Matching Items (139)
Filtering by
- Creators: Phelan, Patrick
- Member of: ASU Electronic Theses and Dissertations
Description
The majority of chronic myeloid leukemia (CML) and some of acute lymphocytic leukemia (ALL) cases are associated with possessing the BCR-Abl fusion protein from an oncogenic translocation, resulting in a constantly active form of Abl and rapid proliferation. CML and ALL cells that possess the BCR-Abl fusion protein are known as Philadelphia chromosome positive (Ph+). Currently, Imatinib (selective Abl inhibitor) is used as therapy against CML and ALL. However, some patients may have malignancies which show resistance to Imatinib. Previous work displays that the transformation of progenitor B cells with the v-Abl oncogene of Abelson murine leukemia virus results in cell cycle progression, rapid proliferation, and potentially malignant transformation while preventing any further differentiation. Progenitor B cells transformed with the temperature-sensitive form of the v-Abl oncogene have served as a model to study cellular response to Imatinib treatment. After some manipulation, very few cells were forced to progress to malignancy, forming tumor in vivo. These cells were no long sensitive to v-Abl inactivation, resembling the Imatinib resistant ALL. Autophagy is the process by which proteins and organelles are broken-down and recycled within the eukaryotic cell and has been hypothesized to play a part in cancer cell survival and drug-resistance. LC3 processing is a widely accepted marker of autophagy induction and progression. It has also been shown that Imatinib treatment of Ph+ leukemia can induce autophagy. In this study, we examined the autophagy induction in response to v-Abl inactivation in a Ph+-B-ALL cell model that shows resistance to Imatinib. In particular, we wonder whether the tumor cell line resistant to v-Abl inactivation may acquire a high level of autophagy to become resistant to apoptosis induced by v-Abl inactivation, and thus become addicted to autophagy. Indeed, this tumor cell line displays a high basal levels of LC3 I and II expression, regardless of v-Abl activity. We further demonstrated that inhibition of the autophagy pathway enhances the tumor line's sensitivity to Imatinib, resulting in cell cycle arrest and massive apoptosis. The combination of autophagy and Abl inhibitions may serve as an effective therapy for BCR-Abl positive CML.
ContributorsArkus, Nohea (Author) / Chang, Yung (Thesis advisor) / Kusumi, Kenro (Committee member) / Lake, Douglas (Committee member) / Jacobs, Bertram (Committee member) / Arizona State University (Publisher)
Created2011
Description
Concrete columns constitute the fundamental supports of buildings, bridges, and various other infrastructures, and their failure could lead to the collapse of the entire structure. As such, great effort goes into improving the fire resistance of such columns. In a time sensitive fire situation, a delay in the failure of critical load bearing structures can lead to an increase in time allowed for the evacuation of occupants, recovery of property, and access to the fire. Much work has been done in improving the structural performance of concrete including reducing column sizes and providing a safer structure. As a result, high-strength (HS) concrete has been developed to fulfill the needs of such improvements. HS concrete varies from normal-strength (NS) concrete in that it has a higher stiffness, lower permeability and larger durability. This, unfortunately, has resulted in poor performance under fire. The lower permeability allows for water vapor to build up causing HS concrete to suffer from explosive spalling under rapid heating. In addition, the coefficient of thermal expansion (CTE) of HS concrete is lower than that of NS concrete. In this study, the effects of introducing a region of crumb rubber concrete into a steel-reinforced concrete column were analyzed. The inclusion of crumb rubber concrete into a column will greatly increase the thermal resistivity of the overall column, leading to a reduction in core temperature as well as the rate at which the column is heated. Different cases were analyzed while varying the positioning of the crumb-rubber region to characterize the effect of position on the improvement of fire resistance. Computer simulated finite element analysis was used to calculate the temperature and strain distribution with time across the column's cross-sectional area with specific interest in the steel - concrete region. Of the several cases which were investigated, it was found that the improvement of time before failure ranged between 32 to 45 minutes.
ContributorsZiadeh, Bassam Mohammed (Author) / Phelan, Patrick (Thesis advisor) / Kaloush, Kamil (Thesis advisor) / Jiang, Hanqing (Committee member) / Arizona State University (Publisher)
Created2011
Description
Locomotion of microorganisms is commonly observed in nature. Although microorganism locomotion is commonly attributed to mechanical deformation of solid appendages, in 1956 Nobel Laureate Peter Mitchell proposed that an asymmetric ion flux on a bacterium's surface could generate electric fields that drive locomotion via self-electrophoresis. Recent advances in nanofabrication have enabled the engineering of synthetic analogues, bimetallic colloidal particles, that swim due to asymmetric ion flux originally proposed by Mitchell. Bimetallic colloidal particles swim through aqueous solutions by converting chemical fuel to fluid motion through asymmetric electrochemical reactions. This dissertation presents novel bimetallic motor fabrication strategies, motor functionality, and a study of the motor collective behavior in chemical concentration gradients. Brownian dynamics simulations and experiments show that the motors exhibit chemokinesis, a motile response to chemical gradients that results in net migration and concentration of particles. Chemokinesis is typically observed in living organisms and distinct from chemotaxis in that there is no particle directional sensing. The synthetic motor chemokinesis observed in this work is due to variation in the motor's velocity and effective diffusivity as a function of the fuel and salt concentration. Static concentration fields are generated in microfluidic devices fabricated with porous walls. The development of nanoscale particles that swim autonomously and collectively in chemical concentration gradients can be leveraged for a wide range of applications such as directed drug delivery, self-healing materials, and environmental remediation.
