Physics

Permanent URI for this collectionhttp://hdl.handle.net/10342/67

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Open Access
Modeling the Impact of Container Material and Geometry on the Uniformity of Dose in Irradiation Calibration
(East Carolina University, July 2024) Snedeker, Marcus
In order to calibrate radiation sources in instruments used by the Optically Stimulated Luminescence Laboratory at ECU, samples are sent in containers to an external gamma source to be irradiated with a known radiation dose. The type of material used for the container can have an effect on the uniformity of dose absorbed by the sample, which can introduce unforeseen sources of error in the calibration. In this study, simulations were performed using DosiVox (via Geant4) to approximate the dose absorbed throughout different sample-container setups. The goal is to quantify dose uniformity and determine which container materials may be used, while still maintaining feasible levels of uniformity. It was ascertained that the container materials which best maintain uniformity for ceramic samples are aluminum, silica, and ceramic. It was also ascertained that the container materials which best maintain uniformity for silica samples are borosilicate glass, silica, and ceramic. Teflon was found to be the container material that maintained uniformity the least for both sample types.
Open Access
Characterization of RAS Protein Using Raman Spectroscopy
(East Carolina University, July 2024) Aryal, Makunda
Ras is a family of related proteins expressed in all animal cells, which is small GTPase anchors to the plasma membrane where it regulates signal transduction for cell proliferation, growth, survival, and other cell functions. Mutation of Ras makes it lost the ability to regulate signal transduction and causes cancer. Three different types of Ras (KRAS, HRAS, NRAS) and their isoforms have been identified in different human cancers. Understanding Ras protein functioning mechanisms is crucial in developing cancer drug and cancer therapy at the molecular level, which is highly related to its primary, secondary, and tertiary structures. At present, X-ray crystallography and NMR are the two major techniques to effectively measure Ras protein structures and its conformational geometries, but they cannot measure Ras protein conformations in cells under physiological conditions. In this study, we intend to develop label-free Raman spectroscopy methods to characterize and quantitate Ras isoforms and their structural conformations with their unique finger-printing vibrational spectra in vivo and in vitro, as well as to monitor the small drug molecule’s binding with Ras molecule in live cells, which is new to Ras based cancer biology. The first part of this dissertation work is to explore the capability of near-infrared Raman spectroscopy and multivariate analysis techniques for the characterization and differentiation of Ras isoforms and their structural conformations with their finger-printing Raman spectra. We have collected Raman spectra from different Ras isoforms. We have developed a principal component analysis (PCA), a discriminant analysis of principal component (DAPC), and Raman barcode methods, and demonstrated that Ras isoforms can be differentiated by their Raman spectra. We have studied the structural conformations of Ras proteins with GDP and GTP loading. By deconvolution of Raman spectra, we were able to obtain new information about Ras conformational structures including protein’s secondary structures, hydrogen bonding condition of phenol side chain, and hydrophobic nature of tyrosine doublet for each Ras isoforms. We have applied Raman spectroscopy for the study of the specific inhibitor (ARS1620 drug) and KRAS G12C interactions, offering new insights into Ras-targeted cancer therapies. These data allow generating a library of Raman spectra of Ras isoforms in vitro, which may serve as the control and platform for developing methods to detect the Ras Raman fingerprint inside a cell. The second part is to develop a vacuum-enhanced micro-Raman spectroscopy (VERS) for the detection of analyte molecules at relatively low concentrations in an aqueous medium. Although Raman spectroscopy is a powerful technique for analyzing biomolecules, the molecular cross-section of Raman scattering is very low, and thus, high analyte concentration in hundreds of mM is typically required for normal Raman spectroscopy. Since Ras proteins are generally available at low concentration either in vitro or inside the live cells, we intend to develop a novel label-free enhanced Raman spectroscopy for the detection of proteins and other molecules at relatively low concentrations. The VERS technique relies on the increase in the molecule’s concentration within the micron-sized excitation volume of laser focus by vacuum evaporation of solvents and does not cause the