Search results for: Karen M. K. Chung
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 339

Search results for: Karen M. K. Chung

129 Preparation and Removal Properties of Hollow Fiber Membranes for Drinking Water

Authors: Seung Moon Woo, Youn Suk Chung, Sang Yong Nam

Abstract:

In the present time, we need advanced water treatment technology for separation of virus and bacteria in effluent which occur epidemic and waterborne diseases. Water purification system is mainly divided into two categorizations like reverse osmosis (RO) and ultrafiltration (UF). Membrane used in these systems requires higher durability because of operating in harsh condition. Of these, the membrane using in UF system has many advantages like higher efficiency and lower energy consume for water treatment compared with RO system. In many kinds of membrane, hollow fiber type membrane is possible to make easily and to get optimized property by control of various spinning conditions such as temperature of coagulation bath, concentration of polymer, addition of additive, air gap and internal coagulation. In this study, polysulfone hollow fiber membrane was successfully prepared by phase inversion method for separation of virus and bacteria. When we prepare the hollow fiber membrane, we controlled various factors such as the polymer concentration, air gap and internal coagulation to investigate effect to membrane property. Morphology of surface and cross section of membrane were measured by field emission scanning electron microscope (FE-SEM). Water flux of membrane was measured using test modules. Mean pore diameter of membrane was calculated using rejection of polystyrene (PS) latex beads for separation of virus and bacteria. Flux and mean flow pore diameter of prepared membrane show 1.5 LPM, 0.03 μm at 1.0 kgf/cm2. The bacteria and virus removal performance of prepared UF membranes were over 6 logs.

Keywords: hollow fiber membrane, drinking water, ultrafiltration, bacteria

Procedia PDF Downloads 220
128 Force Measurement for E-Cadherin-Mediated Intercellular Adhesion Probed by Protein Micropattern and Traction Force Microscopy

Authors: Chieh-Chung Tsou, Chun-Min Lo, Yeh-Shiu Chu

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Cell’s mechanical forces provide important physical cues in regulation of proper cellular functions, such as cell differentiation, proliferation and migration. It is believed that adhesive forces generated by cell-cell interaction are able to transmit to the interior of cell through filamentous cortical cytoskeleton. Prominent among other membrane receptors, Cadherins are prototypical adhesive molecules able to generate remarkable forces to regulate intercellular adhesion. However, the mechanistic steps of mechano-transduction in Cadherin-mediated adhesion remain very controversial. We are interested in understanding how Cadherin protein complexes enable force generation and transmission at cell-cell contact in the initial stage of intercellular adhesion. For providing a better control of time, space, and substrate stiffness, in this study, a combination of protein micropattern, micropipette manipulation, and traction force microscopy is used. Pair micropattern with different forms confines cell spreading area and the gaps in pairs varied from 2 to 8 microns are applied for monitoring the forces that cell pairs generated, measured by traction force microscopy. Moreover, cell clones obtained from epithelial cells undergone genome editing are used to score the importance for known components of Cadherin complexes in force generation. We believe that our results from this combinatory mechanobiological method will provide deep insights on understanding the biophysical principle governing mechano- transduction of Cadherin-mediated intercellular adhesion.

Keywords: cadherin, intercellular adhesion, protein micropattern, traction force microscopy

Procedia PDF Downloads 231
127 A Fast Community Detection Algorithm

Authors: Chung-Yuan Huang, Yu-Hsiang Fu, Chuen-Tsai Sun

Abstract:

Community detection represents an important data-mining tool for analyzing and understanding real-world complex network structures and functions. We believe that at least four criteria determine the appropriateness of a community detection algorithm: (a) it produces useable normalized mutual information (NMI) and modularity results for social networks, (b) it overcomes resolution limitation problems associated with synthetic networks, (c) it produces good NMI results and performance efficiency for Lancichinetti-Fortunato-Radicchi (LFR) benchmark networks, and (d) it produces good modularity and performance efficiency for large-scale real-world complex networks. To our knowledge, no existing community detection algorithm meets all four criteria. In this paper, we describe a simple hierarchical arc-merging (HAM) algorithm that uses network topologies and rule-based arc-merging strategies to identify community structures that satisfy the criteria. We used five well-studied social network datasets and eight sets of LFR benchmark networks to validate the ground-truth community correctness of HAM, eight large-scale real-world complex networks to measure its performance efficiency, and two synthetic networks to determine its susceptibility to resolution limitation problems. Our results indicate that the proposed HAM algorithm is capable of providing satisfactory performance efficiency and that HAM-identified communities were close to ground-truth communities in social and LFR benchmark networks while overcoming resolution limitation problems.

Keywords: complex network, social network, community detection, network hierarchy

Procedia PDF Downloads 194
126 Human Pressure Threaten Swayne’s Hartebeest to Point of Local Extinction from the Savannah Plains of Nech Sar National Park, South Rift Valley, Ethiopia

Authors: Simon Shibru, Karen Vancampenhout, Jozef Deckers, Herwig Leirs

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We investigated the population size of the endemic and endangered Swayne’s Hartebeest (Alcelaphus buselaphus swaynei) in Nech Sar National Park from 2012 to 2014 and document the major threats why the species is on the verge of local extinction. The park was once known for its abundant density of Swayne’s Hartebeest. We used direct total count methods for a census. We administered semi-structured interviews and open-ended questionnaires with senior scouts who are the member of the local communities. Historical records were obtained to evaluate the population trends of the animals since 1974. The density of the animal decreased from 65 in 1974 to 1 individual per 100 km2 in 2014 with a decline of 98.5% in the past 40 years. The respondents agreed that the conservation status of the park was in its worst condition ever now with only 2 Swayne’s Hartebeest left, with a rapid decline from 4 individuals in 2012 and 12 individuals in 2009. Mainly hunting and habitat loss, but also the unsuitable season of reproduction and shortage of forage as minor factors were identified as threats for a local extinction of the Swayne’s Hartebeests. On the other hand, predation, fire, disease, and ticks were not considered a cause for the declining trend. Hunting happens mostly out of some kind of revenge since the local community thought that they were pushed out from the land because of the presence of Swayne's Hartebeest in the area. Respondents agreed that the revenge action of the local communities was in response to their unwillingness to be displaced from the park in 1982/3. This conflict situation is resulting from the exclusionary wildlife management policy of the country. We conclude that the human interventions in general and illegal hunting, in particular, pushed the Swayne’s Hartebeest to a point of local extinction. Therefore, we recommend inclusive wildlife management approach for continuing existence of the park together with its natural resources so that sustainable use of the resources is in place.

