Hyperfiltration-Associated Biomechanical Forces In Glomerular Injury And Response: Potential Role For Eicosanoids., Mukut Sharma, Ram Sharma, Ellen T. Mccarthy, Virginia J. Savin, Tarak Srivastava

Manuscripts, Articles, Book Chapters and Other Papers

Hyperfiltration is a well-known risk factor in progressive loss of renal function in chronic kidney disease (CKD) secondary to various diseases. A reduced number of functional nephrons due to congenital or acquired cause(s) results in hyperfiltration in the remnant kidney. Hyperfiltration-associated increase in biomechanical forces, namely pressure-induced tensile stress and fluid flow-induced shear stress (FFSS) determine cellular injury and response. We believe the current treatment of CKD yields limited success because it largely attenuates pressure-induced tensile stress changes but not the effect of FFSS on podocytes. Studies on glomerular podocytes, tubular epithelial cells and bone osteocytes provide evidence for a …

Identifying The Immune Related Metabolic Properties Of Pancreatic Cancer Using Nuclear Magnetic Resonance Spectroscopy And Dynamic Magnetic Resonance Spectroscopic Imaging With Hyperpolarized Pyruvate, Joseph Weygand

Dissertations and Theses (Open Access)

Despite its relatively low incidence, pancreatic cancer was the fourth leading cause of cancer-related death in the US in 2015. This is due in part to pancreatic cancer’s natural resistance to both chemotherapy and radiotherapy. Immunotherapy presents an attractive potential treatment approach, but initial trials in mice have proved ineffective. Because cancer cells exhibit a significant increase in metabolic activity relative to normal tissue, an understanding of the metabolic function of tumors in systems with different levels of immunocompetence is a critical first step to develop an understanding of the immune-related metabolic properties of the tumor, which have potential application …

High-Throughput Mapping Of The Biological Effects Of Particle Therapy, Lawrence Bronk

Dissertations and Theses (Open Access)

Radiation therapy is an essential tool in the cure of many cancer patients. Charged particle based radiation therapies are gaining momentum as the physical dose distributions of ions are superior to standard photons due their limited range. Additionally, charged particle radiation has been shown to have linear energy transfer (LET) specific relative biological effectiveness (RBE) when compared to photons. It is essential to employ accurate biophysical models for particle beams in order to maximize the therapeutic potential of particle therapy through the introduction of biologically optimized treatment planning. The development of such models requires the support of large amounts of …

Volumetric, Magnetic Resonance-Visible, And Radiation-Sensitive Detectors For Magnetic Resonance Image-Guided Radiation Therapy, Hannah J. Lee

Dissertations and Theses (Open Access)

VOLUMETRIC, MAGNETIC RESONANCE-VISIBLE, AND RADIATION-SENSITIVE DETECTORS FOR MAGNETIC RESONANCE IMAGE-GUIDED RADIATION THERAPY

Hannah Jungeun Lee

Advisory Professor: Geoffrey S. Ibbott, Ph.D.

Due to the superior soft-tissue contrast of magnetic resonance imaging (MRI) compared to conventional computed tomography (CT) and other on-board imaging techniques, several groups have integrated MRI and radiation treatment machine systems. The advent of MR image-guided radiation therapy (MR-IGRT) using systems, such as the 1.5 MRI – 7 MV linear accelerator (MR-Linac), now allow for improved soft-tissue on-board imaging for patient position and tumor target localization verification and the ability to assess functional biological tissue characteristics with MRI, …

Comparison Of Modified Two-Point Dixon And Chemical Shift Encoded Mri Water-Fat Separation Methods For Fetal Fat Quantification: Compare Water-Fat Methods For Fetal Fat, Stephanie A. Giza, Michael R. Miller, Prasiddha Parthasarathy, Barbra De Vrijer, Charles A. Mckenzie

Medical Biophysics Publications

This is the peer reviewed version of the following article: [Comparison of modified two-point dixon and chemical shift encoded MRI water-fat separation methods for fetal fat quantification: Compare Water-Fat Methods for Fetal Fat. Journal of Magnetic Resonance Imaging 48, 1 p274-282 (2018)], which has been published in final form at https://doi.org/10.1002/jmri.25929. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions: https://authorservices.wiley.com/author-resources/Journal-Authors/licensing/self-archiving.html#3.

Numerically Solving A System Of Pdes Modeling Chronic Wounds Treated With Oxygen Therapy, Stefan Stryker

Mahurin Honors College Capstone Experience/Thesis Projects

Chronic wounds such as diabetic foot ulcers are the leading cause of non-traumatic amputations in developed countries. For researchers to better understand the physiology of these wounds, a mathematical model describing oxygen levels at the wound site can be used to help predict healing responses. The model utilizes equations that are modified from work by Guffey (2015) that consists of four variables – oxygen, bacteria, neutrophils, and chemoattractant within a system of partial differential equations. Our research focuses on numerically solving these partial differential equations using a finite volume approach. This numerical solver will be important for future research in …

Capacitive Memory Alters Alternans And Spontaneous Activity In A Minimal Cardiomyocyte Model, Tien Comlekoglu, Seth H. Weinberg

Biology and Medicine Through Mathematics Conference

No abstract provided.

