Matching Items (443)
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
Semiconductor nanowires are featured by their unique one-dimensional structure which makes them promising for small scale electronic and photonic device applications. Among them, III-V material nanowires are particularly outstanding due to their good electronic properties. In bulk, these materials reveal electron mobility much higher than conventional silicon based devices, for example at room temperature, InAs field effect transistor (FET) has electron mobility of 40,000 cm2/Vs more than 10 times of Si FET. This makes such materials promising for high speed nanowire FETs. With small bandgap, such as 0.354 eV for InAs and 1.52 eV for GaAs, it does not need high voltage to turn on such devices which leads to low power consumption devices. Another feature of direct bandgap allows their applications of optoelectronic devices such as avalanche photodiodes. However, there are challenges to face up. Due to their large surface to volume ratio, nanowire devices typically are strongly affected by the surface states. Although nanowires can be grown into single crystal structure, people observe crystal defects along the wires which can significantly affect the performance of devices. In this work, FETs made of two types of III-V nanowire, GaAs and InAs, are demonstrated. These nanowires are grown by catalyst-free MOCVD growth method. Vertically nanowires are transferred onto patterned substrates for coordinate calibration. Then electrodes are defined by e-beam lithography followed by deposition of contact metals. Prior to metal deposition, however, the substrates are dipped in ammonium hydroxide solution to remove native oxide layer formed on nanowire surface. Current vs. source-drain voltage with different gate bias are measured at room temperature. GaAs nanowire FETs show photo response while InAs nanowire FETs do not show that. Surface passivation is performed on GaAs FETs by using ammonium surfide solution. The best results on current increase is observed with around 20-30 minutes chemical treatment time. Gate response measurements are performed at room temperature, from which field effect mobility as high as 1490 cm2/Vs is extracted for InAs FETs. One major contributor for this is stacking faults defect existing along nanowires. For InAs FETs, thermal excitations observed from temperature dependent results which leads us to investigate potential barriers.
ContributorsLiang, Hanshuang (Author) / Yu, Hongbin (Thesis advisor) / Ferry, David (Committee member) / Tracy, Clarence (Committee member) / Arizona State University (Publisher)
Created2011
Description
The concept of vaccination dates back further than Edward Jenner's first vaccine using cowpox pustules to confer immunity against smallpox in 1796. Nevertheless, it was Jenner's success that gave vaccines their name and made vaccinia virus (VACV) of particular interest. More than 200 years later there is still the need to understand vaccination from vaccine design to prediction of vaccine efficacy using mathematical models. Post-exposure vaccination with VACV has been suggested to be effective if administered within four days of smallpox exposure although this has not been definitively studied in humans. The first and second chapters analyze post-exposure prophylaxis of VACV in an animal model using v50ΔB13RMγ, a recombinant VACV expressing murine interferon gamma (IFN-γ) also known as type II IFN. While untreated animals infected with wild type VACV die by 10 days post-infection (dpi), animals treated with v50ΔB13RMγ 1 dpi had decreased morbidity and 100% survival. Despite these differences, the viral load was similar in both groups suggesting that v50ΔB13RMγ acts as an immunoregulator rather than as an antiviral. One of the main characteristics of VACV is its resistance to type I IFN, an effect primarily mediated by the E3L protein, which has a Z-DNA binding domain and a double-stranded RNA (dsRNA) binding domain. In the third chapter a VACV that independently expresses both domains of E3L was engineered and compared to wild type in cells in culture. The dual expression virus was unable to replicate in the JC murine cell line where both domains are needed together for replication. Moreover, phosphorylation of the dsRNA dependent protein kinase (PKR) was observed at late times post-infection which indicates that both domains need to be linked together in order to block the IFN response. Because smallpox has already been eradicated, the utility of mathematical modeling as a tool for predicting disease spread and vaccine efficacy was explored in the last chapter using dengue as a disease model. Current modeling approaches were reviewed and the 2000-2001 dengue outbreak in a Peruvian region was analyzed. This last section highlights the importance of interdisciplinary collaboration and how it benefits research on infectious diseases.
ContributorsHolechek, Susan A (Author) / Jacobs, Bertram L (Thesis advisor) / Castillo-Chavez, Carlos (Committee member) / Frasch, Wayne (Committee member) / Hogue, Brenda (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2011
Description
The purpose of our study was to examine the effectiveness of a cycling intervention on body composition in adolescents with Down syndrome (DS). Participants completed one of three interventions over eight consecutive weeks. The interventions were: 1) Voluntary Cycling (VC), in which participants cycled at their self-selected pedaling rate 2) Assisted Cycling (AC), in which the participants' voluntary pedaling rates were assisted with a motor to ensure the maintenance of 80 rpms. 3) No cycling (NC), in which the participants acted as controls. Participants in the AC intervention did not decrease body fat or increase lean body mass however they did maintain these measures during the intervention as compared to the VC and NO participants who increased body fat and decreased lean body mass. These statistics were not exactly as expected nor were they statistically significant. Future research will try to replicate this data with statistically significant values for more cycling adolescents with DS using more randomized intervention groups.
