Search results for: Carl Brandon C. Barlis
11 Multiaxial Fatigue in Thermal Elastohydrodynamic Lubricated Contacts with Asperities and Slip
Authors: Carl-Magnus Everitt, Bo Alfredsson
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Contact mechanics and tribology have been combined with fundamental fatigue and fracture mechanics to form the asperity mechanism which supplies an explanation for the surface-initiated rolling contact fatigue damage, called pitting or spalling. The cracks causing the pits initiates at one surface point and thereafter they slowly grow into the material before chipping of a material piece to form the pit. In the current study, the lubrication aspects on fatigue initiation are simulated by passing a single asperity through a thermal elastohydrodynamic lubricated, TEHL, contact. The physics of the lubricant was described with Reynolds equation and the lubricants pressure-viscosity relation was modeled by Roelands equation, formulated to include temperature dependence. A pressure dependent shear limit was incorporated. To capture the full phenomena of the sliding contact the temperature field was resolved through the incorporation of the energy flow. The heat was mainly generated due to shearing of the lubricant and from dry friction where metal contact occurred. The heat was then transported, and conducted, away by the solids and the lubricant. The fatigue damage caused by the asperities was evaluated through Findley’s fatigue criterion. The results show that asperities, in the size of surface roughness found in applications, may cause surface initiated fatigue damage and crack initiation. The simulations also show that the asperities broke through the lubricant in the inlet, causing metal to metal contact with high friction. When the asperities thereafter moved through the contact, the sliding provided the asperities with lubricant releasing the metal contact. The release of metal contact was possible due to the high viscosity the lubricant obtained from the high pressure. The metal contact in the inlet caused higher friction which increased the risk of fatigue damage. Since the metal contact occurred in the inlet it increased the fatigue risk more for asperities subjected to negative slip than positive slip. Therefore the fatigue evaluations showed that the asperities subjected to negative slip yielded higher fatigue stresses than the asperities subjected to positive slip of equal magnitude. This is one explanation for why pitting is more common in the dedendum than the addendum on pinion gear teeth. The simulations produced further validation for the asperity mechanism by showing that asperities cause surface initiated fatigue and crack initiation.Keywords: fatigue, rolling, sliding, thermal elastohydrodynamic
Procedia PDF Downloads 12110 Functionalization of Carbon-Coated Iron Nanoparticles with Fluorescent Protein
Authors: A. G. Pershina, P. S. Postnikov, M. E. Trusova, D. O. Burlakova, A. E. Sazonov
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Invention of magnetic-fluorescent nanocomposites is a rapidly developing area of research. The magnetic-fluorescent nanocomposite attractiveness is connected with the ability of simultaneous management and control of such nanocomposites by two independent methods based on different physical principles. These nanocomposites are applied for the solution of various essential scientific and experimental biomedical problems. The aim of this research is development of principle approach to nanobiohybrid structures with magnetic and fluorescent properties design. The surface of carbon-coated iron nanoparticles (Fe@C) were covalently modified by 4-carboxy benzenediazonium tosylate. Recombinant fluorescent protein TagGFP2 (Eurogen) was obtained in E. coli (Rosetta DE3) by standard laboratory techniques. Immobilization of TagGFP2 on the nanoparticles surface was provided by the carbodiimide activation. The amount of COOH-groups on the nanoparticle surface was estimated by elemental analysis (Elementar Vario Macro) and TGA-analysis (SDT Q600, TA Instruments. Obtained nanocomposites were analyzed by FTIR spectroscopy (Nicolet Thermo 5700) and fluorescence microscopy (AxioImager M1, Carl Zeiss). Amount of the protein immobilized on the modified nanoparticle surface was determined by fluorimetry (Cary Eclipse) and spectrophotometry (Unico 2800) with the help of preliminary obtained calibration plots. In the FTIR spectra of modified nanoparticles the adsorption band of –COOH group around 1700 cm-1 and bands in the region of 450-850 cm-1 caused by bending vibrations of benzene ring were observed. The calculated quantity of active groups on the surface was equal to 0,1 mmol/g of material. The carbodiimide activation of COOH-groups on nanoparticles surface results to covalent immobilization of TagGFP2 fluorescent protein (0.2 nmol/mg). The success of immobilization was proved by FTIR spectroscopy. Protein characteristic adsorption bands in the region of 1500-1600 cm-1 (amide I) were presented in the FTIR spectrum of nanocomposite. The fluorescence microscopy analysis shows that Fe@C-TagGFP2 nanocomposite possesses fluorescence properties. This fact confirms that TagGFP2 protein retains its conformation due to immobilization on nanoparticles surface. Magnetic-fluorescent nanocomposite was obtained as a result of unique design solution implementation – the fluorescent protein molecules were fixed to the surface of superparamagnetic carbon-coated iron nanoparticles using original diazonium salts.Keywords: carbon-coated iron nanoparticles, diazonium salts, fluorescent protein, immobilization
