▼ In this thesis we address the problem of mining association rules from databases containing quantitative attributes. Values of many quantitative attributes are distributed as strong concentrations in a few narrow regions across a very wide complete range of possible values. Intervals of equal width for such domains are not meaningful and may miss out on many peculiarities of data. Our methodology consists of a two phase approach. The first phase determines the boundaries around most meaningful intervals of the value range. We seek to maximize the information content of the choice of the selected initial interval boundaries. The second phase executes the association rule mining algorithm which uses these interval boundaries and modifies them, if needed, to determine rules with specified support and confidence levels. The set of generated rules is then examined to keep only the most specific versions by deleting their more general versions from the set. We have run tests with this algorithm using a network traffic database and the results obtained are presented in the thesis. We also contrast the benefits of this approach with the one in which we may start with uniform width, fixed size, intervals for a quantitative attribute. Advisors/Committee Members: Bhatnagar, Raj.

▼ Background: There is compelling evidence in western literature that stress during pregnancy negatively affects birth outcomes resulting in preterm birth (PT) (<37 weeks gestation) and low birth weight (LBW) (<2500g). Life events have been recognized as intervening factors that create stress. There is no evidence that pregnant women in Arabic-speaking countries are exposed to the same stressful life events as women in Western countries, and that they perceive life events to be equally problematic. Studying life events as a risk factor for PT birth and LBW in Arabic-speaking women is limited by the lack of culturally sensitive instruments; there is no known questionnaire that measures life events in this population, which makes this study innovative. The purpose of this study is to modify and validate the Life Events Questionnaire (LEQ) (Norbeck, 1984) for use with Arabic-speaking pregnant women. Theoretical Framework: The conceptual model for this study was developed from stress and coping work by Lazarus and Folkman including ideas about mediating and moderating factors. Method and design: A Convenience sample of 125 pregnant Jordanian women was included in this study. The study used an exploratory sequential mixed method design and was conducted in two phases. The first phases included initial item pool evaluation; translation-back-translation and inclusion and exclusion of items of the LEQ. The second phase was testing the psychometric properties of the Arabic version of LEQ, which included content validity testing, followed by sample development evaluation, predictive validity and convergent validity testing and test-retest reliability. Data collection included a survey to conduct quantitative data and an interview to conduct the qualitative data. Results: Eight new events emerged from the qualitative interviews and combined with 64 existing life events to form the new list of events in the LEQ-A. There was a significant difference in the means of negative scores between pregnant Jordanian women and the means of negative events scores reported in the original LEQ for a sample of western females. The difference was also found in the rating of life events within the same sample of the pregnant Jordanian women. The LEQ-A had an excellent Content Validity Index (CVI) and proved to have adequate convergent and predictive validity as well as test retest reliability when tested in pregnant Jordanian women. Conclusion: The original LEQ content was not inclusive to all events that might be experienced in Arabic-speaking pregnant women, which reinforced the significance of this study and the choice of the exploratory sequential mixed method as the design to accomplish the study objectives. The outcome of this study was a culturally sensitive LEQ-A, which is expected to have a significant contribution to stress, and coping research and the development of interventions to improve birth outcomes in the Arab countries. Advisors/Committee Members: Beery, Theresa.

▼ Bounded Model Checking (BMC) is a formal method of verifying Very Large Scale Integrated (VLSI) circuits. It shows violation of a given circuit property by finding a counter-example to the property along bounded state paths of the circuit. The BMC problem is inherently NP-complete and is traditionally formulated to a boolean SATisfiability (SAT) problem, which is subsequently solved by a SAT solver. Automatic Test Pattern Generation (ATPG), as an alternative to SAT, has already been shown an effective solution to NP-complete problems in many computer-aided design areas. In the field of BMC, ATPG has already achieved promising results for simple properties; its effectiveness for more complicated nested properties, however, remains unknown. This thesis presents the first systematic framework of ATPG-based BMC capable of checking properties in all nested forms on gate level. The negation counterpart to a property is mapped into a structural monitor, which is tailored to a flattened model of the input circuit. A target fault is then injected at the monitor output, and a modified ATPG-based state justification algorithm is used to search a test for this fault. Finding such a test corresponds to formally establishing the property. The framework can easily incorporate any existing ATPG tool with little modification. The proposed framework has been implemented in a computer program called FORMAL, and has been used to check a comprehensive set of properties of GL85 microprocessor and USB 2.0 circuits. Experimental results show that the ATPG-based approach performs better in both capacity and efficiency than the SAT-based techniques, especially for large bounds and for properties that require large search space. Therefore, ATPG-based BMC has been demonstrated an effective supplement to SAT-based BMC in VLSI circuit verification. Advisors/Committee Members: Saab, Daniel G.

▼ The thesis includes two parts. The first part is "Salience, Misperception and Participation in the Security Market." A salient stock has the striking feature to attract investors' more attention but does not necessarily contain more information in its trading than a neglected stock. The information about a salient stock is distributed to investors so broadly that it is beyond individual investors' ability to evaluate correctly. In the first part of this paper investors' misperception of the correlation among their signals leads to short-term momentum and long-term reversal in stock's return, which is consistent with Poterba and Summers (1988). Other implication includes that the arrival of negatively correlated information following several periods when investors' signals are positively correlated, overcorrection occurs. Access costs limit investors' participation in trading in certain classes of stocks. When the participation is determined exogenously, the expected risk premium for both neglected and salient stock increases with participation rate of the neglected stock, investors' risk aversion and the total proportion of investors' initial wealth put in the salient stock, and declines with the total proportion of investors' initial wealth put in the neglected stock. Furthermore, I find that the expected risk premium for the neglected stock is only positively related to its own variance while the expected risk premium for the salient stock is positively associate with both stocks' standard deviation but negatively associate with their correlation. When the participation in trading in the neglected stock is determined endogenously, the expected risk premium for the neglected stock, the salient stock and the market return rises with the square root of the access cost, relative risk aversion and risk free rate.The second part is "Changes of Leverage and Behind Reasoning: Evidence During 1985-1994." Taggart (1985) shows that leverage of Corporate America kept increased from the late 1950s to 1980. I find the weak evidence the leverage of U.S. firms continued to increase until 1993. I investigate two leverage measures: One is the ratio of total liabilities to total assets (TD/TA) and the other the ratio of long-term debt to firm's market value (LD/MV). I document the time series pattern of leverage change. With the leading measure TD/TA the peak year is 1989 while the peak year is 1990 with the leverage measure LD/MV. I also find that although common factors like size have high power in explaining the static magnitude of leverage, they have no power in explaining the leverage change during the sample period. Further investigation of the explaining role of the market for corporate control, antitakeover measures and even the credit crunch argument might be fruitfully promising. Advisors/Committee Members: Buser, Stephen A.

