Search results for: inhibitor designing

Authors: Heiko Jessen, Laura Tanus, Slobodan Ruzicic

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Objectives: The efficacy of Stribild®, an integrase strand transfer inhibitor (INSTI) -based STR, has been evaluated in randomized clinical trials and it has demonstrated durable capability in terms of achieving sustained suppression of HIV-1 RNA-levels. However, differences in monitoring frequency, existing selection bias and profile of patients enrolled in the trials, may all result in divergent efficacy of this regimen in routine clinical settings. The aim of this study was to assess the virologic outcomes, safety and tolerability profile of Stribild® in a routine clinical setting. Methods: This was a retrospective monocentric analysis on HIV-1-infected patients, who started with or were switched to Stribild®. Virological failure (VF) was defined as confirmed HIV-RNA>50 copies/ml. The minimum time of follow-up was 24 weeks. The percentage of patients remaining free of therapeutic failure was estimated using the time-to-loss-of-virologic-response (TLOVR) algorithm, by intent-to-treat analysis. Results: We analyzed the data of 197 patients (56 ART-naïve and 141 treatment-experienced patients), who fulfilled the inclusion criteria. Majority (95.9%) of patients were male. The median time of HIV-infection at baseline was 2 months in treatment-naïve and 70 months in treatment-experienced patients. Median time [IQR] under ART in treatment-experienced patients was 37 months. Among the treatment-experienced patients 27.0% had already been treated with a regimen consisting of two NRTIs and one INSTI, whereas 18.4% of them experienced a VF. The median time [IQR] of virological suppression prior to therapy with Stribild® in the treatment-experienced patients was 10 months [0-27]. At the end of follow-up (median 33 months), 87.3% (95% CI, 83.5-91.2) of treatment-naïve and 80.3% (95% CI, 75.8-84.8) of treatment-experienced patients remained free of therapeutic failure. Considering only treatment-experienced patients with baseline VL<50 copies/ml, 83.0% (95% CI, 78.5-87.5) remained free of therapeutic failure. A total of 17 patients stopped treatment with Stribild®, 5.4% (3/56) of them were treatment-naïve and 9.9% (14/141) were treatment-experienced patients. The Stribild® therapy was discontinued in 2 (1.0%) because of VF, loss to follow-up in 4 (2.0%), and drug-drug interactions in 2 (1.0%) patients. Adverse events were in 7 (3.6%) patients the reason to switch from therapy with Stribild® and further 2 (1.0%) patients decided personally to switch. The most frequently observed adverse events were gastrointestinal side effects (20.0%), headache (8%), rash events (7%) and dizziness (6%). In two patients we observed an emergence of novel resistances in integrase-gene. The N155H evolved in one patient and resulted in VF. In another patient S119R evolved either during or shortly upon switch from therapy with Stribild®. In one further patient with VF two novel mutations in the RT-gene were observed when compared to historical genotypic test result (V106I/M and M184V), whereby it is not clear whether they evolved during or already before the switch to Stribild®. Conclusions: Effectiveness of Stribild® for treatment-naïve patients was consistent with data obtained in clinical trials. The safety and tolerability profile as well as resistance development confirmed clinical efficacy of Stribild® in a daily practice setting.

Keywords: ART, HIV, integrase inhibitor, stribild

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Authors: C. Bala Prashanth Reddy, B. Abhinay, C. Sreekar, D. V. Shobhana Priscilla

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The project aims in designing an emergency pacemaker which is capable of giving shocks to a human heart which has stopped working suddenly. A pacemaker is a machine commonly used by cardiologists. This machine is used in order to shock a human’s heart back into usage. The way the heart works is that there are small cells called pacemakers sending electrical pulses to cardiac muscles that tell the heart when to pump blood. When these electrical pulses stop, the heart stops beating. When this happens, a pacemaker is used to shock the heart muscles and the pacemakers back into action. The way this is achieved is by rubbing the two panels of the pacemaker together to create an adequate electrical current, and then the heart gets back to the normal state. The project aims in designing a system which is capable of continuously displaying the heart beat and blood pressure of a person on LCD. The concerned doctor gets the heart beat and also the blood pressure details continuously through the GSM Modem in the form of SMS alerts. In case of abnormal condition, the doctor sends message format regarding the amount of electric shock needed. Automatically the microcontroller gives the input to the pacemaker which in turn gives the shock to the patient. Heart beat monitor and display system is a portable and a best replacement for the old model stethoscope which is less efficient. The heart beat rate is calculated manually using stethoscope where the probability of error is high because the heart beat rate lies in the range of 70 to 90 per minute whose occurrence is less than 1 sec, so this device can be considered as a very good alternative instead of a stethoscope.

