Search results for: flow function

Authors: Salma A. Mahmoud

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Epigenetic, or alteration in gene expression influenced by extragenetic factors, has emerged as one of the most promising areas that will address some of the gaps in our current knowledge in understanding patterns of human variation. In the last decade, the research investigating epigenetic mechanisms in many fields has flourished and witnessed significant progress. It paved the way for a new era of integrated research especially between anthropology/archeology and life sciences. Skeletal remains are considered the most significant source of information for studying human variations across history, and by utilizing these valuable remains, we can interpret the past events, cultures and populations. In addition to archeological, historical and anthropological importance, studying bones has great implications in other fields such as medicine and science. Bones also can hold within them the secrets of the future as they can act as predictive tools for health, society characteristics and dietary requirements. Bones in their basic forms are composed of cells (osteocytes) that are affected by both genetic and environmental factors, which can only explain a small part of their variability. The primary objective of this project is to examine the epigenetic landscape/signature within bones of archeological remains as a novel marker that could reveal new ways to conceptualize chronological events, gender differences, social status and ecological variations. We attempted here to address discrepancies in common variants such as methylome as well as novel epigenetic regulators such as chromatin remodelers, which to our best knowledge have not yet been investigated by anthropologists/ paleoepigenetists using plethora of techniques (biological, computational, and statistical). Moreover, extracting epigenetic information from bones will highlight the importance of osseous material as a vector to study human beings in several contexts (social, cultural and environmental), and strengthen their essential role as model systems that can be used to investigate and construct various cultural, political and economic events. We also address all steps required to plan and conduct an epigenetic analysis from bone materials (modern and ancient) as well as discussing the key challenges facing researchers aiming to investigate this field. In conclusion, this project will serve as a primer for bioarcheologists/anthropologists and human biologists interested in incorporating epigenetic data into their research programs. Understanding the roles of epigenetic mechanisms in bone structure and function will be very helpful for a better comprehension of their biology and highlighting their essentiality as interdisciplinary vectors and a key material in archeological research.

Keywords: epigenetics, archeology, bones, chromatin, methylome

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Authors: Hsiang-Ru Lin

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Cholesterol plays an essential role in the regulation of the progression of numerous important diseases including atherosclerosis and Alzheimer disease so the generation of suitable cholesterol-lowering reagents is urgent to develop. Liver X receptor (LXR) is a ligand-activated transcription factor whose natural ligands are cholesterols, oxysterols and glucose. Once being activated, LXR can transactivate the transcription action of various genes including CYP7A1, ABCA1, and SREBP1c, involved in the lipid metabolism, glucose metabolism and inflammatory pathway. Essentially, the upregulation of ABCA1 facilitates cholesterol efflux from the cells and attenuates the production of beta-amyloid (ABeta) 42 in brain so LXR is a promising target to develop the cholesterol-lowering reagents and preventative treatment of Alzheimer disease. Engelhardia roxburghiana is a deciduous tree growing in India, China, and Taiwan. However, its chemical composition is only reported to exhibit antitubercular and anti-inflammatory effects. In this study, four compounds, engelheptanoxides A, C, engelhardiol A, and B isolated from the root of Engelhardia roxburghiana were evaluated for their agonistic activity against LXR by the transient transfection reporter assays in the HepG2 cells. Furthermore, their interactive modes with LXR ligand binding pocket were generated by molecular modeling programs. By using the cell-based biological assays, engelheptanoxides A, C, engelhardiol A, and B showing no cytotoxic effect against the proliferation of HepG2 cells, exerted obvious LXR agonistic effects with similar activity as T0901317, a novel synthetic LXR agonist. Further modeling studies including docking and SAR (structure-activity relationship) showed that these compounds can locate in LXR ligand binding pocket in the similar manner as T0901317. Thus, LXR is one of nuclear receptors targeted by pharmaceutical industry for developing treatments of Alzheimer and atherosclerosis diseases. Importantly, the cell-based assays, together with molecular modeling studies suggesting a plausible binding mode, demonstrate that engelheptanoxides A, C, engelhardiol A, and B function as LXR agonists. This is the first report to demonstrate that the extract of Engelhardia roxburghiana contains LXR agonists. As such, these active components of Engelhardia roxburghiana or subsequent analogs may show important therapeutic effects through selective modulation of the LXR pathway.

Keywords: Liver X receptor (LXR), Engelhardia roxburghiana, CYP7A1, ABCA1, SREBP1c, HepG2 cells

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Authors: Mohamed Gaafar, Evan Davies

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Many municipalities within Canada and abroad use chloramination to disinfect drinking water so as to avert the production of the disinfection by-products (DBPs) that result from conventional chlorination processes and their consequential public health risks. However, the long-lasting monochloramine disinfectant (NH2Cl) can pose a significant risk to the environment. As, it can be introduced into stormwater sewers, from different water uses, and thus freshwater sources. Little research has been undertaken to monitor and characterize the decay of NH2Cl and to study the parameters affecting its decomposition in stormwater networks. Therefore, the current study was intended to investigate this decay starting by building a stormwater model and validating its hydraulic and hydrologic computations, and then modelling water quality in the storm sewers and examining the effects of different parameters on chloramine decay. The presented work here is only the first stage of this study. The 30th Avenue basin in Southern Edmonton was chosen as a case study, because the well-developed basin has various land-use types including commercial, industrial, residential, parks and recreational. The City of Edmonton has already built a MIKE-URBAN stormwater model for modelling floods. Nevertheless, this model was built to the trunk level which means that only the main drainage features were presented. Additionally, this model was not calibrated and known to consistently compute pipe flows higher than the observed values; not to the benefit of studying water quality. So the first goal was to complete modelling and updating all stormwater network components. Then, available GIS Data was used to calculate different catchment properties such as slope, length and imperviousness. In order to calibrate and validate this model, data of two temporary pipe flow monitoring stations, collected during last summer, was used along with records of two other permanent stations available for eight consecutive summer seasons. The effect of various hydrological parameters on model results was investigated. It was found that model results were affected by the ratio of impervious areas. The catchment length was tested, however calculated, because it is approximate representation of the catchment shape. Surface roughness coefficients were calibrated using. Consequently, computed flows at the two temporary locations had correlation coefficients of values 0.846 and 0.815, where the lower value pertained to the larger attached catchment area. Other statistical measures, such as peak error of 0.65%, volume error of 5.6%, maximum positive and negative differences of 2.17 and -1.63 respectively, were all found in acceptable ranges.

Keywords: stormwater, urban drainage, simulation, validation, MIKE URBAN

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Authors: Marina Charalambous, Phivos Phylactou, Thekla Elriz, Loukia Psychogios, Jean-Marie Annoni

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Background: Evidence-based practices for the evaluation and treatment of people with aphasia (PWA) in Greek are mainly impairment-based. Functional and multimodal communication is usually under assessed and neglected by clinicians. This study explores the adaptation and psychometric testing of the Greek (GR) version of The Scenario Test. The Scenario Test assesses the everyday functional communication of PWA in an interactive multimodal communication setting with the support of an active communication facilitator. Aims: To define the reliability and validity of The Scenario Test GR and discuss its clinical value. Methods & Procedures: The Scenario Test-GR was administered to 54 people with chronic stroke (6+ months post-stroke): 32 PWA and 22 people with stroke without aphasia. Participants were recruited from Greece and Cyprus. All measures were performed in an interview format. Standard psychometric criteria were applied to evaluate reliability (internal consistency, test-retest, and interrater reliability) and validity (construct and known – groups validity) of the Scenario Test GR. Video analysis was performed for the qualitative examination of the communication modes used. Outcomes & Results: The Scenario Test-GR shows high levels of reliability and validity. High scores of internal consistency (Cronbach’s α = .95), test-retest reliability (ICC = .99), and interrater reliability (ICC = .99) were found. Interrater agreement in scores on individual items fell between good and excellent levels of agreement. Correlations with a tool measuring language function in aphasia (the Aphasia Severity Rating Scale of the Boston Diagnostic Aphasia Examination), a measure of functional communication (the Communicative Effectiveness Index), and two instruments examining the psychosocial impact of aphasia (the Stroke and Aphasia Quality of Life questionnaire and the Aphasia Impact Questionnaire) revealed good convergent validity (all ps< .05). Results showed good known – groups validity (Mann-Whitney U = 96.5, p < .001), with significantly higher scores for participants without aphasia compared to those with aphasia. Conclusions: The psychometric qualities of The Scenario Test-GR support the reliability and validity of the tool for the assessment of functional communication for Greek-speaking PWA. The Scenario Test-GR can be used to assess multimodal functional communication, orient aphasia rehabilitation goal setting towards the activity and participation level, and be used as an outcome measure of everyday communication. Future studies will focus on the measurement of sensitivity to change in PWA with severe non-fluent aphasia.