▼ The APC tumor suppressor is a multifunctional protein involved in cell migration, proliferation, differentiation and apoptosis. It is a component of the Wnt signaling pathway and is best known for its ability to down-regulate beta-catenin and consequent effects on transcriptional regulation. Previous work in our laboratory has demonstrated that APC accelerates apoptosis-associated caspase activity independently of transcription, suggesting novel tumor suppressor functions of APC. In the present study, the transcription-independent mechanisms of APC function in apoptosis were investigated. We mapped the APC apoptosis-accelerating region to amino acids 1-760 by testing a series of non-overlapping APC segments. Interestingly, this segment corresponds to a stable group II caspase cleavage product of APC released during apoptosis that includes the amino-terminal amino acids 1-777. Mutation of the APC aspartic acid residue at position 777 in APC to an alanine completely abolished in vitro cleavage of APC by a recombinant group II caspase. This mutation also rendered the full length protein unable to accelerate apoptosis in vitro. A truncated APC protein associated with familial and sporadic colorectal cancer, and unable to accelerate apoptosis in vitro and in vivo, is resistant to group II caspase cleavage. These results demonstrate that cleavage of APC and the subsequent release of an amino-terminal segment are necessary for the transcription-independent mechanism of APC-mediated apoptosis. Additionally, we have elucidated the mechanism of APC-mediated apoptosis by identifying and characterizing a downstream partner of APC in this apoptotic cascade. hTid-1, a homologue of the Drosophila tumor suppressor Tid 56, is an apoptosis modulator predominantly located in mitochondria. We have demonstrated that the amino-terminal segment of APC (APC 1-777) interacts with hTid-1 directly using co-immunoprecipitation, pull-down assays, and immunofluorescence. Immunofluorescence studies and subcellular fractionation show that the APC amino-terminus, exogenous and endogenous, which is released by caspase cleavage during apoptosis, is translocated to the mitochondria. Finally, over-expression of hTid1 partially rescues the HCT116 cells from apoptosis mediated by APC in the absence and presence of exogenous apoptosis stimuli. These data suggest that the amino-terminal segment of APC promotes cell sensitivity to apoptosis through physical and functional interactions with the apoptosis modulator hTid-1. Advisors/Committee Members: Groden, Joanna.

▼ The small heat shock protein (sHsp) with apparent molecular mass of 20 kD (Hsp20) is one of 10 members of the sHsp family. Interestingly, Hsp20 is the only member within this family that contains a consensus peptide motif (RRAS) for protein kinase A (PKA)/protein kinase G (PKG)-dependent phosphorylation at Ser16. Recent studies have shown that enhanced myocardial function was associated with increased expression levels of Hsp20 and its phosphorylation. To further elucidate the possible mechanisms underlying the inotropic effects of Hsp20 and its phosphorylation, as well as their possible roles in ischemia/reperfusion-induced cardiac injury, the present study employed in vitro adenoviral-gene transfer and in vivo transgenic approaches. Our study firstly revealed that acute overexpression of wild-type Hsp20 by adenoviral infection augmented cardiac myocyte contractility, which was further confirmed in Hsp20-transgenic murine hearts (10-fold overexpression). This hypercontractility was associated with increased activation of phospholamban (PLN), evidenced by ≈ 2-fold higher expression of Ser16/Thr17-phosphorylated PLN in Hsp20-transgenic hearts related to non-transgenic controls. Furthermore, co-immunoprecipitation experiments indicated that Hsp20 was associated with type 1 phosphatase (PP1), suggesting Hsp20 may regulate PP1 activity in the mouse heart. Indeed, PP1 activity was significantly reduced in Hsp20-transgenic hearts, compared to non-transgenic hearts. These results imply that Hsp20 positively regulate cardiac function via inhibition of PP1 activity, and its downstream target, PLN phosphorylation. Secondly, to further assess the functional significance of p-Ser16 Hsp20 in vivo and its possible roles in regulation of I/R-induced apoptosis and autophagy, we generated a transgenic mouse model with cardiac-specific expression of a non-phosphorylatable Hsp20 (Hsp20S16A). Our findings indicate that increased Hsp20S16A expression in the heart failed to protect hearts against ex vivo and in vivo I/R injury, accompanied by impaired autophagy and increased apoptosis. Accordingly, pre-treatment of Hsp20S16A hearts with rapamycin, an activator of autophagy, resulted in improvement of functional recovery, compared with saline-treated Hsp20S16A hearts. Thus, Hsp20 and its Ser16 phosphorylation may be involved in the regulation of I/R-induced cardiac autophagy and cell death. Finally, we generated the Hsp20S16D transgenic mouse model, in which Ser16 is replaced with aspartic acid (D), to further explore the in vivo role of p-Ser16 Hsp20. Surprisingly, we observed that contractile parameters were significantly depressed in Hsp20S16D cardiomyocytes. In vivo contractile function was also significantly impaired in TGs, compared with their non-transgenic littermates. In addition, TG mice developed left ventricular (LV) fibrosis at 6 weeks of age, without evidence of LV hypertrophy or dilation, and their life span was markedly shortened (mean age at death: 9 months). Further electron microscopy examination of the hearts revealed that double-membrane autophagosomes were more prominent in TGs. This was associated with increased lysosomal activity, suggesting that autophagosome accumulation was not due to diminished activity of distal lysosomal pathways. Our data indicate that long-term augmentation of cardiac Hsp20 phosphorylation impairs cardiac function, accentuates pathological remodeling and increases autophagic activity, leading to premature death. Collectively, these studies demonstrate that Hsp20 may be a key regulator of Ca2+-cycling through modulation of PP1-PLN activity, and phosphorylation of Hsp20 is important in the regulation of ischemia/reperfusion-induced cardiac autophagy and cell death. Advisors/Committee Members: Kranias, Evangelia.

▼ This study evaluated the effects of using IntelliFill IV Robot system on IV admixture operations at the Division of Pharmacy, Cincinnati Children’s Hospital Medical Center (CCHMC), Cincinnati, Ohio. A before (without IntelliFill) and after (with IntelliFill) study design was applied. One-minute fixed-interval work sampling technique was used in the evaluation. Return of investment (ROI) analysis also was conducted in determining the break-even point. The data analyses include Chi-square test, frequency analysis, and time unit analysis. Total observations of pharmacy staff on IV admixture operations before and after using IntelliFill IV Robot system were 18,228 minutes and 17,231 minutes, respectively. There was a daily time spent saved of 0.42 FTE for pharmacy staff after using the IntelliFill system. The break-even point for using this IntelliFill IV Robot system was a daily workload of 489 syringes for automated IV admixture. IntelliFill IV Robot system could reduce labor utilization on IV admixture operations. Advisors/Committee Members: Lin, Dr. Alex.

