm peptides against both MRSA and P. aeruginosa.

Keywords: camel milk, whey proteins, antibacterial peptide, anti-biofilm

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Authors: Amani Alsaqqaf, Frederick W. B. Li

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Field trips are essential methods of learning in different subjects, and in recent times, there has been a reduction in the number of field trips (FTs) across all learning levels around the world. Virtual field trips (VFTs) in game environments provide FT experience based on the experiential learning theory (ELT). A conceptual framework for designing virtual field trip games (VFTGs) is developed with an aim to support game designers and educators to produce an effective FT experience where technology would enhance education. The conceptual framework quantifies ELT as an internal economy to link learning elements to game mechanics such as feedback loops which leads to facilitating VFTGs design and implementation. This study assesses the conceptual framework for designing VFTGs by investigating the possibility of applying immersive VFTGs in a secondary classroom and compare them with traditional learning that uses video clips and PowerPoint slides from the viewpoint of students’ perceived motivation, presence, and learning. The assessment is achieved by evaluating the learning performance and learner experience of a prototype VFT game, Island of Volcanoes. A quasi-experiment was conducted with 60 secondary school students. The findings of this study are that the VFTG enhanced learning performance to a better level than did the traditional way of learning, and in addition, it provided motivation and a general feeling of presence in the VFTG environment.

Keywords: conceptual framework, game-based learning, game design, virtual field trip game

Procedia PDF Downloads 194

Authors: Chetna Dhand, Venkatesh Mayandi, Silvia Marrero Diaz, Roger W. Beuerman, Seeram Ramakrishna, Rajamani Lakshminarayanan

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Sturdy Insect Cuticle Sclerotization, Incredible Substrate independent Mussel’s bioadhesion, Tanning of Leather are some of catechol(amine)s mediated natural processes. Chemical contemplation spots toward a mechanism instigated with the formation of the quinone moieties from the respective catechol(amine)s, via oxidation, followed by the nucleophilic addition of the amino acids/proteins/peptides to this quinone leads to the development of highly strong, cross-linked and water-resistant proteinacious structures. Inspired with this remarkable catechol(amine)s chemistry towards amino acids/proteins/peptides, we attempted to design highly stable and water-resistant antifungal wound dressing mats with exceptional durability using collagen (protein), dopamine (catecholamine) and antifungal drugs (Amphotericin B and Caspofungin) as the key materials. Electrospinning technique has been used to fabricate desired nanofibrous mat including Collagen (COLL), COLL/Dopamine (COLL/DP) and calcium incorporated COLL/DP (COLL-DP-Ca2+). The prepared protein-based scaffolds have been studied for their microscopic investigations (SEM, TEM, and AFM), structural analysis (FT-IR), mechanical properties, water wettability characteristics and aqueous stability. Biocompatibility of these scaffolds has been analyzed for dermal fibroblast cells using MTS assay, Cell TrackerTM Green CMFDA and confocal imaging. Being the winner sample, COLL-DP-Ca2+ scaffold has been selected for incorporating two antifungal drugs namely Caspofungin (Peptide based) and Amphotericin B (Non-Peptide based). Antifungal efficiency of the designed mats has been evaluated for eight diverse fungal strains employing different microbial assays including disc diffusion, cell-viability assay, time kill kinetics etc. To confirm the durability of these mats, in term of their antifungal activity, drug leaching studies has been performed and monitored using disc diffusion assay each day. Ex-vivo fungal infection model has also been developed and utilized to validate the antifungal efficacy of the designed wound dressings. Results clearly reveal dopamine mediated crosslinking within COLL-antifungal scaffolds that leads to the generation of highly stable, mechanical tough, biocompatible wound dressings having the zone of inhabitation of ≥ 2 cm for almost all the investigated fungal strains. Leaching studies and Ex-vivo model has confirmed the durability of these wound dressing for more than 3 weeks and certified their suitability for commercialization. A model has also been proposed to enlighten the chemical mechanism involved for the development of these antifungal wound dressings with exceptional robustness.

