Search results for: genetic improvement

Authors: Chieh-Ning Lan, Tzu-Shin Lin, Kun-Hao Lin

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Chinese handwriting skill is one of the basic skills of school-age children in Taiwan, which helps them to learn most academic subjects. Differ from the alphabetic language system, Chinese written language is a logographic script with a complicated 2-dimensional character structure as a morpheme. Visuospatial ability places a great role in Chinese handwriting to maintain good proportion and alignment of these interwoven strokes. In Taiwan, school-age students faced the challenge to recognize and write down Chinese characters, especially in children with written expression difficulties (CWWDs). In this study, we developed an instructional app to help CWWDs practice Chinese handwriting skills, and we aimed to apply the mobile assisted language learning (MALL) system in clinical writing strategies. To understand the feasibility and satisfaction of this auxiliary instructional writing app, we investigated the perceive and value both from school-age students and the clinic therapists, who were the target users and the experts. A group of 8 elementary school children, as well as 8 clinic therapists, were recruited. The school-age students were asked to go through a paper-based instruction and were asked to score the visual expression based on their graphic preference; the clinic therapists were asked to watch an introductive video of this instructional app and complete the online formative questionnaire. In the results of our study, from the perspective of user interface design, school-age students were more attracted to cartoon-liked pictures rather than line drawings or vivid photos. Moreover, compared to text, pictures which have higher semantic transparency were more commonly chosen by children. In terms of the quantitative survey from clinic therapists, they were highly satisfied with this auxiliary instructional writing app, including the concepts such as visual design, teaching contents, and positive reinforcement system. Furthermore, the qualitative results also suggested comprehensive positive feedbacks on the teaching contents and the feasibility of integrating the app into clinical treatments. Interestingly, we found that clinic therapists showed high agreement in approving CWWDs’ writing ability with using orthographic knowledge; however, in the qualitative section, clinic therapists pointed out that CWWDs usually have relative insufficient background knowledge in Chinese character orthographic rules, which because it is not a key-point in conventional handwriting instruction. Also, previous studies indicated that conventional Chinese reading and writing instructions were lacked of utilizing visual-spatial arrangement strategies. Based on the sharing experiences from all participants, we concluded several interesting topics that are worth to dedicate to in the future. In this undergoing app system, improvement and revision will be applied into the system design, and will establish a better and more useful instructional system for CWWDs within their treatments; enlightened by the opinions related to learning content, the importance of orthographic knowledge in Chinese character recognition should be well discussed and involved in CWWDs’ intervention in the future.

Keywords: auxiliary instructional app, children with writing difficulties, Chinese handwriting, orthographic knowledge

Procedia PDF Downloads 173

Authors: I. N. Nwafia, U. C. Ozumba, M. E. Ohanu, S. O. Ebede

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Antibiotic resistance is increasing globally and has become a major health challenge. Extended-spectrum beta-lactamase is clinically important because the ESBL gene are mostly plasmid encoded and these plasmids frequently carry genes encoding resistance to other classes of antimicrobials thereby limiting antibiotic options in the treatment of infections caused by these organisms. The specific objectives of this study were to determine the prevalence of ESBLs production in Escherichia coli, to determine the antibiotic susceptibility pattern of ESBLs producing Escherichia coli, to detect TEM, SHV and CTX-M genes and the risk factors to acquisition of ESBL producing Escherichia coli. The protocol of the study was approved by Health Research and Ethics committee of the University of Nigeria Teaching Hospital (UNTH), Enugu. It was a descriptive cross-sectional study that involved all hospitalized patients in UNTH from whose specimens Escherichia coli was isolated during the period of the study. The samples analysed were urine, wound swabs, blood and cerebrospinal fluid. These samples were cultured in 5% sheep Blood agar and MacConkey agar (Oxoid Laboratories, Cambridge UK) and incubated at 35-370C for 24 hours. Escherichia coli was identified with standard biochemical tests and confirmed using API 20E auxanogram (bioMerieux, Marcy 1'Etoile, France). The antibiotic susceptibility testing was done by disc diffusion method and interpreted according to the Clinical and Laboratory Standard Institute guideline. ESBL production was confirmed using ESBL Epsilometer test strips (Liofilchem srl, Italy). The ESBL bla genes were detected with polymerase chain reaction, after extraction of DNA with plasmid mini-prep kit (Jena Bioscience, Jena, Germany). Data analysis was with appropriate descriptive and inferential statistics. One hundred and six isolates (53.00%) out of the 200 were from urine, followed by isolates from different swabs specimens 53(26.50%) and the least number of the isolates 4(2.00) were from blood (P value = 0.096). Seventy (35.00%) out of the 200 isolates, were confirmed positive for ESBL production. Forty-two (60.00%) of the isolates were from female patients while 28(40.00%) were from male patients (P value = 0.13). Sixty-eight (97.14%) of the isolates were susceptible to imipenem while all of the isolates were resistant to ampicillin, chloramphenicol and tetracycline. From the 70 positive isolates the ESBL genes detected with polymerase chain reaction were blaCTX-M (n=26; 37.14%), blaTEM (n=7; 10.00%), blaSHV (n=2; 2.86%), blaCTX-M/TEM (n=7; 10.0%), blaCTX-M/SHV (n=14; 20.0%) and blaCTX-M/TEM/SHV (n=10; 14.29%). There was no gene detected in 4(5.71%) of the isolates. The most associated risk factors to infections caused by ESBL producing Escherichia coli was previous antibiotics use for the past 3 months followed by admission in the intensive care unit, recent surgery, and urinary catheterization. In conclusion, ESBLs was detected in 4 of every 10 Escherichia coli with the predominant gene detected being CTX-M. This knowledge will enable appropriate measures towards improvement of patient health care, antibiotic stewardship, research and infection control in the hospital.

Keywords: antimicrobial, Escherichia coli, extended spectrum beta lactamase, resistance

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Authors: Andrés Durán, Brian Castellanos, Marta Quicazán, Carlos Zuluaga-Domínguez

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Bee-pollen is an apicultural-derived food product, with a growing appreciation among consumers given the remarkable nutritional and functional composition, in particular, protein (24%), dietary fiber (15%), phenols (15 – 20 GAE/g) and carotenoids (600 – 900 µg/g). These properties are given by the geographical and climatic characteristics of the region where it is collected. There are several countries recognized by their pollen production, e.g. China, United States, Japan, Spain, among others. Beekeepers use traps in the entrance of the hive where bee-pollen is collected. After the removal of foreign particles and drying, this product is ready to be marketed. However, in countries located along the equator, the absence of seasons and a constant tropical climate throughout the year favors a more rapid spoilage condition for foods with elevated water activity. The climatic conditions also trigger the proliferation of microorganisms and insects. This, added to the factor that beekeepers usually do not have adequate processing systems for bee-pollen, leads to deficiencies in the quality and safety of the product. In contrast, the Andean region of South America, lying on equator, typically has a high production of bee-pollen of up to 36 kg/year/hive, being four times higher than in countries with marked seasons. This region is also located in altitudes superior to 2500 meters above sea level, having extremes sun ultraviolet radiation all year long. As a mechanism of defense of radiation, plants produce more secondary metabolites acting as antioxidant agents, hence, plant products such as bee-pollen contain remarkable more phenolics and carotenoids than collected in other places. Considering this, the improvement of bee-pollen processing facilities by technical modifications and the implementation of an integrated cleaning and drying system for the product in an apiary in the area was proposed. The beehives were modified through the installation of alternative bee-pollen traps to avoid sources of contamination. The processing facility was modified according to considerations of Good Manufacturing Practices, implementing the combined use of a cabin dryer with temperature control and forced airflow and a greenhouse-type solar drying system. Additionally, for the separation of impurities, a cyclone type system was implemented, complementary to a screening equipment. With these modifications, a decrease in the content of impurities and the microbiological load of bee-pollen was seen from the first stages, principally with a reduction of the presence of molds and yeasts and in the number of foreign animal origin impurities. The use of the greenhouse solar dryer integrated to the cabin dryer allowed the processing of larger quantities of product with shorter waiting times in storage, reaching a moisture content of about 6% and a water activity lower than 0.6, being appropriate for the conservation of bee-pollen. Additionally, the contents of functional or nutritional compounds were not affected, even observing an increase of up to 25% in phenols content and a non-significant decrease in carotenoids content and antioxidant activity.

