Search results for: 3rd generation modular

Authors: Keroles Akram Saed Ghatas

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The near future will bring significant changes in modern organizations and management due to the growing role of intangible assets and knowledge workers. The area of copyright, intellectual property, digital (intangible) assets and media redistribution appears to be one of the greatest challenges facing business and society in general and management sciences and organizations in particular. The proposed article examines the views and perceptions of fairness in digital media sharing among Harvard Law School's LL.M.s. Students, based on 50 qualitative interviews and 100 surveys. The researcher took an ethnographic approach to her research and entered the Harvard LL.M. in 2016. at, a Face book group that allows people to connect naturally and attend in-person and private events more easily. After listening to numerous students, the researcher conducted a quantitative survey among 100 respondents to assess respondents' perceptions of fairness in digital file sharing in various contexts (based on media price, its availability, regional licenses, copyright holder status, etc.). to understand better . .). Based on the survey results, the researcher conducted long-term, open-ended and loosely structured ethnographic interviews (50 interviews) to further deepen the understanding of the results. The most important finding of the study is that Harvard lawyers generally support digital piracy in certain contexts, despite having the best possible legal and professional knowledge. Interestingly, they are also more accepting of working for the government than the private sector. The results of this study provide a better understanding of how “fairness” is perceived by the younger generation of lawyers and pave the way for a more rational application of licensing laws.

Keywords: cognitive impairments, communication disorders, death penalty, executive function communication disorders, cognitive disorders, capital murder, executive function death penalty, egyptian law absence, justice, political cases piracy, digital sharing, perception of fairness, legal profession

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Authors: Ian Campbell, Gillian Mitchell, Paul James, Na Li, Ella Thompson

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The genetic cause of the majority of multiple-case breast cancer families remains unresolved. Next generation sequencing has emerged as an efficient strategy for identifying predisposing mutations in individuals with inherited cancer. We are conducting whole exome sequence analysis of germ line DNA from multiple affected relatives from breast cancer families, with the aim of identifying rare protein truncating and non-synonymous variants that are likely to include novel cancer predisposing mutations. Data from more than 200 exomes show that on average each individual carries 30-50 protein truncating mutations and 300-400 rare non-synonymous variants. Heterogeneity among our exome data strongly suggest that numerous moderate penetrance genes remain to be discovered, with each gene individually accounting for only a small fraction of families (~0.5%). This scenario marks validation of candidate breast cancer predisposing genes in large case-control studies as the rate-limiting step in resolving the missing heritability of breast cancer. The aim of this study is to screen genes that are recurrently mutated among our exome data in a larger cohort of cases and controls to assess the prevalence of inactivating mutations that may be associated with breast cancer risk. We are using the Agilent HaloPlex Target Enrichment System to screen the coding regions of 168 genes in 1,000 BRCA1/2 mutation-negative familial breast cancer cases and 1,000 cancer-naive controls. To date, our interim analysis has identified 21 genes which carry an excess of truncating mutations in multiple breast cancer families versus controls. Established breast cancer susceptibility gene PALB2 is the most frequently mutated gene (13/998 cases versus 0/1009 controls), but other interesting candidates include NPSR1, GSN, POLD2, and TOX3. These and other genes are being validated in a second cohort of 1,000 cases and controls. Our experience demonstrates that beyond PALB2, the prevalence of mutations in the remaining breast cancer predisposition genes is likely to be very low making definitive validation exceptionally challenging.

Keywords: predisposition, familial, exome sequencing, breast cancer

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Authors: A. T. Toci, M. V. B. Zanoni

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The advanced oxidation processes have been defined as destructive technologies treatment of wastewater. These involve the formation of powerful oxidizing agents (usually hydroxyl radical .OH) capable of reacting with organic compounds present in wastewater, transforming damaging substances in CO2 and H2O (mineralization) or other innocuous products. However, the photochemical degradation with singlet oxygen has been little explored as oxidative pathway for the treatment of effluents containing food colorants. The molecular oxygen is an effective suppressor of organic molecules in the triplet excited state. One of the possible results of the physical withdrawal is the formation of singlet oxygen. Studies with singlet oxygen (1O2) show an high reactivity of the excited state of the molecule with olefins, aromatic hydrocarbons and a number of other organic and inorganic compounds. Its reactivity is about 2500 times larger than the oxygen in the ground state. Thus, in this work, it was studied the degradation of some dyes used in food industry (tartrazine, sunset yellow, erythrosine and carmoisine) by singlet oxygen. The sensitizer used for generating the 1O2 was methylene blue, which has a quantum yield generation of 0.50. Samples were prepared in water at a concentration of 5 ppm and irradiated with a sunlight simulator (Newport brand, model no. 67005) by consecutive 8h. The absorption spectra of UV-Vis molecules were made each hour irradiation. The degradation kinetics for each dye was determined using the maximum length of each dye absorption. The analysis by UV-Vis revealed that the processes were very efficient for the colorants sunset yellow and carmoisine. Both presented degradation kinetics of order zero with degradation constants 0.416 and 0.104, respectively. In the case of sunset yellow degradation reached 53% after 7h irradiation, Demonstrating the process efficiency. The erithrosine presented during the period irradiated a oscillating degradation kinetics, which requires further study. In the other hand, tartrazine was stable in the presence of 1O2. The investigation of the dyes degradation products owned degradation by 1O2 are underway, the techniques used for this are MS and NMR. The results of this study will enable the application of the cleanest methods for the treatment of industrial effluents, as there are other non-toxic and polluting molecules to generate 1O2.

