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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
Biological and immunological characterization of plant-produced HIV-1 Gag/dgp41 virus-like particles
Description
Anti-retroviral drugs and AIDS prevention programs have helped to decrease the rate of new HIV-1 infections in some communities, however, a prophylactic vaccine is still needed to control the epidemic world-wide. Despite over two decades of research, a vaccine against HIV-1 remains elusive, although recent clinical trials have shown promising results. Recent successes have focused on highly conserved, mucosally-targeted antigens within HIV-1 such as the membrane proximal external region (MPER) of the envelope protein, gp41. MPER has been shown to play critical roles in the viral mucosal transmission, though this peptide is not immunogenic on its own. Gag is a structural protein configuring the enveloped virus particles, and has been suggested to constitute a target of the cellular immunity potentially controlling the viral load. It was hypothesized that HIV-1 enveloped virus-like particles (VLPs) consisting of Gag and a deconstructed form of gp41 comprising the MPER, transmembrane, and cytoplasmic domains (dgp41) could be expressed in plants. Plant-optimized HIV-1 genes were constructed and expressed in Nicotiana benthamiana by stable transformation, or transiently using a tobacco mosaic virus-based expression system or a combination of both. Results of biophysical, biochemical and electron microscopy characterization demonstrated that plant cells could support not only the formation of HIV-1 Gag VLPs, but also the accumulation of VLPs that incorporated dgp41. These particles were purified and utilized in mice immunization experiments. Prime-boost strategies combining systemic and mucosal priming with systemic boosting using two different vaccine candidates (VLPs and CTB-MPR - a fusion of MPER and the B-subunit of cholera toxin) were administered to BALB/c mice. Serum antibody responses against both the Gag and gp41 antigens could be elicited in mice systemically primed with VLPs and these responses could be recalled following systemic boosting with VLPs. In addition, mucosal priming with VLPs allowed for a robust boosting response against Gag and gp41 when boosted with either candidate. Functional assays of these antibodies are in progress to test the antibodies' effectiveness in neutralizing and preventing mucosal transmission of HIV-1. This immunogenicity of plant-based Gag/dgp41 VLPs represents an important milestone on the road towards a broadly-efficacious and inexpensive subunit vaccine against HIV-1.
ContributorsKessans, Sarah (Author) / Mor, Tsafrir S (Thesis advisor) / Matoba, Nobuyuki (Committee member) / Mason, Hugh (Committee member) / Hogue, Brenda (Committee member) / Fromme, Petra (Committee member) / Arizona State University (Publisher)
Created2011
Description
In an effort to address the lack of literature in on-campus active travel, this study aims to investigate the following primary questions:<br/>• What are the modes that students use to travel on campus?<br/>• What are the motivations that underlie the mode choice of students on campus?<br/>My first stage of research involved a series of qualitative investigations. I held one-on-one virtual interviews with students in which I asked them questions about the mode they use and why they feel that their chosen mode works best for them. These interviews served two functions. First, they provided me with insight into the various motivations underlying student mode choice. Second, they provided me with an indication of what explanatory variables should be included in a model of mode choice on campus.<br/>The first half of the research project informed a quantitative survey that was released via the Honors Digest to attract student respondents. Data was gathered on travel behavior as well as relevant explanatory variables.<br/>My analysis involved developing a logit model to predict student mode choice on campus and presenting the model estimation in conjunction with a discussion of student travel motivations based on the qualitative interviews. I use this information to make a recommendation on how campus infrastructure could be modified to better support the needs of the student population.