High Performance Computation Of Cardiac Models In Real-Time Using Webgl, Abouzar Kaboudian, Flavio H. Fenton

Biology and Medicine Through Mathematics Conference

No abstract provided.

Unfair Competition Governs The Interaction Of Pcpi-17 With Myosin Phosphatase (Pp1-Mypt1)., Joshua J. Filter, Byron C. Williams, Masumi Eto, David Shalloway, Michael L. Goldberg

Department of Molecular Physiology and Biophysics Faculty Papers

The small phosphoprotein pCPI-17 inhibits myosin light-chain phosphatase (MLCP). Current models postulate that during muscle relaxation, phosphatases other than MLCP dephosphorylate and inactivate pCPI-17 to restore MLCP activity. We show here that such hypotheses are insufficient to account for the observed rapidity of pCPI-17 inactivation in mammalian smooth muscles. Instead, MLCP itself is the critical enzyme for pCPI-17 dephosphorylation. We call the mutual sequestration mechanism through which pCPI-17 and MLCP interact inhibition by unfair competition: MLCP protects pCPI-17 from other phosphatases, while pCPI-17 blocks other substrates from MLCP's active site. MLCP dephosphorylates pCPI-17 at a slow rate that is, nonetheless, …

P27. Acute Impact Of An Extremely Low Frequency Magnetic Stimulus On Human Neurophysiological Function - Magnetophosphene Perception, Cadence M. Baker

Western Research Forum

Background: Magnetophosphenes are classified as colourless, flickering lights that are perceived with closed eyes in the dark, and upon exposure to a magnetic field (MF). Uncertainties exist involving the MF threshold for magnetophosphene perception.

Methods: Forty subjects will be enrolled in this experiment aiming to provide a frequency-response curve of magnetophosphene perception under MF exposure. Subjects will sit in a whole head MF exposure device wearing a 64-channel MRI-compatible EEG cap. Subjects will be exposed to a MF with a frequency of 5-300 Hz, in the form of an increasing flux density ramp (increasing magnetic field flux density from 0-100 …

Mri Ventilation Abnormalities Predict Quality-Of-Life And Lung Function Changes In Mild-To-Moderate Copd: Longitudinal Tincan Study, Miranda Kirby, Rachel L Eddy, Damien Pike, Sarah Svenningsen, Harvey O Coxson, Don D Sin, David G Mccormack, Grace Parraga

Medical Biophysics Publications

CT biomarkers of emphysema (15th percentile of the CT density histogram, HU15%) and airways disease (wall thickness of airways with 10 mm internal perimeter, Pi10) have shown promise for providing prognostic information.2 Although recent data3 showed that the change in CT emphysema may be used to estimate the efficacy of therapy in patients with α-1-antitrypsin-deficiency, thus far none of the currently developed CT biomarkers have been shown to reflect changes in outcomes that are important to patients with COPD. MRI with inhaled noble gases provide highly sensitive and unique microstructural and functional information in COPD.4 MRI biomarkers of COPD are …

Diversity And Plasticity In Signaling Pathways That Regulate Smooth Muscle Responsiveness: Paradigms And Paradoxes For The Myosin Phosphatase, The Master Regulator Of Smooth Muscle Contraction., Masumi Eto, Toshio Kitazawa

Department of Molecular Physiology and Biophysics Faculty Papers

A hallmark of smooth muscle cells is their ability to adapt their functions to meet temporal and chronic fluctuations in their demands. These functions include force development and growth. Understanding the mechanisms underlying the functional plasticity of smooth muscles, the major constituent of organ walls, is fundamental to elucidating pathophysiological rationales of failures of organ functions. Also, the knowledge is expected to facilitate devising innovative strategies that more precisely monitor and normalize organ functions by targeting individual smooth muscles. Evidence has established a current paradigm that the myosin light chain phosphatase (MLCP) is a master regulator of smooth muscle responsiveness …

Biochemical And Biophysical Methods For Analysis Of Poly(Adp-Ribose) Polymerase 1 And Its Interactions With Chromatin., Maggie H. Chassé, Uma M. Muthurajan, Nicholas J. Clark, Michael A. Kramer, Srinivas Chakravarthy, Thomas Irving, Karolin Luger

Manuscripts, Articles, Book Chapters and Other Papers

Poly (ADP-Ribose) Polymerase I (PARP-1) is a first responder to DNA damage and participates in the regulation of gene expression. The interaction of PARP-1 with chromatin and DNA is complex and involves at least two different modes of interaction. In its enzymatically inactive state, PARP-1 binds native chromatin with similar affinity as it binds free DNA ends. Automodification of PARP-1 affects interaction with chromatin and DNA to different extents. Here we describe a series of biochemical and biophysical techniques to quantify and dissect the different binding modes of PARP-1 with its various substrates. The techniques listed here allow for high …

Role Of Translation Initiation In Regulation Of Epithelial Junctions And Cell Motility, Fahda Fawaz Alsharief