▼ Inquiry based teaching has been widespread in the United States as well as in China in the last two decades. It was implemented by many teachers and shown to be effective in both countries. This study examines the extent to which inquiry-based teaching in high-school physics is practiced in US and China through the use of lesson observations and a survey. Nineteen lessons taught by 19 teachers (9 US and 10 Chinese) were observed (N=19). Results show that both US and Chinese teachers know well about the inquiry-based teaching. However, in practice, little inquiry-based teaching was observed in the two countries by different reasons: many of US physics lessons lack rigorous content, while many Chinese lessons failed to include student-centered instruction. Implications of the findings to improve teacher education in both countries are discussed. Advisors/Committee Members: Tosa, Sachiko.

▼ Retroviruses are RNA viruses that replicate through a DNA intermediate, the provirus. Provirus gene expression is dependent on the host machinery. The interplay between the virus and host post-transcriptional armamentarium is complex and the interface with the small RNA pathway has not been characterized. Retroviruses including human immunodeficiency virus type 1 (HIV-1) have evolved multiple strategies to utilize host machinery to execute intricate control of viral gene expression. As introduced in Chapter One of this dissertation, a prominent theme is that viral cis-acting RNA elements interact with cellular RNA binding proteins to modulate balanced viral post-transcriptional expression and sustain virus replication. The work in this dissertation characterized host protein interaction with a post-transcriptional control element (PCE) identified in the 5’ untranslated region (UTR) of at least eight retroviruses that facilitates efficient synthesis of retroviruses structural proteins. In addition, these studies also characterized virus-host interaction presented by the host small RNA pathway, which poses an innate cellular defense against infectious agents and retrotransposons. A growing literature shows that virus-encoded small RNAs and host encoded small RNAs play fundamental roles in animal virus replication. Another focus of the research herein was the characterization of the interaction of HIV-1 with the host small RNA pathway. The results revealed that virus-encoded RNA silencing suppressor activity modulates the activity of host-encoded microRNAs that can attenuate viral translation. Results of Chapter Two demonstrated for the first-time that RNA helicase A (RHA) is the cellular effector protein that operates the PCE/RNA switch. RNA mobility shift assays and RNA co-immunoprecipitation assays revealed that RHA specifically recognizes features of the redundant stem-loop structure of the PCE; the PCE/RHA interaction occurs in both the nucleus and the cytoplasm and is necessary for PCE activity. Downregulation of RHA abolishes PCE activity independently of a change in PCE mRNA stability or its cytoplasmic accumulation. Sucrose gradient analysis showed that RHA facilitates polysome accumulation of PCE-containing retroviral RNA and the cellular junD transcript. JunD is an AP-1 transcription factor and this transcript represents the first example of a cellular PCE/RHA interaction that is necessary for efficient translation. In summary, our results revealed a previously unidentified role for RHA in retrovirus and host cell translation that implicates RHA as an integrative effector of gene expression involved in the continuum of gene expression from transcription to translation. Chapter Three characterizes interplay between the host small RNA pathway and HIV-1. Experiments in plant and animal cell systems demonstrate that HIV-1 Tat regulatory protein exerts RNA silencing suppressor (RSS) activity across the plant and animal kingdoms. HIV-1 Tat and plant virus P19 RSS function similarly to suppress RNA silencing downstream of small RNA maturation. The effect of the host small RNA pathway was characterized by downregulation of the key enzyme of host microRNA biogenesis (Dicer), P19 expression, or by mutation in the conserved double-stranded RNA-binding domain of the Tat RSS. The outcome of the small RNA pathway on HIV-1 replication is attenuation of viral translation. The reversal of HIV-1 translation repression by plant RSS supports the recent finding in Arabidopsis that plant miRNAs operate by inhibition of translation. An implication of our study is that the host small RNA pathway plays a strategic role in the viral accumulation in a newly HIV-1-infected patient. Chapter Four describes results from microRNA microarrays and functional assays that assess the interface between the host small RNA pathway the HIV-1 accessory proteins Vpr and Vif. Profiles of host microRNAs were compared between cells infected with HIV-1 or a strain deficient in vpr/vif. The outcome of this work is a microRNA microarray database that stands a resource to develop testable hypotheses about the role of microRNAs in HIV-1 biology. Protein analysis demonstrated that Vpr/Vif modulates the activity of two miRNAs that downregulate a cellular transcriptional cofactor of Tat. The results of RNA and protein analysis provide an explanation for upregulation of HIV-1 transcription during HIV-1-induced cell cycle arrest. We conclude that modulation of microRNA activity by Vpr and Vif contributes to the positive selection for conservation of vpr in HIV-1 quasispecies in infected patients. In Chapter Five, changes in microRNA profile were evaluated upon infection of human lymphocytes with an HIV-1 strain deficient in Tat RSS activity. Comparative analyses with HIV-1 infection demonstrated that a collection of host microRNAs are modulated by HIV-1 Tat RSS activity and indicated a generalized rather than selective effect of Tat RSS activity on host small RNA activity. Results of ribosomal profile analysis of HIV-1 transfected 293 cells determined that HIV-1 gag RNA accumulates in high molecular weight complexes that co-sediment with puromycin resistant pseudo-polysomes. Pseudo-polysomes are known sites of translational repression by microRNA. The gag transcripts redistribute to polyribosomes upon expression of viral RSS. These results document that the interface between HIV-1 and the host small RNA pathway modulates viral protein synthesis. Perspectives on the experimental results and ideas for future directions are presented in Chapter Six. In conclusion, the work in this dissertation comprehensively characterized specific viral RNA interactions with host protein RNA helicase A and the interaction of HIV-1 regulatory and accessory genes with the host small RNA pathway. Each of these interactions is important for balanced translational control of the retrovirus. Advisors/Committee Members: Boris-Lawrie, Kathleen.

