Biochemistry, Biophysics, and Structural Biology Commons^™

Radiation Exposure Determination In A Secure, Cloud-Based Online Environment, Ben C. Shirley, Eliseos J. Mucaki, Peter Rogan

Biochemistry Publications

Rapid sample processing and interpretation of estimated exposures will be critical for triaging exposed individuals after a major radiation incident. The dicentric chromosome (DC) assay assesses absorbed radiation using metaphase cells from blood. The Automated Dicentric Chromosome Identifier and Dose Estimator System (ADCI) identifies DCs and determines radiation doses. This study aimed to broaden accessibility and speed of this system, while protecting data and software integrity. ADCI Online is a secure web-streaming platform accessible worldwide from local servers. Cloud-based systems containing data and software are separated until they are linked for radiation exposure estimation. Dose estimates are identical to ADCI …

Radiation Exposure Determination In A Secure, Cloudbased Online Environment, Ben C. Shirley, Eliseos J. Mucaki, Joan H.M. Knoll, Peter Rogan

Biochemistry Publications

Rapid sample processing and interpretation of estimated exposures will be critical for triaging exposed individuals after a major radiation incident. The dicentric chromosome (DC) assay assesses absorbed radiation using metaphase cells from blood. The Automated Dicentric Chromosome Identifier and Dose Estimator System (ADCI) identifies DCs and determines radiation doses. This study aimed to broaden accessibility and speed of this system, while protecting data and software integrity. ADCI Online is a secure web-streaming platform accessible worldwide from local servers. Cloud-based systems containing data and software are separated until they are linked for radiation exposure estimation. Dose estimates are identical to ADCI …

Likely Community Transmission Of Covid-19 Infections Between Neighboring, Persistent Hotspots In Ontario, Canada, Ben C. Shirley, Eliseos J. Mucaki, Peter Rogan

Biochemistry Publications

Introduction: This study aimed to produce community-level geo-spatial mapping of confirmed COVID-19 cases in Ontario Canada in near real-time to support decision-making. This was accomplished by area-to-area geostatistical analysis, space-time integration, and spatial interpolation of COVID-19 positive individuals.
Methods: COVID-19 cases and locations were curated for geostatistical analyses from March 2020 through June 2021, corresponding to the first, second, and third waves of infections. Daily cases were aggregated according to designated forward sortation area (FSA), and postal codes (PC) in municipal regions Hamilton, Kitchener/Waterloo, London, Ottawa, Toronto, and Windsor/Essex county. Hotspots were identified with area-to-area tests including Getis-Ord Gi*, Global …

Improved Radiation Expression Profiling In Blood By Sequential Application Of Sensitive And Specific Gene Signatures, Eliseos J. Mucaki, Ben C. Shirley, Peter K. Rogan

Biochemistry Publications

Purpose. Combinations of expressed genes can discriminate radiation-exposed from normal control blood samples by machine learning based signatures (with 8 to 20% misclassification rates). These signatures can quantify therapeutically-relevant as well as accidental radiation exposures. The prodromal symptoms of Acute Radiation Syndrome (ARS) overlap those present in Influenza and Dengue Fever infections. Surprisingly, these human radiation signatures misclassified gene expression profiles of virally infected samples as false positive exposures. The present study investigates these and other confounders, and then mitigates their impact on signature accuracy.

Methods. This study investigated recall by previous and novel radiation signatures independently derived …

Validation Of Arterial Spin Labeling For Longitudinal Monitoring And Differential Diagnosis Of Frontotemporal Dementia, Tracy Ssali

Electronic Thesis and Dissertation Repository

Frontotemporal dementia (FTD) is a devastating neurodegenerative disease characterized by a rapid decline in behavioural, language, and motor abilities. Advances in the understanding of FTD genetics and pathophysiology, and the subsequent development of novel disease modifying treatments have highlighted the need for tools to assess their efficacy. While structural magnetic resonance imaging (MRI) and functional imaging with ¹⁸F-flurodeoxyglucose (FDG) positron emission tomography (PET) are used for clinical diagnosis, structural changes are subtle at the early stages and PET imaging is expensive and access limited. Given the coupling of cerebral blood flow (CBF) to energy metabolism, an attractive alternative is …

