Search results for: development of parental role

Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

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Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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Authors: Syahrir Andi Mangga

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During 1989–1993, the Geological Research and Development Center (recent Geological Survey Institute) Geological Agency, Ministry of Energy and Mineral Resources Republic of Indonesia was the collaboration with British Geological Survey, the United Kingdom to do technical assistance in order to collect data of geology in Sumatra Island. The overall corporation of technical programs was larger concern in stratigraphy, geochemical and age-dating studies. Availability of new data has been stimulated to reassessment of tectonic evolution of Sumatra Island. The study area located in Southern Sumatra within at latitudes 0°-6° S and 99°40’-106’00 E longitudes. The study tectonic is situated within along South Western margin of Sunda land, The Southeast Asia Continental extension arc of the Eurasian Plate and formed as part of Sunda Arc. The oceanic crust of Indian-Australian plate recently is being oblique subduction along the Sunda Trench off the West coast Sumatra. The Mesozoic-Cenozoic of the volcanic and granitic rocks can be divided into northern and southern plutons, defining a series subparallel, controlled by fault, northwest-southeast trending belts, some of the plutons are deformed and under-formed. They are widely exposed along the south-eastern side of the Barisan mountain. Based on the characteristic of minerals and crystallography, rocks found in this study area were granite, granitic, monzogranite and andesitic-Basaltic Volcanic Rock. It belongs to calc Alkaline was predominantly metalumina, I-Type Granite, Volcanic arc granites, Syncollisonal Granites (Syn_COLG) and tholeiitic basalt. It was formed since 169±5 to 20±1 Ma. The origin of magmas in interpreted to be derived from partial melting of igneous rock. The occurrence of the gratoid and volcanic rocks supposed to be closely related to the subduction of the Australian-Hindia oceanic crust beneath the Eurasia/Sunda land Continental Crust as Volcanic arc or continental margin granitic and shown youngest to the southwest. The subduction process having probably been different in position between one terrane to others led to the occurrence of segmentation subduction system. The positional discontinuities of the subduction are probably caused by the difference in time of emplacement and mechanism of volcanic and granitic rock between segments.

Keywords: tectonic setting, I-type granitic, subduction, Southern Sumatra

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Authors: Umedov Mekhroz, Griaznova Svetlana

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In connection with the growth of oncological diseases, the design of centers for diagnostics and the production of radiopharmaceuticals is the most relevant area of healthcare facilities. The design of new nuclear medicine centers should be carried out from the standpoint of solving the following tasks: the availability of medical care, functionality, environmental friendliness, sustainable development, improving the safety of drugs, the use of which requires special care, reducing the rate of environmental pollution, ensuring comfortable conditions for the internal microclimate, adaptability. The purpose of this article is to substantiate architectural and planning solutions, formulate recommendations and principles for the design of nuclear medicine centers and determine the connections between the production and medical functions of a building. The advantages of combining the production of radiopharmaceuticals and the department of medical care: less radiation activity is accumulated, the cost of the final product is lower, and there is no need to hire a transport company with a special license for transportation. A medical imaging department is a structural unit of a medical institution in which diagnostic procedures are carried out in order to gain an idea of the internal structure of various organs of the body for clinical analysis. Depending on the needs of a particular institution, the department may include various rooms that provide medical imaging using radiography, ultrasound diagnostics, and the phenomenon of nuclear magnetic resonance. The production of radiopharmaceuticals is an object intended for the production of a pharmaceutical substance containing a radionuclide and intended for introduction into the human body or laboratory animal for the purpose of diagnosis, evaluation of the effectiveness of treatment, or for biomedical research. The research methodology includes the following subjects: study and generalization of international experience in scientific research, literature, standards, teaching aids, and design materials on the topic of research; An integrated approach to the study of existing international experience of PET / CT scan centers and the production of radiopharmaceuticals; Elaboration of graphical analysis and diagrams based on the system analysis of the processed information; Identification of methods and principles of functional zoning of nuclear medicine centers. The result of the research is the identification of the design principles of nuclear medicine centers with the functions of the production of radiopharmaceuticals and the department of medical imaging. This research will be applied to the design and construction of healthcare facilities in the field of nuclear medicine.

Keywords: architectural planning solutions, functional zoning, nuclear medicine, PET/CT scan, production of radiopharmaceuticals, radiotherapy

Procedia PDF Downloads 89

Authors: Leticia Lengler, Jefferson Oliveira, Vania Estivalete, Jordana Marques Kneipp, Lucia Regina Da Rosa Gama Madruga

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The way social entrepreneurs act and can positively impact on our society engages the interest of academics, companies and governments, who seek solutions to solve or alleviate issues related to the abuse of natural resources, as well as the increase of poverty (social aspects). Studies on social entrepreneurship have been characterized by diverse ramifications and their transdisciplinary character, permeating various disciplines and approaches. Different bibliometric studies were conducted within the theme of social entrepreneurship. In this context, because it is a topic in development and multifaceted, the aim of this article is to present the main interfaces of the studies on the Social Entrepreneur figure in relation to the social concern of sustainability, highlighting the relevant researches and their trends, as well as their relationship with the organizations. Aiming to achieve this purpose, the specific goals are: to identify the most cited authors and articles, to verify the authors and journals with the greatest number of publications and their approaches and to point out their affiliations, countries, and languages of publications. It is still a secondary objective to identify the emerging trends in relation to the social entrepreneur and his social concern stemming from the discussions on sustainability. This way, we analyzed articles from two international databases (Scopus and Web of Science), from 2004 to 2016. The main results were the increase in the number of publications, with most of them in English language, coming mainly from the United States institutions (such as Indiana University and Harvard University) and the United Kingdom (whose main institutions are University of London and Robert Gordon University). Although publications in Spanish and Portuguese are the least expressive in quantity, some tendencies point to publications that discuss the social entrepreneur in terms of gender (that relates to female entrepreneurship) and social class (that relates to the need of building communities that contemplate the Social entrepreneur at the base of the pyramid). It should be noted that the trends of the themes emerged from the analysis of the publication titles only in Portuguese, since this is the native language of the authors who carry out their studies mainly in Brazil. When considering articles in Portuguese (57 indicated by WOS and 9 by Scopus), a previous analysis of the titles was carried out to identify how researchers were approaching the theme social entrepreneur in a joint way to the social dimension of sustainability. However, the analysis of the titles themselves brought a limitation to our study, since it was felt a need to carry out a qualitative study, in which it could be possible to consider the abstracts of the available articles.

Keywords: base of pyramid, social dimension, social entrepreneur, sustainability

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Authors: Loren Clarke, Katie Reed

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The integration of artificial intelligence (AI) in high school education assessment offers transformative potential, providing more personalized, timely, and accurate evaluations of student performance. However, the successful adoption of AI-driven assessment systems requires robust change management strategies to navigate the complexities and resistance that often accompany such technological shifts. This presentation explores effective methods for implementing AI in high school assessment, emphasizing the need for strategic planning and stakeholder engagement. Focusing on a case study of a Victorian high school, it will examine the practical steps taken to integrate AI into teaching and learning. This school has developed innovative processes to support academic integrity and foster authentic cogeneration with AI, ensuring that the technology is used ethically and effectively. By creating comprehensive professional development programs for teachers and maintaining transparent communication with students and parents, the school has successfully aligned AI technologies with their existing curricula and assessment frameworks. The session will highlight how AI has enhanced both formative and summative assessments, providing real-time feedback that supports differentiated instruction and fosters a more personalized learning experience. Participants will learn about best practices for managing the integration of AI in high school settings while maintaining a focus on equity and student-centered learning. This presentation aims to equip high school educators with the insights and tools needed to effectively manage the integration of AI in assessment, ultimately improving educational outcomes and preparing students for future success. Methodologies: The research is a case study of a Victorian high school to examine AI integration in assessments, focusing on practical implementation steps, ethical practices, and change management strategies to enhance personalized learning and assessment. Outcomes: This research explores AI integration in high school assessments, focusing on personalized evaluations, ethical use, and change management. A Victorian school case study highlights best practices to enhance assessments and improve student outcomes. Main Contributions: This research contributes by outlining effective AI integration in assessments, showcasing a Victorian school's implementation, and providing best practices for ethical use, change management, and enhancing personalized learning outcomes.