ContributorsWheat, Philip Matthew (Author) / Posner, Jonathan D (Thesis advisor) / Phelan, Patrick (Committee member) / Chen, Kangping (Committee member) / Buttry, Daniel (Committee member) / Calhoun, Ronald (Committee member) / Arizona State University (Publisher)
Created2011
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
Description
In this thesis the performance of a Hybrid AC System (HACS) is modeled and optimized. The HACS utilizes solar photovoltaic (PV) panels to help reduce the demand from the utility during peak hours. The system also includes an ice Thermal Energy Storage (TES) tank to accumulate cooling energy during off-peak hours. The AC runs continuously on grid power during off-peak hours to generate cooling for the house and to store thermal energy in the TES. During peak hours, the AC runs on the power supplied from the PV, and cools the house along with the energy stored in the TES. A higher initial cost is expected due to the additional components of the HACS (PV and TES), but a lower operational cost due to higher energy efficiency, energy storage and renewable energy utilization. A house cooled by the HACS will require a smaller size AC unit (about 48% less in the rated capacity), compared to a conventional AC system. To compare the cost effectiveness of the HACS with a regular AC system, time-of-use (TOU) utility rates are considered, as well as the cost of the system components and the annual maintenance. The model shows that the HACS pays back its initial cost of $28k in about 6 years with an 8% APR, and saves about $45k in total cost when compared to a regular AC system that cools the same house for the same period of 6 years.
ContributorsJubran, Sadiq (Author) / Phelan, Patrick (Thesis advisor) / Calhoun, Ronald (Committee member) / Trimble, Steve (Committee member) / Arizona State University (Publisher)
Created2011
Description
As the demand for power increases in populated areas, so will the demand for water. Current power plant technology relies heavily on the Rankine cycle in coal, nuclear and solar thermal power systems which ultimately use condensers to cool the steam in the system. In dry climates, the amount of water to cool off the condenser can be extremely large. Current wet cooling technologies such as cooling towers lose water from evaporation. One alternative to prevent this would be to implement a radiative cooling system. More specifically, a system that utilizes the volumetric radiation emission from water to the night sky could be implemented. This thesis analyzes the validity of a radiative cooling system that uses direct radiant emission to cool water. A brief study on potential infrared transparent cover materials such as polyethylene (PE) and polyvinyl carbonate (PVC) was performed. Also, two different experiments to determine the cooling power from radiation were developed and run. The results showed a minimum cooling power of 33.7 W/m2 for a vacuum insulated glass system and 37.57 W/m2 for a tray system with a maximum of 98.61 Wm-2 at a point when conduction and convection heat fluxes were considered to be zero. The results also showed that PE proved to be the best cover material. The minimum numerical results compared well with other studies performed in the field using similar techniques and materials. The results show that a radiative cooling system for a power plant could be feasible given that the cover material selection is narrowed down, an ample amount of land is available and an economic analysis is performed proving it to be cost competitive with conventional systems.
ContributorsOvermann, William (Author) / Phelan, Patrick (Thesis advisor) / Trimble, Steve (Committee member) / Taylor, Robert (Committee member) / Arizona State University (Publisher)
Created2011
Description
A low cost expander, combustor device that takes compressed air, adds thermal energy and then expands the gas to drive an electrical generator is to be designed by modifying an existing reciprocating spark ignition engine. The engine used is the 6.5 hp Briggs and Stratton series 122600 engine. Compressed air that is stored in a tank at a particular pressure will be introduced during the compression stage of the engine cycle to reduce pump work. In the modified design the intake and exhaust valve timings are modified to achieve this process. The time required to fill the combustion chamber with compressed air to the storage pressure immediately before spark and the state of the air with respect to crank angle is modeled numerically using a crank step energy and mass balance model. The results are used to complete the engine cycle analysis based on air standard assumptions and air to fuel ratio of 15 for gasoline. It is found that at the baseline storage conditions (280 psi, 70OF) the modified engine does not meet the imposed constraints of staying below the maximum pressure of the unmodified engine. A new storage pressure of 235 psi is recommended. This only provides a 7.7% increase in thermal efficiency for the same work output. The modification of this engine for this low efficiency gain is not recommended.
