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A NEW DECELLULARIZED MATRIX FOR ENGINEERING AN ESOPHAGEAL CANCER MODEL IN A PERFUSION BIOREACTOR
Title
A NEW DECELLULARIZED MATRIX FOR ENGINEERING AN ESOPHAGEAL CANCER MODEL IN A PERFUSION BIOREACTOR.
Creator
Brennan, Jordan Michael, Kang, Yunqing, Florida Atlantic University, Department of Ocean and Mechanical Engineering, College of Engineering and Computer Science
Abstract/Description
The lack of physiologically relevant human esophageal cancer models has as a result that many esophageal cancer studies are encountering major bottleneck challenges in achieving breakthrough progress. To address the issue, here a 3D esophageal tumor tissue model was engineered using a biomimetic decellularized esophageal matrix in a customized bioreactor. To obtain a biomimetic esophageal matrix, a detergent-free, rapid decellularization method was developed to decellularize porcine esophagus...
Show moreThe lack of physiologically relevant human esophageal cancer models has as a result that many esophageal cancer studies are encountering major bottleneck challenges in achieving breakthrough progress. To address the issue, here a 3D esophageal tumor tissue model was engineered using a biomimetic decellularized esophageal matrix in a customized bioreactor. To obtain a biomimetic esophageal matrix, a detergent-free, rapid decellularization method was developed to decellularize porcine esophagus. The decellularized esophageal matrix (DEM) was characterized and the DEM was utilized for the growth of esophageal cancer cell KYSE30 in well plates and the bioreactor. Then the expression of cancerrelated markers of KYSE30 cells was analyzed and compared with formalin-fixed, paraffin-embedded (FFPE) esophageal squamous cell carcinoma (ESCC) tissue biospecimens. Results show that the detergent-free decellularization method preserved the esophageal matrix components and effectively removed cell nucleus. KYSE30 cancer cells proliferated well on and inside the DEM. KYSE30 cells cultured on the DEM in the dynamic bioreactor show different cancer marker expressions than those in the static well plate, and also share some similarities to the FFPE-ESCC biospecimens.
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Date Issued
2023
PURL
http://purl.flvc.org/fau/fd/FA00014206
Subject Headings
Cancer, Esophageal Neoplasms, Biomimetics
Format
Document (PDF)
Isolation and Semi-synthesis of Marine Diterpenoids
Title
Isolation and Semi-synthesis of Marine Diterpenoids.
Creator
Scesa, Paul D., West, Lyndon, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
Abstract/Description
Natural products play a historical role in the discovery of medicine but present unique challenges for chemical isolation, identification and production. In this work we describe the identification of twenty novel diterpenoids. These were isolated by use of chromatography, and the structures determined by spectroscopic methods, primarily 1D and 2D NMR. Six of these possess unprecedented diterpenoid skeletons and two of them show significant growth inhibitory effects on cancer cell lines in...
Show moreNatural products play a historical role in the discovery of medicine but present unique challenges for chemical isolation, identification and production. In this work we describe the identification of twenty novel diterpenoids. These were isolated by use of chromatography, and the structures determined by spectroscopic methods, primarily 1D and 2D NMR. Six of these possess unprecedented diterpenoid skeletons and two of them show significant growth inhibitory effects on cancer cell lines in vitro (GI50 < 10 μM). The biomimetic semisynthesis of diterpendoids and analogues is also presented. Access to the bielschowskyane carbon skeleton by dearomatization of a furanocembranoid precursor is described. Highlights include a stereoselective alkene epoxidation, a novel kinetic furan dearomatization method, and an efficient [2+2] photochemical cycloaddition. The role of conformational steering was studied spectroscopically using VT 1H-NMR and NOESY as well as quantum chemical calculations at the DFT level of theory. We also disclose a biomimetic synthesis of providencin using a photochemical Norrish-Yang cyclization. This provided the absolute configuration by chemical correlation with the precursor bipinnatin E, the latter determined by x-ray diffraction. An unexpected, regioisomeric byproduct was observed and a possible mechanism is proposed. A biomimetic synthesis of the diterpene alkaloid aceropterine is also described, using an epoxidation-rearrangement cascade. This work led to a revised structure of aceropterine, formulated by spectroscopic methods. Finally, the isolation and structure elucidation of a novel, cyclic lipopeptide from Pseudomonas sp. is described. The compound was obtained using a unique antibiotic crowd sourcing approach and the structure determined by spectroscopic methods and advanced Marfey’s analysis.
