Life Sciences Commons^™

The Investigations Of Nps Modulated Immunity And Immunometabolism, Brittney Leigh Ruedlinger

Biomedical Sciences Theses & Dissertations

Cancers remain in the top noncommunicable diseases responsible for premature mortality. The heterogeneity among cancers and within tumors makes treating them ever more challenging. Our misfortune for developing cures is mocked by cancer, with the lowest probability of success (PoS) through clinical trials and FDA approval. At the basic level, there are generally two broad gaps impeding cancer eradication: the unidentified shared mechanism(s) exploited by all cancers and the therapeutic approach to intervene. Nanosecond pulse stimulation (NPS) offers a unique approach since its broad impacts intersect those often hijacked by oncogenesis. Metabolic pathways, known for dysfunctions among cancers, share a …

Rainfall-Runoff Mechanisms And Flood Mitigation In A Coastal Watershed With Numerous Wetlands And Ponds, Homa Jalaeian Taghadomi

Civil & Environmental Engineering Theses & Dissertations

This study analyzed mechanisms of flooding in Blackwater River Watershed, located in coastal Virginia and hydraulically connected with mid-Atlantic Ocean. The analysis was based on the examination and simulation of the rainfall-runoff relationship, and such an analysis is very important for conventional water resource management and dealing with hydrologic extremes (e.g., floods and droughts, as well as ecological and pollution discharges). The rainfall-runoff relationship is a quantitative description of the hydrologic cycle, a dynamic process that can be interactively influenced by various factors, namely climate, topography, soils, land use and land cover, and land management practice.

In the past 60 …

The Impact Of Nanopulse Treatment On The Tumor Microenvironment In Breast Cancer: Overturning The Treg Immunosuppressive Dominance, Anthony Nanajian

Biomedical Sciences Theses & Dissertations

Nanopulse treatment (NPT) is a high-power electric engineering modality that has been shown to be an effective local tumor treatment approach in multiple cancer models. Our previous studies on the orthotopic 4T1-luc breast cancer model demonstrated that NPT ablated local tumors. The treatment consequently conferred protection against a second live tumor challenge and minimized spontaneous metastasis. This study aims to understand how NPT mounts a potent immune response in a predominantly immunosuppressive tumor.

NPT changed the local and systemic dynamics of immunosuppressive cells by significantly reducing the numbers of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages …

Evaluation Of Horizontal Gene Transfer Between Genetically Engineered Cyanobacteria And Gram-Negative Bacteria, Andriana Chrysovalanti Zourou

Chemistry & Biochemistry Theses & Dissertations

As the world population is increasing and societies become more technology driven, there is an imperative to develop ‘green energy’ sources to protect our planet. Cyanobacteria that have been genetically engineered to produce organic compounds that may be burnt as fuels show great potential, as they are an environmentally friendly and self-renewable, net carbon-neutral option. However, there are potential risks in the development and use of genetically modified organisms (GMOs). We need to understand in advance the risks that GMOs may pose to our environment and to animal and human health. This will enable experimental procedures, containment strategies and policies …

Electrohydrodynamic Simulations Of Capsule Deformation Using A Dual Time-Stepping Lattice Boltzmann Scheme, Charles Leland Armstrong

Mathematics & Statistics Theses & Dissertations

Capsules are fluid-filled, elastic membranes that serve as a useful model for synthetic and biological membranes. One prominent application of capsules is their use in modeling the response of red blood cells to external forces. These models can be used to study the cell’s material properties and can also assist in the development of diagnostic equipment. In this work we develop a three dimensional model for numerical simulations of red blood cells under the combined influence of hydrodynamic and electrical forces. The red blood cell is modeled as a biconcave-shaped capsule suspended in an ambient fluid domain. Cell deformation occurs …

Trials And Tribulations Of Humanizing Mice For Cancer Research, Brittney Ruedlinger, Steven Warsof, Eric Feliberti, Mary Beth Hughes, Ayobami ‘Edwin’ Oshin, Chunqi Jiang, Brittany P. Lassiter, Siqi Guo, Stephen J. Beebe

The Graduate School Posters

Cancers are aggressive, evasive, and ruthless killers, claiming millions of lives every year. Cancers are heterogeneous and there is often no single, clearly defined problem as they harness and manipulate a multitude of fundamental mechanisms at the very essence of life. To investigate these mechanisms and vet potential interventive therapies, humanized mice offer a unique model as a prelude to the use of nanosecond pulse stimulation (NPS), a pulse power technology applying nanosecond duration, high electric field pulses, to ablate human tumors. Immunodeficient mouse strains, NSG and NSG-SGM3, were engrafted with human immune cells and human tumors, which would allow …