Keywords: beekeeping, drying, food processing, food safety

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Authors: Shilpi Bora, Abhirup Chatterjee, Debkumar Chakrabarti

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Organizations of all the sectors around the world are increasingly revisiting their workplace strategies with due concern for women working therein. Limited office space and rigid work arrangements contribute to lesser job satisfaction and greater work impoundments for any organization. Flexible workspace strategies are indispensable to accommodate the progressive rise of modular workstations and involvement of women. Today’s generation of employees deserves malleable office environments with employee-friendly job conditions and strategies. The workplace nowadays stands on rapid organizational changes in progressive and flexible work culture. Occupational well-being practices need to keep pace with the rapid changes in office-based work. Working at the office (workspace) with awkward postures or for long periods can cause pain, discomfort, and injury. The world is stirring towards the era of globalization and progress. The 4000 women police personnel constitute less than one per cent of the total police strength of India. Lots of innovative fields are growing fast, and it is important that we should accommodate women in those arenas. The timeworn trends should be set apart to set out for fresh opportunities and possibilities of development and success through more involvement of women in the workplace. The notion of women policing is gaining position throughout the world, and various countries are putting solemn efforts to mainstream women in policing. As the role of women policing in a society is budding, and thus it is also notable that the accessibility of women at general police stations should be considered. Accordingly, the impact of workspace at police station on the employee productivity has been widely deliberated as a crucial contributor to employee satisfaction leading to better functional motivation. Thus the present research aimed to look into the office workstation design of police station with reference to womanhood specific issues to uplift occupational wellbeing of the policewomen. Personal interview and individual responses collected through administering to a subjective assessment questionnaire on thirty women police as well as to have their views on these issues by purposive non-probability sampling of women police personnel of different ranks posted in Guwahati, Assam, India. Scrutiny of the collected data revealed that office design has a substantial impact on the policewomen job satisfaction in the police station. In this study, the workspace was designed in such a way that the set of factors would impact on the individual to ensure increased productivity. Office design such as furniture, noise, temperature, lighting and spatial arrangement were considered. The primary feature which affected the productivity of policewomen was the furniture used in the workspace, which was found to disturb the everyday and overall productivity of policewomen. Therefore, it was recommended to have proper and adequate ergonomics design intervention to improve the office design for better performance. This type of study is today’s need-of-the-hour to empower women and facilitate their inner talent to come up in service of the nation. The office workspace design also finds critical importance at several other occupations also – where office workstation needs further improvement.

Keywords: office workspace design, policewomen, womanhood concerns at workspace, occupational wellbeing

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Authors: Renu Satish Nair

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Indian higher education system is the third largest in the world next to United States and China. India is experiencing a rapid growth in higher education in terms of student enrollment as well as establishment of new universities, colleges and institutes of national importance. Presently about 22 million students are being enrolled in higher education and more than 46 thousand institutions’ are functioning as centers of higher education. Indian government plays a 'command and control' role in higher education. The main governing body is University Grants Commission, which enforces its standards, advises the government, and helps coordinate between the centre and the state. Accreditation of higher learning is over seen by 12 autonomous institutions established by the University Grants Commission. The present paper is an effort to analyze the strength, weakness, opportunities and threat (SWOT Analysis) of Indian Higher education system. The higher education in India is progressing ahead by virtue of its strength which is being recognized at global level. Several institutions of India, such as Indian Institutes of Technology (IITs), Indian Institutes of Management (IIMs) and National Institutes of Technology (NITs) have been globally acclaimed for their standard of education. Three Indian universities were listed in the Times Higher Education list of the world’s top 200 universities i.e. Indian Institutes of Technology, Indian Institute of Management and Jawahar Lal Nehru University in 2005 and 2006. Six Indian Institutes of Technology and the Birla Institute of Technology and Science - Pilani were listed among the top 20 science and technology schools in Asia by the Asia Week. The school of Business situated in Hyderabad was ranked number 12 in Globe MBA ranking by the Financial Times of London in 2010 while the All India Institute of Medical Sciences has been recognized as a global leader in medical research and treatment. But at the same time, because of vast expansion, the system bears several weaknesses. The Indian higher education system in many parts of the country is in the state of disrepair. In almost half the districts in the country higher education enrollment are very low. Almost two third of total universities and 90% of colleges are rated below average on quality parameters. This can be attributed to the under prepared faculty, unwieldy governance and other obstacles to innovation and improvement that could prohibit India from meeting its national education goals. The opportunities in Indian higher education system are widely ranged. The national institutions are training their products to compete at global level and make them capable to grab opportunities worldwide. The state universities and colleges with their limited resources are giving the products that are capable enough to secure career opportunities and hold responsible positions in various government and private sectors with in the country. This is further creating opportunities for the weaker section of the society to join the main stream. There are several factors which can be defined as threats to Indian higher education system. It is a matter of great concern and needs proper attention. Some important factors are -Conservative society, particularly for women education; -Lack of transparency, -Taking higher education as a means of business

Keywords: Indian higher education system, SWOT analysis, university grants commission, Indian institutes of technology

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Authors: Francesca Fermi, Paola Astegiano, Angelo Martino, Stephanie Heitel, Michael Krail

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In order to achieve the targeted emission reductions for the decarbonisation of the European economy by 2050, fundamental contributions are required from both energy and transport sectors. The objective of this paper is to analyse the impacts of a largescale diffusion of e-vehicles, either battery-based or fuel cells, together with the implementation of transport policies aiming at decreasing the use of motorised private modes in order to achieve greenhouse gas emission reduction goals, in the context of a future high share of renewable energy. The analysis of the impacts and challenges of future scenarios on transport sector is performed with the ASTRA (ASsessment of TRAnsport Strategies) model. ASTRA is a strategic system-dynamic model at European scale (EU28 countries, Switzerland and Norway), consisting of different sub-modules related to specific aspects: the transport system (e.g. passenger trips, tonnes moved), the vehicle fleet (composition and evolution of technologies), the demographic system, the economic system, the environmental system (energy consumption, emissions). A key feature of ASTRA is that the modules are linked together: changes in one system are transmitted to other systems and can feed-back to the original source of variation. Thanks to its multidimensional structure, ASTRA is capable to simulate a wide range of impacts stemming from the application of transport policy measures: the model addresses direct impacts as well as second-level and third-level impacts. The simulation of the different scenarios is performed within the REFLEX project, where the ASTRA model is employed in combination with several energy models in a comprehensive Modelling System. From the transport sector perspective, some of the impacts are driven by the trend of electricity price estimated from the energy modelling system. Nevertheless, the major drivers to a low carbon transport sector are policies related to increased fuel efficiency of conventional drivetrain technologies, improvement of demand management (e.g. increase of public transport and car sharing services/usage) and diffusion of environmentally friendly vehicles (e.g. electric vehicles). The final modelling results of the REFLEX project will be available from October 2018. The analysis of the impacts and challenges of future scenarios is performed in terms of transport, environmental and social indicators. The diffusion of e-vehicles produces a consistent reduction of future greenhouse gas emissions, although the decarbonisation target can be achieved only with the contribution of complementary transport policies on demand management and supporting the deployment of low-emission alternative energy for non-road transport modes. The paper explores the implications through time of transport policy measures on mobility and environment, underlying to what extent they can contribute to a decarbonisation of the transport sector. Acknowledgements: The results refer to the REFLEX project which has received grants from the European Union’s Horizon 2020 research and innovation program under Grant Agreement No. 691685.

Keywords: decarbonisation, greenhouse gas emissions, e-mobility, transport policies, energy

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Authors: Till Gramberg, Erwin Gross, Christoph Birenbaum

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This paper presents the approach of the Easy2IoT research project. Easy2IoT aims to enable companies in the prefabrication sheet metal and sheet metal processing industry to enter the Industrial Internet of Things (IIoT) with a low-threshold and cost-effective approach. It focuses on the development of physical hardware and software to easily capture machine activities from on a sawing machine, benefiting various stakeholders in the SME value chain, including machine operators, tool manufacturers and service providers. The methodological approach of Easy2IoT includes an in-depth requirements analysis and customer interviews with stakeholders along the value chain. Based on these insights, actions, requirements and potential solutions for smart services are derived. The focus is on providing actionable recommendations, competencies and easy integration through no-/low-code applications to facilitate implementation and connectivity within production networks. At the core of the project is a novel, non-invasive measurement and analysis system that can be easily deployed and made IIoT-ready. This system collects machine data without interfering with the machines themselves. It does this by non-invasively measuring the tension on a sawing machine. The collected data is then connected and analyzed using artificial intelligence (AI) to provide smart services through a platform-based application. Three Smart Services are being developed within Easy2IoT to provide immediate benefits to users: Wear part and product material condition monitoring and predictive maintenance for sawing processes. The non-invasive measurement system enables the monitoring of tool wear, such as saw blades, and the quality of consumables and materials. Service providers and machine operators can use this data to optimize maintenance and reduce downtime and material waste. Optimize Overall Equipment Effectiveness (OEE) by monitoring machine activity. The non-invasive system tracks machining times, setup times and downtime to identify opportunities for OEE improvement and reduce unplanned machine downtime. Estimate CO2 emissions for connected machines. CO2 emissions are calculated for the entire life of the machine and for individual production steps based on captured power consumption data. This information supports energy management and product development decisions. The key to Easy2IoT is its modular and easy-to-use design. The non-invasive measurement system is universally applicable and does not require specialized knowledge to install. The platform application allows easy integration of various smart services and provides a self-service portal for activation and management. Innovative business models will also be developed to promote the sustainable use of the collected machine activity data. The project addresses the digitalization gap between large enterprises and SME. Easy2IoT provides SME with a concrete toolkit for IIoT adoption, facilitating the digital transformation of smaller companies, e.g. through retrofitting of existing machines.

