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Full-Text Articles in Biomedical Engineering and Bioengineering

Binding Affinity And Specificity Of Sh2 Domain Interactions In Receptor Tyrosine Kinase Signaling Networks, Tom Ronan Dec 2017

Binding Affinity And Specificity Of Sh2 Domain Interactions In Receptor Tyrosine Kinase Signaling Networks, Tom Ronan

McKelvey School of Engineering Theses & Dissertations

Receptor tyrosine kinase (RTK) signaling mechanisms play a central role in intracellular signaling and control development of multicellular organisms, cell growth, cell migration, and programmed cell death. Dysregulation of these signaling mechanisms results in defects of development and diseases such as cancer. Control of this network relies on the specificity and selectivity of Src Homology 2 (SH2) domain interactions with phosphorylated target peptides. In this work, we review and identify the limitations of current quantitative understanding of SH2 domain interactions, and identify severe limitations in accuracy and availability of SH2 domain interaction data. We propose a framework to address some …


Protein-Nanoparticle Co-Engineering: Self-Assembly, Intracellular Protein Delivery, And Crispr/Cas9-Based Gene Editing, Rubul Mout Nov 2017

Protein-Nanoparticle Co-Engineering: Self-Assembly, Intracellular Protein Delivery, And Crispr/Cas9-Based Gene Editing, Rubul Mout

Doctoral Dissertations

Direct cytoplasmic delivery of gene editing nucleases such CRISPR/Cas9 systems and therapeutic proteins provides enormous opportunities in curing human genetic diseases, and assist research in basic cell biology. One approach to attain such a goal is through engineering nanotechnological tools to mimic naturally existing intra- and extracellular protein delivery/transport systems. Nature builds transport systems for proteins and other biomolecules through evolution-derived sophisticated molecular engineering. Inspired by such natural assemblies, I employed molecular engineering approaches to fabricate self-assembled nanostructures to use as intracellular protein delivery tools. Briefly, proteins and gold nanoparticles were co-engineered to carry complementary electrostatic recognition elements. When these …


Intravenous Administration Of Iron Oxide Nanoparticles In The Chicken Model, Huong Thi Ngoc Le Aug 2017

Intravenous Administration Of Iron Oxide Nanoparticles In The Chicken Model, Huong Thi Ngoc Le

Graduate Theses and Dissertations

To be used in health care, the safety and effectiveness of nanoparticles needs to be tested in a living organism. The objective of this project was to develop the chicken as a convenient animal model to examine tissue targeting of intravenously (i.v.)-injected iron oxide (IO) nanoparticles. In Experiment 1, different doses of IO-COOH were i.v. injected into chickens; blood was collected at 0, 5, 15, 30, and 60 minutes post-injection; liver, spleen, lung, and kidney were collected after the last blood collection. For Experiment 2, IO-COOH and IO-PEG were i.v. injected into chickens; blood and the organs were collected at …


A Multiscale Modeling Study Of The Mammary Gland, Joseph D. Butner Jul 2017

A Multiscale Modeling Study Of The Mammary Gland, Joseph D. Butner

Biomedical Engineering ETDs

Multiscale, hybrid computer modeling has emerged as a valuable tool in the fields of computational systems biology and mathematical oncology. In this work, we present an overview of the motivations for, and development and implementation of, three hybrid multiscale models of the mammary gland system and early stage ductal carcinoma in situ (DCIS) in the gland. Pubertal mammary gland development was described first using a two-dimensional, lattice-based hybrid agent-based model description of the mammary terminal end bud (TEB), and then with a three-dimensional lattice-free TEB model. Both models implement a discrete, agent-based description of the cell scale, and a continuum, …


Detection Of Leukocytes Stained With Acridine Orange Using Unique Spectral Features Acquired From An Image-Based Spectrometer, Courtney J. Hunter May 2017

Detection Of Leukocytes Stained With Acridine Orange Using Unique Spectral Features Acquired From An Image-Based Spectrometer, Courtney J. Hunter