Keywords: artificial intelligence, assessment, curriculum design, teaching and learning, ai in education

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Authors: Suhair Mereish

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This research is aimed at examining the climate for innovation in organisations with the aim of validating the psychometric properties of the Team Climate Inventory (TCI -14) for Jordan’s collectivist society. The innovativeness of teams may be improved or obstructed by the climate within the team. Further, personal factors are considered an important element that influences the climate for innovation. Accordingly, measuring the employees' personality traits using the Big Five Inventory (BFI-44) could provide insights that aid in understanding how to improve innovation. Thus, studying the climate for innovation and its associations with personality traits is valuable, considering the insights it could offer on employee performance, job satisfaction, and well-being. Essentially, the Team Climate Inventory instrument has never been tested in Jordan’s collectivist society. Accordingly, in order to address the existing gap in the literature as a whole and, more specifically, in Jordan, it is essential to investigate its factorial structure and reliability in this particular context. It is also important to explore whether the factorial structure of the Team Climate Inventory in Jordan’s collectivist society demonstrates a similar or different structure to what has been found in individualistic ones. Lastly, examining if there are associations between the Team Climate Inventory and personality traits of Jordanian employees is pivotal. The quantitative study was carried out among Jordanian employees employed in two of the top 20 companies in Jordan, a shipping and logistics company (N=473) and a telecommunications company (N=219). To generalise the findings, this was followed by collecting data from the general population of this country (N=399). The participants completed the Team Climate Inventory. Confirmatory factor analyses and reliability tests were conducted to confirm the factorial structure, validity, and reliability of the inventory. Findings presented that the four-factor structure of the Team Climate Inventory in Jordan revealed a similar structure to the ones in Western culture. The four-factor structure has been confirmed with good fit indices and reliability values. Moreover, for climate for innovation, regression analysis identified agreeableness (positive) and neuroticism (negative) from the Big Five Inventory as significant predictors. This study will contribute to knowledge in several ways. First, by examining the reliability and factorial structure in a Jordanian collectivist context rather than a Western individualistic one. Second, by comparing the Team Climate Inventory structure in Jordan with findings for the Team Climate Inventory from Western individualistic societies. Third, by studying its relationships with personality traits in that country. Furthermore, findings from this study will assist practitioners in the field of organisational psychology and development to improve the climate for innovation for employees working in organisations in Jordan. It is also expected that the results of this research will provide recommendations to professionals in the business psychology sector regarding the characteristics of employees who hold positive and negative perceptions of the workplace climate.

Keywords: big five inventory, climate for innovation, collectivism, individualism, Jordan, team climate inventory

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Authors: Tasleem Zafar, Jiwan Sidhu

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Introduction: Chickpea flour is known to offer many benefits to diabetic persons, especially in maintaining their blood sugar levels in the acceptable range. Under this project we have studied the chemical composition and antioxidant capacity of white flour (WF), whole wheat flour (WWF) and chickpea flour (BF), in addition to the effect of replacement of WF and WWF with BF on the rheological characteristics of these flour blends, with the ultimate objective of producing acceptable quality flat as well as pan-bread for the diabetic consumers. Methods: WF and WWF were replaced with BF ranging from 0 to 40%, to investigate its effect on the rheological properties and functionality of blended flour dough using farinograph, viscoamylograph, mixograph and falling number apparatus as per the AACC standard methods. Texture Profile Analysis (TPA) was carried on the WF, WWF, and their blends with BF using Stable Micro System Texture Analyzer. Effect of certain additives, such as freeze-dried amla fruit powder (Phyllanthus emblica L.), guar gum, and xanthan gum on the dough rheological properties were also studied. Results: Freeze-dried amla fruit powder was found to be very rich in ascorbic acid and other phenolics having higher antioxidant activity. A decreased farinograph water absorption, increased dough development time, higher mixing tolerance index (i.e., weakening of dough), decreased resistance to extension, lower ratio numbers were obtained when the replacement with BF was increased from 0 to 40%. The BF gave lower peak viscosity, lower paste breakdown, and lower setback values when compared with WF. The falling number values were significantly lower in WWF (meaning higher α-amylase activity) than both the WF and BF. Texture Profile Analysis (TPA) carried on the WF, WWF, and their blends with BF showed significant variations in hardness and compressibility values, dough becoming less hard and less compressible when the replacement of WF and WWF with BF was increased from 0 to 40%. Conclusions: To overcome the deleterious effects of adding BF to WF and WWF on the rheological properties will be an interesting challenge when good quality pan bread and Arabic flatbread have to be commercially produced in a bakery. Use of freeze-dried amla fruit powder, guar gum, and xanthan gum did show some promise to improve the mixing characteristics of WF, WWF, and their blends with BF, and these additives are expected to be useful in producing an acceptable quality flat as well as pan-bread on a commercial scale.

Keywords: wheat flour, chickpea flour, amla fruit, rheology

Procedia PDF Downloads 159

Authors: Pichaya Poonlarp, Danai Boonyakiat, C. Chuamuangphan, M. Chanta

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Current consumers’ behavior trends have changed towards more health awareness, the well-being of society and interest of nature and environment. The Royal Project Foundation is, therefore, well aware of organic agriculture. The project only focused on using natural products and utilizing its highland biological merits to increase resistance to diseases and insects for the produce grown. The project also brought in basic knowledge from a variety of available research information, including, but not limited to, improvement of soil fertility and a control of plant insects with biological methods in order to lay a foundation in developing and promoting farmers to grow quality produce with a high health safety. This will finally lead to sustainability for future highland agriculture and a decrease of chemical use on the highland area which is a source of natural watershed. However, there are still shortcomings of the postharvest management in term of quality and losses, such as bruising, rottenness, wilting and yellowish leaves. These losses negatively affect the maintenance and a shelf life of organic vegetables. Therefore, it is important that a research study of the appropriate and effective postharvest management is conducted for an individual organic vegetable to minimize product loss and find root causes of postharvest losses which would contribute to future postharvest management best practices. This can be achieved through surveys and data collection from postharvest processes in order to conduct analysis for causes of postharvest losses of organic pak-choi, baby pak-choi, and choy sum. Consequently, postharvest losses reduction strategies of organic vegetables can be achieved. In this study, postharvest losses of organic pak choi, baby pak-choi, and choy sum were determined at each stage of the supply chain starting from the field after harvesting, at the Development Center packinghouse, at Chiang Mai packinghouse, at Bangkok packing house and at the Royal Project retail shop in Chiang Mai. The results showed that postharvest losses of organic pak-choi, baby pak-choi, and choy sum were 86.05, 89.05 and 59.03 percent, respectively. The main factors contributing to losses of organic vegetables were due to mechanical damage and underutilized parts and/or short of minimum quality standard. Good practices had been developed after causes of losses were identified. Appropriate postharvest handling and management, for example, temperature control, hygienic cleaning, and reducing the duration of the supply chain, postharvest losses of all organic vegetables should be able to remarkably reduced postharvest losses in the supply chain.

