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Molecular chaperones of the endoplasmic reticulum promote hepatitis C virus E2 protein production in plants

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…

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

Fuel Cell Integrated Gas Turbine Hybrid System Under Various Conditions

Description

A novel concept for integration of flame-assisted fuel cells (FFC) with a gas turbine is analyzed in this paper. Six different fuels (CH4, C3H8, JP-4, JP-5, JP-10(L), and H2) are investigated for the analytical model of the FFC integrated gas turbine hybrid system. As equivalence ratio increases, the efficiency of…

A novel concept for integration of flame-assisted fuel cells (FFC) with a gas turbine is analyzed in this paper. Six different fuels (CH4, C3H8, JP-4, JP-5, JP-10(L), and H2) are investigated for the analytical model of the FFC integrated gas turbine hybrid system. As equivalence ratio increases, the efficiency of the hybrid system increases initially then decreases because the decreasing flow rate of air begins to outweigh the increasing hydrogen concentration. This occurs at an equivalence ratio of 2 for CH4. The thermodynamic cycle is analyzed using a temperature entropy diagram and a pressure volume diagram. These thermodynamic diagrams show as equivalence ratio increases, the power generated by the turbine in the hybrid setup decreases. Thermodynamic analysis was performed to verify that energy is conserved and the total chemical energy going into the system was equal to the heat rejected by the system plus the power generated by the system. Of the six fuels, the hybrid system performs best with H2 as the fuel. The electrical efficiency with H2 is predicted to be 27%, CH4 is 24%, C3H8 is 22%, JP-4 is 21%, JP-5 is 20%, and JP-10(L) is 20%. When H2 fuel is used, the overall integrated system is predicted to be 24.5% more efficient than the standard gas turbine system. The integrated system is predicted to be 23.0% more efficient with CH4, 21.9% more efficient with C3H8, 22.7% more efficient with JP-4, 21.3% more efficient with JP-5, and 20.8% more efficient with JP-10(L). The sensitivity of the model is investigated using various fuel utilizations. When CH4 fuel is used, the integrated system is predicted to be 22.7% more efficient with a fuel utilization efficiency of 90% compared to that of 30%.

ContributorsRupiper, Lauren Nicole (Author) / Milcarek, Ryan (Thesis director) / Wang, Liping (Committee member) / Mechanical and Aerospace Engineering Program (Contributor) / School for Engineering of Matter,Transport & Enrgy (Contributor) / Barrett, The Honors College (Contributor)

Created2021-05

A Determination of the Hedonic Properties of Synthetic Cathinones 4-MEC and MDPV Through the Use of Intracranial Self-Stimulation

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…

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

Compressible flow through a porous medium: choking at pore scale and its implications

Description

Production from a high pressure gas well at a high production-rate encounters the risk of operating near the choking condition for a compressible flow in porous media. The unbounded gas pressure gradient near the point of choking, which is located near the wellbore, generates an effective tensile stress on the…

Production from a high pressure gas well at a high production-rate encounters the risk of operating near the choking condition for a compressible flow in porous media. The unbounded gas pressure gradient near the point of choking, which is located near the wellbore, generates an effective tensile stress on the porous rock frame. This tensile stress almost always exceeds the tensile strength of the rock and it causes a tensile failure of the rock, leading to wellbore instability. In a porous rock, not all pores are choked at the same flow rate, and when just one pore is choked, the flow through the entire porous medium should be considered choked as the gas pressure gradient at the point of choking becomes singular. This thesis investigates the choking condition for compressible gas flow in a single microscopic pore. Quasi-one-dimensional analysis and axisymmetric numerical simulations of compressible gas flow in a pore scale varicose tube with a number of bumps are carried out, and the local Mach number and pressure along the tube are computed for the flow near choking condition. The effects of tube length, inlet-to-outlet pressure ratio, the number of bumps and the amplitude of the bumps on the choking condition are obtained. These critical values provide guidance for avoiding the choking condition in practice.