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Date Issued
2020
PURL
http://purl.flvc.org/fau/fd/FA00013539
Subject Headings
Marine natural products, Diterpenoids, Biomimetics
Format
Document (PDF)
Isolation and Biomimetic Synthesis of Marine Natural Products from the Gorgonian Briareum Asbestinum
Title
Isolation and Biomimetic Synthesis of Marine Natural Products from the Gorgonian Briareum Asbestinum.
Creator
Simpson, Johnathon, West, Lyndon M., Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
Abstract/Description
Throughout history, natural products have produced a plethora of biologically active compounds that have established applications in medicine, biology, and pharmacy. The exploration for improved cytotoxic agents has continued to be a crucial path in natural products drug discovery. The focal point of this thesis sheds light on the biosynthetic relationship between the two distinct classes of briarane diterpenoids, the γ-lactone briarane and the briareolate esters. Additionally, this study...
Show moreThroughout history, natural products have produced a plethora of biologically active compounds that have established applications in medicine, biology, and pharmacy. The exploration for improved cytotoxic agents has continued to be a crucial path in natural products drug discovery. The focal point of this thesis sheds light on the biosynthetic relationship between the two distinct classes of briarane diterpenoids, the γ-lactone briarane and the briareolate esters. Additionally, this study elaborates on the discovery and elucidation of structurally unique secondary metabolites from the gorgonian coral Briareum asbestinum. The first chapter of this thesis provides a review of the development and discovery of diverse secondary metabolites. In addition, this chapter describes the role of natural products in drug discovery and summarizes the research progress in marine natural product chemistry in conjunction with a detailed overview of the current marine-derived pharmaceuticals.
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Date Issued
2021
PURL
http://purl.flvc.org/fau/fd/FA00013857
Subject Headings
Marine natural products, Diterpenoids, Biomimetics, Soft corals
Format
Document (PDF)
Swimming control of an underwater vessel with elongated ribbon fin propulsion
Title
Swimming control of an underwater vessel with elongated ribbon fin propulsion.
Creator
Uddin, Mohammad Irfan, Curet, Oscar M., Florida Atlantic University, Department of Ocean and Mechanical Engineering, College of Engineering and Computer Science
Abstract/Description
Navigation of unmanned underwater vehicles in coastal zones, tight spaces and close to structures such as ports, ship hulls and pipelines remains a difficult challenge. Currently Autonomous Underwater Vehicles (AUVs) use a variety of techniques for motion control, including single thrusters with diving planes or hydrofoils, robotic wrists, or a moving mass. However, these techniques provide limited maneuverability. The objective of this work was to understand the mechanics of elongated fin...
Show moreNavigation of unmanned underwater vehicles in coastal zones, tight spaces and close to structures such as ports, ship hulls and pipelines remains a difficult challenge. Currently Autonomous Underwater Vehicles (AUVs) use a variety of techniques for motion control, including single thrusters with diving planes or hydrofoils, robotic wrists, or a moving mass. However, these techniques provide limited maneuverability. The objective of this work was to understand the mechanics of elongated fin propulsion for swimming and motion control of underwater vehicles. This bio-inspired propulsion is used by several fishes that swim by undulating a thin and elongated median fin that allow them to perform forward and directional maneuvers. In the first chapter we present the literature review as well as the mathematical formulation using thrust vectoring approach to achieve forward and turning maneuvers. In the second chapter, we used a robotic vessel with elongated fin propulsion to determine the thrust scaling and efficiency. Using precise force and swimming kinematics measurements with the robotic vessel, the thrust generated by the undulating fin was found to scale with the square of the relative velocity between the free streaming flow and the wave speed. In addition, a hydrodynamic efficiency is presented based on propulsive force measurements and a model on the power required to oscillate the fin laterally.
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Date Issued
2022
PURL
http://purl.flvc.org/fau/fd/FA00014117
Subject Headings
Autonomous underwater vehicles, Biomimetics, Underwater propulsion
Format
Document (PDF)
SYNTHETIC AND MECHANISTIC STUDY OF ENANTIO- AND STEREOSELECTIVE HOUSE–MEINWALD REARRANGEMENT OF CONGESTED TRISUBSTITUTED SPIRO-EPOXIDES
Title
SYNTHETIC AND MECHANISTIC STUDY OF ENANTIO- AND STEREOSELECTIVE HOUSE–MEINWALD REARRANGEMENT OF CONGESTED TRISUBSTITUTED SPIRO-EPOXIDES.
