Engineering Commons^™

Elucidating The Effects Of Metabolic State On Nanoparticle Distribution In Mice And In Vitro Uptake, Kevin James Quigley

Doctoral Dissertations

Since almost 70% of the U.S. population over 20 years old is overweight and 30% is obese, with much of the western world following suit, many patients that will potentially be administered circulating nanoparticles designed to localize to tumors and avoid non-target areas will have significant amounts of white adipose tissue (WAT), enlarged livers, and additional metabolic complications such as type 2 diabetes. However, studies on nanoparticle biodistribution and efficacy take place almost without exception in lean rodents with healthy metabolic states. In this work, I determined the biodistribution of model nanoparticles – neutral filomicelles and polystyrene spheres both carrying …

State Space Analysis Of Dominant Structures In Dynamic Social Systems, Jeremy B. Sato

McKelvey School of Engineering Theses & Dissertations

Many systems involving human relationships are modeled as dynamic systems, as diverse as urban population growth, diffusion of innovations, spread of viruses, and supply chain management. A fundamental assumption is that these systems contain variables which accumulate and deplete over time (people, innovation adoptions, infections, and orders), and whose dynamics are determined by societal rules and human decision making processes. These assumptions allow the system to be formally expressed by ordinary differential equations which are often nonlinear and contain multiple state variables and feedback loops. Analytical methods have been developed to identify the dominant feedback loops which primarily influence the …

Nanobubbles Provide Theranostic Relief To Cancer Hypoxia, Christopher M. Long, Pushpak N. Bhandari, Joseph Irudayaraj

The Summer Undergraduate Research Fellowship (SURF) Symposium

Hypoxia is a common motif among tumors, contributing to metastasis, angiogenesis, cellular epigenetic abnormality, and resistance to cancer therapy. Hypoxia also plays a pivotal role in oncological studies, where it can be used as a principal target for new anti-cancer therapeutic methods. Oxygen nanobubbles were designed in an effort to target the hypoxic tumor regions, thus interrupting the hypoxia-inducible factor-1α (HIF-1α) regulatory pathway and inhibiting tumor progression. At less than 100nm, oxygen nanobubbles act as a vehicle for site-specific oxygen delivery, while also serving as an ultrasound contrast agent for advanced imaging purposes. Through in vitro and in vivo studies, …

Design Of Nanoparticle-Based Carriers For Targeted Drug Delivery, Xiaojiao Yu, Ian Trase, Muqing Ren, Kayla Duval, Xing Guo, Zi Chen

Dartmouth Scholarship

Nanoparticles have shown promise as both drug delivery vehicles and direct antitumor systems, but they must be properly designed in order to maximize efficacy. Computational modeling is often used both to design new nanoparticles and to better understand existing ones. Modeled processes include the release of drugs at the tumor site and the physical interaction between the nanoparticle and cancer cells. In this paper, we provide an overview of three different targeted drug delivery methods (passive targeting, active targeting, and physical targeting) and compare methods of action, advantages, limitations, and the current stages of research. For the most commonly used …

Surface-Initiated Polymerizations For The Rapid Sorting Of Rare Cancer Cells, Jacob L. Lilly

Theses and Dissertations--Chemical and Materials Engineering

Cancer metastasis directly accounts for an estimated 90% of all cancer related deaths and is correlated with the presence of malignant cells in systemic circulation. This observed relationship has prompted efforts to develop a fluid biopsy, with the goal of detecting these rare cells in patient peripheral blood as surrogate markers for metastatic disease as a partial replacement or supplement to tissue biopsies. Numerous platforms have been designed, yet these have generally failed to support a reliable fluid biopsy due to poor performance parameters such as low throughput, low purity of enriched antigen positive cells, and insufficiently low detection thresholds …

Killing Adherent And Nonadherent Cancer Cells With The Plasma Pencil, Mounir Laroussi, Soheila Mohades, Nazir Barekzi

Electrical & Computer Engineering Faculty Publications

The application of low temperature plasmas in biology and medicine may lead to a paradigm shift in the way various diseases can be treated without serious side effects. Low temperature plasmas generated in gas mixtures that contain oxygen or air produce several chemically reactive species that have important biological implications when they interact with eukaryotic or prokaryotic cells. Here, a review of the effects of low temperature plasma generated by the plasma pencil on different cancerous cells is presented. Results indicate that plasma consistently shows a delayed killing effect that is dose dependent. In addition, there is some evidence that …

