Matching Items (151)
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
This dissertation creates models of past potential vegetation in the Southern Levant during most of the Holocene, from the beginnings of farming through the rise of urbanized civilization (12 to 2.5 ka BP). The time scale encompasses the rise and collapse of the earliest agrarian civilizations in this region. The archaeological record suggests that increases in social complexity were linked to climatic episodes (e.g., favorable climatic conditions coincide with intervals of prosperity or marked social development such as the Neolithic Revolution ca. 11.5 ka BP, the Secondary Products Revolution ca. 6 ka BP, and the Middle Bronze Age ca. 4 ka BP). The opposite can be said about periods of climatic deterioration, when settled villages were abandoned as the inhabitants returned to nomadic or semi nomadic lifestyles (e.g., abandonment of the largest Neolithic farming towns after 8 ka BP and collapse of Bronze Age towns and cities after 3.5 ka BP during the Late Bronze Age). This study develops chronologically refined models of past vegetation from 12 to 2.5 ka BP, at 500 year intervals, using GIS, remote sensing and statistical modeling tools (MAXENT) that derive from species distribution modeling. Plants are sensitive to alterations in their environment and respond accordingly. Because of this, they are valuable indicators of landscape change. An extensive database of historical and field gathered observations was created. Using this database as well as environmental variables that include temperature and precipitation surfaces for the whole study period (also at 500 year intervals), the potential vegetation of the region was modeled. Through this means, a continuous chronology of potential vegetation of the Southern Levantwas built. The produced paleo-vegetation models generally agree with the proxy records. They indicate a gradual decline of forests and expansion of steppe and desert throughout the Holocene, interrupted briefly during the Mid Holocene (ca. 4 ka BP, Middle Bronze Age). They also suggest that during the Early Holocene, forest areas were extensive, spreading into the Northern Negev. The two remaining forested areas in the Northern and Southern Plateau Region in Jordan were also connected during this time. The models also show general agreement with the major cultural developments, with forested areas either expanding or remaining stable during prosperous periods (e.g., Pre Pottery Neolithic and Middle Bronze Age), and significantly contracting during moments of instability (e.g., Late Bronze Age).
ContributorsSoto-Berelov, Mariela (Author) / Fall, Patricia L. (Thesis advisor) / Myint, Soe (Committee member) / Turner, Billie L (Committee member) / Falconer, Steven (Committee member) / Arizona State University (Publisher)
Created2011
Description
Woody plant encroachment is a worldwide phenomenon linked to water availability in semiarid systems. Nevertheless, the implications of woody plant encroachment on the hydrologic cycle are poorly understood, especially at the catchment scale. This study takes place in a pair of small semiarid rangeland undergoing the encroachment of Prosopis velutina Woot., or velvet mesquite tree. The similarly-sized basins are in close proximity, leading to equivalent meteorological and soil conditions. One basin was treated for mesquite in 1974, while the other represents the encroachment process. A sensor network was installed to measure ecohydrological states and fluxes, including precipitation, runoff, soil moisture and evapotranspiration. Observations from June 1, 2011 through September 30, 2012 are presented to describe the seasonality and spatial variability of ecohydrological conditions during the North American Monsoon (NAM). Runoff observations are linked to historical changes in runoff production in each watershed. Observations indicate that the mesquite-treated basin generates more runoff pulses and greater runoff volume for small rainfall events, while the mesquite-encroached basin generates more runoff volume for large rainfall events. A distributed hydrologic model is applied to both basins to investigate the runoff threshold processes experienced during the NAM. Vegetation in the two basins is classified into grass, mesquite, or bare soil using high-resolution imagery. Model predictions are used to investigate the vegetation controls on soil moisture, evapotranspiration, and runoff generation. The distributed model shows that grass and mesquite sites retain the highest levels of soil moisture. The model also captures the runoff generation differences between the two watersheds that have been observed over the past decade. Generally, grass sites in the mesquite-treated basin have less plant interception and evapotranspiration, leading to higher soil moisture that supports greater runoff for small rainfall events. For large rainfall events, the mesquite-encroached basin produces greater runoff due to its higher fraction of bare soil. The results of this study show that a distributed hydrologic model can be used to explain runoff threshold processes linked to woody plant encroachment at the catchment-scale and provides useful interpretations for rangeland management in semiarid areas.