Creator
Jeedimalla, Nagalakshmi, Roche, Stephane P., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description
Published Content: Jeedimalla, N.; Jacquet, C.; Bahneva, D.; Youte Tendoung, J.-J.; Roche, S. P. J. Org. Chem. 2018, 83, 12357. The present thesis will be focused on the study of House-Meinwald Rearrangement (HMR) reactions for the congested trisubstituted spiro-epoxide molecules. Including their regio-selective, chemo-selective, enantio- selective selective and stereo-selectivity’s will be discussed in detailed by the mechanistic study approach of HMR reaction of trisubstituted spiro...
Show morePublished Content: Jeedimalla, N.; Jacquet, C.; Bahneva, D.; Youte Tendoung, J.-J.; Roche, S. P. J. Org. Chem. 2018, 83, 12357. The present thesis will be focused on the study of House-Meinwald Rearrangement (HMR) reactions for the congested trisubstituted spiro-epoxide molecules. Including their regio-selective, chemo-selective, enantio- selective selective and stereo-selectivity’s will be discussed in detailed by the mechanistic study approach of HMR reaction of trisubstituted spiro-epoxides. Chapter 1 will present the efforts towards the biomimetic total synthesis of meroterpenoid natural product (+)-liphagal, which possess a recognizable biological activity. The shortcomings associated with its stereochemical assignment, and also the revision of stereochemical assignment of siphonodictyal B, through which the biosynthesis of (+)-liphagal was proposed were discussed. Chapter 2 will focus on the study of regio and chemoselective HMR reaction. In addition, a three-step sequence for the synthesis of α-arylated cyclohexanones and the most challenging cycloheptanones is reported. First, an efficient one-pot synthesis of β, β’-disubstituted benzylidene cycloalkanes using the palladium-catalyzed Barluenga reaction from readily available feedstock chemicals is described. Second, an epoxidation followed by the HMR of spiro-epoxides is reported to produce a number of α -arylated cycloalkanones upon the ring expansion. Reactions catalyzed by bismuth triflate underwent quasi-exclusively ring expansion for all substrates (electronically poor and rich), demonstrating the difficulty to achieve the ring enlargement for electron deficient spiro-epoxides. On the other hand, via catalysis with aluminium trichloride the rearrangement proceeded typically in high yields and with remarkable regioselectivity. In this case, a switch of regioselectivity was achieved for spiro-epoxides with electron-withdrawing substituents which enabled this method to be successfully extended to some chemo specific arene shifts and it can also synthesize aldehydes derivatives bearing a α-quaternary carbon.
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Date Issued
2019
PURL
http://purl.flvc.org/fau/fd/FA00013320
Subject Headings
Epoxy compounds, Epoxides, Biomimetic Materials--chemical synthesis
Format
Document (PDF)
Analyzing the effect of fin morphology on the propulsive performance of an oscillating caudal fin using a robotic model
Title
Analyzing the effect of fin morphology on the propulsive performance of an oscillating caudal fin using a robotic model.
Creator
Fischer, Tyler M., Curet, Oscar M., Florida Atlantic University, College of Engineering and Computer Science, Department of Ocean and Mechanical Engineering
Abstract/Description
A bio-inspired robotic underwater vessel was developed to test the effect of fin morphology on the propulsive performance of caudal fin. The robotic vessel, called The Bullet Fish, features a cylindrical body with a hemisphere at the forward section and a conical body at the stern. The vessel uses an oscillating caudal fin for thrust generation. The robotic vessel was tested in a recirculating flume for seven different caudal fins that range different bio-inspired forms and aspect ratios. The...
Show moreA bio-inspired robotic underwater vessel was developed to test the effect of fin morphology on the propulsive performance of caudal fin. The robotic vessel, called The Bullet Fish, features a cylindrical body with a hemisphere at the forward section and a conical body at the stern. The vessel uses an oscillating caudal fin for thrust generation. The robotic vessel was tested in a recirculating flume for seven different caudal fins that range different bio-inspired forms and aspect ratios. The experiments were performed at four different flow velocities and two flapping frequencies: 0.5 and 1.0 Hz. We found that for 1 Hz flapping frequency that in general as the aspect-ratio decreases both thrust production tends and power decrease resulting in a better propulsive efficiency for aspect ratios between 0.9 and 1.0. A less uniform trend was found for 0.5 Hz, where our data suggest multiple efficiency peaks. Additional experiments on the robotic model could help understand the propulsion aquatic locomotion and help the design of bio-inspired underwater vehicles.