Biomedical Engineering Undergraduate Honors Theses

A leukocyte differential count can be used to diagnosis a myriad blood disorders, such as infections, allergies, and efficacy of disease treatments. In recent years, attention has been focused on developing point-of-care (POC) systems to provide this test in global health settings. Acridine orange (AO) is an amphipathic, vital dye that intercalates leukocyte nucleic acids and acidic vesicles. It has been utilized by POC systems to identify the three main leukocyte subtypes: granulocytes, monocytes, and lymphocytes. Subtypes of leukocytes can be characterized using a fluorescence microscope, where the AO has a 450 nm excitation wavelength and has two peak emission …


Optimizing A Standard Fasting Time For 2-Nbdg Uptake Studies In Murine Breast Cancers, Andrew C. Briley May 2017

Optimizing A Standard Fasting Time For 2-Nbdg Uptake Studies In Murine Breast Cancers, Andrew C. Briley

Biomedical Engineering Undergraduate Honors Theses

Recently, there has been a larger use of 2-NBDG, a fluorescent glucose analog, to study glucose uptake in different cell types. These cell types have ranged anywhere from bacteria to human cancer cells. However, there has yet to be a standard procedure and practice for using 2-NBDG. In this study, our goal is to create a standard fasting time for the cells before introducing 2-NBDG to them. This study uses 4T07 cells, a murine breast cancer cell line, to help optimize this fasting time. These cells were fasted at different time points in order to find the ideal fasting time. …


Role Of Trpv4 In Astrocyte Extracellular Matrix Production, Abby Terlouw May 2017

Role Of Trpv4 In Astrocyte Extracellular Matrix Production, Abby Terlouw

Biomedical Engineering Undergraduate Honors Theses

Traumatic Brain Injury (TBI) is an alteration of brain pathology following damage of the central nervous system (CNS) by an external force. In the CNS, glial scar formation often occurs following TBI, and astrocytes are widely believed to contribute to this scar formation. While the role of astrocytes in extracellular matrix (ECM) production is known, the exact mechanism(s) for this event remain unclear. One possible method is the activation of transient receptor potential vanilloid 4 (TRPV4). TRPV4 is a channel protein found in the astrocyte membrane which has been shown to generate intracellular calcium ions following mechanical stimulation. Previous research …


Investigation Of Chitosan-Based Hydrogels As A Cell Delivery Platform For Adipose-Derived Stem/Stromal Cell Transplantation To Promote Angiogenesis In Ischemic Tissues, Jobanpreet Singh Dhillon Mar 2017

Investigation Of Chitosan-Based Hydrogels As A Cell Delivery Platform For Adipose-Derived Stem/Stromal Cell Transplantation To Promote Angiogenesis In Ischemic Tissues, Jobanpreet Singh Dhillon

Electronic Thesis and Dissertation Repository

Stem cell transplantation is under investigation to stimulate angiogenesis in patients with peripheral artery disease. To develop a cell-delivery platform that enhances cell retention and function post-transplantation, the response of human adipose-derived stem/stromal cells (ASCs) encapsulated within N-methacrylate glycol chitosan (MGC) hydrogels with or without integrin-binding RGD or IKVAV motifs was explored. ASC viability was enhanced in the MGC and MGC-RGD hydrogels relative to the MGC-IKVAV group under hypoxic (2% O­2) culture conditions, with cell spreading and higher metabolic activity noted in MGC-RGD at 14 days. Analysis of angiogenic gene expression revealed similar patterns between all hydrogel …


Biomaterials Approaches For Utilizing The Regenerative Potential Of The Peripheral Nerve Injury Microenvironment, Melissa Renee Wrobel Jan 2017

Biomaterials Approaches For Utilizing The Regenerative Potential Of The Peripheral Nerve Injury Microenvironment, Melissa Renee Wrobel

Wayne State University Dissertations

Clinically available treatments are insufficient to achieve full functional recovery in large (>3cm) peripheral nerve injuries (PNI). The objectives in this thesis were 1) to study often overlooked elements of intrinsic PNI repair including release of inhibitory CSPGs and post-injury responses of inflammatory macrophages and dedifferentiated Schwann cells; 2) to create biomaterial scaf-folds featuring topographical and adhesive cues to enhance neurite outgrowth; and 3) to test the ability of those cues to direct macrophages and Schwann cells towards a pro-regenerative phe-notype. It is hypothesized that recapitulating the positive and negative cues of the PNI microenvi-ronment can better improve regeneration. …