Procedia PDF Downloads 3429 The Production of Reinforced Insulation Bricks out of the Concentration of Ganoderma lucidum Fungal Inoculums and Cement Paste
Authors: Jovie Esquivias Nicolas, Ron Aldrin Lontoc Austria, Crisabelle Belleza Bautista, Mariane Chiho Espinosa Bundalian, Owwen Kervy Del Rosario Castillo, Mary Angelyn Mercado Dela Cruz, Heinrich Theraja Recana De Luna, Chriscell Gipanao Eustaquio, Desiree Laine Lauz Gilbas, Jordan Ignacio Legaspi, Larah Denise David Madrid, Charles Linelle Malapote Mendoza, Hazel Maxine Manalad Reyes, Carl Justine Nabora Saberdo, Claire Mae Rendon Santos
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In response to the global race in discovering the next advanced sustainable material that will reduce our ecological footprint, the researchers aimed to create a masonry unit which is competent in physical edifices and other constructional facets. From different proven researches, mycelium has been concluded that when dried can be used as a robust and waterproof building material that can be grown into explicit forms, thus reducing the processing requirements. Hypothesizing inclusive measures to attest fungi’s impressive structural qualities and absorbency, the researchers projected to perform comparative analyses in creating mycelium bricks from mushroom spores of G. lucidum. Three treatments were intended to classify the most ideal concentration of clay and substrate fixings. The substrate bags fixed with 30% clay and 70% mixings indicated highest numerical frequencies in terms of full occupation of fungal mycelia. Subsequently, sorted parts of white portions from the treatment were settled in a thermoplastic mold and burnt. Three proportional concentrations of cultivated substrate and cement were also prioritized to gather results of variation focused on the weights of the bricks in the Water Absorption Test and Durability Test. Fungal inoculums with solutions of cement showed small to moderate amounts of decrease and increase in load. This proves that the treatments did not show any significant difference when it comes to strength, efficiency and absorption capacity. Each of the concentration is equally valid and could be used in supporting the worldwide demands of creating numerous bricks while also taking into consideration the recovery of our nature.Keywords: mycelium, fungi, fungal mycelia, durability test, water absorption test
Procedia PDF Downloads 1358 Spatial Distribution and Cluster Analysis of Sexual Risk Behaviors and STIs Reported by Chinese Adults in Guangzhou, China: A Representative Population-Based Study
Authors: Fangjing Zhou, Wen Chen, Brian J. Hall, Yu Wang, Carl Latkin, Li Ling, Joseph D. Tucker
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Background: Economic and social reforms designed to open China to the world has been successful, but also appear to have rapidly laid the foundation for the reemergence of STIs since 1980s. Changes in sexual behaviors, relationships, and norms among Chinese contributed to the STIs epidemic. As the massive population moved during the last 30 years, early coital debut, multiple sexual partnerships, and unprotected sex have increased within the general population. Our objectives were to assess associations between residences location, sexual risk behaviors and sexually transmitted infections (STIs) among adults living in Guangzhou, China. Methods: Stratified cluster sampling followed a two-step process was used to select populations aged 18-59 years in Guangzhou, China. Spatial methods including Geographic Information Systems (GIS) were utilized to identify 1400 coordinates with latitude and longitude. Face-to-face household interviews were conducted to collect self-report data on sexual risk behaviors and diagnosed STIs. Kulldorff’s spatial scan statistic was implemented to identify and detect spatial distribution and clusters of sexual risk behaviors and STIs. The presence and location of statistically significant clusters were mapped in the study areas using ArcGIS software. Results: In this study, 1215 of 1400 households attempted surveys, with 368 refusals, resulting in a sample of 751 completed surveys. The prevalence of self-reported sexual risk behaviors was between 5.1% and 50.0%. The self-reported lifetime prevalence of diagnosed STIs was 7.06%. Anal intercourse clustered in an area located along the border within the rural-urban