Keywords: hunting, habitat destruction, local extinction, Nech Sar National Park, Swayne’s Hartebeest

Procedia PDF Downloads 447
125 Providing Support for Minority LGBTQ Students: Developing a Queer Studies Course

Authors: Karen Butler

Abstract:

The LGBTQ youth of color face stigma related to both race and gender identity. Effectively dealing with racial/ethnic discrimination requires strong connections to family and one’s racial/ethnic group. However, LGBTQ youth of color seldom receive support from family, peer groups or church groups. Moreover, ethnic communities often perceive LGBTQ identities as a rejection of ethnic heritage. Thus, stigma places these young people at greater risk for substance use, violence, risky sexual behaviors, suicide, and homelessness. Offering a Queer Studies (QS) class is one way to facilitate a safer and more inclusive environment for LGBTQ students, faculty and staff. The discipline of Queer Studies encompasses theories and thinkers from numerous fields: cultural studies, gay and lesbian studies, race studies, women's studies, media, postmodernism, post-colonialism, psychoanalysis and more. We began our course development by researching existing programs and classes. Several course syllabi were examined and course materials such as readings, videos, and guest speakers were assessed for possible inclusion. We also employed informal survey methods with students and faculty in order to gauge interest in the course. We then developed a sample course syllabus and began the process of new course approval. Feedback thus far indicates that students of various sexual orientations and gender identities are interested in the course and understand the need to offer it; faculty in Psychology, Social Work, and Interdisciplinary Studies are interested in cross-listing the course; library staff is willing to assist with course material acquisition, and the administration is supportive. The purpose of this session is to 1) explore the various health and wellness issues facing LGBTQ students of color and 2) share our experience of developing a QS course in health education in order to address these needs. This process, from initial recognition of the need to a course offering, will be described and discussed in the hopes that participants will increase their awareness of the issues. A QS course would be an appropriate requirement for any number of majors as well as an elective for any major.

Keywords: black colleges, health education, LGBTQ, queer studies

Procedia PDF Downloads 122
124 A Vehicle Monitoring System Based on the LoRa Technique

Authors: Chao-Linag Hsieh, Zheng-Wei Ye, Chen-Kang Huang, Yeun-Chung Lee, Chih-Hong Sun, Tzai-Hung Wen, Jehn-Yih Juang, Joe-Air Jiang

Abstract:

Air pollution and climate warming become more and more intensified in many areas, especially in urban areas. Environmental parameters are critical information to air pollution and weather monitoring. Thus, it is necessary to develop a suitable air pollution and weather monitoring system for urban areas. In this study, a vehicle monitoring system (VMS) based on the IoT technique is developed. Cars are selected as the research tool because it can reach a greater number of streets to collect data. The VMS can monitor different environmental parameters, including ambient temperature and humidity, and air quality parameters, including PM2.5, NO2, CO, and O3. The VMS can provide other information, including GPS signals and the vibration information through driving a car on the street. Different sensor modules are used to measure the parameters and collect the measured data and transmit them to a cloud server through the LoRa protocol. A user interface is used to show the sensing data storing at the cloud server. To examine the performance of the system, a researcher drove a Nissan x-trail 1998 to the area close to the Da’an District office in Taipei to collect monitoring data. The collected data are instantly shown on the user interface. The four kinds of information are provided by the interface: GPS positions, weather parameters, vehicle information, and air quality information. With the VMS, users can obtain the information regarding air quality and weather conditions when they drive their car to an urban area. Also, government agencies can make decisions on traffic planning based on the information provided by the proposed VMS.

Keywords: LoRa, monitoring system, smart city, vehicle

Procedia PDF Downloads 358
123 Influence of the Seat Arrangement in Public Reading Spaces on Individual Subjective Perceptions

Authors: Jo-Han Chang, Chung-Jung Wu

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This study involves a design proposal. The objective of is to create a seat arrangement model for public reading spaces that enable free arrangement without disturbing the users. Through a subjective perception scale, this study explored whether distance between seats and direction of seats influence individual subjective perceptions in a public reading space. This study also involves analysis of user subjective perceptions when reading in the settings on 3 seats at different directions and with 5 distances between seats. The results may be applied to public chair design. This study investigated that (a) whether different directions of seats and distances between seats influence individual subjective perceptions and (b) the acceptable personal space between 2 strangers in a public reading space. The results are shown as follows: (a) the directions of seats and distances between seats influenced individual subjective perceptions. (b) subjective evaluation scores were higher for back-to-back seat directions with Distances A (10 cm) and B (62 cm) compared with face-to-face and side-by-side seat directions; however, when the seat distance exceeded 114 cm (Distance C), no difference existed among the directions of seats. (c) regarding reading in public spaces, when the distance between seats is 10 cm only, we recommend arranging the seats in a back-to-back fashion to increase user comfort and arrangement of face-to-face and side- by-side seat directions should be avoided. When the seat arrangement is limited to face-to-face design, the distance between seats should be increased to at least 62 cm. Moreover, the distance between seats should be increased to at least 114 cm for side- by-side seats to elevate user comfort.

Keywords: individual subjective perceptions, personal space, seat arrangement, direction, distances

Procedia PDF Downloads 401
122 Analysis and Control of Camera Type Weft Straightener

Authors: Jae-Yong Lee, Gyu-Hyun Bae, Yun-Soo Chung, Dae-Sub Kim, Jae-Sung Bae

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In general, fabric is heat-treated using a stenter machine in order to dry and fix its shape. It is important to shape before the heat treatment because it is difficult to revert back once the fabric is formed. To produce the product of right shape, camera type weft straightener has been applied recently to capture and process fabric images quickly. It is more powerful in determining the final textile quality rather than photo-sensor. Positioning in front of a stenter machine, weft straightener helps to spread fabric evenly and control the angle between warp and weft constantly as right angle by handling skew and bow rollers. To process this tricky procedure, the structural analysis should be carried out in advance, based on which, its control technology can be drawn. A structural analysis is to figure out the specific contact/slippage characteristics between fabric and roller. We already examined the applicability of camera type weft straightener to plain weave fabric and found its possibility and the specific working condition of machine and rollers. In this research, we aimed to explore another applicability of camera type weft straightener. Namely, we tried to figure out camera type weft straightener can be used for fabrics. To find out the optimum condition, we increased the number of rollers. The analysis is done by ANSYS software using Finite Element Analysis method. The control function is demonstrated by experiment. In conclusion, the structural analysis of weft straightener is done to identify a specific characteristic between roller and fabrics. The control of skew and bow roller is done to decrease the error of the angle between warp and weft. Finally, it is proved that camera type straightener can also be used for the special fabrics.

