Search results for: frequency of oscillatory flow
Commenced in January 2007
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Edition: International
Paper Count: 8406

Search results for: frequency of oscillatory flow

96 Understanding the Impact of Spatial Light Distribution on Object Identification in Low Vision: A Pilot Psychophysical Study

Authors: Alexandre Faure, Yoko Mizokami, éRic Dinet

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These recent years, the potential of light in assisting visually impaired people in their indoor mobility has been demonstrated by different studies. Implementing smart lighting systems for selective visual enhancement, especially designed for low-vision people, is an approach that breaks with the existing visual aids. The appearance of the surface of an object is significantly influenced by the lighting conditions and the constituent materials of the objects. Appearance of objects may appear to be different from expectation. Therefore, lighting conditions lead to an important part of accurate material recognition. The main objective of this work was to investigate the effect of the spatial distribution of light on object identification in the context of low vision. The purpose was to determine whether and what specific lighting approaches should be preferred for visually impaired people. A psychophysical experiment was designed to study the ability of individuals to identify the smallest cube of a pair under different lighting diffusion conditions. Participants were divided into two distinct groups: a reference group of observers with normal or corrected-to-normal visual acuity and a test group, in which observers were required to wear visual impairment simulation glasses. All participants were presented with pairs of cubes in a "miniature room" and were instructed to estimate the relative size of the two cubes. The miniature room replicates real-life settings, adorned with decorations and separated from external light sources by black curtains. The correlated color temperature was set to 6000 K, and the horizontal illuminance at the object level at approximately 240 lux. The objects presented for comparison consisted of 11 white cubes and 11 black cubes of different sizes manufactured with a 3D printer. Participants were seated 60 cm away from the objects. Two different levels of light diffuseness were implemented. After receiving instructions, participants were asked to judge whether the two presented cubes were the same size or if one was smaller. They provided one of five possible answers: "Left one is smaller," "Left one is smaller but unsure," "Same size," "Right one is smaller," or "Right one is smaller but unsure.". The method of constant stimuli was used, presenting stimulus pairs in a random order to prevent learning and expectation biases. Each pair consisted of a comparison stimulus and a reference cube. A psychometric function was constructed to link stimulus value with the frequency of correct detection, aiming to determine the 50% correct detection threshold. Collected data were analyzed through graphs illustrating participants' responses to stimuli, with accuracy increasing as the size difference between cubes grew. Statistical analyses, including 2-way ANOVA tests, showed that light diffuseness had no significant impact on the difference threshold, whereas object color had a significant influence in low vision scenarios. The first results and trends derived from this pilot experiment clearly and strongly suggest that future investigations could explore extreme diffusion conditions to comprehensively assess the impact of diffusion on object identification. For example, the first findings related to light diffuseness may be attributed to the range of manipulation, emphasizing the need to explore how other lighting-related factors interact with diffuseness.

Keywords: Lighting, Low Vision, Visual Aid, Object Identification, Psychophysical Experiment

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95 Remote BioMonitoring of Mothers and Newborns for Temperature Surveillance Using a Smart Wearable Sensor: Techno-Feasibility Study and Clinical Trial in Southern India

Authors: Prem K. Mony, Bharadwaj Amrutur, Prashanth Thankachan, Swarnarekha Bhat, Suman Rao, Maryann Washington, Annamma Thomas, N. Sheela, Hiteshwar Rao, Sumi Antony

Abstract:

The disease burden among mothers and newborns is caused mostly by a handful of avoidable conditions occurring around the time of childbirth and within the first month following delivery. Real-time monitoring of vital parameters of mothers and neonates offers a potential opportunity to impact access as well as the quality of care in vulnerable populations. We describe the design, development and testing of an innovative wearable device for remote biomonitoring (RBM) of body temperatures in mothers and neonates in a hospital in southern India. The architecture consists of: [1] a low-cost, wearable sensor tag; [2] a gateway device for ‘real-time’ communication link; [3] piggy-backing on a commercial GSM communication network; and [4] an algorithm-based data analytics system. Requirements for the device were: long battery-life upto 28 days (with sampling frequency 5/hr); robustness; IP 68 hermetic sealing; and human-centric design. We undertook pre-clinical laboratory testing followed by clinical trial phases I & IIa for evaluation of safety and efficacy in the following sequence: seven healthy adult volunteers; 18 healthy mothers; and three sets of babies – 3 healthy babies; 10 stable babies in the Neonatal Intensive Care Unit (NICU) and 1 baby with hypoxic ischaemic encephalopathy (HIE). The 3-coin thickness, pebble-design sensor weighing about 8 gms was secured onto the abdomen for the baby and over the upper arm for adults. In the laboratory setting, the response-time of the sensor device to attain thermal equilibrium with the surroundings was 4 minutes vis-a-vis 3 minutes observed with a precision-grade digital thermometer used as a reference standard. The accuracy was ±0.1°C of the reference standard within the temperature range of 25-40°C. The adult volunteers, aged 20 to 45 years, contributed a total of 345 hours of readings over a 7-day period and the postnatal mothers provided a total of 403 paired readings. The mean skin temperatures measured in the adults by the sensor were about 2°C lower than the axillary temperature readings (sensor =34.1 vs digital = 36.1); this difference was statistically significant (t-test=13.8; p<0.001). The healthy neonates provided a total of 39 paired readings; the mean difference in temperature was 0.13°C (sensor =36.9 vs digital = 36.7; p=0.2). The neonates in the NICU provided a total of 130 paired readings. Their mean skin temperature measured by the sensor was 0.6°C lower than that measured by the radiant warmer probe (sensor =35.9 vs warmer probe = 36.5; p < 0.001). The neonate with HIE provided a total of 25 paired readings with the mean sensor reading being not different from the radian warmer probe reading (sensor =33.5 vs warmer probe = 33.5; p=0.8). No major adverse events were noted in both the adults and neonates; four adult volunteers reported mild sweating under the device/arm band and one volunteer developed mild skin allergy. This proof-of-concept study shows that real-time monitoring of temperatures is technically feasible and that this innovation appears to be promising in terms of both safety and accuracy (with appropriate calibration) for improved maternal and neonatal health.

Keywords: public health, remote biomonitoring, temperature surveillance, wearable sensors, mothers and newborns

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94 Financial Policies in the Process of Global Crisis: Case Study Kosovo, Case Kosovo

Authors: Shpetim Rezniqi

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Financial Policies in the process of global crisis the current crisis has swept the world with special emphasis, most developed countries, those countries which have most gross -product world and you have a high level of living.Even those who are not experts can describe the consequences of the crisis to see the reality that is seen, but how far will it go this crisis is impossible to predict. Even the biggest experts have conjecture and large divergence, but agree on one thing: - The devastating effects of this crisis will be more severe than ever before and can not be predicted.Long time, the world was dominated economic theory of free market laws. With the belief that the market is the regulator of all economic problems. The market, as river water will flow to find the best and will find the necessary solution best. Therefore much less state market barriers, less state intervention and market itself is an economic self-regulation. Free market economy became the model of global economic development and progress, it transcends national barriers and became the law of the development of the entire world economy. Globalization and global market freedom were principles of development and international cooperation. All international organizations like the World Bank, states powerful economic, development and cooperation principles laid free market economy and the elimination of state intervention. The less state intervention much more freedom of action was this market- leading international principle. We live in an era of financial tragic. Financial markets and banking in particular economies are in a state of thy good, US stock markets fell about 40%, in other words, this time, was one of the darkest moments 5 since 1920. Prior to her rank can only "collapse" of the stock of Wall Street in 1929, technological collapse of 2000, the crisis of 1973 after the Yom Kippur war, while the price of oil quadrupled and famous collapse of 1937 / '38, when Europe was beginning World war II In 2000, even though it seems like the end of the world was the corner, the world economy survived almost intact. Of course, that was small recessions in the United States, Europe, or Japan. Much more difficult the situation was at crisis 30s, or 70s, however, succeeded the world. Regarding the recent financial crisis, it has all the signs to be much sharper and with more consequences. The decline in stock prices is more a byproduct of what is really happening. Financial markets began dance of death with the credit crisis, which came as a result of the large increase in real estate prices and household debt. It is these last two phenomena can be matched very well with the gains of the '20s, a period during which people spent fists as if there was no tomorrow. All is not away from the mouth of the word recession, that fact no longer a sudden and abrupt. But as much as the financial markets melt, the greater is the risk of a problematic economy for years to come. Thus, for example, the banking crisis in Japan proved to be much more severe than initially expected, partly because the assets which were based more loans had, especially the land that falling in value. The price of land in Japan is about 15 years that continues to fall. (ADRI Nurellari-Published in the newspaper "Classifieds"). At this moment, it is still difficult to çmosh to what extent the crisis has affected the economy and what would be the consequences of the crisis. What we know is that many banks will need more time to reduce the award of credit, but banks have this primary function, this means huge loss.

