Matching Items (70)
Description
Nucleosomes are the basic repetitive unit of eukaryotic chromatin and are responsible for packing DNA inside the nucleus of the cell. They consist of a complex of eight histone proteins (two copies of four proteins H2A, H2B, H3 and H4) around which 147 base pairs of DNA are wrapped in ~1.67 superhelical turns. Although the nucleosomes are stable protein-DNA complexes, they undergo spontaneous conformational changes that occur in an asynchronous fashion. This conformational dynamics, defined by the "site-exposure" model, involves the DNA unwrapping from the protein core and exposing itself transiently before wrapping back. Physiologically, this allows regulatory proteins to bind to their target DNA sites during cellular processes like replication, DNA repair and transcription. Traditional biochemical assays have stablished the equilibrium constants for the accessibility to various sites along the length of the nucleosomal DNA, from its end to the middle of the dyad axis. Using fluorescence correlation spectroscopy (FCS), we have established the position dependent rewrapping rates for nucleosomes. We have also used Monte Carlo simulation methods to analyze the applicability of FRET fluctuation spectroscopy towards conformational dynamics, specifically motivated by nucleosome dynamics. Another important conformational change that is involved in cellular processes is the disassembly of nucleosome into its constituent particles. The exact pathway adopted by nucleosomes is still not clear. We used dual color fluorescence correlation spectroscopy to study the intermediates during nucleosome disassembly induced by changing ionic strength. Studying the nature of nucleosome conformational change and the kinetics is very important in understanding gene expression. The results from this thesis give a quantitative description to the basic unit of the chromatin.
ContributorsGurunathan, Kaushik (Author) / Levitus, Marcia (Thesis advisor) / Lindsay, Stuart (Committee member) / Woodbury, Neal (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2011
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
Healthy mitochondria are essential for cell survival. Described herein is the synthesis of a family of novel aminoquinone antioxidants designed to alleviate oxidative stress and prevent the impairment of cellular function. In addition, a library of bleomycin disaccharide analogues has also been synthesized to better probe the tumor targeting properties of bleomycin. The first study involves the synthesis of a benzoquinone natural product and analogues that closely resemble the redox core of the natural product geldanamycin. The synthesized 5-amino-3-tridecyl-1,4-benzoquinone antioxidants were tested for their ability to protect Friedreich's ataxia (FRDA) lymphocytes from induced oxidative stress. Some of the analogues synthesized conferred cytoprotection in a dose-dependent manner in FRDA lymphocytes at micromolar concentrations. The biological assays suggest that the modification of the 2-hydroxyl and N-(3-carboxypropyl) groups in the natural product can improve its antioxidant activity and significantly enhance its ability to protect mitochondrial function under conditions of oxidative stress. The second project focused on the synthesis of a library of bleomycin disaccharide-dye conjugates and monitored their cellular uptake by fluorescence microscopy. The studies reveal that the position of the carbamoyl group plays an important role in modulating the cellular uptake of the disaccharide. It also led to the discovery of novel disaccharides with improved tumor selectivity.
ContributorsMathilakathu Madathil, Manikandadas (Author) / Hecht, Sidney M. (Thesis advisor) / Rose, Seth (Committee member) / Woodbury, Neal (Committee member) / Arizona State University (Publisher)
Created2013
Description
Laboratory automation systems have seen a lot of technological advances in recent times. As a result, the software that is written for them are becoming increasingly sophisticated. Existing software architectures and standards are targeted to a wider domain of software development and need to be customized in order to use them for developing software for laboratory automation systems. This thesis proposes an architecture that is based on existing software architectural paradigms and is specifically tailored to developing software for a laboratory automation system. The architecture is based on fairly autonomous software components that can be distributed across multiple computers. The components in the architecture make use of asynchronous communication methodologies that are facilitated by passing messages between one another. The architecture can be used to develop software that is distributed, responsive and thread-safe. The thesis also proposes a framework that has been developed to implement the ideas proposed by the architecture. The framework is used to develop software that is scalable, distributed, responsive and thread-safe. The framework currently has components to control very commonly used laboratory automation devices such as mechanical stages, cameras, and also to do common laboratory automation functionalities such as imaging.