Keywords: the scenario test GR, functional communication assessment, people with aphasia (PWA), tool validation

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Authors: Rajkumar Ghosh

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Fly ash, a byproduct of coal combustion, has become a prevalent environmental concern due to its potential impact on both groundwater quality and local climate change. This study aims to provide an in-depth analysis of the various mechanisms through which fly ash contaminates groundwater, as well as the possible consequences of this contamination on local climate change. The presence of fly ash in groundwater not only poses a risk to human health but also has the potential to influence local climate change through complex interactions. Although fly ash has various applications in construction and other industries, improper disposal and lack of containment measures have led to its infiltration into groundwater systems. Through a comprehensive review of existing literature and case studies, the interactions between fly ash and groundwater systems, assess the effects on hydrology, and discuss the implications for the broader climate. This section reviews the pathways through which fly ash enters groundwater, including leaching from disposal sites, infiltration through soil, and migration from surface water bodies. The physical and chemical characteristics of fly ash that contribute to its mobility and persistence in groundwater. The introduction of fly ash into groundwater can alter its chemical composition, leading to an increase in the concentration of heavy metals, metalloids, and other potentially toxic elements. The mechanisms of contaminant transport and highlight the potential risks to human health and ecosystems. Fly ash contamination in groundwater may influence the hydrological cycle through changes in groundwater recharge, discharge, and flow dynamics. This section examines the implications of altered hydrology on local water availability, aquatic habitats, and overall ecosystem health. The presence of fly ash in groundwater may have direct and indirect effects on local climate change. The role of fly ash as a potent greenhouse gas absorber and its contribution to radiative forcing. Additionally, investigation of the possible feedback mechanisms between groundwater contamination and climate change, such as altered vegetation patterns and changes in local temperature and precipitation patterns. In this section, potential mitigation and remediation techniques to minimize fly ash contamination in groundwater are analyzed. These may include improved waste management practices, engineered barriers, groundwater remediation technologies, and sustainable fly ash utilization. This paper highlights the critical link between fly ash contamination in groundwater and its potential contribution to local climate change. It emphasizes the importance of addressing this issue promptly through a combination of preventive measures, effective management strategies, and continuous monitoring. By understanding the interconnections between fly ash contamination, groundwater quality, and local climate, towards creating a more resilient and sustainable environment for future generations. The findings of this research can assist policymakers and environmental managers in formulating sustainable strategies to mitigate fly ash contamination and minimize its contribution to climate change.

Keywords: groundwater, climate, sustainable environment, fly ash contamination

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Authors: Pratima Pokharel

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When sewer overflow due to rainfall in urban areas, this leads to public health risks when an individual is exposed to that contaminated floodwater. Nevertheless, it is still unclear the extent to which the infections pose a risk to public health. This study analyzed reported diarrheal cases by month and age in Bangkok, Thailand. The results showed that the cases are reported higher in the wet season than in the dry season. It was also found that in Bangkok, the probability of infection with diarrheal diseases in the wet season is higher for the age group between 15 to 44. However, the probability of infection is highest for kids under 5 years, but they are not influenced by wet weather. Further, this study introduced a vulnerability that leads to health risks from urban flooding. This study has found some vulnerability variables that contribute to health risks from flooding. Thus, for vulnerability analysis, the study has chosen two variables, economic status, and age, that contribute to health risk. Assuming that the people's economic status depends on the types of houses they are living in, the study shows the spatial distribution of economic status in the vulnerability maps. The vulnerability map result shows that people living in Sukhumvit have low vulnerability to health risks with respect to the types of houses they are living in. In addition, from age the probability of infection of diarrhea was analyzed. Moreover, a field survey was carried out to validate the vulnerability of people. It showed that health vulnerability depends on economic status, income level, and education. The result depicts that people with low income and poor living conditions are more vulnerable to health risks. Further, the study also carried out 1D Hydrodynamic Advection-Dispersion modelling with 2-year rainfall events to simulate the dispersion of fecal coliform concentration in the drainage network as well as 1D/2D Hydrodynamic model to simulate the overland flow. The 1D result represents higher concentrations for dry weather flows and a large dilution of concentration on the commencement of a rainfall event, resulting in a drop of the concentration due to runoff generated after rainfall, whereas the model produced flood depth, flood duration, and fecal coliform concentration maps, which were transferred to ArcGIS to produce hazard and risk maps. In addition, the study also simulates the 5-year and 10-year rainfall simulations to show the variation in health hazards and risks. It was found that even though the hazard coverage is very high with a 10-year rainfall events among three rainfall events, the risk was observed to be the same with a 5-year and 10-year rainfall events.

Keywords: urban flooding, risk, hazard, vulnerability, health risk, framework

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Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay

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Background: Cervical cancer is the third major cause of cancer in women and the second most frequent cause of cancer related deaths causing 300,000 deaths annually worldwide. Evasion of immune response by Human Papilloma Virus (HPV), the key contributing factor behind cancer and pre-cancerous lesions of the uterine cervix, makes immunotherapy a necessity to treat this disease. Objective: A Heat killed fraction of Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium has been shown to exhibit cytotoxic effects on different cancer cells, including human cervical carcinoma cell line HeLa. However, the underlying mechanisms remain unknown. The aim of this study is to decipher the mechanism of MIP induced HeLa cell death. Methods: The cytotoxicity of Mycobacterium indicus pranii against HeLa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and Propidium iodide (PI) staining. The assessment of reactive oxygen species (ROS) generation and cell cycle analysis were measured by flow cytometry. The expression of apoptosis associated genes was analyzed by real time PCR. Result: MIP could inhibit the proliferation of HeLa cell in a time and dose dependent manner but caused minor damage to normal cells. The induction of apoptosis was confirmed by the cell surface presentation of phosphatidyl serine, DNA fragmentation, and mitochondrial damage. MIP caused very early (as early as 30 minutes) transcriptional activation of p53, followed by a higher activation (32 fold) at 24 hours suggesting prime importance of p53 in MIP-induced apoptosis in HeLa cell. The up regulation of p53 dependent pro-apoptotic genes Bax, Bak, PUMA, and Noxa followed a lag phase that was required for the transcriptional p53 program. MIP also caused the transcriptional up regulation of Toll like receptor 2 and 4 after 30 minutes of MIP treatment suggesting recognition of MIP by toll like receptors. Moreover, MIP caused the inhibition of expression of HPV anti apoptotic gene E6, which is known to interfere with p53/PUMA/Bax apoptotic cascade. This inhibition might have played a role in transcriptional up regulation of PUMA and subsequently apoptosis. ROS was generated transiently which was concomitant with the highest transcription activation of p53 suggesting a plausible feedback loop network of p53 and ROS in the apoptosis of HeLa cells. Scavenger of ROS, such as N-acetyl-L-cysteine, decreased apoptosis suggesting ROS is an important effector of MIP induced apoptosis. Conclusion: Taken together, MIP possesses full potential to be a novel therapeutic agent in the clinical treatment of cervical cancer.

Keywords: cancer, mycobacterium, immunity, immunotherapy.

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Authors: Hugo Badia

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This research answers which is the most suitable transit network structure to serve specific demand requirements in an increasing urban dispersion process. Two main approaches of network design are found in the literature. On the one hand, a traditional answer, widespread in our cities, that develops a high number of lines to connect most of origin-destination pairs by direct trips; an approach based on the idea that users averse to transfers. On the other hand, some authors advocate an alternative design characterized by simple networks where transfer is essential to complete most of trips. To answer which of them is the best option, we use a two-step methodology. First, by means of an analytical model, three basic network structures are compared: a radial scheme, starting point for the other two structures, a direct trip-based network, and a transfer-based one, which represent the two alternative transit network designs. The model optimizes the network configuration with regard to the total cost for each structure. For a scenario of dispersion, the best alternative is the structure with the minimum cost. This dispersion degree is defined in a simple way considering that only a central area attracts all trips. If this area is small, we have a high concentrated mobility pattern; if this area is too large, the city is highly decentralized. In this first step, we can determine the area of applicability for each structure in function to that urban dispersion degree. The analytical results show that a radial structure is suitable when the demand is so centralized, however, when this demand starts to scatter, new transit lines should be implemented to avoid transfers. If the urban dispersion advances, the introduction of more lines is no longer a good alternative, in this case, the best solution is a change of structure, from direct trips to a network based on transfers. The area of applicability of each network strategy is not constant, it depends on the characteristics of demand, city and transport technology. In the second step, we translate analytical results to a real case study by the relationship between the parameters of dispersion of the model and direct measures of dispersion in a real city. Two dimensions of the urban sprawl process are considered: concentration, defined by Gini coefficient, and centralization by area based centralization index. Once it is estimated the real dispersion degree, we are able to identify in which area of applicability the city is located. In summary, from a strategic point of view, we can obtain with this methodology which is the best network design approach for a city, comparing the theoretical results with the real dispersion degree.