Keywords: postharvest losses, organic vegetables, handling improvement, shelf life, supply chain

Procedia PDF Downloads 475

Authors: Binay Pattanayak

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Multilingual state, Jharkhand is home to more than 19 tribal and regional languages. These are used by more than 33 communities in the state. The state has declared 12 of these languages as official languages of the state. However, schools in the state do not recognize any of these community languages even in early grades! Children, who speak in their mother tongues at home, local market and playground, find it very difficult to understand their teacher and textbooks in school. They fail to acquire basic literacy and numeracy skills in early grades. Out of frustration due to lack of comprehension, the majority of children leave school. Jharkhand sees the highest dropout in early grades in India. To address this, the state under the guidance of the author designed a mother tongue based pre-school education programme named Bhasha Puliya and bilingual picture dictionaries in 9 tribal and regional mother tongues of children. This contributed significantly to children’s school readiness in the school. Followed by this, the state designed a mother-tongue based multilingual education programme (MTB-MLE) for multilingual context. The author guided textbook development in 5 tribal (Santhali, Mundari, Ho, Kurukh and Kharia) and two regional (Odia and Bangla) languages. Teachers and community members were trained for MTB-MLE in around 1,000 schools of the concerned language pockets. Community resource groups were constituted along with their academic calendars in each school to promote story-telling, singing, painting, dancing, riddles, etc. with community support. This, on the one hand, created rich learning environments for children. On the other hand, the communities have discovered a great potential in the process of developing a wide variety of learning materials for children in own mother-tongue using their local stories, songs, riddles, paintings, idioms, skits, etc. as a process of their literary, cultural and technical enrichment. The majority of children are acquiring strong early grade reading skills (basic literacy and numeracy) in grades I-II thereby getting well prepared for higher studies. In a phased manner they are learning Hindi and English after 4-5 years of MTB-MLE using the foundational language learning skills. Community members have started designing new books, audio-visual learning materials in their mother-tongues seeing a great potential for their cultural and technological rejuvenation.

Keywords: community resource groups, MTB-MLE, multilingual, socio-linguistic survey, learning

Procedia PDF Downloads 197

Authors: Ira V. Stancheva, Ely G. Zayova, Maria P. Geneva, Marieta G. Hristozkova, Lyudmila I. Dimitrova, Maria I. Petrova

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The study describes a highly efficient and low-cost protocol for rapid and mass in vitro propagation of medicinal and aromatic plant species (Hyssopus officinalis L., Lamiaceae). Hyssop is an important aromatic herb used for its medicinal values because of its antioxidant, anti-inflammatory and antimicrobial properties. The protocol for large-scale multiplication of this aromatic plant was developed using young stem tips explants. The explants were sterilized with 0.04% mercuric chloride (HgCl₂) solution for 20 minutes and washing three times with sterile distilled water in 15 minutes. The cultural media was full and half strength Murashige and Skoog medium containing indole-3-butyric acid. Full and ½ Murashige and Skoog media without auxin were used as controls. For each variant 20 glass tubes with two plants were used. In each tube two tip and nodal explants were inoculated. Maximum shoot and root number were obtained on ½ Murashige and Skoog medium supplemented with 0.1 mg L-1 indole-3-butyric acid at the same time after four weeks of culture. The number of shoots per explant and shoot height were considered. The data on rooting percentage, the number of roots per plant and root length were collected after the same cultural period. The highest percentage of survival 85% for this medicinal plant was recorded in mixture of soil, sand and perlite (2:1:1 v/v/v). This mixture was most suitable for acclimatization of all propagated plants. Ex vitro acclimatization was carried out at 24±1 °C and 70% relative humidity under 16 h illuminations (50 μmol m⁻²s⁻¹). After adaptation period, the all plants were transferred to the field. The plants flowered within three months after transplantation. Phenotypic variations in the acclimatized plants were not observed. An average of 90% of the acclimatized plants survived after transferring into the field. All the in vitro propagated plants displayed normal development under the field conditions. Developed in vitro techniques could provide a promising alternative tool for large-scale propagation that increases the number of homologous plants for field cultivation. Acknowledgments: This study was conducted with financial support from National Science Fund at the Bulgarian Ministry of Education and Science, Project DN06/7 17.12.16.

Keywords: Hyssopus officinalis L., in vitro culture, micro propagation, acclimatization

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Authors: Golnush Masghati-Amoli, Paul Chin

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Over the past recent years, with the rapid increases in data availability and computing power, Machine Learning (ML) techniques have been called on in a range of different industries for their strong predictive capability. However, the use of Machine Learning in commercial banking has been limited due to a special challenge imposed by numerous regulations that require lenders to be able to explain their analytic models, not only to regulators but often to consumers. In other words, although Machine Leaning techniques enable better prediction with a higher level of accuracy, in comparison with other industries, they are adopted less frequently in commercial banking especially for scoring purposes. This is due to the fact that Machine Learning techniques are often considered as a black box and fail to provide information on why a certain risk score is given to a customer. In order to bridge this gap between the explain-ability and performance of Machine Learning techniques, a Hybrid Model is developed at Dun and Bradstreet that is focused on blending Machine Learning algorithms with traditional approaches such as scorecards. The Hybrid Model maximizes efficiency of traditional scorecards by merging its practical benefits, such as explain-ability and the ability to input domain knowledge, with the deep insights of Machine Learning techniques which can uncover patterns scorecard approaches cannot. First, through development of Machine Learning models, engineered features and latent variables and feature interactions that demonstrate high information value in the prediction of customer risk are identified. Then, these features are employed to introduce observed non-linear relationships between the explanatory and dependent variables into traditional scorecards. Moreover, instead of directly computing the Weight of Evidence (WoE) from good and bad data points, the Hybrid Model tries to match the score distribution generated by a Machine Learning algorithm, which ends up providing an estimate of the WoE for each bin. This capability helps to build powerful scorecards with sparse cases that cannot be achieved with traditional approaches. The proposed Hybrid Model is tested on different portfolios where a significant gap is observed between the performance of traditional scorecards and Machine Learning models. The result of analysis shows that Hybrid Model can improve the performance of traditional scorecards by introducing non-linear relationships between explanatory and target variables from Machine Learning models into traditional scorecards. Also, it is observed that in some scenarios the Hybrid Model can be almost as predictive as the Machine Learning techniques while being as transparent as traditional scorecards. Therefore, it is concluded that, with the use of Hybrid Model, Machine Learning algorithms can be used in the commercial banking industry without being concerned with difficulties in explaining the models for regulatory purposes.