Keywords: catecholamine chemistry, electrospinning technique, antifungals, wound dressings, collagen

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Authors: Fatma Al Abdullah, Shahad Al Ameer, Ritaj Jaragh, Fatimah Khajah, Rawan Qambar, Amr Nounou

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Kuwait currently manufactures its tankers in foreign countries. Oil tankers play a role in the supply chain of the oil industry. Therefore, with Kuwait’s sufficient financial resources, the country should secure itself strategically in order to protect its oil industry to sustain economic development. The purpose of this report is designing an oil tankers’ shipyard facility. Basing the shipyard facility in Kuwait will have great economic rewards. The shipbuilding industry directly enhances the industrial chain in terms of new job and business opportunities as well as educational fields. Heavy Engineering Industries & Shipbuilding Co. K.S.C. (HEISCO) was chosen as a host due to benefits that will result from HEISCO’s existing infrastructure and expertise to reduce cost. The Facility Design methodology chosen has been used because it covers all aspects needed for the report. The oil tanker market is witnessing a shift from crude tankers to product tankers. Therefore the Panamax tanker (product tanker) was selected to be manufactured in the facility. The different departments needed in shipyards were identified based on studying different global shipyards. Technologies needed to build ships helped in the process design. It was noticed that ships are engineer to order. The new layout development of the proposed shipyard is currently in progress. A feasibility study will be conducted to ensure the success of the facility after developing the shipyard’s layout.

Keywords: oil tankers, shipbuilding, shipyard, facility design, Kuwait

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Authors: Federico Cevoli

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Purinergic P2X7 receptors (P2X7R) are ligand-gated non-selective cation channels involved in several physiological and pathological processes. They are particularly promising pharmacological targets as they are present in an increasing number of different cells types. P2X7R activation is triggered following elevated concentrations of extracellular ATP, similarly to those observed in tissues injury, chronic inflammation and T-cell activation, as well as in the scrambling of phospholipids leading to membrane blebbing and apoptosis. Another hallmark of P2X7 is cell permeabilization, commonly known as “macropore” formation allowing the passage of nanometer-sized molecules up to 900Da. Recently, full-length P2X7 Cryo-EM structures revealed unique functional sites, including two cytoplasmic domains - the cytoplasmic "anchor" and "ballast". To date, the molecular units/complex by which P2X7R exerts its pathophysiological functions are unknown. Using custom-made cell-penetrating HIV-1 TAT peptides, we show for the first-time potential implications of P2X7 cytoplasmic anchor in the regulation of caspase3/7 activation as well as TNFα regulation.

Keywords: P2X7R, immunology, TAT-peptide, cell death

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Authors: Toktam Khatibi

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Self-supervised learning (SSL) includes machine learning models that are trained on one aspect and/or one part of the input to learn other aspects and/or part of it. SSL models are divided into two different categories, including pre-text task-based models and contrastive learning ones. Pre-text tasks are some auxiliary tasks learning pseudo-labels, and the trained models are further fine-tuned for downstream tasks. However, one important disadvantage of SSL using pre-text task solving is defining an appropriate pre-text task for each image dataset with a variety of image modalities. Therefore, it is required to design an appropriate pretext task automatically for each dataset and each downstream task. To the best of our knowledge, the automatic designing of pretext tasks for image analysis has not been considered yet. In this paper, we present a framework based on In-context learning that describes each task based on its input and output data using a pre-trained image transformer. Our proposed method combines the input image and its learned description for optimizing the pre-text task design and its hyper-parameters using Meta-learning models. The representations learned from the pre-text tasks are fine-tuned for solving the downstream tasks. We demonstrate that our proposed framework outperforms the compared ones on unseen tasks and image modalities in addition to its superior performance for previously known tasks and datasets.

Keywords: in-context learning (ICL), meta learning, self-supervised learning (SSL), vision-language domain, transformers

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Authors: Alaa Mostafa, Samuel Dagogo-Jack, Vivian Thieu, Maria Yu, Nan Zhang, Dara Schuster, Luis-Emilio Garcia-Perez