Keywords: analytical network design model, network structure, public transport, urban dispersion

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Authors: Pablo Chico De Guzman, Cesar Sanchez

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Microservices are a software development methodology in which applications are built by composing a set of independently deploy-able, small, modular services. Each service runs a unique process and it gets instantiated and deployed in one or more machines (we assume that different microservices are deployed into different machines). Microservices are becoming the de facto standard for developing distributed cloud applications due to their reduced release cycles. In principle, the responsibility of a microservice can be as simple as implementing a single function, which can lead to the following issues: - Resource fragmentation due to the virtual machine boundary. - Poor communication performance between microservices. Two composition techniques can be used to optimize resource fragmentation and communication performance: aggregation and embedding of microservices. Aggregation allows the deployment of a set of microservices on the same machine using a proxy server. Aggregation helps to reduce resource fragmentation, and is particularly useful when the aggregated services have a similar scalability behavior. Embedding deals with communication performance by deploying on the same virtual machine those microservices that require a communication channel (localhost bandwidth is reported to be about 40 times faster than cloud vendor local networks and it offers better reliability). Embedding can also reduce dependencies on load balancer services since the communication takes place on a single virtual machine. For example, assume that microservice A has two instances, a1 and a2, and it communicates with microservice B, which also has two instances, b1 and b2. One embedding can deploy a1 and b1 on machine m1, and a2 and b2 are deployed on a different machine m2. This deployment configuration allows each pair (a1-b1), (a2-b2) to communicate using the localhost interface without the need of a load balancer between microservices A and B. Aggregation and embedding techniques are complex since different microservices might have incompatible runtime dependencies which forbid them from being installed on the same machine. There is also a security concern since the attack surface between microservices can be larger. Luckily, container technology allows to run several processes on the same machine in an isolated manner, solving the incompatibility of running dependencies and the previous security concern, thus greatly simplifying aggregation/embedding implementations by just deploying a microservice container on the same machine as the aggregated/embedded microservice container. Therefore, a wide variety of deployment configurations can be described by combining aggregation and embedding to create an efficient and robust microservice architecture. This paper presents a formal method that receives a declarative definition of a microservice architecture and proposes different optimized deployment configurations by aggregating/embedding microservices. The first prototype is based on i2kit, a deployment tool also submitted to ICWS 2018. The proposed prototype optimizes the following parameters: network/system performance, resource usage, resource costs and failure tolerance.

Keywords: aggregation, deployment, embedding, resource allocation

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Authors: Jing (Claire) LI

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The topic of corporate social responsibility (CSR) is significant for pharmaceutical companies in China at this current stage. This is because, as a rapid growth industry in China in recent years, the pharmaceutical industry in China has been undergone continuous and terrible incidents relating to CSR. However, there is limited research and practice of CSR in Chinese pharmaceutical companies. Also, there is an urgent call for more research in an international context to understand the implications of corporate life cycle on CSR performance. To respond to the research need and research call, this study examines the relationship between corporate life cycle and CSR performance of Chinese listed companies in pharmaceutical industry. This research studies Chinese listed companies in pharmaceutical industry for the period of 2010-2017, where the data is available in database. Following the literature, this study divides CSR performance with regards to CSR dimensions, including shareholders, creditors, employees, customers, suppliers, the government, and the society. This study uses CSR scores of HEXUN database and financial measures of these CSR dimensions to measure the CSR performance. This study performed regression analysis to examine the relationship between corporate life cycle stages and CSR performance with regards to CSR dimensions for pharmaceutical listed companies in China. Using cash flow pattern as proxy of corporate life cycle to classify corporate life cycle stages, this study found that most (least) pharmaceutical companies in China are in maturity (decline) stage. This study found that CSR performance for most dimensions are highest (lowest) in maturity (decline) stage as well. Among these CSR dimensions, performing responsibilities for shareholder is the most important among all CSR responsibilities for pharmaceutical companies. This study is the first to provide important empirical evidence from Chinese pharmaceutical industry on the association between life cycle and CSR performance, supporting that corporate life cycle is a key factor in CSR performance. The study expands corporate life cycle and CSR literatures and has both empirical and theoretical contributions to the literature. From perspective of empirical contributions, the findings contribute to the argument that whether there is a relationship between CSR performance and various corporate life cycle stages in the literature. This study also provides empirical evidence that companies in different corporate life cycles have difference in CSR performance. From perspective of theoretical contributions, this study relates CSR and stakeholders to corporate life cycle stages and complements the corporate life cycle and CSR literature. This study has important implications for managers and policy makers. First, the results will be helpful for managers to have an understanding in the essence of CSR, and their company’s current and future CSR focus over corporate life cycle. This study provides a reference for their actions and may help them make more wise resources allocation decisions of CSR investment. Second, policy makers (in the government, stock exchanges, and securities commission) may consider corporate life cycle as an important factor in formulating future regulations for companies. Future research can explore the "process-based" differences in CSR performance and more industries.

Keywords: China, corporate life cycle, corporate social responsibility, pharmaceutical industry

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Authors: Francesca Schiavello

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This work aims to create a hybrid algorithm, combining Quantum Approximate Optimization Algorithm (QAOA) with an Evolutionary Algorithm (EA) in the place of traditional gradient based optimization processes. QAOA’s were first introduced in 2014, where, at the time, their algorithm performed better than the traditional best known classical algorithm for Max-cut graphs. Whilst classical algorithms have improved since then and have returned to being faster and more efficient, this was a huge milestone for quantum computing, and their work is often used as a benchmarking tool and a foundational tool to explore variants of QAOA’s. This, alongside with other famous algorithms like Grover’s or Shor’s, highlights to the world the potential that quantum computing holds. It also presents the reality of a real quantum advantage where, if the hardware continues to improve, this could constitute a revolutionary era. Given that the hardware is not there yet, many scientists are working on the software side of things in the hopes of future progress. Some of the major limitations holding back quantum computing are the quality of qubits and the noisy interference they generate in creating solutions, the barren plateaus that effectively hinder the optimization search in the latent space, and the availability of number of qubits limiting the scale of the problem that can be solved. These three issues are intertwined and are part of the motivation for using EAs in this work. Firstly, EAs are not based on gradient or linear optimization methods for the search in the latent space, and because of their freedom from gradients, they should suffer less from barren plateaus. Secondly, given that this algorithm performs a search in the solution space through a population of solutions, it can also be parallelized to speed up the search and optimization problem. The evaluation of the cost function, like in many other algorithms, is notoriously slow, and the ability to parallelize it can drastically improve the competitiveness of QAOA’s with respect to purely classical algorithms. Thirdly, because of the nature and structure of EA’s, solutions can be carried forward in time, making them more robust to noise and uncertainty. Preliminary results show that the EA algorithm attached to QAOA can perform on par with the traditional QAOA with a Cobyla optimizer, which is a linear based method, and in some instances, it can even create a better Max-Cut. Whilst the final objective of the work is to create an algorithm that can consistently beat the original QAOA, or its variants, due to either speedups or quality of the solution, this initial result is promising and show the potential of EAs in this field. Further tests need to be performed on an array of different graphs with the parallelization aspect of the work commencing in October 2023 and tests on real hardware scheduled for early 2024.

