Indiana University-Purdue University Indianapolis (IUPUI) / Population estimations for the year 2000 indicate an increase in poor and minorities in the United States (Loden & Rosener, 1991). In view of this growth trend, Berger (1989) suggests a need for social workers with sensitivity to such populations. The presence of minority perspectives provides a valuable contribution to service delivery (Mullen et al., 1993). Efforts to enhance student persistence in graduate schools of social work will contribute to the pool of social workers available in the next century. The purpose of this study is to determine the factors that contribute to African American student persistence in graduate schools of social work. This study applies aspects of Astin's, Tinto's and Green's theories of persistence. Astin's theory of involvement (1975) considers student investment of time in educational pursuits. Tinto's (1975) theory of departure includes background, social and academic aspects in persistence decisions. Green's (1997) theory focuses on the ability of the student to cope with racial issues (racial resilience) and the racial climate of the school (racial responsiveness). One hundred and thirty-five students from two predominantly white and two historically black universities participated in surveys administered to determine the effect of involvement, background, academic, social, resilience factors, and college type upon student persistence outcomes. Interviews held with administrative personnel at each institution provided contextual data. Correlations were used to examine the relationships among all of the variables in the study. T-Tests were conducted to compare outcomes due to university type. Multiple regressions were used to explore the relationships between significant independent variables and persistence. The findings of this study indicate that persistence outcomes of African American graduate social work students are influenced by: (a) academic performance, faculty-student relationships, (c) health, (d) the ability to deal with stress, and (e) ethnic pride (impressions of ethnic group). These findings suggest that social work programs that incorporate aggressive grade monitoring practices, provide diverse opportunities for student-faculty interaction, offer opportunities for health care, stress alternatives, and a culturally relevant curriculum, may positively influence African American student persistence.

Indiana University-Purdue University Indianapolis (IUPUI) / IL-17-producing T cells are critical to the development of pathogen and tumor immunity, but also contribute to the pathology of autoimmune diseases and allergic inflammation. CD8+ (Tc17) and CD4+ (Th17) IL-17-secreting T cells develop in response to a cytokine environment that activates Signal Transducer and Activator of Transcription (STAT) proteins, though the mechanisms underlying Tc17/Th17 development and stability are still unclear. In vivo, Tc17 cells clear vaccinia virus infection and acquire cytotoxic potential, that is independent of IL-17 production and the acquisition of IFN-γ-secreting potential, but partially dependent on Fas ligand, suggesting that Tc17-mediated vaccinia virus clearance is through cell killing independent of an acquired Tc1 phenotype. In contrast, memory Th cells and NKT cells display STAT4-dependent IL-23-induced IL-17 production that correlates with Il23r expression. IL-23 does not activate STAT4 nor do other STAT4-activating cytokines induce Il23r expression in these populations, suggesting a T cell-extrinsic role for STAT4 in mediating IL-23 responsiveness. Although IL-23 is important for the maintenance of IL-17-secreting T cells, it also promotes their instability, often resulting in a pathogenic Th1-like phenotype in vitro and in vivo. In vitro-derived Th17 cells are also flexible when cultured under polarizing conditions that promote Th2 or Th9 differentiation, adopting the respective effector programs, and decreasing IL-17 production. However, in models of allergic airway disease, Th17 cells do not secrete alternative cytokines nor adopt other effector programs, and remain stable IL-17-secretors. In contrast to Th1-biased pro-inflammatory environments that induce Th17 instability in vivo, during allergic inflammatory disease, Th17 cells are comparatively stable, and retain the potential to produce IL-17. Together these data document that the inflammatory environment has distinct effects on the stability of IL-17-secreting T cells in vivo.