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Dulaglutide (DU), a once-weekly glucagon-like peptide-1 receptor agonist, was studied in the AWARD clinical trial program in adult patients with type 2 diabetes (T2D) and demonstrated significant hemoglobin A1c (A1c) reduction and potential for weight loss. To evaluate the efficacy and safety of DU 1.5 mg and DU 0.75 mg in patients with T2D by baseline A1c <8.5% or ≥8.5%, a post-hoc analysis was conducted on AWARD-1 to -6 and -8 at 6 months. Across 7 studies, 55% to 82% of the DU-treated patients had a baseline A1c <8.5%, and 18% to 45% had a baseline A1c ≥8.5%. The ranges of A1c reductions with baseline A1c <8.5% and ≥8.5%, respectively, were: DU 1.5 mg: -0.67% to -1.25% and -1.22% to -2.37%; DU 0.75 mg: -0.53% to -1.07% and -1.37% to -2.19%. The A1c reduction from the pooled analysis was greater in patients with baseline A1c ≥8.5% than patients with baseline A1c <8.5%, respectively: DU 1.5 mg: -1.86% and -1.02%; DU 0.75 mg: -1.75% and -0.83%. DU treatments were well tolerated among baseline A1c subgroups. Across the AWARD program, DU 1.5 mg and DU 0.75 mg demonstrated significant A1c reduction in both subgroups with an acceptable safety profile. Compared to patients with baseline A1c <8.5%, patients with baseline A1c ≥8.5% had greater A1c reduction. Disclosures: This study was supported and conducted by Eli Lilly and Company, Indianapolis, IN, USA.

Keywords: A1c reduction, dulaglutide, type 2 diabetes, weight loss

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Authors: Shryas Bhurat, Aryan Vashistha, Sampreet Dinakar Nayak, Ayush Gupta

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As the technology is advancing more towards high computational resources, there is a paradigm shift in the usage of these resources to optimize the design process. This paper discusses the usage of ‘Generative Design using Artificial Intelligence’ to build better models that adapt the operations like selection, mutation, and crossover to generate results. The human mind thinks of the simplest approach while designing an object, but the intelligence learns from the past & designs the complex optimized CAD Models. Generative Design takes the boundary conditions and comes up with multiple solutions with iterations to come up with a sturdy design with the most optimal parameter that is given, saving huge amounts of time & resources. The new production techniques that are at our disposal allow us to use additive manufacturing, 3D printing, and other innovative manufacturing techniques to save resources and design artistically engineered CAD Models. Also, this paper discusses the Genetic Algorithm, the Non-Domination technique to choose the right results using biomimicry that has evolved for current habitation for millions of years. The computer uses parametric models to generate newer models using an iterative approach & uses cloud computing to store these iterative designs. The later part of the paper compares the topology optimization technology with Generative Design that is previously being used to generate CAD Models. Finally, this paper shows the performance of algorithms and how these algorithms help in designing resource-efficient models.

Keywords: genetic algorithm, bio mimicry, generative modeling, non-dominant techniques

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Authors: Alena Semeradtova, Marcel Stofik, Lucie Mareckova, Petr Maly, Ondrej Stanek, Jan Maly

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Recently, novel strategies based on so-called molecular evolution were shown to be effective for the production of various peptide ligand libraries with high affinities to molecular targets of interest comparable or even better than monoclonal antibodies. The major advantage of these peptide scaffolds is mainly their prevailing low molecular weight and simple structure. This study describes a new high-affinity binding molecules based immunesensor using a simple optical system for human serum albumin (HSA) detection as a model molecule. We present a comparison of two variants of recombinant binders based on albumin binding domain of the protein G (ABD) performed on micropatterned glass chip. Binding domains may be tailored to any specific target of interest by molecular evolution. Micropatterened glass chips were prepared using UV-photolithography on chromium sputtered glasses. Glass surface was modified by (3-aminopropyl)trietoxysilane and biotin-PEG-acid using EDC/NHS chemistry. Two variants of high-affinity binding molecules were used to detect target molecule. Firstly, a variant is based on ABD domain fused with TolA chain. This molecule is in vivo biotinylated and each molecule contains one molecule of biotin and one ABD domain. Secondly, the variant is ABD domain based on streptavidin molecule and contains four gaps for biotin and four ABD domains. These high-affinity molecules were immobilized to the chip surface via biotin-streptavidin chemistry. To eliminate nonspecific binding 1% bovine serum albumin (BSA) or 6% fetal bovine serum (FBS) were used in every step. For both variants range of measured concentrations of fluorescently labelled HSA was 0 – 30 µg/ml. As a control, we performed a simultaneous assay without high-affinity binding molecules. Fluorescent signal was measured using inverse fluorescent microscope Olympus IX 70 with COOL LED pE 4000 as a light source, related filters, and camera Retiga 2000R as a detector. The fluorescent signal from non-modified areas was substracted from the signal of the fluorescent areas. Results were presented in graphs showing the dependence of measured grayscale value on the log-scale of HSA concentration. For the TolA variant the limit of detection (LOD) of the optical immunosensor proposed in this study is calculated to be 0,20 µg/ml for HSA detection in 1% BSA and 0,24 µg/ml in 6% FBS. In the case of streptavidin-based molecule, it was 0,04 µg/ml and 0,07 µg/ml respectively. The dynamical range of the immunosensor was possible to estimate just in the case of TolA variant and it was calculated to be 0,49 – 3,75 µg/ml and 0,73-1,88 µg/ml respectively. In the case of the streptavidin-based the variant we didn´t reach the surface saturation even with the 480 ug/ml concentration and the upper value of dynamical range was not estimated. Lower value was calculated to be 0,14 µg/ml and 0,17 µg/ml respectively. Based on the obtained results, it´s clear that both variants are useful for creating the bio-recognizing layer on immunosensors. For this particular system, it is obvious that the variant based on streptavidin molecule is more useful for biosensing on glass planar surfaces. Immunosensors based on this variant would exhibit better limit of detection and wide dynamical range.