Keywords: evolutionary algorithm, max cut, parallel simulation, quantum optimization

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Authors: Eva Laryea, Clement Yeboah Authors

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A pretest-posttest within subjects, experimental design was employed to examine the effects of a computerized basic statistics learning game on achievement and statistics-related anxiety of students enrolled in introductory graduate statistics course. Participants (N = 34) were graduate students in a variety of programs at state-funded research university in the Southeast United States. We analyzed pre-test posttest differences using paired samples t-tests for achievement and for statistics anxiety. The results of the t-test for knowledge in statistics were found to be statistically significant indicating significant mean gains for statistical knowledge as a function of the game-based intervention. Likewise, the results of the t-test for statistics-related anxiety were also statistically significant indicating a decrease in anxiety from pretest to posttest. The implications of the present study are significant for both teachers and students. For teachers, using computer games developed by the researchers can help to create a more dynamic and engaging classroom environment, as well as improve student learning outcomes. For students, playing these educational games can help to develop important skills such as problem solving, critical thinking, and collaboration. Students can develop interest in the subject matter and spend quality time to learn the course as they play the game without knowing that they are even learning the presupposed hard course. The future directions of the present study are promising, as technology continues to advance and become more widely available. Some potential future developments include the integration of virtual and augmented reality into educational games, the use of machine learning and artificial intelligence to create personalized learning experiences, and the development of new and innovative game-based assessment tools. It is also important to consider the ethical implications of computer game-based pedagogy, such as the potential for games to perpetuate harmful stereotypes and biases. As the field continues to evolve, it will be crucial to address these issues and work towards creating inclusive and equitable learning experiences for all students. This study has the potential to revolutionize the way basic statistics graduate students learn and offers exciting opportunities for future development and research. It is an important area of inquiry for educators, researchers, and policymakers, and will continue to be a dynamic and rapidly evolving field for years to come.

Keywords: pretest-posttest within subjects, experimental design, achievement, statistics-related anxiety

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Authors: Mjellma Rexhepi, Blerta Rexhepi Kelmendi, Blana Krasniqi, Shaip Krasniqi

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Rheumatoid arthritis is a chronic disease that causes inflammation of the joints which can be so severe that can cause not only deformities but also impairment of function that limits movement. This also contributes to the pain that accompanies this disease. This remains a problematic and challenging disease of modern medicine because treatment is still symptomatic. The main purpose of drug treatment is to reduce the activity of the disease, achieve remission, avoid disability and death. The etiology of the disease is idiopathic, but can also be linked to genetic, nongenetic factors such as hormonal, environmental or infectious. Current scientific evidence shows that vitamin D plays an important role in immune regulation mechanisms. Lack of this vitamin has been linked to loss of immune tolerance and the appearance of autoimmune processes, including rheumatoid arthritis. The purpose of the work was to define Vitamin D in patients hospitalized with rheumatoid arthritis in University Clinical Center of Kosova, as a basis of their connection with lifestyle and physical inactivity. The sample for the work was selected from patients with criteria met for rheumatoid arthritis who were hospitalized at the tertiary level of health care in Kosova. During the work have been investigated 100 consecutive patients fulfilling diagnostic criteria for rheumatoid arthritis, whereas in addition to the general characteristics are also determined the values of vitamin D at the beginning of hospitalization. The average age of the sample analyzed was 50.9±5.7 years old, with an average duration of rheumatoid arthritis disease 7.8±3.4 years. At the beginning of hospitalization, before treatment was initiated, the average value of vitamin D was 15.86±3.43, which according to current reference values is classified into the category of insufficient values. Correlating the duration of the disease, from the time of diagnosis to the day of hospitalization, on one side and the level of vitamin D on the other side, the negative correlation of a lower degree derived (r =-0.1). Physical activity affects the concentration of vitamin D in the blood through increased metabolism of fat and the release of vitamin D and its metabolites from adipose tissue. To now it is evident that physical activity is also accompanied by higher levels of vitamin D. In patients with rheumatoid arthritis, vitamin D levels were low compared to normal. Future works should be oriented toward investigating in detail the bone structure, quality of life and pain in patients with rheumatoid arthritis. More detailed scientific projects, with larger numbers of participants, should be designed for the future to clarify more possible mechanisms as factors related to this phenomenon, such as inactivity, lifestyle and the duration of the disease, as well as the importance of keeping vitamin D values at normal limits.

Keywords: hospitalization, lifestyle, rheumatoid arthritis, vitamin D.

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Authors: Jun Won Kim

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Objective: Theta-phase gamma-amplitude coupling (TGC) was used as a novel evidence-based tool to reflect the dysfunctional cortico-thalamic interaction in patients with schizophrenia. However, to our best knowledge, no studies have reported the diagnostic utility of the TGC in the resting-state electroencephalographic (EEG) of neuroleptic-naive patients with schizophrenia compared to healthy controls. Thus, the purpose of this EEG study was to understand the underlying mechanisms in patients with schizophrenia by comparing the TGC at rest between two groups and to evaluate the diagnostic utility of TGC. Method: The subjects included 90 patients with schizophrenia and 90 healthy controls. All patients were diagnosed with schizophrenia according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) by two independent psychiatrists using semi-structured clinical interviews. Because patients were either drug-naïve (first episode) or had not been taking psychoactive drugs for one month before the study, we could exclude the influence of medications. Five frequency bands were defined for spectral analyses: delta (1–4 Hz), theta (4–8 Hz), slow alpha (8–10 Hz), fast alpha (10–13.5 Hz), beta (13.5–30 Hz), and gamma (30-80 Hz). The spectral power of the EEG data was calculated with fast Fourier Transformation using the 'spectrogram.m' function of the signal processing toolbox in Matlab. An analysis of covariance (ANCOVA) was performed to compare the TGC results between the groups, which were adjusted using a Bonferroni correction (P < 0.05/19 = 0.0026). Receiver operator characteristic (ROC) analysis was conducted to examine the discriminating ability of the TGC data for schizophrenia diagnosis. Results: The patients with schizophrenia showed a significant increase in the resting-state TGC at all electrodes. The delta, theta, slow alpha, fast alpha, and beta powers showed low accuracies of 62.2%, 58.4%, 56.9%, 60.9%, and 59.0%, respectively, in discriminating the patients with schizophrenia from the healthy controls. The ROC analysis performed on the TGC data generated the most accurate result among the EEG measures, displaying an overall classification accuracy of 92.5%. Conclusion: As TGC includes phase, which contains information about neuronal interactions from the EEG recording, TGC is expected to be useful for understanding the mechanisms the dysfunctional cortico-thalamic interaction in patients with schizophrenia. The resting-state TGC value was increased in the patients with schizophrenia compared to that in the healthy controls and had a higher discriminating ability than the other parameters. These findings may be related to the compensatory hyper-arousal patterns of the dysfunctional default-mode network (DMN) in schizophrenia. Further research exploring the association between TGC and medical or psychiatric conditions that may confound EEG signals will help clarify the potential utility of TGC.

Keywords: quantitative electroencephalography (QEEG), theta-phase gamma-amplitude coupling (TGC), schizophrenia, diagnostic utility

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Authors: Grigoria Athanasaki, Veerarajan Vimala, A. M. Kannan, Louis Cindrella

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Energy usage has been increased throughout the years, leading to severe environmental impacts. Since the majority of the energy is currently produced from fossil fuels, there is a global need for clean energy solutions. Proton Exchange Membrane Fuel Cells (PEMFCs) offer a very promising solution for transportation applications because of their solid configuration and low temperature operations, which allows them to start quickly. One of the main components of PEMFCs is the Gas Diffusion Layer (GDL), which manages water and gas transport and shows direct influence on the fuel cell performance. In this work, a novel dual-layer GDL with gradient porosity was prepared, using polyethylene glycol (PEG) as pore former, to improve the gas diffusion and water management in the system. The microporous layer (MPL) of the fabricated GDL consists of carbon powder PUREBLACK, sodium dodecyl sulfate as a surfactant, 34% wt. PTFE and the gradient porosity was created by applying one layer using 30% wt. PEG on the carbon substrate, followed by a second layer without using any pore former. The total carbon loading of the microporous layer is ~ 3 mg.cm-2. For the assembly of the catalyst layer, Nafion membrane (Ion Power, Nafion Membrane NR211) and Pt/C electrocatalyst (46.1% wt.) were used. The catalyst ink was deposited on the membrane via microspraying technique. The Pt loading is ~ 0.4 mg.cm-2, and the active area is 5 cm2. The sample was ex-situ characterized via wetting angle measurement, Scanning Electron Microscopy (SEM), and Pore Size Distribution (PSD) to evaluate its characteristics. Furthermore, for the performance evaluation in-situ characterization via Fuel Cell Testing using H2/O2 and H2/air as reactants, under 50, 60, 80, and 100% relative humidity (RH), took place. The results were compared to a single layer GDL, fabricated with the same carbon powder and loading as the dual layer GDL, and a commercially available GDL with MPL (AvCarb2120). The findings reveal high hydrophobic properties of the microporous layer of the GDL for both PUREBLACK based samples, while the commercial GDL demonstrates hydrophilic behavior. The dual layer GDL shows high and stable fuel cell performance under all the RH conditions, whereas the single layer manifests a drop in performance at high RH in both oxygen and air, caused by catalyst flooding. The commercial GDL shows very low and unstable performance, possibly because of its hydrophilic character and thinner microporous layer. In conclusion, the dual layer GDL with PEG appears to have improved gas diffusion and water management in the fuel cell system. Due to its increasing porosity from the catalyst layer to the carbon substrate, it allows easier access of the reactant gases from the flow channels to the catalyst layer, and more efficient water removal from the catalyst layer, leading to higher performance and stability.