Keywords: missing R wave, PWM, demand pacemaker, heart

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Authors: Mirna Febriani

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The use of stainless steel wires in the field of dentistry is widely used, especially for orthodontic and prosthodontic treatment using stainless steel wire. The oral cavity is the ideal environment for corrosion, which can be caused by saliva. Prevention of corrosion on stainless steel wires can be done by using an organic or non-organic corrosion inhibitor. One of the organic inhibitors that can be used to prevent corrosion is the leaves of breadfruit. The method used for this research using Atomic Absorption Spectrophotometric test. The results showed that the difference of chromium ion releases on soaking in saliva and breadfruit leaf extracts on days 1, 3, 7 and 14. Statically calculation with independent T-test with p < 0,05 showed the significant difference. The conclusion of this study shows that breadfruit leaf extract can inhibit the corrosion rate of stainless steel wires.

Keywords: chromium ion, stainless steel, artificial saliva, breadfruit leaf

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Authors: Rajesh Kumar G

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A challenging aspect of any clinical trial is to carefully plan the study design to meet the study objective in optimum way and to validate the assumptions made during protocol designing. And when it is a pediatric study, there is the added challenge of stringent guidelines and difficulty in recruiting the necessary subjects. Unlike adult trials, there is not much historical data available for pediatrics, which is required to validate assumptions for planning pediatric trials. Typically, pediatric studies are initiated as soon as approval is obtained for a drug to be marketed for adults, so with the adult study historical information and with the available pediatric pilot study data or simulated pediatric data, the pediatric study can be well planned. Generalizing the historical adult study for new pediatric study is a tedious task; however, it is possible by integrating various statistical techniques and utilizing the advantage of hybrid study design, which will help to achieve the study objective in a smoother way even with the presence of many constraints. This research paper will explain how well the hybrid study design can be planned along with integrated technique (SEV) to plan the pediatric study; In brief the SEV technique (Simulation, Estimation (using borrowed adult data and applying Bayesian methods)) incorporates the use of simulating the planned study data and getting the desired estimates to Validate the assumptions.This method of validation can be used to improve the accuracy of data analysis, ensuring that results are as valid and reliable as possible, which allow us to make informed decisions well ahead of study initiation. With professional precision, this technique based on the collected data allows to gain insight into best practices when using data from historical study and simulated data alike.

Keywords: adaptive design, simulation, borrowing data, bayesian model

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Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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Authors: Malihe Ahmadi

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Nowadays, stress, tension and neural problems are among the most important concerns of the present age. The environment plays key role on improving mental health and reducing stress of citizens. Establishing balance and appropriate relationship between city and natural environment is of the most important approaches of present century. Type of approach and logical planning for urban green spaces as one of the basic sections of integration with nature, not only plays key role on quality and efficiency of comprehensive urban planning; but also it increases the system of distributing social activities and happiness and lively property of urban environments that leads to permanent urban development. The main purpose of recovering urban identity is considering culture, history and human life style in past. This is a documentary-library research that evaluates the historical properties of Iranian gardens in compliance with climate condition. Results of this research reveal that in addition to following Iranian gardens from common principles of land lot, structure of flowers and plants, water, specific buildings during different ages, the role of climate at different urban areas is among the basics of determining method of designing green spaces and different buildings located at diverse areas i.e. Iranian gardens are a space for merging natural and artificial elements that has inseparable connection with semantic principles and guarantees different functions. Some of the necessities of designing present urban gardens are including: recognition and recreation.

Keywords: historical gardens, climate, properties of Iranian gardens, Iran

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Authors: Al-Naqdi Ibtehal Abdulmonem, Hameed Reem Majeed

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Kindergarten buildings are essential for early childhood education, providing a secure environment for children's development. However, they are susceptible to seismic forces, which can endanger occupants during earthquakes. This article emphasizes the importance of conducting thorough seismic analysis and implementing proper structural design to protect the well-being of children, staff, and visitors. By prioritizing structural integrity and considering functional requirements, engineers can mitigate risks associated with seismic events. The use of specialized software like ETABS is crucial for designing earthquake-resistant kindergartens. An analysis using ETABS software compared the structural performance of a single-story kindergarten in Iraq's Ministry of Education, designed with and without seismic considerations. The analysis aimed to assess the impact of seismic design on structural integrity and safety. The kindergarten was designed with seismic considerations, including moment frames. In contrast, the same kindergarten was analyzed without seismic effects, revealing a lack of structural elements to resist lateral forces, rendering it vulnerable to structural failure during an earthquake. Maximum major shear increased over 4 times and over 5 times for bending moment in the kindergarten designed with seismic considerations induced by lateral loads and seismic forces. This component of shear force is vital for designing elements to resist lateral loads and ensure structural stability.

Keywords: seismic analysis, structural design, lateral loads, earthquake resistance, major shear, ETABS

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Authors: Aboagye Boye Gilbert

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Teaching and learning (Education), not only in Ghana but the whole world is regarded as the (Stepping stone) vehicle to accelerate the country’s economy, development and social growth. Basically the ingredients for human development and the country in general is Vocational and Technical education and this has been stressed in Ghana’s education system since Pre-independence. To this effect, this research seeks to determine using demonstration method of Teachings sewing to improve the skills of form 3 Fashion Designing students of Baworo Integrated Community Centre for Employable Skills. In this research, reviewed literature on opinions of other researchers and what other people have done and said on related articles or topics, analyzed the research design used, translate the data gathered in the study. The study was design to gather information from the school on how they use Teaching methods to teach sewing. The targeted respondent contacted to give assistance Consist of students from BICCES, fashion teachers and tailored garment makers. The sample size consisted of 5 teachers, 20 students and 5 tailors were selected to answer questionnaire items that were used to gather the data for the study. The study revealed that most teachers and students agreed to the fact that demonstration, teaching and learning materials had a positive attitude towards the students in learning sewing. The study recommends that there should be more mechanisms in place to serve as a guide.