Keywords: camera type weft straightener, structure analysis, control, skew and bow roller

Procedia PDF Downloads 271
121 Development of a Web-Based Application for Intelligent Fertilizer Management in Rice Cultivation

Authors: Hao-Wei Fu, Chung-Feng Kao

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In the era of rapid technological advancement, information technology (IT) has become integral to modern life, exerting significant influence across diverse sectors and serving as a catalyst for development in various industries. Within agriculture, the integration of IT offers substantial benefits, notably enhancing operational efficiency. Real-time monitoring systems, for instance, have been widely embraced in agriculture, effectively improving crop management practices. This study specifically addresses the management of rice panicle fertilizer, presenting the development of a web application tailored to handle data associated with rice panicle fertilizer management. Leveraging the normalized difference red edge index, this application optimizes the quantity of rice panicle fertilizer used, providing recommendations to agricultural stakeholders and service providers in the agricultural information sector. The overarching objective is to minimize costs while maximizing yields. Furthermore, a robust database system has been established to store and manage relevant data for future reference in rice cultivation management. Additionally, the study utilizes the Representational State Transfer software architectural style to construct an application programming interface (API), facilitating data creation, retrieval, updating, and deletion for users via the HyperText Transfer Protocol methods. Future plans involve integrating this API with third-party services to incorporate it into larger frameworks, thus catering to the diverse requirements of various third-party services.

Keywords: application programming interface, HyperText Transfer Protocol, nitrogen fertilizer intelligent management, web-based application

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120 Estimation of Carbon Uptake of Seoul City Street Trees in Seoul and Plans for Increase Carbon Uptake by Improving Species

Authors: Min Woo Park, Jin Do Chung, Kyu Yeol Kim, Byoung Uk Im, Jang Woo Kim, Hae Yeul Ryu

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Nine representative species of trees among all the street trees were selected to estimate the absorption amount of carbon dioxide emitted from street trees in Seoul calculating the biomass, amount of carbon saved, and annual absorption amount of carbon dioxide in each of the species. Planting distance of street trees in Seoul was 1,851,180 m, the number of planting lines was 1,287, the number of planted trees was 284,498 and 46 species of trees were planted as of 2013. According to the result of plugging the quantity of species of street trees in Seoul on the absorption amount of each of the species, 120,097 ton of biomass, 60,049.8 ton of amount of carbon saved, and 11,294 t CO2/year of annual absorption amount of carbon dioxide were calculated. Street ratio mentioned on the road statistics in Seoul in 2022 is 23.13%. If the street trees are assumed to be increased in the same rate, the number of street trees in Seoul was calculated to be 294,823. The planting distance was estimated to be 1,918,360 m, and the annual absorption amount of carbon dioxide was measured to be 11,704 t CO2/year. Plans for improving the annual absorption amount of carbon dioxide from street trees were established based on the expected amount of absorption. First of all, it is to improve the annual absorption amount of carbon dioxide by increasing the number of planted street trees after adjusting the planting distance of street trees. If adjusting the current planting distance to 6 m, it was turned out that 12,692.7 t CO2/year was absorbed on an annual basis. Secondly, it is to change the species of trees to tulip trees that represent high absorption rate. If increasing the proportion of tulip trees to 30% up to 2022, the annual absorption rate of carbon dioxide was calculated to be 17804.4 t CO2/year.

Keywords: absorption of carbon dioxide, source of absorbing carbon dioxide, trees in city, improving species

Procedia PDF Downloads 337
119 Gamification Teacher Professional Development: Engaging Language Learners in STEMS through Game-Based Learning

Authors: Karen Guerrero

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Kindergarten-12th grade teachers engaged in teacher professional development (PD) on game-based learning techniques and strategies to support teaching STEMSS (STEM + Social Studies with an emphasis on geography across the curriculum) to language learners. Ten effective strategies have supported teaching content and language in tandem. To provide exiting teacher PD on summer and spring breaks, gamification has integrated these strategies to engage linguistically diverse student populations to provide informal language practice while students engage in the content. Teachers brought a STEMSS lesson to the PD, engaged in a wide variety of games (dice, cards, board, physical, digital, etc.), critiqued the games based on gaming elements, then developed, brainstormed, presented, piloted, and published their game-based STEMSS lessons to share with their colleagues. Pre and post-surveys and focus groups were conducted to demonstrate an increase in knowledge, skills, and self-efficacy in using gamification to teach content in the classroom. Provide an engaging strategy (gamification) to support teaching content and language to linguistically diverse students in the K-12 classroom. Game-based learning supports informal language practice while developing academic vocabulary utilized in the game elements/content focus, building both content knowledge through play and language development through practice. The study also investigated teacher's increase in knowledge, skills, and self-efficacy in using games to teach language learners. Mixed methods were used to investigate knowledge, skills, and self-efficacy prior to and after the gamification teacher training (pre/post) and to understand the content and application of developing and utilizing game-based learning to teach. This study will contribute to the body of knowledge in applying game-based learning theories to the K-12 classroom to support English learners in developing English skills and STEMSS content knowledge.

Keywords: gamification, teacher professional development, STEM, English learners, game-based learning

Procedia PDF Downloads 59
118 L-Carnitine vs Extracorporeal Elimination for Acute Valproic Acid Intoxication: A Systemic Review

Authors: Byung Keun Yang, Jae Eun Ku, Young Seon Joo, Je Sung You, Sung Phil Chung, Hahn Shick Lee

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The purpose of this study is to review the evidence comparing the efficacy and safety between L-carnitine and extracorporeal elimination therapy in the management of acute valproic acid L-carnitine vs Extracorporeal Elimination for Acute Valproic acid Intoxication. PubMed, Embase, Cochrane library, Web of Science, KoreaMed, KMbase, and KISS were searched, using the terms carnitine and valproic acid. All studies, regardless of design, reporting efficacy or safety endpoints were included. Reference citations from identified publications were reviewed. Both English and Korean languages were included. Two authors extracted primary data elements including poisoning severity, presenting features, clinical management, and outcomes. Thirty two articles including 33 cases were identified. Poisoning severity was classified as 3 mild, 11 moderate, and 19 severe cases. Nine cases were treated with L-carnitine while 24 cases received extracorporeal therapy without L-carnitine. All patients except one expired patient treated with hemodialysis recovered clinically and no adverse effects were noted. A case report comparing two patients who ingested the same amount of valproic acid showed increased ICU stay (3 vs. 11 days) in case of delayed extracorporeal therapy. Published evidence comparing L-carnitine with extracorporeal therapy is limited. Based on the available evidence, it is reasonable to consider L-carnitine for patients with acute valproic acid overdose. In case of severe poisoning, extracorporeal therapy would also be considered in the early phase of treatment.