ContributorsPierini, Nicole A (Author) / Vivoni, Enrique R (Thesis advisor) / Wang, Zhi-Hua (Committee member) / Mays, Larry W. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Two critical limitations for hyperspatial imagery are higher imagery variances and large data sizes. Although object-based analyses with a multi-scale framework for diverse object sizes are the solution, more data sources and large amounts of testing at high costs are required. In this study, I used tree density segmentation as the key element of a three-level hierarchical vegetation framework for reducing those costs, and a three-step procedure was used to evaluate its effects. A two-step procedure, which involved environmental stratifications and the random walker algorithm, was used for tree density segmentation. I determined whether variation in tone and texture could be reduced within environmental strata, and whether tree density segmentations could be labeled by species associations. At the final level, two tree density segmentations were partitioned into smaller subsets using eCognition in order to label individual species or tree stands in two test areas of two tree densities, and the Z values of Moran's I were used to evaluate whether imagery objects have different mean values from near segmentations as a measure of segmentation accuracy. The two-step procedure was able to delineating tree density segments and label species types robustly, compared to previous hierarchical frameworks. However, eCognition was not able to produce detailed, reasonable image objects with optimal scale parameters for species labeling. This hierarchical vegetation framework is applicable for fine-scale, time-series vegetation mapping to develop baseline data for evaluating climate change impacts on vegetation at low cost using widely available data and a personal laptop.
ContributorsLiau, Yan-ting (Author) / Franklin, Janet (Thesis advisor) / Turner, Billie (Committee member) / Myint, Soe (Committee member) / Arizona State University (Publisher)
Created2013
Description
Land transformation under conditions of rapid urbanization has significantly altered the structure and functioning of Earth's systems. Land fragmentation, a characteristic of land transformation, is recognized as a primary driving force in the loss of biological diversity worldwide. However, little is known about its implications in complex urban settings where interaction with social dynamics is intense. This research asks: How do patterns of land cover and land fragmentation vary over time and space, and what are the socio-ecological drivers and consequences of land transformation in a rapidly growing city? Using Metropolitan Phoenix as a case study, the research links pattern and process relationships between land cover, land fragmentation, and socio-ecological systems in the region. It examines population growth, water provision and institutions as major drivers of land transformation, and the changes in bird biodiversity that result from land transformation. How to manage socio-ecological systems is one of the biggest challenges of moving towards sustainability. This research project provides a deeper understanding of how land transformation affects socio-ecological dynamics in an urban setting. It uses a series of indices to evaluate land cover and fragmentation patterns over the past twenty years, including land patch numbers, contagion, shapes, and diversities. It then generates empirical evidence on the linkages between land cover patterns and ecosystem properties by exploring the drivers and impacts of land cover change. An interdisciplinary approach that integrates social, ecological, and spatial analysis is applied in this research. Findings of the research provide a documented dataset that can help researchers study the relationship between human activities and biotic processes in an urban setting, and contribute to sustainable urban development.
ContributorsZhang, Sainan (Author) / Boone, Christopher G. (Thesis advisor) / York, Abigail M. (Committee member) / Myint, Soe (Committee member) / Arizona State University (Publisher)
Created2013
Description
Cancer is one of the most serious global diseases. We have focused on cancer immunoprevention. My thesis projects include developing a prophylactic primary and metastatic cancer vaccines, early cancer detection and investigation of genes involved in tumor development. These studies were focused on frame-shift (FS) antigens. The FS antigens are generated by genomic mutations or abnormal RNA processing, which cause a portion of a normal protein to be translated out of frame. The concept of the prophylactic cancer vaccine is to develop a general cancer vaccine that could prevent healthy people from developing different types of cancer. We have discovered a set of cancer specific FS antigens. One of the FS candidates, structural maintenance of chromosomes protein 1A (SMC1A) FS, could start to accumulate at early stages of tumor and be specifically exposed to the immune system by tumor cells. Prophylactic immunization with SMC1A-FS could significantly inhibit primary tumor development in different murine tumor models and also has the potential to inhibit tumor metastasis. The SMC1A-FS transcript was detected in the plasma of the 4T1/BALB/c mouse tumor model. The tumor size was correlated with the transcript ratio of the SMC1A-FS verses the WT in plasma, which could be measured by regular RT-PCR. This unique cancer biomarker has a practical potential for a large population cancer screen, as well as clinical tumor monitoring. With a set of mimotope peptides, antibodies against SMC1A-FS peptide were detected in different cancer patients, including breast cancer, pancreas cancer and lung cancer with a 53.8%, 56.5% and 12.5% positive rate respectively. This suggested that the FS antibody could be a biomarker for early cancer detection. The characterization of SMC1A suggested that: First, the deficiency of the SMC1A is common in different tumors and able to promote tumor initiation and development; second, the FS truncated protein may have nucleolus function in normal cells. Mis-control of this protein may promote tumor development. In summary, we developed a systematic general cancer prevention strategy through the variety immunological and molecular methods. The results gathered suggest the SMC1A-FS may be useful for the detection and prevention of cancer.