▼ Two homologous series of potentially mesomorphic monomers, 4,4′-bis(n-(acryloyloxy)alkyloxy) biphenyl (BnA) and 2,6-bis(n-(acryloyloxy)alkyloxy) naphthyl (NnA) were synthesized. Researches in three different areas were conducted based on above monomers: i. The first three chapters concern about topochemically controlled polymerization of BnA in mesophases. Generally two liquid crystalline phases were observed for BnA homologues, S B and S E. All the BnA-S E phases assume a tilted bilayer structure and have well defined 3-dimensional (solid-like) structures. Long range order exists in the smectic layer normal direction as well as in the lateral direction. The third chapter describes the photopolymerization of monomer B5A. Polymers (PB5A's) with different liquid crystalline structures were obtained. When B5A was cured in the S E phase, a quasi-topochemical reaction was involved and the resulting polymer was also in a S E phase. Two smectic B phases (PB5A-S B α and β phases) with different molecular arrangements were obtained when B5A was cured in the S B phase. When B5A was cured in the isotropic state, only a nematic LC structure was obtained. The molecular organization within th e monomer dictates the resulting polymer structure. ii. The fourth chapter examines the spacer concept in side chain liquid crystal polymers. The mesophase formation is thought to be realized due to the decoupling of the motions of the isotropic backbone and the anisotropic mesogenic side chain by the use of a flexible spacer group. In this study, a detailed investigation of the effect of spacer length on the structural ordering of side-chain LC polymers was carried out based on two homologous series of polymeric systems, PBnA and PNnA. It was found that as n increases, the decoupling of motions between the backbone and side-chain mesogenic group increases, and consequently, the LC order within the polymeric system increases. iii. Finally, in the fifth chapter, an attempt was made to estimate the glass transition of polymethylene. We employed a group contribution approach to the problem, i.e. extrapolation of the transition temperature of two homologous series of polymers (PBnA and PNnA) with increasing methylene group content. The monomers were photopolymerized in the isotropic state so that amorphous polymethylene was obtained. (Abstract shortened by UMI. Advisors/Committee Members: Litt, Morton H.

▼ Today in urban China, it is common to refer to highly-educated women who are still single in their late twenties as “leftover ladies”; however, empirical research has yet to examine the impact of education and age on marriage. This study pools four years of the Chinese General Social Survey (2003, 2005, 2006, and 2008) data to investigate the gendered patterns of marriage by education and age in the early years of the twenty-first century in urban China. Results show that the gender gap in marriage rates has reversed from favoring women to favoring men as education increases. Particularly, the female disadvantage in marriage markets is only experienced by highly educated women at older ages (i.e., 30 – 49). Log-linear models indicate a gender asymmetry in assortative marriage patterns: men display a tendency to marry younger, less-educated women than themselves, and women display a tendency to marry older, better-educated men than themselves, net of the disparate marginal distributions of age and educational attainment of both sexes. The educational hypergamy pattern does not change as women marry later, but is more likely to occur as men marry at older ages. These results indicate gender-asymmetric patterns of marriage formation and assortative mating by education and age in urban China. Advisors/Committee Members: Qian, Zhenchao.

▼ The purpose of this study is to develop a communication model of employee cynicism toward organizational change. The few studies on employee cynicism were mainly conducted in the fields of management and psychology. The role of communication in shaping employee cynicism was rarely highlighted. Using the theoretical framework of social information processing (SIP), this study explored the communication variables in the social context which contribute to employee cynicism toward organizational change in a higher education institution. In the model, the three variables reflecting the social context, specifically, perceived quality of information, cynicism of colleagues, trust in the administration, are hypothesized to predict change-specific cynicism, which in turn, leads to intention to resist change. Participation in decision making (PDM) is hypothesized to predict intention to resist change both directly and indirectly through the mediating role of change-specific cynicism.The research was conducted in a Midwestern university which was undergoing a comprehensive strategic planning process. An online survey was administered to all full time tenure track faculty in this university. Path analysis was used to test the overall model fit. The findings of the study suggest that the proposed model explained a significant amount of variance in the outcome variables. However, contrary to the theoretical assumptions, PDM did not have significant causal effects on the outcome variables. Based on the empirical data, the proposed model was revised. The revised model fit the empirical data under study and all path coefficients were statistically significant at the .05 level. The revised model suggests that perceived quality of information had the largest causal effect on change-specific cynicism, followed by cynicism of colleagues, and finally trust in administration. Change-specific cynicism explained 79% of the variance in intention to resist change.The results of the study support SIP theory by indicating that change-specific cynicism emerges from the work environment. Future studies are called for to explore cynicism from the communication perspective. Further, more research should be conducted to investigate employee cynicism in the changing higher education environment. This study has significant practical implications for administrators in higher education institutions. Advisors/Committee Members: Daniels, Tom D.

▼ Marek's disease virus (MDV) causes malignant T cell lymphoma in chickens and is the major pathogen in poultry industry. The viral gene meq is abundantly expressed in MDV-transformed cell lines and MDV tumor samples. It contains a basic leucine-zipper region highly homologous to those of jun and fos, and a C-terminal proline-rich region including two and one-half repeat sequence (PRRs). In this report, we demonstrate that the proline-rich domain in the C-terminus of Meq is able to transactivate transcription when fused to the Ga14 DNA-binding domain, with the last 33 amino acids being essential for this activity. Full activity also requires at least one PRR, although fusion of itself alone with the DNA-binding domain represses transcription. Meq is able to dimerize with C-Jun and activate meq transcription through an AP-1-like motif in the meq promoter. The optimal binding sites of Meq/C-Jun and Meq/Meq are determined. Meq/C-Jun heterodimers bind a consensus with a core TRE/CRE site PuPuTGAC(G)TCAT. Meq homodimers bind two groups of DNA sequences. Group I site has a consensus GAGTGATGAC(G)TCATC, group II PuACACACAPy. By methylation interference assays and mutagenesis analysis, crucial nucleotides for the binding are identified. By computer simulation and circular pe rmutation assays, we further suggest that group II binding sites are intrinsically bent, and the DNA bending is necessary for the recognition by Meq/Meq. These results provide crucial information in the search of the functional targets of Meq, and shed new light on the general mechanism of DNA recognition by bZIP proteins Advisors/Committee Members: Kung, Hsing-Jien.

▼ The Veterans’ Glass City Skyway (VGCS) is a long span cable stayed bridge that carries I-280 over the Maumee River in Northwestern Ohio. Composed of 8,800 feet of precast, post-tensioned segmental box girders, the VGCS features a 1,225 feet cable stay span with a single plane of stays and was designed by FIGG Bridge Engineers, Inc. The Ohio Department of Transportation (ODOT) contracted the University Research Team (URT) composed of faculty and students from the University of Toledo and the University of Cincinnati to instrument the main span of the VGCS throughout construction and early service life. 128 vibrating wire strain gages were installed in eight segments at four cross sections to monitor the long-term behavior of this bridge. Data from these gages has been collected since the casting date of each segment. In this thesis, an overview of the long term strains and stresses was completed. The focus was on behavior during construction. Strain time histories were organized and compared to the construction time line. Approximate experimental stresses were derived from the strain data. The experimental stresses were compared to the stresses calculated by the contractor. The strain time histories were consistent with the construction logs and the experimental stresses were consistent with the analytical stresses. Overall, it was shown that the strain monitoring system was functioning properly and provided an accurate reflection of the actual strains on the VGCS. Advisors/Committee Members: Nims, Douglas.