Keywords: food colourants, singlet oxygen, degradation, wastewater, oxidative

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Authors: Evgeny V. Blagin, Aleksandr I. Dovgjallo, Dmitry A. Uglanov

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This article deals with research of the working process in the thermocompressor which operates on cryogenic working fluid. Thermocompressor is device suited for the conversation of heat energy directly to the potential energy of pressure. Suggested thermocompressor is suited for operation during liquid natural gas (LNG) re-gasification and is placed after evaporator. Such application of thermocompressor allows using of the LNG cold energy for rising of working fluid pressure, which then can be used for electricity generation or another purpose. Thermocompressor consists of two chambers divided by the regenerative heat exchanger. Calculation algorithm for unsteady calculation of thermocompressor working process was suggested. The results of this investigation are to change of thermocompressor’s chambers temperature and pressure during the working cycle. These distributions help to find out the parameters, which significantly influence thermocompressor efficiency. These parameters include regenerative heat exchanger coefficient of the performance (COP) dead volume of the chambers, working frequency of the thermocompressor etc. Exergy analysis was performed to estimate thermocompressor efficiency. Cryogenic thermocompressor operated on nitrogen working fluid was chosen as a prototype. Calculation of the temperature and pressure change was performed with taking into account heat fluxes through regenerator and thermocompressor walls. Temperature of the cold chamber significantly differs from the results of steady calculation, which is caused by friction of the working fluid in regenerator and heat fluxes from the hot chamber. The rise of the cold chamber temperature leads to decreasing of thermocompressor delivery volume. Temperature of hot chamber differs negligibly because losses due to heat fluxes to a cold chamber are compensated by the friction of the working fluid in the regenerator. Optimal working frequency was selected. Main results of the investigation: -theoretical confirmation of thermocompressor operation capability on the cryogenic working fluid; -optimal working frequency was found; -value of the cold chamber temperature differs from the starting value much more than the temperature of the hot chamber; -main parameters which influence thermocompressor performance are regenerative heat exchanger COP and heat fluxes through regenerator and thermocompressor walls.

Keywords: cold energy, liquid natural gas, thermocompressor, regenerative heat exchanger

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Authors: S. Kozlovski, S.W. Feigelson, R. Alon

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The b2 integrin ligands ICAM-1 ICAM-2 and the endothelial VLA-4 integrin ligand VCAM-1 are constitutively expressed on different lung vessels and on high endothelial venules (HEVs), the main portal for lymphocyte entry from the blood into lung draining lymph nodes. ICAMs are also ubiquitously expressed by many antigen-presenting leukocytes and have been traditionally suggested as critical for the various antigen-specific immune synapses generated by these distinct leukocytes and specific naïve and effector T cells. Loss of both ICAM-1 and ICAM-2 on the lung vasculature reduces the ability to patrol monocytes and Tregs to patrol the lung vasculature at a steady state. Our new findings suggest, however, that in terms of innate leukocyte trafficking into the lung lamina propria, both constitutively expressed and virus-induced vascular VCAM-1 can functionally compensate for the loss of these ICAMs. In a mouse model for influenza infection, neutrophil and NK cell recruitment and clearance of influenza remained normal in mice deficient in both ICAMs. Strikingly, mice deficient in both ICAMs also mounted normal influenza-specific CD8 proliferation and differentiation. In addition, these mice normally combated secondary influenza infection, indicating that the presence of ICAMs on conventional dendritic cells (cDCs) that present viral antigens are not required for immune synapse formation between these APCs and naïve CD8 T cells as previously suggested. Furthermore, long-lasting humoral responses critical for protection from a secondary homosubtypic influenza infection were also normal in mice deficient in both ICAM-1 and ICAM-2. Collectively, our results suggest that the expression of ICAM-1 and ICAM-2 on lung endothelial and epithelial cells, as well as on DCs and B cells, is not critical for the generation of innate or adaptive anti-viral immunity in the lungs. Our findings also suggest that endothelial VCAM-1 can substitute for the functions of vascular ICAMs in leukocyte trafficking into various lung compartments.

Keywords: emigration, ICAM-1, lymph nodes, VCAM-1

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Authors: Marie-Claude Richard, Amelie Bolduc-Mokhtar, Mathieu Parent

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People who have experienced maltreatment in childhood subsequently face many parenting issues of their own, in particular when it comes to distancing themselves from the abusive behaviors they were exposed and had access to positive role models. Few studies have explored the factors explaining the ability to break the generational cycle of child maltreatment. However, deeper knowledge of the factors associated with intergenerational discontinuity could facilitate the development of innovative interventions and increase the preventive potential of existing programs. This poster presentation will be about a better understanding of the intergenerational transmission of maltreatment (IGTM) from the perspective of both youth protection workers and parents receiving child protection services. The data used to meet this goal were collected from a group interview with eight youth protection workers whose caseloads involved IGTM situations and through semi-structured interviews with four parents with a history of child protection services and who were currently receiving such services for at least one of their children. In the view of the youth protection workers, the IGTM refers to everything that is transmitted and not transmitted from one generation to the next within a family. The study participants painted quite a bleak portrait of the families affected by IGTM. However, three main avenues of intervention were mentioned by the participants: working within the network, favoring long-term interventions and being empathic. The results also show that the mothers were in a trajectory of intergenerational discontinuity in child maltreatment. Support from their families and friends as well as from formal support services brought out some possible explanatory factors for intergenerational discontinuity in child maltreatment. From a prevention perspective, developing meaningful and trusting relationships seems a source of resilience for parents who were placed in the care of the child protection system as children. The small number of participants limits the generalizability of these results. The difficulty of recruiting parents is a substantial challenge regarding gaining knowledge on the intergenerational transmission of child maltreatment. Future studies should examine this question and seek to develop effective strategies to help recruit study participants.

Keywords: child maltreatment, intergenerational transmission, prevention, qualitative data

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Authors: Haifeng Shi, Kun Song, Yili Zhao

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In China, with the extensive promotion of the ‘aging in place’ pension policy as the background, most of the elders will choose to remain in their current homes and communities, finding out of preference or necessity that they will need to remodel their homes to fit their changing needs. This generation elder born in the 1960s to 1970s almost live in the same form of housing-condominium built from 1982 to 2012. Based on the survey of existing multi-family housing, especially in Tianjin, it is found that the current ‘double two-thirds principles’ is becoming the threshold for modification to existing house, particularly in the project of elevators addition to existing condominium (built from 1982 to 2016 without elevators below 6 floors according to the previous building code). Firstly, this article concludes the local policies of elevator addition nationwide, most of which has determined the importance and necessity of the community-based self-organization principle in the operation of the elevator addition. Secondly, by comparing the three existing community management systems (owners' congress, property management system and community committee) in instances, find that the community-based ‘two-thirds’ principle is not conducive to implement for multi-owned property renovation in the community or common accessibility modification in the building. However, analysis the property and other community management related laws, pointing out the shortcomings of the existing community-based ‘two-thirds’ decision-making norms. The analyzation showed that the unit-based and ‘100% principle’ method is more capable of common accessibility in the condominium in China. Differing from existing laws, the unit-based principle will be effective for the process of decision-making and ‘100% principle’ will protect closely profit-related householders for condominium modification in the multi-owned area. These three aspects of the analysis suggest that the establishment of the unit-based self-organization mechanism is a preferred and inevitable method to solve the problem of elevators addition to the existing condominium in China.