alteration in normal Raman spectra. We demonstrate that an enhancement factor of ~103-104 was observed for glucose and protein samples, and the enhancement factor depends on the size of the sample holder and the volume of the liquid sample used. We show that VERS can be used to detect ciprofloxacin antibiotics in human urine at a level of 2 μg/ml. We also show that the VERS technique is particularly useful for detecting biomolecules resolved in a solvent such as dimethyl sulfoxide (DMSO) that has an intense Raman background due to the evaporation of the solvent. Traditional enhancer materials like metal nanoparticles are not needed in VERS technique. The third part is to develop the surface-enhanced Raman scattering (SERS) spectroscopy and SERS-based super-resolution Raman imaging techniques for the detection and chemical imaging of analytes at the single-molecule level. Since the intrinsic Raman scattering of Ras protein and other biomolecules has very low probability and the intra-cellular concentration of Ras is extremely low (in nanomole level), we intend to introduce nano-sized metallic particles (SERS substrate) to bind with the target molecules and use their SERS signals to detect the target molecules with an ultrahigh sensitivity and precisely determine the spatial location of the molecules. We built a home-made experimental setup that allows simultaneous observation of the Raman images of hot spots and acquisition of time-lapse Raman spectra of a single hot particle. We explored the dynamic behavior of SERS of hot particles at the single-molecule level, focusing on the influence of environmental conditions and laser power on the stability of SERS Raman signals. It was observed that SERS intensity fluctuations were more pronounced at the atmospheric pressure than at a low pressure. The experimental data further revealed that as the laser power increased (~ 8.9 μW and above), there was a notable increase in SERS signal fluctuations and blinking, probably due to thermal or photo-induced changes in nanoparticle clusters. We proved that the use of bright field microscopy and Raman imaging for tracking hotspots together with ThunderSTORM software, was effective in accurately identifying and analyzing the change in hot particle’s center position. These findings underscore the importance of precise experimental control on both laser parameters and environmental conditions to optimize SERS applications at single molecule levels, which advances our understanding of SERS at the nanoscale, promoting its application in nanotechnology and materials science.
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Fluence Perturbations Associated with Electron Film Dosimetry
(1993-04) Sgroi, Denise E.
Open Access
Magnetic Control of NanoEL via Magneto-Mechanical Actuation: A proof of Concept for a Potential Nanotherapeutic Approach
(East Carolina University, 2023-05-03) Kanber, Mohammad
Cancer treatment is one of the major health problems that burdens society. According to the latest publication of the American Cancer Society, the cancer mortality rate has reached 32% in 2022 in the US. To address these alarming numbers, some gold standards, including therapeutic targeting, are being used to treat cancer. However, when tumor grows beyond a critical size, its vascular system differentiates abnormally and erratically creating heterogeneous endothelial barriers that further restricts drug deliveries into tumors. One way to overcome this problem is to induce endothelial leakiness using nanoparticles (NanoEL), so therapeutic drugs can be successfully delivered. While several methods exist, none has been established as a valid clinical approach. The most concerning complication is related to the fact that uncontrolled NanoEL prompts subsequent tumor migration and the appearance of new metastatic sites. In this research, we propose a new non-invasive approach based on magneto-mechanical actuation to remotely control the NanoEL by implementing PEGylated superparamagnetic iron oxide nanoparticles (PEG SPIONs), which are actuated by non-heating super low-frequency magnetic fields. As proof of concept, we developed a 2D cell culture model based on human umbilical vein endothelial cells (HUVEC). Our findings indicate that PEG-SPIONs can assemble within the actin filaments. When magnetically actuated, magnetic forces are translated into mechanical agitation, which induced actin remodeling and subsequent disruption of VE-cadherin junctions. This enabled us to deliver therapeutic drugs across the endothelium in a controlled manner. This approach has the potential to avert cancer migration and provides a remotely controlled drug delivery method harnessing the physics and biology of endothelial adherens junctions. This approach can open up new avenues for targeted drug delivery into anatomic regions within the body for a broad range of disease interventions.