ContributorsYuan, Jing (Author) / Chen, Kangping (Thesis advisor) / Wang, Liping (Committee member) / Huang, Huei-Ping (Committee member) / Arizona State University (Publisher)

Created2013

Challenging the versatility of the Tesla turbine: working fluid variations and turbine performance

Description

Tesla turbo-machinery offers a robust, easily manufactured, extremely versatile prime mover with inherent capabilities making it perhaps the best, if not the only, solution for certain niche applications. The goal of this thesis is not to optimize the performance of the Tesla turbine, but to compare its performance with various…

Tesla turbo-machinery offers a robust, easily manufactured, extremely versatile prime mover with inherent capabilities making it perhaps the best, if not the only, solution for certain niche applications. The goal of this thesis is not to optimize the performance of the Tesla turbine, but to compare its performance with various working fluids. Theoretical and experimental analyses of a turbine-generator assembly utilizing compressed air, saturated steam and water as the working fluids were performed and are presented in this work. A brief background and explanation of the technology is provided along with potential applications. A theoretical thermodynamic analysis is outlined, resulting in turbine and rotor efficiencies, power outputs and Reynolds numbers calculated for the turbine for various combinations of working fluids and inlet nozzles. The results indicate the turbine is capable of achieving a turbine efficiency of 31.17 ± 3.61% and an estimated rotor efficiency 95 ± 9.32%. These efficiencies are promising considering the numerous losses still present in the current design. Calculation of the Reynolds number provided some capability to determine the flow behavior and how that behavior impacts the performance and efficiency of the Tesla turbine. It was determined that turbulence in the flow is essential to achieving high power outputs and high efficiency. Although the efficiency, after peaking, begins to slightly taper off as the flow becomes increasingly turbulent, the power output maintains a steady linear increase.

ContributorsPeshlakai, Aaron (Author) / Phelan, Patrick (Thesis advisor) / Trimble, Steve (Committee member) / Wang, Liping (Committee member) / Arizona State University (Publisher)

Created2012

Dynamic Cryothermal Measurements of VO2-Based Fabry-Perot Emitter

Description

This work summarizes the development of a dynamic measurement platform in a cryostat to measure sample temperature response to space-like conditions and the creation a MATLAB theoretical model to predict sample temperature responses in the platform itself. An interesting variable-emittance sample called a Fabry-Perot emitter was studied for its thermal…

This work summarizes the development of a dynamic measurement platform in a cryostat to measure sample temperature response to space-like conditions and the creation a MATLAB theoretical model to predict sample temperature responses in the platform itself. An interesting variable-emittance sample called a Fabry-Perot emitter was studied for its thermal homeostasis behavior using the two developments. Using the measurement platform, it was shown that there was no thermal homeostatic behavior demonstrated by the sample at steady state temperatures. Theoretical calculations show other ways to demonstrate the cooling homeostasis behavior through time-varying heat inputs. Factors within the system such as heat loss and thermal mass contributed to an inhibited sample performance in the platform. Future work will have to be conducted, not only to verify the findings of the initial experiments but also to improve the measurement platform and the theoretical model.

ContributorsBoman, Neal D (Author) / Wang, Liping (Thesis director) / Taylor, Syndey (Committee member) / Mechanical and Aerospace Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)

Created2021-05

Switchable Mid-Infrared Filter Based on Thermochromic Vanadium Dioxide

Description

A thermochromic mid-infrared filter is designed, where a spectrally-selective transmittance peak exists while vanadium dioxide layers are below their transition temperature but broad opaqueness is observed below the transition temperature. This filter takes advantage of interference effects between a silicon spacer and insulating vanadium dioxide to create the transmittance peak…

A thermochromic mid-infrared filter is designed, where a spectrally-selective transmittance peak exists while vanadium dioxide layers are below their transition temperature but broad opaqueness is observed below the transition temperature. This filter takes advantage of interference effects between a silicon spacer and insulating vanadium dioxide to create the transmittance peak and the drastic optical property change between insulating and metallic vanadium dioxide. The theoretical performance of the filter in energy dissipation and thermal camouflaging applications is analyzed and can be optimized by tuning the thicknesses of the thin-film layers.

ContributorsChao, Jeremy (Author) / Wang, Liping (Thesis director) / Taylor, Sydney (Committee member) / Mechanical and Aerospace Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)

Created2021-05

The Effects of Diet on Glucose Metabolsim of Maturing Rats

Description

Background: Both puberty and diets composed of high levels of saturated fats have been shown to result in central adiposity, fasting hyperinsulinemia, insulin resistance and impaired glucose tolerance. While a significantly insulinogenic phenotypic change occurs in these two incidences, glucose homeostasis does not appear to be affected. Methods: Male, Sprague-dawley…