Keywords: aging in place, condominium, modification, multi own

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Authors: Oktay Celenk, Ugur Karanfil, Iskender Demir, Samir Lamrini, Jorg Neumann, Arif Demir

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Due to its favourable material characteristics, fiber reinforced plastics are amongst the main topics of all actual lightweight construction megatrends. Especially in transportation trends ranging from aeronautics over the automotive industry to naval transportation (yachts, cruise liners) the expected economic and environmental impact is huge. In naval transportation components like yacht bodies, antenna masts, decorative structures like deck lamps, light houses and pool areas represent cheap and robust solutions. Commercially available laser tools like carbon dioxide gas lasers (CO₂), frequency tripled solid state UV lasers, and Neodymium-YAG (Nd:YAG) lasers can be used. These tools have emission wavelengths of 10 µm, 0.355 µm, and 1.064 µm, respectively. The scientific goal is first of all the generation of a parameter matrix for laser processing of each used material for a Tm-fiber laser system (wavelength 2 µm). These parameters are the heat affected zone, process gas pressure, work piece feed velocity, intensity, irradiation time etc. The results are compared with results obtained with well-known material processing lasers, such as a Yb-fiber lasers (wavelength 1 µm). Compared to the CO₂-laser, the Tm-laser offers essential advantages for future laser processes like cutting, welding, ablating for repair and drilling in composite part manufacturing (components of cruise liners, marine pipelines). Some of these are the possibility of beam delivery in a standard fused silica fiber which enables hand guided processing, eye safety which results from the wavelength, excellent beam quality and brilliance due to the fiber nature. There is one more feature that is economically absolutely important for boat, automotive and military projects manufacturing that the wavelength of 2 µm is highly absorbed by the plastic matrix and thus enables selective removal of it for repair procedures.

Keywords: Thulium (Tm) fiber laser, laser processing of fiber-reinforced plastics (FRP), composite, heat affected zone

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Authors: Sandeep Mehmi, Harsh Verma, A. L. Sangal

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Ever since the idea of using computing services as commodity that can be delivered like other utilities e.g. electric and telephone has been floated, the scientific fraternity has diverted their research towards a new area called utility computing. New paradigms like cluster computing and grid computing came into existence while edging closer to utility computing. With the advent of internet the demand of anytime, anywhere access of the resources that could be provisioned dynamically as a service, gave rise to the next generation computing paradigm known as cloud computing. Today, cloud computing has become one of the most aggressively growing computer paradigm, resulting in growing rate of applications in area of IT outsourcing. Besides catering the computational and storage demands, cloud computing has economically benefitted almost all the fields, education, research, entertainment, medical, banking, military operations, weather forecasting, business and finance to name a few. Smart grid is another discipline that direly needs to be benefitted from the cloud computing advantages. Smart grid system is a new technology that has revolutionized the power sector by automating the transmission and distribution system and integration of smart devices. Cloud based smart grid can fulfill the storage requirement of unstructured and uncorrelated data generated by smart sensors as well as computational needs for self-healing, load balancing and demand response features. But, security issues such as confidentiality, integrity, availability, accountability and privacy need to be resolved for the development of smart grid cloud. In recent years, a number of intrusion prevention techniques have been proposed in the cloud, but hackers/intruders still manage to bypass the security of the cloud. Therefore, precise intrusion detection systems need to be developed in order to secure the critical information infrastructure like smart grid cloud. Considering the success of artificial neural networks in building robust intrusion detection, this research proposes an artificial neural network based model for detecting attacks in smart grid cloud.

Keywords: artificial neural networks, cloud computing, intrusion detection systems, security issues, smart grid

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Authors: Zakiullah Kalwar, Shabeer Ahmed Abbasi

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This research encompasses the study of Cretaceous Sembar Formation Shale Gas potential at Hajipur area. This study has been done with the approach of geophysical data integration. The structure is NE – SW trending anticline with two map able compartments at Cretaceous Sembar level. The study area is located within proven petroleum system. Cretaceous Sembar/Goru formation is in a Wet gas window and Tertiary source is possibly in the oil window. Potential seals are present in Upper Ranikot shale beds and Intra-Lower Ranikot shales. The effectiveness and presence of source and reservoir rocks are favorable in the area of interest. Cretaceous Sembar Shale and Goru Shale beds with good organic content (TOC upto 4%, Type II/III) are currently in gas generation window in the area. Source rock intervals are also reported in Eocene Kirthar Group (TOC upto 8%, Type –II). Good reservoir quality Paleocene Lower Ranikot and Cretaceous Sembar shale beds exist in the area. The collision between Indian and Eurasian Plates during Tertiary initiated folding and thrusting. The first phase of thrusting involved ophiolite emplacement along the western margins of the Indian Plate (west of the area under review). The main phase of thrusting in the Sulaiman region was from Late Miocene to the present. The study area contains Permian to Recent clastics and carbonates. The succession generally is younger in the southeast than in northwest. Intraformational sedimentation breaks are pronounced in Permian and Jurassic. Sulaiman Range is bounded by the Western Sulaiman Transform Fault Zone (of which the Kingri Fault is the major fault) to the west and by the Domanda Fault to the east. The Domanda Fault also constitutes the western boundary of the Sulaiman Foredeep, lies in sulaiman foredeep where subsurface having prominent independent closure. Several reservoir horizons of Jurassic to Eocene are established hydrocarbon producers in the Hajipur area.

Keywords: enough size, good potential, shale gas, structure closure

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Authors: Azizah M. Nahari, Peter Doerner

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Phosphate (Pi) is one of the essential macronutrients in plant growth and development, and it plays a central role in metabolic processes in plants, particularly photosynthesis and respiration. Limitation of crop productivity by Pi is widespread and is likely to increase in the future. Applications of Pi fertilizers have improved soil Pi fertility and crop production; however, they have also caused environmental damage. Therefore, in order to reduce dependence on unsustainable Pi fertilizers, a better understanding of phosphate use efficiency (PUE) is required for engineering nutrient-efficient crop plants. Enhanced Pi efficiency can be achieved by improved productivity per unit Pi taken up. We aim to identify, by using association mapping, general features of the most important loci that contribute to increased PUE to allow us to delineate the physiological pathways involved in defining this trait in the model plant Arabidopsis. As PUE is in part determined by the efficiency of uptake, we designed a hydroponic system to avoid confounding effects due to differences in root system architecture leading to differences in Pi uptake. In this system, 18 parental lines and 217 lines of the MAGIC population (a Multiparent Advanced Generation Inter-Cross) grown in high and low Pi availability conditions. The results showed revealed a large variation of PUE in the parental lines, indicating that the MAGIC population was well suited to identify PUE loci and pathways. 2 of 18 parental lines had the highest PUE in low Pi while some lines responded strongly and increased PUE with increased Pi. Having examined the 217 MAGIC population, considerable variance in PUE was found. A general feature was the trend of most lines to exhibit higher PUE when grown in low Pi conditions. Association mapping is currently in progress, but initial observations indicate that a wide variety of physiological processes are involved in influencing PUE in Arabidopsis. The combination of hydroponic growth methods and genome-wide association mapping is a powerful tool to identify the physiological pathways underpinning complex quantitative traits in plants.