Embargo
RADIOSENSITIZATION OF PROSTATE CARCINOMA CELLS BY PEGYLATED METALLIC NANOPARTICLES TO PROTON IRRADIATION
(East Carolina University, 2023-05-01) Gaddis, Tristan K
One of the main goals of cancer radiation therapy is to reduce the dose to healthy tissues while maximizing the dose to malignant tissue. A special class of materials known as "radiosensitizers" has emerged that can help achieve this goal by increasing the response of cells and tissues to radiation. High-Z metallic nanoparticles, such as gold nanoparticles, have been studied as radiosensitizers due to their associated increase in secondary electron emission when irradiated leading to an increase in DNA damage. To increase the biocompatilibity of metallic nanoparticles, different surface coatings have been explored, including Polyethylene-glycol (PEG). This research explored the use of PEG-coated metallic nanoparticles as radiosensitizers in prostate cancer (22Rv1) cells. These cells were plated in the ECU Cell Culture Laboratory and then transferred to the ECU Accelerator Laboratory where they were irradiated with a 3-MeV proton beam. The radiosensitization effect of the PEG-coated metallic nanoparticles was determined using PrestoBlue assays to construct cell survival curves. Several parameters including the concentration and material of the nanoparticles were explored. By enhancing the sensitivity of the cells to radiation with these PEG-coated metallic nanoparticles, the overall dose applied to patients undergoing radiation therapy could be lowered while still effectively treating the cancerous tissue. This reduction of dose would spare surrounding healthy tissue resulting in fewer side effects.
Open Access
Fiducial Marker Placement and Selection Study for Real-Time Lung Tumor Tracking
(East Carolina University, 2023-04-26) Belcher, Wesley
Introduction: Lung cancer remains one of the most fatal forms of cancer globally. Lung cancer is often treated by surgical removal of the malignant tissue however, surgery is not often an option for lung cancer. Radiation is the next treatment technique for non-small cell cancer. Radiation treatment of lung cancer is complicated by respiratory motion. As a patient breathes their lung inflates and deflates causing the lung tissue and the tumor to move. There are many techniques to account for the lung motion. A technique to accommodate lung tumor motion is tracking. Lung tumor tracking can be performed in multiple ways, but one way is fiducial marker directed tracking. Tracking helps the tumor to be located and treated continuously in real time. This allows the treatment margins to be smaller and gets better patient outcomes. However, the accuracy of the fiducials' motion matching tumor motion has yet to be depicted. This study aims to show how well fiducial motion matches tumor motion. The machine tracks a fiducial centroid, which is the center of mass of one or more objects. The study will also look at what makes fiducial centroids track the tumor well. The dosimetric effect of switching centroids will be observed. Patterns will be searched for to improve the fiducial marker placement recommendations. The current recommendations for fiducial marker selection are to select the fiducials closest to the tumor. These are not always the best tracking fiducials. The patterns in good fiducial centroids will also be used to improve the fiducial marker selection recommendations. Methods: This was an IRB approved retrospective study that included 27 patients receiving planning 4DCT for SBRT treatment of either primary or metastatic lung cancer. 20 patients had upper lung tumors with 79 fiducials placed. There were 7 lower lung tumor patients and 23 fiducials. It is expected for there to be more upper lung tumor cases than lower lung tumor cases. In total 102 fiducials were placed. The center of mass (COM) of each fiducial and the pre-contoured tumor were found in every phase of the breathing cycle, using a MATLAB[registered] program. The fiducials were then checked to see if they tracked the tumor well or not. If the fiducial kept a consistent distance within 2 mm of the tumor's COM, it was deemed a good tracking fiducial. Every fiducial combination was found and searched to see what centroid kept the most consistent distance from the tumor and which centroid was closest to the tumor's COM. These centroids were compared with the tracked centroid. The planned dose was shifted by the differences in the centroids locations compared to the tracked centroid. The type of bracketing around the tumor was checked in the centroids of interest. This analysis was done again on upper and lower lung patients separately. Results: The distance was not a determining factor on if the fiducial would track the tumor well. The centroid that was closest to the tumor's COM was closer than the tracked centroid by 4.1 [plus-minus] 1.2 mm (p[less-than]0.05) and the centroid that followed the tumor's motion the best kept the distance more consistently than the tracked centroid by 0.23 [plus-minus]0.05 mm (p[less-than]0.05). The shifted dose profiles were worse for tumor coverage than the original dose profiles but some other organs at risk had better dose sparing. Following analyze of the bracketing present in the centroids of interest, it is most important for the tumor to be bracketed in the superior/inferior and anterior/posterior directions. The superior/inferior bracketing is given higher priority for lower lung tumor patients and the anterior/posterior bracketing is given higher priority for upper lung tumor patients.