▼ In modern microprocessors, more memory hierarchy and larger caches are integrated on chip to bridge the performance gap between high-speed CPU core and low speed memory. Large set-associative L2 caches draw a lot of power, generate a large amount of heat, and reduce the overall yield of the chip. As a result, large power consumption of the cache memory system has become a new bottleneck for many microprocessors. In this research, we analyze the performance of a location cache which works with a low power L2 cache system implemented by the drowsy cache technique. A small direct-mapped location cache is added to the traditional L2 cache system. It caches the way location information for the L2 cache access. With this way location information, the L2 cache can be accessed as direct-mapped cache to save both dynamic and leakage power consumption. Detailed mathematical analysis of the location cache power saving rate is presented in this work. To evaluate the power consumption of the location cache system on real world workloads, both SPEC CPU2000 and SPEC CPU2006 benchmark applications are simulated with the reference input set. Simulation results demonstrate that the location cache system can save a significant amount of power for all benchmark applications in L1 write through policy, and save power for benchmark applications with high L1 miss rate in L1 write back policy. Advisors/Committee Members: Jone, Dr. Wen-Ben.

▼ Coxeter groups arise in many parts of mathematics as groups generated by reflections. They provide an important source of examples in geometric group theory, where "virtual" properties of infinite groups, that is, properties of subgroups of finite index, are of strong interest. This dissertation focuses on virtual properties of infinite Coxeter groups. The following results are proved: (1) The intersection of a collection of parabolic subgroups of a Coxeter group is a parabolic subgroup; (2) The center of any finite index subgroup of an irreducible, infinite, non-affine Coxeter group is trivial; (3) Any finite index subgroup of an irreducible, infinite, non-affine Coxeter group cannot be expressed as a product of two nontrivial subgroups. Then, a unique decomposition theorem for subgroups of finite index in a Coxeter group without spherical or affine factors is proved based on (2) and (3). It is also proved that the orbit of each element other than the identity under the conjugation action in an irreducible, infinite, non-affine Coxeter group is an infinite set, which implies that an irreducible, infinite Coxeter group is affine if and only if it contains an abelian subgroup of finite index. Besides these, new proofs are given for the statement that the center of an irreducible, infinite Coxeter group is trivial, and a stronger version of this statement. Advisors/Committee Members: Davis, Michael.

▼ Linda Markowitz (2000) expanded the concept of a successful union campaign from beyond merely recognition to include post campaign solidarity. While making strides in the study of labor, Markowitz ignores what many others have missed as well, the changing labor market has segregated workers in the same industry across numerous buildings and cities, thus increasing the challenges unions face in building solidarity among members. This, combined with a demographically diverse workforce, and the cleavages that may result, makes union organizing ever more difficult. Even when a union is successful in obtaining recognition, long term solidarity may be at risk if specific demographic groups have unique concerns. This is particularly problematic if local tensions are ignored during the initial organizing drives. To assess these issues, I examine one union campaign spread across two major cities. Through focusing on the two primary locations of a wide spread janitors’ campaign, it becomes apparent that while an important victory was won, union organizers were unaware of concerns that arose from the unique demographics of the city. Specific factors that may influence solidarity after a successful campaign in relation to local demographics allows for a better understanding of the larger movement. Advisors/Committee Members: Martin, Andrew.

▼ The folate receptor (FR) type Beta, which is expressed in about 70% of acute myelogenous leukemia (AML) and can be selectively up-regulated by all-trans retinoic acid (ATRA), is a promising target for therapeutic intervention in AML. Using KG-1 and MV4-11 AML cells and recombinant 293 cells, we show that the histone deacetylase (HDAC) inhibitors Trichostatin A (TSA), valproic acid (VPA) and FK228 potentiate ATRA induction of FR-Beta. ATRA and/or TSA did not induce de novo FR synthesis in any of a variety of FR-negative cell lines tested. These results indicate that the combination of ATRA and innocuous HDAC inhibitors may be expected to facilitate selective FR-Beta-targeted therapies in AML. Mechanistic studies showed that (1) TSA did not alter the effect of ATRA on the expression of retinoic acid receptors (RARs) Alpha, Beta or Gamma, (2) ATRA increased the association of RAR Alpha with the basal FR-Beta promoter; (3) the enhancement of the ATRA effect by TSA was associated with increased acetylation of the core histones H3 and H4 at or near the basal FR-Beta promoter, (4) TSA caused a striking ATRA-dependent increase in Sp1 binding at the promoter without a further change in the association of RAR Alpha or an increase in Sp1 expression; (5) TSA further decreased the availability of putative repressor AP-1 protein(s). We further demonstrate that FR-Beta selectively mediated cell growth inhibition by the (6S) diastereoisomer of dideaza tetrahydrofolate in a manner that was potentiated by ATRA and HDAC inhibition. This study also found that ATRA induced apoptosis in MV4-11 cells but increased FR-Beta expression in the surviving cells. These surviving cells resistant to ATRA induced apoptosis can mimic the residual cells refractory to ATRA differentiation therapy. Thus this cell line can serve as a model cell line to establish FR-Beta-targeted therapy for minimal residual disease in APL. Sublines of MV4-11 cells that have uniform cell populations were isolated. Preliminary data showed that ATRA treatment increased the expression of FR-Beta in the cells collected from NOD/SCID mouse bone marrow engrafted with two such sublines demonstrating the feasibility of using this approach to develop novel FR-Beta-targeted-therapies for minimal residual disease in APL. Advisors/Committee Members: Ratnam, Ph.D., Manohar.

▼ The first two projects describe new applications of flow injection capillary electrophoresis (CE). The first study focuses on the determination of lactate or oxalate using injected lactate oxidase (LO) and peroxidase with UV detection. Two reactions, catalyzed by (LO) and peroxidase, are initiated by a single injection of the enzymes and the substrate 2,2’-azino-bis(3-ethylene-thiazoline-6-sulfonic acid) (ABTS) into the capillary previously filled with the sample (lactate or lactate-oxalate mixture) and the running buffer containing NADH. The oxidized ABTS product upon reaction with NADH is converted to NAD+, which is detected at 266 nm with a sample throughput of 7 min including wash steps. Linearity for lactate is established from 0.0025 – 1mM and serum samples are analyzed with an average recovery of 101%. This method can also be applied to the determination of oxalate as an inhibitor of LO. The second topic describes the determination of the concentration of cardiolipin using CE with on-line N-nonylacridine orange (NAO) dye interaction and spectrophotometric detection at 497 nm. Other phospholipids do not interfere and a detection limit of 0.05 ìM was found. In a blind study, actual mitochondrial cell membrane samples in the µL range, taken from cells before or after UV light exposure, are analyzed using the CE method. The last two topics describe preconcentration of pharmaceuticals and phospholipids with nano-electrospray ionization mass spectrometry (nano-ESI MS). An analytical method is developed for the quantitative determination of dicyclomine in serum with cyclopentolate as the internal standard by off-line nano-ESI MS with reversed phase mini-solid phase extraction (mini-SPE). Different length (0.5cm, 1cm) reversed phase (C4 and C18) mini-SPE cartridges are prepared by packing gel-loader pipette tips for optimization of the preconcentration effect. A factor of 100 is possible using the 1 cm C18 or C4 cartridge. Spiked serum samples are quantitatively determined using the C18 cartridge. Preconcentration of phospholipids is first studied for nano-ESI MS by weak anion exchange SPE. With aminopropyl SPE, detection limits are lowered 2-2000 times for different phospholipids as compared to no SPE. With aminopropyl mini-SPE and mixed mode C18/aminopropyl (1:1) mini-SPE, the detection limits for eight different phospholipids are lowered another factor of 5 better (about 0.05 to 5 pmol/ìL) than those for weak anion exchange SPE. Linear calibration curves are able to be established. Advisors/Committee Members: Danielson, Neil D.