Keywords: carnitine, overdose, poisoning, renal dialysis, valproic acid

Procedia PDF Downloads 345
117 Using MALDI-TOF MS to Detect Environmental Microplastics (Polyethylene, Polyethylene Terephthalate, and Polystyrene) within a Simulated Tissue Sample

Authors: Kara J. Coffman-Rea, Karen E. Samonds

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Microplastic pollution is an urgent global threat to our planet and human health. Microplastic particles have been detected within our food, water, and atmosphere, and found within the human stool, placenta, and lung tissue. However, most spectrometric microplastic detection methods require chemical digestion which can alter or destroy microplastic particles and makes it impossible to acquire information about their in-situ distribution. MALDI TOF MS (Matrix-assisted laser desorption ionization-time of flight mass spectrometry) is an analytical method using a soft ionization technique that can be used for polymer analysis. This method provides a valuable opportunity to both acquire information regarding the in-situ distribution of microplastics and also minimizes the destructive element of chemical digestion. In addition, MALDI TOF MS allows for expanded analysis of the microplastics including detection of specific additives that may be present within them. MALDI TOF MS is particularly sensitive to sample preparation and has not yet been used to analyze environmental microplastics within their specific location (e.g., biological tissues, sediment, water). In this study, microplastics were created using polyethylene gloves, polystyrene micro-foam, and polyethylene terephthalate cable sleeving. Plastics were frozen using liquid nitrogen and ground to obtain small fragments. An artificial tissue was created using a cellulose sponge as scaffolding coated with a MaxGel Extracellular Matrix to simulate human lung tissue. Optimal preparation techniques (e.g., matrix, cationization reagent, solvent, mixing ratio, laser intensity) were first established for each specific polymer type. The artificial tissue sample was subsequently spiked with microplastics, and specific polymers were detected using MALDI-TOF-MS. This study presents a novel method for the detection of environmental polyethylene, polyethylene terephthalate, and polystyrene microplastics within a complex sample. Results of this study provide an effective method that can be used in future microplastics research and can aid in determining the potential threats to environmental and human health that they pose.

Keywords: environmental plastic pollution, MALDI-TOF MS, microplastics, polymer identification

Procedia PDF Downloads 223
116 Computer-Aided Diagnosis System Based on Multiple Quantitative Magnetic Resonance Imaging Features in the Classification of Brain Tumor

Authors: Chih Jou Hsiao, Chung Ming Lo, Li Chun Hsieh

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Brain tumor is not the cancer having high incidence rate, but its high mortality rate and poor prognosis still make it as a big concern. On clinical examination, the grading of brain tumors depends on pathological features. However, there are some weak points of histopathological analysis which can cause misgrading. For example, the interpretations can be various without a well-known definition. Furthermore, the heterogeneity of malignant tumors is a challenge to extract meaningful tissues under surgical biopsy. With the development of magnetic resonance imaging (MRI), tumor grading can be accomplished by a noninvasive procedure. To improve the diagnostic accuracy further, this study proposed a computer-aided diagnosis (CAD) system based on MRI features to provide suggestions of tumor grading. Gliomas are the most common type of malignant brain tumors (about 70%). This study collected 34 glioblastomas (GBMs) and 73 lower-grade gliomas (LGGs) from The Cancer Imaging Archive. After defining the region-of-interests in MRI images, multiple quantitative morphological features such as region perimeter, region area, compactness, the mean and standard deviation of the normalized radial length, and moment features were extracted from the tumors for classification. As results, two of five morphological features and three of four image moment features achieved p values of <0.001, and the remaining moment feature had p value <0.05. Performance of the CAD system using the combination of all features achieved the accuracy of 83.18% in classifying the gliomas into LGG and GBM. The sensitivity is 70.59% and the specificity is 89.04%. The proposed system can become a second viewer on clinical examinations for radiologists.

Keywords: brain tumor, computer-aided diagnosis, gliomas, magnetic resonance imaging

Procedia PDF Downloads 233
115 Numerical Investigation of the Needle Opening Process in a High Pressure Gas Injector

Authors: Matthias Banholzer, Hagen Müller, Michael Pfitzner

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Gas internal combustion engines are widely used as propulsion systems or in power plants to generate heat and electricity. While there are different types of injection methods including the manifold port fuel injection and the direct injection, the latter has more potential to increase the specific power by avoiding air displacement in the intake and to reduce combustion anomalies such as backfire or pre-ignition. During the opening process of the injector, multiple flow regimes occur: subsonic, transonic and supersonic. To cover the wide range of Mach numbers a compressible pressure-based solver is used. While the standard Pressure Implicit with Splitting of Operators (PISO) method is used for the coupling between velocity and pressure, a high-resolution non-oscillatory central scheme established by Kurganov and Tadmor calculates the convective fluxes. A blending function based on the local Mach- and CFL-number switches between the compressible and incompressible regimes of the developed model. As the considered operating points are well above the critical state of the used fluids, the ideal gas assumption is not valid anymore. For the real gas thermodynamics, the models based on the Soave-Redlich-Kwong equation of state were implemented. The caloric properties are corrected using a departure formalism, for the viscosity and the thermal conductivity the empirical correlation of Chung is used. For the injector geometry, the dimensions of a diesel injector were adapted. Simulations were performed using different nozzle and needle geometries and opening curves. It can be clearly seen that there is a significant influence of all three parameters.

Keywords: high pressure gas injection, hybrid solver, hydrogen injection, needle opening process, real-gas thermodynamics

Procedia PDF Downloads 436
114 The Role of a Novel DEAD-Box Containing Protein in NLRP3 Inflammasome Activation

Authors: Yi-Hui Lai, Chih-Hsiang Yang, Li-Chung Hsu

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The inflammasome is a protein complex that modulates caspase-1 activity, resulting in proteolytic cleavage of proinflammatory cytokines such as IL-1β and IL-18, into their bioactive forms. It has been shown that the inflammasomes play a crucial role in the clearance of pathogenic infection and tissue repair. However, dysregulated inflammasome activation contributes to a wide range of human diseases such as cancers and auto-inflammatory diseases. Yet, regulation of NLRP3 inflammasome activation remains largely unknown. We discovered a novel DEAD box protein, whose biological function has not been reported, not only negatively regulates NLRP3 inflammasome activation by interfering NLRP3 inflammasome assembly and cellular localization but also mitigate pyroptosis upon pathogen evasion. The DEAD-box protein is the first DEAD-box protein gets involved in modulation of the inflammasome activation. In our study, we found that caspase-1 activation and mature IL-1β production were largely enhanced upon LPS challenge in the DEAD box-containing protein- deleted THP-1 macrophages and bone marrow-derived macrophages (BMDMs). In addition, this DEAD box-containing protein migrates from the nucleus to the cytoplasm upon LPS stimulation, which is required for its inhibitory role in NLRP3 inflammasome activation. The DEAD box-containing protein specifically interacted with the LRR motif of NLRP3 via its DEAD domain. Furthermore, due to the crucial role of the NLRP3 LRR domain in the recruitment of NLRP3 to mitochondria and binding to its adaptor ASC, we found that the interaction of NLRP3 and ASC was downregulated in the presence of the DEAD box-containing protein. In addition to the mechanical study, we also found that this DEAD box protein protects host cells from inflammasome-triggered cell death in response to broad-ranging pathogens such as Candida albicans, Streptococcus pneumoniae, etc., involved in nosocomial infections and severe fever shock. Collectively, our results suggest that this novel DEAD box molecule might be a key therapeutic strategy for various infectious diseases.