continuum (p=0.001). High rate clusters for alcohol or other drugs using before sex (p=0.008) and migrants who lived in Guangzhou less than one year (p=0.007) overlapped this cluster. Excess cases for sex without a condom (p=0.031) overlapped the cluster for college students (p<0.001). Conclusions: Short-term migrants and college students reported greater sexual risk behaviors. Programs to increase safer sex within these communities to reduce the risk of STIs are warranted in Guangzhou. Spatial analysis identified geographical clusters of sexual risk behaviors, which is critical for optimizing surveillance and targeting control measures for these locations in the future.Keywords: cluster analysis, migrant, sexual risk behaviors, spatial distribution
Procedia PDF Downloads 3407 Faculty Use of Geospatial Tools for Deep Learning in Science and Engineering Courses
Authors: Laura Rodriguez Amaya
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Advances in science, technology, engineering, and mathematics (STEM) are viewed as important to countries’ national economies and their capacities to be competitive in the global economy. However, many countries experience low numbers of students entering these disciplines. To strengthen the professional STEM pipelines, it is important that students are retained in these disciplines at universities. Scholars agree that to retain students in universities’ STEM degrees, it is necessary that STEM course content shows the relevance of these academic fields to their daily lives. By increasing students’ understanding on the importance of these degrees and careers, students’ motivation to remain in these academic programs can also increase. An effective way to make STEM content relevant to students’ lives is the use of geospatial technologies and geovisualization in the classroom. The Geospatial Revolution, and the science and technology associated with it, has provided scientists and engineers with an incredible amount of data about Earth and Earth systems. This data can be used in the classroom to support instruction and make content relevant to all students. The purpose of this study was to find out the prevalence use of geospatial technologies and geovisualization as teaching practices in a USA university. The Teaching Practices Inventory survey, which is a modified version of the Carl Wieman Science Education Initiative Teaching Practices Inventory, was selected for the study. Faculty in the STEM disciplines that participated in a summer learning institute at a 4-year university in the USA constituted the population selected for the study. One of the summer learning institute’s main purpose was to have an impact on the teaching of STEM courses, particularly the teaching of gateway courses taken by many STEM majors. The sample population for the study is 97.5 of the total number of summer learning institute participants. Basic descriptive statistics through the Statistical Package for the Social Sciences (SPSS) were performed to find out: 1) The percentage of faculty using geospatial technologies and geovisualization; 2) Did the faculty associated department impact their use of geospatial tools?; and 3) Did the number of years in a teaching capacity impact their use of geospatial tools? Findings indicate that only 10 percent of respondents had used geospatial technologies, and 18 percent had used geospatial visualization. In addition, the use of geovisualization among faculty of different disciplines was broader than the use of geospatial technologies. The use of geospatial technologies concentrated in the engineering departments. Data seems to indicate the lack of incorporation of geospatial tools in STEM education. The use of geospatial tools is an effective way to engage students in deep STEM learning. Future research should look at the effect on student learning and retention in science and engineering programs when geospatial tools are used.Keywords: engineering education, geospatial technology, geovisualization, STEM
Procedia PDF Downloads 2526 Complex Decision Rules in Quality Assurance Processes for Quick Service Restaurant Industry: Human Factors Determining Acceptability
Authors: Brandon Takahashi, Marielle Hanley, Gerry Hanley
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The large-scale quick-service restaurant industry is a complex business to manage optimally. With over 40 suppliers providing different ingredients for food preparation and thousands of restaurants serving over 50 unique food offerings across a wide range of regions, the company must implement a quality assurance process. Businesses want to deliver quality food efficiently, reliably, and successfully at a low cost that the public wants to buy. They also want to make sure that their food offerings are never unsafe to eat or of poor quality. A good reputation (and profitable business) developed over the years can be gone in an instant if customers fall ill eating your food. Poor quality also results in food waste, and the cost