Open Access
EVALUATING THE USE OF TURBIDIMETRY FOR STUDYING FIBRIN STRUCTURAL PROPERTIES
(East Carolina University, 2023-04-21) Belcher, Heather A
A fibrin fiber mesh forms the structural backbone of blood clots. Many pathological conditions result in fibrin gels with altered structural properties, so there is interest in developing rapid and accurate ways to characterize fibrin features. One method of determining the diameter and mass-length ratio of fibers is turbidimetry, which uses light scattering theory for randomly oriented, thin, cylindrical rods to estimate fibrin fiber structural properties from scattering data. There are several different approaches that use turbidimetry to solve for these parameters, each of which has different simplifications and assumptions of full light scattering theory. Although these different approaches are all commonly utilized, the validity of their approximations has not been investigated and the accuracy of the fitting parameters has not been tested against experimental data under a range of physiologically relevant conditions. Therefore, this research will evaluate the accuracy of the commonly utilized turbidimetric approaches by theoretically comparing them to full light scattering theory, and by comparing the acquired diameter values to those obtained experimentally using SEM and super-resolution imaging. The summation of this work will provide a framework for utilizing turbidimetry to study fibrin and pave a path for utilizing turbidimetry in a clinical setting.
Open Access
The Shear Viscosity of Parton Matter Under Anisotropic Scatterings
(2022-10-17) MacKay, Noah M.; Lin, Zi-Wei
Open Access
An Investigation of Bubble Resonance and its Implications for Sound Production by Deep-Water Fishes
(2022-07-12) Sprague, Mark W.; Fine, Michael L.; Cameron, Timothy M.
Open Access
Implication of Two-Baryon Azimuthal Correlations in pp Collisions at LHC Energies on the QGP
(2022-04-02) Lin, Zi-Wei; et al
Open Access
Introductory Physics Labs: A Tale of Two Transformations
(2022-05-02) Wolf, Steven Frederick; Sprague, Mark W.
Open Access
Lèvy noise induced steady states
(East Carolina University, 2022-06-08) Yuvan, Steven
Systems far from equilibrium organize themselves to accommodate energy throughput. It is also in these nonequilibrium systems where noise has often been found to follow alpha-stable distributions, commonly called Lèvy noise, rather than Gaussian distributions. There is no general theory that links these alpha-stable distributions to the resultant thermodynamic behavior of a system as a whole. Here two different model systems are investigated for which the assumption of Lèvy noise leads to behavior that deviates from that seen at equilibrium. We begin by examining trajectories of overdamped noise-driven particles in a harmonic potential. These trajectories display broken time reversal symmetry due to the large displacements inherent to Lèvy noise. A parameter to measure this symmetry breaking and estimate the stability parameter, ɑ, of the underlying noise is proposed. This parameter is applied to a time series of solar x-ray irradiance and compared to previous methods. Next, we study the same overdamped particles in a 2D system with simple semi-circular cavities. Lèvy noise in such a system will lead to a preferential accumulation of particles in one cavity. The nonhomogeneous steady-state represents a lower entropy configuration in comparison to equilibrium. The chosen system leads to concise expressions for the distribution of particles within the cavities as well as the concomitant entropy reduction. Such structures maintained in nonequilibrium have been referred to as dissipative structures because they may aid the system in transporting or dissipating energy.