Keywords: inflammasome, inflammation, innate immunity, pyroptosis

Procedia PDF Downloads 259
113 Development of Programmed Cell Death Protein 1 Pathway-Associated Prognostic Biomarkers for Bladder Cancer Using Transcriptomic Databases

Authors: Shu-Pin Huang, Pai-Chi Teng, Hao-Han Chang, Chia-Hsin Liu, Yung-Lun Lin, Shu-Chi Wang, Hsin-Chih Yeh, Chih-Pin Chuu, Jiun-Hung Geng, Li-Hsin Chang, Wei-Chung Cheng, Chia-Yang Li

Abstract:

The emergence of immune checkpoint inhibitors (ICIs) targeting proteins like PD-1 and PD-L1 has changed the treatment paradigm of bladder cancer. However, not all patients benefit from ICIs, with some experiencing early death. There's a significant need for biomarkers associated with the PD-1 pathway in bladder cancer. Current biomarkers focus on tumor PD-L1 expression, but a more comprehensive understanding of PD-1-related biology is needed. Our study has developed a seven-gene risk score panel, employing a comprehensive bioinformatics strategy, which could serve as a potential prognostic and predictive biomarker for bladder cancer. This panel incorporates the FYN, GRAP2, TRIB3, MAP3K8, AKT3, CD274, and CD80 genes. Additionally, we examined the relationship between this panel and immune cell function, utilizing validated tools such as ESTIMATE, TIDE, and CIBERSORT. Our seven-genes panel has been found to be significantly associated with bladder cancer survival in two independent cohorts. The panel was also significantly correlated with tumor infiltration lymphocytes, immune scores, and tumor purity. These factors have been previously reported to have clinical implications on ICIs. The findings suggest the potential of a PD-1 pathway-based transcriptomic panel as a prognostic and predictive biomarker in bladder cancer, which could help optimize treatment strategies and improve patient outcomes.

Keywords: bladder cancer, programmed cell death protein 1, prognostic biomarker, immune checkpoint inhibitors, predictive biomarker

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112 Early Outcomes and Lessons from the Implementation of a Geriatric Hip Fracture Protocol at a Level 1 Trauma Center

Authors: Peter Park, Alfonso Ayala, Douglas Saeks, Jordan Miller, Carmen Flores, Karen Nelson

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Introduction Hip fractures account for more than 300,000 hospital admissions every year. Many present as fragility fractures in geriatric patients with multiple medical comorbidities. Standardized protocols for the multidisciplinary management of this patient population have been shown to improve patient outcomes. A hip fracture protocol was implemented at a Level I Trauma center with a focus on pre-operative medical optimization and early surgical care. This study evaluates the efficacy of that protocol, including the early transition period. Methods A retrospective review was performed of all patients ages 60 and older with isolated hip fractures who were managed surgically between 2020 and 2022. This included patients 1 year prior and 1 year following the implementation of a hip fracture protocol at a Level I Trauma center. Results 530 patients were identified: 249 patients were treated before, and 281 patients were treated after the protocol was instituted. There was no difference in mean age (p=0.35), gender (p=0.3), or Charlson Comorbidity Index (p=0.38) between the cohorts. Following the implementation of the protocol, there were observed increases in time to surgery (27.5h vs. 33.8h, p=0.01), hospital length of stay (6.3d vs. 9.7d, p<0.001), and ED LOS (5.1h vs. 6.2h, p<0.001). There were no differences in in-hospital mortality (2.01% pre vs. 3.20% post, p=0.39) and complication rates (25% pre vs 26% post, p=0.76). A trend towards improved outcomes was seen after the early transition period but failed to yield statistical significance. Conclusion Early medical management and surgical intervention are key determining factors affecting outcomes following fragility hip fractures. The implementation of a hip fracture protocol at this institution has not yet significantly affected these parameters. This could in part be due to the restrictions placed at this institution during the COVID-19 pandemic. Despite this, the time to OR pre-and post-implementation was quicker than figures reported elsewhere in literature. Further longitudinal data will be collected to determine the final influence of this protocol. Significance/Clinical Relevance Given the increasing number of elderly people and the high morbidity and mortality associated with hip fractures in this population finding cost effective ways to improve outcomes in the management of these injuries has the potential to have enormous positive impact for both patients and hospital systems.

Keywords: hip fracture, geriatric, treatment algorithm, preoperative optimization

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111 A Systematic Review for the Association between Active Smoking and Latent Tuberculosis Infection

Authors: Pui Hong Chung, Wing Chi Ho, Jun Li, Cyrus Leung, Ek Yeoh

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Background: Cigarette smoking is associated with poor tuberculosis (TB) outcomes in terms of progression of active TB, relapse of TB and TB-related mortality, but the association with latent tuberculosis infection (LTBI) is unclear. The systematic review conducted aimed at studying the association between active smoking and LTBI, and likelihood of dose-response relationship. Methods: Two independent reviewers searched three electronic databases comprising PudMed, Medline by EBSCOHOST, ExcerptaMedica Database (EMBASE), from inception up to 31st Dec 2015 for studies reporting data on current smoking and the LTBI with tuberculin skin test (TST) or interferon-γ release assays (IGRAs) results, comparing the odds ratios (ORs) of outcome measure of TST or IGRAs among current smokers with 95% confidence intervals (CI). Results: Seven studies were identified, including six cross-sectional studies and one longitudinal cohort study. The outcome measures from three studies were in TST, three studies in IGRAs and one for both tests. For TST, OR ranging from 1.39 to 3.40 (95% CI) with all studies shown positive association between cigarette smoking and LTBI. For IGRAs, OR ranging from 0.47 to 1.89 (95% CI) with one study shown the negative association that might be related to impaired interferon-gamma production in immunosuppressive persons. One identified study demonstrated positive dose-response relationship in TST result. Conclusions: Cigarette smoking is likely to be a risk factor of LTBI. There is the important implication for TB and tobacco control program to halt TB by empowering public health policy. Further study is also needed to provide more evidence of the dose-response model/relationship.