Keywords: machine learning algorithms, scorecard, commercial banking, consumer risk, feature engineering

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Authors: Raju K. Thadikkaran

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Introduction: The IPR have come to the centre stage of development discourse today for a variety of reasons: It ranges from the arbitrariness in the enforcement, overlapping and mismatch with various international agreements and conventions, divergence in the definition, nature and content and the duration as well as severe adverse consequences to technologically weak developing countries. In turn, the IPR have acquired prominence in the foreign policy making as well as in the relations among nations. Quite naturally, there is ample scope for an examination of the correlation between Technology, IPR and International Relations in the contemporary world. Nature and Scope: A cursory examination of the realm of IPR and its protection shall reveals the acute divergence that exists in the perspectives, on all matters related to the very definition, nature, content, scope and duration. The proponents of stronger protection, mostly technologically advanced countries, insist on a stringent IP Regime whereas technologically weak developing countries seem to advocate for flexibilities. From the perspective of developing countries like India, one of the most crucial concerns is related to the patenting of life forms and the protection of TK and BD. There have been several instances of Bio-piracy and Bio-prospecting of the resources related to BD and TK from the Bio-rich Global South. It is widely argued that many provisions in the TRIPS are capable of offsetting the welcome provisions in the CBD such as the Access and Benefit Sharing and Prior Informed Consent. The point that is being argued out is as to how the mismatch between the provisions in the TRIPS Agreement and the CBD could be addressed in a healthy manner so that the essential minimum legitimate interests of all stakeholders could be secured thereby introducing a new direction to the international relations. The findings of this study reveal that the challenges roused by the TRIPS Regime over-weigh the opportunities. The mismatch in the provisions in this regard has generated various crucial issues such as Bio-piracy and Bio-prospecting. However, there is ample scope for managing and protecting IP through institutional innovation, legislative, executive and administrative initiative at the global, national and regional levels. The Indian experience is quite reflective of the same and efforts are being made through the new national IPR policy. This paper, employing Historical Analytical Method, has Three Sections. The First Section shall trace the correlation between the Technology, IPR and international relations. The Second Section shall review the issues and potential concerns in the protection and management of IP related to the BD and TK in the developing countries in the wake of the TRIPS and the CBD. The Final Section shall analyze the Indian Experience in this regard and the experience of the bio-rich Kerala in particular.

Keywords: IPR, technology and international relations, bio-diversity, traditional knowledge

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Authors: Caroline Kim

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Scholars have long disputed the relationship between the origins of language and human behavior. Historically, behaviorist psychologist B. F. Skinner argued that language is one instance of the general stimulus-response phenomenon that characterizes the essence of human behavior. Another, more recent approach argues, by contrast, that language is an innate cognitive faculty and does not arise from behavior, which might develop and reinforce linguistic facility but is not its source. Pinker, among others, proposes that linguistic defects arise from damage to the brain, both congenital and acquired in life. Much of his argument is based on case studies in which damage to the Broca’s and Wernicke’s areas of the brain results in loss of the ability to produce coherent grammatical expressions when speaking or writing; though affected speakers often utter quite fluent streams of sentences, the words articulated lack discernible semantic content. Pinker concludes on this basis that language is an innate component of specific, classically language-correlated regions of the human brain. Taking a notorious 1970s case of linguistic maladaptation, this paper queries the dominant materialist paradigm of language-correlated regions. Susan “Genie” Wiley was physically isolated from language interaction in her home and beaten by her father when she attempted to make any sort of sound. Though without any measurable resulting damage to the brain, Wiley was never able to develop the level of linguistic facility normally achieved in adulthood. Having received a negative reinforcement of language acquisition from her father and lacking the usual language acquisition period, in adulthood Wiley was able to develop language only at a quite limited level in later life. From a contemporary behaviorist perspective, this case confirms the possibility of language deficiency without brain pathology. Wiley’s potential language-determining areas in the brain were intact, and she was exposed to language later in her life, but she was unable to achieve the normal level of communication skills, deterring socialization. This phenomenon and others like it in the case limited literature on linguistic maladaptation pose serious clinical, scientific, and indeed philosophical difficulties for both of the major competing theories of language acquisition, innateness, and linguistic stimulus-response. The implications of such cases for future research in language acquisition are explored, with a particular emphasis on the interaction of innate capacity and stimulus-based development in early childhood.

Keywords: behaviorism, innateness hypothesis, language, Susan "Genie" Wiley

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Authors: Kuladip Jana, Bhaswati Banerjee, Parimal C. Sen

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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems along with carcinogenesis in skin, prostate, ovary, lung and mammary glands. Our study was focused on elucidating the molecular mechanism of B(a)P induced male reproductive toxicity and its prevention with phytochemical like resveratrol. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of Wistar rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased Reactive Oxygen Species (ROS), altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38 mitogen activated protein kinase (p38MAPK), cytosolic translocation of cytochrome-c, upregulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of poly ADP ribose polymerase (PARP) and down regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like steroidogenic acute regulatory protein (StAR), cytochrome P450 IIA1 (CYPIIA1), 3β hydroxy steroid dehydrogenase (3β HSD), 17β hydroxy steroid dehydrogenase (17β HSD) showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis. Next we investigated the role of resveratrol on B(a)P induced male reproductive toxicity. Our study highlighted that resveratrol co-treatment with B(a)P maintained testicular redox potential, increased serum testosterone level and prevented steroidogenic dysfunction with enhanced expression of major testicular steroidogenic proteins (CYPIIA1, StAR, 3β HSD,17β HSD) relative to treatment with B(a)P only. Resveratrol suppressed B(a)P-induced testicular activation of p38 MAPK, ATF2, iNOS and ROS production; cytosolic translocation of Cytochome c and Caspase 3 activation thereby prevented oxidative stress of testis and inhibited apoptosis. Resveratrol co-treatment also decreased B(a)P-induced AhR protein level, its nuclear translocation and subsequent CYP1A1 promoter activation, thereby decreased protein and mRNA levels of testicular cytochrome P4501A1 (CYP1A1) and prevented BPDE-DNA adduct formation. Our findings cumulatively suggest that resveratrol prevents activation of B(a)P by modulating the transcriptional regulation of CYP1A1 and acting as an antioxidant thus prevents B(a)P-induced oxidative stress and testicular apoptosis.

Keywords: benzo(a)pyrene, resveratrol, testis, apoptosis, cytochrome P450 1A1 (CYP1A1), aryl hydrocarbon receptor (AhR), p38 MAPK/ATF2/iNOS

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Authors: Raj Chavan

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At present, the United States is home to more than 14,000 Water Resource Recovery Facilities (WRRFs), of which approximately 35% have implemented nutrient limits of some kind. These WRRFs contribute 10 to 15% of the total nutrient burden to surface rivers in the United States and account for approximately 1% of total power demand and 2% of total greenhouse gas emissions (GHG). There are several factors that have influenced the development of densification technologies in the direction of more compact and energy-efficient nutrient removal processes. Prior to surface water discharge, existing facilities that necessitate capacity expansion or biomass densification for greater treatability within the same footprint are being subjected to stricter nutrient removal requirements. Densification of activated sludge as a method for nutrient removal and process intensification at WRRFs has garnered considerable attention in recent times. The biological processes take place within the aerobic sediment granules, which form the basis of the technology. The possibility of generating granular sludge through continuous (or conventional) activated sludge processes (CAS) or densification of biomass through the transfer of activated sludge flocs to a denser biomass aggregate as an exceptionally efficient intensification technique has generated considerable interest. This presentation aims to furnish attendees with a foundational comprehension of densification through the illustration of practical concerns and insights. The subsequent subjects will be deliberated upon. What are some potential techniques for producing and preserving densified granules? What processes are responsible for the densification of biological flocs? How do physical selectors contribute to the process of biological flocs becoming denser? What viable strategies exist for the management of densified biological flocs, and which design parameters of physical selection influence the retention of densified biological flocs? determining operational solutions for floc and granule customization in order to meet capacity and performance objectives? The answers to these pivotal questions will be derived from existing full-scale treatment facilities, bench-scale and pilot-scale investigations, and existing literature data. By the conclusion of the presentation, the audience will possess a fundamental comprehension of the densification concept and its significance in attaining effective effluent treatment. Additionally, case studies pertaining to the design and operation of densification procedures will be incorporated into the presentation.