Keywords: hydroponic system growth, phosphate use efficiency (PUE), Genome-wide association mapping, MAGIC population

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Authors: Mohammad Parvaresh, Mahdi Babaee, Bahareh Arghand, Davood Nourmohammadi

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Environmental degradation is caused by social inequalities and the inappropriate use of nature and a factor in the violation of human rights. Indeed, the right to a safe, healthy and ecologically-balanced environment is an independent human right. Therefore, the relationship between human rights and environmental protection is crucial for the study of social justice and sustainable development, and environmental problems are a result of the failure to realize social and economic justice. In this regard, 'article 50 of the constitution of the Islamic Republic of Iran as a general principle have many of the concepts of sustainable development, including: the growth and improvement of human life, the rights of present and future generations, and the integrity of the inner and outer generation, the prohibition of any environmental degradation'. Also, Charter on Citizen’s Rights, which was conveyed by the President of the Islamic Republic of Iran, Mr. Rouhani refers to the right to a healthy environment and sustainable development. In this regard in 2013, Tehran Province Water and Wastewater Co. defined a plan called 'Tehran’s Health Line' was includes Western and Eastern part by about 26 kilometers of water transferring pipelines varied 1000 to 2000 mm diameters. This project aims to: (1) Transfer water from the northwest water treatment plant to the southwest areas, which suffer from qualitative and quantitative water, in order to mix with the improper wells’ water; (2) Reducing the water consumption provided by harvesting from wells which results in improving the underground water resources, causing the large settlements and stopping the immigrating slums into the center or north side of the city. All of the financial resources accounted for 53,000,000 US$ which is mobilized by Tehran Province Water and Wastewater Co. to expedite the work. The present study examines the Tehran Health Line plan and the purpose of implementation of this plan to achieve environmental protection, environmental justice and citizenship rights for all people who live in Tehran.

Keywords: environmental justice, international environmental law, erga omnes, charter on citizen's rights, Tehran health line

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Authors: Dimitrios Dimitriou, Maria Sartzetaki

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In the early days of the of civil aviation, airports are totally state-owned companies under the control of national authorities or regional governmental bodies. From that time the picture has totally changed and airports privatisation and airport business commercialisation are key success factors to stimulate air transport demand, generate revenues and attract investors, linked to reliable and resilience of air transport system. Nowadays, airport's corporate strategy deals with policies and actions, affecting essential the business plans, the financial targets and the economic footprint in a regional economy they serving. Therefore, exploring airport corporate strategy is essential to support the decision in business planning, management efficiency, sustainable development and investment attractiveness on one hand; and define policies towards traffic development, revenues generation, capacity expansion, cost efficiency and corporate social responsibility. This paper explores key outputs in airport corporate strategy for different ownership schemes. The airport corporations are grouped in three major schemes: (a) Public, in which the public airport operator acts as part of the government administration or as a corporised public operator; (b) Mixed scheme, in which the majority of the shares and the corporate strategy is driven by the private or the public sector; and (c) Private, in which the airport strategy is driven by the key aspects of globalisation and liberalisation of the aviation sector. By a systemic approach, the key drivers in corporate strategy for modern airport business structures are defined. Key objectives are to define the key strategic opportunities and challenges and assess the corporate goals and risks towards sustainable business development for each scheme. The analysis based on an extensive cross-sectional dataset for a sample of busy European airports providing results on corporate strategy key priorities, risks and business models. The conventional wisdom is to highlight key messages to authorities, institutes and professionals on airport corporate strategy trends and directions.

Keywords: airport corporate strategy, airport ownership, airports business models, corporate risks

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Authors: Wojciech Górecki, Anna Sowiżdżał, Grzegorz Machowski, Tomasz Maćkowski, Bartosz Papiernik, Michał Stefaniuk

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The article shows results of the project which aims at evaluating possibilities of effective development and exploitation of natural gas from argillaceous series of the Autochthonous Miocene in the Carpathian Foredeep. To achieve the objective, the research team develop a world-trend based but unique methodology of processing and interpretation, adjusted to data, local variations and petroleum characteristics of the area. In order to determine the zones in which maximum volumes of hydrocarbons might have been generated and preserved as shale gas reservoirs, as well as to identify the most preferable well sites where largest gas accumulations are anticipated a number of task were accomplished. Evaluation of petrophysical properties and hydrocarbon saturation of the Miocene complex is based on laboratory measurements as well as interpretation of well-logs and archival data. The studies apply mercury porosimetry (MICP), micro CT and nuclear magnetic resonance imaging (using the Rock Core Analyzer). For prospective location (e.g. central part of Carpathian Foredeep – Brzesko-Wojnicz area) reprocessing and reinterpretation of detailed seismic survey data with the use of integrated geophysical investigations has been made. Construction of quantitative, structural and parametric models for selected areas of the Carpathian Foredeep is performed on the basis of integrated, detailed 3D computer models. Modeling are carried on with the Schlumberger’s Petrel software. Finally, prospective zones are spatially contoured in a form of regional 3D grid, which will be framework for generation modelling and comprehensive parametric mapping, allowing for spatial identification of the most prospective zones of unconventional gas accumulation in the Carpathian Foredeep. Preliminary results of research works indicate a potentially prospective area for occurrence of unconventional gas accumulations in the Polish part of Carpathian Foredeep.