Keywords: globalisation, finance, crisis, recomandation, bank, credits

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93 Global News Coverage of the Pandemic: Towards an Ethical Framework for Media Professionalism

Authors: Anantha S. Babbili

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This paper analyzes the current media practices dominant in global journalistic practices within the framework of world press theories of Libertarian, Authoritarian, Communist, and Social Responsibility to evaluate their efficacy in addressing their role in the coverage of the coronavirus, also known as COVID-19. The global media flows, determinants of news coverage, and international awareness and the Western view of the world will be critically analyzed within the context of the prevalent news values that underpin free press and media coverage of the world. While evaluating the global discourse paramount to a sustained and dispassionate understanding of world events, this paper proposes an ethical framework that brings clarity devoid of sensationalism, partisanship, right-wing and left-wing interpretations to a breaking and dangerous development of a pandemic. As the world struggles to contain the coronavirus pandemic with death climbing close to 6,000 from late January to mid-March, 2020, the populations of the developed as well as the developing nations are beset with news media renditions of the crisis that are contradictory, confusing and evoking anxiety, fear and hysteria. How are we to understand differing news standards and news values? What lessons do we as journalism and mass media educators, researchers, and academics learn in order to construct a better news model and structure of media practice that addresses science, health, and media literacy among media practitioners, journalists, and news consumers? As traditional media struggles to cover the pandemic to its audience and consumers, social media from which an increasing number of consumers get their news have exerted their influence both in a positive way and in a negative manner. Even as the world struggles to grasp the full significance of the pandemic, the World Health Organization (WHO) has been feverishly battling an additional challenge related to the pandemic in what it termed an 'infodemic'—'an overabundance of information, some accurate and some not, that makes it hard for people to find trustworthy sources and reliable guidance when they need it.' There is, indeed, a need for journalism and news coverage in times of pandemics that reflect social responsibility and ethos of public service journalism. Social media and high-tech information corporations, collectively termed GAMAF—Google, Apple, Microsoft, Amazon, and Facebook – can team up with reliable traditional media—newspapers, magazines, book publishers, radio and television corporates—to ease public emotions and be helpful in times of a pandemic outbreak. GAMAF can, conceivably, weed out sensational and non-credible sources of coronavirus information, exotic cures offered for sale on a quick fix, and demonetize videos that exploit peoples’ vulnerabilities at the lowest ebb. Credible news of utility delivered in a sustained, calm, and reliable manner serves people in a meaningful and helpful way. The world’s consumers of news and information, indeed, deserve a healthy and trustworthy news media – at least in the time of pandemic COVID-19. Towards this end, the paper will propose a practical model for news media and journalistic coverage during times of a pandemic.

Keywords: COVID-19, international news flow, social media, social responsibility

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92 Transitioning Towards a Circular Economy in the Textile Industry: Approaches to Address Environmental Challenges

Authors: Atefeh Salehipoor

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Textiles play a vital role in human life, particularly in the form of clothing. However, the alarming rate at which textiles end up in landfills presents a significant environmental risk. With approximately one garbage truck per second being filled with discarded textiles, urgent measures are required to mitigate this trend. Governments and responsible organizations are calling upon various stakeholders to shift from a linear economy to a circular economy model in the textile industry. This article highlights several key approaches that can be undertaken to address this pressing issue. These approaches include the creation of renewable raw material sources, rethinking production processes, maximizing the use and reuse of textile products, implementing reproduction and recycling strategies, exploring redistribution to new markets, and finding innovative means to extend the lifespan of textiles. However, the rapid accumulation of textiles in landfills poses a significant threat to the environment. This article explores the urgent need for the textile industry to transition from a linear economy model to a circular economy model. The linear model, characterized by the creation, use, and disposal of textiles, is unsustainable in the long term. By adopting a circular economy approach, the industry can minimize waste, reduce environmental impact, and promote sustainable practices. This article outlines key approaches that can be undertaken to drive this transition. Approaches to Address Environmental Challenges: 1. Creation of Renewable Raw Materials Sources: Exploring and promoting the use of renewable and sustainable raw materials, such as organic cotton, hemp, and recycled fibers, can significantly reduce the environmental footprint of textile production. 2. Rethinking Production Processes: Implementing cleaner production techniques, optimizing resource utilization, and minimizing waste generation are crucial steps in reducing the environmental impact of textile manufacturing. 3. Maximizing Use and Reuse of Textile Products: Encouraging consumers to prolong the lifespan of textile products through proper care, maintenance, and repair services can reduce the frequency of disposal and promote a culture of sustainability. 4. Reproduction and Recycling Strategies: Investing in innovative technologies and infrastructure to enable efficient reproduction and recycling of textiles can close the loop and minimize waste generation. 5. Redistribution of Textiles to New Markets: Exploring opportunities to redistribute textiles to new and parallel markets, such as resale platforms, can extend their lifecycle and prevent premature disposal. 6. Improvising Means to Extend Textile Lifespan: Encouraging design practices that prioritize durability, versatility, and timeless aesthetics can contribute to prolonging the lifespan of textiles. Conclusion The textile industry must urgently transition from a linear economy to a circular economy model to mitigate the adverse environmental impact caused by textile waste. By implementing the outlined approaches, such as sourcing renewable raw materials, rethinking production processes, promoting reuse and recycling, exploring new markets, and extending the lifespan of textiles, stakeholders can work together to create a more sustainable and environmentally friendly textile industry. These measures require collective action and collaboration between governments, organizations, manufacturers, and consumers to drive positive change and safeguard the planet for future generations.

Keywords: textiles, circular economy, environmental challenges, renewable raw materials, production processes, reuse, recycling, redistribution, textile lifespan extension

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91 The Impact of China’s Waste Import Ban on the Waste Mining Economy in East Asia

Authors: Michael Picard

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This proposal offers to shed light on the changing legal geography of the global waste economy. Global waste recycling has become a multi-billion-dollar industry. NASDAQ predicts the emergence of a worldwide 1,296G$ waste management market between 2017 and 2022. Underlining this evolution, a new generation of preferential waste-trade agreements has emerged in the Pacific. In the last decade, Japan has concluded a series of bilateral treaties with Asian countries, and most recently with China. An agreement between Tokyo and Beijing was formalized on 7 May 2008, which forged an economic partnership on waste transfer and mining. The agreement set up International Recycling Zones, where certified recycling plants in China process industrial waste imported from Japan. Under the joint venture, Chinese companies salvage the embedded value from Japanese industrial discards, reprocess them and send them back to Japanese manufacturers, such as Mitsubishi and Panasonic. This circular economy is designed to convert surplus garbage into surplus value. Ever since the opening of Sino-Japanese eco-parks, millions of tons of plastic and e-waste have been exported from Japan to China every year. Yet, quite unexpectedly, China has recently closed its waste market to imports, jeopardizing Japan’s billion-dollar exports to China. China notified the WTO that, by the end of 2017, it would no longer accept imports of plastics and certain metals. Given China’s share of Japanese waste exports, a complete closure of China’s market would require Japan to find new uses for its recyclable industrial trash generated domestically every year. It remains to be seen how China will effectively implement its ban on waste imports, considering the economic interests at stake. At this stage, what remains to be clarified is whether China's ban on waste imports will negatively affect the recycling trade between Japan and China. What is clear, though, is the rapid transformation in the legal geography of waste mining in East-Asia. For decades, East-Asian waste trade had been tied up in an ‘ecologically unequal exchange’ between the Japanese core and the Chinese periphery. This global unequal waste distribution could be measured by the Environmental Stringency Index, which revealed that waste regulation was 39% weaker in the Global South than in Japan. This explains why Japan could legally export its hazardous plastic and electronic discards to China. The asymmetric flow of hazardous waste between Japan and China carried the colonial heritage of international law. The legal geography of waste distribution was closely associated to the imperial construction of an ecological trade imbalance between the Japanese source and the Chinese sink. Thus, China’s recent decision to ban hazardous waste imports is a sign of a broader ecological shift. As a global economic superpower, China announced to the world it would no longer be the planet’s junkyard. The policy change will have profound consequences on the global circulation of waste, re-routing global waste towards countries south of China, such as Vietnam and Malaysia. By the time the Berlin Conference takes place in May 2018, the presentation will be able to assess more accurately the effect of the Chinese ban on the transboundary movement of waste in Asia.

Keywords: Asia, ecological unequal exchange, global waste trade, legal geography

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90 Mesenchymal Stem Cells (MSC)-Derived Exosomes Could Alleviate Neuronal Damage and Neuroinflammation in Alzheimer’s Disease (AD) as Potential Therapy-Carrier Dual Roles

Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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89 Gamification of eHealth Business Cases to Enhance Rich Learning Experience

Authors: Kari Björn

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Introduction of games has expanded the application area of computer-aided learning tools to wide variety of age groups of learners. Serious games engage the learners into a real-world -type of simulation and potentially enrich the learning experience. Institutional background of a Bachelor’s level engineering program in Information and Communication Technology is introduced, with detailed focus on one of its majors, Health Technology. As part of a Customer Oriented Software Application thematic semester, one particular course of “eHealth Business and Solutions” is described and reflected in a gamified framework. Learning a consistent view into vast literature of business management, strategies, marketing and finance in a very limited time enforces selection of topics relevant to the industry. Health Technology is a novel and growing industry with a growing sector in consumer wearable devices and homecare applications. The business sector is attracting new entrepreneurs and impatient investor funds. From engineering education point of view the sector is driven by miniaturizing electronics, sensors and wireless applications. However, the market is highly consumer-driven and usability, safety and data integrity requirements are extremely high. When the same technology is used in analysis or treatment of patients, very strict regulatory measures are enforced. The paper introduces a course structure using gamification as a tool to learn the most essential in a new market: customer value proposition design, followed by a market entry game. Students analyze the existing market size and pricing structure of eHealth web-service market and enter the market as a steering group of their company, competing against the legacy players and with each other. The market is growing but has its rules of demand and supply balance. New products can be developed with an R&D-investment, and targeted to market with unique quality- and price-combinations. Product cost structure can be improved by investing to enhanced production capacity. Investments can be funded optionally by foreign capital. Students make management decisions and face the dynamics of the market competition in form of income statement and balance sheet after each decision cycle. The focus of the learning outcome is to understand customer value creation to be the source of cash flow. The benefit of gamification is to enrich the learning experience on structure and meaning of financial statements. The paper describes the gamification approach and discusses outcomes after two course implementations. Along the case description of learning challenges, some unexpected misconceptions are noted. Improvements of the game or the semi-gamified teaching pedagogy are discussed. The case description serves as an additional support to new game coordinator, as well as helps to improve the method. Overall, the gamified approach has helped to engage engineering student to business studies in an energizing way.

