BEE 4530 - 2021 Student Papers

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    Still a Threat: Polychlorinated Biphenyl (PCB) Metabolism in Cells & Formation of Cancer-Causing DNA Adducts
    Chang, Wei-Ann; Taveras, Alwany Angeles; Saadatmand, Bahareh; Gaul, Larissa (2021-05)
    Despite PCBs having been banned from manufacturing processes for decades, polychlorinated biphenyls or PCBs can still enter the environment through various means, such as improper waste disposal methods, and wreak havoc. Current PCB-containing products are those that predate the ban but persistent health risks still exist due to the PCB chemical stability in the environment. Exposure to PCBs through inhalation, ingestion, increase risk of developing multiple medical problems, particularly cancer. Once PCBs diffuse into a cell, metabolites are produced by a cascade of reactions. PCB metabolites can then bind to DNA to create DNA adducts. This process results in mutations that can gradually develop into cancer. We hope to gain a better understanding of the impact of PCB exposure by modeling cellular PCB metabolism and DNA adduct formation with COMSOL Multiphysics 5.5. Mass transfer modules (including reaction, partitioning, and diffusion) were used to model PCB and PCB metabolite movement and accumulation in a cell over time. We modelled one spherical cell with 1D axisymmetric geometry divided into five distinct domains. Factors including temperature, pH level, and organelle interactions (besides the nucleus) were disregarded. We also assumed a uniform enzyme concentration of 0.25 𝞵M for all enzymatic reactions. Key parameters including diffusion coefficients, some rate constants, and partitioning coefficients were referenced from similar work by Chaudhry et al. and the SABIO-RK database. Damage to the cell was quantified via the number of DNA adducts formed. Model validation was done by comparing the DNA adducts concentration of our COMSOL model, with published literature values. The final number of DNA adducts calculated by our COMSOL model was 104 times greater than the DNA adducts values from literature. The sensitivity analysis found the DNA adduct formation rate constant to be the most sensitive rate constant impacting the final DNA adduct concentration. It is possible that an incorrect DNA adduct formation rate could result in deviation from experimental results. It is also possible for incorrect rate constants to have a comparatively smaller effect on final DNA adduct values. Accurate quantification of DNA adducts formed from a specified PCB exposure time and concentration may allow quantification of a cancer risk from DNA adduct formation. If a specified level of acceptable DNA adduct formation and cancer risk was selected, maximum allowable exposure time and concentration will be known. Maximum allowable concentration can act as a design constraint for water treatment, soil remediation, and other treatment efforts. Accurate quantification of DNA adduct formation may further replace or supplement in vitro experimentation requiring 32P-post labeling or high performance liquid chromatography (HPLC), as well as in vivo experimentation, saving resources involved with live cell experiments.
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    Frostbyte: Multi-Phase Lower Digital Freezing
    Cooke, Benjamin; Jaicks, John; Kitzinger, Cameron; Sheppard, TJ (2021-05)
    Though frostbite is an affliction that has been commonly known for hundreds of years, its direct effect and dynamics have rarely been studied. With modern technology and an understanding of the human body, tissue freezing can now be modeled to fully understand its progression and once and for all resolve its procession. Here we used a high definition, multilayered, anatomically accurate 3D model of a foot subjected to a subfreezing environment to develop a novel understanding of the crucial parameters in frostbite prevention. The results, as shown in the form of cross-sectional temperature profile images, tell us that the toes freeze within the two-hour runtime where the middle of the foot does not. With little research before this, we believe that this model will be of great use to the scientific community and will likely lead to real solutions to come.