ContributorsMirtich, Laura Christine (Author) / Salon, Deborah (Thesis director) / Fang, Kevin (Committee member) / School of Public Affairs (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
ABSTRACT Group III-nitride semiconductor materials have been commercially used in fabrication of light-emitting diodes (LEDs) and laser diodes (LDs) covering the spectral range from UV to visible and infrared, and exhibit unique properties suitable for modern optoelectronic applications. Great advances have recently happened in the research and development in high-power and high-efficiency blue-green-white LEDs, blue LDs and other optoelectronic applications. However, there are still many unsolved challenges with these materials. In this dissertation, several issues concerning structural, electronic and optical properties of III-nitrides have been investigated using a combination of transmission electron microscopy (TEM), electron holography (EH) and cathodoluminescence (CL) techniques. First, a trend of indium chemical inhomogeneity has been found as the indium composition increases for the InGaN epitaxial layers grown by hydride vapor phase epitaxy. Second, different mechanisms contributing to the strain relaxation have been studied for non-polar InGaN epitaxial layers grown on zinc oxide (ZnO) substrate. Third, various structural morphologies of non-polar InGaN epitaxial layers grown on free-standing GaN substrate have been investigated. Fourth, the effect of the growth temperature on the performance of GaN lattice-matched InAlN electron blocking layers has been studied. Finally, the electronic and optical properties of GaN nanowires containing a AlN/GaN superlattice structure have been investigated showing relatively small internal electric field and superlattice- and defect-related emissions along the nanowires.
ContributorsSun, Kewei (Author) / Ponce, Fernando (Thesis advisor) / Smith, David (Committee member) / Treacy, Michael (Committee member) / Drucker, Jeffery (Committee member) / Schmidt, Kevin (Committee member) / Arizona State University (Publisher)
Created2011
Description
In this dissertation, remote plasma interactions with the surfaces of low-k interlayer dielectric (ILD), Cu and Cu adhesion layers are investigated. The first part of the study focuses on the simultaneous plasma treatment of ILD and chemical mechanical polishing (CMP) Cu surfaces using N2/H2 plasma processes. H atoms and radicals in the plasma react with the carbon groups leading to carbon removal for the ILD films. Results indicate that an N2 plasma forms an amide-like layer on the surface which apparently leads to reduced carbon abstraction from an H2 plasma process. In addition, FTIR spectra indicate the formation of hydroxyl (Si-OH) groups following the plasma exposure. Increased temperature (380 °C) processing leads to a reduction of the hydroxyl group formation compared to ambient temperature processes, resulting in reduced changes of the dielectric constant. For CMP Cu surfaces, the carbonate contamination was removed by an H2 plasma process at elevated temperature while the C-C and C-H contamination was removed by an N2 plasma process at elevated temperature. The second part of this study examined oxide stability and cleaning of Ru surfaces as well as consequent Cu film thermal stability with the Ru layers. The ~2 monolayer native Ru oxide was reduced after H-plasma processing. The thermal stability or islanding of the Cu film on the Ru substrate was characterized by in-situ XPS. After plasma cleaning of the Ru adhesion layer, the deposited Cu exhibited full coverage. In contrast, for Cu deposition on the Ru native oxide substrate, Cu islanding was detected and was described in terms of grain boundary grooving and surface and interface energies. The thermal stability of 7 nm Ti, Pt and Ru ii interfacial adhesion layers between a Cu film (10 nm) and a Ta barrier layer (4 nm) have been investigated in the third part. The barrier properties and interfacial stability have been evaluated by Rutherford backscattering spectrometry (RBS). Atomic force microscopy (AFM) was used to measure the surfaces before and after annealing, and all the surfaces are relatively smooth excluding islanding or de-wetting phenomena as a cause of the instability. The RBS showed no discernible diffusion across the adhesion layer/Ta and Ta/Si interfaces which provides a stable underlying layer. For a Ti interfacial layer RBS indicates that during 400 °C annealing Ti interdiffuses through the Cu film and accumulates at the surface. For the Pt/Cu system Pt interdiffuion is detected which is less evident than Ti. Among the three adhesion layer candidates, Ru shows negligible diffusion into the Cu film indicating thermal stability at 400 °C.