Keywords: engineering education, integrated curriculum, learning experience, learning outcomes

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88 Recognition of a Stacked Wave-Tide Dominated Fluvio-Marine Depositional System in an Ancient Rock Record, Proterozoic Simla Group, Lesser Himalaya, India

Authors: Ananya Mukhopadhyay, Priyanka Mazumdar, Tithi Banerjee, Alono Thorie

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Outcrop-based facies analysis of the Proterozoic rock successions in the Simla Basin, Lesser Himalaya was combined with the application of sequence stratigraphy to delineate the stages of wave-tide dominated fluvio-marine depositional system development. On this basis, a vertical profile depositional model has been developed. Based on lateral and vertical facies transitions, twenty lithofacies have been delineated from the lower-middle-upper part of the Simla Group, which are categorized into four major facies (FA1, FA2, FA3 and FA4) belts. FA1 documented from the Basantpur Formation (lower part of the Simla Group) indicates evolution of a distally steepened carbonate ramp deposits) highly influenced by sea level fluctuations, where outer, mid and inner ramp sub environments were identified. This transition from inner-mid to outer ramp is marked by a distinct slope break that has been widely cited as an example of a distally steepened ramp. The Basantpur carbonate ramp represents two different systems tracts: TST and HST which developed at different stages of sea level fluctuations. FA2 manifested from the Kunihar Formation (uncorformably overlying the Basantpur Formation) indicates deposition in a rimmed shelf (rich in microbial activity) sub-environment and bears the signature of an HST. FA3 delineated from the Chhaosa Formation (unconformably overlying the Kunihar mixed siliciclastic carbonates, middle part of the Simla Group) provides an excellent example of tide- and wave influenced deltaic deposit (FA3) which is characterized by wave dominated shorefacies deposit in the lower part, sharply overlain by fluvio-tidal channel and/or estuarine bay successions in the middle part followed by a tide dominated muddy tidal flat in the upper part. Despite large-scale progradation, the Chhaosa deltaic deposits are volumetrically dominated by transgressive estuarine deposits. The transgressive deposits are overlain by highstand units which are characterized by muddy tidal flat deposit. The Sanjauli Formation (upper part of the Simla Basin) records a major marine regression leading to the shifting of the shoreline basinward thereby resulting in fluvial incision on the top of the Chhaosa deltaic succession. The development of a braided fluvial system (FA4) with prominent fluvial incision is marked by presence of conglomerate-sandstone facies associations. Prominent fluvial incision on top of the delta deposits indicates the presence of sub-aerial TYPE 1 unconformity. The fluvial deposits mark the closure of sedimentation in the Simla basin that evolved during high frequency periods of coastal progradation and retrogradation. Each of the depositional cycles represents shoreline regression followed by transgression which is bounded by flooding surfaces and further followed by regression. The proposed depositional model in the present work deals with lateral facies variation due to shift in shore line along with fluctuations in accommodation space on a wave-tide influenced depositional system owing to fluctuations of sea level. This model will probably find its applicability in similar depositional setups.

Keywords: proterozoic, carbonate ramp, tide dominated delta, braided fluvial system, TYPE 1 unconformity

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87 Design and Implementation of a Hardened Cryptographic Coprocessor with 128-bit RISC-V Core

Authors: Yashas Bedre Raghavendra, Pim Vullers

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This study presents the design and implementation of an abstract cryptographic coprocessor, leveraging AMBA(Advanced Microcontroller Bus Architecture) protocols - APB (Advanced Peripheral Bus) and AHB (Advanced High-performance Bus), to enable seamless integration with the main CPU(Central processing unit) and enhance the coprocessor’s algorithm flexibility. The primary objective is to create a versatile coprocessor that can execute various cryptographic algorithms, including ECC(Elliptic-curve cryptography), RSA(Rivest–Shamir–Adleman), and AES (Advanced Encryption Standard) while providing a robust and secure solution for modern secure embedded systems. To achieve this goal, the coprocessor is equipped with a tightly coupled memory (TCM) for rapid data access during cryptographic operations. The TCM is placed within the coprocessor, ensuring quick retrieval of critical data and optimizing overall performance. Additionally, the program memory is positioned outside the coprocessor, allowing for easy updates and reconfiguration, which enhances adaptability to future algorithm implementations. Direct links are employed instead of DMA(Direct memory access) for data transfer, ensuring faster communication and reducing complexity. The AMBA-based communication architecture facilitates seamless interaction between the coprocessor and the main CPU, streamlining data flow and ensuring efficient utilization of system resources. The abstract nature of the coprocessor allows for easy integration of new cryptographic algorithms in the future. As the security landscape continues to evolve, the coprocessor can adapt and incorporate emerging algorithms, making it a future-proof solution for cryptographic processing. Furthermore, this study explores the addition of custom instructions into RISC-V ISE (Instruction Set Extension) to enhance cryptographic operations. By incorporating custom instructions specifically tailored for cryptographic algorithms, the coprocessor achieves higher efficiency and reduced cycles per instruction (CPI) compared to traditional instruction sets. The adoption of RISC-V 128-bit architecture significantly reduces the total number of instructions required for complex cryptographic tasks, leading to faster execution times and improved overall performance. Comparisons are made with 32-bit and 64-bit architectures, highlighting the advantages of the 128-bit architecture in terms of reduced instruction count and CPI. In conclusion, the abstract cryptographic coprocessor presented in this study offers significant advantages in terms of algorithm flexibility, security, and integration with the main CPU. By leveraging AMBA protocols and employing direct links for data transfer, the coprocessor achieves high-performance cryptographic operations without compromising system efficiency. With its TCM and external program memory, the coprocessor is capable of securely executing a wide range of cryptographic algorithms. This versatility and adaptability, coupled with the benefits of custom instructions and the 128-bit architecture, make it an invaluable asset for secure embedded systems, meeting the demands of modern cryptographic applications.

Keywords: abstract cryptographic coprocessor, AMBA protocols, ECC, RSA, AES, tightly coupled memory, secure embedded systems, RISC-V ISE, custom instructions, instruction count, cycles per instruction

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86 Decreased Tricarboxylic Acid (TCA) Cycle Staphylococcus aureus Increases Survival to Innate Immunity

Authors: Trenten Theis, Trevor Daubert, Kennedy Kluthe, Austin Nuxoll

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Staphylococcus aureus is a gram-positive bacterium responsible for an estimated 23,000 deaths in the United States and 25,000 deaths in the European Union annually. Recurring S. aureus bacteremia is associated with biofilm-mediated infections and can occur in 5 - 20% of cases, even with the use of antibiotics. Despite these infections being caused by drug-susceptible pathogens, they are surprisingly difficult to eradicate. One potential explanation for this is the presence of persister cells—a dormant type of cell that shows a high tolerance to antibiotic treatment. Recent studies have shown a connection between low intracellular ATP and persister cell formation. Specifically, this decrease in ATP, and therefore increase in persister cell formation, is due to an interrupted tricarboxylic acid (TCA) cycle. However, S. aureus persister cells’ role in pathogenesis remains unclear. Initial studies have shown that a fumC (TCA cycle gene) knockout survives challenge from aspects of the innate immune system better than wild-type S. aureus. Specifically, challenges from two antimicrobial peptides--LL-37 and hBD-3—show a log increase in survival of the fumC::N∑ strain compared to wild type S. aureus after 18 hours. Furthermore, preliminary studies show that the fumC knockout has a log more survival within a macrophage. These data lead us to hypothesize that the fumC knockout is better suited to other aspects of the innate immune system compared to wild-type S. aureus. To further investigate the mechanism for increased survival of fumC::N∑ within a macrophage, we tested bacterial growth in the presence of reactive oxygen species (ROS), reactive nitrogen species (RNS), and a low pH. Preliminary results suggest that the fumC knockout has increased growth compared to wild-type S. aureus in the presence of all three antimicrobial factors; however, no difference was observed in any single factor alone. To investigate survival within a host, a nine-day biofilm-associated catheter infection was performed on 6–8-week-old male and female C57Bl/6 mice. Although both sexes struggled to clear the infection, female mice were trending toward more frequently clearing the HG003 wild-type infection compared to the fumC::N∑ infection. One possible reason for the inability to reduce the bacterial burden is that biofilms are largely composed of persister cells. To test this hypothesis further, flow cytometry in conjunction with a persister cell marker was used to measure persister cells within a biofilm. Cap5A (a known persister cell marker) expression was found to be increased in a maturing biofilm, with the lowest levels of expression seen in immature biofilms and the highest expression exhibited by the 48-hour biofilm. Additionally, bacterial cells in a biofilm state closely resemble persister cells and exhibit reduced membrane potential compared to cells in planktonic culture, further suggesting biofilms are largely made up of persister cells. These data may provide an explanation as to why infections caused by antibiotic-susceptible strains remain difficult to treat.