ContributorsBennett, Kristen Leigh (Author) / Ringenbach, Shannon (Thesis director) / Brown, Steven (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-05
Description
This research study examined the effects of assisted cycling using a stationary recumbent bicycle that had an internal motor to help participants pedal at a desired cadence. The participants were either placed in an Assisted Cycling (AC), Voluntary Cycling (VC), or No Cycling (NC) intervention group. Those placed in the AC of VC groups then came to a laboratory setting 3 days a week for 8 weeks to cycle for 30 minutes. This research specifically analyzes the Vineland Adaptive Behavior Scale II to analyze the changes in daily living skills and maladaptive behaviors pre and post the exercise intervention. After analyzing the VABS II scores it was found that those in the VC intervention had statistically significant improvements in maladaptive behaviors. An interpretation of this finding is that the VC intervention had an increased heart rate over the span of the intervention and had a larger power output than those in the AC group. A limitation of this research is that it was a self-reported questionnaire that was given to the caregivers of the participant. The caregivers were not always controlled for, so in some cases two different caregivers were given the questionnaire for a single participant. A suggestion for future research would be to use the participant's mental age versus their chronological age when using the VABS-II and to use the Adaptive Behaviors Assessment System III (ABAS-III).
ContributorsJenkins, Cayla Marie (Author) / Ringenbach, Shannon (Thesis director) / Kulinna, Pamela (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-05
Description
ABSTRACT In terms of prevalence, human suffering and costs dengue infections are the most important arthropod-borne viral disease worldwide. Dengue virus (DENV) is a mosquito-borne flavivirus and the etiological agent of dengue fever and dengue hemorrhagic fever. Thus, development of a safe and efficient vaccine constitutes an urgent necessity. Besides the traditional strategies aim at generating immunization options, the usage of viral vectors to deliver antigenic stimulus in order to elicit protection are particularly attractive for the endeavor of a dengue vaccine. The viral vector (MVvac2) is genetically equivalent to the currently used measles vaccine strain Moraten, which adds practicality to my approach. The goal of the present study was to generate a recombinant measles virus expressing structural antigens from two strains of DENV (DENV2 and DENV4) The recombinant vectors replication profile was comparable to that of the parental strain and expresses either membrane bound or soluble forms of DENV2 and DENV4 E glycoproteins. I discuss future experiments in order to demonstrate its immunogenicity in our measles-susceptible mouse model.
ContributorsAbdelgalel, Rowida (Author) / Reyes del Valle, Jorge (Thesis advisor) / Hogue, Brenda (Committee member) / Frasch, Wayne D (Committee member) / Arizona State University (Publisher)
Created2013
Description
Vaccinia virus (VACV) is the current vaccine for the highly infectious smallpox disease. Since the eradication of smallpox, VACV has been developed extensively as a heterologous vaccine vector for several pathogens. However, due to the complications associated with this replication competent virus, the safety and efficacy of VACV vaccine vector has been reevaluated. To evaluate the safety and efficacy of VACV, we study the interactions between VACV and the host innate immune system, especially the type I interferon (IFN) signaling pathways. In this work, we evaluated the role of protein kinase R (PKR) and Adenosine Deaminase Acting on RNA 1(ADAR1), which are induced by IFN, in VACV infection. We found that PKR is necessary but is not sufficient to activate interferon regulatory factor 3 (IRF3) in the induction of type I IFN; and the activation of the stress-activated protein kinase/ c-Jun NH2-terminal kinase is required for the PKR-dependent activation of IRF3 during VACV infection. Even though PKR was found to have an antiviral effect in VACV, ADAR1 was found to have a pro-viral effect by destabilizing double stranded RNA (dsRNA), rescuing VACVΔE3L, VACV deleted of the virulence factor E3L, when provided in trans. With the lessons we learned from VACV and host cells interaction, we have developed and evaluated a safe replication-competent VACV vaccine vector for HIV. Our preliminary results indicate that our VACV vaccine vector can still induce the IFN pathway while maintaining the ability to replicate and to express the HIV antigen efficiently. This suggests that this VACV vector can be used as a safe and efficient vaccine vector for HIV.