of corrective actions is compounded by the reduction in revenue. Product compliance evaluation assesses if the supplier’s ingredients are within compliance with the specifications of several attributes (physical, chemical, organoleptic) that a company will test to ensure that a quality, safe to eat food is given to the consumer and will deliver the same eating experience in all parts of the country. The technical component of the evaluation includes the chemical and physical tests that produce numerical results that relate to shelf-life, food safety, and organoleptic qualities. The psychological component of the evaluation includes organoleptic, which is acting on or involving the use of the sense organs. The rubric for product compliance evaluation has four levels: (1) Ideal: Meeting or exceeding all technical (physical and chemical), organoleptic, & psychological specifications. (2) Deviation from ideal but no impact on quality: Not meeting or exceeding some technical and organoleptic/psychological specifications without impact on consumer quality and meeting all food safety requirements (3) Acceptable: Not meeting or exceeding some technical and organoleptic/psychological specifications resulting in reduction of consumer quality but not enough to lessen demand and meeting all food safety requirements (4) Unacceptable: Not meeting food safety requirements, independent of meeting technical and organoleptic specifications or meeting all food safety requirements but product quality results in consumer rejection of food offering. Sampling of products and consumer tastings within the distribution network is a second critical element of the quality assurance process and are the data sources for the statistical analyses. Each finding is not independently assessed with the rubric. For example, the chemical data will be used to back up/support any inferences on the sensory profiles of the ingredients. Certain flavor profiles may not be as apparent when mixed with other ingredients, which leads to weighing specifications differentially in the acceptability decision. Quality assurance processes are essential to achieve that balance of quality and profitability by making sure the food is safe and tastes good but identifying and remediating product quality issues before they hit the stores. Comprehensive quality assurance procedures implement human factors methodologies, and this report provides recommendations for systemic application of quality assurance processes for quick service restaurant services. This case study will review the complex decision rubric and evaluate processes to ensure the right balance of cost, quality, and safety is achieved.Keywords: decision making, food safety, organoleptics, product compliance, quality assurance
Procedia PDF Downloads 1885 Nature Manifestations: An Archetypal Analysis of Selected Nightwish Songs
Authors: Suzanne Strauss, Leandi Steenkamp
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The Finnish symphonic metal band Nightwish is the brainchild of songwriter and lyricist TuomasHolopainen and the band recorded their first demonstration recording in 1996. The band has since produced nine full-length studio albums, the most recent being the 2020 album Human. :||: Nature., and has reached massive international success. The band is well known for songs about fantasy and escapism and employs many sonic, visual and branding tools and techniques to communicate these constructs to the audience. Among these, is the band’s creation of the so-called “Nightwish world and mythology” with a set of recurring characters and narratives which, in turn, creates a psychological anchor and safe space for Nightwish fans around the globe. Nature and the reverence of nature are central themes in Nightwish’s self-created mythology.Swiss psychologist Carl Jung’s theory of the collective unconscious identified a mysterious reservoir of psychological constructs common to all people, being derived from ancestral memory and experience, common to all humankind, and distinct from the individual’s personal unconscious. Furthermore, he defined archetypes as timeless collective patterns and images that springs forth from the collective unconscious. Archetypes can be actualized when they enter consciousness as images in interaction with the outside world. Archetypal patterns or images can manifest in different ways across world cultures, but follow common patterns, also known as archetypal themes and symbols. The Jungian approach to the psyche places great emphasis on nature, positing a direct link betweenthe concept of wholeness and responsible care for nature and the environment.In our proposed paper, we examine, by means of thematic content analysis, how Nightwish makes use of archetypal themes and symbols referring to nature and the environment in selected songs from their ninth full-length album Human. II Nature. Furthermore, we argue that the longing for and reverence of nature in selected Nightwish songs may serve as a type of “social intervention” and social critique on modern capitalist society. The type of social critique that the band offers is generally connoted intertextually and is not equally explicit in their songs. The band uses a unique combination of escapism, fantasy, and nature narratives to inspire a sense of wonder, enchantment, and magic in the listener. In this way, escapism, fantasy, and nature serve as postmodern frames of reference that aim to “re-enchant” the disenchanted and de-spiritualized. In this way, re-enchantment could also refer to spiritual and/or psychological healing and rebirth.Keywords: archetypes, metal music, nature, Nightwish, social interventions