Keywords: antibiotic tolerance, Staphylococcus aureus, host-pathogen interactions, microbial pathogenesis

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85 Contribution of Research to Innovation Management in the Traditional Fruit Production

Authors: Camille Aouinaït, Danilo Christen, Christoph Carlen

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Introduction: Small and Medium-sized Enterprises (SMEs) are facing different challenges such as pressures on environmental resources, the rise of downstream power, and trade liberalization. Remaining competitive by implementing innovations and engaging in collaborations could be a strategic solution. In Switzerland, the Federal Institute for Research in Agriculture (Agroscope), the Federal schools of technology (EPFL and ETHZ), Cantonal universities and Universities of Applied Sciences (UAS) can provide substantial inputs. UAS were developed with specific missions to match the labor markets and society needs. Research projects produce patents, publications and improved networks of scientific expertise. The study’s goal is to measure the contribution of UAS and research organization to innovation and the impact of collaborations with partners in the non-academic environment in Swiss traditional fruit production. Materials and methods: The European projects Traditional Food Network to improve the transfer of knowledge for innovation (TRAFOON) and Social Impact Assessment of Productive Interactions between science and society (SIAMPI) frame the present study. The former aims to fill the gap between the needs of traditional food producing SMEs and innovations implemented following European projects. The latter developed a method to assess the impacts of scientific research. On one side, interviews with market players have been performed to make an inventory of needs of Swiss SMEs producing apricots and berries. The participative method allowed matching the current needs and the existing innovations coming from past European projects. Swiss stakeholders (e.g. producers, retailers, an inter-branch organization of fruits and vegetables) directly rated the needs on a five-Likert scale. To transfer the knowledge to SMEs, training workshops have been organized for apricot and berries actors separately, on specific topics. On the other hand, a mapping of a social network is drawn to characterize the links between actors, with a focus on the Swiss canton of Valais and UAS Valais Wallis. Type and frequency of interactions among actors have identified thanks to interviews. Preliminary results: A list of 369 SMEs needs grouped in 22 categories was produced with 37 fulfilled questionnaires. Swiss stakeholders rated 31 needs very important. Training workshops on apricot are focusing on varietal innovations, storage, disease (bacterial blight), pest (Drosophila suzukii), sorting and rootstocks. Entrepreneurship was targeted through trademark discussions in berry production. The UAS Valais Wallis collaborated on a few projects with Agroscope along with industries, at European and national levels. Political and public bodies interfere with the central area of agricultural vulgarization that induces close relationships between the research and the practical side. Conclusions: The needs identified by Swiss stakeholders are becoming part of training workshops to incentivize innovations. The UAS Valais Wallis takes part in collaboration projects with the research environment and market players that bring innovations helping SMEs in their contextual environment. Then, a Strategic Research and Innovation Agenda will be created in order to pursue research and answer the issues facing by SMEs.

Keywords: agriculture, innovation, knowledge transfer, university and research collaboration

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84 Anajaa-Visual Substitution System: A Navigation Assistive Device for the Visually Impaired

Authors: Juan Pablo Botero Torres, Alba Avila, Luis Felipe Giraldo

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Independent navigation and mobility through unknown spaces pose a challenge for the autonomy of visually impaired people (VIP), who have relied on the use of traditional assistive tools like the white cane and trained dogs. However, emerging visually assistive technologies (VAT) have proposed several human-machine interfaces (HMIs) that could improve VIP’s ability for self-guidance. Hereby, we introduce the design and implementation of a visually assistive device, Anajaa – Visual Substitution System (AVSS). This system integrates ultrasonic sensors with custom electronics, and computer vision models (convolutional neural networks), in order to achieve a robust system that acquires information of the surrounding space and transmits it to the user in an intuitive and efficient manner. AVSS consists of two modules: the sensing and the actuation module, which are fitted to a chest mount and belt that communicate via Bluetooth. The sensing module was designed for the acquisition and processing of proximity signals provided by an array of ultrasonic sensors. The distribution of these within the chest mount allows an accurate representation of the surrounding space, discretized in three different levels of proximity, ranging from 0 to 6 meters. Additionally, this module is fitted with an RGB-D camera used to detect potentially threatening obstacles, like staircases, using a convolutional neural network specifically trained for this purpose. Posteriorly, the depth data is used to estimate the distance between the stairs and the user. The information gathered from this module is then sent to the actuation module that creates an HMI, by the means of a 3x2 array of vibration motors that make up the tactile display and allow the system to deliver haptic feedback. The actuation module uses vibrational messages (tactones); changing both in amplitude and frequency to deliver different awareness levels according to the proximity of the obstacle. This enables the system to deliver an intuitive interface. Both modules were tested under lab conditions, and the HMI was additionally tested with a focal group of VIP. The lab testing was conducted in order to establish the processing speed of the computer vision algorithms. This experimentation determined that the model can process 0.59 frames per second (FPS); this is considered as an adequate processing speed taking into account that the walking speed of VIP is 1.439 m/s. In order to test the HMI, we conducted a focal group composed of two females and two males between the ages of 35-65 years. The subject selection was aided by the Colombian Cooperative of Work and Services for the Sightless (COOTRASIN). We analyzed the learning process of the haptic messages throughout five experimentation sessions using two metrics: message discrimination and localization success. These correspond to the ability of the subjects to recognize different tactones and locate them within the tactile display. Both were calculated as the mean across all subjects. Results show that the focal group achieved message discrimination of 70% and a localization success of 80%, demonstrating how the proposed HMI leads to the appropriation and understanding of the feedback messages, enabling the user’s awareness of its surrounding space.

Keywords: computer vision on embedded systems, electronic trave aids, human-machine interface, haptic feedback, visual assistive technologies, vision substitution systems

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83 Investigating Role of Autophagy in Cispaltin Induced Stemness and Chemoresistance in Oral Squamous Cell Carcinoma

Authors: Prajna Paramita Naik, Sujit Kumar Bhutia

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Background: Regardless of the development multimodal treatment strategies, oral squamous cell carcinoma (OSCC) is often associated with a high rate of recurrence, metastasis and chemo- and radio- resistance. The present study inspected the relevance of CD44, ABCB1 and ADAM17 expression as a putative stem cell compartment in oral squamous cell carcinoma (OSCC) and deciphered the role of autophagy in regulating the expression of aforementioned proteins, stemness and chemoresistance. Methods: A retrospective analysis of CD44, ABCB1 and ADAM17 expression with respect to the various clinicopathological factors of sixty OSCC patients were determined via immunohistochemistry. The correlation among CD44, ABCB1 and ADAM17 expression was established. Sphere formation assay, flow cytometry and fluorescence microscopy were conducted to elucidate the stemness and chemoresistance nature of established cisplatin-resistant oral cancer cells (FaDu). The pattern of expression of CD44, ABCB1 and ADAM17 in parental (FaDu-P) and resistant FaDu cells (FaDu-CDDP-R) were investigated through fluorescence microscopy. Western blot analysis of autophagy marker proteins was performed to compare the status of autophagy in parental and resistant FaDu cell. To investigate the role of autophagy in chemoresistance and stemness, sphere formation assay, immunofluorescence and Western blot analysis was performed post transfection with siATG14 and the level of expression of autophagic proteins, mitochondrial protein and stemness-associated proteins were analyzed. The statistical analysis was performed by GraphPad Prism 4.0 software. p-value was defined as follows: not significant (n.s.): p > 0.05;*: p ≤ 0.05; **: p ≤ 0.01; ***: p ≤ 0.001; ****: p ≤ 0.0001 were considered statistically significant. Results: In OSCC, high CD44, ABCB1 and ADAM17 expression were significantly correlated with higher tumor grades and poor differentiation. However, the expression of these proteins was not related to the age and sex of OSCC patients. Moreover, the expression of CD44, ABCB1 and ADAM17 were positively correlated with each other. In vitro and OSCC tissue double labeling experiment data showed that CD44+ cells were highly associated with ABCB1 and ADAM17 expression. Further, FaDu-CDDP-R cells showed higher sphere forming capacity along with increased fraction of the CD44+ population and β-catenin expression FaDu-CDDP-R cells also showed accelerated expression of CD44, ABCB1 and ADAM17. A comparatively higher autophagic flux was observed in FaDu-CDDP-R against FaDu-P cells. The expression of mitochondrial proteins was noticeably reduced in resistant cells as compared to parental cells indicating the occurrence of autophagy-mediated mitochondrial degradation in oral cancer. Moreover, inhibition of autophagy was coupled with the decreased formation of orospheres suggesting autophagy-mediated stemness in oral cancer. Blockade of autophagy was also found to induce the restoration of mitochondrial proteins in FaDu-CDDP-R cells indicating the involvement of mitophagy in chemoresistance. Furthermore, a reduced expression of CD44, ABCB1 and ADAM17 was also observed in ATG14 deficient cells FaDu-P and FaDu-CDDP-R cells. Conclusion: The CD44+ ⁄ABCB1+ ⁄ADAM17+ expression in OSCC might be associated with chemoresistance and a putative CSC compartment. Further, the present study highlights the contribution of mitophagy in chemoresistance and confirms the potential involvement of autophagic regulation in acquisition of stem-like characteristics in OSCC.