Keywords: gas diffusion layer, microporous layer, proton exchange membrane fuel cells, relative humidity

Procedia PDF Downloads 121

Authors: Kevin De Castro Cogle, Mirian Kubo, Maria Anastasiadi, Fady Mohareb, Claire Rossi

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Background: The bioaccessibility of bioactive compounds is a critical determinant of the nutritional quality of various food products. Despite its importance, there is a limited number of comprehensive studies aimed at assessing how the composition of a food matrix influences the bioaccessibility of a compound of interest. This knowledge gap has prompted a growing need to investigate the intricate relationship between food matrix formulations and the bioaccessibility of bioactive compounds. One such class of bioactive compounds that has attracted considerable attention is curcuminoids. These naturally occurring phytochemicals, extracted from the roots of Curcuma longa, have gained popularity owing to their purported health benefits and also well known for their poor bioaccessibility Project aim: The primary objective of this research project is to systematically assess the influence of matrix composition on the bioaccessibility of curcuminoids. Additionally, this study aimed to develop a series of predictive models for bioaccessibility, providing valuable insights for optimising the formula for functional foods and provide more descriptive nutritional information to potential consumers. Methods: Food formulations enriched with curcuminoids were subjected to in vitro digestion simulation, and their bioaccessibility was characterized with chromatographic and spectrophotometric techniques. The resulting data served as the foundation for the development of predictive models capable of estimating bioaccessibility based on specific physicochemical properties of the food matrices. Results: One striking finding of this study was the strong correlation observed between the concentration of macronutrients within the food formulations and the bioaccessibility of curcuminoids. In fact, macronutrient content emerged as a very informative explanatory variable of bioaccessibility and was used, alongside other variables, as predictors in a Bayesian hierarchical model that predicted curcuminoid bioaccessibility accurately (optimisation performance of 0.97 R2) for the majority of cross-validated test formulations (LOOCV of 0.92 R2). These preliminary results open the door to further exploration, enabling researchers to investigate a broader spectrum of food matrix types and additional properties that may influence bioaccessibility. Conclusions: This research sheds light on the intricate interplay between food matrix composition and the bioaccessibility of curcuminoids. This study lays a foundation for future investigations, offering a promising avenue for advancing our understanding of bioactive compound bioaccessibility and its implications for the food industry and informed consumer choices.

Keywords: bioactive bioaccessibility, food formulation, food matrix, machine learning, probabilistic modelling

Procedia PDF Downloads 66

Authors: A. D. Rao, Sachiko Mohanty

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The Internal Waves (IWs) are generated by the flow of barotropic tide over the rapidly varying and steep topographic features like continental shelf slope, subsurface ridges, and the seamounts, etc. The IWs of the tidal frequency are generally known as internal tides. These waves have a significant influence on the vertical density and hence causes mixing in the region. Such waves are also important in submarine acoustics, underwater navigation, offshore structures, ocean mixing and biogeochemical processes, etc. over the shelf-slope region. The seasonal variability of internal tides in the Bay of Bengal with special emphasis on its energetics is examined by using three-dimensional MITgcm model. The numerical simulations are performed for different periods covering August-September, 2013; November-December, 2013 and March-April, 2014 representing monsoon, post-monsoon and pre-monsoon seasons respectively during which high temporal resolution in-situ data sets are available. The model is initially validated through the spectral estimates of density and the baroclinic velocities. From the estimates, it is inferred that the internal tides associated with semi-diurnal frequency are more dominant in both observations and model simulations for November-December and March-April. However, in August, the estimate is found to be maximum near-inertial frequency at all the available depths. The observed vertical structure of the baroclinic velocities and its magnitude are found to be well captured by the model. EOF analysis is performed to decompose the zonal and meridional baroclinic tidal currents into different vertical modes. The analysis suggests that about 70-80% of the total variance comes from Mode-1 semi-diurnal internal tide in both observations as well as in the model simulations. The first three modes are sufficient to describe most of the variability for semidiurnal internal tides, as they represent 90-95% of the total variance for all the seasons. The phase speed, group speed, and wavelength are found to be maximum for post-monsoon season compared to other two seasons. The model simulation suggests that the internal tide is generated all along the shelf-slope regions and propagate away from the generation sites in all the months. The model simulated energy dissipation rate infers that its maximum occurs at the generation sites and hence the local mixing due to internal tide is maximum at these sites. The spatial distribution of available potential energy is found to be maximum in November (20kg/m²) in northern BoB and minimum in August (14kg/m²). The detailed energy budget calculation are made for all the seasons and results are analysed.

Keywords: available potential energy, baroclinic energy flux, internal tides, Bay of Bengal

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Authors: Piret Pernik

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Based on strategic, operational, and technical analysis of the ongoing armed conflict in Ukraine, this paper will examine the opportunities and risks of using small commercial drones (dual-use unmanned aerial vehicles, UAV) for military purposes. The paper discusses the opportunities and risks in the information domain, encompassing both cyber and electromagnetic interference and attacks. The paper will draw conclusions on a possible strategic impact to the battlefield outcomes in the modern armed conflicts by the widespread use of dual-use UAVs. This article will contribute to filling the gap in the literature by examining based on empirical data cyberattacks and electromagnetic interference. Today, more than one hundred states and non-state actors possess UAVs ranging from low cost commodity models, widely are dual-use, available and affordable to anyone, to high-cost combat UAVs (UCAV) with lethal kinetic strike capabilities, which can be enhanced with Artificial Intelligence (AI) and Machine Learning (ML). Dual-use UAVs have been used by various actors for intelligence, reconnaissance, surveillance, situational awareness, geolocation, and kinetic targeting. Thus they function as force multipliers enabling kinetic and electronic warfare attacks and provide comparative and asymmetric operational and tactical advances. Some go as far as argue that automated (or semi-automated) systems can change the character of warfare, while others observe that the use of small drones has not changed the balance of power or battlefield outcomes. UAVs give considerable opportunities for commanders, for example, because they can be operated without GPS navigation, makes them less vulnerable and dependent on satellite communications. They can and have been used to conduct cyberattacks, electromagnetic interference, and kinetic attacks. However, they are highly vulnerable to those attacks themselves. So far, strategic studies, literature, and expert commentary have overlooked cybersecurity and electronic interference dimension of the use of dual use UAVs. The studies that link technical analysis of opportunities and risks with strategic battlefield outcomes is missing. It is expected that dual use commercial UAV proliferation in armed and hybrid conflicts will continue and accelerate in the future. Therefore, it is important to understand specific opportunities and risks related to the crowdsourced use of dual-use UAVs, which can have kinetic effects. Technical countermeasures to protect UAVs differ depending on a type of UAV (small, midsize, large, stealth combat), and this paper will offer a unique analysis of small UAVs both from the view of opportunities and risks for commanders and other actors in armed conflict.