Exogenous Surfactant As A Delivery Vehicle For Intrapulmonary Therapeutics, Brandon J. Baer

Electronic Thesis and Dissertation Repository

As an organ system, the lung has unique advantages and disadvantages for direct drug delivery. Its contact with the external environment allows for the airways to be easily accessible to intrapulmonary delivery. However, its complex structure, which divides into more narrow airways with each branch, can make direct delivery to the remote alveoli challenging. The objective of this thesis was to overcome this issue by using exogenous surfactant, a lipoprotein complex used to treat neonatal respiratory distress syndrome, as a carrier for pulmonary therapeutics. It was hypothesized that therapeutics administered with a surfactant vehicle would display enhanced delivery to the …

Understanding The Role Of Rhamm In Tumor Load– Mediated Tumor Invasiveness Of Triple Negative Breast Cancer, Ashwin Sritharan, Britney Messam

Undergraduate Student Research Internships Conference

1.Compare the levels of proliferation between RHAMM+/+ and RHAMM -/- MDA-MB-231 spheroids as determined by ki67 and Caspase 3 signaling 2.Compare levels of RHAMM, CD44, Has2, and p-ERK activation between RHAMM+/+ and RHAMM -/- MDA-MB-231 spheroids

Pathway‐Extended Gene Expression Signatures Integrate Novel Biomarkers That Improve Predictions Of Patient Responses To Kinase Inhibitors, Ashis Bagchee‐Clark, Eliseos J. Mucaki, Tyson Whitehead, Peter Rogan

Biochemistry Publications

Cancer chemotherapy responses have been related to multiple pharmacogenetic biomarkers, often for the same drug. This study utilizes machine learning to derive multi‐gene expression signatures that predict individual patient responses to specific tyrosine kinase inhibitors, including erlotinib, gefitinib, sorafenib, sunitinib, lapatinib and imatinib. Support vector machine (SVM) learning was used to train mathematical models that distinguished sensitivity from resistance to these drugs using a novel systems biology‐based approach. This began with expression of genes previously implicated in specific drug responses, then expanded to evaluate genes whose products were related through biochemical pathways and interactions. Optimal pathway‐extended SVMs predicted responses in …

Estimating Partial Body Ionizing Radiation Exposure By Automated Cytogenetic Biodosimetry, Peter Rogan

Biochemistry Publications

Purpose: Inhomogeneous exposures to ionizing radiation can be detected and quantified with the Dicentric Chromosome Assay (DCA) of metaphase cells. Complete automation of interpretation of the DCA for whole body irradiation has significantly improved throughput without compromising accuracy, however low levels of residual false positive dicentric chromosomes (DCs) have confounded its application for partial body exposure determination.

Materials and Methods: We describe a method of estimating and correcting for false positive DCs in digitally processed images of metaphase cells. Nearly all DCs detected in unirradiated calibration samples are introduced by digital image processing. DC frequencies of irradiated calibration …

Meeting Radiation Dosimetry Capacity Requirements Of Population-Scale Exposures By Geostatistical Sampling., Peter K Rogan, Eliseos J Mucaki, Ruipeng Lu, Ben C Shirley, Edward Waller, Joan H M Knoll

Biochemistry Publications

BACKGROUND: Accurate radiation dose estimates are critical for determining eligibility for therapies by timely triaging of exposed individuals after large-scale radiation events. However, the universal assessment of a large population subjected to a nuclear spill incident or detonation is not feasible. Even with high-throughput dosimetry analysis, test volumes far exceed the capacities of first responders to measure radiation exposures directly, or to acquire and process samples for follow-on biodosimetry testing.

AIM: To significantly reduce data acquisition and processing requirements for triaging of treatment-eligible exposures in population-scale radiation incidents.