Keywords: densification, intensification, nutrient removal, granular sludge

Procedia PDF Downloads 74

Authors: Lilian Mbinya Muasa

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Climate change is inevitable and a global challenge with long term implications to the sustainable development of many countries today. The negative impacts of climate change are creating far reaching social, economic and environmental problems threatening lives and livelihoods of millions of people in the world. Developing countries especially sub-Saharan countries are more vulnerable to climate change due to their weak ecosystem, low adaptive capacity and high dependency on rain fed agriculture. Countries in Sub-Saharan Africa are more vulnerable to climate change impacts due to their weak adaptive capacity and over-reliance on rain fed agriculture. In Kenya, 78% of the rural communities are poor farmers who heavily rely on rain fed agriculture thus are directly affected by climate change impacts.Currently, many parts of Kenya are experiencing successive droughts which are contributing to persistently unstable and declining agricultural productivity especially in semi arid eastern Kenya. As a result, thousands of rural communities repeatedly experience food insecurity which plunge them to an ever over-reliance on relief food from the government and Non-Governmental Organization In addition, they have adopted poverty coping strategies to diversify their income, for instance, deforestation to burn charcoal, sand harvesting and overgrazing which instead contribute to environmental degradation.This research was conducted in Makueni County which is classified as one of the most food insecure counties in Kenya and experiencing acute environmental degradation. The study aimed at analyzing the adaptive capacity to climate change across farming households of Makueni County in Kenya by, 1) analyzing adaptive capacity to climate change and agricultural productivity across farming households, 2) identifying factors that contribute to differences in adaptive capacity across farming households, and 3) understanding the relationship between climate change, agricultural productivity and adaptive capacity. Analytical Hierarchy Process (AHP) was applied to determine adaptive capacity and Total Factor Productivity (TFP) to determine Agricultural productivity per household. Increase in frequency of prolonged droughts and scanty rainfall. Preliminary findings indicate a magnanimous decline in agricultural production in the last 10 years in Makueni County. In addition, there is an over reliance of households on indigenous knowledge which is no longer reliable because of the unpredictability nature of climate change impacts. These findings on adaptive capacity across farming households provide the first step of developing and implementing action-oriented climate change policies in Makueni County and Kenya.

Keywords: adaptive capacity, agricultural productivity, climate change, vulnerability

Procedia PDF Downloads 326

Authors: Bill D. Geis

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Even with significantly increased spending, suicide rates continue to climb—with alarming increases among traditionally low-risk groups. This has caused clinicians and researchers to call for a complete rethinking of all assumptions about suicide prevention, assessment, and intervention. A form of therapy--Internal Family Systems Therapy--affords tremendous promise in sustained diminishment of lethal suicide risk. Though a form of therapy that is most familiar to trauma therapists, Internal Family Systems Therapy, involving direct work with suicidal parts, is a promising therapy for meaningful and sustained reduction in suicide deaths. Developed by Richard Schwartz, Internal Family Systems Therapy proposes that we are all influenced greatly by internal parts, frozen by development adversities, and these often-contradictory parts contribute invisibly to mood, distress, and behavior. In making research videos of patients from our database and discussing their suicide attempts, it is clear that many persons who attempt suicide are in altered states at the time of their attempt and influenced by factors other than conscious intent. Suicide intervention using this therapy involves direct work with suicidal parts and other interacting parts that generate distress and despair. Internal Family Systems theory posits that deep experiences of pain, fear, aloneness, and distress are defended by a range of different parts that attempt to contain these experiences of pain through various internal activities that unwittingly push forward inhibition, fear, self-doubt, hopelessness, desires to cut and engage in destructive behavior, addictive behavior, and even suicidal actions. These suicidal parts are often created (and “frozen”) at young ages, and these very young parts do not understand the consequences of this influence. Experience suggests that suicidal parts can create impulsive risk behind the scenes when pain is high and emotional support reduced—with significant crisis potential. This understanding of latent suicide risk is consistent with many of our video accounts of serious suicidal acts—compiled in a database of 1104 subjects. Since 2016, consent has been obtained and records kept of 23 highly suicidal patients, with initial Intention-to-Die ratings (0= no intent, 10 = conviction to die) between 5 and 10. In 67% of these cases using IFST parts-work intervention, these highly suicidal patients’ risk was reduced to 0-1, and 83% of cases were reduced to 4 or lower. There were no suicide deaths. Case illustrations will be offered.

Keywords: suicide, internal family systems therapy, crisis management, suicide prevention

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Authors: Nozar Kishi, Babak Kamrani, Filmon Habte

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Natural hazards such as earthquakes and tropical storms, are very frequent and highly destructive in Japan. Japan experiences, every year on average, more than 10 tropical cyclones that come within damaging reach, and earthquakes of moment magnitude 6 or greater. We have developed stochastic catastrophe models to address the risk associated with the entire suite of damaging events in Japan, for use by insurance, reinsurance, NGOs and governmental institutions. KCC’s (Karen Clark and Company) catastrophe models are procedures constituted of four modular segments: 1) stochastic events sets that would represent the statistics of the past events, hazard attenuation functions that could model the local intensity, vulnerability functions that would address the repair need for local buildings exposed to the hazard, and financial module addressing policy conditions that could estimates the losses incurring as result of. The events module is comprised of events (faults or tracks) with different intensities with corresponding probabilities. They are based on the same statistics as observed through the historical catalog. The hazard module delivers the hazard intensity (ground motion or wind speed) at location of each building. The vulnerability module provides library of damage functions that would relate the hazard intensity to repair need as percentage of the replacement value. The financial module reports the expected loss, given the payoff policies and regulations. We have divided Japan into regions with similar typhoon climatology, and earthquake micro-zones, within each the characteristics of events are similar enough for stochastic modeling. For each region, then, a set of stochastic events is developed that results in events with intensities corresponding to annual occurrence probabilities that are of interest to financial communities; such as 0.01, 0.004, etc. The intensities, corresponding to these probabilities (called CE, Characteristics Events) are selected through a superstratified sampling approach that is based on the primary uncertainty. Region specific hazard intensity attenuation functions followed by vulnerability models leads to estimation of repair costs. Extensive economic exposure model addresses all local construction and occupancy types, such as post-linter Shinand Okabe wood, as well as concrete confined in steel, SRC (Steel-Reinforced Concrete), high-rise.