Keywords: VOTEC, BECE, BICCES, SHS

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Authors: Lu-Yin Lin

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The morphology of electroactive material is highly related to energy storage ability. Structure-directing agent (SDA) can design electroactive materials with favorable surface properties. Zeolitic imidazolate framework 67 (ZIF67) is one of the potential electroactive materials for energy storage devices. The SDA concept is less applied to designing ZIF67 derivatives in previous studies. An in-situ technique with ammonium fluoride (NH₄F) as SDA is proposed to produce a ZIF67 derivative with highly improved energy storage ability. Attracted by the effective in-situ technique, the NH₄F, ammonium bifluoride (NH₄HF₂), and ammonium tetrafluoroborate (NH₄BF₄) are first used as SDA to synthesize ZIF67 derivatives in one-step solution process as electroactive material of energy storage devices. The mechanisms of forming ZIF67 derivatives synthesized with different SDAs are discussed to explain the SDA effects on physical and electrochemical properties. The largest specific capacitance (CF) of 1527.0 Fg-¹ and the capacity of 296.9 mAhg-¹ are obtained for the ZIF67 derivative prepared using NH₄BF₄ as SDA. The energy storage device composed of the optimal ZIF67 derivative and carbon electrodes presents a maximum energy density of 15.1 Whkg-¹ at the power density of 857 Wkg-¹. The CF retention of 90% and Coulombic efficiency larger than 98% are also obtained after 5000 cycles.

Keywords: ammonium bifluoride, ammonium tetrafluoroborate, energy storage device, one-step solution process, structure-directing agent, zeolitic imidazolate framework 67

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Authors: Ikra Khan, Reenu Singh

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Composition is essential when designing the interiors of residential spaces. The ability to adopt a unique style of using design principles and design elements is another. This research report explores how the visual aesthetic within a space is achieved through the use of design principles and design elements while maintaining a signature style. It also observes the relationship between design styles and compositions that are achieved as a result of the implementation of the principles. Information collected from books and the internet helped to understand how a composition can be achieved in residential interiors by resorting to design principles and design elements as tools for achieving an aesthetic composition. It also helped determine the results of authentic representation of design ideas and how they make one’s work exceptional. A questionnaire survey was also conducted to understand the impact of a visually aesthetic residential interior of a signature style on the lifestyle of individuals residing in them. The findings denote a pattern in the application of design principles and design elements. Individual principles and elements or a combination of the same are used to achieve an aesthetically pleasing composition. This was supported by creating CAD illustrations of two different residential projects with varying approaches and design styles. These illustrations include mood boards, 3D models, and sectional elevations as rendered views to understand the concept design and its translation via these mediums. A direct relation is observed between the application of design principles and design elements to achieve visually aesthetic residential interiors that suit an individual’s taste. These practices can be applied when designing bespoke commercial as well as industrial interiors that are suited to specific aesthetic and functional needs.

Keywords: composition, design principles, elements, interiors, residential spaces

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Authors: Ambrish Singh

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The corrosion inhibition performance of pyran (AP) and benzimidazole (BI) derivatives on J55 steel in 3.5% NaCl solution saturated with CO₂ was investigated by electrochemical, weight loss, surface characterization, and theoretical studies. The electrochemical studies included electrochemical impedance spectroscopy (EIS), potentiodynamic polarization (PDP), electrochemical frequency modulation (EFM), and electrochemical frequency modulation trend (EFMT). Surface characterization was done using contact angle, scanning electron microscopy (SEM), and atomic force microscopy (AFM) techniques. DFT and molecular dynamics (MD) studies were done using Gaussian and Materials Studio softwares. All the studies suggested the good inhibition by the synthesized inhibitors on J55 steel in 3.5% NaCl solution saturated with CO₂ due to the formation of a protective film on the surface. Molecular dynamic simulation was applied to search for the most stable configuration and adsorption energies for the interaction of the inhibitors with Fe (110) surface.

