Matching Items (519)
Description
Infections caused by the Hepatitis C Virus (HCV) are very common worldwide, affecting up to 3% of the population. Chronic infection of HCV may develop into liver cirrhosis and liver cancer which is among the top five of the most common cancers. Therefore, vaccines against HCV are under intense study in order to prevent HCV from harming people's health. The envelope protein 2 (E2) of HCV is thought to be a promising vaccine candidate because it can directly bind to a human cell receptor and plays a role in viral entry. However, the E2 protein production in cells is inefficient due to its complicated matured structure. Folding of E2 in the endoplasmic reticulum (ER) is often error-prone, resulting in production of aggregates and misfolded proteins. These incorrect forms of E2 are not functional because they are not able to bind to human cells and stimulate antibody response to inhibit this binding. This study is aimed to overcome the difficulties of HCV E2 production in plant system. Protein folding in the ER requires great assistance from molecular chaperones. Thus, in this study, two molecular chaperones in the ER, calreticulin and calnexin, were transiently overexpressed in plant leaves in order to facilitate E2 folding and production. Both of them showed benefits in increasing the yield of E2 and improving the quality of E2. In addition, poorly folded E2 accumulated in the ER may cause stress in the ER and trigger transcriptional activation of ER molecular chaperones. Therefore, a transcription factor involved in this pathway, named bZIP60, was also overexpressed in plant leaves, aiming at up-regulating a major family of molecular chaperones called BiP to assist protein folding. However, our results showed that BiP mRNA levels were not up-regulated by bZIP60, but they increased in response to E2 expression. The Western blot analysis also showed that overexpression of bZIP60 had a small effect on promoting E2 folding. Overall, this study suggested that increasing the level of specific ER molecular chaperones was an effective way to promote HCV E2 protein production and maturation.
ContributorsHong, Fan (Author) / Mason, Hugh (Thesis advisor) / Gaxiola, Roberto (Committee member) / Chang, Yung (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2011
Description
Fluoroquinolone antibiotics have been known to cause severe, multisystem adverse side effects, termed fluoroquinolone toxicity (FQT). This toxicity syndrome can present with adverse effects that vary from individual to individual, including effects on the musculoskeletal and nervous systems, among others. The mechanism behind FQT in mammals is not known, although various possibilities have been investigated. Among the hypothesized FQT mechanisms, those that could potentially explain multisystem toxicity include off-target mammalian topoisomerase interactions, increased production of reactive oxygen species, oxidative stress, and oxidative damage, as well as metal chelating properties of FQs. This review presents relevant information on fluoroquinolone antibiotics and FQT and explores the mechanisms that have been proposed. A fluoroquinolone-induced increase in reactive oxygen species and subsequent oxidative stress and damage presents the strongest evidence to explain this multisystem toxicity syndrome. Understanding the mechanism of FQT in mammals is important to aid in the prevention and treatment of this condition.
ContributorsHall, Brooke Ashlyn (Author) / Redding, Kevin (Thesis director) / Wideman, Jeremy (Committee member) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
In this thesis, we present the study of several physical properties of relativistic mat- ters under extreme conditions. We start by deriving the rate of the nonleptonic weak processes and the bulk viscosity in several spin-one color superconducting phases of quark matter. We also calculate the bulk viscosity in the nonlinear and anharmonic regime in the normal phase of strange quark matter. We point out several qualitative effects due to the anharmonicity, although quantitatively they appear to be relatively small. In the corresponding study, we take into account the interplay between the non- leptonic and semileptonic weak processes. The results can be important in order to relate accessible observables of compact stars to their internal composition. We also use quantum field theoretical methods to study the transport properties in monolayer graphene in a strong magnetic field. The corresponding quasi-relativistic system re- veals an anomalous quantum Hall effect, whose features are directly connected with the spontaneous flavor symmetry breaking. We study the microscopic origin of Fara- day rotation and magneto-optical transmission in graphene and show that their main features are in agreement with the experimental data.