Keywords: typhoon, earthquake, Japan, catastrophe modelling, stochastic modeling, stratified sampling, loss model, ERM

Procedia PDF Downloads 269

Authors: Nurten Akgun, Dilum Dissanayake, Neil Thorpe, Margaret C. Bell

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Cycling has gained a great attention with comparable speeds, low cost, health benefits and reducing the impact on the environment. The main challenge associated with cycling is the provision of safety for the people choosing to cycle as their main means of transport. From the road safety point of view, cyclists are considered as vulnerable road users because they are at higher risk of serious casualty in the urban network but more specifically at roundabouts. This research addresses the development of an enhanced mathematical model by including a broad spectrum of casualty related variables. These variables were geometric design measures (approach number of lanes and entry path radius), speed limit, meteorological condition variables (light, weather, road surface) and socio-demographic characteristics (age and gender), as well as contributory factors. Contributory factors included driver’s behavior related variables such as failed to look properly, sudden braking, a vehicle passing too close to a cyclist, junction overshot, failed to judge other person’s path, restart moving off at the junction, poor turn or manoeuvre and disobeyed give-way. Tyne and Wear in the UK were selected as a case study area. The cyclist casualty data was obtained from UK STATS19 National dataset. The reference categories for the regression model were set to slight and serious cyclist casualties. Therefore, binary logistic regression was applied. Binary logistic regression analysis showed that approach number of lanes was statistically significant at the 95% level of confidence. A higher number of approach lanes increased the probability of severity of cyclist casualty occurrence. In addition, sudden braking statistically significantly increased the cyclist casualty severity at the 95% level of confidence. The result concluded that cyclist casualty severity was highly related to approach a number of lanes and sudden braking. Further research should be carried out an in-depth analysis to explore connectivity of sudden braking and approach number of lanes in order to investigate the driver’s behavior at approach locations. The output of this research will inform investment in measure to improve the safety of cyclists at roundabouts.

Keywords: binary logistic regression, casualty severity, cyclist safety, roundabout

Procedia PDF Downloads 177

Authors: Vanda Ferreira Ribeiro, Daiane Tomacheski, Douglas Naue Simões, Michele Pitto, Ruth Marlene Campomanes Santana

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Indoor environments, such as car cabins and public transportation vehicles are places where users are subject to air quality. Microorganisms (bacteria, fungi, yeasts) enter these environments through windows, ventilation systems and may use the organic particles present as a growth substrate. In addition, atmospheric pollutants can act as potential carbon and nitrogen sources for some microorganisms. Compounds base SEBS copolymers, poly(styrene-b-(ethylene-co-butylene)-b-styrene, are a class of thermoplastic elastomers (TPEs), fully recyclable and largely used in automotive parts. Metals, such as cooper and silver, have biocidal activities and the production of the SEBS compounds by melting blending with these agents can be a good option for producing compounds for use in plastic parts of ventilation systems and automotive air-conditioning, in order to minimize the problems caused by growth of pathogenic microorganisms. In this sense, the aim of this work was to evaluate the effect of copper microparticles as antimicrobial agent in compositions based on SEBS/PP/oil/calcite. Copper microparticles were used in weight proportion of 0%, 1%, 2% and 4%. The compounds were prepared using a co-rotating double screw extruder (L/D ratio of 40/1 and 16 mm screw diameter). The processing parameters were 300 rpm of screw rotation rate, with a temperature profile between 150 to 190°C. SEBS based TPE compounds were injection molded. The compounds emission were characterized by gravimetric fogging test. Compounds were characterized by physical (density and staining by contact), mechanical (hardness and tension properties) and rheological properties (melt volume rate – MVR). Antibacterial properties were evaluated against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) strains. To avaluate the abilities toward the fungi have been chosen Aspergillus niger (A. niger), Candida albicans (C. albicans), Cladosporium cladosporioides (C. cladosporioides) and Penicillium chrysogenum (P. chrysogenum). The results of biological tests showed a reduction on bacteria in up to 88% in E.coli and up to 93% in S. aureus. The tests with fungi showed no conclusive results because the sample without copper also demonstrated inhibition of the development of these microorganisms. The copper addition did not cause significant variations in mechanical properties, in the MVR and the emission behavior of the compounds. The density increases with the increment of copper in compounds.

Keywords: air conditioner, antimicrobial, cooper, SEBS

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Authors: Ana Teixeira, Joao Orvalho

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This paper describes experiments using Scratch games, to check the feasibility of employing cerebral palsy users gestures as an alternative of interaction with a computer carried out by students of Master Human Computer Interaction (HCI) of IPC Coimbra. The main focus of this work is to study the usability of a Web Camera as a motion tracking device to achieve a virtual human-computer interaction used by individuals with CP. An approach for Human-computer Interaction (HCI) is present, where individuals with cerebral palsy react and interact with a scratch game through the use of a webcam as an external interaction device. Motion tracking interaction is an emerging technology that is becoming more useful, effective and affordable. However, it raises new questions from the HCI viewpoint, for example, which environments are most suitable for interaction by users with disabilities. In our case, we put emphasis on the accessibility and usability aspects of such interaction devices to meet the special needs of people with disabilities, and specifically people with CP. Despite the fact that our work has just started, preliminary results show that, in general, computer vision interaction systems are very useful; in some cases, these systems are the only way by which some people can interact with a computer. The purpose of the experiments was to verify two hypothesis: 1) people with cerebral palsy can interact with a computer using their natural gestures, 2) scratch games can be a research tool in experiments with disabled young people. A game in Scratch with three levels is created to be played through the use of a webcam. This device permits the detection of certain key points of the user’s body, which allows to assume the head, arms and specially the hands as the most important aspects of recognition. Tests with 5 individuals of different age and gender were made throughout 3 days through periods of 30 minutes with each participant. For a more extensive and reliable statistical analysis, the number of both participants and repetitions in further investigations should be increased. However, already at this stage of research, it is possible to draw some conclusions. First, and the most important, is that simple scratch games on the computer can be a research tool that allows investigating the interaction with computer performed by young persons with CP using intentional gestures. Measurements performed with the assistance of games are attractive for young disabled users. The second important conclusion is that they are able to play scratch games using their gestures. Therefore, the proposed interaction method is promising for them as a human-computer interface. In the future, we plan to include the development of multimodal interfaces that combine various computer vision devices with other input devices improvements in the existing systems to accommodate more the special needs of individuals, in addition, to perform experiments on a larger number of participants.

Keywords: motion tracking, cerebral palsy, rehabilitation, HCI

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Authors: Dali Nikolaishvili, Nino Khareba, Mariam Tsitsagi

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Tbilisi has been a capital of Georgia since the 5ᵗʰ century. City area was covered by forest in historical past. Nowadays the situation has been changing dramatically. Dozens of problems are caused by damages/destruction of green cover and solution, at one glance, seems to be uncomplicated (planting trees and creating green quarters), but on the other hand, according to the increasing tendency, the built up of areas still remains unsolved. Finding out the ways to overcome such obstacles is important even for protecting the health of society. Making of Retrospective cartography of the forest area of Tbilisi with use of GIS technology and remote sensing was the main aim of the research. Research about the dynamic of forest-cover in Tbilisi and its surroundings included the following steps: assessment of the dynamic of forest in Tbilisi and its surroundings. The survey was mainly based on the retrospective mapping method. Using of GIS technology, studying, comparing and identifying the narrative sources was the next step. And the last one was analyzed of the changes from the 80s to the present days on the basis of decryption of remotely sensed images. After creating a unified cartographic basis, the mapping and plans of different periods have been linked to this geodatabase. Data about green parks, individual old plants existing in the private yards and respondents' Information (according to a questionnaire created in advance) was added to the basic database, the general plan of Tbilisi and Scientific works as well. On the basis of analysis of historic, including cartographic sources, forest-cover maps for different periods of time were made. In addition, was made the catalog of individual green parks (location, area, typical composition, name and so on), which was the basis of creating several thematic maps. Areas with a high rate of green area degradation were identified. Several maps depicting the dynamics of forest cover of Tbilisi were created and analyzed. The methods of linking the data of the old cartographic sources to the modern basis were developed too, the result of which may be used in Urban Planning of Tbilisi. Understanding, perceiving and analyzing the real condition of green cover in Tbilisi and its problems, in turn, will help to take appropriate measures for the maintenance of ancient plants, to develop forests and to plan properly parks, squares, and recreational sites. Because the healthy environment is the main condition of human health and implies to the rational development of the city.