Keywords: high affinity binding molecules, human serum albumin, optical immunosensor, protein G, UV-photolitography

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Authors: Youngjae Jin, Daeshik Kim

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This paper describes a cycle accurate simulation results of weight values learned by an auto-encoder behavior model in terms of pre-route simulation. Given the results we visualized the first layer representations with natural images. Many common deep learning threads have focused on learning high-level abstraction of unlabeled raw data by unsupervised feature learning. However, in the process of handling such a huge amount of data, the learning method’s computation complexity and time limited advanced research. These limitations came from the fact these algorithms were computed by using only single core CPUs. For this reason, parallel-based hardware, FPGAs, was seen as a possible solution to overcome these limitations. We adopted and simulated the ready-made auto-encoder to design a behavior model in Verilog HDL before designing hardware. With the auto-encoder behavior model pre-route simulation, we obtained the cycle accurate results of the parameter of each hidden layer by using MODELSIM. The cycle accurate results are very important factor in designing a parallel-based digital hardware. Finally this paper shows an appropriate operation of behavior model based pre-route simulation. Moreover, we visualized learning latent representations of the first hidden layer with Kyoto natural image dataset.

Keywords: auto-encoder, behavior model simulation, digital hardware design, pre-route simulation, Unsupervised feature learning

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Authors: Su Mon Saw, Joe Rothnagel

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Short open reading frames (sORFs) located in 5’UTR of mRNAs are known as uORFs. Characterization of uORF-encoded peptides (uPEPs) i.e., a subset of short open reading frame encoded peptides (sPEPs) and their translation regulation lead to understanding of causes of genetic disease, proteome complexity and development of treatments. Existence of uORFs within cellular proteome could be detected by LC-MS/MS. The ability of uORF to be translated into uPEP and achievement of uPEP identification will allow uPEP’s characterization, structures, functions, subcellular localization, evolutionary maintenance (conservation in human and other species) and abundance in cells. It is hypothesized that a subset of sORFs are translatable and that their encoded sPEPs are functional and are endogenously expressed contributing to the eukaryotic cellular proteome complexity. This project aimed to investigate whether sORFs encode functional peptides. Liquid chromatography-mass spectrometry (LC-MS) and bioinformatics were thus employed. Due to probable low abundance of sPEPs and small in sizes, the need for efficient peptide enrichment strategies for enriching small proteins and depleting the sub-proteome of large and abundant proteins is crucial for identifying sPEPs. Low molecular weight proteins were extracted using SDS-PAGE from Human Embryonic Kidney (HEK293) cells and Strong Cation Exchange Chromatography (SCX) from secreted HEK293 cells. Extracted proteins were digested by trypsin to peptides, which were detected by LC-MS/MS. The MS/MS data obtained was searched against Swiss-Prot using MASCOT version 2.4 to filter out known proteins, and all unmatched spectra were re-searched against human RefSeq database. ProteinPilot v5.0.1 was used to identify sPEPs by searching against human RefSeq, Vanderperre and Human Alternative Open Reading Frame (HaltORF) databases. Potential sPEPs were analyzed by bioinformatics. Since SDS PAGE electrophoresis could not separate proteins <20kDa, this could not identify sPEPs. All MASCOT-identified peptide fragments were parts of main open reading frame (mORF) by ORF Finder search and blastp search. No sPEP was detected and existence of sPEPs could not be identified in this study. 13 translated sORFs in HEK293 cells by mass spectrometry in previous studies were characterized by bioinformatics. Identified sPEPs from previous studies were <100 amino acids and <15 kDa. Bioinformatics results showed that sORFs are translated to sPEPs and contribute to proteome complexity. uPEP translated from uORF of SLC35A4 was strongly conserved in human and mouse while uPEP translated from uORF of MKKS was strongly conserved in human and Rhesus monkey. Cross-species conserved uORFs in association with protein translation strongly suggest evolutionary maintenance of coding sequence and indicate probable functional expression of peptides encoded within these uORFs. Translation of sORFs was confirmed by mass spectrometry and sPEPs were characterized with bioinformatics.