Keywords: ABCB1, ADAM17, autophagy, CD44, chemoresistance, mitophagy, OSCC, stemness

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82 Experimental Study of the Behavior of Elongated Non-spherical Particles in Wall-Bounded Turbulent Flows

Authors: Manuel Alejandro Taborda Ceballos, Martin Sommerfeld

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Transport phenomena and dispersion of non-spherical particle in turbulent flows are found everywhere in industrial application and processes. Powder handling, pollution control, pneumatic transport, particle separation are just some examples where the particle encountered are not only spherical. These types of multiphase flows are wall bounded and mostly highly turbulent. The particles found in these processes are rarely spherical but may have various shapes (e.g., fibers, and rods). Although research related to the behavior of regular non-spherical particles in turbulent flows has been carried out for many years, it is still necessary to refine models, especially near walls where the interaction fiber-wall changes completely its behavior. Imaging-based experimental studies on dispersed particle-laden flows have been applied for many decades for a detailed experimental analysis. These techniques have the advantages that they provide field information in two or three dimensions, but have a lower temporal resolution compared to point-wise techniques such as PDA (phase-Doppler anemometry) and derivations therefrom. The applied imaging techniques in dispersed two-phase flows are extensions from classical PIV (particle image velocimetry) and PTV (particle tracking velocimetry) and the main emphasis was simultaneous measurement of the velocity fields of both phases. In a similar way, such data should also provide adequate information for validating the proposed models. Available experimental studies on the behavior of non-spherical particles are uncommon and mostly based on planar light-sheet measurements. Especially for elongated non-spherical particles, however, three-dimensional measurements are needed to fully describe their motion and to provide sufficient information for validation of numerical computations. For further providing detailed experimental results allowing a validation of numerical calculations of non-spherical particle dispersion in turbulent flows, a water channel test facility was built around a horizontal closed water channel. Into this horizontal main flow, a small cross-jet laden with fiber-like particles was injected, which was also solely driven by gravity. The dispersion of the fibers was measured by applying imaging techniques based on a LED array for backlighting and high-speed cameras. For obtaining the fluid velocity fields, almost neutrally buoyant tracer was used. The discrimination between tracer and fibers was done based on image size which was also the basis to determine fiber orientation with respect to the inertial coordinate system. The synchronous measurement of fluid velocity and fiber properties also allow the collection of statistics of fiber orientation, velocity fields of tracer and fibers, the angular velocity of the fibers and the orientation between fiber and instantaneous relative velocity. Consequently, an experimental study the behavior of elongated non-spherical particles in wall bounded turbulent flows was achieved. The development of a comprehensive analysis was succeeded, especially near the wall region, where exists hydrodynamic wall interaction effects (e.g., collision or lubrication) and abrupt changes of particle rotational velocity. This allowed us to predict numerically afterwards the behavior of non-spherical particles within the frame of the Euler/Lagrange approach, where the particles are therein treated as “point-particles”.

Keywords: crossflow, non-spherical particles, particle tracking velocimetry, PIV

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81 Correlation of Clinical and Sonographic Findings with Cytohistology for Diagnosis of Ovarian Tumours

Authors: Meenakshi Barsaul Chauhan, Aastha Chauhan, Shilpa Hurmade, Rajeev Sen, Jyotsna Sen, Monika Dalal

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Introduction: Ovarian masses are common forms of neoplasm in women and represent 2/3rd of gynaecological malignancies. A pre-operative suggestion of malignancy can guide the gynecologist to refer women with suspected pelvic mass to a gynecological oncologist for appropriate therapy and optimized treatment, which can improve survival. In the younger age group preoperative differentiation into benign or malignant pathology can decide for conservative or radical surgery. Imaging modalities have a definite role in establishing the diagnosis. By using International Ovarian Tumor Analysis (IOTA) classification with sonography, costly radiological methods like Magnetic Resonance Imaging (MRI) / computed tomography (CT) scan can be reduced, especially in developing countries like India. Thus, this study is being undertaken to evaluate the role of clinical methods and sonography for diagnosis of the nature of the ovarian tumor. Material And Methods: This prospective observational study was conducted on 40 patients presenting with ovarian masses, in the Department of Obstetrics and Gynaecology, at a tertiary care center in northern India. Functional cysts were excluded. Ultrasonography and color Doppler were performed on all the cases.IOTA rules were applied, which take into account locularity, size, presence of solid components, acoustic shadow, dopper flow etc . Magnetic Resonance Imaging (MRI) / computed tomography (CT) scans abdomen and pelvis were done in cases where sonography was inconclusive. In inoperable cases, Fine needle aspiration cytology (FNAC) was done. The histopathology report after surgery and cytology report after FNAC was correlated statistically with the pre-operative diagnosis made clinically and sonographically using IOTA rules. Statistical Analysis: Descriptive measures were analyzed by using mean and standard deviation and the Student t-test was applied and the proportion was analyzed by applying the chi-square test. Inferential measures were analyzed by sensitivity, specificity, negative predictive value, and positive predictive value. Results: Provisional diagnosis of the benign tumor was made in 16(42.5%) and of the malignant tumor was made in 24(57.5%) patients on the basis of clinical findings. With IOTA simple rules on sonography, 15(37.5%) were found to be benign, while 23 (57.5%) were found to be malignant and findings were inconclusive in 2 patients (5%). FNAC/Histopathology reported that benign ovarian tumors were 14 (35%) and 26(65%) were malignant, which was taken as the gold standard. The clinical finding alone was found to have a sensitivity of 66.6% and a specificity of 90.9%. USG alone had a sensitivity of 86% and a specificity of 80%. When clinical findings and IOTA simple rules of sonography were combined (excluding inconclusive masses), the sensitivity and specificity were 83.3% and 92.3%, respectively. While including inconclusive masses, sensitivity came out to be 91.6% and specificity was 89.2. Conclusion: IOTA's simple sonography rules are highly sensitive and specific in the prediction of ovarian malignancy and also easy to use and easily reproducible. Thus, combining clinical examination with USG will help in the better management of patients in terms of time, cost and better prognosis. This will also avoid the need for costlier modalities like CT, and MRI.

Keywords: benign, international ovarian tumor analysis classification, malignant, ovarian tumours, sonography

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80 International Coffee Trade in Solidarity with the Zapatista Rebellion: Anthropological Perspectives on Commercial Ethics within Political Antagonistic Movements

Authors: Miria Gambardella

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The influence of solidarity demonstrations towards the Zapatista National Liberation Army has been constantly present over the years, both locally and internationally, guaranteeing visibility to the cause, shaping the movement’s choices, and influencing its hopes of impact worldwide. Most of the coffee produced by the autonomous cooperatives from Chiapas is exported, therefore making coffee trade the main income from international solidarity networks. The question arises about the implications of the relations established between the communities in resistance in Southeastern Mexico and international solidarity movements, specifically on the strategies adopted to conciliate army's demands for autonomy and economic asymmetries between Zapatista cooperatives producing coffee and European collectives who hold purchasing power. In order to deepen the inquiry on those topics, a year-long multi-site investigation was carried out. The first six months of fieldwork were based in Barcelona, where Zapatista coffee was first traded in Spain and where one of the historical and most important European solidarity groups can be found. The last six months of fieldwork were carried out directly in Chiapas, in contact with coffee producers, Zapatista political authorities, international activists as well as vendors, and the rest of the network implicated in coffee production, roasting, and sale. The investigation was based on qualitative research methods, including participatory observation, focus groups, and semi-structured interviews. The analysis did not only focus on retracing the steps of the market chain as if it could be considered a linear and unilateral process, but it rather aimed at exploring actors’ reciprocal perceptions, roles, and dynamics of power. Demonstrations of solidarity and the money circulation they imply aim at changing the system in place and building alternatives, among other things, on the economic level. This work analyzes the formulation of discourse and the organization of solidarity activities that aim at building opportunities for action within a highly politicized economic sphere to which access must be regularly legitimized. The meaning conveyed by coffee is constructed on a symbolic level by the attribution of moral criteria to transactions. The latter participate in the construction of imaginaries that circulate through solidarity movements with the Zapatista rebellion. Commercial exchanges linked to solidarity networks turned out to represent much more than monetary transactions. The social, cultural, and political spheres are invested by ethics, which penetrates all aspects of militant action. It is at this level that the boundaries of different collective actors connect, contaminating each other: merely following the money flow would have been limiting in order to account for a reality within which imaginary is one of the main currencies. The notions of “trust”, “dignity” and “reciprocity” are repeatedly mobilized to negotiate discontinuous and multidirectional flows in the attempt to balance and justify commercial relations in a politicized context that characterizes its own identity through demonizing “market economy” and its dehumanizing powers.

Keywords: coffee trade, economic anthropology, international cooperation, Zapatista National Liberation Army

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79 A Quantitative Case Study Analysis of Store Format Contributors to U.S. County Obesity Prevalence in Virginia

Authors: Bailey Houghtaling, Sarah Misyak

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Food access; the availability, affordability, convenience, and desirability of food and beverage products within communities, is influential on consumers’ purchasing and consumption decisions. These variables may contribute to lower dietary quality scores and a higher obesity prevalence documented among rural and disadvantaged populations in the United States (U.S.). Current research assessing linkages between food access and obesity outcomes has primarily focused on distance to a traditional grocery/supermarket store as a measure of optimality. However, low-income consumers especially, including U.S. Department of Agriculture’s Supplemental Nutrition Assistance Program (SNAP) participants, seem to utilize non-traditional food store formats with greater frequency for household dietary needs. Non-traditional formats have been associated with less nutritious food and beverage options and consumer purchases that are high in saturated fats, added sugars, and sodium. Authors’ formative research indicated differences by U.S. region and rurality in the distribution of traditional and non-traditional SNAP-authorized food store formats. Therefore, using Virginia as a case study, the purpose of this research was to determine if a relationship between store format, rurality, and obesity exists. This research applied SNAP-authorized food store data (food access points for SNAP as well as non-SNAP consumers) and obesity prevalence data by Virginia county using publicly available databases: (1) SNAP Retailer Locator, and; (2) U.S. County Health Rankings. The alpha level was set a priori at 0.05. All Virginia SNAP-authorized stores (n=6,461) were coded by format – grocery, drug, mass merchandiser, club, convenience, dollar, supercenter, specialty, farmers market, independent grocer, and non-food store. Simple linear regression was applied primarily to assess the relationship between store format and obesity. Thereafter, multiple variables were added to the regression to account for potential moderating relationships (e.g., county income, rurality). Convenience, dollar, non-food or restaurant, mass merchandiser, farmers market, and independent grocer formats were significantly, positively related to obesity prevalence. Upon controlling for urban-rural status and income, results indicated the following formats to be significantly related to county obesity prevalence with a small, positive effect: convenience (p=0.010), accounting for 0.3% of the variance in obesity prevalence; dollar (p=0.005; 0.5% of the variance), and; non-food (p=0.030; 1.3% of the variance) formats. These results align with current literature on consumer behavior at non-traditional formats. For example, consumers’ food and beverage purchases at convenience and dollar stores are documented to be high in saturated fats, added sugars, and sodium. Further, non-food stores (i.e., quick-serve restaurants) often contribute to a large portion of U.S. consumers’ dietary intake and thus poor dietary quality scores. Current food access research investigates grocery/supermarket access and obesity outcomes. These results suggest more research is needed that focuses on non-traditional food store formats. Nutrition interventions within convenience, dollar, and non-food stores, for example, that aim to enhance not only healthy food access but the affordability, convenience, and desirability of nutritious food and beverage options may impact obesity rates in Virginia. More research is warranted utilizing the presented investigative framework in other U.S. and global regions to explore the role and the potential of non-traditional food store formats to prevent and reduce obesity.