Keywords: corrosion, inhibitor, EFM, AFM, DFT, MD

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Authors: Justine Kiiza, Xu Jiafang

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The world’s demand for energy is increasing rapidly due to population growth and a reduction in shallow conventional oil and gas reservoirs, resorting to deeper and mostly unconventional reserves like shale oil and gas. Most shale formations contain a large amount of expansive sodium montmorillonite (Na-Mnt), due to high water adsorption, hydration, and when the drilling fluid filtrate enters the formation with high Mnt content, the wellbore wall can be unstable due to hydration and swelling, resulting to shrinkage, sticking, balling, time wasting etc., and well collapse in extreme cases causing complex downhole accidents and high well costs. Recently, polyamines like 1, 6 – hexane diamine (HEDA) have been used as typical drilling fluid shale inhibitors to minimize and/or cab clay mineral swelling and maintain the wellbore stability. However, their application is limited to shallow drilling due to their sensitivity to elevated temperature and pressure. Inorganic potassium salts i.e., KCl, have long been applied for restriction of shale formation hydration expansion in deep wells, but their use is limited due to toxicity. Understanding the adsorption behaviour of HEDA on Na-Mnt surfaces in present of organo-salts, organic K-salts e.g., HCO₂K - main component of organo-salt drilling fluid, is of great significance in explaining the inhibitory performance of polyamine inhibitors. Molecular dynamic simulations (MD) were applied to investigate the influence of HCO₂K and KCl on the adsorption mechanism of HEDA on the Na-Mnt surface. Simulation results showed that adsorption configurations of HEDA are mainly by terminal amine groups with a flat-lying alkyl hydrophobic chain. Its interaction with the clay surface decreased the H-bond number between H₂O-clay and neutralized the negative charge of the Mnt surface, thus weakening the surface hydration ability of Na-Mnt. The introduction of HCO₂K greatly improved inhibition ability, coordination of interlayer ions with H₂O as they were replaced by K+, and H₂O-HCOO- coordination reduced H₂O-Mnt interactions, mobility and transport capability of H₂O molecules were more decreased. While KCl showed little ability and also caused more hydration with time, HCO₂K can be used as an alternative for offshore drilling instead of toxic KCl, with a maximum concentration noted in this study as 1.65 wt%. This study provides a theoretical elucidation for the inhibition mechanism and adsorption characteristics of HEDA inhibitor on Na-Mnt surfaces in the presence of K+-salts and may provide more insight into the evaluation, selection, and molecular design of new clay-swelling high-performance WBDF systems used in oil and gas complex offshore drilling well sections.

Keywords: shale, hydration, inhibition, polyamines, organo-salts, simulation

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Authors: Nosheen Fatima Warraich

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One of the most often used models in information system (IS) research is the technology acceptance model (TAM). This meta-analysis aims to measure the relationship between TAM variables, Perceived Ease of Use (PEOU), and Perceived Usefulness (PU) with users’ attitudes and behavioral intention (BI) in mobile and digital libraries context. It also examines the relationship of external variables (information quality and system quality) with TAM variables (PEOU and PU) in digital libraries settings. This meta-analysis was performed through PRISMA-P guidelines. Four databases (Google Scholar, Web of Science, Scopus, and LISTA) were utilized for searching, and the search was conducted according to defined criteria. The findings of this study revealed a large effect size of PU and PEOU with BI. There was also a large effect size of PU and PEOU with attitude. A medium effect size was found between SysQ -> PU, InfoQ-> PU, and SysQ -> PEOU. However, there was a small effect size between InfoQ and PEOU. It fills the literature gap and also confirms that TAM is a valid model for the acceptance and use of technology in mobile and digital libraries context. Thus, its findings would be helpful for developers and designers in designing and developing mobile library apps. It will also be beneficial for library authorities and system librarians in designing and developing digital libraries in academic settings.

Keywords: technology acceptance model (tam), perceived ease of use, perceived usefulness, information quality, system quality, meta-analysis, systematic review, digital libraries, and mobile library apps.

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Authors: Merna Ibrahim

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Designing buildings which are sustainable and can control and reduce the solar radiation penetrated from the building facades is such an architectural turn. One of the most important methods of saving energy in a building is carefully designing its facade. Building’s facade is one of the most significant contributors to the energy budget as well as the comfort parameters of a building. Responsive architecture adapts to the surrounding environment causing alteration in the envelope configuration to perform in a more effective way. One of the objectives of the responsive facades is to protect the building’s users from the external environment and to achieve a comfortable indoor environment. Solar radiation is one of the aspects that affects the comfortable indoor environment, as well as affects the energy consumption consumed by the HVAC systems for maintaining the indoor comfortable conditions. The aim of the paper is introducing and comparing between four different proposed responsive facade designs in terms of solar radiation reduction on the west facade of a building located in the hot arid region. In addition, the paper highlights the reducing amount of solar radiation for each proposed responsive facade on the west facade. At the end of the paper, a proposal is introduced which combines the four different axis of movements which reduces the solar radiation the most. Moreover, the paper highlights the definition and aim of the responsive architecture, as well as the focusing on the solar radiation aspect in the hot arid zones. Besides, the paper analyzes an international responsive façade building in Essen, Germany, focusing on the type of responsive facades, angle of rotation, mechanism of movement and the effect of the responsive facades on the building’s performance.