Keywords: bioinformatics, HEK293 cells, liquid chromatography-mass spectrometry, ProteinPilot, Strong Cation Exchange Chromatography, SDS-PAGE, sPEPs

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Authors: Yeng Min Yi, Rosli Md Illias, Salehhuddin Hamdan

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Industrial biocatalysis is mainly based on the use of cell free or intracellular enzyme systems. However, the expensive cost and relatively lower operational stability of free enzymes limit practical use in industries. Cell surface display system can be used as a cost-efficient alternative to overcome the laborious purification and substrate transport limitation. In this research, TibA autotransporter from E. coli was used to display Aspergillus fumigatus xylanase (xyn). The amplified xyn was fused in between N-terminal signal peptide and C-terminal β-barrel of TibA. The cloned was transformed and expressed in E. coli BL21 (DE3). Outer membrane localization of TibA-xyn fusion protein was confirmed by SDS PAGE and western blot with expected size of 62.5 kDa. Functional display of xyn was examined by activity assay. Cell surface displayed xyn exhibited the highest activity at 37 °c, 0.3 mM IPTG. As a summary, TibA displaying system has the potential for further industrial applications. Moreover, this is the first report of the display of xylanase using TibA on the surface of E. coli.

Keywords: biocatalysis, cell surface display, Escherichia coli, TibA autotransporter

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Authors: Mojtaba Aghajari, Alireza Aghasi

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The first challenge which the current research faced has been the identification or determination of the level of knowledge in Isfahan public transportation corporation, and the second challenge has been the recognition and choice of a proper approach for the instructional system design. Responding these two challenges will present an appropriate model of instructional system design. In order to respond the first challenge or question, Nonaka and Takeuchi KM model has been utilized due to its universality among the 26 models proposed so far. The statistical population of this research included 2200 people, among which 200 persons were chosen as the sample of the research by the use of Morgan’s method. The data gathering has been carried out by the means of a questionnaire based on Nonaka and Takeuchi KM model, analysis of which has been done by SPSS program. The output of this questionnaire, yielding the point of 1.96 (out of 5 points), revealed that the general condition of Isfahan public transportation corporation is weak concerning its being knowledge-centered. After placing this output on Jonassen’s continuum, it was revealed that the appropriate approach for instructional system design is the system (or behavioral) approach. Accordingly, different steps of the general model of ADDIE, which covers all of the ISO10015 standards, were adopted in the act of designing. Such process in Isfahan public transportation corporation was designed and divided into three main steps, including: instructional designing and planning, instructional course planning, determination of the evaluation and the effectiveness of the instructional courses.

