Matching Items (295)
Description
The use of synthetic cathinones or "bath salts" has risen dramatically in recent years with one of the most popular being Methylendioxypyrovalerone (MDPV). Following the temporary legislative ban on the sale and distribution of this compound , a multitude of other cathinone derivatives have been synthesized. The current study seeks to compare the abuse potential of MDPV with one of the emergent synthetic cathinones 4-methylethcathinone (4-MEC), based on their respective ability to lower current thresholds in an intracranial self-stimulation (ICSS) paradigm. Following acute administration (0.1, 0.5, 1 and 2 mg/kg i.p.) MDPV was found to significantly lower ICSS thresholds at all doses tested (F4,35=11.549, p<0.001). However, following acute administration (0.3,1,3,10,30 mg/kg i.p) 4-MEC produced no significant ICSS threshold depression (F5,135= 0.622, p = 0.684). Together these findings suggest that while MDPV may possess significant abuse potential, other synthetic cathinones such as 4-MEC may have a drastically reduced potential for abuse.
ContributorsWegner, Scott Andrew (Author) / Olive, M. Foster (Thesis director) / Presson, Clark (Committee member) / Sanabria, Federico (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Department of Psychology (Contributor)
Created2013-05
Description
Pathogenic Gram-negative bacteria employ a variety of molecular mechanisms to combat host defenses. Two-component regulatory systems (TCR systems) are the most ubiquitous signal transduction systems which regulate many genes required for virulence and survival of bacteria. In this study, I analyzed different TCR systems in two clinically-relevant Gram-negative bacteria, i.e., oral pathogen Porphyromonas gingivalis and enterobacterial Escherichia coli. P. gingivalis is a major causative agent of periodontal disease as well as systemic illnesses, like cardiovascular disease. A microarray study found that the putative PorY-PorX TCR system controls the secretion and maturation of virulence factors, as well as loci involved in the PorSS secretion system, which secretes proteinases, i.e., gingipains, responsible for periodontal disease. Proteomic analysis (SILAC) was used to improve the microarray data, reverse-transcription PCR to verify the proteomic data, and primer extension assay to determine the promoter regions of specific PorX regulated loci. I was able to characterize multiple genetic loci regulated by this TCR system, many of which play an essential role in hemagglutination and host-cell adhesion, and likely contribute to virulence in this bacterium. Enteric Gram-negative bacteria must withstand many host defenses such as digestive enzymes, low pH, and antimicrobial peptides (AMPs). The CpxR-CpxA TCR system of E. coli has been extensively characterized and shown to be required for protection against AMPs. Most recently, this TCR system has been shown to up-regulate the rfe-rff operon which encodes genes involved in the production of enterobacterial common antigen (ECA), and confers protection against a variety of AMPs. In this study, I utilized primer extension and DNase I footprinting to determine how CpxR regulates the ECA operon. My findings suggest that CpxR modulates transcription by directly binding to the rfe promoter. Multiple genetic and biochemical approaches were used to demonstrate that specific TCR systems contribute to regulation of virulence factors and resistance to host defenses in P. gingivalis and E. coli, respectively. Understanding these genetic circuits provides insight into strategies for pathogenesis and resistance to host defenses in Gram negative bacterial pathogens. Finally, these data provide compelling potential molecular targets for therapeutics to treat P. gingivalis and E. coli infections.
ContributorsLeonetti, Cori (Author) / Shi, Yixin (Thesis advisor) / Stout, Valerie (Committee member) / Nickerson, Cheryl (Committee member) / Sandrin, Todd (Committee member) / Arizona State University (Publisher)
Created2013
Description
The study of bacterial resistance to antimicrobial peptides (AMPs) is a significant area of interest as these peptides have the potential to be developed into alternative drug therapies to combat microbial pathogens. AMPs represent a class of host-mediated factors that function to prevent microbial infection of their host and serve as a first line of defense. To date, over 1,000 AMPs of various natures have been predicted or experimentally characterized. Their potent bactericidal activities and broad-based target repertoire make them a promising next-generation pharmaceutical therapy to combat bacterial pathogens. It is important to understand the molecular mechanisms, both genetic and physiological, that bacteria employ to circumvent the bactericidal activities of AMPs. These understandings will allow researchers to overcome challenges posed with the development of new drug therapies; as well as identify, at a fundamental level, how bacteria are able to adapt and survive within varied host environments. Here, results are presented from the first reported large scale, systematic screen in which the Keio collection of ~4,000 Escherichia coli deletion mutants were challenged against physiologically significant AMPs to identify genes required for resistance. Less than 3% of the total number of genes on the E. coli chromosome was determined to contribute to bacterial resistance to at least one AMP analyzed in the screen. Further, the screen implicated a single cellular component (enterobacterial common antigen, ECA) and a single transporter system (twin-arginine transporter, Tat) as being required for resistance to each AMP class. Using antimicrobial resistance as a tool to identify novel genetic mechanisms, subsequent analyses were able to identify a two-component system, CpxR/CpxA, as a global regulator in bacterial resistance to AMPs. Multiple previously characterized CpxR/A members, as well as members found in this study, were identified in the screen. Notably, CpxR/A was found to transcriptionally regulate the gene cluster responsible for the biosynthesis of the ECA. Thus, a novel genetic mechanism was uncovered that directly correlates with a physiologically significant cellular component that appears to globally contribute to bacterial resistance to AMPs.