Keywords: latent tuberculosis infection, systematic review, active smoking, model

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110 The Relationship between the Content of Inner Human Experience and Well-Being: An Experience Sampling Study

Authors: Xinqi Guo, Karen R. Dobkins

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Background and Objectives: Humans are probably the only animals whose minds are constantly filled with thoughts, feelings and emotions. Previous studies have investigated human minds from different dimensions, including its proportion of time for not being present, its representative format, its personal relevance, its temporal locus, and affect valence. The current study aims at characterizing human mind by employing Experience Sampling Methods (ESM), a self-report research procedure for studying daily experience. This study emphasis on answering the following questions: 1) How does the contents of the inner experience vary across demographics, 2) Are certain types of inner experiences correlated with level of mindfulness and mental well-being (e.g., are people who spend more time being present happier, and are more mindful people more at-present?), 3) Will being prompted to report one’s inner experience increase mindfulness and mental well-being? Methods: Participants were recruited from the subject pool of UC San Diego or from the social media. They began by filling out two questionnaires: 1) Five Facet Mindfulness Questionnaire-Short Form, and 2) Warwick-Edinburgh Mental Well-being Scale, and demographic information. Then they participated in the ESM part by responding to the prompts which contained questions about their real-time inner experience: if they were 'at-present', 'mind-wandering', or 'zoned-out'. The temporal locus, the clarity, and the affect valence, and the personal importance of the thought they had the moment before the prompt were also assessed. A mobile app 'RealLife Exp' randomly delivered these prompts 3 times/day for 6 days during wake-time. After the 6 days, participants completed questionnaire (1) and (2) again. Their changes of score were compared to a control group who did not participate in the ESM procedure (yet completed (1) and (2) one week apart). Results: Results are currently preliminary as we continue to collect data. So far, there is a trend that participants are present, mind-wandering and zoned-out, about 53%, 23% and 24% during wake-time, respectively. The thoughts of participants are ranked to be clearer and more neutral if they are present vs. mind-wandering. Mind-wandering thoughts are 66% about the past, consisting 80% of inner speech. Discussion and Conclusion: This study investigated the subjective account of human mind by a tool with high ecological validity. And it broadens the understanding of the relationship between contents of mind and well-being.

Keywords: experience sampling method, meta-memory, mindfulness, mind-wandering

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109 Eudesmane-Type Sesquiterpenes from Laggera alata Inhibiting Angiogenesis

Authors: Liang Ning, Chung Hau Yin

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Angiogenesis is the process of new blood vessel development. It has been recognized as a therapeutic target for blocking cancer growth four decades ago. Vascular sprouting is initiated by pro-angiogenic factors. Vascular endothelial cell growth factor (VEGF) plays a central role in angiogenic initiation, many patients with cancer or ocular neovascularization have been benefited from anti-VEGF therapy. Emerging approaches impacting in the later stages of vessel remodeling and maturation are expected to improve clinical efficacy. TIE receptor as well as the corresponding angiopoietin ligands, were identified as another endothelial cell specific receptor tyrosine kinase signaling system. Much efforts were made to reduce the activity of angiopoietin-TIE receptor axis. Two eudesmane-type sesquiterpenes from laggera alata, namely, 15-dihydrocostic acid and ilicic acid were found with strong anti-angiogenic properties in zebrafish model. Meanwhile, the mRNA expression levels of VEGFR2 and TIE2 pathway related genes were down-regulated in the sesquiterpenes treated zebrafish embryos. Besides, in human umbilical vein endothelial cells (HUVECs), the sesquiterpenes have the ability to inhibit VEGF-induced HUVECs proliferation and migration at non-toxic concentration. Moreover, angiopoietin-2 induced TIE2 phosphorylation was inhibited by the sesquiterpenes, the inhibitory effect was detected in angiopoietin-1 induced HUVECs proliferation as well. Thus, we hypothesized the anti-angiogenic activity of the compounds may via the inhibition of VEGF and TIE2 related pathways. How the compounds come into play as the pathways inhibitors need to be evaluated in the future.

Keywords: Laggera alata, eudesmane-type sesquiterpene, anti-angiogenesis, VEGF, angiopoietin, TIE2

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108 Site-Specific Delivery of Hybrid Upconversion Nanoparticles for Photo-Activated Multimodal Therapies of Glioblastoma

Authors: Yuan-Chung Tsai, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu

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In order to enhance the photodynamic/photothermal therapeutic efficacy on glioblastoma, the functionized upconversion nanoparticles with the capability of converting the deep tissue penetrating near-infrared light into visible wavelength for activating photochemical reaction were developed. The drug-loaded nanoparticles (NPs) were obtained from the self-assembly of oleic acid-coated upconversion nanoparticles along with maleimide-conjugated poly(ethylene glycol)-cholesterol (Mal-PEG-Chol), as the NP stabilizer, and hydrophobic photosensitizers, IR-780 (for photothermal therapy, PTT) and mTHPC (for photodynamic therapy, PDT), in aqueous phase. Both the IR-780 and mTHPC were loaded into the hydrophobic domains within NPs via hydrophobic association. The peptide targeting ligand, angiopep-2, was further conjugated with the maleimide groups at the end of PEG adducts on the NP surfaces, enabling the affinity coupling with the low-density lipoprotein receptor-related protein-1 of tumor endothelial cells and malignant astrocytes. The drug-loaded NPs with the size of ca 80 nm in diameter exhibit a good colloidal stability in physiological conditions. The in vitro data demonstrate the successful targeting delivery of drug-loaded NPs toward the ALTS1C1 cells (murine astrocytoma cells) and the pronounced cytotoxicity elicited by combinational effect of PDT and PTT. The in vivo results show the promising brain orthotopic tumor targeting of drug-loaded NPs and sound efficacy for brain tumor dual-modality treatment. This work shows great potential for improving photodynamic/photothermal therapeutic efficacy of brain cancer.

Keywords: drug delivery, orthotopic brain tumor, photodynamic/photothermal therapies, upconversion nanoparticles

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107 Intermediate-Term Impact of Taiwan High-Speed Rail (HSR) and Land Use on Spatial Patterns of HSR Travel

Authors: Tsai Yu-hsin, Chung Yi-Hsin

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The employment of an HSR system, resulting in elevation in the inter-city/-region accessibility, is likely to promote spatial interaction between places in the HSR and extended territory. The inter-city/-region travel via HSR could be, among others, affected by the land use, transportation, and location of the HSR station at both trip origin and destination ends. However, relatively few insights have been shed on these impacts and spatial patterns of the HSR travel. The research purposes, as phase one of a series of HSR related research, of this study are threefold: to analyze the general spatial patterns of HSR trips, such as the spatial distribution of trip origins and destinations; to analyze if specific land use, transportation characteristics, and trip characteristics affect HSR trips in terms of the use of HSR, the distribution of trip origins and destinations, and; to analyze the socio-economic characteristics of HSR travelers. With the Taiwan HSR starting operation in 2007, this study emphasizes on the intermediate-term impact of HSR, which is made possible with the population and housing census and industry and commercial census data and a station area intercept survey conducted in the summer 2014. The analysis will be conducted at the city, inter-city, and inter-region spatial levels, as necessary and required. The analysis tools include descriptive statistics and multivariate analysis with the assistance of SPSS, HLM and ArcGIS. The findings, on the one hand, can provide policy implications for associated land use, transportation plan and the site selection of HSR station. On the other hand, on the travel the findings are expected to provide insights that can help explain how land use and real estate values could be affected by HSR in following phases of this series of research.

