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Mountain Scholar

Mountain Scholar is an open access repository service that collects, preserves, and provides access to digitized library collections and other scholarly and creative works from Colorado State University and the University Press of Colorado. It also serves as a dark archive for the Open Textbook Library.

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Recent Submissions

  • Item type:Item, Access status: Open Access ,
    The role of developmental experience in the career development of fire chiefs in the United States
    (2007) Jones, Warren D., author; Feller, Richard, advisor; Grosse, Larry, advisor; Banning, James, committee member; Littrell, John, committee member
    This study examined the career experiences of fire chiefs. It goes beyond an examination of the traditional technical competencies and time in position elements of a fire chief's career development by focusing on specific experiences that produced change in their leadership and management behaviors. These are called developmental experiences. The audience for this study is fire chiefs, those that aspire to this position and other fire service professionals seeking to better understand the career development of fire chiefs. The research approach used was qualitative and the methodology was multiple case study using narrative analysis technique. Developmental experience has emerged as an experiential learning strategy that improves a leader's ability to adapt to and positively influence organizational success under conditions of change. The literature indicates that positive changes in leadership and management behaviors derived from developmental experience come from challenging on-the-job experiences, which result in personal learning and changes in leadership and management behaviors. The results of this study indicate that the 14 participants described nine common themes that met the definition of developmental experience in accordance with the Center for Creative Leadership developmental experience model. The participants furthermore described 26 examples of personal learning in seven developmental experience themes and 23 examples of changes in leadership and management behavior in four developmental experience themes. Two developmental experience themes, (1) the first fire chief and (2) hardship produced the strongest learning and change in leadership and management behaviors. The results of this study challenge the conventional fire service career development systems in place today. It recommends that (1) developmental experience opportunities be made available to fire service personnel much earlier in their careers, especially for those who display leadership talent; (2) that more focus be placed on leadership and management experience in the early career; (3) that learning from hardship be incorporated into leadership development; and (4) that more opportunities be provided to learn political skills outside the confines of the internally focused fire service world.
  • Item type:Item, Access status: Open Access ,
    The dual roles of DNA-PKcs, NBS1, and TRF2 proteins in DNA repair and telomere end-capping
    (2007) Williams, Eli Stowe, author; Ullrich, Robert L., advisor; Bailey, Susan M., committee member; Bedford, Joel S., committee member; Cornforth, Michael N., committee member; Ranu, Rajinder S., committee member
    Telomeres are the nucleoprotein structures located at the ends of linear chromosomes that distinguish naturally occurring chromosome ends from DNA double-strand breaks (DSBs). The ability to properly distinguish telomeres as such is critical to long term cellular survival as failure to do so can result in genomic instability and favor the progression towards cancer, cellular senescence or apoptosis. Cells unable to efficiently cap their chromosome ends are recognized cytogenetically as dicentric chromosomes which maintain telomere sequence at the point of fusion (telomere fusions). It has been shown that deficiencies in Telomere Repeat Binding Factor 2 (TRF2), a telomere binding protein, results in massive telomere dysfunction characterized by high numbers of telomere fusions, thus establishing TRF2 as an essential telomere end-capping protein. Surprisingly, TRF2 is rapidly and abundantly recruited to laser microbeam-induced damage, implicating this telomere protein in the early cellular response to DNA damage. We demonstrate that TRF2 is, in fact, not recruited to localized IR- or UV-induced DNA damage, arguing against a role for TRF2 in the DNA damage response, as well as illustrating important differences between damage produced by laser microbeams, as compared to other types of radiation. An abundance of evidence, however, confirms significant overlap between DNA repair proteins and telomeres. Most strikingly, deficiencies of key proteins involved in the cellular response to DNA damage, particularly the catalytic subunit of the DNA dependent protein kinase (DNA-PKcs), also lead to the formation of telomere fusions, suggesting a role for these proteins in telomere end-capping. We show here that auto-phosphorylation of DNA-PKcs is critical for its function at telomeres, as well as establish the utility of the BALB/c mouse in investigating the contribution of telomere dysfunction in driving genomic instability. NBS1, a homologous recombination (HR) protein critical in the cell's initial response to damage, has also been implicated in telomere end-capping. We demonstrate that cells depleted of NBS1 show an increase in telomere associations. Overall, this study helps to further clarify the complex interplay between DNA repair proteins and telomeres.