Keywords: autochthonous Miocene, Carpathian foredeep, Poland, shale gas

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Authors: Amna Khaliq

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In this research paper, a comparison study has been undertaken between Canada and Denmark to analyze the education system between the countries in entrepreneurship. Denmark, a land of high wages and high taxes, and Canada, a land of immigrants and opportunities, have seen a positive relationship in entrepreneurs' growth. They are both considered one of the top ten countries to start a business and to have government support globally. However, education is entirely free to Danish students, including university degrees, compared to Canadians, which can further hurdle for Canadian millennials to grow in the business world—the business experience more growth with educated entrepreneurs with international backgrounds in new immigrants. Denmark has seen a gradual increase in female entrepreneurs over the decade but is still lower than OECD countries. Compassionate management and work-life balance are prioritized in Denmark, unlike in Canada. Danish are early adopters of technology and have excellent infrastructure to support the technology industry, whereas Canada is still a service-oriented and manufacturer-based country. 2018 has been the highest number of opening businesses for Canada and Denmark. Some companies offer high wages, hiring bonuses, flexible working hours, wellness, and mental health benefits during Pandemic to keep the companies running and keep their workers' morale high. Pandemic has taught consumers new patterns to shop online. It is essential now to use technology and automation to increase productivity in businesses. Only those companies will survive that are applying this strategy. The Pandemic has ultimately changed entrepreneurs' and employees' behavior in the business world. Along with Ph.D. professors, entrepreneurs should be allowed to teach at learning intuitions. Millennials turn out to be the most entrepreneurial generation in both countries. Entrepreneurship education will only be beneficial when students create businesses and learn from real-life experiences. Managing physical, mental, emotional, and psychological health while dealing with high pressure in entrepreneurship are soft skills learned through practical work.

Keywords: entrepreneurship education, millennials, pandemic, Denmark, Canada

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Authors: Adolfo Martucci, Iulian Mihai

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By means of the expansion through a Conical Nozzle and the low pressure inside the Test Chamber, a large hypersonic stable flow takes place for a duration of up to 30 minutes. Downstream the Test Chamber, the diffuser has the function of reducing the flow velocity to subsonic values, and as a consequence, the temperature increases again. In order to cool down the flow, a heat exchanger is present at the end of the diffuser. The Vacuum System generates the necessary vacuum conditions for the correct hypersonic flow generation, and the DeNOx system, which follows the Vacuum System, reduces the nitrogen oxide concentrations created inside the plasma flow behind the limits imposed by Italian law. This very large, powerful, and complex facility allows researchers and engineers to reproduce entire re-entry trajectories of space vehicles into the atmosphere. One of the most important parameters for a hypersonic flowfield representative of re-entry conditions is the specific total enthalpy. This is the whole energy content of the fluid, and it represents how severe could be the conditions around a spacecraft re-entering from a space mission or, in our case, inside a hypersonic wind tunnel. It is possible to reach very high values of enthalpy (up to 45 MJ/kg) that, together with the large allowable size of the models, represent huge possibilities for making on-ground experiments regarding the atmospheric re-entry field. The maximum nozzle exit section diameter is 1950 mm, where values of Mach number very much higher than 1 can be reached. The specific total enthalpy is evaluated by means of a number of measurements, each of them concurring with its value and its uncertainty. The scope of the present paper is the evaluation of the sensibility of the uncertainty of the specific total enthalpy versus all the parameters and measurements involved. The sensors that, if improved, could give the highest advantages have so been individuated. Several simulations in Python with the METAS library and by means of Monte Carlo simulations are presented together with the obtained results and discussions about them.

Keywords: hypersonic, uncertainty, enthalpy, simulations

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Authors: Ankit Shah, R. K. Shrivastava

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Flood and drought are two main features of hydrology which affect the human life. Floods are natural disasters which cause millions of rupees’ worth of damage each year in India and the whole world. Flood causes destruction in form of life and property. An accurate estimate of the flood damage potential is a key element to an effective, nationwide flood damage abatement program. Also, the increase in demand of water due to increase in population, industrial and agricultural growth, has let us know that though being a renewable resource it cannot be taken for granted. We have to optimize the use of water according to circumstances and conditions and need to harness it which can be done by construction of hydraulic structures. For their safe and proper functioning of hydraulic structures, we need to predict the flood magnitude and its impact. Hydraulic structures play a key role in harnessing and optimization of flood water which in turn results in safe and maximum use of water available. Mainly hydraulic structures are constructed on ungauged sites. There are two methods by which we can estimate flood viz. generation of Unit Hydrographs and Flood Frequency Analysis. In this study, Regional Flood Frequency Analysis has been employed. There are many methods for estimating the ‘Regional Flood Frequency Analysis’ viz. Index Flood Method. National Environmental and Research Council (NERC Methods), Multiple Regression Method, etc. However, none of the methods can be considered universal for every situation and location. The Narmada basin is located in Central India. It is drained by most of the tributaries, most of which are ungauged. Therefore it is very difficult to estimate flood on these tributaries and in the main river. As mentioned above Artificial Neural Network (ANN)s and Multiple Regression Method is used for determination of Regional flood Frequency. The annual peak flood data of 20 sites gauging sites of Narmada Basin is used in the present study to determine the Regional Flood relationships. Homogeneity of the considered sites is determined by using the Index Flood Method. Flood relationships obtained by both the methods are compared with each other, and it is found that ANN is more reliable than Multiple Regression Method for the present study area.

Keywords: artificial neural network, index flood method, multi layer perceptrons, multiple regression, Narmada basin, regional flood frequency

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Authors: Muhammad Dawood Idrees, Maria Hafeez, Arsalan Ansari

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Toll tax collection is the earliest method of tax collection and revenue generation. This revenue is utilized for the development of roads networks, maintenance, and connecting to roads and highways across the country. Pakistan is one of the biggest countries, covers a wide area of land, roads networks, and motorways are important source of connecting cities. Every day millions of people use motorways, and they have to stop at toll plazas to pay toll tax as majority of toll plazas are manually collecting toll tax. The purpose of this study is to calculate the waiting time of vehicles at Karachi Hyderabad (M-9) motorway. As Karachi is the biggest city of Pakistan and hundreds of thousands of people use this route to approach other cities. Currently, toll tax collection is manual system which is a major cause for long time waiting at toll plaza. This study calculates the waiting time of vehicles, fuel consumed in waiting time, manpower employed at toll plaza as all process is manual, and it also leads to mental and physical fatigue of driver. All wastages of sources are also calculated, and a most feasible automatic toll tax collection system is proposed which is not only beneficial to reduce waiting time but also beneficial in reduction of fuel, reduction of manpower employed, and reduction in physical and mental fatigue. A cost comparison in terms of wastages is also shown between manual and automatic toll tax collection system (E-Z Pass). Results of this study reveal that, if automatic tool collection system is implemented at Karachi to Hyderabad motorway (M-9), there will be a significance reduction in waiting time of vehicles, which leads to reduction of fuel consumption, environmental pollution, mental and physical fatigue of driver. All these reductions are also calculated in terms of money (Pakistani rupees) and it is obtained that millions of rupees can be saved by using automatic tool collection system which will lead to improve the economy of country.