Keywords: smart services, IIoT, IIoT-platform, industrie 4.0, big data

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Authors: Milada Krejci, Martin Hill, Vaclav Hosek, Dobroslava Jandova, Jiri Kajzar, Pavel Blaha

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The paper declares effects of exercise intervention of the research project “Basic research of balance changes in seniors”, granted by the Czech Science Foundation. The objective of the presented study is to define predictors, which influence bio-psycho-social consequences and effects of balance ability in senior 65 years old and above. We focused on the Fall-Efficacy Scale changes evaluation in seniors. Comprehensive hypothesis of the project declares, that motion uncertainty (dyskinesia) can negatively affect the well-being of a senior in bio-psycho-social context. In total, random selection and testing of 100 seniors (30 males, 70 females) from Prague and Central Bohemian region was provided. The sample was divided by stratified random selection into experimental and control groups, who underwent input and output testing. For diagnostics the methods of Medical Anamnesis, Functional anthropological examinations, Tinetti Balance Assessment Tool, SF-36 Health Survey, Anamnestic comparative self-assessment scale were used. Intervention method called "Life in Balance" based on yoga techniques was applied in four-week cycle. Results of multivariate regression were verified by repeated measures ANOVA: subject factor, phase of intervention (between-subject factor), body fluid (within-subject factor) and phase of intervention × body fluid interaction). ANOVA was performed with a repetition involving the factors of subjects, experimental/control group, phase of intervention (independent variable), and x phase interaction followed by Bonferroni multiple comparison assays with a test strength of at least 0.8 on the probability level p < 0.05. In the paper results of the first-year investigation of the three years running project are analysed. Results of balance tests confirmed no significant difference between females and males in pre-test. Significant improvements in balance and walking ability were observed in experimental group in females comparing to males (F = 128.4, p < 0.001). In the females control group, there was no significant change in post- test, while in the female experimental group positive changes in posture and spine flexibility in post-tests were found. It seems that females even in senior age react better to incentives of intervention in balance and spine flexibility. On the base of results analyses, we can declare the significant improvement in social balance markers after intervention in the experimental group (F = 10.5, p < 0.001). In average, seniors are used to take four drugs daily. Number of drugs can contribute to allergy symptoms and balance problems. It can be concluded that static balance and walking ability of seniors according Tinetti Balance scale correlate significantly with psychic and social monitored markers.

Keywords: exercises, balance, seniors 65+, health, mental and social balance

Procedia PDF Downloads 137

Authors: Teresita Lopez Joy, Jose A. Acevedo Suarez, Martha I. Gomez Acosta, Ana Julia Acevedo Urquiaga

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Current trends in business competitiveness indicate the need to manage businesses as supply chains and not in isolation. The use of strategies aimed at maximum satisfaction of customers in a network and based on inter-company cooperation; contribute to obtaining successful joint results. In the Cuban economic context, the development of productive linkages to achieve integrated management of supply chains is considering a key aspect. In order to achieve this jump, it is necessary to develop acting capabilities in the entities that make up the chains through a systematic procedure that allows arriving at a management model in consonance with the environment. The objective of the research focuses on: designing a model and procedure for the development of integrated management of supply chains in economic entities. The results obtained are: the Model and the Procedure for the Development of the Supply Chains Integrated Management (MP-SCIM). The Model is based on the development of logistics in the network actors, the joint work between companies, collaborative planning and the monitoring of a main indicator according to the end customers. The application Procedure starts from the well-founded need for development in a supply chain and focuses on training entrepreneurs as doers. The characterization and diagnosis is done to later define the design of the network and the relationships between the companies. It takes into account the feedback as a method of updating the conditions and way to focus the objectives according to the final customers. The MP-SCIM is the result of systematic work with a supply chain approach in companies that have consolidated as coordinators of their network. The cases of the edible oil chain and explosives for construction sector reflect results of more remarkable advances since they have applied this approach for more than 5 years and maintain it as a general strategy of successful development. The edible oil trading company experienced a jump in sales. In 2006, the company started the analysis in order to define the supply chain, apply diagnosis techniques, define problems and implement solutions. The involvement of the management and the progressive formation of performance capacities in the personnel allowed the application of tools according to the context. The company that coordinates the explosives chain for construction sector shows adequate training with independence and opportunity in the face of different situations and variations of their business environment. The appropriation of tools and techniques for the analysis and implementation of proposals is a characteristic feature of this case. The coordinating entity applies integrated supply chain management to its decisions based on the timely training of the necessary action capabilities for each situation. Other cases of study and application that validate these tools are also detailed in this paper, and they highlight the results of generalization in the quantitative and qualitative improvement according to the final clients. These cases are: teaching literature in universities, agricultural products of local scope and medicine supply chains.

Keywords: integrated management, logistic system, supply chain management, tactical-operative planning

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Authors: B. Sudhakara Reddy

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This study provides a snapshot of the sustainability of selected Indian cities by employing 70 indicators in four dimensions to develop an overall city sustainability index. In recent years, the concept of ‘urban sustainability’ has become prominent due to its complexity. Urban areas propel growth and at the same time poses a lot of ecological, social and infrastructural problems and risks. In case of developing countries, the high population density of and the continuous in-migration run the highest risk in natural and man-made disasters. These issues combined with the inability of policy makers in providing basic services makes the cities unsustainable. To assess whether any given policy is moving towards or against urban sustainability it is necessary to consider the relationships among its various dimensions. Hence, in recent years, while preparing the sustainability index, an integral approach involving indicators of different dimensions such as ‘economic’, ‘environmental’ and 'social' is being used. It is also important for urban planners, social analysts and other related institutions to identify and understand the relationships in this complex system. The objective of the paper is to develop a city performance index (CPI) to measure and evaluate the urban regions in terms of sustainable performances. The objectives include: i) Objective assessment of a city’s performance, ii) setting achievable goals iii) prioritise relevant indicators for improvement, iv) learning from leaders, iv) assessment of the effectiveness of programmes that results in achieving high indicator values, v) Strengthening of stakeholder participation. Using the benchmark approach, a conceptual framework is developed for evaluating 25 Indian cities. We develop City Sustainability index (CSI) in order to rank cities according to their level of sustainability. The CSI is composed of four dimensions: Economic, Environment, Social, and Institutional. Each dimension is further composed of multiple indicators: (1) Economic that considers growth, access to electricity, and telephone availability; (2) environmental that includes waste water treatment, carbon emissions, (3) social that includes, equity, infant mortality, and 4) institutional that includes, voting share of population, urban regeneration policies. The CSI, consisting of four dimensions disaggregate into 12 categories and ultimately into 70 indicators. The data are obtained from public and non-governmental organizations, and also from city officials and experts. By ranking a sample of diverse cities on a set of specific dimensions the study can serve as a baseline of current conditions and a marker for referencing future results. The benchmarks and indices presented in the study provide a unique resource for the government and the city authorities to learn about the positive and negative attributes of a city and prepare plans for a sustainable urban development. As a result of our conceptual framework, the set of criteria we suggest is somewhat different to any already in the literature. The scope of our analysis is intended to be broad. Although illustrated with specific examples, it should be apparent that the principles identified are relevant to any monitoring that is used to inform decisions involving decision variables. These indicators are policy-relevant and, hence they are useful tool for decision-makers and researchers.

Keywords: benchmark, city, indicator, performance, sustainability

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Authors: Soledad Coronel Poma, Lorena Alvarado Rodriguez

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The purpose of this project is to design public space through urban-architectural strategies that help to the sustainable recovery of the Huayla estuary and the revival of tourism in this area. This design considers other sustainable and architectural ideas used in similar cases, along with national and international regulations for saving shorelines in danger. To understand the situation of this location, Puerto Bolivar is the main port of the Province of El Oro and of the south of the country, where 90,000 national and foreign tourists pass through all year round. For that reason, a physical-urban, social, and environmental analysis of the area was carried out through surveys and conversations with the community. This analysis showed that around 70% of people feel unsatisfied and concerned about the estuary and its surroundings. Crime, absence of green areas, bad conservation of shorelines, lack of tourists, poor commercial infrastructure, and the spread of informal commerce are the main issues to be solved. As an intervention project whose main goal is that residents and tourists have contact with native nature and enjoy doing local activities, three main strategies: mobility, ecology, and urban –architectural are proposed to recover the estuary and its surroundings. First of all, the design of this public space is based on turning the estuary location into a linear promenade that could be seen as a tourist corridor, which would help to reduce pollution, increase green spaces and improve tourism. Another strategy aims to improve the economy of the community through some local activities like fishing and sailing and the commerce of fresh seafood, both raw products and in restaurants. Furthermore, in support of the environmental approach, some houses are rebuilt as sustainable houses using local materials and rearranged into blocks closer to the commercial area. Finally, the planning incorporates the use of many plants such as palms, sameness trees, and mangroves around the area to encourage people to get in touch with nature. The results of designing this space showed an increase in the green area per inhabitant index. It went from 1.69 m²/room to 10.48 m²/room, with 12 096 m² of green corridors and the incorporation of 5000 m² of mangroves at the shoreline. Additionally, living zones also increased with the creation of green areas taking advantage of the existing nature and implementing restaurants and recreational spaces. Moreover, the relocation of houses and buildings helped to free estuary's shoreline, so people are now in more comfortable places closer to their workplaces. Finally, dock spaces are increased, reaching the capacity of the boats and canoes, helping to organize the area in the estuary. To sum up, this project searches the improvement of the estuary environment with its shoreline and surroundings that include the vegetation, infrastructure and people with their local activities, achieving a better quality of life, attraction of tourism, reduction of pollution and finally getting a full recovered estuary as a natural ecosystem.