Keywords: kinetic facades, mechanism of movement, responsive architecture, solar radiation

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Authors: Shian Saroop, Dhiren Allopi

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In order to stay competitive and to meet upcoming stricter environmental regulations and customer requirements, designers have a key role in designing civil infrastructure so that it is environmentally sustainable. There is an urgent need for engineers to apply technologies and methods that deliver better and more sustainable performance of civil infrastructure as well as a need to establish a standard of measurement for greener infrastructure, rather than merely use tradition solutions. However, there are no systems in place at the design stage that assesses the environmental impact of design decisions on township infrastructure projects. This paper identifies alternative eco-efficient civil infrastructure design solutions and developed sustainability criteria and a toolkit to analyse the eco efficiency of infrastructure projects. The proposed toolkit is aimed at promoting high-performance, eco-efficient, economical and environmentally friendly design decisions on stormwater, roads, water and sanitation related to township infrastructure projects. These green solutions would bring a whole new class of eco-friendly solutions to current infrastructure problems, while at the same time adding a fresh perspective to the traditional infrastructure design process. A variety of projects were evaluated using the green infrastructure toolkit and their results are compared to each other, to assess the results of using greener infrastructure verses the traditional method of designing infrastructure. The application of ‘green technology’ would ensure a sustainable design of township infrastructure services assisting the design to consider alternative resources, the environmental impacts of design decisions, ecological sensitivity issues, innovation, maintenance and materials, at the design stage of a project.

Keywords: eco-efficiency, green infrastructure, infrastructure design, sustainable development

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Authors: Ferjani Hanen, El Arem Amira, Boussema Ayed Imen, Bacha Hassen

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Tacrolimus (TAC), a calcineurin inhibitor, is clinically used as an immunosuppressive agent in the transplant recipient, but its use associated-hepatotoxicity. Mycophenolate mofetil (MMF), an anti-metabolite, is a potent immunosuppressive drug. MMF is not hepatotoxic and is the most common adjunctive immunosuppressant for TAC. The effects of TAC and MMF combination in the liver is still not well understood. This work aimed to investigate their combined effect against in liver in rats Wistar after 24 h. The oral median lethal doses (LD50) of TAC and MMF alone were evaluated in rats are 240 mg/kg and 500 mg/kg respectively. Oral administration of the MMF at 50 mg/kg to male Wistar intoxicated with TAC at 60 mg/kg, demonstrated a significant protective effect by lowering the levels of hepatic markers enzymes (AST, ALT) in the serum rat. MMF attenuated oxidative stress by restoring the activities of SOD, CAT and by reducing the malondialdehyde (MDA) and protein carbonyl levels liver. This study provided evidence that MMF protects rat liver from TAC-induced injury and suggests a most combination use for organ transplantation.

Keywords: tacrolimus, mycophenolate mofetil, combination, liver, rat

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Authors: Ambalika Ekka

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In today’s world, the growing demand for urban built forms has resulted in the production and consumption of building materials i.e. embodied energy in building construction, leading to pollution and greenhouse gas (GHG) emissions. Therefore, new buildings will offer a unique opportunity to implement more energy efficient building without compromising on building performance of the building. Embodied energy of building materials forms major contribution to embodied energy in buildings. The paper results in an approach towards designing an energy efficient apartment building through embodied energy assessment. This paper discusses the trend of residential development in Rourkela, which includes three case studies of the contemporary houses, followed by architectural elements, number of storeys, predominant material use and plot sizes using primary data. It results in identification of predominant material used and other characteristics in urban area. Further, the embodied energy coefficients of various dominant building materials and alternative materials manufactured in Indian Industry is taken in consideration from secondary source i.e. literature study. The paper analyses the embodied energy by estimating materials and operational energy of proposed building followed by altering the specifications of the materials based on the building components i.e. walls, flooring, windows, insulation and roof through res build India software and comparison of different options is assessed with consideration of sustainable parameters. This paper results that autoclaved aerated concrete block only reaches the energy performance Index benchmark i.e. 69.35 kWh/m² yr i.e. by saving 4% of operational energy and as embodied energy has no particular index, out of all materials it has the highest EE 23206202.43  MJ.

Keywords: energy efficient, embodied energy, EPI, building materials

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Authors: Shao-Ju Chien, Yi-Chien Wu, Ting-Ying Huang, Li-Tsen Li, You-Jin Chen, Cheng-Nan Chen

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Homocysteine and pro-inflammatory mediators such as cyclooxygenase-2 (COX-2) have been linked to vascular dysfunction and risks of cardiovascular diseases. Fulvic acid (FA) is class of compounds of humic substances and possesses various pharmacological properties. However, the effect of FA on inflammatory responses of the monocytes remains unclear. We investigated the regulatory effect of FA on homocysteine-induced COX-2 expression in human monocytes. Peripheral blood monocytes and U937 cells were kept as controls or pre-treated with FA, and then stimulated with homocysteine. The results show that pretreating monocytes with FA inhibited the homocysteine-induced COX-2 expression in a dose-dependent manner. The inhibitor for nuclear factor-kB (NF-kB) attenuated homocysteine-induced COX-2 expression. Our findings provide a molecular mechanism by which FA inhibit homocysteine-induced COX-2 expression in monocytes, and a basis for using FA in pharmaceutical therapy against inflammation.