ContributorsLiu, Xin (Author) / Nemanich, Robert (Thesis advisor) / Chamberlin, Ralph (Committee member) / Chen, Tingyong (Committee member) / Smith, David (Committee member) / Ponce, Fernando (Committee member) / Arizona State University (Publisher)
Created2012
Description
The energy band gap of a semiconductor material critically influences the operating wavelength of an optoelectronic device. Realization of any desired band gap, or even spatially graded band gaps, is important for applications such as lasers, light-emitting diodes (LEDs), solar cells, and detectors. Compared to thin films, nanowires offer greater flexibility for achieving a variety of alloy compositions. Furthermore, the nanowire geometry permits simultaneous incorporation of a wide range of compositions on a single substrate. Such controllable alloy composition variation can be realized either within an individual nanowire or between distinct nanowires across a substrate. This dissertation explores the control of spatial composition variation in ternary alloy nanowires. Nanowires were grown by the vapor-liquid-solid (VLS) mechanism using chemical vapor deposition (CVD). The gas-phase supersaturation was considered in order to optimize the deposition morphology. Composition and structure were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive x-ray spectroscopy (EDS), and x-ray diffraction (XRD). Optical properties were investigated through photoluminescence (PL) measurements. The chalcogenides selected as alloy endpoints were lead sulfide (PbS), cadmium sulfide (CdS), and cadmium selenide (CdSe). Three growth modes of PbS were identified, which included contributions from spontaneously generated catalyst. The resulting wires were found capable of lasing with wavelengths over 4000 nm, representing the longest known wavelength from a sub-wavelength wire. For CdxPb1-xS nanowires, it was established that the cooling process significantly affects the alloy composition and structure. Quenching was critical to retain metastable alloys with x up to 0.14, representing a new composition in nanowire form. Alternatively, gradual cooling caused phase segregation, which created heterostructures with light emission in both the visible and mid-infrared regimes. The CdSSe alloy system was fully explored for spatial composition variation. CdSxSe1-x nanowires were grown with composition variation across the substrate. Subsequent contact printing preserved the designed composition gradient and led to the demonstration of a variable wavelength photodetector device. CdSSe axial heterostructure nanowires were also achieved. The growth process involved many variables, including a deliberate and controllable change in substrate temperature. As a result, both red and green light emission was detected from single nanowires.
ContributorsNichols, Patricia (Author) / Ning, Cun-Zheng (Thesis advisor) / Carpenter, Ray (Committee member) / Bennett, Peter (Committee member) / Smith, David (Committee member) / Arizona State University (Publisher)
Created2012
Description
Of the potential technologies for pre-combustion capture, membranes offer the advantages of being temperature resistant, able to handle large flow rates, and having a relatively small footprint. A significant amount of research has centered on the use of polymeric and microporous inorganic membranes to separate CO2. These membranes, however, have limitations at high temperature resulting in poor permeation performance. To address these limitations, the use of a dense dual-phase membrane has been studied. These membranes are composed of conductive solid and conductive liquid phases that have the ability to selectively permeate CO2 by forming carbonate ions that diffuse through the membrane at high temperature. The driving force for transport through the membrane is a CO2 partial pressure gradient. The membrane provides a theoretically infinite selectivity. To address stability of the ceramic-carbonate dual-phase membrane for CO2 capture at high temperature, the ceramic phase of the membrane was studied and replaced with materials previously shown to be stable in harsh conditions. The permeation properties and stability of La0.6Sr0.4Co0.8Fe0.2O3-δ (LSCF)-carbonate, La0.85Ce0.1Ga0.3Fe0.65Al0.05O3-δ (LCGFA)-carbonate, and Ce0.8Sm0.2O1.9 (SDC)-carbonate membranes were examined under a wide range of experimental conditions at high temperature. LSCF-carbonate membranes were shown to be unstable without the presence of O2 due to reaction of CO2 with the ceramic phase. In the presence of O2, however, the membranes showed stable permeation behavior for more than one month at 900oC. LCGFA-carbonate membranes showed great chemical and permeation stability in the presence of various conditions including exposure to CH4 and H2, however, the permeation performance was quite low when compared to membranes in the literature. Finally, SDC-carbonate membranes showed great chemical and permeation stability both in a CO2:N2 environment for more than two weeks at 900oC as well as more than one month of exposure to simulated syngas conditions at 700oC. Ceramic phase chemical stability increased in the order of LSCF < LCGFA < SDC while permeation performance increased in the order of LCGFA < LSCF < SDC.