Theses and Dissertations

The integrity and barrier properties of intestinal epithelium are determined by specialized adhesive structures known as intercellular junctions; composed of adherens junctions (AJs), tight junctions (TJs) and focal adhesions that mediate cell-cell and cell matrix interactions, respectively. These two types of epithelial cell adhesions regulate each other during disruption and restitution of the epithelial barrier. Inflammatory cytokines such as interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) are elevated during intestinal inflammation. The most notable effects of IFNγ and TNFα on intestinal epithelial homeostasis involve disruption of apical junctions and attenuation of cell migration. Although molecular mechanisms underlying these …

Mobilising Expertise And Resources To Close The Radiotherapy Gap In Cancer Care., D Rodin, J Longo, T Sherertz, M M Shah, O Balagun, N Wendling, Jacob Van Dyk, C N Coleman, M J Xu, S Grover

Oncology Publications

Closing the gap in cancer care within low- and middle-income countries and in indigenous and geographically isolated populations in high-income countries requires investment and innovation. This is particularly true for radiotherapy, for which the global disparity is one of the largest in healthcare today. New models and paradigms and non-traditional collaborations have been proposed to improve global equity in cancer control. We describe recent initiatives from within the radiation oncology community to increase access to treatment, build the low- and middle-income countries' radiation oncology workforce, mobilise more professionals from within high-income countries and raise awareness of the global need for …

Analysis Of Global Radiotherapy Needs And Costs By Geographic Region And Income Level., E Zubizarreta, Jacob Van Dyk, Y Lievens

Oncology Publications

Recent years have seen various reviews on the lack of access to radiotherapy often based on geographic regions of the world such as Africa, Asia Pacific, Europe, Latin America and North America. Countries are often defined by their national income per capita levels based on World Bank definitions of high income, upper middle income, lower middle income and low income. Within the world regions, there are significant variations in gross national income (GNI) per capita among the different countries, and even within similar income levels, large variations exist. This report presents the actual status of radiotherapy and analyses the current …

The Role Of The Mir-200 Family On The Tumor Suppressor Rassf2 And The Effect On Mapk Pathway Activity In Colorectal Cancer., Jane V. Carter

Electronic Theses and Dissertations

This dissertation investigated the role of the miR-200 family in normal colon epithelial (CCD 841) and Dukes’ C (HT-29) colorectal cancer (CRC) cell lines. Our aim was to characterize expression of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429) in colorectal cell lines, study their effect on the tumor suppressor Ras Associated Domain-Containing Protein (RASSF) 2 and on subsequent activity within the mitogen-activated protein kinase (MAPK) signaling pathway. We wanted to determine whether regulation of miR-200 family members could change cell behavior towards more “cancer-like” in a normal colon epithelium (CCD 841) cell line, or less “cancer-like” in a …

Accuracy Requirements And Uncertainties In Radiotherapy: A Report Of The International Atomic Energy Agency., Debbie Van Der Merwe, Jacob Van Dyk, Brendan Healy, Eduardo Zubizarreta, Joanna Izewska, Ben Mijnheer, Ahmed Meghzifene

Oncology Publications

BACKGROUND: Radiotherapy technology continues to advance and the expectation of improved outcomes requires greater accuracy in various radiotherapy steps. Different factors affect the overall accuracy of dose delivery. Institutional comprehensive quality assurance (QA) programs should ensure that uncertainties are maintained at acceptable levels. The International Atomic Energy Agency has recently developed a report summarizing the accuracy achievable and the suggested action levels, for each step in the radiotherapy process. Overview of the report: The report seeks to promote awareness and encourage quantification of uncertainties in order to promote safer and more effective patient treatments. The radiotherapy process and the radiobiological …

Radiation Oncology Quality And Safety Considerations In Low Resource Settings: A Medical Physics Perspective, Jacob Van Dyk, Ahmed Meghzifene

Oncology Publications

The last few years have seen a significant growth of interest in the global radiation therapy crisis. Various organizations have quantified the need and are providing aid in support of addressing the shortfalls existing in many low-to-middle income countries (LMICs). With the tremendous demand for new facilities, equipment and personnel, it is very important to recognize the quality and safety challenges and to address them directly. An examination of publications on quality and safety in radiation therapy indicates a consistency in a number of the recommendations; however, these authoritative reports were generally based on input from high-resourced contexts. Here we …

Effect Of Left Atrial Wall Thickness On Radiofrequency Ablation Success., Jiro Inoue, Allan C Skanes, Lorne J Gula, Maria Drangova

Medical Biophysics Publications

INTRODUCTION: Radiofrequency (RF) ablation in thicker regions of the left atrium (LA) may require increased ablation energy in order to achieve effective transmural lesions. Consequently, many cases of recurrent atrial fibrillation (AF) postablation may be due to thicker-than-normal atrial tissue. The aim of this study was to test the hypotheses that patients with recurrent AF have thicker tissue overall and that electrical reconnection is more likely in regions of thicker tissue.

METHODS AND RESULTS: Retrospective analysis was performed on 86 CT images acquired preoperatively from a cohort of 119 patients who had undergone RF ablation for AF. Of these, 33 …