ContributorsWeatherspoon-Griffin, Natasha (Author) / Shi, Yixin (Thesis advisor) / Clark-Curtiss, Josephine (Committee member) / Misra, Rajeev (Committee member) / Nickerson, Cheryl (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2013
Description
The discovery of DNA helical structure opened the door of modern molecular biology. Ned Seeman utilized DNA as building block to construct different nanoscale materials, and introduced a new field, know as DNA nanotechnology. After several decades of development, different DNA structures had been created, with different dimension, different morphology and even with complex curvatures. In addition, after construction of enough amounts DNA structure candidates, DNA structure template, with excellent spatial addressability, had been used to direct the assembly of different nanomaterials, including nanoparticles and proteins, to produce different functional nanomaterials. However there are still many challenges to fabricate functional DNA nanostructures. The first difficulty is that the present finite sized template dimension is still very small, usually smaller than 100nm, which will limit the application for large amount of nanomaterials assembly or large sized nanomaterials assembly. Here we tried to solve this problem through developing a new method, superorigami, to construct finite sized DNA structure with much larger dimension, which can be as large as 500nm. The second problem will be explored the ability of DNA structure to assemble inorganic nanomaterials for novel photonic or electronic properties. Here we tried to utilize DNA Origami method to assemble AuNPs with controlled 3D spacial position for possible chiral photonic complex. We also tried to assemble SWNT with discrete length for possible field effect transistor device. In addition, we tried to mimic in vivo compartment with DNA structure to study internalized enzyme behavior. From our results, constructed DNA cage origami can protect encapsulated enzyme from degradation, and internalized enzyme activity can be boosted for up to 10 folds. In summary, DNA structure can serve as an ideal template for construction of functional nanomaterials with lots of possibilities to be explored.
ContributorsZhao, Zhao (Author) / Yan, Hao (Thesis advisor) / Liu, Yan (Thesis advisor) / Chen, Julian (Committee member) / Seo, Dong-Kyun (Committee member) / Arizona State University (Publisher)
Created2013
Description
Food system and health characteristics were evaluated across the last Waorani hunter-gatherer group in Amazonian Ecuador and a remote neighboring Kichwa indigenous subsistence agriculture community. Hunter-gatherer food systems like the Waorani foragers may not only be nutritionally, but also pharmaceutically beneficial because of high dietary intake of varied plant phytochemical compounds. A modern diet that reduces these dietary plant defense phytochemicals below levels typical in human evolutionary history may leave humans vulnerable to diseases that were controlled through a foraging diet. Few studies consider the health impact of the recent drastic reduction of plant phytochemical content in the modern global food system, which has eliminated essential components of food because they are not considered "nutrients". The antimicrobial and anti-inflammatory nature of the food system may not only regulate infectious pathogens and inflammatory disease, but also support beneficial microbes in human hosts, reducing vulnerability to chronic diseases. Waorani foragers seem immune to certain infections with very low rates of chronic disease. Does returning to certain characteristics of a foraging food system begin to restore the human body microbe balance and inflammatory response to evolutionary norms, and if so, what implication does this have for the treatment of disease? Several years of data on dietary and health differences across the foragers and the farmers was gathered. There were major differences in health outcomes across the board. In the Waorani forager group there were no signs of infection in serious wounds such as 3rd degree burns and spear wounds. The foragers had one-degree lower body temperature than the farmers. The Waorani had an absence of signs of chronic diseases including vision and blood pressure that did not change markedly with age while Kichwa farmers suffered from both chronic diseases and physiological indicators of aging. In the Waorani forager population, there was an absence of many common regional infectious diseases, from helminthes to staphylococcus. Study design helped control for confounders (exercise, environment, genetic factors, non-phytochemical dietary intake). This study provides evidence of the major role total phytochemical dietary intake plays in human health, often not considered by policymakers and nutritional and agricultural scientists.
ContributorsLondon, Douglas (Author) / Tsuda, Takeyuki (Thesis advisor) / Beezhold, Bonnie L (Committee member) / Hruschka, Daniel (Committee member) / Eder, James (Committee member) / Arizona State University (Publisher)
Created2012
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
Thiol functionalization is one potentially useful way to tailor physical and chemical properties of graphene oxides (GOs) and reduced graphene oxides (RGOs). Despite the ubiquitous presence of thiol functional groups in diverse chemical systems, efficient thiol functionalization has been challenging for GOs and RGOs, or for carbonaceous materials in general. In this work, thionation of GOs has been achieved in high yield through two new methods that also allow concomitant chemical reduction/thermal reduction of GOs; a solid-gas metathetical reaction method with boron sulfides (BxSy) gases and a solvothermal reaction method employing phosphorus decasulfide (P4S10). The thionation products, called "mercapto reduced graphene oxides (m-RGOs)", were characterized by employing X-ray photoelectron spectroscopy, powder X-ray diffraction, UV-Vis spectroscopy, FT-IR spectroscopy, Raman spectroscopy, electron probe analysis, scanning electron microscopy, (scanning) transmission electron microscopy, nano secondary ion mass spectrometry, Ellman assay and atomic force microscopy. The excellent dispersibility of m-RGOs in various solvents including alcohols has allowed fabrication of thin films of m-RGOs. Deposition of m-RGOs on gold substrates was achieved through solution deposition and the m-RGOs were homogeneously distributed on gold surface shown by atomic force microscopy. Langmuir-Blodgett (LB) films of m-RGOs were obtained by transferring their Langmuir films, formed by simple drop casting of m-RGOs dispersion on water surface, onto various substrates including gold, glass and indium tin oxide. The m-RGO LB films showed low sheet resistances down to about 500 kΩ/sq at 92% optical transparency. The successful results make m-RGOs promising for applications in transparent conductive coatings, biosensing, etc.
ContributorsJeon, Kiwan (Author) / Seo, Dong-Kyun (Thesis advisor) / Jones, Anne K (Committee member) / Yarger, Jeffery (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