Keywords: toll tax collection, waiting time, wastages, driver fatigue

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Authors: Srikanth Pandurangi, Basheer Mohammed, Nezar Al Sayegh

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In order to meet the increasing demand for housing care for Kuwaiti citizens, the government authorities in Kuwait are undertaking a series of projects in the form of new large cities, outside the current urban area. Al Mutlaa City located to the north-west of the Kuwait Metropolitan Area is one such project out of the 15 planned new cities. The city accommodates a wide variety of residential developments, employment opportunities, commercial, recreational, health care and institutional uses. This paper examines the application of comprehensive transportation demand modeling works undertaken in VISUM platform to understand the future intracity and intercity travel distribution patterns in Kuwait. The scope of models developed varied in levels of detail: strategic model update, sub-area models representing future demand of Al Mutlaa City, sub-area models built to estimate the demand in the residential neighborhoods of the city. This paper aims at offering model update framework that facilitates easy integration between sub-area models and strategic national models for unified traffic forecasts. This paper presents the transportation demand modeling results utilized in informing the planning of multi-modal transportation system for Al Mutlaa City. This paper also presents the household survey data collection efforts undertaken using GPS devices (first time in Kuwait) and notebook computer based digital survey forms for interviewing representative sample of citizens and residents. The survey results formed the basis of estimating trip generation rates and trip distribution coefficients used in the strategic base year model calibration and validation process.

Keywords: innovative methods in transportation data collection, integrated public transportation system, traffic forecasts, transportation modeling, travel behavior

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Authors: Thummalapalli CSM Gupta, Banti Sidhiwala

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Mineral oils of naphthenic and paraffinic type have been traditionally been used as insulating liquids in the transformer applications to protect the solid insulation from moisture and ensures effective heat transfer/cooling. The performance of these type of oils have been proven in the field over many decades and the condition monitoring and diagnosis of transformer performance have been successfully monitored through oil properties and dissolved gas analysis methods successfully. Different type of gases representing various types of faults due to components or operating conditions effectively. While large amount of data base has been generated in the industry on dissolved gas analysis for mineral oil based transformer oils and various models for predicting the fault and analysis, oil specifications and standards have also been modified to include stray gassing limits which cover the low temperature faults and becomes an effective preventative maintenance tool that can benefit greatly to know the reasons for the breakdown of electrical insulating materials and related components. Natural esters have seen a rise in popularity in recent years due to their "green" credentials. Some of its benefits include biodegradability, a higher fire point, improvement in load capability of transformer and improved solid insulation life than mineral oils. However, the Stray gases evolution like hydrogen and hydrocarbons like methane (CH4) and ethane (C2H6) show very high values which are much higher than the limits of mineral oil standards. Though the standards for these type esters are yet to be evolved, the higher values of hydrocarbon gases that are available in the market is of concern which might be interpreted as a fault in transformer operation. The current paper focuses on developing a natural ester based transformer oil which shows very levels of stray gassing by standard test methods show much lower values compared to the products available currently and experimental results on various test conditions and the underlying mechanism explained.

Keywords: biodegadability, fire point, dissolved gassing analysis, stray gassing

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Authors: Sohail Bawani, Kausar S. Khan, Rozina Karmaliani, Shehnaz Mir

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Action research (AR) is one of the types of health systems research (HSR), and participatory action research (PAR) is known for being effective in health systems strengthening (HSS). The current literature on PAR for HSS cites numerous examples and case studies that led to improve health services; build child health information system; increase knowledge and awareness of people about health problems, and identify pathways for institutional and policy change by engaging people in research. But examples of marginalized communities being agents of change in health governance are not common in health systems research (HSR). This approach to PAR is at the heart of Paolo Freire’s Social Transformation Theory and Critical Consciousness building, which was used to design a community-based PAR study in the Northern/mountainous areas of Pakistan. The purpose of the study was to understand the place and role of marginalized communities in strengthening existing health governance structure (health facility and village health committees and health boards) by taking marginalized communities as partners. Community meetings were carried out to identify who is living at the social, political, cultural and economic margins in 40 different villages. Participatory reflection and analysis (PRA) tools were used during the meeting to facilitate identification. Focus group discussions were conducted with marginalized groups using PRA tools and family ethnographies with marginalized families identified through group discussions. Findings of the study revealed that for the marginalized health systems constitute more than just delivery of health services, but it also embraces social determinants that surround systems and its governance. The paper argues that from Frerian perspective people’s participation should not only be limited to knowledge generation. People must be seen active users of the knowledge that they generate for achieving better health outcomes that they want to achieve in the time to come. PAR provides a pathway to the marginalized in playing a role in health governance. The study dissemination planned shall engage the marginalized in a dialogue with service providers so that together a role for the marginalized can be outlined.

Keywords: participatory action research, health systems, marginalized, health services

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Authors: Mpho Mokoatle, Darlington Mapiye, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

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Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on $k$-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0%, 80.5%, 80.5%, 63.6%, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms.

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

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Authors: Darlington Mapiye, Mpho Mokoatle, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on k-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0 %, 80.5 %, 80.5 %, 63.6 %, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

Procedia PDF Downloads 159

Authors: Abdul Murad Zainal Abidin, Azahar Mohd, Nor Idayu Arifin, Siti Nor Azila Khalid, Mohd Julzaha Zahari Mohamad Yusof