Keywords: recover, public space, stuary, sustainable

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Authors: R. Ueda

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Today global society is seeking resilient partnership in local organizations and individuals, which realizes multi-stakeholders relationship. Although it is proposed by modern global framework of sustainable development, it is conceivable that such affiliation can be found out in the traditional local community in Japan, and that traditional spirit is tacitly sustaining in modern context of disaster mitigation in society and economy. Then this research is aiming to clarify and analyze implication for the global world by actual case studies. Regional and urban resilience is the ability of multi-stakeholders to cooperate flexibly and to adapt in response to changes in the circumstances caused by disasters, but there are various conflicts affecting coordination of disaster relief measures. These conflicts arise not only from a lack of communication and an insufficient network, but also from the difficulty to jointly draw common context from fragmented information. This is because of the weakness of our modern engineering which focuses on maintenance and restoration of individual systems. Here local ‘circles’ holistically includes local community and interacts periodically. Focusing on examples of resilient organizations and wisdom created in communities, what can be seen throughout history is a virtuous cycle where the information and the knowledge are structured, the context to be adapted becomes clear, and an adaptation at a higher level is made possible, by which the collaboration between organizations is deepened and expanded. And the wisdom of a solid and autonomous disaster prevention formed by the historical community called’ Waju’ – an area surrounded by circle embankment to protect the settlement from flood – lives on in government efforts of the coastal industrial island of today. Industrial company there collaborates to create a circle including common evacuation space, road access improvement and infrastructure recovery. These days, people here adopts new interface technology. Large-scale AR- Augmented Reality for more than hundred people is expressing detailed hazard by tsunami and liquefaction. Common experiences of the major disaster space and circle of mutual discussion are enforcing resilience. Collaboration spirit lies in the center of circle. A consistent key point is a virtuous cycle where the information and the knowledge are structured, the context to be adapted becomes clear, and an adaptation at a higher level is made possible, by which the collaboration between organizations is deepened and expanded. This writer believes that both self-governing human organizations and the societal implementation of technical systems are necessary. Infrastructure should be autonomously instituted by associations of companies and other entities in industrial areas for working closely with local governments. To develop advanced disaster prevention and multi-stakeholder collaboration, partnerships among industry, government, academia and citizens are important.

Keywords: industrial recovery, multi-sakeholders, traditional culture, user experience, Waju

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Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

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Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

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Authors: Carlos E. Rodríguez-Rodríguez, Karla Ruiz-Hidalgo, Kattia Madrigal-Zúñiga, Juan Salvador Chin-Pampillo, Mario Masís-Mora, Elizabeth Carazo-Rojas

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One of the main causes of contamination linked to agricultural activities is the spillage and disposal of pesticides, especially during the loading, mixing or cleaning of agricultural spraying equipment. One improvement in the handling of pesticides is the use of biopurification systems (BPS), simple and cheap degradation devices where the pesticides are biologically degraded at accelerated rates. The biologically active core of BPS is the biomixture, which is constituted by soil pre-exposed to the target pesticide, a lignocellulosic substrate to promote the activity of ligninolitic fungi and a humic component (peat or compost), mixed at a volumetric proportion of 50:25:25. Considering the known ability of lignocellulosic fungi to degrade a wide range of organic pollutants, and the high amount of lignocellulosic waste used in biomixture preparation, the bioaugmentation of biomixtures with these fungi represents an interesting approach for improving biomixtures. The present work aimed at evaluating the effect of the bioaugmentation of rice husk based biomixtures with the fungus Trametes versicolor in the removal of the insectice/nematicide carbofuran (CFN) and to optimize the composition of the biomixture to obtain the best performance in terms of CFN removal and mineralization, reduction in formation of transformation products and decrease in residual toxicity of the matrix. The evaluation of several lignocellulosic residues (rice husk, wood chips, coconut fiber, sugarcane bagasse or newspaper print) revealed the best colonization by T. versicolor in rice husk. Pre-colonized rice husk was then used in the bioaugmentation of biomixtures also containing soil pre-exposed to CFN and either peat (GTS biomixture) or compost (GCS biomixture). After spiking with 10 mg/kg CBF, the efficiency of the biomixture was evaluated through a multi-component approach that included: monitoring of CBF removal and production of CBF transformation products, mineralization of radioisotopically labeled carbofuran (14C-CBF) and changes in the toxicity of the matrix after the treatment (Daphnia magna acute immobilization test). Estimated half-lives of CBF in the biomixtures were 3.4 d and 8.1 d in GTS and GCS, respectively. The transformation products 3-hydroxycarbofuran and 3-ketocarbofuran were detected at the moment of CFN application, however their concentration continuously disappeared. Mineralization of 14C-CFN was also faster in GTS than GCS. The toxicological evaluation showed a complete toxicity removal in the biomixtures after 48 d of treatment. The composition of the GCS biomixture was optimized using a central composite design and response surface methodology. The design variables were the volumetric content of fungally pre-colonized rice husk and the volumetric ratio compost/soil. According to the response models, maximization of CFN removal and mineralization rate, and minimization in the accumulation of transformation products were obtained with an optimized biomixture of composition 30:43:27 (pre-colonized rice husk:compost:soil), which differs from the 50:25:25 composition commonly employed in BPS. Results suggest that fungal bioaugmentation may enhance the performance of biomixtures in CFN removal. Optimization reveals the importance of assessing new biomixture formulations in order to maximize their performance.

Keywords: bioaugmentation, biopurification systems, degradation, fungi, pesticides, toxicity

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Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi

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Drug-resistant tuberculosis, together with the associated comorbidities like pulmonary fibrosis and silicosis, has been one of the most serious global public health threats that requires immediate action to curb or mitigate it. This prolongs hospital stays, increases the cost of medication, and increases the death toll recorded annually. Crinum asiaticum bulb (CAE) and betulin (BET) are known for their biological and pharmacological effects. Pharmacological effects reported on CAE include antimicrobial, anti-inflammatory, anti-pyretic, anti-analgesic, and anti-cancer effects. Betulin has exhibited a multitude of powerful pharmacological properties ranging from antitumor, anti-inflammatory, anti-parasitic, anti-microbial, and anti-viral activities. This work sought to investigate the anti-tuberculosis and resistant modulatory effects and also assess their effects on mitigating pulmonary fibrosis and silicosis. In the anti-tuberculosis and resistant modulatory effects, both CAE and BET showed strong antimicrobial activities (31.25 ≤ MIC ≤ 500) µg/ml against the studied microorganisms and also produced significant anti-efflux pump and biofilm inhibitory effects (ρ < 0.0001) as well as exhibiting resistance modulatory and synergistic effects when combined with standard antibiotics. Crinum asiaticum bulbs extract and betulin were shown to possess anti-pulmonary fibrosis effects. There was an increased survival rate in the CAE and BET treatment groups compared to the BLM-induced group. There was a marked decrease in the levels of hydroxyproline and collagen I and III in the CAE and BET treatment groups compared to the BLM-treated group. The treatment groups of CAE and BET significantly downregulated the levels of pro-fibrotic and pro-inflammatory cytokine concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increase in the BLM-treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM-induced pulmonary fibrosis in mice. The study showed improved lung functions with a wide focal area of viable alveolar spaces and few collagen fibers deposition on the lungs of the treatment groups. In the anti-silicosis and pulmonoprotective effects of CAE and BET, the levels of NF-κB, TNF-α, IL-1β, IL-6 and hydroxyproline, collagen types I and III were significantly reduced by CAE and BET (ρ < 0.0001). Both CAE and BET significantly (ρ < 0.0001) inhibited the levels of hydroxyproline, collagen I and III when compared with the negative control group. On BALF biomarkers such as macrophages, lymphocytes, monocytes, and neutrophils, CAE and BET were able to reduce their levels significantly (ρ < 0.0001). The CAE and BET were examined for anti-oxidant activity and shown to raise the levels of catalase (CAT) and superoxide dismutase (SOD) while lowering the level of malondialdehyde (MDA). There was an improvement in lung function when lung tissues were examined histologically. Crinum asiaticum bulbs extract and betulin were discovered to exhibit anti-tubercular and resistance-modulatory properties, as well as the capacity to minimize TB comorbidities such as pulmonary fibrosis and silicosis. In addition, CAE and BET may act as protective mechanisms, facilitating the preservation of the lung's physiological integrity. The outcomes of this study might pave the way for the development of leads for producing single medications for the management of drug-resistant tuberculosis and its accompanying comorbidities.