METHODS: Physical radiation plumes modelled nuclear detonation scenarios of simulated exposures at …

Radiation Dose Estimation By Completely Automated Interpretation Of The Dicentric Chromosome Assay, Peter Rogan, Yanxin Li, Ben Shirley, Ruth Wilkins, Farrah Norton, Joan Knoll

Biochemistry Publications

Accuracy of the automated dicentric chromosome (DC) assay relies on metaphase image selection. This study validates a software framework to find the best image selection models that mitigate inter-sample variability. Evaluation methods to determine model quality include the Poisson goodness-of-fit of DC distributions for each sample, residuals after calibration curve fitting and leave-one-out dose estimation errors. The process iteratively searches a pool of selection model candidates by modifying statistical and filter cut-offs to rank the best candidates according to their respective evaluation scores. Evaluation scores minimize the sum of squared errors relative to the actual radiation dose of the calibration …

Effects Of Maternal Protein Restriction On The Pulmonary Surfactant System During The Early Life And Adulthood, Reza Khazaee

Electronic Thesis and Dissertation Repository

Fetal growth restriction (FGR) is defined by low birth weight and contributes to a variety of adult-onset diseases with different severities between males and females. However, the effects of FGR on the pulmonary surfactant are not fully elucidated. In this thesis, first, we investigated the FGR effects on the lung function and the surfactant system at the early postnatal life. It was hypothesized that FGR contributes to alterations of lung mechanics and the surfactant system during the neonatal period. Second, we assessed the FGR effects on the surfactant system in response to sepsis in adulthood. It was hypothesized that FGR …

Accurate Cytogenetic Biodosimetry Through Automated Dicentric Chromosome Curation And Metaphase Cell Selection, Jin Liu, Yanxin Li, Ruth Wilkins, Canadian Nuclear Laboratories, Joan H. Knoll, Peter Rogan

Biochemistry Publications

Accurate digital image analysis of abnormal microscopic structures relies on high quality images and on minimizing the rates of false positive (FP) and negative objects in images. Cytogenetic biodosimetry detects dicentric chromosomes (DCs) that arise from exposure to ionizing radiation, and determines radiation dose received based on DC frequency. Improvements in automated DC recognition increase the accuracy of dose estimates by reclassifying FP DCs as monocentric chromosomes or chromosome fragments. We also present image segmentation methods to rank high quality digital metaphase images and eliminate suboptimal metaphase cells. A set of chromosome morphology segmentation methods selectively filtered out FP DCs …

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the …

Assessment Of Post-Treatment Imaging Changes Following Radiotherapy Using Magnetic Susceptibility Techniques, Jean-Guy Belliveau

Electronic Thesis and Dissertation Repository

Radiation therapy (RT) is a common treatment for brain neoplasms and is used alone or in combination with other therapies. The use of RT has been found to be successful in controlling tumors and extending the overall survival of patients; however, there are many unanswered questions regarding radiotherapy effects in the normal brain surrounding or infiltrated by tumor. Changes to the vascular and parenchyma have been documented, and more recently inflammatory mechanisms have been postulated to play a role in radiation injury. Traditional imaging techniques used within the clinic (CT and MRI) are often lacking in their ability to differentiate …

Regulation Of Phosphatase And Tensin Homolog Expression And Activity By Transforming Growth-Factor Beta In The Trabecular Meshwork Cells: Implications For Primary Open Angle Glaucoma, Nikoleta Tellios

Electronic Thesis and Dissertation Repository

Glaucoma is a multifactorial condition caused, in part, by fibrosis of the sieve-like trabecular meshwork (TM) tissue, which impedes drainage of aqueous humor (AH), leading to increased intraocular pressure and associated optic nerve damage and blindness. Fibrosis of the TM is mainly caused by the increased levels of active transforming growth factor-β 2 (TGFβ2) in the AH of glaucoma patients.

Previous reports have shown that TGFβ decreases the expression of Phosphatase and Tensin Homolog (PTEN) gene and that PTEN is a major regulator of ECM deposition. In this study we investigate the regulation of PTEN protein expression and …

The Role Of Bone Sialoprotein In The Tendon-Bone Insertion, Ryan M. Marinovich

Electronic Thesis and Dissertation Repository

Tendons and ligaments insert into bone through a transitional tissue termed the enthesis which is susceptible to injury and difficult to repair. Entheses contain a region of calcified fibrocartilage (CFC), however mineral-associated proteins in this tissue remain poorly characterized. Bone sialoprotein (BSP) is a phosphoprotein associated with mineralizing tissues. In these studies BSP was identified in the CFC of entheses by immunohistochemistry. Analysis of the entheses of Bsp^-/- mice indicate abnormalities in the CFC. Compared to controls, the CFC of the quadriceps tendon enthesis is 28% and 41 % longer in 15 week and 14 month old Bsp^{-/- …}