  • Item type:Item, Access status: Open Access ,
    Loss analysis and loss based seismic design for woodframe structures
    (2007) Pei, Shiling, author; van de Lindt, John W., advisor; Criswell, Marvin E., committee member; Heyliger, Paul R., committee member; Hoeting, Jennifer A., committee member
    Light frame wood structures serve as the vast majority of construction type for residential structures throughout North America. This type of structure utilizes mainly wood shearwalls and a joist-sheathing floor system to resist the live and dead loads. Compared to concrete and steel structures, light frame wood structures typically have a relatively low construction cost, i.e. overall value. However, recent earthquake surveys and studies revealed that the costs involved in repairing these structures after earthquakes can be quite significant even when the structure survives the event without collapse. As a result of the large stock of residential construction in the U.S., earthquake-induced losses for this type of structure could have a detrimental financial impact on both the building owner and the community as a whole. During the 1994 Northridge earthquake in California, the economic loss directly connected with residential wood structures was more than $20 billion, and provides the impetus for this study. The limitation of current woodframe structural design philosophy is that it focuses only on life safety and does not address providing damage-limitations. The idea that financial losses for a structure during an earthquake should be addressed during the design stage leads to loss-based seismic design, which falls under a more comprehensive framework, performance-based seismic design (PBSD). The objective of this study is twofold. The first objective is to develop a method to establish a probabilistic model for earthquake-induced loss of existing or newly designed wood frame structures for a given period of time into the future; then this method is to be incorporated into a performance-based seismic design framework to conduct loss-based design/optimization for wood frame structures. The first objective involves the modeling of the structural behavior during earthquake loading, financial loss estimation of the structures, and probabilistic modeling/simulation of the seismic hazard. An improved non-linear structural model for light frame wood structures was proposed and used in the structural analysis. A vulnerability based loss estimation framework was developed to incorporate multiple uncertainty sources which contribute to financial losses. Bayesian techniques were used in the modeling of the framework elements in order to include as much usable information as possible. An alternative loss estimation procedure based on Monte-Carlo simulation was also proposed with the ability to consider more realistic situations such as damage accumulation and structural degradation. The results of the long-term earthquake-induced loss were obtained in the form of simulated sample pools conditional on time span. Based on the results from the first objective, simplified loss estimation in the design stage was introduced in order to obtain the vulnerability target for loss-based optimization. This optimization procedure was later used to implement loss-based design in the numerical examples. The most significant anticipated contribution of this study to the woodframe design and research communities will be the development of a long-term seismic induced loss estimation framework/procedure for woodframe structures that enables loss-based design and evaluations. Although this procedure will only be applied to woodframe structures in this dissertation, the general solution can also be used to analyze other structure types provided the necessary details are addressed. The automated analysis package developed in this study will essentially be a practical implementation of the performance-based seismic design (PBSD) concept for most commonly constructed residential structures (in North America). Other contributions will include a new formulation for the hysteretic models for wood shearwalls, a performance-based seismic design procedure for woodframe residential buildings, and a generalized user-friendly woodframe building seismic analysis tool package for the research community.