Keywords: dual-use technology, cyber attacks, electromagnetic warfare, case studies of cyberattacks in armed conflicts

Procedia PDF Downloads 101

Authors: Laura Kupers, Julie Piérard, Niki Cauberg

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The use of exposed concrete (sometimes referred to as architectural concrete), keeps gaining popularity. Exposed concrete has the advantage to combine the structural properties of concrete with an aesthetic finish. However, for a successful aesthetic finish, much attention needs to be paid to the execution (formwork, release agent, curing, weather conditions…), the concrete composition (choice of the raw materials and mix proportions) as well as to its fresh properties. For the latter, a simple on-site pass/fail test could halt the casting of concrete not suitable for architectural concrete and thus avoid expensive repairs later. When architects opt for an exposed concrete, they usually want a smooth, uniform and nearly blemish-free surface. For this choice, a standard ‘construction’ concrete does not suffice. An aesthetic surface finishing requires the concrete to contain a minimum content of fines to minimize the risk of segregation and to allow complete filling of more complex shaped formworks. The concrete may neither be too viscous as this makes it more difficult to compact and it increases the risk of blow holes blemishing the surface. On the other hand, too much bleeding may cause color differences on the concrete surface. An easy pass/fail test, which can be performed on the site just before the casting, could avoid these problems. In case the fresh concrete fails the test, the concrete can be rejected. Only in case the fresh concrete passes the test, the concrete would be cast. The pass/fail tests are intended for a concrete with a consistency class S4. Five tests were selected as possible onsite pass/fail test. Two of these tests already exist: the K-slump test (ASTM C1362) and the Bauer Filter Press Test. The remaining three tests were developed by the BBRI in order to test the segregation resistance of fresh concrete on site: the ‘dynamic sieve stability test’, the ‘inverted cone test’ and an adapted ‘visual stability index’ (VSI) for the slump and flow test. These tests were inspired by existing tests for self-compacting concrete, for which the segregation resistance is of great importance. The suitability of the fresh concrete mixtures was also tested by means of a laboratory reference test (resistance to segregation) and by visual inspection (blow holes, structure…) of small test walls. More than fifteen concrete mixtures of different quality were tested. The results of the pass/fail tests were compared with the results of this laboratory reference test and the test walls. The preliminary laboratory results indicate that concrete mixtures ‘suitable’ for placing as exposed concrete (containing sufficient fines, a balanced grading curve etc.) can be distinguished from ‘inferior’ concrete mixtures. Additional laboratory tests, as well as tests on site, will be conducted to confirm these preliminary results and to set appropriate pass/fail values.

Keywords: exposed concrete, testing fresh concrete, segregation resistance, bleeding, consistency

Procedia PDF Downloads 423

Authors: Aitor Bilbao, Dragos Axinte, John Billingham

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The inverse problem in Energy Beam (EB) Processes consists of defining the control parameters, in particular the 2D beam path (position and orientation of the beam as a function of time), to arrive at a prescribed solution (freeform surface). This inverse problem is well understood for conventional machining, because the cutting tool geometry is well defined and the material removal is a time independent process. In contrast, EB machining is achieved through the local interaction of a beam of particular characteristics (e.g. energy distribution), which leads to a surface-dependent removal rate. Furthermore, EB machining is a time-dependent process in which not only the beam varies with the dwell time, but any acceleration/deceleration of the machine/beam delivery system, when performing raster paths will influence the actual geometry of the surface to be generated. Two different EB processes, Abrasive Water Machining (AWJM) and Pulsed Laser Ablation (PLA), are studied. Even though they are considered as independent different technologies, both can be described as time-dependent processes. AWJM can be considered as a continuous process and the etched material depends on the feed speed of the jet at each instant during the process. On the other hand, PLA processes are usually defined as discrete systems and the total removed material is calculated by the summation of the different pulses shot during the process. The overlapping of these shots depends on the feed speed and the frequency between two consecutive shots. However, if the feed speed is sufficiently slow compared with the frequency, then consecutive shots are close enough and the behaviour can be similar to a continuous process. Using this approximation a generic continuous model can be described for both processes. The inverse problem is usually solved for this kind of process by simply controlling dwell time in proportion to the required depth of milling at each single pixel on the surface using a linear model of the process. However, this approach does not always lead to the good solution since linear models are only valid when shallow surfaces are etched. The solution of the inverse problem is improved by using a discrete adjoint optimization algorithm. Moreover, the calculation of the Jacobian matrix consumes less computation time than finite difference approaches. The influence of the dynamics of the machine on the actual movement of the jet is also important and should be taken into account. When the parameters of the controller are not known or cannot be changed, a simple approximation is used for the choice of the slope of a step profile. Several experimental tests are performed for both technologies to show the usefulness of this approach.

Keywords: abrasive waterjet machining, energy beam processes, inverse problem, pulsed laser ablation

Procedia PDF Downloads 275

Authors: Mina Rabipour, Elena Pallaske, Floyd Hassenrück, Rocio Rebollido-Rios

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Protein tyrosine kinases, including Lyn kinase of the Src family kinases (SFK), regulate cell proliferation, survival, and differentiation. Lyn kinase has been implicated in various cancers, positioning it as a promising therapeutic target. However, the conserved ATP-binding pocket across SFKs makes developing selective inhibitors challenging. This study aims to address this limitation by exploring the potential for allosteric modulation of Lyn kinase, focusing on how its structural dynamics and specific oncogenic mutations impact its conformation and function. To achieve this, we combined homology modeling, molecular dynamics simulations, and data science techniques to conduct microsecond-length simulations. Our approach allowed a detailed investigation into the interplay between Lyn’s catalytic and regulatory domains, identifying key conformational states involved in allosteric regulation. Additionally, we evaluated the structural effects of Dasatinib, a competitive inhibitor, and ATP binding on Lyn active conformation. Notably, our simulations show that cancer-related mutations, specifically I364L/N and E290D/K, shift Lyn toward an inactive conformation, contrasting with the active state of the wild-type protein. This may suggest how these mutations contribute to aberrant signaling in cancer cells. We conducted a dynamical network analysis to assess residue-residue interactions and the impact of mutations on the Lyn intramolecular network. This revealed significant disruptions due to mutations, especially in regions distant from the ATP-binding site. These disruptions suggest potential allosteric sites as therapeutic targets, offering an alternative strategy for Lyn inhibition with higher specificity and fewer off-target effects compared to ATP-competitive inhibitors. Our findings provide insights into Lyn kinase regulation and highlight allosteric sites as avenues for selective drug development. Targeting these sites may modulate Lyn activity in cancer cells, reducing toxicity and improving outcomes. Furthermore, our computational strategy offers a scalable approach for analyzing other SFK members or kinases with similar properties, facilitating the discovery of selective allosteric modulators and contributing to precise cancer therapies.

Keywords: lyn tyrosine kinase, mutation analysis, conformational changes, dynamic network analysis, allosteric modulation, targeted inhibition

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Authors: Surupa Shaw, Debjyoti Banerjee

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Enhancing heat transfer in compact volumes is a challenge when constrained by cost issues, especially those associated with requirements for minimizing pumping power consumption. This is particularly acute for electronic chip cooling applications. Technological advancements in microelectronics have led to development of chip architectures that involve increased power consumption. As a consequence packaging, technologies are saddled with needs for higher rates of power dissipation in smaller form factors. The increasing circuit density, higher heat flux values for dissipation and the significant decrease in the size of the electronic devices are posing thermal management challenges that need to be addressed with a better design of the cooling system. Maximizing surface area for heat exchanging surfaces (e.g., extended surfaces or “fins”) can enable dissipation of higher levels of heat flux. Fractal structures have been shown to maximize surface area in compact volumes. Self-replicating structures at multiple length scales are called “Fractals” (i.e., objects with fractional dimensions; unlike regular geometric objects, such as spheres or cubes whose volumes and surface area values scale as integer values of the length scale dimensions). Fractal structures are expected to provide an appropriate technology solution to meet these challenges for enhanced heat transfer in the microelectronic devices by maximizing surface area available for heat exchanging fluids within compact volumes. In this study, the effect of different fractal micro-channel architectures and flow structures on the enhancement of transport phenomena in heat exchangers is explored by parametric variation of fractal dimension. This study proposes a model that would enable cost-effective solutions for thermal-fluid transport for energy applications. The objective of this study is to ascertain the sensitivity of various parameters (such as heat flux and pressure gradient as well as pumping power) to variation in fractal dimension. The role of the fractal parameters will be instrumental in establishing the most effective design for the optimum cooling of microelectronic devices. This can help establish the requirement of minimal pumping power for enhancement of heat transfer during cooling. Results obtained in this study show that the proposed models for fractal architectures of microchannels significantly enhanced heat transfer due to augmentation of surface area in the branching networks of varying length-scales.