Keywords: food access, food store format, non-traditional food stores, obesity prevalence

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78 Implementation of Smart Card Automatic Fare Collection Technology in Small Transit Agencies for Standards Development

Authors: Walter E. Allen, Robert D. Murray

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Many large transit agencies have adopted RFID technology and electronic automatic fare collection (AFC) or smart card systems, but small and rural agencies remain tied to obsolete manual, cash-based fare collection. Small countries or transit agencies can benefit from the implementation of smart card AFC technology with the promise of increased passenger convenience, added passenger satisfaction and improved agency efficiency. For transit agencies, it reduces revenue loss, improves passenger flow and bus stop data. For countries, further implementation into security, distribution of social services or currency transactions can provide greater benefits. However, small countries or transit agencies cannot afford expensive proprietary smart card solutions typically offered by the major system suppliers. Deployment of Contactless Fare Media System (CFMS) Standard eliminates the proprietary solution, ultimately lowering the cost of implementation. Acumen Building Enterprise, Inc. chose the Yuma County Intergovernmental Public Transportation Authority (YCIPTA) existing proprietary YCAT smart card system to implement CFMS. The revised system enables the purchase of fare product online with prepaid debit or credit cards using the Payment Gateway Processor. Open and interoperable smart card standards for transit have been developed. During the 90-day Pilot Operation conducted, the transit agency gathered the data from the bus AcuFare 200 Card Reader, loads (copies) the data to a USB Thumb Drive and uploads the data to the Acumen Host Processing Center for consolidation of the data into the transit agency master data file. The transition from the existing proprietary smart card data format to the new CFMS smart card data format was transparent to the transit agency cardholders. It was proven that open standards and interoperability design can work and reduce both implementation and operational costs for small transit agencies or countries looking to expand smart card technology. Acumen was able to avoid the implementation of the Payment Card Industry (PCI) Data Security Standards (DSS) which is expensive to develop and costly to operate on a continuing basis. Due to the substantial additional complexities of implementation and the variety of options presented to the transit agency cardholder, Acumen chose to implement only the Directed Autoload. To improve the implementation efficiency and the results for a similar undertaking, it should be considered that some passengers lack credit cards and are averse to technology. There are more than 1,300 small and rural agencies in the United States. This grows by 10 fold when considering small countries or rural locations throughout Latin American and the world. Acumen is evaluating additional countries, sites or transit agency that can benefit from the smart card systems. Frequently, payment card systems require extensive security procedures for implementation. The Project demonstrated the ability to purchase fare value, rides and passes with credit cards on the internet at a reasonable cost without highly complex security requirements.

Keywords: automatic fare collection, near field communication, small transit agencies, smart cards

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77 Temporal and Spacial Adaptation Strategies in Aerodynamic Simulation of Bluff Bodies Using Vortex Particle Methods

Authors: Dario Milani, Guido Morgenthal

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Fluid dynamic computation of wind caused forces on bluff bodies e.g light flexible civil structures or high incidence of ground approaching airplane wings, is one of the major criteria governing their design. For such structures a significant dynamic response may result, requiring the usage of small scale devices as guide-vanes in bridge design to control these effects. The focus of this paper is on the numerical simulation of the bluff body problem involving multiscale phenomena induced by small scale devices. One of the solution methods for the CFD simulation that is relatively successful in this class of applications is the Vortex Particle Method (VPM). The method is based on a grid free Lagrangian formulation of the Navier-Stokes equations, where the velocity field is modeled by particles representing local vorticity. These vortices are being convected due to the free stream velocity as well as diffused. This representation yields the main advantages of low numerical diffusion, compact discretization as the vorticity is strongly localized, implicitly accounting for the free-space boundary conditions typical for this class of FSI problems, and a natural representation of the vortex creation process inherent in bluff body flows. When the particle resolution reaches the Kolmogorov dissipation length, the method becomes a Direct Numerical Simulation (DNS). However, it is crucial to note that any solution method aims at balancing the computational cost against the accuracy achievable. In the classical VPM method, if the fluid domain is discretized by Np particles, the computational cost is O(Np2). For the coupled FSI problem of interest, for example large structures such as long-span bridges, the aerodynamic behavior may be influenced or even dominated by small structural details such as barriers, handrails or fairings. For such geometrically complex and dimensionally large structures, resolving the complete domain with the conventional VPM particle discretization might become prohibitively expensive to compute even for moderate numbers of particles. It is possible to reduce this cost either by reducing the number of particles or by controlling its local distribution. It is also possible to increase the accuracy of the solution without increasing substantially the global computational cost by computing a correction of the particle-particle interaction in some regions of interest. In this paper different strategies are presented in order to extend the conventional VPM method to reduce the computational cost whilst resolving the required details of the flow. The methods include temporal sub stepping to increase the accuracy of the particles convection in certain regions as well as dynamically re-discretizing the particle map to locally control the global and the local amount of particles. Finally, these methods will be applied on a test case and the improvements in the efficiency as well as the accuracy of the proposed extension to the method are presented. The important benefits in terms of accuracy and computational cost of the combination of these methods will be thus presented as long as their relevant applications.

Keywords: adaptation, fluid dynamic, remeshing, substepping, vortex particle method

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76 Phenotype and Psychometric Characterization of Phelan-Mcdermid Syndrome Patients

Authors: C. Bel, J. Nevado, F. Ciceri, M. Ropacki, T. Hoffmann, P. Lapunzina, C. Buesa

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Background: The Phelan-McDermid syndrome (PMS) is a genetic disorder caused by the deletion of the terminal region of chromosome 22 or mutation of the SHANK3 gene. Shank3 disruption in mice leads to dysfunction of synaptic transmission, which can be restored by epigenetic regulation with both Lysine Specific Demethylase 1 (LSD1) inhibitors. PMS subjects result in a variable degree of intellectual disability, delay or absence of speech, autistic spectrum disorders symptoms, low muscle tone, motor delays and epilepsy. Vafidemstat is an LSD1 inhibitor in Phase II clinical development with a well-established and favorable safety profile, and data supporting the restoration of memory and cognition defects as well as reduction of agitation and aggression in several animal models and clinical studies. Therefore, vafidemstat has the potential to become a first-in-class precision medicine approach to treat PMS patients. Aims: The goal of this research is to perform an observational trial to psychometrically characterize individuals carrying deletions in SHANK3 and build a foundation for subsequent precision psychiatry clinical trials with vafidemstat. Methodology: This study is characterizing the clinical profile of 20 to 40 subjects, > 16-year-old, with genotypically confirmed PMS diagnosis. Subjects will complete a battery of neuropsychological scales, including the Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, Escala de Observación para el Diagnostico del Autismo (Autism Diagnostic Observational Scale) (ADOS)-2, the Battelle Developmental Inventory and the Behavior Problems Inventory (BPI). Results: By March 2021, 19 patients have been enrolled. Unsupervised hierarchical clustering of the results obtained so far identifies 3 groups of patients, characterized by different profiles of cognitive and behavioral scores. The first cluster is characterized by low Battelle age, high ADOS and low Vineland, RBQ and BPI scores. Low Vineland, RBQ and BPI scores are also detected in the second cluster, which in contrast has high Battelle age and low ADOS scores. The third cluster is somewhat in the middle for the Battelle, Vineland and ADOS scores while displaying the highest levels of aggression (high BPI) and repeated behaviors (high RBQ). In line with the observation that female patients are generally affected by milder forms of autistic symptoms, no male patients are present in the second cluster. Dividing the results by gender highlights that male patients in the third cluster are characterized by a higher frequency of aggression, whereas female patients from the same cluster display a tendency toward higher repetitive behavior. Finally, statistically significant differences in deletion sizes are detected comparing the three clusters (also after correcting for gender), and deletion size appears to be positively correlated with ADOS and negatively correlated with Vineland A and C scores. No correlation is detected between deletion size and the BPI and RBQ scores. Conclusions: Precision medicine may open a new way to understand and treat Central Nervous System disorders. Epigenetic dysregulation has been proposed to be an important mechanism in the pathogenesis of schizophrenia and autism. Vafidemstat holds exciting therapeutic potential in PMS, and this study will provide data regarding the optimal endpoints for a future clinical study to explore vafidemstat ability to treat shank3-associated psychiatric disorders.