ContributorsHuynh, Trung Phuoc (Author) / Jacobs, Bertram L (Thesis advisor) / Hogue, Brenda (Committee member) / Chang, Yung (Committee member) / Ugarova, Tatiana (Committee member) / Arizona State University (Publisher)
Created2013
Description
ABSTRACT An Ensemble Monte Carlo (EMC) computer code has been developed to simulate, semi-classically, spin-dependent electron transport in quasi two-dimensional (2D) III-V semiconductors. The code accounts for both three-dimensional (3D) and quasi-2D transport, utilizing either 3D or 2D scattering mechanisms, as appropriate. Phonon, alloy, interface roughness, and impurity scattering mechanisms are included, accounting for the Pauli Exclusion Principle via a rejection algorithm. The 2D carrier states are calculated via a self-consistent 1D Schrödinger-3D-Poisson solution in which the charge distribution of the 2D carriers in the quantization direction is taken as the spatial distribution of the squared envelope functions within the Hartree approximation. The wavefunctions, subband energies, and 2D scattering rates are updated periodically by solving a series of 1D Schrödinger wave equations (SWE) over the real-space domain of the device at fixed time intervals. The electrostatic potential is updated by periodically solving the 3D Poisson equation. Spin-polarized transport is modeled via a spin density-matrix formalism that accounts for D'yakanov-Perel (DP) scattering. Also, the code allows for the easy inclusion of additional scattering mechanisms and structural modifications to devices. As an application of the simulator, the current voltage characteristics of an InGaAs/InAlAs HEMT are simulated, corresponding to nanoscale III-V HEMTs currently being fabricated by Intel Corporation. The comparative effects of various scattering parameters, material properties and structural attributes are investigated and compared with experiments where reasonable agreement is obtained. The spatial evolution of spin-polarized carriers in prototypical Spin Field Effect Transistor (SpinFET) devices is then simulated. Studies of the spin coherence times in quasi-2D structures is first investigated and compared to experimental results. It is found that the simulated spin coherence times for GaAs structures are in reasonable agreement with experiment. The SpinFET structure studied is a scaled-down version of the InGaAs/InAlAs HEMT discussed in this work, in which spin-polarized carriers are injected at the source, and the coherence length is studied as a function of gate voltage via the Rashba effect.
ContributorsTierney, Brian David (Author) / Goodnick, Stephen (Thesis advisor) / Ferry, David (Committee member) / Akis, Richard (Committee member) / Saraniti, Marco (Committee member) / Vasileska, Dragica (Committee member) / Arizona State University (Publisher)
Created2011
Description
This research study examined the bilateral asymmetry found in muscle pairs including the right and left sides of the upper rectus abdominis, lower rectus abdominis, external oblique, and internal oblique in college-aged, apparently fit men and women. Bilateral symmetry was found using surface electromyography (EMG) during three core exercises: 1) ab-slides using paper plates (paper), 2) planks, and 3) ab-slides using a commercial AbSlide® roller device by comparing maximal voluntary contractions (MVCs) of the four muscles previously listed. This research analyzed the percentage of muscle activation during these exercises to each person’s MVC using Noraxon® software. Analysis found that asymmetry for each muscle group was present although there is no measure of clinical significance for symmetry scores of the core muscles yet.
Asymmetry scores were calculated for all three exercises. The exercise that produced the greatest absolute, average asymmetry score was the ab-slide using the roller device. The muscle that the greatest absolute asymmetry was found was the internal oblique. This means that during the three exercises and MVC, the greatest difference between right and left side pair muscles was observed in the internal obliques. The standard deviation of symmetry scores for all exercises and muscles was great as there was much variation in the skill levels in the participants of this study. Bilateral asymmetry was found by visually comparing the asymmetry scores. In conclusion, bilateral asymmetry was found in the core muscles of college-aged individuals during bilateral abdominal exercises.
Asymmetry scores were calculated for all three exercises. The exercise that produced the greatest absolute, average asymmetry score was the ab-slide using the roller device. The muscle that the greatest absolute asymmetry was found was the internal oblique. This means that during the three exercises and MVC, the greatest difference between right and left side pair muscles was observed in the internal obliques. The standard deviation of symmetry scores for all exercises and muscles was great as there was much variation in the skill levels in the participants of this study. Bilateral asymmetry was found by visually comparing the asymmetry scores. In conclusion, bilateral asymmetry was found in the core muscles of college-aged individuals during bilateral abdominal exercises.
ContributorsFavaro, Miguel Angel (Author) / Berger, Christopher (Thesis director) / Lorenz, Kent (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-05
Description
This study examines cognitive planning in adolescents with Down syndrome (DS) following an 8-week assisted cycling therapy intervention. Forty-three participants were randomly assigned to assisted cycling (AC) (i.e., at least 30% faster than self-selected cadence accomplished by a motor), voluntary cycling (VC) (self-selected cadence), and no cycling (NC) control group. Both AC and VC rode a stationary bicycle three times/week, 30 minutes/session, for eight weeks in duration. Participants completed cognitive testing that assessed cognitive planning at the beginning (i.e., pretest) and end (i.e., posttest) of the 8-week intervention. Consistent with our hypothesis, the results showed that cognitive planning improved following eight weeks of cycling for the AC group. The same results were not seen for individuals in the VC or NC groups. Our results suggest that assisted cycling therapy may induce permanent changes in the prefrontal cortex in adolescents with DS.
ContributorsMillar, Kelsey Leann (Author) / Ringenbach, Shannon (Thesis director) / Amazeen, Eric (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-05