Keywords: fractals, microelectronics, constructal theory, heat transfer enhancement, pumping power enhancement

Procedia PDF Downloads 318

Authors: Angela T. H. Kwan, Saman Arfaie, Joseph Therriault, Zahra Azizi, Firoza Z. Lussier, Cecile Tissot, Mira Chamoun, Gleb Bezgin, Stijn Servaes, Jenna Stevenon, Nesrine Rahmouni, Vanessa Pallen, Serge Gauthier, Pedro Rosa-Neto

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Alzheimer’s disease (AD) can be detected in living people using in vivo biomarkers of amyloid-β (Aβ) and tau, even in the absence of cognitive impairment during the preclinical phase. [¹⁸F]-MK-6420 is a high affinity positron emission tomography (PET) tracer that quantifies tau neurofibrillary tangles, but its ability to predict cognitive changes associated with early AD symptoms, such as memory decline, is unclear. Here, we assess the prognostic accuracy of baseline [18F]-MK-6420 tau PET for predicting longitudinal memory decline in asymptomatic elderly individuals. In a longitudinal observational study, we evaluated a cohort of cognitively normal elderly participants (n = 111) from the Translational Biomarkers in Aging and Dementia (TRIAD) study (data collected between October 2017 and July 2020, with a follow-up period of 12 months). All participants underwent tau PET with [¹⁸F]-MK-6420 and Aβ PET with [¹⁸F]-AZD-4694. The exclusion criteria included the presence of head trauma, stroke, or other neurological disorders. There were 111 eligible participants who were chosen based on the availability of Aβ PET, tau PET, magnetic resonance imaging (MRI), and APOEε4 genotyping. Among these participants, the mean (SD) age was 70.1 (8.6) years; 20 (18%) were tau PET positive, and 71 of 111 (63.9%) were women. A significant association between baseline Braak I-II [¹⁸F]-MK-6240 SUVR positivity and change in composite memory score was observed at the 12-month follow-up, after correcting for age, sex, and years of education (Logical Memory and RAVLT, standardized beta = -0.52 (-0.82-0.21), p < 0.001, for dichotomized tau PET and -1.22 (-1.84-(-0.61)), p < 0.0001, for continuous tau PET). Moderate cognitive decline was observed for A+T+ over the follow-up period, whereas no significant change was observed for A-T+, A+T-, and A-T-, though it should be noted that the A-T+ group was small.Our results indicate that baseline tau neurofibrillary tangle pathology is associated with longitudinal changes in memory function, supporting the use of [¹⁸F]-MK-6420 PET to predict the likelihood of asymptomatic elderly individuals experiencing future memory decline. Overall, [¹⁸F]-MK-6420 PET is a promising tool for predicting memory decline in older adults without cognitive impairment at baseline. This is of critical relevance as the field is shifting towards a biological model of AD defined by the aggregation of pathologic tau. Therefore, early detection of tau pathology using [¹⁸F]-MK-6420 PET provides us with the hope that living patients with AD may be diagnosed during the preclinical phase before it is too late.

Keywords: alzheimer’s disease, braak I-II, in vivo biomarkers, memory, PET, tau

Procedia PDF Downloads 76

Authors: Ivonete Teresinha Schulter Buss Heidemann, Michelle Kuntz Durand, Aline Megumi Arakawa-Belaunde, Sandra Mara Corrêa, Leandro Martins Costa Do Araujo, Kamila Soares Maciel

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Primary Health Care is defined as the level of a system of services that enables the achievement of answers to health needs. This level of care produces services and actions of attention to the person in the life cycle and in their health conditions or diseases. Primary Health Care refers to a conception of care model and organization of the health system that in Brazil seeks to reorganize the principles of the Unified Health System. This system is based on the principle of health as a citizen's right and duty of the State. Primary health care has family health as a priority strategy for its organization according to the precepts of the Unified Health System, structured in the logic of new sectoral practices, associating clinical work and health promotion. Thus, this study seeks to know the possibilities and limits of the care developed by professionals working in Primary Health Care. It was conducted by a qualitative approach of the participant action type, based on Paulo Freire's Research Itinerary, which corresponds to three moments: Thematic Investigation; Encoding and Decoding; and, Critical Unveiling. The themes were investigated in a health unit with the development of a culture circle with 20 professionals, from a municipality in southern Brazil, in the first half of 2021. The participants revealed as possibilities the involvement, bonding and strengthening of the interpersonal relationships of the professionals who work in the context of primary care. Promoting welcoming in primary care has favoured care and teamwork, as well as improved access. They also highlighted that care planning, the use of technologies in the process of communication and the orientation of the population enhances the levels of problem-solving capacity and the organization of services. As limits, the lack of professional recognition and the scarce material and human resources were revealed, conditions that generate tensions for health care. The reduction in the number of professionals and the low salary are pointed out as elements that boost the motivation of the health team for the development of the work. The participants revealed that due to COVID-19, the flow of care had as a priority the pandemic situation, which affected health care in primary care, and prevention and health promotion actions were canceled. The study demonstrated that empowerment and professional involvement are fundamental to promoting comprehensive and problem-solving care. However, limits of the teams are observed when exercising their activities, these are related to the lack of human and material resources, and the expansion of public health policies is urgent.

Keywords: health promotion, primary health care, health professionals, welcoming.

Procedia PDF Downloads 97

Authors: Kobauri Sophio, Kantaria Tengiz, Tugushi David, Puiggali Jordi, Katsarava Ramaz

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Biodegradable biomaterials (BB) are of high interest for numerous applications in modern medicine as resorbable surgical materials and drug delivery systems. This kind of materials can be cleared from the body after the fulfillment of their function that excludes a surgical intervention for their removal. One of the most promising BBare amino acids based biodegradable poly(ester amide)s (PEAs) which are composed of naturally occurring (α-amino acids) and non-toxic building blocks such as fatty diols and dicarboxylic acids. Key bis-nucleophilic monomers for synthesizing the PEAs are diamine-diesters-di-p-toluenesulfonic acid salts of bis-(α-amino acid)-alkylenediesters (TAADs) which form the PEAs after step-growth polymerization (polycondensation) with bis-electrophilic counter-partners - activated diesters of dicarboxylic acids. The PEAs combine all advantages of the 'parent polymers' – polyesters (PEs) and polyamides (PAs): Ability of biodegradation (PEs), a high affinity with tissues and a wide range of desired mechanical properties (PAs). The scopes of applications of thePEAs can substantially be expanded by their functionalization, e.g. through the incorporation of hydrophobic fragments into the polymeric backbones. Hydrophobically modified PEAs can form non-covalent adducts with various compounds that make them attractive as drug carriers. For hydrophobic modification of the PEAs, we selected so-called 'Azlactone Method' based on the application of p-phenylene-bis-oxazolinons (bis-azlactones, BALs) as active bis-electrophilic monomers in step-growth polymerization with TAADs. Interaction of BALs with TAADs resulted in the PEAs with low MWs (Mw2,800-19,600 Da) and poor material properties. The high-molecular-weight PEAs (Mw up to 100,000) with desirable material properties were synthesized after replacement of a part of BALs with activated diester - di-p-nitrophenylsebacate, or a part of TAAD with alkylenediamine – 1,6-hexamethylenediamine. The new hydrophobically modified PEAs were characterized by FTIR, NMR, GPC, and DSC. It was shown that after the hydrophobic modification the PEAs retain the biodegradability (in vitro study catalyzed by α-chymptrypsin and lipase), and are of interest for constructing resorbable surgical and pharmaceutical devices including drug delivering containers such as microspheres. The new PEAs are insoluble in hydrophobic organic solvents such as chloroform or dichloromethane (swell only) that allowed elaborating a new technology of fabricating microspheres.

Keywords: amino acids, biodegradable polymers, bis-azlactones, microspheres

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Authors: John Christian Lequiron, Gerry Bagtasa, Olivia Cabrera, Leoncio Amadore, Tolentino Moya

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Changes in air surface temperature play an important role in the Philippine’s economy, industry, health, and food production. While increasing global mean temperature in the recent several decades has prompted a number of climate change and variability studies in the Philippines, most studies still focus on rainfall and tropical cyclones. This study aims to investigate the trend and variability of observed air surface temperature and determine its major influencing factor/s in the Philippines. A non-parametric Mann-Kendall trend test was applied to monthly mean temperature of 17 synoptic stations covering 56 years from 1960 to 2015 and a mean change of 0.58 °C or a positive trend of 0.0105 °C/year (p < 0.05) was found. In addition, wavelet decomposition was used to determine the frequency of temperature variability show a 12-month, 30-80-month and more than 120-month cycles. This indicates strong annual variations, interannual variations that coincide with ENSO events, and interdecadal variations that are attributed to PDO and CO2 concentrations. Air surface temperature was also correlated with smoothed sunspot number and galactic cosmic rays, the results show a low to no effect. The influence of ENSO teleconnection on temperature, wind pattern, cloud cover, and outgoing longwave radiation on different ENSO phases had significant effects on regional temperature variability. Particularly, an anomalous anticyclonic (cyclonic) flow east of the Philippines during the peak and decay phase of El Niño (La Niña) events leads to the advection of warm southeasterly (cold northeasterly) air mass over the country. Furthermore, an apparent increasing cloud cover trend is observed over the West Philippine Sea including portions of the Philippines, and this is believed to lessen the effect of the increasing air surface temperature. However, relative humidity was also found to be increasing especially on the central part of the country, which results in a high positive trend of heat index, exacerbating the effects on human discomfort. Finally, an assessment of gridded temperature datasets was done to look at the viability of using three high-resolution datasets in future climate analysis and model calibration and verification. Several error statistics (i.e. Pearson correlation, Bias, MAE, and RMSE) were used for this validation. Results show that gridded temperature datasets generally follows the observed surface temperature change and anomalies. In addition, it is more representative of regional temperature rather than a substitute to station-observed air temperature.