▼ The history of cosmetics dates back to 10,000 B. C., spanning at least 6000 years in the human history. People’s purpose of using the cosmetics is almost the same; they want to make themselves more beautiful and attractive. Therefore, the cosmetics are very important to people, especially women. L’Oreal/Maybelline company has achieved a big success after entering the Chinese market. A lot of factors contribute to its growth in sales and profits, such as appropriate marketing and advertising strategies, innovations with the technologies, etc. In 2010, sales in China rose to $1.38 billion, an 11.1 percent increase over the previous year. In 2010, L’Oreal China has become the third-largest market in China. The thesis focuses on comparing the Chinese and American print advertisements and TV commercials for L’Oreal/Maybelline’s lipsticks products. There are a lot of similarities and differences existing between the L’Oreal/Maybelline company’s Chinese and American advertisements, because of the cultural and traditions differences. Even though L’Oreal/Maybelline is a western company, its advertisements successfully adjust to the taste of the Chinese audiences and are well received by the Chinese people. Therefore, it is important for other companies, especially the western companies, to learn from the successful advertising strategies used by L’Oreal/Maybelline company. Advisors/Committee Members: Measell, James.

▼ In the cell, translation is the process by which polypeptides are synthesized on the ribosome based on the genetic information encoded in the messenger RNA (mRNA). The first step of translation, initiation involves recognition of the start codon by the initiator tRNA (fMet-tRNAfMet in bacteria) in the ribosomal peptidyl (P) site. The correct start codon is selected primarily based on the complementarity of codon-anticodon pairing. Initiation factors IF1 and IF3 have been implicated to negatively regulate translation initiation to promote its accuracy. 16S ribosomal RNA (rRNA) undoubtedly plays a role in initiation, but precisely how it participates in the process remains unclear. In this work, we use a combination of genetic and biochemistry approaches to investigate the role of 16S rRNA in start codon selection. We first screened a number of P-site mutations for their effects on start codon selection. Our results showed that most of these P-site mutations, while generally reducing the efficiency of translation, increase the stringency of start codon selection. These mutations confer a defect in fMet-tRNA binding, which likely makes initiation depend more heavily on the cognate codon-anticodon pairing. One exception, G1338A confers a higher affinity for tRNAfMet, which could partially compensate for the mismatches in the codon-anticodon helix and thereby allow initiation from non-canonical start codon. These data provide evidence that the affinity of the initiator tRNA for the 30S P site is tuned to balance efficiency and accuracy of initiation. Unlike G1338A, 30S subunits harboring A790G show defect in IF3 binding. We suspect that reduced IF3 binding explains the loss of fidelity in that case. Next, we employed random mutagenesis in a genetic screen and identified additional 16S rRNA mutations that increase initiation from non-canonical start codons. Most interestingly, a cluster maps to helix 44 (h44) just ‘down’ from the A site, a region known to be distorted by IF1. Several h44 mutations (e.g. A1413C) are predicted to change the non-canonical pair to a Watson-Crick pair, suggesting that they may decrease fidelity of translation initiation by altering the conformation of h44. Indeed, our subsequent work showed that these h44 mutations stimulate the second step of initiation (50S docking), which may explain for their defects in start codon recognition in vivo. To reveal possible structural changes of 16S rRNA upon start codon recognition, we used chemical probing methods to monitor 16S rRNA in canonical and non-canonical 30S initiation complex. Of ~110 nucleotides targeted, 6 showed altered reactivity in response to the nature of start codon. One of them is A1408, which lies in h44. In particular, the high reactivity of A1408 attributed to IF1 is specifically reduced in 30S initiation complexes containing AUG, even though the level of IF1 binding remains unchanged. Additionally, either mutation A1413C or streptomycin similarly reduces the reactivity of A1408. In light of the fact that both A1413C and streptomycin can stimulate premature 50S docking, we propose that the docking is controlled in part by a conformational switch in the 1408 region. IF1 stabilizes the A1408 region in a docking unfavorable conformation, which is reversed upon start codon recognition. Another group of the nucleotides lie in or near the P site. These nucleotides, which are protected by fMet-tRNA in the canonical 30S initiation complexes, are either unprotected or less protected in the non-canonical 30S initiation complexes. The loss of protections suggests that P site is largely unoccupied in the presence of non-canonical start codon. We propose that in this situation, fMet-tRNA associates to the 30S subunits in a liable manner. Finally, we also show that the selectivity of 30S.mRNA.fMet-tRNA ternary complex formation is high (K(AUG)/K(AUC)~100) in the absence of initiation factors – high enough to account for the accuracy in vivo. In the presence of all three factors, the selectivity is similar. Omission of IF3 in the latter case decreases selectivity to 4. These data support a simple model in which IF3 kinetically counteracts the stabilizing effects of the other factors to allow the inherent selectivity of the 30S P site to be utilized. Advisors/Committee Members: Fredrick, Kurt.