Nanopore Guided Regional Assembly, Eleni Adam, Desh Ranjan, Harold Riethman

College of Sciences Posters

The telomeres are the “caps” of the chromosomes and their vital role is to protect them. Possible telomere dysfunction caused by telomere rearrangements can be fatal for the cell and result in age-related diseases, including cancer. The telomeres and subtelomeres are regions that are hard to investigate. The current technology cannot provide their complete sequence, instead the DNA is given in multiple pieces. Current methods of assembling the pieces of these regions are not accurate enough due to the region’s high variability and complex repeated patterns. We propose a hybrid assembly method, the NPGREAT, which utilizes two of the latest …

Musculoskeletal Modeling Of The Pelvis And Lumbar Spine During Running, Ruth Higgins, Maryam Moeini, Hunter Bennett, Stacie Ringleb

College of Engineering & Technology (Batten) Posters

Musculoskeletal modeling provides an alternative to in-vivo characteristics that are difficult to directly measure for movements such as running, especially for trunk muscles and joints. The full-body-lumbar-spine (FBLS) model by Raabe and Chaudhari, 2016 is an OpenSim model created for simulations of jogging. The lifting full-body (LFB) model by Beaucage-Gauvreau et al., 2018 is an adaptation of the FBLS created for estimating spinal loads during lifting. PURPOSE: Determine validity of the FBLS and LFB models in simulating pelvis and lumbar spine kinematics during running. METHODS: Inverse Kinematics were executed using experimental data for the FBLS and LFB models. To …

Cyclophilin D Is A Sensor Of Nano-Pulse Stimulation, Brittney Ruedlinger, Bani Hani Maisoun, Lucas Potter, Nicola Lai, Stephen J. Beebe

The Graduate School Posters

Nano-Pulse Stimulation (NPS), a pulsed power-derived technology, stimulates structural and functional changes in plasma membranes and cellular organelles. NPS induces a Ca²⁺ influx and opening of the mitochondrial permeability transition pore (mPTP) that dissipates the mitochondrial membrane potential (ΔΨ_m) and, when sustained, induces regulated cell death. Here we show that in rat cardiomyoblasts (H9C2) cyclophilin D (CypD) is a mitochondrial sensor for NPS as defined by observations that loss of ΔΨ_m is Ca²⁺ and mitochondrial reactive oxygen species (mROS) dependent and cyclosporin A (CsA)-sensitive, which are diagnostic qualities for effects on CypD and the mPTP. …

Moderate Heat-Assisted Gene Electrotransfer For Intradermal Dna Vaccination And Protein Replacement Therapy In The Skin, Chelsea Marie Edelblute

Biomedical Sciences Theses & Dissertations

Gene electrotransfer (GET) holds great promise for the delivery of therapeutic agents. The skin serves as an attractive target for GET due to its availability and unique cellular composition. Protein replacement therapy and DNA vaccination are potential applications for intradermal GET. The combination of moderate tissue preheating and GET has been shown to achieve elevated gene expression levels while reducing the necessary applied voltage. In the current work, we utilized a 16-pin multi-electrode array (MEA) and incorporated nine optical fibers, connected to an infrared laser, to pre-heat the tissue to 43°C before application of GET. In a guinea pig model, …

Predictions Of Knee Joint Contact Forces Using Only Kinematic Inputs With A Recurrent Neural Network, Kaileigh Elisabeth Estler

Human Movement Studies & Special Education Theses & Dissertations

BACKGROUND: Knee joint contact (bone on bone) forces are commonly estimated using surrogate measures such as external knee adduction moments (with limited success) or musculoskeletal modeling (more successful). Despite its capabilities, modeling is not optimal for clinicians or persons with limited experience and knowledge. Therefore, the purpose of this study was to design a novel prediction method for knee joint contact forces that is equal or more accurate than modeling, yet simplistic in terms of required inputs. METHODS: This study included all six subjects’ (71.3±6.5kg, 1.7±0.1m) data from the opensource “Grand Challenge” datasets (simtk.org) and two subjects from the "CAMS" …

Large-Scale Variation In Wave Attenuation Of Oyster Reef Living Shorelines And The Influence Of Inundation Duration, Rebecca L. Morris, Megan K. La Peyre, Bret M. Webb, Danielle A. Marshall, Donna M. Bilkovic, Just Cebrian, Giovanna Mcclenachan, Kelly M. Kibler, Linda J. Walters, David Bushek, Eric L. Sparks, Nigel A. Temple, Joshua Moody, Kory Angstadt, Joshua Goff, Maura Boswell, Paul Sacks, Stephen E. Swearer

Civil & Environmental Engineering Faculty Publications

One of the paramount goals of oyster reef living shorelines is to achieve sustained and adaptive coastal protection, which requires meeting ecological (i.e., develop a self-sustaining oyster population) and engineering (i.e., provide coastal defense) targets. In a large-scale comparison along the Atlantic and Gulf coasts of the United States, the efficacy of various designs of oyster reef living shorelines at providing wave attenuation was evaluated accounting for the ecological limitations of oysters with regards to inundation duration. A critical threshold for intertidal oyster reef establishment is 50% inundation duration. Living shorelines that spent less than half of the time ( …