Keywords: catalogue of green area, GIS, historical cartography, cartography, remote sensing, Tbilisi

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Authors: Ana M. Lara, Manuela Llano, Felipe Gaitán, Rosa H. Bustos, Ana Maria Perdomo-Arciniegas, Ximena Bonilla

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Umbilical cord blood is used as a source of progenitor and stem cells for the regeneration of the hematopoietic and immune system to treat patients with different hematological or non-hematological diseases. This stem cell source represents an advantage over the use of bone marrow or mobilized peripheral blood because it has a lower incidence rate of graft-versus-host disease, probably due to fewer immunological compatibility restrictions. However, its low cellular dose limits its use in pediatric patients. This work proposes the standardization of a cell expansion technique to compensate for the dose of infused cells through the ex-vivo manipulation of hematopoietic progenitor cells from umbilical cord blood before transplantation. The expansion model is carried out through co-cultures with mesenchymal stem cells (MSC) from bone marrow (BM) and less explored fetal tissues such as Wharton's jelly (WJ) and umbilical cord blood (UCB). Initially, a master cell bank of primary mesenchymal stem cells isolated from different sources was established and characterized following International Society of Cell Therapies (ISCT) indications. Additionally, we assessed the effect of a short 25 Gy cycle of gamma irradiation on cell cycle arrest of mesenchymal cells over the support capacity for the expansion of hematopoietic stem cells from umbilical cord blood was evaluated. The results show that co-cultures with MSC from WJ and UCB allow the cellular dose of HSPC to be maximized between 5 and 16 times having a similar support capacity as BM. In addition, was evaluated the hematopoietic stem progenitor cell's HSPC functionality through the evaluation of migration capacity, their differentiation capacity during culture time by flow cytometry to evaluate the expression of membrane markers associated with lineage-committed progenitors, their clonogenic potential, and the evaluation of secretome profile in the expansion process was evaluated. So far, the treatment with gamma irradiation maintains the hematopoietic support capacity of mesenchymal stem cells from the three sources studied compared to treatments without irradiation, favoring the use of fetal tissues that are generally waste to obtain mesenchymal cell lines for ex-vivo expansion systems. With the results obtained, a standardized protocol that will contribute to the development of ex-vivo expansion with MSC on a larger scale will be achieved, enabling its clinical use and expanding its application in adults.

Keywords: ex-vivo expansion, hematopoietic stem cells, hematopoietic stem cell transplantation, mesenchymal stem cells, umbilical cord blood

Procedia PDF Downloads 115

Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson

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MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.

Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3

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Authors: Rodrigo Fernandes da Silva, Daniela Maira Cardozo, Paulo Cesar Martins Alves, Sophie Françoise Derchain, Fernando Guimarães

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T-reg lymphocytes are important for the control of peripheral tolerance. They control the adaptive immune system and prevent autoimmunity through its suppressive action on CD4+ and CD8+ lymphocytes. The suppressive action also includes B lymphocytes, dendritic cells, monocytes/macrophages and recently, studies have shown that T-reg are also able to inhibit NK cells, therefore they exert their control of the immune response from innate to adaptive response. Most tumors express self-ligands, therefore it is believed that T-reg cells induce tolerance of the immune system, hindering the development of successful immunotherapies. T-reg cells have been linked to the suppression mechanisms of the immune response against tumors, including ovarian cancer. The goal of this study was to disclose the sub-population of the expanded CD3+ lymphocytes reported by previous studies, using the long-term culture model designed by Carlens et al 2001, to generate effector cell suspensions enriched with cytotoxic CD3-CD56+ NK cells, from PBMC of ovarian neoplasia patients. Methods and Results: Blood was collected from 12 patients with ovarian neoplasia after signed consent: 7 benign (Bng) and 5 malignant (Mlg). Mononuclear cells were separated by Ficoll-Paque gradient. Long-term culture was conducted by a 21 day culturing process with SCGM CellGro medium supplemented with anti-CD3 (10ng/ml, first 5 days), IL-2 (1000UI/ml) and FBS (10%). After 21 days of expansion, there was an increase in the population of CD3+ lymphocytes in the benign and malignant group. Within CD3+ population, there was a significant decrease in the population of CD4+ lymphocytes in the benign (median Bgn D-0=73.68%, D-21=21.05%) (p<0.05) and malignant (median Mlg D-0=64.00%, D-21=11.97%) (p < 0.01) group. Inversely, after 21 days of expansion, there was an increase in the population of CD8+ lymphocytes within the CD3+ population in the benign (median Bgn D-0=16.80%, D-21=38.56%) and malignant (median Mlg D-0=27.12%, D-21=72.58%) group. However, this increase was only significant on the malignant group (p<0.01). Within the CD3+CD4+ population, there was a significant increase (p < 0.05) in the population of T-reg lymphocytes in the benign (median Bgn D-0=9.84%, D-21=39.47%) and malignant (median Mlg D-0=3.56%, D-21=16.18%) group. Statistical analysis inter groups was performed by Kruskal-Wallis test and intra groups by Mann Whitney test. Conclusion: The CD4+ and CD8+ sub-population of CD3+ lymphocytes shifts with the culturing process. This might be due to the process of the immune system to produce a cytotoxic response. At the same time, T-reg lymphocytes increased within the CD4+ population, suggesting a modulation of the immune response towards cells of the immune system. The expansion of the T-reg population can hinder an immune response against cancer. Therefore, an immunotherapy using this expansion procedure should aim to halt the expansion of T-reg or its immunosuppresion capability.

Keywords: regulatory T cells, CD8+ T cells, CD4+ T cells, NK cell expansion

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Authors: Abdelmanie Suleimat, Nagham Abu Shaqra, Sawsan Majali, Issam Adawi, Heba Abo Shindi, Anas Al Mohtaseb

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The Government of Jordan recognizes that maternal mortality constitutes a grave public health problem. Over the past two decades, there has been significant progress in improving the quality of maternal health services, resulting in improved maternal and child health outcomes. Despite these efforts, measurement and analysis of maternal mortality remained a challenge, with significant discrepancies from previous national surveys that inhibited accuracy. In response with support from USAID, the Jordan Maternal Mortality Surveillance Response (JMMSR) System was established to collect, analyze, and equip policymakers with data for decision-making guided by interdisciplinary multi-levelled advisory groups aiming to eliminate preventable maternal deaths, A 2016 Public Health Bylaw required the notification of deaths among women of reproductive age. The JMMSR system was launched in 2018 and continues annually, analyzing data received from health facilities, to guide policy to prevent avoidable deaths. To date, there have been four annual national maternal mortality reports (2018-2021). Data is collected, reviewed by advisory groups, and then consolidated in an annual report to inform and guide the Ministry of Health (MOH); JMMSR collects the necessary information to calculate an accurate maternal mortality ratio and assists in identifying leading causes and contributing factors for each maternal death. Based on this data, national response plans are created. A monitoring and evaluation plan was designed to define, track, and improve implementation through indicators. Over the past four years, one of these indicators, ‘percent of facilities notifying respective health directorates of all deaths of women of reproductive age,’ increased annually from 82.16%, 92.95%, and 92.50% to 97.02%, respectively. The Government of Jordan demonstrated commitment to the JMMSR system by designating the MOH to primarily host the system and lead the development and dissemination of policies and procedures to standardize implementation. The data was translated into practical and evidence-based recommendations. The successful impact of results deepened the understanding of maternal mortality in Jordan, which convinced the MOH to amend the Bylaw now mandating electronic reporting of all births and neonatal deaths from health facilities to empower the JMMSR system, by developing a stillbirths and neonatal mortality surveillance and response system.