Keywords: fibrosis, crinum, tuberculosis, antiinflammation, drug resistant

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Authors: Tesfaye Dagne, Dagmawit Solomon, Firmaye Bogale, Yosef Gebreyohannes, Samson Mideksa, Mamuye Hadis, Desalegn Ararso, Ermias Woldie, Tsegaye Getachew, Sabit Ababor, Zelalem Kebede

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Globally, road traffic accident (RTA) is causing millions of deaths and injuries every year. It is one of the leading causes of death among people of all age groups and the problem is worse among young reproductive age group. Moreover the problem is increasing with an increasing number of vehicles. The majority of the problem happen in low and middle income countries (LMIC), even if the number of vehicles in these countries is low compared to their population. So, the objective of this paper is to summarize the best available evidence on interventions that can reduce road traffic accidents in low and middle income countries (LMIC). Method: A rapid evidence synthesis approach adapted from the SURE Rapid Response Service was applied to search, appraise and summarize the best available evidence on effective intervention in reducing road traffic injury. To answer the question under review, we searched for relevant studies from databases including PubMed, the Cochrane Library, TRANSPORT, Health system evidence, Epistemonikos, and SUPPORT summary. The following key terms were used for searching: Road traffic accident, RTA, Injury, Reduc*, Prevent*, Minimiz*, “Low and middle-income country”, LMIC. We found 18 articles through a search of different databases mentioned above. After screening for the titles and abstracts of the articles, four of them which satisfy the inclusion criteria were included in the final review. Then we appraised and graded the methodological quality of systematic reviews that are deemed to be highly relevant using AMSTAR. Finding: The identified interventions to reduce road traffic accidents were legislation and enforcement, public awareness/education, speed control/ rumble strips, road improvement, mandatory motorcycle helmet, graduated driver license, street lighting. Legislation and Enforcement: Legislation focusing on mandatory motorcycle helmet usage, banning cellular phone usage when driving, seat belt laws, decreasing the legal blood alcohol content (BAC) level from 0.06 g/L to 0.02 g/L bring the best result where enforcement is there. Public Awareness/Education: focusing on seat belt use, child restraint use, educational training in health centers and schools/universities, and public awareness with media through the distribution of videos, posters/souvenirs, and pamphlets are effective in the short run. Speed Control: through traffic calming bumps, or speed bumps, rumbled strips are effective in reducing accidents and fatality. Mandatory Motorcycle Helmet: is associated with reduction in mortality. Graduated driver’s license (GDL): reduce road traffic injury by 19%. Street lighting: is a low-cost intervention which may reduce road traffic accidents.

Keywords: evidence synthesis, injury, rapid review, reducing, road traffic accident

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Authors: Jothilakshmy Nagammal

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This research paper deals with the different case studies, where the Form-Based Codes are adopted in general and the different implementation methods in particular are discussed to develop a method for formulating a new planning model. The organizing principle of the Form-Based Codes, the transect is used to zone the city into various context specific transects. An approach is adopted to develop the new planning model, city Specific Planning Model (CSPM), as a tool to achieve sustainability for any city in general. A case study comparison method in terms of the planning tools used, the code process adopted and the various control regulations implemented in thirty two different cities are done. The analysis shows that there are a variety of ways to implement form-based zoning concepts: Specific plans, a parallel or optional form-based code, transect-based code /smart code, required form-based standards or design guidelines. The case studies describe the positive and negative results from based zoning, Where it is implemented. From the different case studies on the method of the FBC, it is understood that the scale for formulating the Form-Based Code varies from parts of the city to the whole city. The regulating plan is prepared with the organizing principle as the transect in most of the cases. The various implementation methods adopted in these case studies for the formulation of Form-Based Codes are special districts like the Transit Oriented Development (TOD), traditional Neighbourhood Development (TND), specific plan and Street based. The implementation methods vary from mandatory, integrated and floating. To attain sustainability the research takes the approach of developing a regulating plan, using the transect as the organizing principle for the entire area of the city in general in formulating the Form-Based Codes for the selected Special Districts in the study area in specific, street based. Planning is most powerful when it is embedded in the broader context of systemic change and improvement. Systemic is best thought of as holistic, contextualized and stake holder-owned, While systematic can be thought of more as linear, generalisable, and typically top-down or expert driven. The systemic approach is a process that is based on the system theory and system design principles, which are too often ill understood by the general population and policy makers. The system theory embraces the importance of a global perspective, multiple components, interdependencies and interconnections in any system. In addition, the recognition that a change in one part of a system necessarily alters the rest of the system is a cornerstone of the system theory. The proposed regulating plan taking the transect as an organizing principle and Form-Based Codes to achieve sustainability of the city has to be a hybrid code, which is to be integrated within the existing system - A Systemic Approach with a Systematic Process. This approach of introducing a few form based zones into a conventional code could be effective in the phased replacement of an existing code. It could also be an effective way of responding to the near-term pressure of physical change in “sensitive” areas of the community. With this approach and method the new Context Specific Planning Model is created towards achieving sustainability is explained in detail this research paper.

Keywords: context based planning model, form based code, transect, systemic approach

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Authors: Jason Ceavers, Travis Thompson, Juan Torres, Ramanakumar Anam, Alan Wong, Andrei Carvalho, Shane Quo, Shawn Alonso, Moises Cintron, Ricardo C. Carrero, German Lopez, Vamsi Garimella, German Giese

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Introduction: Advance directives (AD) are essential for patients to communicate their wishes when they are not able to. Ideally, these discussions should not occur for the first time when a patient is hospitalized with an acute life-threatening illness. There is a large number of patients who do not have clearly documented ADs, resulting in the misutilization of resources and additional patient harm. This is a nationwide issue, and the Joint Commission has it as one of its national quality metrics. Presented here is a proposed protocol to increase the number of documented AD discussions in a community-based, internal medicine residency primary care clinic in South Florida. Methods: The SMART Aim for this quality improvement project is to increase documentation of AD discussions in the outpatient setting by 25% within three months in medicare patients. A survey was sent to stakeholders (clinic attendings, residents, medical assistants, front desk staff, and clinic managers), asking them for three factors they believed contributed most to the low documentation rate of AD discussions. The two most important factors were time constraints and systems issues (such as lack of a standard method to document ADs and ADs not being uploaded to the chart) which were brought up by 25% and 21.2% of the 32 survey responders, respectively. Pre-intervention data from clinic patients in 2020-2021 revealed 17.05% of patients had clear, actionable ADs documented. To address these issues, an AD pocket card was created to give to patients. One side of the card has a brief explanation of what ADs are. The other side has a column of interventions (cardiopulmonary resuscitation, mechanical ventilation, dialysis, tracheostomy, feeding tube) with boxes patients check off if they want the intervention done, do not want the intervention, do not want to discuss the topic, or need more information. These cards are to be filled out and scanned into their electronic chart to be reviewed by the resident before their appointment. The interventions that patients want more information on will be discussed by the provider. If any changes are made, the card will be re-scanned into their chart. After three months, we will chart review the patients seen in the clinic to determine how many medicare patients have a pocket card uploaded and how many have advance directives discussions documented in a progress note or annual wellness note. If there is not enough time for an AD discussion, a follow-up appointment can be scheduled for that discussion. Discussion: ADs are a crucial part of patient care, and failure to understand a patient’s wishes leads to improper utilization of resources, avoidable litigation, and patient harm. Time constraints and systems issues were identified as two major factors contributing to the lack of advance directive discussion in our community-based resident primary care clinic. Our project aims at increasing the documentation rate for ADs through a simple pocket card intervention. These are self-explanatory, easy to read and allow the patients to clearly express what interventions they desire or what they want to discuss further with their physician.

Keywords: advance directives, community-based, pocket card, primary care clinic

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Authors: Sharon Harel, Rachel Kizony, Yoram Feldman, Gabi Zeilig, Mordechai Shani

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Multiple Sclerosis (MS) is a neurological disease that may cause restriction in participation in daily activities of young adults. Main symptoms include fatigue, weakness and cognitive decline. The appearance of symptoms, their severity and deterioration rate, change between patients. The challenge of health services is to provide long-term rehabilitation services to people with MS. The objective of this presentation is to describe a course of tele-rehabilitation service of a woman with MS. Methods; R is a 48 years-old woman, diagnosed with MS when she was 22. She started to suffer from weakness of her non-dominant left upper extremity about ten years after the diagnosis. She was referred to the tele-rehabilitation service by her rehabilitation team, 16 years after diagnosis. Her goals were to improve ability to use her affected upper extremity in daily activities. On admission her score in the Mini-Mental State Exam was 30/30. Her Fugl-Meyer Assessment (FMA) score of the left upper extremity was 48/60, indicating mild weakness and she had a limitation of her shoulder abduction (90 degrees). In addition, she reported little use of her arm in daily activities as shown in her responses to the Motor Activity Log (MAL) that were equal to 1.25/5 in amount and 1.37 in quality of use. R. received two 30 minutes on-line sessions per week in the tele-rehabilitation service, with the CogniMotion system. These were complemented by self-practice with the system. The CogniMotion system provides a hybrid (synchronous-asynchronous), the home-based tele-rehabilitation program to improve the motor, cognitive and functional status of people with neurological deficits. The system consists of a computer, large monitor, and the Microsoft’s Kinect 3D sensor. This equipment is located in the client’s home and connected to a clinician’s computer setup in a remote clinic via WiFi. The client sits in front of the monitor and uses his body movements to interact with games and tasks presented on the monitor. The system provides feedback in the form of ‘knowledge of results’ (e.g., the success of a game) and ‘knowledge of performance’ (e.g., alerts for compensatory movements) to enhance motor learning. The games and tasks were adapted for R. motor abilities and level of difficulty was gradually increased according to her abilities. The results of her second assessment (after 35 on-line sessions) showed improvement in her FMA score to 52 and shoulder abduction to 140 degrees. Moreover, her responses to the MAL indicated an increased amount (2.4) and quality (2.2) of use of her left upper extremity in daily activities. She reported high level of enjoyment from the treatments (5/5), specifically the combination of cognitive challenges while moving her body. In addition, she found the system easy to use as reflected by her responses to the System Usability Scale (85/100). To-date, R. continues to receive treatments in the tele-rehabilitation service. To conclude, this case report shows the potential of using tele-rehabilitation for people with MS to provide strategies to enhance the use of the upper extremity in daily activities as well as for maintaining motor function.