ContributorsWang, Xinyang, Ph.D (Author) / Shovkovy, Igor (Thesis advisor) / Belitsky, Andrei (Committee member) / Easson, Damien (Committee member) / Peng, Xihong (Committee member) / Vachaspati, Tanmay (Committee member) / Arizona State University (Publisher)
Created2013
Description
Numerical simulations are very helpful in understanding the physics of the formation of structure and galaxies. However, it is sometimes difficult to interpret model data with respect to observations, partly due to the difficulties and background noise inherent to observation. The goal, here, is to attempt to bridge this gap between simulation and observation by rendering the model output in image format which is then processed by tools commonly used in observational astronomy. Images are synthesized in various filters by folding the output of cosmological simulations of gasdynamics with star-formation and dark matter with the Bruzual- Charlot stellar population synthesis models. A variation of the Virgo-Gadget numerical simulation code is used with the hybrid gas and stellar formation models of Springel and Hernquist (2003). Outputs taken at various redshifts are stacked to create a synthetic view of the simulated star clusters. Source Extractor (SExtractor) is used to find groupings of stellar populations which are considered as galaxies or galaxy building blocks and photometry used to estimate the rest frame luminosities and distribution functions. With further refinements, this is expected to provide support for missions such as JWST, as well as to probe what additional physics are needed to model the data. The results show good agreement in many respects with observed properties of the galaxy luminosity function (LF) over a wide range of high redshifts. In particular, the slope (alpha) when fitted to the standard Schechter function shows excellent agreement both in value and evolution with redshift, when compared with observation. Discrepancies of other properties with observation are seen to be a result of limitations of the simulation and additional feedback mechanisms which are needed.
ContributorsMorgan, Robert (Author) / Windhorst, Rogier A (Thesis advisor) / Scannapieco, Evan (Committee member) / Rhoads, James (Committee member) / Gardner, Carl (Committee member) / Belitsky, Andrei (Committee member) / Arizona State University (Publisher)
Created2012
Description
Understanding the temperature structure of protoplanetary disks (PPDs) is paramount to modeling disk evolution and future planet formation. PPDs around T Tauri stars have two primary heating sources, protostellar irradiation, which depends on the flaring of the disk, and accretional heating as viscous coupling between annuli dissipate energy. I have written a "1.5-D" radiative transfer code to calculate disk temperatures assuming hydrostatic and radiative equilibrium. The model solves for the temperature at all locations simultaneously using Rybicki's method, converges rapidly at high optical depth, and retains full frequency dependence. The likely cause of accretional heating in PPDs is the magnetorotational instability (MRI), which acts where gas ionization is sufficiently high for gas to couple to the magnetic field. This will occur in surface layers of the disk, leaving the interior portions of the disk inactive ("dead zone"). I calculate temperatures in PPDs undergoing such "layered accretion." Since the accretional heating is concentrated far from the midplane, temperatures in the disk's interior are lower than in PPDs modeled with vertically uniform accretion. The method is used to study for the first time disks evolving via the magnetorotational instability, which operates primarily in surface layers. I find that temperatures in layered accretion disks do not significantly differ from those of "passive disks," where no accretional heating exists. Emergent spectra are insensitive to active layer thickness, making it difficult to observationally identify disks undergoing layered vs. uniform accretion. I also calculate the ionization chemistry in PPDs, using an ionization network including multiple charge states of dust grains. Combined with a criterion for the onset of the MRI, I calculate where the MRI can be initiated and the extent of dead zones in PPDs. After accounting for feedback between temperature and active layer thickness, I find the surface density of the actively accreting layers falls rapidly with distance from the protostar, leading to a net outward flow of mass from ~0.1 to 3 AU. The clearing out of the innermost zones is possibly consistent with the observed behavior of recently discovered "transition disks."