Keywords: homocysteine, monocytes, cyclooxygenase-2, fulvic acid, anti-inflammation

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Authors: Norihiro Kato, Yuriko Takayama

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Some gram-negative bacteria enable the simultaneous activation of gene expression involved in N-acylhomoserine lactone (AHL) dependent cell-to-cell communication system. Such regulatory system for the bacterial group behavior is termed as quorum sensing (QS) because a diffusible AHL signal can accumulate around the cell during the increase of the cell density and trigger activation of the sequential QS process. By blocking the QS, the expression of diverse genes related to infection, antibiotic production, and biofilm formation is inhibited. Conditioning of QS by regulation of the DNA-receptor-AHL interaction is a potential target for enhancing host defenses against pathogenicity. We focused on engineered application of transcriptional regulator SpnR produced in opportunistic human pathogen Serratia marcescens. The SpnR can interact with AHL signals at an N-terminal domain and also with a promoter region of a QS target gene at a C-terminal domain. As the initial process of the QS activation, the SpnR forms a complex with the AHL to enhance the expression of pig cluster; the SpnR normally acts as an activator for the expression of the QS-dependent gene. In this research, we attempt to artificially control QS by changing the role of SpnR. The QS-dependent prodigiosin production is expected to inhibit by externally added SpnR in the culture broth of AS-1 strain because the AHL concentration was kept below the threshold by AHL-SpnR complex formation. Maltose-binding protein (MBP)-tagged SpnR (MBP-SpnR) was overexpressed in Escherichia coli and purified using an affinity chromatography equipped with an amylose resin column. The specific interaction between AHL and MBP-SpnR was demonstrated by quartz crystal microbalance (QCM) sensor. AHL with amino end-group was coupled with COOH-terminated self-assembled monolayer prepared on a gold electrode of 27-MHz quartz crystal sensor using water-soluble carbodiimide. After the injection of MBP-SpnR into a cup-type sensor cell filled with the buffer solution, time course of resonant frequency change (ΔFs) was determined. A decrease of ΔFs clearly showed the uptake of MBP-SpnR onto the AHL-immobilized electrode. Furthermore, no binding affinity was observed after the heat-inactivation of MBP-SpnR at 80ºC. These results suggest that MBP-SpnR possesses a specific affinity for AHL. MBP-SpnR was added to the culture medium as an AHL trap to study inhibitory effects on intracellularly accumulated prodigiosin. With approximately 2 µM MBP-SpnR, the amount of prodigiosin induced was half that of the control without any additives. In conclusion, the function of SpnR could be switched by adding it to the cell culture. Exogenously added MBP-SpnR possesses high affinity for AHL derived from cells and acts as an inhibitor of AHL-mediated QS.

Keywords: intracellular signaling, microbial biotechnology, quorum sensing, transcriptional regulator

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Authors: M. R. Akshaya, Veena Rao

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Pet population in India is increasing phenomenally owing to the changes in urban lifestyle with increasing number of single professionals, single parents, delayed parenthood etc. The animal companionship as a means of reducing stress levels, deriving emotional support, and unconditional love provided by dogs are a few reasons attributed for increasing pet ownership. The consequence is the booming of the pet care products and dog care centers catering to the different requirements of rearing the pets. Dog care centers quite popular in tier 1 metros of India cater to the requirement of the dog owners providing space for the dogs in absence of the owner. However, it is often reported that the absence of the owner leads to destructive and exploratory behavior issues; the main being the anxiety disorders. In the above context, it becomes imperative for a designer to design dog boarding centers that help in reducing the separation anxiety in dogs keeping in mind the different interior design parameters. An exploratory research with focus group discussion is employed involving a group of dog owners, behaviorists, proprietors of day care as well as boarding centers, and veterinarians to understand their perception on the significance of different interior parameters of color, texture, ventilation, aroma therapy and acoustics as a means of reducing the stress levels in dogs sent to the boarding centers. The data collected is organized as thematic networks thus enabling the listing of the interior design parameters that needs to be considered in designing dog boarding centers. 

Keywords: behavioral response, design parameters, dog boarding centers, interior environment

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Authors: Heba M. Jahin, Ali F. Bakr, Zeyad T. Elsayad

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As smart spaces can be defined as any working environment which integrates embedded computers, information appliances and multi-modal sensors to remain focused on the interaction between the users, their activity, and their behavior in the space; hence, smart space must be aware of their contexts and automatically adapt to their changing context-awareness, by interacting with their physical environment through natural and multimodal interfaces. Also, by serving the information used proactively. This paper suggests a dynamic framework through the architectural design process of the space based on the principles of computational methods and context-awareness principles to help in creating a field of changes and modifications. It generates possibilities, concerns about the physical, structural and user contexts. This framework is concerned with five main processes: gathering and analyzing data to generate smart design scenarios, parameters, and attributes; which will be transformed by coding into four types of models. Furthmore, connecting those models together in the interaction model which will represent the context-awareness system. Then, transforming that model into a virtual and ambient environment which represents the physical and real environments, to act as a linkage phase between the users and their activities taking place in that smart space . Finally, the feedback phase from users of that environment to be sure that the design of that smart space fulfill their needs. Therefore, the generated design process will help in designing smarts spaces that can be adapted and controlled to answer the users’ defined goals, needs, and activity.