Keywords: high speed rail, land use, travel, spatial pattern

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106 Quantitative Evaluation of Mitral Regurgitation by Using Color Doppler Ultrasound

Authors: Shang-Yu Chiang, Yu-Shan Tsai, Shih-Hsien Sung, Chung-Ming Lo

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Mitral regurgitation (MR) is a heart disorder which the mitral valve does not close properly when the heart pumps out blood. MR is the most common form of valvular heart disease in the adult population. The diagnostic echocardiographic finding of MR is straightforward due to the well-known clinical evidence. In the determination of MR severity, quantification of sonographic findings would be useful for clinical decision making. Clinically, the vena contracta is a standard for MR evaluation. Vena contracta is the point in a blood stream where the diameter of the stream is the least, and the velocity is the maximum. The quantification of vena contracta, i.e. the vena contracta width (VCW) at mitral valve, can be a numeric measurement for severity assessment. However, manually delineating the VCW may not accurate enough. The result highly depends on the operator experience. Therefore, this study proposed an automatic method to quantify VCW to evaluate MR severity. Based on color Doppler ultrasound, VCW can be observed from the blood flows to the probe as the appearance of red or yellow area. The corresponding brightness represents the value of the flow rate. In the experiment, colors were firstly transformed into HSV (hue, saturation and value) to be closely align with the way human vision perceives red and yellow. Using ellipse to fit the high flow rate area in left atrium, the angle between the mitral valve and the ultrasound probe was calculated to get the vertical shortest diameter as the VCW. Taking the manual measurement as the standard, the method achieved only 0.02 (0.38 vs. 0.36) to 0.03 (0.42 vs. 0.45) cm differences. The result showed that the proposed automatic VCW extraction can be efficient and accurate for clinical use. The process also has the potential to reduce intra- or inter-observer variability at measuring subtle distances.

Keywords: mitral regurgitation, vena contracta, color doppler, image processing

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105 IgA/λ Plasma Cell Myeloma with λ Light Chain Amyloidosis: A Case Report

Authors: Kai Pei Huang, Ting Chung Hung, Li Ching Wu

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Amyloidosis refers to a variety of conditions wherein amyloid proteins are abnormally deposited in organ or tissues and cause harm. Among the several forms of amyloidosis, the principal types of that in inpatient medical services are the AL amyloidosis (primary) and AA amyloidois (secondary). AL Amyloidois is due to deposition of protein derived from overproduction of immunoglobulin light chain in plasma cell myeloma. Furthermore, it is a systemic disorder that can present with a variety of symptoms, including heavy proteinemia and edema, heptosplenomegaly, otherwise unexplained heart failure. We reported a 78-year-old female presenting dysuria, oliguria and leg edema for several months. Laboratory data showed proteinuria (UPCR:1679.8), leukocytosis (WBC:16.2 x 10^3/uL), results of serum urea nitrogen (39mg/dL), creatinine (0.76 mg/dL), IgG (748 mg/dL.), IgA (635 mg/dL), IgM (63 mg/dL), kappa light chain(18.8 mg/dL), lambda light chain (110.0 mg/dL) and kappa/lambda ratio (0.17). Renal biopsy found amyloid fibrils in glomerular mesangial area, and Congo red stain highlights amyloid deposition in glomeruli. Additional lab studies included serum protein electrophoresis, which shows a major monoclonal peak in β region and minor small peak in gamma region, and the immunotyping studies for serum showed two IgA/λ type. We treated sample with beta-mercaptoethanol which reducing the polymerized immunoglobulin to clarify two IgA/λ are secreted from the same plasma cell clone in bone marrow. Later examination confirmed it existed plasma cell infiltration in bone marrow, and the immunohistochemical staining showed monotypic for λ light chain and are positive for IgA. All findings mentioned above reveal it is a case of plasma cell myeloma with λ Light Chain Amyloidosis.

Keywords: amyloidosis, immunoglobulin light chain, plasma cell myeloma, serum protein electrophoresis

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104 Tommy: Communication in Education about Disability

Authors: Karen V. Lee

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The background and significance of this study involve communication in education by a faculty advisor exploring story and music that informs others about a disabled teacher. Social issues draw deep reflection about the emotional turmoil. As a musician becoming a teacher is a passionate yet complex endeavor, the faculty advisor shares a poetic but painful story about a disabled teacher being inducted into the teaching profession. The qualitative research method as theoretical framework draws on autoethnography of music and story where the faculty advisor approaches a professor for advice. His musicianship shifts her forward, backward, and sideways through feelings that evoke and provoke curriculum to remove communication barriers in education. They discover they do not transfer knowledge from educational method classes. Instead, the autoethnography embeds musical language as a metaphorical conduit for removing communication barriers in teacher education. Sub-themes involve communication barriers and educational technologies to ensure teachers receive social, emotional, physical, spiritual, and intervention disability resources that evoke visceral, emotional responses from the audience. Major findings of the study discover how autoethnography of music and story bring the authors to understand wider political issues of the practicum internship for teachers with disabilities. An epiphany reveals the irony of living in a culture of both uniformity and diversity. They explore the constructs of secrecy, ideology, abnormality, and marginalization by evoking visceral and emotional responses from the audience. As the voices harmonize plot, climax, characterization, and denouement, they dramatize meaning that is episodic yet incomplete to highlight the circumstances surrounding the disabled protagonist’s life. In conclusion, the qualitative research method argues for embracing storied experiences that depict communication in education. Scholarly significance embraces personal thoughts and feelings as a way of understanding social phenomena while highlighting the importance of removing communication barriers in education. The circumstance about a teacher with a disability is not uncommon in society. Thus, the authors resolve to removing barriers in education by using stories to transform the personal and cultural influences that provoke new ways of thinking about the curriculum for a disabled teacher.

Keywords: communication in education, communication barriers, autoethnography, teaching

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103 Understanding the Semantic Network of Tourism Studies in Taiwan by Using Bibliometrics Analysis

Authors: Chun-Min Lin, Yuh-Jen Wu, Ching-Ting Chung

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The formulation of tourism policies requires objective academic research and evidence as support, especially research from local academia. Taiwan is a small island, and its economic growth relies heavily on tourism revenue. Taiwanese government has been devoting to the promotion of the tourism industry over the past few decades. Scientific research outcomes by Taiwanese scholars may and will help lay the foundations for drafting future tourism policy by the government. In this study, a total of 120 full journal articles published between 2008 and 2016 from the Journal of Tourism and Leisure Studies (JTSL) were examined to explore the scientific research trend of tourism study in Taiwan. JTSL is one of the most important Taiwanese journals in the tourism discipline which focuses on tourism-related issues and uses traditional Chinese as the study language. The method of co-word analysis from bibliometrics approaches was employed for semantic analysis in this study. When analyzing Chinese words and phrases, word segmentation analysis is a crucial step. It must be carried out initially and precisely in order to obtain meaningful word or word chunks for further frequency calculation. A word segmentation system basing on N-gram algorithm was developed in this study to conduct semantic analysis, and 100 groups of meaningful phrases with the highest recurrent rates were located. Subsequently, co-word analysis was employed for semantic classification. The results showed that the themes of tourism research in Taiwan in recent years cover the scope of tourism education, environmental protection, hotel management, information technology, and senior tourism. The results can give insight on the related issues and serve as a reference for tourism-related policy making and follow-up research.