Keywords: maternal health, maternal mortality, preventable maternal deaths, maternal morbidity

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Authors: Guillermo E. Quintero, Edwin G. Perez, Oriel Sanchez, Christian Espinosa-Bustos, Denis Fuentealba, Margarita E. Aliaga

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Bisulfite ion (HSO3-) has been used as a preservative in food, drinks, and medication. However, it is well-known that HSO3- can cause health problems like asthma and allergic reactions in people. Due to the above, the development of analytical methods for detecting this ion has gained great interest. In line with the above, the current use of colorimetric and/or fluorescent probes as a detection technique has acquired great relevance due to their high sensitivity and accuracy. In this context, 2-quinolinone derivatives have been found to possess promising activity as antiviral agents, sensitizers in solar cells, antifungals, antioxidants, and sensors. In particular, 7-(diethylamino)-2-quinolinone derivatives have attracted attention in recent years since their suitable photophysical properties become promising fluorescent probes. In Addition, there is evidence that photophysical properties and reactivity can be affected by the study medium, such as micellar media. Based on the above background, 7-(diethylamino)-2-quinolinone derivatives based chalcone will be able to be incorporated into a cationic micellar environment (Cetyltrimethylammonium bromide, CTAB). Furthermore, the supramolecular control induced by the micellar environment will increase the reactivity of these derivatives towards nucleophilic analytes such as HSO3- (Michael-type addition reaction), leading to the generation of new colorimetric and/or fluorescent probes. In the present study, two derivatives of 7-(diethylamino)-2-quinolinone based chalcone DQD1-2 were synthesized according to the method reported by the literature. These derivatives were structurally characterized by 1H, 13C NMR, and HRMS-ESI. In addition, UV-VIS and fluorescence studies determined absorption bands near 450 nm, emission bands near 600 nm, fluorescence quantum yields near 0.01, and fluorescence lifetimes of 5 ps. In line with the foregoing, these photophysical properties aforementioned were improved in the presence of a cationic micellar medium using CTAB thanks to the formation of adducts presenting association constants of the order of 2,5x105 M-1, increasing the quantum yields to 0.12 and the fluorescence lifetimes corresponding to two lifetimes near to 120 and 400 ps for DQD1 and DQD2. Besides, thanks to the presence of the micellar medium, the reactivity of these derivatives with nucleophilic analytes, such as HSO3-, was increased. This was achieved through kinetic studies, which demonstrated an increase in the bimolecular rate constants in the presence of a micellar medium. Finally, probe DQD1 was chosen as the best sensor since it was assessed to detect HSO3- with excellent results.

Keywords: bisulfite detection, cationic micelle, colorimetric probes, quinolinone derivatives

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Authors: Gudrun Görlitz, Christian Schölzel, Alexander Vollmar

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Sites of Jewish Life in Berlin 1933-1945. Between Persecution and Self-assertion” was realized in a project funded by the European Regional Development Fund. A smartphone app, and a associated web site enable tourists and other participants of this educational offer to learn in a serious way more about the life of Jews in the German capital during the Nazi era. Texts, photos, video and audio recordings communicate the historical content. Interactive maps (both current and historical) make it possible to use predefined or self combined routes. One of the manifold challenges was to create a broad ranged guide, in which all detailed information are well linked with each other. This enables heterogeneous groups of potential users to find a wide range of specific information, corresponding with their particular wishes and interests. The multitude of potential ways to navigate through the diversified information causes (hopefully) the users to utilize app and web site for a second or third time and with a continued interest. Therefore 90 locations, a lot of them situated in Berlin’s city centre, have been chosen. For all of them text-, picture and/or audio/video material gives extensive information. Suggested combinations of several of these “site stories” are leading to the offer of detailed excursion routes. Events and biographies are also presented. A few of the implemented biographies are especially enriched with source material concerning the aspect of (forced) migration of these persons during the Nazi time. All this was done in a close and fruitful interdisciplinary cooperation of computer scientists and historians. The suggested conference paper aims to show the challenges shaping complex source material for practical use by different user-groups in a proper technical and didactic way. Based on the historical research in archives, museums, libraries and digital resources the quantitative dimension of the project can be sized as follows: The paper focuses on the following historiographical and technical aspects: - Shaping the text material didactically for the use in new media, especially a Smartphone-App running on differing platforms; - Geo-referencing of the sites on historical and current map material; - Overlay of old and new maps to present and find the sites; - Using Augmented Reality technologies to re-visualize destroyed buildings; - Visualization of black-/white-picture-material; - Presentation of historical footage and the resulting problems to need too much storage space; - Financial and juridical aspects in gaining copyrights to present archival material.

Keywords: smartphone app, history, tourists, German

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Authors: Shyam lamsal

Abstract:

Introduction: Karnali Academy of Health Sciences (KAHS) has been established in 2011, by an Act of parliament of Nepal, in Jumla, to provide health services in easy way in backward areas, to produce skilled health professionals & conduct research. The backward areas mentioned in act of KAHS are Humla, Jumla, Kalikot, Dolpa, Mugu districts of Karnali zone, Jajarkot district of Bheri zone & Bajura, Baghang & Achham districts of Seti zone in Nepal occupying around 25 % of the total national geography. Backward area of Nepal is specific to having worst health indicators with life expectancy (47 years), HDI (0.35), Literacy rate (58%), global acute malnutrition (13%), crude birth rate (33.6), crude death rate (9.6), Total fertility rate (4.2), infant mortality rate (61.5 per 1000 live births), under five mortality rate (59 per 1000 live births) and maternal mortality ratio (400 per 1000 live births). History of health facilities in backward region: All the nine districts of this region have a district hospital with very few grass root level health manpower. Government of Nepal regularly deploys one or two medical officers to each district who generally are not regular to their care. Jumla district itself was having one medical officer before the establishment of KAHS. Development activities: Establishment of 100 bedded specialty teaching hospital with 10 medical officers and five specialists, accredited its own nursing school for running diploma nursing programme, started “Karnali health survey” which covers 55 thousand households of backward region, started community care and school health camps, planning phase completed for 300 bedded teaching hospital construction. Future Plan: Expansion of the teaching hospital to 300 beds within 3 years, start health assistant and bachelor midwifery course in 2015 AD, start bachelor in laboratory and bachelor in public health course in 2016 AD and start MBBS course in 2018 AD. Deploy the medical officers and family physicians to all the district hospitals within 3 years. KAHS provides reservation up to 45% students from backward region with the commitment to stay for at least five years of their service period. Conclusion: This institution may be the example for the rest of the world in providing nursing care, education in remote areas as well as the best model for nursing manpower retention in remote areas of developing countries.

Keywords: backward area, nursing school

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Authors: Michio Kurosu

Abstract:

Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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