ContributorsNorton, Tyler (Author) / Lin, Jerry Y.S. (Thesis advisor) / Alford, Terry (Committee member) / Lind, Mary Laura (Committee member) / Smith, David (Committee member) / Torres, Cesar (Committee member) / Arizona State University (Publisher)
Created2013
Description
Group III-nitride semiconductors have wide application in optoelectronic devices. Spontaneous and piezoelectric polarization effects have been found to be critical for electric and optical properties of group III-nitrides. In this dissertation, firstly, the crystal orientation dependence of the polarization is calculated and in-plane polarization is revealed. The in-plane polarization is sensitive to the lateral characteristic dimension determined by the microstructure. Specific semi-polar plane growth is suggested for reducing quantum-confined Stark effect. The macroscopic electrostatic field from the polarization discontinuity in the heterostructures is discussed, b ased on that, the band diagram of InGaN/GaN quantum well/barrier and AlGaN/GaN heterojunction is obtained from the self-consistent solution of Schrodinger and Poisson equations. New device design such as triangular quantum well with the quenched polarization field is proposed. Electron holography in the transmission electron microscopy is used to examine the electrostatic potential under polarization effects. The measured potential energy profiles of heterostructure are compared with the band simulation, and evidences of two-dimensional hole gas (2DHG) in a wurtzite AlGaN/ AlN/ GaN superlattice, as well as quasi two-dimensional electron gas (2DEG) in a zinc-blende AlGaN/GaN are found. The large polarization discontinuity of AlN/GaN is the main source of the 2DHG of wurtzite nitrides, while the impurity introduced during the growth of AlGaN layer provides the donor states that to a great extent balance the free electrons in zinc-blende nitrides. It is also found that the quasi-2DEG concentration in zinc-blende AlGaN/GaN is about one order of magnitude lower than the wurtzite AlGaN/GaN, due to the absence of polarization. Finally, the InAlN/GaN lattice-matched epitaxy, which ideally has a zero piezoelectric polarization and strong spontaneous polarization, is experimentally studied. The breakdown in compositional homogeneity is triggered by threading dislocations with a screw component propagating from the GaN underlayer, which tend to open up into V-grooves at a certain thickness of the InxAl1-xN layer. The V-grooves coalesce at 200 nm and are filled with material that exhibits a significant drop in indium content and a broad luminescence peak. The structural breakdown is due to heterogeneous nucleation and growth at the facets of the V-grooves.
ContributorsWei, Qiyuan (Author) / Ponce, Fernando A. (Thesis advisor) / Tsen, Kong-Thon (Committee member) / Shumway, John (Committee member) / Menéndez, Jose (Committee member) / Smith, David (Committee member) / Arizona State University (Publisher)
Created2012
Description
Over the past decade, several high-value proteins have been produced using plant-based transient expression systems. However, these studies exposed some limitations that must be overcome to allow plant expression systems to reach their full potential. These limitations are the low level of recombinant protein accumulation achieved in some cases, and lack of efficient co-expression vectors for the production of multi-protein complexes. This study report that tobacco Extensin (Ext) gene 3' untranslated region (UTR) can be broadly used to enhance recombinant protein expression in plants. Extensin is the hydroxyproline-rich glycoprotein that constitutes the major protein component of cell walls. Using transient expression, it was found that the Ext 3' UTR increases recombinant protein expression up to 13.5- and 6-fold in non-replicating and replicating vector systems, respectively, compared to previously established terminators. Enhanced protein accumulation was correlated with increased mRNA levels associated with reduction in read-through transcription. Regions of Ext 3' UTR essential for maximum gene expression included a poly-purine sequence used as a major poly-adenylation site. Furthermore, modified bean yellow dwarf virus (BeYDV)-based vectors designed to allow co-expression of multiple recombinant genes were constructed and tested for their performance in driving transient expression in plants. Robust co-expression and assembly of heavy and light chains of the anti-Ebola virus monoclonal antibody 6D8, as well as E. coli heat-labile toxin (LT) were achieved with the modified vectors. The simultaneous co-expression of three fluoroproteins using the single replicon, triple cassette is demonstrated by confocal microscopy. In conclusion, this study provides an excellent tool for rapid, cost-effective, large-scale manufacturing of recombinant proteins for use in medicine and industry.