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A thermoelectric cooler (TEC) is an electronic component that uses ‘peltier’ effect to create a temperature difference by transferring heat between two electrical junctions of two different types of materials. TEC can also be used for heating by reversing the electric current flow and even power generation. A heat flow meter (HFM) is an equipment for measuring thermal conductivity of building materials. During the test, water is used as heat transfer medium to cool the HFM. The existing re-circulating cooler in the market is very costly, and the alternative is to use piped tap water to extract heat from HFM. However, the tap water temperature is insufficiently low to enable heat transfer to take place. The operating temperature for isothermal plates in the HFM is 40°C with the range of ±0.02°C. When the temperature exceeds the operating range, the HFM stops working, and the test cannot be conducted. The aim of the research is to develop a low-cost but energy-efficient TEC prototype that enables heat transfer without compromising the function of the HFM. The objectives of the research are a) to identify potential of TEC as a cooling device by evaluating its cooling rate and b) to determine the amount of water savings using TEC compared to normal tap water. Four (4) peltier sets were used, with two (2) sets used as pre-cooler. The cooling water is re-circulated from the reservoir into HFM using a water pump. The thermal conductivity readings, the water flow rate, and the power consumption were measured while the HFM was operating. The measured data has shown decrease in average cooling temperature difference (ΔTave) of 2.42°C and average cooling rate of 0.031°C/min. The water savings accrued from using the TEC is projected to be 8,332.8 litres/year with the application of water re-circulation. The results suggest the prototype has achieved required objectives. Further research will include comparing the cooling rate of TEC prototype against conventional tap water and to optimize its design and performance in terms of size and portability. The possible application of the prototype could also be expanded to portable storage for medicine and beverages.

Keywords: energy efficiency, thermoelectric cooling, pre-cooling device, heat flow meter, sustainable technology, thermal conductivity

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Authors: Pinn Tsin Isabel Yee

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With the advent of internet technologies, students are increasingly turning toward social media and cross-platform messaging apps such as WhatsApp, Line, and WeChat to support their teaching and learning processes. Although each messaging app has varying features, WhatsApp remains one of the most popular cross-platform apps that allow for fast, simple, secure messaging and free calls anytime, anywhere. With a plethora of advantages, students could easily assimilate WhatsApp as a supportive technology in their learning process. There could be peer to peer learning, and a teacher will be able to share knowledge digitally via the creation of WhatsApp groups. Content analysis techniques were utilized to analyze data collected by closed-ended question forms. Studies demonstrated that 98.8% of college students (n=80) from the Monash University foundation year agreed that the employment of WhatsApp groups was helpful as a learning tool. Approximately 71.3% disagreed that notifications and alerts from the WhatsApp group were disruptions in their studies. Students commented that they could silence the notifications and hence, it would not disturb their flow of thoughts. In fact, an overwhelming majority of students (95.0%) found it enjoyable to participate in WhatsApp groups for educational purposes. It was a common perception that some students felt pressured to post a reply in such groups, but data analysis showed that 72.5% of students did not feel pressured to comment or reply. It was good that 93.8% of students felt satisfactory if their posts were not responded to speedily, but was eventually attended to. Generally, 97.5% of students found it useful if their teachers provided their handphone numbers to be added to a WhatsApp group. If a teacher posts an explanation or a mathematical working in the group, all students would be able to view the post together, as opposed to individual students asking their teacher a similar question. On whether students preferred using Facebook as a learning tool, there was a 50-50 divide in the replies from the respondents as 51.3% of students liked WhatsApp, while 48.8% preferred Facebook as a supportive technology in teaching and learning. Taken altogether, the utilization of WhatsApp groups as a supportive technology in teaching and learning should be implemented in all classes to continuously engage our generation Y students in the ever-changing digital landscape.-

Keywords: education, learning, messaging app, technology, WhatsApp groups

Procedia PDF Downloads 157

Authors: Marianna Maiaru, Gregory M. Odegard, Josh Kemppainen, Ivan Gallegos, Michael Olaya

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Ceramic matrix composites (CMCs) are typically used in applications that require long-term mechanical integrity at elevated temperatures. CMCs are usually fabricated using a polymer precursor that is initially polymerized in situ with fiber reinforcement, followed by a series of cycles of pyrolysis to transform the polymer matrix into a rigid glass or ceramic. The pyrolysis step typically generates volatile gasses, which creates porosity within the polymer matrix phase of the composite. Subsequent cycles of monomer infusion, polymerization, and pyrolysis are often used to reduce the porosity and thus increase the durability of the composite. Because of the significant expense of such iterative processing cycles, new generations of CMCs with improved durability and manufacturability are difficult and expensive to develop using standard Edisonian approaches. The goal of this research is to develop a computational process-modeling-based approach that can be used to design the next generation of CMC materials with optimized material and processing parameters for maximum strength and efficient manufacturing. The process modeling incorporates computational modeling tools, including molecular dynamics (MD), to simulate the material at multiple length scales. Results from MD simulation are used to inform the continuum-level models to link molecular-level characteristics (material structure, temperature) to bulk-level performance (strength, residual stresses). Processing parameters are optimized such that process-induced residual stresses are minimized and laminate strength is maximized. The multiscale process modeling method developed with this research can play a key role in the development of future CMCs for high-temperature and high-strength applications. By combining multiscale computational tools and process modeling, new manufacturing parameters can be established for optimal fabrication and performance of CMCs for a wide range of applications.

Keywords: digital engineering, finite elements, manufacturing, molecular dynamics

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Authors: Kazunori Takai, Weng Kaiwei, Sadao Araki, Hideki Yamamoto

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HFC and PFC gases have been commonly and widely used as refrigerant of air conditioner and as etching agent of semiconductor manufacturing process, because of their higher heat of vaporization and chemical stability. On the other hand, HFCs and PFCs gases have the high global warming effect on the earth. Therefore, we have to be decomposed these gases emitted from chemical apparatus like as refrigerator. Until now, disposal of these gases were carried out by using combustion method like as Rotary kiln treatment mainly. However, this treatment needs extremely high temperature over 1000 °C. In the recent year, in order to reduce the energy consumption, a hydrolytic decomposition method using catalyst and plasma decomposition treatment have been attracted much attention as a new disposal treatment. However, the decomposition of fluorine-containing gases under the wet condition is not able to avoid the generation of hydrofluoric acid. Hydrofluoric acid is corrosive gas and it deteriorates catalysts in the decomposition process. Moreover, an additional process for the neutralization of hydrofluoric acid is also indispensable. In this study, the decomposition of C2F6 using zeolite and zeolite/CaO mixture as reactant was evaluated in the dry condition at 923 K. The effect of the chemical structure of zeolite on the decomposition reaction was confirmed by using H-Y, H-Beta, H-MOR and H-ZSM-5. The formation of CaF2 in zeolite/CaO mixtures after the decomposition reaction was confirmed by XRD measurements. The decomposition of C2F6 using zeolite as reactant showed the closely similar behaviors regardless the type of zeolite (MOR, Y, ZSM-5, Beta type). There was no difference of XRD patterns of each zeolite before and after reaction. On the other hand, the difference in the C2F6 decomposition for each zeolite/CaO mixtures was observed. These results suggested that the rate-determining process for the C2F6 decomposition on zeolite alone is the removal of fluorine from reactive site. In other words, the C2F6 decomposition for the zeolite/CaO improved compared with that for the zeolite alone by the removal of the fluorite from reactive site. HMOR/CaO showed 100% of the decomposition for 3.5 h and significantly improved from zeolite alone. On the other hand, Y type zeolite showed no improvement, that is, the almost same value of Y type zeolite alone. The descending order of C2F6 decomposition was MOR, ZSM-5, beta and Y type zeolite. This order is similar to the acid strength characterized by NH3-TPD. Hence, it is considered that the C-F bond cleavage is closely related to the acid strength.