Background: Both puberty and diets composed of high levels of saturated fats have been shown to result in central adiposity, fasting hyperinsulinemia, insulin resistance and impaired glucose tolerance. While a significantly insulinogenic phenotypic change occurs in these two incidences, glucose homeostasis does not appear to be affected. Methods: Male, Sprague-dawley rats were fed diets consisting of CHOW or low fat (LF), High Fat Diet and High Fat Diet (HFD) with supplementary Canola Oil (Monounsaturated fat). These rats were given these diets at 4-5 weeks old and given intraperitoneal and oral glucose tolerance tests(IPGTT; OGTT) at 4 and 8 weeks to further understand glucose and insulin behavior under different treatments. (IPGTT: LF-n=14, HFD-n=16, HFD+CAN-n=12; OGTT: LF-n=8, HFD-n=8, HFD+CAN-n=6). Results: When comparing LF fed rats at 8 weeks with 4 week glucose challenge test, area under the curve (AUC) of glucose was 1.2 that of 4 weeks. At 8 weeks, HFD fed rats AUCg was much greater than LF fed rats under both IPGTT and OGTT. When supplemented with Canola oil, HFD fed rats AUC returned to LF data range. Despite the alleviating glucose homeostasis affects of Canola oil the AUC of insulin curve, which was elevated by HFD, remained high. Conclusion: HFD in maturing rats elevates fasting insulin levels, increases insulin resistance and lowers glucose homeostasis. When given a monounsaturated fatty acid (MUFA) supplement fasting hyperinsulinemia, and late hyperinsulinemia still occur though glucose homeostasis is regained. For OGTT HFD also induced late hyper c-peptide levels and compared to LF and HFD+CAN, a higher c-peptide level over time.

ContributorsRay, Tyler John (Author) / Caplan, Michael (Thesis director) / Herman, Richard (Committee member) / Towner, Kali (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / W. P. Carey School of Business (Contributor) / School of Human Evolution and Social Change (Contributor)

Created2015-05

Validating a Model for Catalytic Function in 9°N Polymerase Based on Structural Conservation

Description

Nucleic acids encode the information required to create life, and polymerases are the gatekeepers charged with maintaining the storage and flow of this genetic information. Synthetic biologists utilize this universal property to modify organisms and other systems to create unique traits or improve the function of others. One of the…

Nucleic acids encode the information required to create life, and polymerases are the gatekeepers charged with maintaining the storage and flow of this genetic information. Synthetic biologists utilize this universal property to modify organisms and other systems to create unique traits or improve the function of others. One of the many realms in synthetic biology involves the study of biopolymers that do not exist naturally, which is known as xenobiology. Although life depends on two biopolymers for genetic storage, it may be possible that alternative molecules (xenonucleic acids – XNAs), could be used in their place in either a living or non-living system. However, implementation of an XNA based system requires the development of polymerases that can encode and decode information stored in these artificial polymers. A strategy called directed evolution is used to modify or alter the function of a protein of interest, but identifying mutations that can modify polymerase function is made problematic by their size and overall complexity. To reduce the amount of sequence space that needs to be samples when attempting to identify polymerase variants, we can try to make informed decisions about which amino acid residues may have functional roles in catalysis. An analysis of Family B polymerases has shown that residues which are involved in substrate specificity are often highly conserved both at the sequence and structure level. In order to validate the hypothesis that a strong correlation exists between structural conservation and catalytic activity, we have selected and mutated residues in the 9°N polymerase using a loss of function mutagenesis strategy based on a computational analysis of several homologues from a diverse range of taxa. Improvement of these models will hopefully lead to quicker identification of loci which are ideal engineering targets.

ContributorsHaeberle, Tyler Matthew (Author) / Chaput, John (Thesis director) / Chen, Julian (Committee member) / Larsen, Andrew (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)

Created2015-05

Immunosignature System for Diagnosis of Lung Cancer

Description

Lung cancer is the leading cause of cancer-related deaths in the US. Low-dose computed tomography (LDCT) scans are speculated to reduce lung cancer mortality. However LDCT scans impose multiple risks including false-negative results, false- positive results, overdiagnosis, and cancer due to repeated exposure to radiation. Immunosignaturing is a new method…

Lung cancer is the leading cause of cancer-related deaths in the US. Low-dose computed tomography (LDCT) scans are speculated to reduce lung cancer mortality. However LDCT scans impose multiple risks including false-negative results, false- positive results, overdiagnosis, and cancer due to repeated exposure to radiation. Immunosignaturing is a new method proposed to screen and detect lung cancer, eliminating the risks associated with LDCT scans. Known and blinded primary blood sera from participants with lung cancer and no cancer were run on peptide microarrays and analyzed. Immunosignatures for each known sample collectively indicated 120 peptides unique to lung cancer and non-cancer participants. These 120 peptides were used to determine the status of the blinded samples. Verification of the results from Vanderbilt is pending.

ContributorsNguyen, Geneva Trieu (Author) / Woodbury, Neal (Thesis director) / Zhao, Zhan-Gong (Committee member) / Stafford, Phillip (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Department of Psychology (Contributor)

Created2015-05