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    An Injectable Oxygen and VEGF Releasing Hydrogel for Cardiac Tissue Regeneration
    Li, Linda; Lubinus, Ariadna; Murundi, Shamanth; Prakash, Gayatri (2021-05)
    The purpose of this study was to determine the design requirements of an injectable fibrin hydrogel as a viable tool in delivering sufficient oxygen (O2) and vascular endothelial growth factor (VEGF) to hypoxic tissue to prevent scar tissue formation and simultaneously regenerate cardiac tissue. This study modeled changes in hydrogel size, solute concentration, and tissue damage to maximize delivery of oxygen and VEGF through an infarcted tissue region of 1.50 cm by 3.50 cm. Using COMSOL software, a 2D model of the injected hydrogel was generated to show oxygen and VEGF concentration as a function of time and space while the hydrogel deswelled following pseudo-first order kinetics. To determine the minimum effective amount of VEGF and oxygen needed in the hydrogel to regenerate wounded cardiac tissue, different solute concentrations were tested. The hydrogel loading conditions that gave the highest average concentration over 24 hours were selected. Using this method, the hydrogel was loaded with ml/m3 O2 and 0.8 ml/m3 8 × 10 VEGF, and the 5 therapeutic concentrations were reached at 22 hours for O2 ( ml O2 /m3 2 × 10 blood) and 24 −5 hours for VEGF (0.00137 ml VEGF/m3 ). Plots of concentration vs. position were made at 4 points in time to visualize the effective diffusion distance of the hydrogel’s contents and time required for delivery. VEGF diffusion had a radially symmetric distribution, while O2 had an asymmetric diffusion pattern due to oxygen provided by the bloodstream at the inner surface of the ventricle. From the asymmetric diffusion distribution, the location of optimal injection in the myocardial wall was concluded to be ⅓ of the distance from the heart surface to the ventricle. A sensitivity analysis was also done for all the parameters, and the final concentration of oxygen and VEGF in the damaged tissue was found to be most sensitive to hydrogel radius, which impacted the design recommendations. Determination of the proper concentration of dissolved substituents, hydrogel size, and diffusion time will assist surgeons, bioengineers, and material scientists in designing a viable injectable hydrogel.
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    Murdering the Murder Hornet: Heat and CO2 Exchange in a Bee-ball
    Shack, Jasmine; Yu, Evelyn (Zichen); Yu, Ruoqian Lin; Fang, Ye (2021-05)
    Bee-balling is a defensive technique employed by Japanese honeybees, Apis cerana japonica, against the predatory Asian giant hornet, Vespa mandarinia. Upon recognition of the hornet intruder within the hive, hundreds of honeybees surround and restrain the hornet; forming a bee-ball. Subsequently the bee-ball experiences three distinct phases of temperature change (heating, heat retaining, and break up). The bees simultaneously elevate CO2 levels and temperature within the bee-ball, which jointly act to kill the hornet. To gain an improved mechanistic understanding of this process, a computational model of heat transfer and carbon dioxide transfer specifically examining the heating and heat retaining phase within the bee-ball was developed. The manipulation of model parameters to simulate different environmental conditions, bee arrangement and production rates provides insight into the process that would otherwise be difficult or near impossible to obtain through pure experimentation. In this study, we considered the honeybees and the hornet to generate heat and CO2, while also exchanging heat to each other, and losing CO2 to the surroundings. To investigate the mechanism of the bee-balling behavior, we used COMSOL, a multiphysics finite element analysis and simulation software, to develop a simple geometry and replicate the heat and CO2 exchanging properties of the honeybees and the hornet during heating and heat retaining phase of the bee-balling process. The results of this study provide insight behind why bee-balls form, how the honeybees utilize heat and CO2 and modulate their movement, heat and CO2 production rate to effectively murder the murder hornet.
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    A Model of Transdermal Drug Delivery through Electroporation
    Adair, James; Chou, Emily; Metzloff, Matt; Tse, Truman (2021-05)
    Electroporation is a technique that applies high voltage pulses over short time periods, resulting in strong electric fields, to create micropores in cell membranes. When applied to the skin, electroporation causes Joule heating that creates local transport regions (LTRs) in the lipid bilayer of the stratum corneum (SC), which is the outermost layer of the epidermis that is most resistant to drug transport. The combined effect of micropores and LTR formation results in a significant increase in transdermal drug transport. Previous studies only model the drug profile through the skin layers during the electric pulse, on the scale of 300 ms. Furthermore, previous studies only account for a pore that crosses the SC, not the epidermis and dermis. Based on the anatomy of hair follicles and sweat glands, more accurate models should model pores that extend past the SC. We used COMSOL Multiphysics®: a finite element analysis, solver, and multiphysics simulation software for our modeling. We modeled transdermal delivery of a DNA-based drug assisted by electroporation, using skin property values determined by in vitro studies for large charged molecules. The model covered 24 hours starting with a 300 ms electric pulse. Our cylindrical geometry accounts for the gel, SC, epidermis, and dermis. At the axis of the cylinder, a pore extends through all the skin layers, containing the gel with the drug. We modeled Joule heating that results in LTR formation, as well as the mass transfer during and after the pulse. Our results demonstrate LTR formation during electroporation and its lasting impact after 24 hours. The concentration of drug at 24 hours decreases going down the LTR in the SC, with a slower decline in the epidermis and dermis. We validated our model through a mesh convergence analysis, comparison with another computational model, and comparison with an experimental study. Through a sensitivity analysis, we reinforced the importance of SC thickness in slowing drug transport. This model can be used as a more accurate representation of electroporation as a proof of concept before clinical trials.