Keywords: hexafluoroethane, zeolite, calcium oxide, decomposition

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Authors: Azeb Degife

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Over the past few years, the volume of international investment in agricultural land has increased globally. In recent times, Ethiopian government uses agricultural investment as one of the most important and effective strategies for economic growth, food security and poverty reduction in rural areas. Since the mid-2000s, government has awarded millions of hectares of most fertile land to rich countries and some of the world's most wealthy people to export various kinds of crop, often in long-term leases and at bargain prices. This study focuses on the pros and cons of large-scale agriculture investment Gambella region, Ethiopia. The main results were generated both from primary and secondary data sources. Primary data are obtained through interview, direct observation and a focus group discussion (FGDs). The secondary data are obtained from published documents, reports from governmental and non-governmental institutions. The findings of the study demonstrated that agriculture investment has advantages on the socio-economic and disadvantages on socio-environmental aspects. The main benefits agriculture investments in the region are infrastructural development and generation employment for the local people. Further, the Ethiopian government also generates foreign currency from the agriculture investment opportunities. On the other hand, Gambella people are strongly tied to the land and the rivers that run through in the region. However, now large-scale agricultural investment by foreign and local investors on an industrial scale results deprives people livelihoods and natural resources of the region. Generally, the negative effects of agriculture investment include increasing food insecurity, and displacement of smallholder farmers and pastoralists. Moreover, agriculture investment has strong adverse environmental impacts on natural resources such as land, water, forests and biodiversity. Therefore, an Ethiopian government strategy needs to focus on integration approach and sustainable agricultural growth.

Keywords: agriculture investment, cons, displacement, Gambella, integration approach, pros, socio-economic, socio-environmental

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Authors: P. Annapurna, Cecil Ross, Sudhir Krishna, Sweta Srivastava

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Irradiation plays a pivotal role in cervical cancer treatment, however some tumors exhibit resistance to therapy while some exhibit relapse, due to better repair and enhanced resistance mechanisms operational in their cells. The present study aims to understand the signaling mechanism operational in resistance phenotype and in the present study we report the role of Rho GTPase associated protein kinase (ROCK) signaling in cervical carcinoma radio-resistance. ROCK signaling has been implicated in several tumor progressions and is important for DNA repair. Irradiation of spheroid cultures of SiHa cervical carcinoma derived cell line at 6Gy resulted in generation of resistant cells in vitro which had better clonogenic abilities and formed larger and more colonies, in soft agar colony formation assay, as compared to the non-irradiated cells. These cells also exhibited an enhanced motility phenotype. Cell cycle profiling showed the cells to be blocked in G2M phase with enhanced pCDC2 levels indicating onset of possible DNA repair mechanism. Notably, 3 days post-irradiation, irradiated cells showed increased ROCK2 translocation to the nucleus with enhanced protein expression as compared to the non-irradiated cells. Radio-sensitization of the resistant cells was enhanced using Y27632, an inhibitor to ROCK signaling. The treatment of resistant cells with Y27632 resulted in increased cell death upon further irradiation. This observation has been confirmed using inhibitory antibodies to ROCK1/2. Result show that both ROCK1/2 have a functional contribution in radiation resistance of cervical cancer cells derived from cell lines. Interestingly enrichment of stem like cells (Hoechst negative cells) was also observed upon irradiation and these cells were markedly sensitive to Y27632 treatment. Our results thus suggest the role of ROCK signaling in radio-resistance in cervical carcinoma. Further studies with human biopsies, mice models and mechanistic of ROCK signaling in the context of radio-resistance will clarify the role of this molecule further and allow for therapeutics development.

Keywords: cervical carcinoma, radio-resistance, ROCK signaling, cancer treatment

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Authors: Swarkar Sharma, Ekta Rai, Ankit Mahajan, Parvinder Kumar, Manoj K Dhar, Sushil Razdan, Kumarasamy Thangaraj, Carol Wise, Shiro Ikegawa M.D., K.K. Pandita M.D.

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Rare disorders are poorly understood hence, remain uncharacterized or patients are misdiagnosed and get poor medical attention. A rare mysterious skeletal disorder that remained unidentified for decades and rendered many people physically challenged and disabled for life has been reported in an isolated remote village ‘Arai’ of Poonch district of Jammu and Kashmir. This village is located deep in mountains and the population residing in the region is highly consanguineous. In our survey of the region, 70 affected people were reported, showing similar phenotype, in the village with a population of approximately 5000 individuals. We were able to collect samples from two multi generational extended families from the village. Through Whole Exome sequencing (WES), we identified a rare variation NM_003880.3:c.156C>A NP_003871.1:p.Cys52Ter, which results in introduction of premature stop codon in WISP3 gene. We found this variation perfectly segregating with the disease in one of the family. However, this variation was absent in other family. Interestingly, a novel splice site mutation at position c.643+1G>A of WISP3 gene, perfectly segregating with the disease was observed in the second family. Thus, exploiting WES and putting different evidences together (familial histories and genetic data, clinical features, radiological and biochemical tests and findings), the disease has finally been diagnosed as a very rare recessive hereditary skeletal disease “Progressive Pseudorheumatoid Arthropathy of Childhood” (PPAC) also known as “Spondyloepiphyseal Dysplasia Tarda with Progressive Arthropathy” (SEDT-PA). This genetic characterization and identification of the disease causing mutations will aid in genetic counseling, critically required to curb this rare disorder and to prevent its appearance in future generations in the population. Further, understanding of the role of WISP3 gene the biological pathways should help in developing treatment for the disorder.

Keywords: whole exome sequencing, Next Generation Sequencing, rare disorders

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