Laboratory Study Of The Effects Of Flexible Vegetation On Solute Diffusion In Unidirectional Flow, Sha Lou, Hao Wang, Hongzhe Liu, Guihui Zhong, Larisa Dorzhievna Radnaeva, Elena Nikitina, Gangfeng Ma, Shuguang Liu

Civil & Environmental Engineering Faculty Publications

Background

Flexible vegetation is an important part of the riverine ecosystem, which can reduce flow velocity, change turbulence structure, and affect the processes of solute transport. Compared with the flow with rigid vegetation, which has been reported in many previous studies, bending of flexible vegetation increases the complexity of the flow-vegetation-solute interactions. In this study, laboratory experiments are carried out to investigate the influence of flexible vegetation on solute transport, and methods for estimating the lateral and longitudinal diffusion coefficients in the rigid vegetated flow are examined for their applications to the flow with flexible vegetation.

Results

The experimental observations …

Stobe Photography Mapping Of Cell Membrane Potential With Nanosecond Resolution, Allen S. Kiester, Bennett L. Ibey, Zachary N. Coker, Andrei G. Pakhomov, Joel N. Bixler

Bioelectrics Publications

The ability to directly observe membrane potential charging dynamics across a full microscopic field of view is vital for understanding interactions between a biological system and a given electrical stimulus. Accurate empirical knowledge of cell membrane electrodynamics will enable validation of fundamental hypotheses posited by the single shell model, which includes the degree of voltage change across a membrane and cellular sensitivity to external electric field non-uniformity and directionality. To this end, we have developed a high-speed strobe microscopy system with a time resolution of ~ 6 ns that allows us to acquire time-sequential data for temporally repeatable events (non-injurious …

Plasma-Treated Solutions (Pts) In Cancer Therapy, Hiromasa Tanaka, Sander Bekeschus, Dayun Yan, Masaru Hori, Michael Keidar, Mounir Laroussi

Electrical & Computer Engineering Faculty Publications

Cold physical plasma is a partially ionized gas generating various reactive oxygen and nitrogen species (ROS/RNS) simultaneously. ROS/RNS have therapeutic effects when applied to cells and tissues either directly from the plasma or via exposure to solutions that have been treated beforehand using plasma processes. This review addresses the challenges and opportunities of plasma-treated solutions (PTSs) for cancer treatment. These PTSs include plasma-treated cell culture media in experimental research as well as clinically approved solutions such as saline and Ringer’s lactate, which, in principle, already qualify for testing in therapeutic settings. Several types of cancers were found to succumb to …

Joint Modeling Of Rnaseq And Radiomics Data For Glioma Molecular Characterization And Prediction, Zeina A. Shboul, Norou Diawara, Arastoo Vossough, James Y. Chen, Khan M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

RNA sequencing (RNAseq) is a recent technology that profiles gene expression by measuring the relative frequency of the RNAseq reads. RNAseq read counts data is increasingly used in oncologic care and while radiology features (radiomics) have also been gaining utility in radiology practice such as disease diagnosis, monitoring, and treatment planning. However, contemporary literature lacks appropriate RNA-radiomics (henceforth, radiogenomics) joint modeling where RNAseq distribution is adaptive and also preserves the nature of RNAseq read counts data for glioma grading and prediction. The Negative Binomial (NB) distribution may be useful to model RNAseq read counts data that addresses potential shortcomings. …

The Resistive Barrier Discharge: A Brief Review Of The Device And Its Biomedical Applications, Mounir Laroussi

Electrical & Computer Engineering Faculty Publications

This paper reviews the principles behind the design and operation of the resistive barrier discharge, a low temperature plasma source that operates at atmospheric pressure. One of the advantages of this plasma source is that it can be operated using either DC or AC high voltages. Plasma generated by the resistive barrier discharge has been used to efficiently inactivate pathogenic microorganisms and to destroy cancer cells. These biomedical applications of low temperature plasma are of great interest because in recent times bacteria developed increased resistance to antibiotics and because present cancer therapies often are accompanied by serious side effects. Low …

Covid-19 And Biocybersecurity's Increasing Role On Defending Forward, Xavier Palmer, Lucas N. Potter, Saltuk Karahan

Electrical & Computer Engineering Faculty Publications

The evolving nature of warfare has been changing with cybersecurity and the use of advanced biotechnology in each aspect of the society is expanding and overlapping with the cyberworld. This intersection, which has been described as “biocybersecurity” (BCS), can become a major front of the 21st-century conflicts. There are three lines of BCS which make it a critical component of overall cybersecurity: (1) cyber operations within the area of BCS have life threatening consequences to a greater extent than other cyber operations, (2) the breach in health-related personal data is a significant tool for fatal attacks, and (3) health-related misinformation …