Keywords: autism, epigenetics, LSD1, personalized medicine

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75 Transformers in Gene Expression-Based Classification

Authors: Babak Forouraghi

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A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations of previous approaches, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with attention mechanism. In a previous work on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: transformers, generative ai, gene expression design, classification

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74 Simulation-based Decision Making on Intra-hospital Patient Referral in a Collaborative Medical Alliance

Authors: Yuguang Gao, Mingtao Deng

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The integration of independently operating hospitals into a unified healthcare service system has become a strategic imperative in the pursuit of hospitals’ high-quality development. Central to the concept of group governance over such transformation, exemplified by a collaborative medical alliance, is the delineation of shared value, vision, and goals. Given the inherent disparity in capabilities among hospitals within the alliance, particularly in the treatment of different diseases characterized by Disease Related Groups (DRG) in terms of effectiveness, efficiency and resource utilization, this study aims to address the centralized decision-making of intra-hospital patient referral within the medical alliance to enhance the overall production and quality of service provided. We first introduce the notion of production utility, where a higher production utility for a hospital implies better performance in treating patients diagnosed with that specific DRG group of diseases. Then, a Discrete-Event Simulation (DES) framework is established for patient referral among hospitals, where patient flow modeling incorporates a queueing system with fixed capacities for each hospital. The simulation study begins with a two-member alliance. The pivotal strategy examined is a "whether-to-refer" decision triggered when the bed usage rate surpasses a predefined threshold for either hospital. Then, the decision encompasses referring patients to the other hospital based on DRG groups’ production utility differentials as well as bed availability. The objective is to maximize the total production utility of the alliance while minimizing patients’ average length of stay and turnover rate. Thus the parameter under scrutiny is the bed usage rate threshold, influencing the efficacy of the referral strategy. Extending the study to a three-member alliance, which could readily be generalized to multi-member alliances, we maintain the core setup while introducing an additional “which-to-refer" decision that involves referring patients with specific DRG groups to the member hospital according to their respective production utility rankings. The overarching goal remains consistent, for which the bed usage rate threshold is once again a focal point for analysis. For the two-member alliance scenario, our simulation results indicate that the optimal bed usage rate threshold hinges on the discrepancy in the number of beds between member hospitals, the distribution of DRG groups among incoming patients, and variations in production utilities across hospitals. Transitioning to the three-member alliance, we observe similar dependencies on these parameters. Additionally, it becomes evident that an imbalanced distribution of DRG diagnoses and further disparity in production utilities among member hospitals may lead to an increase in the turnover rate. In general, it was found that the intra-hospital referral mechanism enhances the overall production utility of the medical alliance compared to individual hospitals without partnership. Patients’ average length of stay is also reduced, showcasing the positive impact of the collaborative approach. However, the turnover rate exhibits variability based on parameter setups, particularly when patients are redirected within the alliance. In conclusion, the re-structuring of diagnostic disease groups within the medical alliance proves instrumental in improving overall healthcare service outcomes, providing a compelling rationale for the government's promotion of patient referrals within collaborative medical alliances.

Keywords: collaborative medical alliance, disease related group, patient referral, simulation

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73 Flood Early Warning and Management System

Authors: Yogesh Kumar Singh, T. S. Murugesh Prabhu, Upasana Dutta, Girishchandra Yendargaye, Rahul Yadav, Rohini Gopinath Kale, Binay Kumar, Manoj Khare

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The Indian subcontinent is severely affected by floods that cause intense irreversible devastation to crops and livelihoods. With increased incidences of floods and their related catastrophes, an Early Warning System for Flood Prediction and an efficient Flood Management System for the river basins of India is a must. Accurately modeled hydrological conditions and a web-based early warning system may significantly reduce economic losses incurred due to floods and enable end users to issue advisories with better lead time. This study describes the design and development of an EWS-FP using advanced computational tools/methods, viz. High-Performance Computing (HPC), Remote Sensing, GIS technologies, and open-source tools for the Mahanadi River Basin of India. The flood prediction is based on a robust 2D hydrodynamic model, which solves shallow water equations using the finite volume method. Considering the complexity of the hydrological modeling and the size of the basins in India, it is always a tug of war between better forecast lead time and optimal resolution at which the simulations are to be run. High-performance computing technology provides a good computational means to overcome this issue for the construction of national-level or basin-level flash flood warning systems having a high resolution at local-level warning analysis with a better lead time. High-performance computers with capacities at the order of teraflops and petaflops prove useful while running simulations on such big areas at optimum resolutions. In this study, a free and open-source, HPC-based 2-D hydrodynamic model, with the capability to simulate rainfall run-off, river routing, and tidal forcing, is used. The model was tested for a part of the Mahanadi River Basin (Mahanadi Delta) with actual and predicted discharge, rainfall, and tide data. The simulation time was reduced from 8 hrs to 3 hrs by increasing CPU nodes from 45 to 135, which shows good scalability and performance enhancement. The simulated flood inundation spread and stage were compared with SAR data and CWC Observed Gauge data, respectively. The system shows good accuracy and better lead time suitable for flood forecasting in near-real-time. To disseminate warning to the end user, a network-enabled solution is developed using open-source software. The system has query-based flood damage assessment modules with outputs in the form of spatial maps and statistical databases. System effectively facilitates the management of post-disaster activities caused due to floods, like displaying spatial maps of the area affected, inundated roads, etc., and maintains a steady flow of information at all levels with different access rights depending upon the criticality of the information. It is designed to facilitate users in managing information related to flooding during critical flood seasons and analyzing the extent of the damage.

Keywords: flood, modeling, HPC, FOSS

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72 A Model for Analysing Argumentative Structures and Online Deliberation in User-Generated Comments to the Website of a South African Newspaper

Authors: Marthinus Conradie

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The conversational dynamics of democratically orientated deliberation continue to stimulate critical scholarship for its potential to bolster robust engagement between different sections of pluralist societies. Several axes of deliberation that have attracted academic attention include face-to-face vs. online interaction, and citizen-to-citizen communication vs. engagement between citizens and political elites. In all these areas, numerous researchers have explored deliberative procedures aimed at achieving instrumental goals such a securing consensus on policy issues, against procedures that prioritise expressive outcomes such as broadening the range of argumentative repertoires that discursively construct and mediate specific political issues. The study that informs this paper, works in the latter stream. Drawing its data from the reader-comments section of a South African broadsheet newspaper, the study investigates online, citizen-to-citizen deliberation by analysing the discursive practices through which competing understandings of social problems are articulated and contested. To advance this agenda, the paper deals specifically with user-generated comments posted in response to news stories on questions of race and racism in South Africa. The analysis works to discern and interpret the various sets of discourse practices that shape how citizens deliberate contentious political issues, especially racism. Since the website in question is designed to encourage the critical comparison of divergent interpretations of news events, without feeding directly into national policymaking, the study adopts an analytic framework that traces how citizens articulate arguments, rather than the instrumental effects that citizen deliberations might exert on policy. The paper starts from the argument that such expressive interactions are particularly crucial to current trends in South African politics, given that the precise nature of race and racism remain contested and uncertain. Centred on a sample of 2358 conversational moves in 814 posts to 18 news stories emanating from issues of race and racism, the analysis proceeds in a two-step fashion. The first stage conducts a qualitative content analysis that offers insights into the levels of reciprocity among commenters (do readers engage with each other or simply post isolated opinions?), as well as the structures of argumentation (do readers support opinions by citing evidence?). The second stage involves a more fine-grained discourse analysis, based on a theorisation of argumentation that delineates it into three components: opinions/conclusions, evidence/data to support opinions/conclusions and warrants that explicate precisely how evidence/data buttress opinions/conclusions. By tracing the manifestation and frequency of specific argumentative practices, this study contributes to the archive of research currently aggregating around the practices that characterise South Africans’ engagement with provocative political questions, especially racism and racial inequity. Additionally, the study also contributes to recent scholarship on the affordances of Web 2.0 software by eschewing a simplistic bifurcation between cyber-optimist vs. pessimism, in favour of a more nuanced and context-specific analysis of the patterns that structure online deliberation.

Keywords: online deliberation, discourse analysis, qualitative content analysis, racism

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71 Techno-Economic Assessment of Distributed Heat Pumps Integration within a Swedish Neighborhood: A Cosimulation Approach

Authors: Monica Arnaudo, Monika Topel, Bjorn Laumert

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Within the Swedish context, the current trend of relatively low electricity prices promotes the electrification of the energy infrastructure. The residential heating sector takes part in this transition by proposing a switch from a centralized district heating system towards a distributed heat pumps-based setting. When it comes to urban environments, two issues arise. The first, seen from an electricity-sector perspective, is related to the fact that existing networks are limited with regards to their installed capacities. Additional electric loads, such as heat pumps, can cause severe overloads on crucial network elements. The second, seen from a heating-sector perspective, has to do with the fact that the indoor comfort conditions can become difficult to handle when the operation of the heat pumps is limited by a risk of overloading on the distribution grid. Furthermore, the uncertainty of the electricity market prices in the future introduces an additional variable. This study aims at assessing the extent to which distributed heat pumps can penetrate an existing heat energy network while respecting the technical limitations of the electricity grid and the thermal comfort levels in the buildings. In order to account for the multi-disciplinary nature of this research question, a cosimulation modeling approach was adopted. In this way, each energy technology is modeled in its customized simulation environment. As part of the cosimulation methodology: a steady-state power flow analysis in pandapower was used for modeling the electrical distribution grid, a thermal balance model of a reference building was implemented in EnergyPlus to account for space heating and a fluid-cycle model of a heat pump was implemented in JModelica to account for the actual heating technology. With the models set in place, different scenarios based on forecasted electricity market prices were developed both for present and future conditions of Hammarby Sjöstad, a neighborhood located in the south-east of Stockholm (Sweden). For each scenario, the technical and the comfort conditions were assessed. Additionally, the average cost of heat generation was estimated in terms of levelized cost of heat. This indicator enables a techno-economic comparison study among the different scenarios. In order to evaluate the levelized cost of heat, a yearly performance simulation of the energy infrastructure was implemented. The scenarios related to the current electricity prices show that distributed heat pumps can replace the district heating system by covering up to 30% of the heating demand. By lowering of 2°C, the minimum accepted indoor temperature of the apartments, this level of penetration can increase up to 40%. Within the future scenarios, if the electricity prices will increase, as most likely expected within the next decade, the penetration of distributed heat pumps can be limited to 15%. In terms of levelized cost of heat, a residential heat pump technology becomes competitive only within a scenario of decreasing electricity prices. In this case, a district heating system is characterized by an average cost of heat generation 7% higher compared to a distributed heat pumps option.