ContributorsShen, Luhui (Author) / Johnston, Stephen Albert (Thesis advisor) / Chang, Yung (Committee member) / Miller, Laurence (Committee member) / Sykes, Kathryn (Committee member) / Jacobs, Bertram (Committee member) / Arizona State University (Publisher)
Created2012
Description
Recombinant protein expression is essential to biotechnology and molecular medicine, but facile methods for obtaining significant quantities of folded and functional protein in mammalian cell culture have been lacking. Here I describe a novel 37-nucleotide in vitro selected sequence that promotes unusually high transgene expression in a vaccinia driven cytoplasmic expression system. Vectors carrying this sequence in a monocistronic reporter plasmid produce >1,000-fold more protein than equivalent vectors with conventional vaccinia promoters. Initial mechanistic studies indicate that high protein expression results from dual activity that impacts both transcription and translation. I suggest that this motif represents a powerful new tool in vaccinia-based protein expression and vaccine development technology.
ContributorsFlores, Julia Anne (Author) / Chaput, John C (Thesis advisor) / Jacobs, Bertram (Committee member) / LaBaer, Joshua (Committee member) / Arizona State University (Publisher)
Created2012
Description
Vaccinia virus (VV) is a prototype virus of the Orthopox viruses. The large dsDNA virus composed of 200kbp genome contains approximately 200 genes and replicates entirely in the cytosol. Since its use as a live vaccine against smallpox that leads to the successful eradication of smallpox, Vaccinia has been intensely studied as a vaccine vector since the large genome allows for the insertion of multiple genes. It is also studied as a molecular tool for gene therapy and gene functional study. Despite its success as a live vaccine, the vaccination causes some mild to serious bur rare adverse events in vaccinees such as generalized Vaccinia and encepharitis. Therefore, identification of virulence genes and removal of these genes to create a safer vaccine remain an important tasks. In this study, the author seeks to elucidate the possible relationship between immune evading proteins E3 and B19. VV did not allow double deletions of E3 and B19, indicating the existence of a relationship between the two genes.
ContributorsBarclay, Shizuka (Author) / Jacobs, Bertram (Thesis director) / Ugarova, Tatiana (Committee member) / Kibler, Karen (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
In the United States, a dispute has arisen over the safety and need for vaccination, particularly in regard to compulsory vaccination laws. New outlets and social media sites publish countless reports about the dangers of vaccines or of known adverse reactions as well as imagined or unproven worries. Individuals' rights to choose to get vaccinated or allow their children to be vaccinated comes to direct conflict with measures needed to protect communities from preventable viral diseases. The controversy surrounding vaccines is not new, nor necessarily are the fundamental reasons for skepticism. Looking back through the history of vaccines as a medical tool, the evolution of the controversy can be observed taking place with each new historical context, scientific development, and social conditions. Despite scientific research and assurances of vaccine safety, opposition and unease about vaccination appear to take Looking individually at the development and distribution of the smallpox (variola virus), polio (poliovirus) and human papilloma virus(HPV) vaccines, concerns regarding the violation of personal rights, safety of vaccines themselves, and social stigmas and connotations surrounding vaccines can be seen to evolve and change. Due to the way doubt can manifest in different ways over time, it may be impossible to fully end the vaccine debate. However, nderstanding the sociological factors behind anti-vaccine sentiment may allow healthcare professionals to work with concerned people with a particular care to address these visceral and sometimes irrational fears surrounding vaccination.
ContributorsStevens, Luke Christian (Author) / Jacobs, Bertram (Thesis director) / Washo-Krupps, Delon (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
Utilizing a compilation of existing literature, theory and current praxis, a clear case for instituting a needle exchange in Maricopa County is visible.. Research on HIV rates are consulted to establish a foundation for understanding the value of needle exchange programs nationally and in Maricopa County. Case studies on existing needle exchange efficacy are also used to support the proposal and outline the success of needle exchanges in reducing rates of infection.
ContributorsGuntermann, Christel Young Shin (Author) / Jacobs, Bertram (Thesis director) / Jackson, Danielle (Committee member) / Taylor, Emily (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / School of Community Resources and Development (Contributor)
Created2013-05