Two-Dimensional Layered Mos2 Biosensors Enable Highly Sensitive Detection Of Biomolecules, Joonhyung Lee, Piyush Dak, Yeonsung Lee, Heekyeong Park, Woong Choi, Muhammad Ashraful Alam, Sunkook Kim

Birck and NCN Publications

We present a MoS₂ biosensor to electrically detect prostate specific antigen (PSA) in a highly sensitive and label-free manner. Unlike previous MoS₂-FET-based biosensors, the device configuration of our biosensors does not require a dielectric layer such as HfO₂ due to the hydrophobicity of MoS₂. Such an oxide-free operation improves sensitivity and simplifies sensor design. For a quantitative and selective detection of PSA antigen, anti-PSA antibody was immobilized on the sensor surface. Then, introduction of PSA antigen, into the anti-PSA immobilized sensor surface resulted in a lable-free immunoassary format. Measured off-state current of the device …

Effect Of Chemotherapeutic Treatment Schedule On A Tissue Transport Model, Dan E. Ganz

Masters Theses

Current chemotherapeutic treatment schedule prediction methods rely heavily on PK/PD-based models and overlook the important contribution of tissue-level transport and binding. Tissue-level transport and binding phenomena are essential to understanding drug delivery and efficacy in tumors. Drugs with desirable PK/PD properties often fail in vivo due to poor tissue-level transport. We developed an in silico method to predict the effect of treatment schedule on efficacy that couples PK/PD with tissue-level transport. Treatment schedules were implemented on theoretical drugs with different PK/PD and transport properties. For each drug with a given clearance rate, diffusivity, and binding, treatment schedules consisting of one …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

The Spatial Distribution Of Cancer Incidence In Fars Province: A Gis-Based Analysis Of Cancer Registry Data, Ali Goli, Mahbobeh Oroei, Mehdi Jalalpour, Hossein Faramarzi, Mehrdad Askarian

Civil and Environmental Engineering Faculty Publications

Background: Cancer is a major health problem in the developing countries. Variations of its incidence rate among geographical areas are due to various contributing factors. This study was performed to assess the spatial patterns of cancer incidence in the Fars Province, based on cancer registry data and to determine geographical clusters.

Methods: In this cross sectional study, the new cases of cancer were recorded from 2001 to 2009. Crude incidence rate was estimated based on age groups and sex in the counties of the Fars Province. Age standardized incidence rates (ASR) per 100,000 was calculated in each year. …

A Review Of Autoimmune Diseases Associated With Cancer, Patricia Tai, Edward Yu, Kurian Joseph, Thomas Miale

Oncology Publications

The focus of this review is on the relationships between autoimmune diseases and cancer from two closely related perspectives: 1.Those autoimmune diseases which are often associated with malignancies. 2.Those prevalent cancers which may increase the risks of developing autoimmune disorders. The review concludes with a brief discussion of some selected innovative approaches to cancer immunotherapy.

Prostate Cancer Region Prediction Using Maldi Mass Spectra, Ayyappa Vadlamudi, Shao-Hui Chuang, Xiaoyan Sun, Lisa Cazares, Julius Nyalwidhe, Dean Troyer, O. John Semmes, Jiang Li, Frederic D. Mckenzie

Electrical & Computer Engineering Faculty Publications

For the early detection of prostate cancer, the analysis of the Prostate-specific antigen (PSA) in serum is currently the most popular approach. However, previous studies show that 15% of men have prostate cancer even their PSA concentrations are low. MALDI Mass Spectrometry (MS) proves to be a better technology to discover molecular tools for early cancer detection. The molecular tools or peptides are termed as biomarkers. Using MALDI MS data from prostate tissue samples, prostate cancer biomarkers can be identified by searching for molecular or molecular combination that can differentiate cancer tissue regions from normal ones. Cancer tissue regions are …

Summary Of Workshop To Review An Omb Report On Regulatory Risk Assessment And Management, John S. Evans, John D. Graham, George M. Gray, Adrienne Hollis

RISK: Health, Safety & Environment (1990-2002)

Summary of the results of an invitational workshop conducted to peer review the 1990 OMB report, CURRENT REGULATORY ISSUES IN Risk ASSESSMENT AND Risk MANAGENMENTIN REGULATORY PROGRAM OF THE UNITED STATES GOVERNMENT, APRIL 1, 1990 - MARCH 31, 1991.