ContributorsJoy, Lijin (Author) / Trimble, Steve (Thesis advisor) / Davidson, Joseph (Committee member) / Phelan, Patrick (Committee member) / Arizona State University (Publisher)
Created2011
Description
Passive cooling designs & technologies offer great promise to lower energy use in buildings. Though the working principles of these designs and technologies are well understood, simplified tools to quantitatively evaluate their performance are lacking. Cooling by night ventilation, which is the topic of this research, is one of the well known passive cooling technologies. The building's thermal mass can be cooled at night by ventilating the inside of the space with the relatively lower outdoor air temperatures, thereby maintaining lower indoor temperatures during the warmer daytime period. Numerous studies, both experimental and theoretical, have been performed and have shown the effectiveness of the method to significantly reduce air conditioning loads or improve comfort levels in those climates where the night time ambient air temperature drops below that of the indoor air. The impact of widespread adoption of night ventilation cooling can be substantial, given the large fraction of energy consumed by air conditioning of buildings (about 12-13% of the total electricity use in U.S. buildings). Night ventilation is relatively easy to implement with minimal design changes to existing buildings. Contemporary mathematical models to evaluate the performance of night ventilation are embedded in detailed whole building simulation tools which require a certain amount of expertise and is a time consuming approach. This research proposes a methodology incorporating two models, Heat Transfer model and Thermal Network model, to evaluate the effectiveness of night ventilation. This methodology is easier to use and the run time to evaluate the results is faster. Both these models are approximations of thermal coupling between thermal mass and night ventilation in buildings. These models are modifications of existing approaches meant to model dynamic thermal response in buildings subject to natural ventilation. Effectiveness of night ventilation was quantified by a parameter called the Discomfort Reduction Factor (DRF) which is the index of reduction of occupant discomfort levels during the day time from night ventilation. Daily and Monthly DRFs are calculated for two climate zones and three building heat capacities. It is verified that night ventilation is effective in seasons and regions when day temperatures are between 30 oC and 36 oC and night temperatures are below 20 oC. The accuracy of these models may be lower than using a detailed simulation program but the loss in accuracy in using these tools more than compensates for the insights provided and better transparency in the analysis approach and results obtained.
ContributorsEndurthy, Akhilesh Reddy (Author) / Reddy, T Agami (Thesis advisor) / Phelan, Patrick (Committee member) / Addison, Marlin (Committee member) / Arizona State University (Publisher)
Created2011
Description
While much effort in Stirling engine development is placed on making the high-temperature region of the Stirling engine warmer, this research explores methods to lower the temperature of the cold region by improving heat transfer in the cooler. This paper presents heat transfer coefficients obtained for a Stirling engine heat exchanger with oscillatory flow. The effects of oscillating frequency and input heat rate on the heat transfer coefficients are evaluated and details on the design and development of the heat exchanger test apparatus are also explained. Featured results include the relationship between overall heat transfer coefficients and oscillation frequency which increase from 21.5 to 46.1 Wm-2K-1 as the oscillation frequency increases from 6.0 to 19.3 Hz. A correlation for the Nusselt number on the inside of the heat exchange tubes in oscillatory flow is presented in a concise, dimensionless form in terms of the kinetic Reynolds number as a result of a statistical analysis. The test apparatus design is proven to be successful throughout its implementation due to the usefulness of data and clear trends observed. The author is not aware of any other publicly-available research on a Stirling engine cooler to the extent presented in this paper. Therefore, the present results are analyzed on a part-by-part basis and compared to segments of other research; however, strong correlations with data from other studies are not expected. The data presented in this paper are part of a continuing effort to better understand heat transfer properties in Stirling engines as well as other oscillating flow applications.
ContributorsEppard, Erin (Author) / Phelan, Patrick (Thesis advisor) / Trimble, Steve (Committee member) / Calhoun, Ronald (Committee member) / Arizona State University (Publisher)
Created2011
Description
Processed pyro-gel contains castor oil with solid component of boehmite (Al-OOH). The pyro-gel is synthesized by heat to convert boehmite to gamma-Al2O3 and to a certain extent alpha-Al2O3 nano-particles and castor oil into carbon residue. The effect of heat on pyro-gel is analyzed in a series of experiments using two burning chambers with the initial temperature as the main factor. The obtained temperature distribution profiles are studied and it is observed that the gel behaves very close to the theoretical prediction under heat. The carbon residue with Al2O3 is then processed for twelve hours and then analyzed to obtain the pore distribution of the Al2O3 nano-particles and the relation between the pore volume and the pre-heat temperature is analyzed. The obtained pore distribution shows the pore volume of Al2O3 nano-particles has direct relation to the pre-heat temperature. The experimental process involving the cylindrical reactor is simulated by using a finite rate chemistry eddy-dissipation model in a non-premixed and a porous mesh. The temperature distribution profile of the processed gel for both the meshes is obtained and a comparison is done with the data obtained in the experimental analysis. The temperature distribution obtained from the simulations show they follow a very similar profile to the temperature distribution obtained from experimental analysis, thus confirming the accuracy of both the models. The variation in numerical values between the experimental and simulation analysis is discussed. A physical model is proposed to determine the pore formation based on the temperature distribution obtained from experimental analysis and simulation.
ContributorsSagi, Varun (Author) / Lee, Taewoo (Thesis advisor) / Phelan, Patrick (Committee member) / Chen, Kangping (Committee member) / Arizona State University (Publisher)
Created2010