Fmri Feature Extraction Model For Adhd Classification Using Convolutional Neural Network, Senuri De Silva, Sanuwani Udara Dayarathna, Gangani Ariyarathne, Dulani Meedeniya, Sampath Jayarathna

Computer Science Faculty Publications

Biomedical intelligence provides a predictive mechanism for the automatic diagnosis of diseases and disorders. With the advancements of computational biology, neuroimaging techniques have been used extensively in clinical data analysis. Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder, with the symptomology of inattention, impulsivity, and hyperactivity, in which early diagnosis is crucial to prevent unwelcome outcomes. This study addresses ADHD identification using functional magnetic resonance imaging (fMRI) data for the resting state brain by evaluating multiple feature extraction methods. The features of seed-based correlation (SBC), fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) are comparatively applied to …

Photodynamic Therapy Of Inorganic Complexes For The Treatment Of Cancer, Chloe B. Smith, Lindsay C. Days, Duaa R. Alajroush, Khadija Faye, Yara Khodour, Stephen J. Beebe, Alvin Holder

Chemistry & Biochemistry Faculty Publications

Photodynamic therapy (PDT) is a medicinal tool that uses a photosensitiser and a light source to treat several conditions, including cancer. PDT uses reactive oxygen species (ROS) such as cytotoxic singlet oxygen ¹O₂ to induce cell death in cancer cells. Chemotherapy has historically utilized the cytotoxic effects of many metals, especially transition-metal complexes. However, chemotherapy is a systemic treatment so all cells in a patient's body are exposed to the same cytotoxic effects. Transition metal complexes have also shown high cytotoxicity as PDT agents. PDT is a potential localized method for treating several cancer types by using inorganic …

The Role Of Reactive Oxygen Species In The Immunity Induced By Nano-Pulse Stimulation, Siqi Guo, Niculina I. Burcus, Megan Scott, Yu Jing, Iurii Semenov

Bioelectrics Publications

Reactive oxygen species (ROS) are byproducts of tumor cells treated with Nano-Pulse Stimulation (NPS). Recently, ROS have been suggested as a contributing factor in immunogenic cell death and T cell-mediated immunity. This research further investigated the role of NPS induced ROS in antitumor immunity. ROS production in 4T1-luc breast cancer cells was characterized using three detection reagents, namely, Amplex Red, MitoSox Red, and Dihydroethidium. The efficiency of ROS quenching was evaluated in the presence or absence of ROS scavengers and/or antioxidants. The immunogenicity of NPS treated tumor cells was assessed by ex vivo dendritic cell activation, in vivo vaccination assay …

Connexin Hemichannel Activation By S-Nitrosoglutathione Synergizes Strongly With Photodynamic Therapy Potentiating Anti-Tumor Bystander Killing, Chiara Nardin, Chiara Peres, Sabrina Putti, Tiziana Orsini, Claudia Colussi, Flavia Mazzarda, Marcello Raspa, Ferdinando Scavizzi, Anna Maria Salvatore, Francesco Chiani, Abraham Tettey-Matey, Yuanyuan Kuang, Guang Yang, Mauricio A. Retamal, Fabio Mammano

Bioelectrics Publications

In this study, we used B16-F10 cells grown in the dorsal skinfold chamber (DSC) preparation that allowed us to gain optical access to the processes triggered by photodynamic therapy (PDT). Partial irradiation of a photosensitized melanoma triggered cell death in non-irradiated tumor cells. Multiphoton intravital microscopy with genetically encoded fluorescence indicators revealed that bystander cell death was mediated by paracrine signaling due to adenosine triphosphate (ATP) release from connexin (Cx) hemichannels (HCs). Intercellular calcium (Ca²⁺) waves propagated from irradiated to bystander cells promoting intracellular Ca²⁺ transfer from the endoplasmic reticulum (ER) to mitochondria and rapid activation of …

Effect Of He Plasma Jet Versus Surface Plasma On The Metabolites Of Acute Myeloid Leukemia Cells, Dehui Xu, Ning Ning, Yujing Xu, Wenjie Xia, Hai-Lan Chen, Michael G. Kong

Bioelectrics Publications

Cold atmospheric plasma, including plasma jet and surface plasma, can promote the apoptosis of cancer cells without causing significant damage to surrounding normal cells, which was hopeful to be applied to the clinical cancer therapy. However, experimental plasma devices used directly to clinical experiments has challenges in technology and methods, especially the difference in killing tumor cells efficiency of these two common plasma sources. Therefore, it is great necessity to explore the differences in treating tumors between different plasma sources. This paper achieved good killing efficiency by using two kinds of cold atmospheric plasma generating devices, namely plasma jet and …