Procedia PDF Downloads 1114 Exploring the Lived Experiences of Breast Cancer Survivors Post-Treatment
Authors: Nova Grail S. Luminang, Gwyneth B. Gortiza, Alvin E. Haboc, Marinol K. Hate, Rhean Mitchel N. Joven, Kara Kate D. Lammao, Rosemarie M. Lambayung, Elmo Carl D. Lardizabal, Zyra B. Linggayo, Rizza Mae G. Liwag, Ronalyn O. Songcuan
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Breast cancer survivorship represents a complex and continuous journey extending beyond the completion of treatment, involving coping with physical, emotional, and psychological aspects of life post-treatment. This study aimed to explore the lived experiences of breast cancer survivors after successful treatment in Tabuk City, focusing on their post-treatment experiences, coping mechanisms, and necessary lifestyle changes. Researchers have selected Tabuk City as their research locale. Utilizing Martin Heidegger’s descriptive phenomenological design, this qualitative research included six participants, allowing for data saturation. Purposive sampling was employed to select participants. Researchers used Colaizzi’s Phenomenological Method in analyzing the data in order to achieve a reliable understanding of the participants’ experiences. The findings revealed three main themes: going through post-treatment hurdles, building resilience, and transformative wellness adjustments. Breast cancer survivors faced significant challenges, including physical adversities, emotional turmoil, limited social life, memory lapses, decreased sexual intimacy, and economic constraints. To cope, survivors adjusted their thoughts and attitudes, accepted their situation, relied on religious beliefs, and joined the support group Kalinga Cancer Care Ministry INC. Additionally, they strived to return to a normal life and embraced gratitude. Survivors made essential changes to their daily routines, modifying their diets, exploring herbal remedies, and incorporating physical activities such as walking and household chores. These adjustments helped improve their overall well-being and prevent cancer recurrence. The researchers concluded that the journey of breast cancer survivors is marked by significant challenges and inspiring resilience. The impact of breast cancer treatment extends beyond physical recovery, encompassing profound emotional and social dimensions. Despite these difficulties, survivors demonstrate remarkable strength and adaptability, making positive lifestyle changes that offer a hopeful and inspiring narrative of recovery and perseverance.Keywords: breast cancer, lived experiences, breast cancer survivor, post-treatment hurdles, emotional turmoil
Procedia PDF Downloads 323 Characteristics of Bio-hybrid Hydrogel Materials with Prolonged Release of the Model Active Substance as Potential Wound Dressings
Authors: Katarzyna Bialik-Wąs, Klaudia Pluta, Dagmara Malina, Małgorzata Miastkowska
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In recent years, biocompatible hydrogels have been used more and more in medical applications, especially as modern dressings and drug delivery systems. The main goal of this research was the characteristics of bio-hybrid hydrogel materials incorporated with the nanocarrier-drug system, which enable the release in a gradual and prolonged manner, up to 7 days. Therefore, the use of such a combination will provide protection against mechanical damage and adequate hydration. The proposed bio-hybrid hydrogels are characterized by: transparency, biocompatibility, good mechanical strength, and the dual release system, which allows for gradual delivery of the active substance, even up to 7 days. Bio-hybrid hydrogels based on sodium alginate (SA), poly(vinyl alcohol) (PVA), glycerine, and Aloe vera solution (AV) were obtained through the chemical crosslinking method using poly(ethylene glycol) diacrylate as a crosslinking agent. Additionally, a nanocarrier-drug system was incorporated into SA/PVA/AV hydrogel matrix. Here, studies were focused on the release profiles of active substances from bio-hybrid hydrogels using the USP4 method (DZF II Flow-Through System, Erweka GmbH, Langen, Germany). The equipment incorporated seven in-line flow-through diffusion cells. The membrane was placed over support with an orifice of 1,5 cm in diameter (diffusional area, 1.766 cm²). All the cells were placed in a cell