ContributorsLesniak, Michael V., III (Author) / Desch, Steven J. (Thesis advisor) / Scannapieco, Evan (Committee member) / Timmes, Francis (Committee member) / Starrfield, Sumner (Committee member) / Belitsky, Andrei (Committee member) / Arizona State University (Publisher)
Created2012
Description
This thesis deals with the first measurements done with a cold neutron beam at the Spallation Neutron Source at Oak Ridge National Laboratory. The experimental technique consisted of capturing polarized cold neutrons by nuclei to measure parity-violation in the angular distribution of the gamma rays following neutron capture. The measurements presented here for the nuclei Chlorine ( 35Cl) and Aluminum ( 27Al ) are part of a program with the ultimate goal of measuring the asymmetry in the angular distribution of gamma rays emitted in the capture of neutrons on protons, with a precision better than 10-8, in order to extract the weak hadronic coupling constant due to pion exchange interaction with isospin change equal with one ( hπ 1). Based on theoretical calculations asymmetry in the angular distribution of the gamma rays from neutron capture on protons has an estimated size of 5·10-8. This implies that the Al parity violation asymmetry and its uncertainty have to be known with a precision smaller than 4·10-8. The proton target is liquid Hydrogen (H2) contained in an Aluminum vessel. Results are presented for parity violation and parity-conserving asymmetries in Chlorine and Aluminum. The systematic and statistical uncertainties in the calculation of the parity-violating and parity-conserving asymmetries are discussed.
ContributorsBalascuta, Septimiu (Author) / Alarcon, Ricardo (Thesis advisor) / Belitsky, Andrei (Committee member) / Doak, Bruce (Committee member) / Comfort, Joseph (Committee member) / Schmidt, Kevin (Committee member) / Arizona State University (Publisher)
Created2012
Description
Cancer claims hundreds of thousands of lives every year in US alone. Finding ways for early detection of cancer onset is crucial for better management and treatment of cancer. Thus, biomarkers especially protein biomarkers, being the functional units which reflect dynamic physiological changes, need to be discovered. Though important, there are only a few approved protein cancer biomarkers till date. To accelerate this process, fast, comprehensive and affordable assays are required which can be applied to large population studies. For this, these assays should be able to comprehensively characterize and explore the molecular diversity of nominally "single" proteins across populations. This information is usually unavailable with commonly used immunoassays such as ELISA (enzyme linked immunosorbent assay) which either ignore protein microheterogeneity, or are confounded by it. To this end, mass spectrometric immuno assays (MSIA) for three different human plasma proteins have been developed. These proteins viz. IGF-1, hemopexin and tetranectin have been found in reported literature to show correlations with many diseases along with several carcinomas. Developed assays were used to extract entire proteins from plasma samples and subsequently analyzed on mass spectrometric platforms. Matrix assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) mass spectrometric techniques where used due to their availability and suitability for the analysis. This resulted in visibility of different structural forms of these proteins showing their structural micro-heterogeneity which is invisible to commonly used immunoassays. These assays are fast, comprehensive and can be applied in large sample studies to analyze proteins for biomarker discovery.
ContributorsRai, Samita (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Borges, Chad (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2012
Description
Bacteria play a vital role in the world ecosystem, more importantly human health and disease. The capability to differentiate and identify these microorganisms serves as an important research objective. In past years, separations-based approaches have served as a way to observe and identify bacteria based on their characteristics. Gradient insulator dielectrophoresis (g-iDEP) provides benefits in identifying serotypes of a single species with precise separation. Separation of Staphylococcus epidermidis in a single g-iDEP microchannel is conducted exploiting their electrophoretic and electrokinetic properties. The cells were captured and concentrated at gates with interacting forces within the microchannel to clearly distinguish between the two strains. These results provide support for g-iDEP serving as a separating method and, furthermore, future clinical applications.