▼ This work combines the use of biochemical and structural modeling approaches to characterize the FHA domains from human Chk2 and Caenorhabditis elegans Chk2 proteins. The DNA damage checkpoint pathway is vital to the maintenance of genomic integrity. Chk2 plays key roles on this pathway by phosphorylating several important cell cycle control modulators, such as tumor suppressor p53. The exact functions of the FHA domain of Chk2 are still not clearly known, while it has been generally considered as the regulator to the Chk2 kinase activities. In this dissertation, efforts have been put to express and purify the unstable Chk2 FHA domain. After fine tuning the conditions, great improvements have been observed on the NMR spectrums, which are the essentials for the future structural work. Well-resolved 2D and 3D spectra have been obtained. Seeking to identify binding substrates for Chk2 FHA domain, combinatorial peptide library screenings have been utilized to determine the consensus sequence of the target phosphopeptides. Chk2FHA was found to bind to phosphotyrosyl peptides containing pYXXXL motif. A phosphopeptide from p53 centered by (pY107)GFRL was identified with mild affinity (KD = 6.1¦ÌM) to Chk2 FHA domain. Chk2 complex structure with this pY-peptide was proposed by structural modeling. It features similar global structure as the recently solved Chk2FHA-pT-peptide complex, while the interaction details between Chk2FHA and phosphopeptides might be different. The consensus sequence identified by pT-peptide library screening displays strong selection of Ile at the +3 position. A phosphopeptide with sequence containing pT329LQI from p53 was shown to bind to Chk2FHA (KD = 11.7 ¦ÌM) and perturb its global structure, though the physiological impact of this binding event still needs to be elucidated. Another pT-peptide containing pT1851YLI from tumor suppressor BRCA1 has also been investigated and it exhibits decent affinity (KD = 1.2 ¦ÌM) to Chk2FHA. C. elegans Chk2 was recently discovered and very little is known about its functions. Ce-Chk2 has been demonstrated to play key roles in meiotic recombination, while it conserves the function of a DNA damage checkpoint at the pachytene stage. Investigation on Ce-Chk2 will shed more light on the properties of the Chk2 family. While no report on Ce-Chk2 at the protein level has been published to date, we have successfully expressed the full-length, FHA domain and kinase domain of Ce-Chk2 in E. coli. Purification of Ce-Chk2 FHA domain was achieved and combinatorial peptide library screenings were carried out to search for the binding targets of Ce-Chk2FHA. It was found that Ce-Chk2FHA, similar to Chk2FHA, strongly selects Leu at the +4 position in pY-peptides. The pT- and pS-peptide libraries have also been screened. Advisors/Committee Members: Tsai, Ming-Daw.

▼ Growth factor independence-1 (Gfi-1) is a zinc-finger transcriptional repressor that plays a critical role in hematopoiesis. Gfi-1 regulates the development of myeloid and lymphoid cells, and controls hematopoietic stem cell self-renewal. Gfi-1 is weakly oncogenic but strongly cooperates with oncoprotein Myc in lymphomagenesis. How Gfi-1 functions in hematopoiesis remains poorly understood. Data presented here demonstrate that Gfi-1 represses p21Cip1 and MBP through two distinct mechanisms. Gfi-1 interacts with Myc-interacting zinc-finger protein (Miz-1), a transcriptional activator regulating cell cycle progression and apoptosis, and is recruited by Miz-1 to the promoter of Miz-1 target gene p21Cip1 which encodes a potent cell cycle inhibitor, leading to transcriptional repression. Repression of p21Cip1 by Gfi-1 is independent of direct DNA-binding. Knockdown or deficiency of Gfi-1 results in augmented p21Cip1 expression. Interestingly, Gfi-1 forms a ternary Gfi-1/Miz-1/Myc complex on the p21Cip1 promoter and collaborates with Myc in the repression of p21Cip1. This Miz-1-dependent transcriptional repression by Gfi-1 also applies to other Miz-1 target genes encoding cell cycle inhibitors p15Ink4b and p27Kip1. Consistent with the mechanism of Miz-1-dependent transcriptional repression, Gfi-1 also represses growth inhibitory cytokine TGF-β-activated p21Cip1 independent of DNA-binding. Interestingly, Gfi-1 expression is downregulated by TGF-β, suggesting a role of Gfi-1 in TGF-β-mediated growth inhibition. MBP encodes a cytotoxic granule protein expressed in eosinophils and basophils. Our data identify MBP as a new target of Gfi-1-mediated transcriptional repression. Unlike p21Cip1, however, the repression of MBP by Gfi-1 requires Gfi-1 direct DNA-binding as evidenced by the fact that the Gfi-1 dominant negative mutant N382S, which is defective for DNA-binding, relieves the transcriptional repression of MBP by Gfi-1. Indeed, knockdown of Gfi-1 results in enhanced expression of MBP. Expression of the N382S mutant has been shown to cause premature apoptosis of myeloid cells induced to differentiate by G-CSF. Interestingly, overexpression of MBP also results in increased apoptosis during G-CSF-stimulated terminal neutrophilic differentiation, indicating that elevated MBP expression may contribute to the N382S-associated apoptosis of differentiating myeloid cells. These data suggest that the transcriptional repression of MBP by Gfi-1 may contribute to the role of Gfi-1 in regulating granulocyte development. Taken together, our study demonstrates Gfi-1-mediated transcriptional repression of p21Cip1 and MBP by two different mechanisms. Gfi-1, via binding to Miz-1, is recruited to p21Cip1 and other Miz-1 target genes leading to transcriptional repression, and Gfi-1 represses MBP, however, through direct DNA-binding. These findings provide new insights into the transcriptional regulation by Gfi-1 and may have broad implications for better understanding the role of Gfi-1 in normal hematopoiesis and tumorigenesis. Advisors/Committee Members: Dong, Fan.

▼ Common fragile sites are conserved regions of mammalian chromosomes that are exquisitely sensitive to forming gaps or breaks on metaphase chromosomes after partial inhibition of DNA synthesis. Studies revealing that fragile sites and fragile site genes are deleted or rearranged in many cancer-derived cells have demonstrated the importance of these loci in genome instability in cancer. Our laboratory has primarily been working on two common fragile site genes, FHIT and WWOX, which are located at FRA3B and FRA16D, respectively, the two most frequently expressed and best-characterized fragile sites in the human genome. FHIT and WWOX are both tumor suppressor genes that frequently show reduction or loss of expression in various human cancers. In this research which is focused on identifying signal pathways affected by these tumor suppressors, we demonstrated that: 1) Fhit down-modulates the expression of a cell cycle regulatory protein, cyclin D1, in various cells and experimental conditions. Cyclin D1, an oncogenic protein up-regulated in many human cancers, was down-modulated by Fhit overexpression by contributing to degradation of cyclin D1 through the proteosome pathway. 2) The WWOX gene has a role in prostate cancer development; Wwox expression was reduced or lost in prostate cancer-derived cells and tissues, in part due to DNA hypermethylation in the WWOX regulatory region. Both WWOX mRNA and protein expression can be restored after inhibition of DNA methylation and histone deacetylation. Restoration of WWOX suppressed prostate cancer growth and induced apoptosis in vitro and in vivo. Furthermore, Wwox suppressed prostate cancer-derived cell growth through binding and cytoplasmic sequestration of the transcription factor Ap2gamma, preventing Ap2gamma from entering the nucleus to activate ErbB2, and blocking ErbB2-mediated androgen receptor signaling. Advisors/Committee Members: Huebner, Kay F.