Keywords: instructional system design, system approach, knowledge management, employees

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Authors: Fengmei Li, Li Xu, Guoliang Xia

Abstract:

Whey acidic proteins (WAP) domain-containing proteins in crustacean are involved in innate immune response against microbial invasion. In the present study, a novel double WAP domain (DWD)-containing protein gene 3 was identified from Chinese mitten crab Eriocheir sinensis (designated EsDWD3) by expressed sequence tag (EST) analysis and PCR techniques. The full-length cDNA of EsDWD3 was of 1223 bp, consisting of a 5′-terminal untranslated region (UTR) of 74 bp, a 3′ UTR of 727 bp with a polyadenylation signal sequence AATAAA and a polyA tail, and an open reading frame (ORF) of 423 bp. The ORF encoded a polypeptide of 140 amino acids with a signal peptide of 22 amino acids. The deduced protein sequence EsDWD3 showed 96.4 % amino acid similar to other reported EsDWD1 from E. sinensis, and phylogenetic tree analysis revealed that EsDWD3 had closer relationships with the reported two double WAP domain-containing proteins of E. sinensis species.

Keywords: Chinese mitten crab, Eriocheir sinensis, cloning, double WAP domain-containing protein

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Authors: Wenliang Song, Yu Zhang, Hua Jin, Il Kim

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The self-assembly of the polypeptide (PP) into well-defined structures at different length scales is both biomimetic relevant and fundamentally interesting. Although there are various reports of nanostructures fabricated by the self-assembly of various PPs, directed self-assembly of PP into three-dimensional (3D) hierarchical structure has proven to be difficult, despite their importance for biological applications. Herein, an efficient method has been developed through living polymerization of phenylalanine N-Carboxy anhydride (NCA) towards the linear and cyclic polyphenylalanine, and the new invented swelling methodology can form diverse hierarchical polypeptide crystals. The solvent-dependent self-assembly behaviors of these homopolymers were characterized by high-resolution imaging tools such as atomic force microscopy, transmission electron microscopy, scanning electron microscope. The linear and cyclic polypeptide formed 3D nano hierarchical shapes, such as a sphere, cubic, stratiform and hexagonal star in different solvents. Notably, a crystalline packing model was proposed to explain the formation of 3D nanostructures based on the various diffraction patterns, looking forward to give an insight for their dissimilar shape inflection during the self-assembly process.

Keywords: self-assembly, polypeptide, bio-polymer, crystalline polymer

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Authors: K. Tejasri, K. Suvarna Vani, S. Prathyusha, S. Ramya

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Proteins are chained sequences of amino acids which are brought together by the peptide bonds. Many varying formations of the chains are possible due to multiple combinations of amino acids and rotation in numerous positions along the chain. Protein structure prediction is one of the crucial goals worked towards by the members of bioinformatics and theoretical chemistry backgrounds. Among the four different structure levels in proteins, we emphasize mainly the secondary level structure. Generally, the secondary protein basically comprises alpha-helix and beta-sheets. Multi-class classification problem of data with disparity is truly a challenge to overcome and has to be addressed for the beta strands. Imbalanced data distribution constitutes a couple of the classes of data having very limited training samples collated with other classes. The secondary structure data is extracted from the protein primary sequence, and the beta-strands are predicted using suitable machine learning algorithms.

Keywords: proteins, secondary structure elements, beta-sheets, beta-strands, alpha-helices, machine learning algorithms

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Authors: Zahra Hamedani, Ebrahim Solgi, Henry Skates, Gillian Isoardi

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Daylighting plays a pivotal role in promoting productivity and user satisfaction in office spaces. There is an ongoing trend in designing office buildings with a high proportion of glazing which relatively increases the risk of high visual discomfort. Providing a more realistic lighting analysis can be of high value at the early stages of building design when necessary changes can be made at a very low cost. This holistic approach can be achieved by incorporating subjective evaluation and user behaviour in computer simulation and provide a comprehensive lighting analysis. In this research, a detailed computer simulation model has been made using Radiance and Daysim. Afterwards, this model was validated by measurements and user feedback. The case study building is the school of science at Griffith University, Gold Coast, Queensland, which features highly glazed office spaces. In this paper, the visual comfort predicted by the model is compared with a preliminary survey of the building users to evaluate how user behaviour such as desk position, orientation selection, and user movement caused by daylight changes and other visual variations can inform perceptions of visual comfort. This work supports preliminary design analysis of visual comfort incorporating the effects of gaze shift patterns and views with the goal of designing effective layout for office spaces.