Keywords: motor function, multiple-sclerosis, tele-rehabilitation, daily activities

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Authors: Amanda Kavner, Richard Lamb

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Faster growth in science and technology of other nations may make staying globally competitive more difficult without shifting focus on how science is taught in US classes. An integral part of learning science involves visual and spatial thinking since complex, and real-world phenomena are often expressed in visual, symbolic, and concrete modes. The primary barrier to spatial thinking and visual literacy in Science, Technology, Engineering, and Math (STEM) fields is representational competence, which includes the ability to generate, transform, analyze and explain representations, as opposed to generic spatial ability. Although the relationship is known between the foundational visual literacy and the domain-specific science literacy, science literacy as a function of science learning is still not well understood. Moreover, the need for a more reliable measure is necessary to design resources which enhance the fundamental visuospatial cognitive processes behind scientific literacy. To support the improvement of students’ representational competence, first visualization skills necessary to process these science representations needed to be identified, which necessitates the development of an instrument to quantitatively measure visual literacy. With such a measure, schools, teachers, and curriculum designers can target the individual skills necessary to improve students’ visual literacy, thereby increasing science achievement. This project details the development of an artificial neural network capable of measuring science literacy using functional Near-Infrared Spectroscopy (fNIR) data. This data was previously collected by Project LENS standing for Leveraging Expertise in Neurotechnologies, a Science of Learning Collaborative Network (SL-CN) of scholars of STEM Education from three US universities (NSF award 1540888), utilizing mental rotation tasks, to assess student visual literacy. Hemodynamic response data from fNIRsoft was exported as an Excel file, with 80 of both 2D Wedge and Dash models (dash) and 3D Stick and Ball models (BL). Complexity data were in an Excel workbook separated by the participant (ID), containing information for both types of tasks. After changing strings to numbers for analysis, spreadsheets with measurement data and complexity data were uploaded to RapidMiner’s TurboPrep and merged. Using RapidMiner Studio, a Gradient Boosted Trees artificial neural network (ANN) consisting of 140 trees with a maximum depth of 7 branches was developed, and 99.7% of the ANN predictions are accurate. The ANN determined the biggest predictors to a successful mental rotation are the individual problem number, the response time and fNIR optode #16, located along the right prefrontal cortex important in processing visuospatial working memory and episodic memory retrieval; both vital for science literacy. With an unbiased measurement of science literacy provided by psychophysiological measurements with an ANN for analysis, educators and curriculum designers will be able to create targeted classroom resources to help improve student visuospatial literacy, therefore improving science literacy.

Keywords: artificial intelligence, artificial neural network, machine learning, science literacy, neuroscience

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Authors: Fstemeh Rais Esmaili, Ehsan Ranjbar

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Pedestrian streets as one type of urban public spaces have an important role in improving the quality of urban life. In Iran, planning and designing of pedestrian streets is in its primary steps. In spite of starting this approach in Iran, and designing several pedestrian streets, there are still not organized studies about quality assessment of pedestrian streets. As a result, the strength and weakness points of the initial experiences have not been utilized. This inattention to quality assessment have caused designing pedestrian streets to be limited to just vehicles traffic control and preliminary actions like paving; so that, special potentials of pedestrian streets for creating social, livable and dynamic public spaces have not been used. This article, as an organized study about quality assessment of pedestrian streets in Iran, tries to reach two main goals: first, introducing a framework for quality assessment of pedestrian streets in Iran, and second, creating a context for improving the quality of pedestrian streets especially for further experiences. The main research methods are description and context analyzing. With respect to comparative analysis of ideas about quality, considering international and local case studies and analyzing existing condition of Saf Pedestrian Street, a particular model for quality assessment has been introduced. In this model, main components and assessment criteria have been presented. On the basis of this model, questionnaire and checklist for assessment have been prepared. The questionnaire and interview have been used to assess qualities which are in direct contact with people and the checklist has been used for analyzing visual qualities by authors through observation. Some results of questionnaire and checklist show that 7 of 11 primary components, diversity, flexibility, cleanness, legibility and imaginably, identity, livability, form and physical setting are rated low and very low in quality degree. Three components, efficiency, comfort and distinctiveness, have medium and low quality degree and one component, access, linkage and permeability has high quality degree. Therefore, based on implemented analyzing process, Saf Pedestrian Street needs to be improved and these quality improvement priorities are determined based on presented criteria. Adaption of final results with existing condition illustrates the shortage of services for satisfying user’s needs, inflexibility and impossibility of using spaces in various times, lack of facilities for different climatic conditions, lack of facilities such as drinking fountain, inappropriate designing of existing urban furniture like garbage cans, and creating pollution and unsuitable view, lack of visual attractions, neglecting disabled persons in designing entrances, shortage of benches and their undesirable designing, lack of vegetation, absence of special characters making it different from other streets, preventing people taking part in the space causing lack of affiliation, lack of appropriate elements for leisure time and lack of exhilaration in the space. On the other hand, these results present high access and permeability, high safety, less sound pollution and more relief, comfortable movement along the way due to suitable pavement and economic efficiency, as the strength points of Saf pedestrian street.

Keywords: pedestrian streets, quality assessment, quality criteria, Saf Pedestrian Street

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Authors: Vasundhara Arora, Anupam Jhobta, Suresh Thakur, Sanjiv Sharma

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Aims and Objectives: Intracranial tuberculosis (TB) is one of the most devastating manifestations of TB and a challenging public health issue of considerable importance and magnitude world over. This study elaborates on the imaging spectrum of neurotuberculosis on magnetic resonance imaging (MRI) in 29 clinically suspected cases from a tertiary care hospital. Materials and Methods: The prospective hospital based evaluation of MR imaging features of neuro-tuberculosis in 29 clinically suspected cases was carried out in Department of Radio-diagnosis, Indira Gandhi Medical Hospital from July 2017 to August 2018. MR Images were obtained on a 1.5 T Magnetom Avanto machine and were analyzed to identify any abnormal meningeal enhancement or parenchymal lesions. Microbiological and Biochemical CSF analysis was performed in radio-logically suspected cases and the results were compared with the imaging data. Clinical follow up of the patients started on anti-tuberculous treatment was done to evaluate the response to treatment and clinical outcome. Results: Age range of patients in the study was between 1 year to 73 years. The mean age of presentation was 11.5 years. No significant difference in the distribution of cerebral tuberculosis was noted among the two genders. Imaging findings of neuro-tuberculosis obtained were varied and non specific ranging from lepto-meningeal enhancement, cerebritis to space occupying lesions such as tuberculomas and tubercular abscesses. Complications presenting as hydrocephalus (n= 7) and infarcts (n=9) was noted in few of these patients. 29 patients showed radiological suspicion of CNS tuberculosis with meningitis alone observed in 11 cases, tuberculomas alone were observed in 4 cases, meningitis with parenchymal tuberculomas in 11 cases. Tubercular abscess and cerebritis were observed in one case each. Tuberculous arachnoiditis was noted in one patient. Gene expert positivity was obtained in 11 out of 29 radiologically suspected patients; none of the patients showed culture positivity. Meningeal form of the disease alone showed higher positivity rate of gene Xpert (n=5) followed by combination of meningeal and parenchymal forms of disease (n=4). The parenchymal manifestation of disease alone showed least positivity rates (n= 3) with gene xpert testing. All 29 patients were started on anti tubercular treatment based on radiological suspicion of the disease with clinical improvement observed in 27 treated patients. Conclusions: In our study, higher incidence of neuro- tuberculosis was noted in paediatric population with predominance of the meningeal form of the disease. Gene Xpert positivity obtained was low due to paucibacillary nature of cerebrospinal fluid (CSF) with even lower positivity of CSF samples in parenchymal form of the manifestation. MRI showed high accuracy in detecting CNS lesions in neuro-tuberculosis. Hence, it can be concluded that MRI plays a crucial role in the diagnosis because of its inherent sensitivity and specificity and is an indispensible imaging modality. It caters to the need of early diagnosis owing to poor sensitivity of microbiological tests more so in the parenchymal manifestation of the disease.