ContributorsKuppuswamy, Venkataramanan (Author) / Meldrum, Deirdre (Thesis advisor) / Collofello, James (Thesis advisor) / Sarjoughian, Hessam S. (Committee member) / Johnson, Roger (Committee member) / Arizona State University (Publisher)
Created2012
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
It has been well established that mitochondria play a critical role in the pathology of Friedreich's Ataxia. This disease is believed to be caused by a deficiency of frataxin, which research suggests is responsible for iron sulfur cluster assembly. This incomplete assembly of iron sulfur clusters is believed to be linked with dysfunctional complexes in the mitochondrial respiratory chain, increased oxidative stress, and potential cell death. Increased understanding of the pathophysiology of this disease has enabled the development of various therapeutic strategies aimed at restoring mitochondrial respiration. This thesis contains an analysis of the biological activity of several classes of antioxidants against oxidative stress induced by diethyl maleate in Friedreich's Ataxia lymphocytes and CEM leukemia cells. Analogues of vitamin E α-tocopherol have been shown to protect cells under oxidative stress. However, these same analogues show various levels of inhibition towards the electron transport chain complex I. Bicyclic pyridinols containing a ten carbon substituent provided favorable cytoprotection. N-hydroxy-4-pyridone compounds were observed to provide little protection. Similarly, analogues of CoQ10 in the form of pyridinol and pyrimidinol compounds also preserved cell viability at low concentrations.
ContributorsJaruvangsanti, Jennifer (Author) / Hecht, Sidney (Thesis advisor) / Woodbury, Neal (Committee member) / Skibo, Edward (Committee member) / Arizona State University (Publisher)
Created2012
Description
Single cell analysis has become increasingly important in understanding disease onset, progression, treatment and prognosis, especially when applied to cancer where cellular responses are highly heterogeneous. Through the advent of single cell computerized tomography (Cell-CT), researchers and clinicians now have the ability to obtain high resolution three-dimensional (3D) reconstructions of single cells. Yet to date, no live-cell compatible version of the technology exists. In this thesis, a microfluidic chip with the ability to rotate live single cells in hydrodynamic microvortices about an axis parallel to the optical focal plane has been demonstrated. The chip utilizes a novel 3D microchamber design arranged beneath a main channel creating flow detachment into the chamber, producing recirculating flow conditions. Single cells are flowed through the main channel, held in the center of the microvortex by an optical trap, and rotated by the forces induced by the recirculating fluid flow. Computational fluid dynamics (CFD) was employed to optimize the geometry of the microchamber. Two methods for the fabrication of the 3D microchamber were devised: anisotropic etching of silicon and backside diffuser photolithography (BDPL). First, the optimization of the silicon etching conditions was demonstrated through design of experiment (DOE). In addition, a non-conventional method of soft-lithography was demonstrated which incorporates the use of two positive molds, one of the main channel and the other of the microchambers, compressed together during replication to produce a single ultra-thin (<200 µm) negative used for device assembly. Second, methods for using thick negative photoresists such as SU-8 with BDPL have been developed which include a new simple and effective method for promoting the adhesion of SU-8 to glass. An assembly method that bonds two individual ultra-thin (<100 µm) replications of the channel and the microfeatures has also been demonstrated. Finally, a pressure driven pumping system with nanoliter per minute flow rate regulation, sub-second response times, and < 3% flow variability has been designed and characterized. The fabrication and assembly of this device is inexpensive and utilizes simple variants of conventional microfluidic fabrication techniques, making it easily accessible to the single cell analysis community.
ContributorsMyers, Jakrey R (Author) / Meldrum, Deirdre (Thesis advisor) / Johnson, Roger (Committee member) / Frakes, David (Committee member) / Arizona State University (Publisher)
Created2012
Description
The field of biomedical research relies on the knowledge of binding interactions between various proteins of interest to create novel molecular targets for therapeutic purposes. While many of these interactions remain a mystery, knowledge of these properties and interactions could have significant medical applications in terms of understanding cell signaling and immunological defenses. Furthermore, there is evidence that machine learning and peptide microarrays can be used to make reliable predictions of where proteins could interact with each other without the definitive knowledge of the interactions. In this case, a neural network was used to predict the unknown binding interactions of TNFR2 onto LT-ɑ and TRAF2, and PD-L1 onto CD80, based off of the binding data from a sampling of protein-peptide interactions on a microarray. The accuracy and reliability of these predictions would rely on future research to confirm the interactions of these proteins, but the knowledge from these methods and predictions could have a future impact with regards to rational and structure-based drug design.
ContributorsPoweleit, Andrew Michael (Author) / Woodbury, Neal (Thesis director) / Diehnelt, Chris (Committee member) / Chiu, Po-Lin (Committee member) / School of Molecular Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05