Keywords: bibliometrics, co-word analysis, word segmentation, tourism research, policy

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102 The Foucaultian Relationship between Power and Knowledge: Genealogy as a Method for Epistemic Resistance

Authors: Jana Soler Libran

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The primary aim of this paper is to analyze the relationship between power and knowledge suggested in Michel Foucault's theory. Taking into consideration the role of power in knowledge production, the goal is to evaluate to what extent genealogy can be presented as a practical method for epistemic resistance. To do so, the methodology used consists of a revision of Foucault’s literature concerning the topic discussed. In this sense, conceptual analysis is applied in order to understand the effect of the double dimension of power on knowledge production. In its negative dimension, power is conceived as an organ of repression, vetoing certain instances of knowledge considered deceitful. In opposition, in its positive dimension, power works as an organ of the production of truth by means of institutionalized discourses. This double declination of power leads to the first main findings of the present analysis: no truth or knowledge can lie outside power’s action, and power is constituted through accepted forms of knowledge. To second these statements, Foucaultian discourse formations are evaluated, presenting external exclusion procedures as paradigmatic practices to demonstrate how power creates and shapes the validity of certain epistemes. Thus, taking into consideration power’s mechanisms to produce and reproduce institutionalized truths, this paper accounts for the Foucaultian praxis of genealogy as a method to reveal power’s intention, instruments, and effects in the production of knowledge. In this sense, it is suggested to consider genealogy as a practice which, firstly, reveals what instances of knowledge are subjugated to power and, secondly, promotes aforementioned peripherical discourses as a form of epistemic resistance. In order to counterbalance these main theses, objections to Foucault’s work from Nancy Fraser, Linda Nicholson, Charles Taylor, Richard Rorty, Alvin Goldman, or Karen Barad are discussed. In essence, the understanding of the Foucaultian relationship between power and knowledge is essential to analyze how contemporary discourses are produced by both traditional institutions and new forms of institutionalized power, such as mass media or social networks. Therefore, Michel Foucault's practice of genealogy is relevant, not only for its philosophical contribution as a method to uncover the effects of power in knowledge production but also because it constitutes a valuable theoretical framework for political theory and sociological studies concerning the formation of societies and individuals in the contemporary world.

Keywords: epistemic resistance, Foucault’s genealogy, knowledge, power, truth

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101 Aberrant Genome‐Wide DNA Methylation Profiles of Peripheral Blood Mononuclear Cells from Patients Hospitalized with COVID-19

Authors: Inam Ridha, Christine L. Kuryla, Madhuranga Thilakasiri Madugoda Ralalage Don, Norman J. Kleiman, Yunro Chung, Jin Park, Vel Murugan, Joshua LaBaer

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To date, more than 275 million people worldwide have been diagnosed with COVID-19 and the rapid spread of the omicron variant suggests many millions more will soon become infected. Many infections are asymptomatic, while others result in mild to moderate illness. Unfortunately, some infected individuals exhibit more serious symptoms including respiratory distress, thrombosis, cardiovascular disease, multi-organ failure, cognitive difficulties, and, in roughly 2% of cases, death. Studies indicate other coronaviruses can alter the host cell's epigenetic profile and lead to alterations in the immune response. To better understand the mechanism(s) by which SARS-CoV-2 infection causes serious illness, DNA methylation profiles in peripheral blood mononuclear cells (PBMCs) from 90 hospitalized severely ill COVID-19 patients were compared to profiles from uninfected control subjects. Exploratory epigenome-wide DNA methylation analyses were performed using multiplexed methylated DNA immunoprecipitation (MeDIP) followed by pathway enrichment analysis. The findings demonstrated significant DNA methylation changes in infected individuals as compared to uninfected controls. Pathway analysis indicated that apoptosis, cell cycle control, Toll-like receptors (TLR), cytokine interactions, and T cell differentiation were among the most affected metabolic processes. In addition, changes in specific gene methylation were compared to SARS-CoV-2 induced changes in RNA expression using published RNA-seq data from 3 patients with severe COVID-19. These findings demonstrate significant correlations between differentially methylated and differentially expressed genes in a number of critical pathways.

Keywords: COVID19, epigenetics, DNA mathylation, viral infection

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100 Tumour-Associated Tissue Eosinophilia as a Prognosticator in Oral Squamous Cell Carcinoma

Authors: Karen Boaz, C. R. Charan

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Background: The infiltration of tumour stroma by eosinophils, Tumor-Associated Tissue Eosinophilia (TATE), is known to modulate the progression of Oral Squamous Cell Carcinoma (OSCC). Eosinophils have direct tumoricidal activity by release of cytotoxic proteins and indirectly they enhance permeability into tumor cells enabling penetration of tumoricidal cytokines. Also, eosinophils may promote tumor angiogenesis by production of several angiogenic factors. Identification of eosinophils in the inflammatory stroma has been proven to be an important prognosticator in cancers of mouth, oesophagus, larynx, pharynx, breast, lung, and intestine. Therefore, the study aimed to correlate TATE with clinical and histopathological variables, and blood eosinophil count to assess the role of TATE as a prognosticator in Oral Squamous Cell Carcinoma (OSCC). Methods: Seventy two biopsy-proven cases of OSCC formed the study cohort. Blood eosinophil counts and TNM stage were obtained from the medical records. Tissue sections (5µm thick) were stained with Haematoxylin and Eosin. The eosinophils were quantified at invasive tumour front (ITF) in 10HPF (40x magnification) with an ocular grid. Bryne’s grading of ITF was also performed. A subset of thirty cases was also assessed for association of TATE with recurrence, involvement of lymph nodes and surgical margins. Results: 1) No statistically significant correlation was found between TATE and TNM stage, blood eosinophil counts and most parameters of Bryne’s grading system. 2) Statistically significant relation of intense degree of TATE was associated with the absence of distant metastasis, increased lympho-plasmacytic response and increased survival (diseasefree and overall) of OSCC patients. 3) In the subset of 30 cases, tissue eosinophil counts were higher in cases with lymph node involvement, decreased survival, without margin involvement and in cases that did not recur. Conclusion: While the role of eosinophils in mediating immune responses seems ambiguous as eosinophils support cell-mediated tumour immunity in early stages while inhibiting the same in advanced stages, TATE may be used as a surrogate marker for determination of prognosis in oral squamous cell carcinoma.

Keywords: tumour-associated tissue eosinophilia, oral squamous cell carcinoma, prognosticator, tumoral immunity

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