Keywords: neurotuberculosis, tubercular abscess, tuberculoma, tuberculous meningitis

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Authors: Priyanka Jain, Ashish K. Sharma, Esha Shukla, K. J. Mukherjee

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We propose a paradigm shift in our approach to design improved platforms for recombinant protein production, by addressing system level issues rather than the individual steps associated with recombinant protein synthesis like transcription, translation, etc. We demonstrate that by controlling and modulating the cellular stress response (CSR), which is responsible for feedback control of protein synthesis, we can generate hyper-producing strains. We did transcriptomic profiling of post-induction cultures, expressing different types of protein, to analyze the nature of this cellular stress response. We found significant down-regulation of substrate utilization, translation, and energy metabolism genes due to generation CSR inside the host cell. However, transcription profiling has also shown that many genes are up-regulated post induction and their role in modulating the CSR is unclear. We hypothesized that these up-regulated genes trigger signaling pathways, generating the CSR and concomitantly reduce the recombinant protein yield. To test this hypothesis, we knocked out the up-regulated genes, which did not have any downstream regulatees, and analyzed their impact on cellular health and recombinant protein expression. Two model proteins i.e., GFP and L-Asparaginase were chosen for this analysis. We observed a significant improvement in expression levels, with some knock-outs showing more than 7-fold higher expression compared to control. The 10 best single knock-outs were chosen to make 45 combinations of all possible double knock-outs. A further increase in expression was observed in some of these double knock- outs with GFP levels being highest in a double knock-out ΔyhbC + ΔelaA. However, for L-Asparaginase which is a secretory protein, the best results were obtained using a combination of ΔelaA+ΔcysW knock-outs. We then tested all the knock outs for their ability to enhance the expression of a 'difficult-to-express' protein. The Rubella virus E1 protein was chosen and tagged with sfGFP at the C-terminal using a linker peptide for easy online monitoring of expression of this fusion protein. Interestingly, the highest increase in Rubella-sGFP levels was obtained in the same double knock-out ΔelaA + ΔcysW (5.6 fold increase in expression yield compared to the control) which gave the highest expression for L-Asparaginase. However, for sfGFP alone, the ΔyhbC+ΔmarR knock-out gave the highest level of expression. These results indicate that there is a fair degree of commonality in the nature of the CSR generated by the induction of different proteins. Transcriptomic profiling of the double knock out showed that many genes associated with the translational machinery and energy biosynthesis did not get down-regulated post induction, unlike the control where these genes were significantly down-regulated. This confirmed our hypothesis of these genes playing an important role in the generation of the CSR and allowed us to design a strategy for making better expression hosts by simply knocking out key genes. This strategy is radically superior to the previous approach of individually up-regulating critical genes since it blocks the mounting of the CSR thus preventing the down-regulation of a very large number of genes responsible for sustaining the flux through the recombinant protein production pathway.

Keywords: cellular stress response, GFP, knock-outs, up-regulated genes

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Authors: Antonio Boggia, Luisa Paolotti, Gianluca Massei, Lucia Rocchi, Elaine Pace, Maria Attard

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The aim of this paper is to present a methodology and a computer model for sustainability assessment based on the integration of Multi-criteria Decision Analysis (MCDA) with a Geographic Information System (GIS). It presents the result of a study for the implementation of a model for measuring sustainability to address the policy actions for the improvement of sustainability at territory level. The aim is to rank areas in order to understand the specific technical and/or financial support that is required to develop sustainable growth. Assessing sustainable development is a multidimensional problem: economic, social and environmental aspects have to be taken into account at the same time. The tool for a multidimensional representation is a proper set of indicators. The set of indicators must be integrated into a model, that is an assessment methodology, to be used for measuring sustainability. The model, developed by the Environmental Laboratory of the University of Perugia, is called GeoUmbriaSUIT. It is a calculation procedure developed as a plugin working in the open-source GIS software QuantumGIS. The multi-criteria method used within GeoUmbriaSUIT is the algorithm TOPSIS (Technique for Order Preference by Similarity to Ideal Design), which defines a ranking based on the distance from the worst point and the closeness to an ideal point, for each of the criteria used. For the sustainability assessment procedure, GeoUmbriaSUIT uses a geographic vector file where the graphic data represent the study area and the single evaluation units within it (the alternatives, e.g. the regions of a country, or the municipalities of a region), while the alphanumeric data (attribute table), describe the environmental, economic and social aspects related to the evaluation units by means of a set of indicators (criteria). The use of the algorithm available in the plugin allows to treat individually the indicators representing the three dimensions of sustainability, and to compute three different indices: environmental index, economic index and social index. The graphic output of the model allows for an integrated assessment of the three dimensions, avoiding aggregation. The presence of separate indices and graphic output make GeoUmbriaSUIT a readable and transparent tool, since it doesn’t produce an aggregate index of sustainability as final result of the calculations, which is often cryptic and difficult to interpret. In addition, it is possible to develop a “back analysis”, able to explain the positions obtained by the alternatives in the ranking, based on the criteria used. The case study presented is an assessment of the level of sustainability in the six regions of Malta, an island state in the middle of the Mediterranean Sea and the southernmost member of the European Union. The results show that the integration of MCDA-GIS is an adequate approach for sustainability assessment. In particular, the implemented model is able to provide easy to understand results. This is a very important condition for a sound decision support tool, since most of the time decision makers are not experts and need understandable output. In addition, the evaluation path is traceable and transparent.

Keywords: GIS, multi-criteria analysis, sustainability assessment, sustainable development

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Authors: Pavel Baroch, Jiri Rezek, Michal Prochazka, Tomas Kozak, Jiri Houska

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Transparent semiconducting amorphous IGZO films have attracted great attention due to their excellent electrical properties and possible utilization in thin film transistors or in photovoltaic applications as they show 20-50 times higher mobility than that of amorphous silicon. It is also known that the properties of IGZO films are highly sensitive to process parameters, especially to oxygen partial pressure. In this study we have focused on the comparison of properties of transparent semiconducting amorphous indium gallium zinc oxide (IGZO) thin films prepared by conventional sputtering methods and those prepared by high power impulse magnetron sputtering (HiPIMS) method. Furthermore we tried to optimize electrical and optical properties of the IGZO thin films and to investigate possibility to apply these coatings on thermally sensitive flexible substrates. We employed dc, pulsed dc, mid frequency sine wave and HiPIMS power supplies for magnetron deposition. Magnetrons were equipped with sintered ceramic InGaZnO targets. As oxygen vacancies are considered to be the main source of the carriers in IGZO films, it is expected that with the increase of oxygen partial pressure number of oxygen vacancies decreases which results in the increase of film resistivity. Therefore in all experiments we focused on the effect of oxygen partial pressure, discharge power and pulsed power mode on the electrical, optical and mechanical properties of IGZO thin films and also on the thermal load deposited to the substrate. As expected, we have observed a very fast transition between low- and high-resistivity films depending on oxygen partial pressure when deposition using conventional sputtering methods/power supplies have been utilized. Therefore we established and utilized HiPIMS sputtering system for enlargement of operation window for better control of IGZO thin film properties. It is shown that with this system we are able to effectively eliminate steep transition between low and high resistivity films exhibited by DC mode of sputtering and the electrical resistivity can be effectively controlled in the wide resistivity range of 10-² to 10⁵ Ω.cm. The highest mobility of charge carriers (up to 50 cm2/V.s) was obtained at very low oxygen partial pressures. Utilization of HiPIMS also led to significant decrease in thermal load deposited to the substrate which is beneficial for deposition on the thermally sensitive and flexible polymer substrates. Deposition rate as a function of discharge power and oxygen partial pressure was also systematically investigated and the results from optical, electrical and structure analysis will be discussed in detail. Most important result which we have obtained demonstrates almost linear control of IGZO thin films resistivity with increasing of oxygen partial pressure utilizing HiPIMS mode of sputtering and highly transparent films with low resistivity were prepared already at low pO2. It was also found that utilization of HiPIMS technique resulted in significant improvement of surface smoothness in reactive mode of sputtering (with increasing of oxygen partial pressure).