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Date Issued
2017
PURL
http://purl.flvc.org/fau/fd/FA00004944, http://purl.flvc.org/fau/fd/FA00004944
Subject Headings
Robotics., Robots--Kinematics., Artificial intelligence., Biomimetics., Bioinformatics., Stereotypes (Social psychology)
Format
Document (PDF)
DEVELOPMENT OF AN ACELLULAR EXTRACELLULAR MATRIX AS A THREE-DIMENSIONAL SCAFFOLD FOR ESOPHAGEAL TUMOR ENGINEERING
Title
DEVELOPMENT OF AN ACELLULAR EXTRACELLULAR MATRIX AS A THREE-DIMENSIONAL SCAFFOLD FOR ESOPHAGEAL TUMOR ENGINEERING.
Creator
Chaitin, Hersh, Kang, Yunqing, Florida Atlantic University, Department of Biological Sciences, Charles E. Schmidt College of Science
Abstract/Description
Human esophageal squamous cell carcinoma (hESCC) is a very aggressive form of cancer due to its ability to easily metastasize into proximal lymph nodes and adjacent organs. The role of the extracellular matrix (ECM) and its stromal cells in metastasis remains unclear. To better understand the effect of the ECM and fibroblast cells on esophagus cancer cell migration and invasion, we propose a biomimetic human esophagus model cultured with hESCC and human primary fibroblast cells (fibroblast)....
Show moreHuman esophageal squamous cell carcinoma (hESCC) is a very aggressive form of cancer due to its ability to easily metastasize into proximal lymph nodes and adjacent organs. The role of the extracellular matrix (ECM) and its stromal cells in metastasis remains unclear. To better understand the effect of the ECM and fibroblast cells on esophagus cancer cell migration and invasion, we propose a biomimetic human esophagus model cultured with hESCC and human primary fibroblast cells (fibroblast). To mimic the extracellular matrix of human esophagus we use decellularized porcine esophagus matrix (DEM) to culture with hESCC and fibroblasts in static conditions. This DEM can recapitulate the human esophagus tumor microenvironment with relevant cues. This model will provide valuable information regarding esophagus cancer cell migration with respect to the heterogeneous extracellular matrix and stromal fibroblast cells. We expect to discover the mechanisms by which extracellular matrix and stromal cells affect cancer migration and invasion in vitro. Characterizing this process will provide vital insight towards the effects of fibroblasts cells on facilitating migration and invasion of esophageal cancer cells. This esophagus cancer model also provides promising potential to study drug screening and develop new strategies against esophagus metastasis.
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Date Issued
2020
PURL
http://purl.flvc.org/fau/fd/FA00013534
Subject Headings
Esophageal Squamous Cell Carcinoma, Extracellular matrix, Metastasis, Fibroblasts, Biomimetics, Stromal Cells
Format
Document (PDF)
Development of a Flapping Actuator Based on Oscillating Electromagnetic Fields
Title
Development of a Flapping Actuator Based on Oscillating Electromagnetic Fields.
Creator
Spragg, Donald Oakley, Curet, Oscar M., Florida Atlantic University, College of Engineering and Computer Science, Department of Ocean and Mechanical Engineering
Abstract/Description
In this work a bio-inspired flapping actuator based on varied magnetic fields is developed, controlled and characterized. The actuator is sought to contribute to the toolbox of options for bio-mimetics research. The design is that of a neodymium bar magnet on one end of an armature which is moved by two air core electromagnetic coils in the same manner as agonist and antagonist muscle pairs function in biological systems. The other end of the armature is fitted to a rigid fin extending beyond...
Show moreIn this work a bio-inspired flapping actuator based on varied magnetic fields is developed, controlled and characterized. The actuator is sought to contribute to the toolbox of options for bio-mimetics research. The design is that of a neodymium bar magnet on one end of an armature which is moved by two air core electromagnetic coils in the same manner as agonist and antagonist muscle pairs function in biological systems. The other end of the armature is fitted to a rigid fin extending beyond the streamline enclosure body to produce propulsion. A series of tests in still water were performed to measure the kinematics and propulsive force for different control schemes including the effect of adding antagonistic resistance to the control schemes. Control methods based on armature position and based on setpoint error were tested and antagonist force was found to increase consistency of control of the systems in certain cases.
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Date Issued
2016
PURL
http://purl.flvc.org/fau/fd/FA00004699, http://purl.flvc.org/fau/fd/FA00004699
Subject Headings
Actuators -- Materials, Artificial intelligence -- Biological applications, Biomimetics, Biophysics, Natural computation, Robotics, Robots -- Kinematics
Format
Document (PDF)