  • Item type:Item, Access status: Open Access ,
    Evaluation and characterization of tuberculosis serodiagnostic biomarkers
    (2007) Sartain, Mark Jonathan, author; Belisle, John T., advisor; Curthoys, Norman P., committee member; Reardon, Kenneth F., committee member; Schweizer, Herbert P., committee member; Slayden, Richard A., committee member
    Detection of the antibody response has the potential to provide early and sensitive diagnosis of infection and disease, a critical element of tuberculosis control. The objective of this study was to discover and evaluate Mycobacterium tuberculosis antigens with protein microarray technology. Techniques were established for separation of native M. tuberculosis cytosol and culture filtrate proteins, resulting in 960 protein fractions that were used to generate protein microarrays. Evaluation of serological reactivity from 42 patients in three tuberculosis disease states and healthy purified-protein-derivative positive individuals demonstrated distinct reactivity profiles. Identification of antigens within the reactive fractions yielded eleven products recognized by both cavitary and noncavitary TB patients, and four proteins (HspX, MPT64, PstS1, and TrxC) specific to cavitary tuberculosis patients. Moreover, this approach identified four novel B cell antigens (BfrB, LppZ, SodC, and TrxC) of human tuberculosis, and the seroreactivity of these antigens was validated with more conventional techniques. SodC is one of two superoxide dismutases produced by M. tuberculosis and was previously shown to contribute to virulence. SodC is also a putative lipoprotein and like other sec-translocated mycobacterial proteins it was suggested to be modified with glycosyl residues. The objective of this study was to define the sites and extent of SodC glycosylation. An approach was developed that combined site-directed mutagenesis, lectin binding, and mass spectrometry. Six O-glycosylated residues within a 13 amino acid region were identified near the N-terminus. Each residue was modified with one to three hexosyl units, and the most dominant SodC glycoform was modified with nine hexosyl units. In addition to O-glycosylation of threonine residues, this study provides the first evidence of serine O-glycosylation in mycobacteria. When combined with bioinformatic analyses, the clustering of Oglycosylation appeared to occur in a region of SodC with a disordered structure and not in regions important to the enzymatic activity of SodC. The use of recombinant amino acid substitutions to alter glycosylation sites provided further evidence that glycosylation influences proteolytic processing and ultimately positioning of cell wall proteins.
  • Item type:Item, Access status: Open Access ,
    The role of immunity to mosquito salivary proteins in the pathogenesis of flaviviruses (Flavivirus:Flaviviridae)
    (2007) Machain Williams, Carlos Ignacio, author; Blair, Carol D., advisor; Beaty, Barry J., committee member; Bowen, R. A., committee member; Olson, Kenneth E., committee member; Zeidner, Nordin, committee member
    Mosquito salivary proteins (MSP) have been implicated in the enhancement of arthropod-borne virus pathogenesis. Dengue viruses (DENV) are emerging pathogens transmitted mainly by Aedes aegypti mosquitoes. West Nile virus (WNV) is also considered an emerging pathogen that recently has been introduced into the Western Hemisphere. WNV is transmitted by mosquitoes from Culex species. Mosquito salivary proteins were obtained by a novel technique involving collection in a salivation buffer and concentration by trichloroacetic acid (TCA) precipitation. Immunoreactive proteins from Cx. tarsalis and Ae. aegypti were proposed to be related to viral pathogenesis. In a retrospective study in Thai patients who had DENV2 secondary infections with disease severity ranging from dengue fever (DF) to dengue hemorrhagic fever (DHF), it was found that the proportion of patients with DF who had antibodies reacting against the 36 kDa Ae. aegypti MSP (71.4%) was significantly higher compared to those who had DHF (62%). In contrast, a higher proportion (36%) of DHF patients reacted to an Ae. aegypti protein identified as apyrase than those with anti-apyrase antibodies presenting with DF (14.3%). To investigate the potential role of immune response to MSP in virus pathogenesis, NIH-Swiss mice were immunized with Cx. tarsalis mosquito salivary gland homogenates followed by challenge by WNV-infected mosquitoes. In vaccinated mice, viremia was first detected by RT-PCR 48 hours after mosquito bite; in contrast, the unvaccinated control group presented viremia as early as 24 hours after mosquito challenge. WNV RNA was detected in brains of unvaccinated mice at day four post challenge; in contrast no viral RNA was detected by RT-PCR in the brains of vaccinated mice by day four. By day eight post challenge all the mice had viral RNA in their brains detectable by RT-PCR. The anti-WNV antibody titers were also higher in the vaccinated group than in unvaccinated mice (P<0.0008). When Th1/Th2 specific cytokines were analyzed by Q-RT-PCR, IL-2, IFNγ and TNFα were increased in the vaccinated group. In contrast, IL-4 was up-regulated in the unvaccinated group.