Keywords: charge carrier mobility, HiPIMS, IGZO, resistivity

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Authors: Irene T. Ho

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Students with Autism Spectrum Disorder (ASD) studying in mainstream schools often face difficulties adjusting to school life and teachers often find it challenging to meet the needs of these students. The Hong Kong Jockey Club Autism Support Network (JC A-Connect) is an initiative launched in 2015 to enhance support for students with ASD as well as their families and schools. The School Support Programme of the Project aims at building the capacity of schools to provide quality education for these students. The present report provides a summary of the main features of the support model and the related evaluation results. The school support model was conceptualized in response to four observed needs: (1) inadequate teacher expertise in dealing with the related challenges, (2) the need to promote evidence-based practices in schools, (3) less than satisfactory home-school collaboration and whole-school participation, and (4) lack of concerted effort by different parties involved in providing support to schools. The resulting model had partnership and capacity building as two guiding tenets for the School Support Programme. There were two levels of partnership promoted in the project. At the programme support level, a platform that enables effective collaboration among major stakeholders was established, including the funding body that provides the necessary resources, the Education Bureau that helps to engage schools, university experts who provide professional leadership and research support, as well as non-governmental organization (NGO) professionals who provide services to the schools. At the programme implementation level, tripartite collaboration among teachers, parents and professionals was emphasized. This notion of partnership permeated efforts at capacity building targeting students with ASD, school personnel, parents and peers. During 2015 to 2018, school-based programmes were implemented in over 400 primary and secondary schools with the following features: (1) spiral Tier 2 (group) training for students with ASD to enhance their adaptive skills, led by professionals but with strong teacher involvement to promote transfer of knowledge and skills; (2) supplementary programmes for teachers, parents and peers to enhance their capability to support students with ASD; and (3) efforts at promoting continuing or transfer of learning, on the part of both students and teachers, to Tier 1 (classroom practice) and Tier 3 (individual training) contexts. Over 5,000 students participated in the Programme, representing about 50% of students diagnosed with ASD in mainstream public sector schools in Hong Kong. Results showed that the Programme was effective in helping students improve to various extents at three levels: achievement of specific training goals, improvement in adaptive skills in school, and change in ASD symptoms. The sense of competence of teachers and parents in dealing with ASD-related issues, measured by self-report rating scales, was also significantly enhanced. Moreover, effects on enhancing the school system to provide support for students with ASD, assessed according to indicators of inclusive education, were seen. The process and results of this Programme illustrate how obstacles to inclusive education for students with ASD could be overcome by strengthening the necessary partnerships and building the required capabilities of all parties concerned.

Keywords: autism, school support, skills training, teacher development, three-tier model

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Authors: Fathonah Siti, Ardiana Irma

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Indonesia is currently on its track to achieve Universal Health Coverage (UHC) by 2019. The program aims to address issues on disintegration in the implementation and coverage of various health insurance schemes and fragmented fund pooling. Family planning service is covered as one of benefit packages under preventive care. However, little has been done to examine how family planning program are appropriately managed across levels of governments and how family planning services are delivered to the end user. The study is performed through focus group discussion to related policy makers and selected programmers at central and district levels. The study is also benefited from relevant studies on family planning in the UHC scheme and other supporting data. The study carefully investigates some programmatic implications when family planning is integrated in the UHC program encompassing the need to recalculate contraceptive logistics for beneficiaries (eligible couple); policy reformulation for contraceptive service provision including supply chain management; establishment of family planning standard of procedure; and a call to update Management Information System. The study confirms that there is a significant increase in the numbers of contraceptive commodities needs to be procured by the government. Holding an assumption that contraceptive prevalence rate and commodities cost will be as expected increasing at 0.5% annually, the government need to allocate almost IDR 5 billion by 2019, excluded fee for service. The government shifts its focus to maintain eligible health facilities under National Population and Family Planning Board networks. By 2019, the government has set strategies to anticipate the provision of family planning services to 45.340 health facilities distributed in 514 districts and 7 thousand sub districts. Clear division of authorities has been established among levels of governments. Three models of contraceptive supply planning have been developed and currently in the process of being institutionalized. Pre service training for family planning services has been piloted in 10 prominent universities. The position of private midwives has been appreciated as part of the system. To ensure the implementation of quality and health expenditure control, family planning standard has been established as a reference to determine set of services required to deliver to the clients properly and types of health facilities to conduct particular family planning services. Recognition to individual status of program participation has been acknowledged in the Family Enumeration since 2015. The data is precisely recorded by name by address for each family and its members. It supplies valuable information to 15.131 Family Planning Field Workers (FPFWs) to provide information and education related to family planning in an attempt to generate demand and maintain the participation of family planning acceptors who are program beneficiaries. Despite overwhelming efforts described above, some obstacles remain. The program experiences poor socialization and yet removes geographical barriers for those living in remote areas. Family planning services provided for this sub population conducted outside the scheme as a complement strategy. However, UHC program has brought remarkable improvement in access and quality of family planning services.

Keywords: beneficiary, family planning services, national population and family planning board, universal health coverage

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Authors: Jing Jiang, Wenhuan XU, Lei Zhang, Shiyi Zhang, Tongli Wang

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Climate data quality significantly affects the reliability of ecological modeling. In the Asia Pacific (AP) region, low-quality climate data hinders ecological modeling. ClimateAP, a software developed in 2017, generates high-quality climate data for the AP region, benefiting researchers in forestry and agriculture. However, its adoption remains limited. This study aims to confirm the validity of biologically relevant variable data generated by ClimateAP during the normal climate period through comparison with the currently available gridded data. Climate data from 2,366 weather stations were used to evaluate the prediction accuracy of ClimateAP in comparison with the commonly used gridded data from WorldClim1.4. Univariate regressions were applied to 48 monthly biologically relevant variables, and the relationship between the observational data and the predictions made by ClimateAP and WorldClim was evaluated using Adjusted R-Squared and Root Mean Squared Error (RMSE). Locations were categorized into mountainous and flat landforms, considering elevation, slope, ruggedness, and Topographic Position Index. Univariate regressions were then applied to all biologically relevant variables for each landform category. Random Forest (RF) models were implemented for the climatic niche modeling of Cunninghamia lanceolata. A comparative analysis of the prediction accuracies of RF models constructed with distinct climate data sources was conducted to evaluate their relative effectiveness. Biologically relevant variables were obtained from three unpublished Chinese meteorological datasets. ClimateAPv3.0 and WorldClim predictions were obtained from weather station coordinates and WorldClim1.4 rasters, respectively, for the normal climate period of 1961-1990. Occurrence data for Cunninghamia lanceolata came from integrated biodiversity databases with 3,745 unique points. ClimateAP explains a minimum of 94.74%, 97.77%, 96.89%, and 94.40% of monthly maximum, minimum, average temperature, and precipitation variances, respectively. It outperforms WorldClim in 37 biologically relevant variables with lower RMSE values. ClimateAP achieves higher R-squared values for the 12 monthly minimum temperature variables and consistently higher Adjusted R-squared values across all landforms for precipitation. ClimateAP's temperature data yields lower Adjusted R-squared values than gridded data in high-elevation, rugged, and mountainous areas but achieves higher values in mid-slope drainages, plains, open slopes, and upper slopes. Using ClimateAP improves the prediction accuracy of tree occurrence from 77.90% to 82.77%. The biologically relevant climate data produced by ClimateAP is validated based on evaluations using observations from weather stations. The use of ClimateAP leads to an improvement in data quality, especially in non-mountainous regions. The results also suggest that using biologically relevant variables generated by ClimateAP can slightly enhance climatic niche modeling for tree species, offering a better understanding of tree species adaptation and resilience compared to using gridded data.

Keywords: climate data validation, data quality, Asia pacific climate, climatic niche modeling, random forest models, tree species

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Authors: Armin Nabaei, M. Omair Ahmad, M. N. S. Swamy

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Many facial expression and emotion recognition methods in the traditional approaches of using LDA, PCA, and EBGM have been proposed. In recent years deep learning models have provided a unique platform addressing by automatically extracting the features for the detection of facial expression and emotions. However, deep networks require large training datasets to extract automatic features effectively. In this work, we propose an efficient emotion detection algorithm using face images when only small datasets are available for training. We design a deep network whose feature extraction capability is enhanced by utilizing several parallel modules between the input and output of the network, each focusing on the extraction of different types of coarse features with fined grained details to break the symmetry of produced information. In fact, we leverage long range dependencies, which is one of the main drawback of CNNs. We develop this work by introducing a Dynamic Soft-Margin SoftMax.The conventional SoftMax suffers from reaching to gold labels very soon, which take the model to over-fitting. Because it’s not able to determine adequately discriminant feature vectors for some variant class labels. We reduced the risk of over-fitting by using a dynamic shape of input tensor instead of static in SoftMax layer with specifying a desired Soft- Margin. In fact, it acts as a controller to how hard the model should work to push dissimilar embedding vectors apart. For the proposed Categorical Loss, by the objective of compacting the same class labels and separating different class labels in the normalized log domain.We select penalty for those predictions with high divergence from ground-truth labels.So, we shorten correct feature vectors and enlarge false prediction tensors, it means we assign more weights for those classes with conjunction to each other (namely, “hard labels to learn”). By doing this work, we constrain the model to generate more discriminate feature vectors for variant class labels. Finally, for the proposed optimizer, our focus is on solving weak convergence of Adam optimizer for a non-convex problem. Our noteworthy optimizer is working by an alternative updating gradient procedure with an exponential weighted moving average function for faster convergence and exploiting a weight decay method to help drastically reducing the learning rate near optima to reach the dominant local minimum. We demonstrate the superiority of our proposed work by surpassing the first rank of three widely used Facial Expression Recognition datasets with 93.30% on FER-2013, and 16% improvement compare to the first rank after 10 years, reaching to 90.73% on RAF-DB, and 100% k-fold average accuracy for CK+ dataset, and shown to provide a top performance to that provided by other networks, which require much larger training datasets.

Keywords: computer vision, facial expression recognition, machine learning, algorithms, depp learning, neural networks

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Authors: Hosein Maghsoudi

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Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

Procedia PDF Downloads 391