Keywords: computational methods, context-awareness, design process, smart spaces

Procedia PDF Downloads 293

Authors: Eun Jung Sohn, Hwan Tae Park

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Autophagy is a cellular response to stress or environment on cell survival. Here, we investigated the role of ectopic expression of miR 200c-3p in autophagy. Ectopic expression of miR 200c-3p increased the expression of IRE1alpha, ATF6 and CHOP by western blot and RT-qPCR. Furthermore, the level of microRNA 200c-3p was enhanced by treatment of TG or overexpression of GRP 78. Also, ectopic expression of miR200c-3p increased the LC3 II expression by western blot and RT-qPCR. Also, we found that western blot assay showed that miR200c-3p inhibitor was blocked the starvation–induced LC3II levels. Furthermore, starvation stress increased the level of miR200c-3p in different kinetics. Ectopic expression of miR200c-3p attenuated LC3II expression in IRE1 siRNA transfected PC3 cells. Here, we first demonstrate that miR200c-3p regulates autophagy via ER stress pathway.

Keywords: Autophagy, ER stress, LC3II, miR200c-3p

Procedia PDF Downloads 262

Authors: Nurul Ain Haron, Saiful Hazmi Bachek, Hafez Zainudin

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This study is aimed to establish the importance and contribution of Original Design Manufacturing (ODM) in Malaysian Furniture Industry and to close the gap between the players in the industry. The study confirms that today’s furniture industry favor Original Equipment Manufacturing (OEM) basis. Thus, resulting in the local industry lacking the expertise of designing furniture to a state of no contest. This study method used consists of literature reviews, observation, questionnaire and sessions of interviews. The result shows that the public has from minimum to almost no knowledge of the term Original Design Manufacturing (ODM) concept and the impact towards our current future industry. The manufacturers however, prefers Original Equipment Manufacturing (OEM) concept due to its easy and fast investment returns with the need of product designing process, while the interviews carried out with the authorized council had some convincing urges of doing their part promoting the awareness through trainings and seminars. Findings show that, in the rush of archiving ODM status needs extensive cooperation from many parties that are authorized council, furniture manufacturers, designers and also the public perceptions of labeling local made goods as the black goat. The current mind set of OEM manufacturers need to be change for industry’s future. As Malaysia’s living status constantly increases, so will the demands of a better salary. If these current issues are not resolved, OEM international buyers will definitely have to shift to some other lower cost manufacturer like China or Taiwan. When vendors stopped to order, today’s OEM manufacturers will no longer exist in the future.

Keywords: design manufacturing, furniture design, original design manufacturing, original equipment manufacturing

Procedia PDF Downloads 418

Authors: Syed Asif Hassan, Ritu Barthwal

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Topoisomerase I and II α plays a crucial role in the DNA-maintenance in all living cells, and for this reason, inhibitors of this enzyme have been much studied. In this paper, we have described the inhibitory effect of the aqueous extract of Picrorrhiza kurroa on human topoisomerases by measuring the relaxation of superhelical plasmid pBR322 DNA. The aqueous extract inhibited topoisomerase I and II α in a concentration-dependent manner (Inhibitory concentration (IC) ≈ 25 and 50 µg, respectively). By stabilization studies of topoisomerase I-DNA complex and preincubation studies of topoisomerase I and II α with the extract; we conclude that the possible mechanism of inhibition is both; 1) stabilization of covalent complex of topo I-DNA complex and 2) direct inhibition of the enzyme topoisomerases. These findings might explain the antineoplastic activity of Picrorrhiza kurroa and encourage new studies to elucidate the usefulness of the extract as a potent antineoplastic agent.

Keywords: Picrorrhiza kurroa, topoisomerase I and II α, inhibition, antineoplastic agent

Procedia PDF Downloads 311

Authors: Vinaya Kambappa, Chinnadurai Mani, Komaraiah Palle

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Non-small cell-lung cancer (NSCLC) cells have increased expression of EGFR, which makes them a potential target for cancer therapy. Based on molecular docking and previous reports, we designed and synthesized quinazoline derivatives as potent EGFR inhibitors. Among the derivatives, three compounds showed good antiproliferative activity against A-549 and H-1299 cells. Furthermore, these compounds inhibited EGFR signaling exhibiting diminishing p-EGFR and its downstream proteins like p-Akt, p-Erk1/2, and p-mTOR; however, it did not alter the levels of EGFR, Akt, Erk1/2 and mTOR proteins. Flow cytometric analysis indicated the accumulation of cells at G1 phase suggesting induction of apoptosis, which was further confirmed by annexin V/propidium iodide staining. Our study suggested that quinazoline scaffold can be developed as novel EGFR kinase inhibitors for cancer therapy.