ContributorsDavis, Paige Elizabeth (Author) / Hayes, Mark (Thesis director) / Borges, Chad (Committee member) / Jones, Paul (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor)
Created2015-05
Description
Is it possible to treat the mouth as a natural environment, and determine new methods to keep the microbiome in check? The need for biodiversity in health may suggest that every species carries out a specific function that is required to maintain equilibrium and homeostasis within the oral cavity. Furthermore, the relationship between the microbiome and its host is mutually beneficial because the host is providing microbes with an environment in which they can flourish and, in turn, keep their host healthy. Reviewing examples of larger scale environmental shifts could provide a window by which scientists can make hypotheses. Certain medications and healthcare treatments have been proven to cause xerostomia. This disorder is characterized by a dry mouth, and known to be associated with a change in the composition, and reduction, of saliva. Two case studies performed by Bardow et al, and Leal et al, tested and studied the relationships of certain medications and confirmed their side effects on the salivary glands [2,3]. Their results confirmed a relationship between specific medicines, and the correlating complaints of xerostomia. In addition, Vissink et al conducted case studies that helped to further identify how radiotherapy causes hyposalivation of the salivary glands [4]. Specifically patients that have been diagnosed with oral cancer, and are treated by radiotherapy, have been diagnosed with xerostomia. As stated prior, studies have shown that patients having an ecologically balanced and diverse microbiome tend to have healthier mouths. The oral cavity is like any biome, consisting of commensalism within itself and mutualism with its host. Due to the decreased salivary output, caused by xerostomia, increased parasitic bacteria build up within the oral cavity thus causing dental disease. Every human body contains a personalized microbiome that is essential to maintaining health but capable of eliciting disease. The Human Oral Microbiomics Database (HOMD) is a set of reference 16S rRNA gene sequences. These are then used to define individual human oral taxa. By conducting metagenomic experiments at the molecular and cellular level, scientists can identify and label micro species that inhabit the mouth during parasitic outbreaks or a shifting of the microbiome. Because the HOMD is incomplete, so is our ability to cure, or prevent, oral disease. The purpose of the thesis is to research what is known about xerostomia and its effects on the complex microbiome of the oral cavity. It is important that researchers determine whether this particular perspective is worth considering. In addition, the goal is to create novel experiments for treatment and prevention of dental diseases.
ContributorsHalcomb, Michael Jordan (Author) / Chen, Qiang (Thesis director) / Steele, Kelly (Committee member) / Barrett, The Honors College (Contributor) / College of Letters and Sciences (Contributor)
Created2015-05
Description
Background: High risk types of human papillomavirus (HPV) are known to cause cancer, including cervical (99%) and oropharyngeal cancer (70%). HPV type 16 is the most common subtype. Three antigens that are critical for integration or tumor progression are E2, E6 and E7. In this study, we developed a systematic approach to identify naturally-processed HPV16-derived HLA class I epitopes for immunotherapy development. Methods: K562 cells, which lack HLA expression, were transduced with each HPV16 antigen using lentivirus and supertransfected with HLA-A2 by nucleofection. Stable cell lines expressing each antigen were selected for and maintained throughout the investigation. In order to establish a Gateway-compatible vector for robust transient gene expression, a Gateway recombination expression cloning cassette was inserted into the commercial Lonza pMAX GFP backbone, which has been experimentally shown to display high transfection expression efficiency. GFP was cloned into the vector and plain K562 cells were transfected with the plasmid by nucleofection. Results: Expression of K562-A2 was tested at various time points by flow cytometry and A2 expression was confirmed. Protein expression was shown for the transduced K562 E7 by Western blot analysis. High transfection efficiency of the pMAX_GFP_Dest vector (up to 97% GFP+ cells) was obtained 48 hours post transfection, comparable to the commercial GFP-plasmid. Conclusion: We have established a rapid system for target viral antigen co-expression with single HLA molecules for analysis of antigen presentation. Using HPV as a model system, our goal is to identify specific antigenic peptide sequences to develop immunotherapeutic treatments for HPV-associated cancers.
ContributorsVarda, Bianca Marie (Author) / Anderson, Karen (Thesis director) / Borges, Chad (Committee member) / Krishna, Sri (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05