ContributorsRosenthal, Sun Hee (Author) / Mason, Hugh (Thesis advisor) / Mor, Tsafrir (Committee member) / Chang, Yung (Committee member) / Arntzen, Charles (Committee member) / Arizona State University (Publisher)
Created2012
Description
Recently a new materials platform consisting of semiconductors grown on GaSb and InAs substrates with lattice constants close to 6.1 A was proposed by our group for various electronic and optoelectronic applications. This materials platform consists of both II-VI (MgZnCdHg)(SeTe) and III-V (InGaAl)(AsSb) compound semiconductors, which have direct bandgaps spanning the entire energy spectrum from far-IR (~0 eV) up to UV (~3.4 eV). The broad range of bandgaps and material properties make it very attractive for a wide range of applications in optoelectronics, such as solar cells, laser diodes, light emitting diodes, and photodetectors. Moreover, this novel materials system potentially offers unlimited degrees of freedom for integration of electronic and optoelectronic devices onto a single substrate while keeping the best possible materials quality with very low densities of misfit dislocations. This capability is not achievable with any other known lattice-matched semiconductors on any available substrate. In the 6.1-A materials system, the semiconductors ZnTe and GaSb are almost perfectly lattice-matched with a lattice mismatch of only 0.13%. Correspondingly, it is expected that high quality ZnTe/GaSb and GaSb/ZnTe heterostructures can be achieved with very few dislocations generated during growth. To fulfill the task, their MBE growth and material properties are carefully investigated. High quality ZnTe layers grown on various III-V substrates and GaSb grown on ZnTe are successfully achieved using MBE. It is also noticed that ZnTe and GaSb have a type-I band-edge alignment with large band offsets (delta_Ec=0.934 eV, delta_Ev=0.6 eV), which provides strong confinement for both electrons and holes. Furthermore, a large difference in refractive index is found between ZnTe and GaSb (2.7 and 3.9, respectively, at 0.7 eV), leading to excellent optical confinement of the guided optical modes in planar semiconductor lasers or distributed Bragg reflectors (DBR) for vertical-cavity surface-emitting lasers. Therefore, GaSb/ZnTe double-heterostructure and ZnTe/GaSb DBR structure are suitable for use in light emitting devices. In this thesis work, experimental demonstration of these structures with excellent structural and optical properties is reported. During the exploration on the properties of various ZnTe heterostructures, it is found that residual tensile strains exist in the thick ZnTe epilayers when they are grown on GaAs, InP, InAs and GaSb substrates. The presence of tensile strains is due to the difference in thermal expansion coefficients between the epilayers and the substrates. The defect densities in these ZnTe layers become lower as the ZnTe layer thickness increases. Growth of high quality GaSb on ZnTe can be achieved using a temperature ramp during growth. The influence of temperature ramps with different ramping rates in the optical properties of GaSb layer is studied, and the samples grown with a temperature ramp from 360 to 470 C at a rate of 33 C/min show the narrowest bound exciton emission peak with a full width at half maximum of 15 meV. ZnTe/GaSb DBR structures show excellent reflectivity properties in the mid-infrared range. A peak reflectance of 99% with a wide stopband of 480 nm centered at 2.5 um is measured from a ZnTe/GaSb DBR sample of only 7 quarter-wavelength pairs.
ContributorsFan, Jin (Author) / Zhang, Yong-Hang (Thesis advisor) / Smith, David (Committee member) / Yu, Hongbin (Committee member) / Menéndez, Jose (Committee member) / Johnson, Shane (Committee member) / Arizona State University (Publisher)
Created2012