Keywords: apoptosis, non-small cell-lung cancer cells, EGFR, quinazoline

Procedia PDF Downloads 158

Authors: Elsayed G. Zaki, Nora A. Hamad, Hadeel G. El-Shorbagy

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The effect of watermelon rind extract as green inhibitors for the formation of calcium sulphate scale have been investigated using conductivity measurements concurrently with the scanning electron microscopy (SEM), and optical microscopic examinations. Mineral scales were deposited from the brine solution by cathodic polarization of the steel surface. The results show up that the anti-scaling property of the extracts could be attributed to the presence of citrulline. In solution, citrulline retards calcium sulphate precipitation via formation of a complex with the calcium cations. Thin, smooth and non adherent film formed over the steel surface, under cathodic polarization, by the deposition of the calcium- citrulline complex. The stability of the aqueous extracts with time was also investigated.

Keywords: anti-scaling, scale inhibitor, green extracts, water treatment

Procedia PDF Downloads 238

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

Procedia PDF Downloads 152

Authors: Hadi Mousavi, Majid Davoudi Nasr

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Executives can maximize profits by recognizing the factors that affect investment and using them to obtain the optimal level of investment. Inefficient markets have shortcomings that can impact the optimal level of investment, leading to the process of over-investment or under-investment. In the present study, the relationship between the overconfidence of senior managers and abnormal cash fluctuations with respect to financial flexibility in companies listed in the Tehran stock exchange from 2009 to 2013 were evaluated. In this study, the sample consists of 84 companies selected by a systematic elimination method and 420 year-companies in total. In this research, EVIEWS software was used to test the research hypotheses by linear regression and correlation coefficient and after designing and testing the research hypothesis. After designing and testing research hypotheses that have been used to each hypothesis, it was concluded that there was a significant relationship between the overconfidence of senior managers and abnormal cash fluctuations, and this relationship was not significant at any level of financial flexibility. Moreover, the findings of the research showed that there was a significant relationship between senior manager’s overconfidence and positive abnormal cash flow fluctuations in firms, and this relationship is significant only at the level of companies with high financial flexibility. Finally, the results indicate that there is no significant relationship between senior managers 'overconfidence and negative cash flow abnormalities, and the relationship between senior managers' overconfidence and negative cash flow fluctuations at the level of companies with high financial flexibility was confirmed.

Keywords: abnormal cash fluctuations, overconfidence of senior managers, financial flexibility, accounting

Procedia PDF Downloads 103

Authors: Nagda Ibrahim Mady, Shimaa Mohamed Atiha

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In light of actual needs of elderly people and the changes that accompany age in eyesight, hearing, dexterity, mobility, and memory which make aged people unable to carry out the simplest living affairs especially clothing demands. These needs are almost neglected in the current clothing market obligate aged peoples to wear the available choices without any consideration to their actual desires and needs. Fashion designer has gained many experiences that can gather between ergonomics and stages of fashion designing process. Fashion designer can determine the actual needs of aged people and reply these needs with designs that can achieve Improvement to the life quality of aged people besides maintaining good appearance. Thus Fashion designer can help elderly people to avoid negative impacts age leaves on them, either it is psychological or kinetic or that of dementia. Ergonomics in clothing is considered the tools and mechanisms that are used to fit aged people satisfactions supporting them to improve their living using the least time and effort. Providing the elderly with comfort besides maintaining good appearance that can make self–confidence besides independence. From this point of view the research is looking forward to improve the life of aged people through addressing functional clothes that can make elderly independent in the wearing process. Providing in these designs comfort, quality, and practicality and economic cost. Suggesting the suitable fabrics and materials and applying it to the designs to help the elderly perform their daily living customs. Reaching the successful designs that can be acceptable to specialists and to consumers whom they confirm: it supplies their clothing needs and provides the atheistic and functional performance and therefore it gives them better life.

Keywords: ergonomic, design garments, elderly people, life quality

Procedia PDF Downloads 535

Authors: A. Papadopoulou

Abstract:

When people are asked to provide an oral description of a space they usually provide a Tour description, which is a dynamic type of spatial narrative centered on the narrator’s body, rather than a Map description, which is a static type of spatial narrative focused on the organization of the space as seen from above. Also, subjects with training in the architecture discipline tend to adopt a Tour perspective of space when the narrative refers to a space they have actually experienced but tend to adopt a Map perspective when the narrative refers to a space they have merely imagined. This pilot study aims to investigate whether the Tour description, which is the most common mode in the oral descriptions of experienced space, is a cognitive perspective taken in the process of designing a space. The study investigates whether a spatial description provided by a subject with architecture training in the type of a Tour description would be accurately translated into a spatial layout by other subjects with architecture training. The subjects were given the Tour description in written form and were asked to make a plan drawing of the described space. The results demonstrate that when we conceive and design space we do not adopt the same rules and cognitive patterns that we adopt when we reconstruct space from our memory. As shown by the results of this pilot study, the rules that underlie the Tour description were not detected in the translation from narratives to drawings. In a different phase, the study also investigates how would subjects with architecture training describe space when forced to take a Tour perspective in their oral description of a space. The results of this second phase demonstrate that if intentionally taken, the Tour perspective leads to descriptions of space that are more detailed and focused on experiential aspects.

Keywords: architecture, design process, embodied cognition, map description, oral narratives, tour description

Procedia PDF Downloads 131