warmer connected with the Erweka heater DH 2000i and the Erweka piston pump HKP 720. The piston pump transports the receptor fluid via seven channels to the flow-through cells and automatically adapts the setting of the flow rate. All volumes were measured by gravimetric methods by filling the chambers with Milli-Q water and assuming a density of 1 g/ml. All the determinations were made in triplicate for each cell. The release study of the model active substance was carried out using a regenerated cellulose membrane Spectra/Por®Dialysis Membrane MWCO 6-8,000 Carl Roth® Company. These tests were conducted in buffer solutions – PBS at pH 7.4. A flow rate of receptor fluid of about 4 ml /1 min was selected. The experiments were carried out for 7 days at a temperature of 37°C. The released concentration of the model drug in the receptor solution was analyzed using UV-Vis spectroscopy (Perkin Elmer Company). Additionally, the following properties of the modified materials were studied: physicochemical, structural (FT-IR analysis), morphological (SEM analysis). Finally, the cytotoxicity tests using in vitro method were conducted. The obtained results exhibited that the dual release system allows for the gradual and prolonged delivery of the active substances, even up to 7 days.Keywords: wound dressings, SA/PVA hydrogels, nanocarrier-drug system, USP4 method
Procedia PDF Downloads 1472 Women's Perceptions of Zika Virus Prevention Recommendations: A Tale of Two Cities within Fortaleza, Brazil
Authors: Jeni Stolow, Lina Moses, Carl Kendall
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Zika virus (ZIKV) reemerged as a global threat in 2015 with Brazil at its epicenter. Brazilians have a long history of combatting Aedes aegypti mosquitos as it is a common vector for dengue, chikungunya, and yellow fever. As a response to the epidemic, public health authorities promoted ZIKV prevention behaviors such as mosquito bite prevention, reproductive counseling for women who are pregnant or contemplating pregnancy, pregnancy avoidance, and condom use. Most prevention efforts from Brazil focused on the mosquito vector- utilizing recycled dengue approaches without acknowledging the context in which women were able to adhere to these prevention messages. This study used qualitative methods to explore how women in Fortaleza, Brazil perceive ZIKV, the Brazilian authorities’ ZIKV prevention recommendations, and the feasibility of adhering to these recommendations. A core study aim was to look at how women perceive their physical, social, and natural environment as it impacts women’s ability to adhere to ZIKV prevention behaviors. A Rapid Anthropological Assessment (RAA) containing observations, informational interviews, and semi-structured in-depth interviews were utilized for data collection. The study utilized Grounded Theory as the systematic inductive method of analyzing the data collected. Interviews were conducted with 35 women of reproductive age (15-39 years old), who primarily utilize the public health system. It was found that women’s self-identified economic class was associated with how strongly women felt they could prevent ZIKV. All women interviewed technically belong to the C-class, the middle economic class. Although all members of the same economic class, there was a divide amongst participants as to who perceived themselves as higher C-class versus lower C-class. How women saw their economic status was dictated by how they perceived their physical, social, and natural environment. Women further associated their environment and their economic class to their likelihood of contracting ZIKV, their options for preventing ZIKV, their ability to prevent ZIKV, and their willingness to attempt to prevent ZIKV. Women’s perceived economic status was found to relate to their structural environment (housing quality, sewage, and locations to supplies), social environment (family and peer norms), and natural environment (wetland areas, natural mosquito breeding sites, and cyclical nature of vectors). Findings from this study suggest that women’s perceived environment and economic status impact their perceived feasibility and desire to attempt behaviors to prevent ZIKV. Although ZIKV has depleted from epidemic to endemic status, it is suggested that the virus will return as cyclical outbreaks like that seen with similar arboviruses such as dengue and chikungunya. As the next ZIKV epidemic approaches it is essential to understand how women perceive themselves, their abilities, and their environments to best aid the prevention of ZIKV.Keywords: Aedes aegypti, environment, prevention, qualitative, zika
Procedia PDF Downloads 1331 Computational Approaches to Study Lineage Plasticity in Human Pancreatic Ductal Adenocarcinoma
Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles
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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.Keywords: deconvolution, imaging, microenvironment, PDAC
Procedia PDF Downloads 128