Keywords: lighting simulation, office buildings, user behaviour, validation, visual comfort

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Authors: Asma Ben Hmidene, Mizuho Hanaki, Kazuma Murakami, Kazuhiro Irie, Hiroko Isoda, Hideyuki Shigemori

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Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are characterized as a peripheral metabolic disorder and a degenerative disease of the central nervous system, respectively. It is now widely recognized that T2DM and AD share many pathophysiological features including glucose metabolism, increased oxidative stress and amyloid aggregation. Amyloid beta (Aβ) is the components of the amyloid deposits in the AD brain and while the component of the amyloidogenic peptide deposit in the pancreatic islets of Langerhans is identified as human islet amyloid polypeptide (hIAPP). These two proteins are originated from the amyloid precursor protein and have a high sequence similarity. Although the amino acid sequences of amyloidogenic proteins are diverse, they all adopt a similar structure in aggregates called cross-beta-spine. Add at that, extensive studies in the past years have found that like Aβ1-42, IAPP forms early intermediate assemblies as spherical oligomers, implicating that these oligomers possess a common folding pattern or conformation. These similarities can be used in the search for effective pharmacotherapy for DM, since potent therapeutic agents such as antioxidants with a catechol moiety, proved to inhibit Aβ aggregation, may play a key role in the inhibit the aggregation of hIAPP treatment of patients with DM. Tamarix gallica is one of the halophyte species having a powerful antioxidant system. Although it was traditionally used for the treatment of various liver metabolic disorders, there is no report about the use of this plant for the treatment or prevention of T2DM and AD. Therefore, the aim of this work is to investigate their protective effect towards T2DM and AD by isolation and identification of α-glucosidase inhibitors, with antioxidant potential, that play an important role in the glucose metabolism in diabetic patient, as well as, the polymerization of hIAPP and Aβ aggregation inhibitors. Structure-activity relationship study was conducted for both assays. And as for α-glucosidase inhibitors, their mechanism of action and their synergistic potential when applied with a very low concentration of acarbose were also suggesting that they can be used not only as α-glucosidase inhibitors but also be combined with established α-glucosidase inhibitors to reduce their adverse effect. The antioxidant potential of the purified substances was evaluated by DPPH and SOD assays. Th-T assay using 42-mer amyloid β-protein (Aβ42) for AD and hIAPP which is a 37-residue peptide secreted by the pancreatic β –cells for T2DM and Transmission electronic microscopy (TEM) were conducted to evaluate the amyloid aggragation of the actives substances. For α-glucosidase, p-NPG and glucose oxidase assays were performed for determining the inhibition potential and structure-activity relationship study. The Enzyme kinetic protocol was used to study the mechanism of action. From this research, it was concluded that polyphenols playing a role in the glucose metabolism and oxidative stress can also inhibit the amyloid aggregation, and that substances with a catechol and glucuronide moieties inhibiting amyloid-β aggregation, might be used to inhibit the aggregation of hIAPP.

Keywords: α-glucosidase inhibitors, amyloid aggregation inhibition, mechanism of action, polyphenols, structure activity relationship, synergistic potential, tamarix gallica

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Authors: Wann-Ming Wey

Abstract:

In recent years, the problems of global climate change and natural disasters have induced the concerns and attentions of environmental sustainability issues for the public. Aside from the environmental planning efforts done for human environment, Transit-Oriented Development (TOD) has been widely used as one of the future solutions for the sustainable city development. In order to be more consistent with the urban sustainable development, the development of the built environment planning based on the concept of Green TOD which combines both TOD and Green Urbanism is adapted here. The connotation of the urban development under the green TOD including the design toward environment protect, the maximum enhancement resources and the efficiency of energy use, use technology to construct green buildings and protected areas, natural ecosystems and communities linked, etc. Green TOD is not only to provide the solution to urban traffic problems, but to direct more sustainable and greener consideration for future urban development planning and design. In this study, we use both the TOD and Green Urbanism concepts to proceed to the study of the built environment planning and design. Fuzzy Delphi Technique (FDT) is utilized to screen suitable criteria of the green TOD. Furthermore, Fuzzy Analytic Network Process (FANP) and Quality Function Deployment (QFD) were then developed to evaluate the criteria and prioritize the alternatives. The study results can be regarded as the future guidelines of the built environment planning and designing under green TOD development in Taiwan.

Keywords: green TOD, built environment, fuzzy delphi technique, quality function deployment, fuzzy analytic network process

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