Open Access
SAFE HAVENS AND HOT SPOTS: IONIZING RADIATION IN MARTIAN PERMAFROST AND ITS INFLUENCE ON THE SURVIVAL OF ANCIENT LIFE
(East Carolina University, 2022-06-20) Osunkwor, Offormata Emmanuel
Permafrost on Mars is considered a primary target for the search for life. On a microscopic scale permafrost is highly non-uniform and the effective radiation dose absorbed by a microbe, and thus its survival probability, depends strongly on its microscopic location and its environment. The goal of this work was to determine how long microbes will survive in a dormant state under the influence of radiation from radionuclides in the Martian regolith, and how fast radiation will destroy the remnants of dead microbes. Our approach was to model the radiation environment that microbes are exposed to in the Martian subsurface using the Geant4 Monte Carlo programs DosiSed and DosiVox. This dissertation describes the methodologies and results of this study. The reliability and precision of DosiVox and DosiSed simulations were rigorously tested on dose distributions measured with Al2O3:C dosimeters buried in terrestrial samples and by reproducing published data. The optimum simulation parameters were determined for the infinite dimensional models for the Martian subsurface and dose rate distributions were determined. Finally, the results and limitations of our calculated survival probabilities and probabilities of preservation of biomarkers in the Martian subsurface are presented and discussed. Our result shows that microbes can survive for as long 50 billion years depending on their location and whether they are exposed to the full spectrum of the radiation or only gamma radiation. For microbes that are exposed to only gamma radiation, the most radio-resistant of them can survive up to 350 billion years while those that are exposed to the full spectrum will not survive for more than 500 million years.
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DEVELOPMENT OF A NEW SPECTROPHOTOMETRIC METHOD FOR FULL CHARACTERIZATION OF TURBIDITY
(East Carolina University, 2022-07-21) Mutisya, Stephen M
Characterization of turbid materials by determining their inherent optical properties have attracted strong research interest for potentially wide applications in fields such as material analysis and biomedical optics. The response of a homogeneous turbid sample to an optical excitation can be accurately described by absorption coefficient μa, scattering coefficient μs, and anisotropy factor g based on the radiative transfer theory. Existing spectrophotometric methods typically uses integrating spheres to acquire the light signals. These approaches, however, are difficult to be translated into instruments for users without special training. The research goal of this dissertation research project is two-fold: (1) Develop and validate a new spectrophotometric method without integrating sphere to characterize turbidity for optically thick samples by three optical parameters of μa(λ), μs(λ) and g(λ). (2) Demonstrate the applicability of the new spectrophotometric method as a label-free assay of cell suspension samples treated by a chemotherapy drug. An experimental system has been developed to measure signals of diffuse reflectance Rd, diffuse transmittance Td and forward transmittance Tf as functions of wavelength λ between 460 and 1000nm from two types of samples. We have inversely determined the optical parameters of polystyrene microsphere samples by an in-house build individual photon Monte Carlo (iMC) simulation software. Validation of the new method has been achieved by comparing the optical parameters determined from the measured signals to those predicted by the Mie theory. In addition, we have applied the validated method to obtain the optical properties of MCF-7 cell samples treated by an apoptosis inducing drug doxorubicin for three different doses and three post-treatment times. By comparing to apoptosis measurement results of MTT assay and fluorescent flow cytometry, we were able to qualitatively demonstrate the potential applications of the new spectrophotometric method as a label-free assay to detect cellular apoptosis in treated samples.
Open Access
Accumulation of Particles and Formation of a Dissipative Structure in a Nonequilibrium Bath
(2022-01-27) Yuvan, Steven; Bier, Martin, 1959-
Open Access
Von Willebrand Factor A1 Domain Stability and Affinity for GPIbα are Differentially Regulated by its O-glycosylated N- and Clinker
(2022-05-09) Hudson, Nathan E.; Bonazza, Klaus
Open Access
The Effect of Grain Size on Porewater Radiolysis
(2022) DeWitt, J.; McMahon, S.; Parnell, J.
Open Access
The Applicability of Current Turbidimetric Approaches for Analyzing Fibrin Fibers and Other Filamentous Networks
(2022-06-09) Belcher, Heather A.; Hudson, Nathan E.; Litwa, Karen; Guthold, Martin
Open Access
Hybrid Computational Pregnant Female Phantom Construction for Radiation Dosimetry Applications
(2022-09-30) Makkia, Rasha; Nelson, Keith; Dingfelder, Michael; Zaidi, Habib
Open Access
Analysis of Polarized Diffraction Images of Human Red Blood Cells: A Numerical Study
(2022-02-03) Hu, Xin-Hua; Wang, Wenjin

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