Keywords: air surface temperature, carbon dioxide, ENSO, galactic cosmic rays, smoothed sunspot number

Procedia PDF Downloads 321

Authors: Chetra Mang, Ahmadali Tahmasebimoradi, Xavier Lorang

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Lattice structures are widely used in various applications, especially in aeronautic, aerospace, and medical applications because of their high performance properties. Thanks to advancement of the additive manufacturing technology, the lattice structures can be manufactured by different methods such as laser beam melting technology. However, the presence of geometric defects in the lattice structures is inevitable due to the manufacturing process. The geometric defects may have high impact on the mechanical strength of the structures. This work analyzes the correlation between the manufacturing parameters and the mechanical strengths of the lattice structures. To do that, two types of the lattice structures; body-centered cubic with z-struts (BCCZ) structures made of Inconel718, and body-centered cubic (BCC) structures made of Scalmalloy, are manufactured by laser melting beam machine using Taguchi design of experiment. Each structure is placed on the substrate with a specific position and orientation regarding the roller direction of deposed metal powder. The position and orientation are considered as the manufacturing parameters. The geometric defects of each beam in the lattice are characterized and used to build the geometric model in order to perform simulations. Then, the mechanical strengths are defined by the homogeneous response as Young's modulus and yield strength. The distribution of mechanical strengths is observed as a function of manufacturing parameters. The mechanical response of the BCCZ structure is stretch-dominated, i.e., the mechanical strengths are directly dependent on the strengths of the vertical beams. As the geometric defects of vertical beams are slightly changed based on their position/orientation on the manufacturing substrate, the mechanical strengths are less dispersed. The manufacturing parameters are less influenced on the mechanical strengths of the structure BCCZ. The mechanical response of the BCC structure is bending-dominated. The geometric defects of inclined beam are highly dispersed within a structure and also based on their position/orientation on the manufacturing substrate. For different position/orientation on the substrate, the mechanical responses are highly dispersed as well. This shows that the mechanical strengths are directly impacted by manufacturing parameters. In addition, this work is carried out to study the uncertainty propagation of the geometric defects on the mechanical strength of the BCC lattice structure made of Scalmalloy. To do that, we observe the distribution of mechanical strengths of the lattice according to the distribution of the geometric defects. A probability density law is determined based on a statistical hypothesis corresponding to the geometric defects of the inclined beams. The samples of inclined beams are then randomly drawn from the density law to build the lattice structure samples. The lattice samples are then used for simulation to characterize the mechanical strengths. The results reveal that the distribution of mechanical strengths of the structures with the same manufacturing parameters is less dispersed than one of the structures with different manufacturing parameters. Nevertheless, the dispersion of mechanical strengths due to the structures with the same manufacturing parameters are unneglectable.

Keywords: geometric defects, lattice structure, mechanical strength, uncertainty propagation

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Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

Abstract:

Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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Authors: George Pavlidis, Ana Vivas

Abstract:

The demographic change into an aging population has stimulated the examination of seniors’ mental health and ability to live independently. The corresponding literature depicts the relation between cognitive decline and everyday functionality with aging, focusing largely in individuals that are reaching or have bridged the threshold of various forms of neuropathology and disability. In this context, recent meta-analysis depicts a moderate relation between cognitive performance and everyday functionality in AD sufferers. However, there has not been an analogous effort for the examination of this relation in the healthy spectrum of aging (i.e, in samples that are not challenged from a neurodegenerative disease). There is a consensus that the assessment tools designed to detect neuropathology with those that assess cognitive performance in healthy adults are distinct, thus their universal use in cognitively challenged and in healthy adults is not always valid. The same accounts for the assessment of everyday functionality. In addition, it is argued that everyday functionality should be examined with cultural adjusted assessment tools, since many vital everyday tasks are heterotypical among distinct cultures. Therefore, this study was set out to examine the relation between cognitive performance and everyday functionality a) in the healthy spectrum of aging and b) by adjusting the everyday functionality tools EPT and OTDL-R in the Greek cultural context. In Greece, 107 cognitively healthy seniors ( Mage = 62.24) completed a battery of neuropsychological tests and everyday functionality tests. Both were carefully chosen to be sensitive in fluctuations of performance in the healthy spectrum of cognitive performance and everyday functionality. The everyday functionality assessment tools were modified to reflect the local cultural context (i.e., EPT-G and OTDL-G). The results depicted that performance in all everyday functionality measures decline with age (.197 < r > .509). Statistically significant correlations emerged between cognitive performance and everyday functionality assessments that range from r =0.202 to r=0.510. A series of independent regression analysis including the scores of cognitive assessments has yield statistical significant models that explained 20.9 < AR2 > 32.4 of the variance in everyday functionality scored indexes. All everyday functionality measures were independently predicted by the TMT B-A index, and indicator of executive function. Stepwise regression analyses depicted that TMT B-A and age were statistically significant independent predictors of EPT-G and OTDL-G. It was concluded that everyday functionality is declining with age and that cognitive performance and everyday functional may be related in the healthy spectrum of aging. Age seems not to be the sole contributing factor in everyday functionality decline, rather executive control as well. Moreover, it was concluded that the EPT-G and OTDL-G are valuable tools to assess everyday functionality in Greek seniors that are not cognitively challenged, especially for research purposes. Future research should examine the contributing factors of a better cognitive vitality especially in executive control, as vital for the maintenance of independent living capacity with aging.

Keywords: cognition, everyday functionality, aging, cognitive decline, healthy aging, Greece

Procedia PDF Downloads 522

Authors: Utsav Bhardwaj, Shyama Prasad Das

Abstract:

To meet the extensive requirements of thermal management of the circuit card assemblies (CCAs), satellites, PCBs, microprocessors, any other electronic circuitry, pulsating heat pipes (PHPs) have emerged in the recent past as one of the best solutions technically. But industrial application of PHPs is still unexplored up to a large extent due to their poor reliability. There are several systems as well as operational parameters which not only affect the performance of an operating PHP, but also decide whether the PHP can operate sustainably or not. Functioning may completely be halted for some particular combinations of the values of system and operational parameters. Among the system parameters, adiabatic length is one of the important ones. In the present work, a simplest single branch PHP system with an adiabatic section has been considered. It is assumed to have only one vapour bubble and one liquid plug. First, the system has been mathematically modeled using film evaporation/condensation model, followed by the steps of recognition of equilibrium zone, non-dimensionalization and linearization. Then proceeding with a periodical solution of the linearized and reduced differential equations, stability analysis has been performed. Slow and fast variables have been identified, and averaging approach has been used for the slow ones. Ultimately, temporal evolution of the PHP is predicted by numerically solving the averaged equations, to know whether the oscillations are likely to sustain/decay temporally. Stability threshold has also been determined in terms of some non-dimensional numbers formed by different groupings of system and operational parameters. A combined analytical and numerical approach has been used, and it has been found that for each combination of all other parameters, there exists a maximum length of the adiabatic section beyond which the PHP cannot function at all. This length has been called as “Critical Adiabatic Length (L_ac)”. For adiabatic lengths greater than “L_ac”, oscillations are found to be always decaying sooner or later. Dependence of “L_ac” on some other parameters has also been checked and correlated at certain evaporator & condenser section temperatures. “L_ac” has been found to be linearly increasing with increase in evaporator section length (L_e), whereas the condenser section length (L_c) has been found to have almost no effect on it upto a certain limit. But at considerably large condenser section lengths, “L_ac” is expected to decrease with increase in “L_c” due to increased wall friction. Rise in static pressure (p_r) exerted by the working fluid reservoir makes “L_ac” rise exponentially whereas it increases cubically with increase in the inner diameter (d) of PHP. Physics of all such variations has been given a good insight too. Thus, a methodology for quantification of the critical adiabatic length for any possible set of all other parameters of PHP has been established.

Keywords: critical adiabatic length, evaporation/condensation, pulsating heat pipe (PHP), thermal management

Procedia PDF Downloads 225