▼ This thesis presents a model to predict the pavement response using Falling Weight Deflectometer (FWD) deflection data for asphalt concrete (AC) pavement. Evercalc 5.0 and Elmod 6.0 were chosen to conduct the backcalculation of pavement layer moduli using FWD deflections. Everstress 5.0 was used to do the forward calculation using backcalculated layer moduli. Predicted pavement responses (tensile strain at the bottom of the AC layer) were compared to the measured pavement responses from U.S. Route 30 to check the validity and accuracy of the selected prediction model. The predicted results show a good agreement with the measured responses. A comparison between FWD and truck load conditions was also conducted. The results show that FWD can accurately simulate the magnitude and the duration of a moving single wheel load. Advisors/Committee Members: Sargand, Shad.

▼ A new dual-process cognitive and affective trust in leadership framework is proposed and tested in a field study. 504 undergraduate students participated in the study and structural equation modeling was employed to perform the analysis. Cognition-based trust perception works together with cognitive reaction toward the leader to form cognitive trust determinant, while relationship-based trust perception works together with affective reaction toward the leader to form affective trust determinant. The cognitive and affective trust determinants influence trust willingness at the same time. Most of the hypothesized paths were supported. In addition, the relationships between memory systems and different trust processes were tested using an experimental design. It was proposed that semantic memory has a stronger connection to the cognitive trust path; whereas, episodic memory has a stronger connection to the affective trust path. However, results did not support these hypotheses. Instead, results suggested that the memory conditions equally influence cognitive and affective trust paths to trust willingness. Exploratory analyses were conducted on organizational antecedents and outcomes for cognition-based trust perception and relationship-based trust perception. Explanations and practical implications of findings, future directions of research and limitations of this study are discussed. Advisors/Committee Members: Hall, Rosalie.

▼ De-inked paper sludge (DPS) was pyrolyzed at 600 °C, 750 °C and 900 °C in nitrogen to synthesize carbon-calcium-based adsorbents. The performance of the synthesized adsorbents for the gas-phase adsorption of elemental mercury (Hg), sulfur dioxide (SO2), and isoamyl acetate (IAA) vapor was investigated, and the performance was compared to that of commercially available activated carbon (BPL, Calgon Carbon Corporation). The physical and chemical properties of the pyrolyzed DPS and BPL were characterized to assess their chemical and physical differences, and those differences were used to hypothesize reasons for differences in their adsorption performance for the selected test compounds (elemental Hg, SO2 and IAA). Characterization of the adsorbents was conducted using BET surface area, X-ray diffraction, TGA, scanning electron microscopy, electron dispersion spectroscopy, and FTIR. Gas chromatography was used to analyze IAA collected through out adsorption process. Adsorption capacities of pyrolyzed DPS and BPL were investigated in different experimental conditions (temperature, steam, etc). Advisors/Committee Members: Almquist, Catherine.

▼ Multicarrier CDMA has emerged recently as a promising candidate for the next generation broad-band mobile networks. Since multicarrier CDMA combines the multicarrier technique and the spread-spectrum CDMA technique, many multiuser detection methods used in DS-CDMA can be applied to multicarrier CDMA system. In this thesis, we propose a direct blind multiuser detection method for multicarrier CDMA based on linear prediction. Using only the spreading code of the desired user, we extract the column vector subspace corresponding to the signal of interest from the channel matrix of the received complex signal. And then zero-forcing (ZF) and minimum mean square error (MMSE) detectors are constructed. Our algorithms do not require channel estimation and avoid the channel estimation error. Simulations show that in most conditions, our algorithms outperform the typical subspace-based algorithm and the eigen-method used in a multicarrier system. Advisors/Committee Members: Fan, Dr. Howard.

▼ The purpose of this study was to investigate the effect of divergent selection for serum insulin-like growth factor I (IGF-I) concentration on mature weight estimated using growth curve functions in Angus cattle. Multiple serum IGF-I measurements (d 28, d 42, d 56 of the 140-d postweaning period and the average of these 3, mean IGF) from a total of 2,514 animals and weight records from birth to at least 3 yr of age from a total of 172 animals were collected from an ongoing divergent selection experiment involving IGF-I that was initiated in 1989. Four growth curve functions (Brody, Logistic, Gompertz, Von Bertalanffy) were used to estimate the parameters for mature weight (A) and maturing rate (k) using the NLIN procedure in SAS (SAS Inst. Inc., Cary, NC). Based on the criteria of R2, MSE, AIC, and Log Likelihood, the Brody function fitted the weight-age data best, followed by the Von Bertalanffy function. The heritability estimates for serum IGF-I concentration at different ages and growth curve parameters from each function were obtained using a multiple-trait, derivative-free, REML program (MTDFREML). Genetic, environmental, and phenotypic correlations between mean IGF-I and growth curve parameters A and k were also obtained. The direct heritability (h2) estimates for serum IGF-I at d 28, 42, and 56 of the postweaning test were 0.42, 0.42, and 0.33, respectively. The h2 estimates for A from the 4 growth functions ranged from 0.77 to 1.00 in single-trait analyses. In 2-trait analyses, however, such estimates ranged from 0.26 to 0.41. The h2 estimates for k ranged from 0.12 to 0.33 in single-trait analyses, which were consistent with the results from the 2-trait analyses. The genetic correlations between mean IGF-I and A within each growth curve function ranged from -0.38 to -0.06. Although serum IGF-I was negatively genetically correlated with mature weight, the phenotypic correlation between these 2 traits was moderate (from 0.50 to 0.59) due to highly positive environmental correlations (mostly converged to 1.00). The growth curves for the low IGF-I selection line were exceeded the growth curves for the high IGF-I selection line in weight with an average difference of 10 kg after approximately 3 yr of age. This result suggests that selection for IGF-I may affect mature weight in Angus cattle and that the cows from the high IGF-I selection line may be more economical due to lighter mature weights and thus lower maintenance requirements. Advisors/Committee Members: Davis, Michael.

▼ A thorough review of past and current projects involving intraoperative imaging is conducted. A general purpose intraoperative imaging tool was designed and its application was tested on tissue-mimic phantom and in-vitro tissue. The results show improved efficiency in the detection of disease margins by using the intraoperative imaging tool. Two methods for fabricating contrast agents with dual-mode image enhancement were discussed and evaluated. With ink-encapsulated microbubbles, we were able to get enhanced image for both ultrasound and photo acoustic modalities. With ICG encapsulated microbubbles, both fluorescence and ultrasound images can be taken simultaneously. Finally, an integrated dual-mode intraoperative imaging system for wound is discussed. Wound perfusion and oxygenation can be simultaneously assessed by this dual-mode imaging system. Advisors/Committee Members: Xu, Ronald.