Keywords: cosimulation, distributed heat pumps, district heating, electrical distribution grid, integrated energy systems

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70 Spatial Assessment of Creek Habitats of Marine Fish Stock in Sindh Province

Authors: Syed Jamil H. Kazmi, Faiza Sarwar

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The Indus delta of Sindh Province forms the largest creeks zone of Pakistan. The Sindh coast starts from the mouth of Hab River and terminates at Sir Creek area. In this paper, we have considered the major creeks from the site of Bin Qasim Port in Karachi to Jetty of Keti Bunder in Thatta District. A general decline in the mangrove forest has been observed that within a span of last 25 years. The unprecedented human interventions damage the creeks habitat badly which includes haphazard urban development, industrial and sewage disposal, illegal cutting of mangroves forest, reduced and inconsistent fresh water flow mainly from Jhang and Indus rivers. These activities not only harm the creeks habitat but affected the fish stock substantially. Fishing is the main livelihood of coastal people but with the above-mentioned threats, it is also under enormous pressure by fish catches resulted in unchecked overutilization of the fish resources. This pressure is almost unbearable when it joins with deleterious fishing methods, uncontrolled fleet size, increase trash and by-catch of juvenile and illegal mesh size. Along with these anthropogenic interventions study area is under the red zone of tropical cyclones and active seismicity causing floods, sea intrusion, damage mangroves forests and devastation of fish stock. In order to sustain the natural resources of the Indus Creeks, this study was initiated with the support of FAO, WWF and NIO, the main purpose was to develop a Geo-Spatial dataset for fish stock assessment. The study has been spread over a year (2013-14) on monthly basis which mainly includes detailed fish stock survey, water analysis and few other environmental analyses. Environmental analysis also includes the habitat classification of study area which has done through remote sensing techniques for 22 years’ time series (1992-2014). Furthermore, out of 252 species collected, fifteen species from estuarine and marine groups were short-listed to measure the weight, health and growth of fish species at each creek under GIS data through SPSS system. Furthermore, habitat suitability analysis has been conducted by assessing the surface topographic and aspect derivation through different GIS techniques. The output variables then overlaid in GIS system to measure the creeks productivity. Which provided the results in terms of subsequent classes: extremely productive, highly productive, productive, moderately productive and less productive. This study has revealed the Geospatial tools utilization along with the evaluation of the fisheries resources and creeks habitat risk zone mapping. It has also been identified that the geo-spatial technologies are highly beneficial to identify the areas of high environmental risk in Sindh Creeks. This has been clearly discovered from this study that creeks with high rugosity are more productive than the creeks with low levels of rugosity. The study area has the immense potential to boost the economy of Pakistan in terms of fish export, if geo-spatial techniques are implemented instead of conventional techniques.

Keywords: fish stock, geo-spatial, productivity analysis, risk

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69 Identification of a Panel of Epigenetic Biomarkers for Early Detection of Hepatocellular Carcinoma in Blood of Individuals with Liver Cirrhosis

Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

Abstract:

Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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68 Signature Bridge Design for the Port of Montreal

Authors: Juan Manuel Macia

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The Montreal Port Authority (MPA) wanted to build a new road link via Souligny Avenue to increase the fluidity of goods transported by truck in the Viau Street area of Montreal and to mitigate the current traffic problems on Notre-Dame Street. With the purpose of having a better integration and acceptance of this project with the neighboring residential surroundings, this project needed to include an architectural integration, bringing some artistic components to the bridge design along with some landscaping components. The MPA is required primarily to provide direct truck access to Port of Montreal with a direct connection to the future Assomption Boulevard planned by the City of Montreal and, thus, direct access to Souligny Avenue. The MPA also required other key aspects to be considered for the proposal and development of the project, such as the layout of road and rail configurations, the reconstruction of underground structures, the relocation of power lines, the installation of lighting systems, the traffic signage and communication systems improvement, the construction of new access ramps, the pavement reconstruction and a summary assessment of the structural capacity of an existing service tunnel. The identification of the various possible scenarios began by identifying all the constraints related to the numerous infrastructures located in the area of the future link between the port and the future extension of Souligny Avenue, involving interaction with several disciplines and technical specialties. Several viaduct- and tunnel-type geometries were studied to link the port road to the right-of-way north of Notre-Dame Street and to improve traffic flow at the railway corridor. The proposed design took into account the existing access points to Port of Montreal, the built environment of the MPA site, the provincial and municipal rights-of-way, and the future Notre-Dame Street layout planned by the City of Montreal. These considerations required the installation of an engineering structure with a span of over 60 m to free up a corridor for the future urban fabric of Notre-Dame Street. The best option for crossing this span length was identified by the design and construction of a curved bridge over Notre-Dame Street, which is essentially a structure with a deck formed by a reinforced concrete slab on steel box girders with a single span of 63.5m. The foundation units were defined as pier-cap type abutments on drilled shafts to bedrock with rock sockets, with MSE-type walls at the approaches. The configuration of a single-span curved structure posed significant design and construction challenges, considering the major constraints of the project site, a design for durability approach, and the need to guarantee optimum performance over a 75-year service life in accordance with the client's needs and the recommendations and requirements defined by the standards used for the project. These aspects and the need to include architectural and artistic components in this project made it possible to design, build, and integrate a signature infrastructure project with a sustainable approach, from which the MPA, the commuters, and the city of Montreal and its residents will benefit.

Keywords: curved bridge, steel box girder, medium span, simply supported, industrial and urban environment, architectural integration, design for durability

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67 Al2O3-Dielectric AlGaN/GaN Enhancement-Mode MOS-HEMTs by Using Ozone Water Oxidization Technique

Authors: Ching-Sung Lee, Wei-Chou Hsu, Han-Yin Liu, Hung-Hsi Huang, Si-Fu Chen, Yun-Jung Yang, Bo-Chun Chiang, Yu-Chuang Chen, Shen-Tin Yang

Abstract:

AlGaN/GaN high electron mobility transistors (HEMTs) have been intensively studied due to their intrinsic advantages of high breakdown electric field, high electron saturation velocity, and excellent chemical stability. They are also suitable for ultra-violet (UV) photodetection due to the corresponding wavelengths of GaN bandgap. To improve the optical responsivity by decreasing the dark current due to gate leakage problems and limited Schottky barrier heights in GaN-based HEMT devices, various metal-oxide-semiconductor HEMTs (MOS-HEMTs) have been devised by using atomic layer deposition (ALD), molecular beam epitaxy (MBE), metal-organic chemical vapor deposition (MOCVD), liquid phase deposition (LPD), and RF sputtering. The gate dielectrics include MgO, HfO2, Al2O3, La2O3, and TiO2. In order to provide complementary circuit operation, enhancement-mode (E-mode) devices have been lately studied using techniques of fluorine treatment, p-type capper, piezoneutralization layer, and MOS-gate structure. This work reports an Al2O3-dielectric Al0.25Ga0.75N/GaN E-mode MOS-HEMT design by using a cost-effective ozone water oxidization technique. The present ozone oxidization method advantages of low cost processing facility, processing simplicity, compatibility to device fabrication, and room-temperature operation under atmospheric pressure. It can further reduce the gate-to-channel distance and improve the transocnductance (gm) gain for a specific oxide thickness, since the formation of the Al2O3 will consume part of the AlGaN barrier at the same time. The epitaxial structure of the studied devices was grown by using the MOCVD technique. On a Si substrate, the layer structures include a 3.9 m C-doped GaN buffer, a 300 nm GaN channel layer, and a 5 nm Al0.25Ga0.75N barrier layer. Mesa etching was performed to provide electrical isolation by using an inductively coupled-plasma reactive ion etcher (ICP-RIE). Ti/Al/Au were thermally evaporated and annealed to form the source and drain ohmic contacts. The device was immersed into the H2O2 solution pumped with ozone gas generated by using an OW-K2 ozone generator. Ni/Au were deposited as the gate electrode to complete device fabrication of MOS-HEMT. The formed Al2O3 oxide thickness 7 nm and the remained AlGaN barrier thickness is 2 nm. A reference HEMT device has also been fabricated in comparison on the same epitaxial structure. The gate dimensions are 1.2 × 100 µm 2 with a source-to-drain spacing of 5 μm for both devices. The dielectric constant (k) of Al2O3 was characterized to be 9.2 by using C-V measurement. Reduced interface state density after oxidization has been verified by the low-frequency noise spectra, Hooge coefficients, and pulse I-V measurement. Improved device characteristics at temperatures of 300 K-450 K have been achieved for the present MOS-HEMT design. Consequently, Al2O3-dielectric Al0.25Ga0.75N/GaN E-mode MOS-HEMTs by using the ozone water oxidization method are reported. In comparison with a conventional Schottky-gate HEMT, the MOS-HEMT design has demonstrated excellent enhancements of 138% (176%) in gm, max, 118% (139%) in IDS, max, 53% (62%) in BVGD, 3 (2)-order reduction in IG leakage at VGD = -60 V at 300 (450) K. This work is promising for millimeter-wave integrated circuit (MMIC) and three-terminal active UV photodetector applications.

Keywords: MOS-HEMT, enhancement mode, AlGaN/GaN, passivation, ozone water oxidation, gate leakage

Procedia PDF Downloads 252