Indiana University-Purdue University Indianapolis (IUPUI) / In recent years, magnesium alloys, due to their high strength and biocompatibility, have attracted significant interest in medical applications, such as cardiovascular stents, orthopedic implants, and devices. To overcome the high corrosion rate of magnesium alloys, coatings have been developed on the alloy surface. Most coating methods, such as anodic oxidation, polymer coating and chemical conversion coating, cannot produce satisfactory coating to be used in human body environment. Recent studies demonstrate that micro-arc oxidation (MAO) technique can produce hard, dense, wear-resistant and well-adherent oxide coatings for light metals such as aluminum, magnesium, and titanium. Though there are many previous studies, the understanding of processing conditions on coating performance remains elusive. Moreover, previous tests were done in simulated body fluid. No test has been done in a cell culture medium, which is much closer to human body environment than simulated body fluid. In this study, the effect of MAO processing time (1 minute, 5 minutes, 15 minutes, and 20 minutes) on the electrochemical behaviors of the coating in both conventional simulated body fluid and a cell culture medium has been investigated. Additionally a new electrolyte (12 g/L Na2SiO3, 4 g/L NaF and 4 ml/L C3H8O3) has been used in the MAO coating process. Electrochemical behaviors were measured by performing potentiodynamic polarization and electrochemical impedance spectroscopy tests. In addition to the tests in simulated body fluid, the MAO-coated and uncoated samples were immersed in a cell culture medium to investigate the corrosion behaviors and compare the difference in these two kinds of media. The results show that in the immersion tests in conventional simulated body fluid, the 20-minute MAO coated sample has the best resistance to corrosion due to the largest coating thickness. In contrast, in the cell culture medium, all MAO coated samples demonstrate a similar high corrosion resistance behavior, independent of MAO processing time. This is probably due to the organic passive layers formed on the coating surfaces. Additionally, a preliminary finite element model has been developed to simulate the immersion test of magnesium alloy in simulated body fluid. Comparison between the predicted corrosion current density and experimental data is discussed.

Indiana University-Purdue University Indianapolis (IUPUI) / The positive identification of human remains that are decomposed, burnt, or otherwise disfigured can prove especially challenging in forensic anthropology, resulting in the need for specialized methods of analysis. Due to the unique morphological characteristics of the frontal sinus, a positive identification can be made in cases of unknown human remains, even when remains are highly cremated or decomposed. This study retrospectively reviews 3D CBCT images of a total of 43 Caucasian patients between the ages of 20-38 from the Indiana University School of Dentistry to quantify frontal sinus differences between adult males and females and investigate the usefulness of frontal sinus morphology for forensic identification. Digit codes with six sections and eleven-digit numbers were created to classify each individual sinus. It was shown that 3D CBCT images of the frontal sinus could be used to make a positive forensic identification. Metric measurements displayed a high degree of variability between sinuses and no two digit codes were identical. However, it was also shown that there were almost no quantifiable and significant sexually dimorphic differences between male and female frontal sinuses. This study confirms that sex determination should not be a primary goal of frontal sinus analysis and highlights the importance of creating a standard method of frontal sinus evaluation based on metric measurements.

Indiana University-Purdue University Indianapolis (IUPUI) / Crashworthiness design is gaining more importance in the automotive industry due to high competition and tight safety norms. Further there is a need for light weight structures in the automotive design. Structural optimization in last two decades have been widely explored to improve existing designs or conceive new designs with better crashworthiness and reduced mass. Although many gradient based and heuristic methods for topology and topometry based crashworthiness design are available these days, most of them result in stiff structures that are suitable only for a set of vehicle components in which maximizing the energy absorption or minimizing the intrusion is the main concern. However, there are some other components in a vehicle structure that should have characteristics of both stiffness and flexibility. Moreover, the load paths within the structure and potential buckle modes also play an important role in efficient functioning of such components. For example, the front bumper, side frame rails, steering column, and occupant protection devices like the knee bolster should all exhibit controlled deformation and collapse behavior. This investigation introduces a methodology to design dynamically crushed thin-walled tubular structures for crashworthiness applications. Due to their low cost, high energy absorption efficiency, and capacity to withstand long strokes, thin-walled tubular structures are extensively used in the automotive industry. Tubular structures subjected to impact loading may undergo three modes of deformation: progressive crushing/buckling, dynamic plastic buckling, and global bending or Euler-type buckling. Of these, progressive buckling is the most desirable mode of collapse because it leads to a desirable deformation characteristic, low peak reaction force, and higher energy absorption efficiency. Progressive buckling is generally observed under pure axial loading; however, during an actual crash event, tubular structures are often subjected to oblique impact loads in which Euler-type buckling is the dominating mode of deformation. This undesired behavior severely reduces the energy absorption capability of the tubular structure. The design methodology presented in this paper relies on the ability of a compliant mechanism to transfer displacement and/or force from an input to desired output port locations. The suitable output port locations are utilized to enforce desired buckle zones, mitigating the natural Euler-type buckling effect. The problem addressed in this investigation is to find the thickness distribution of a thin-walled structure and the output port locations that maximizes the energy absorption while maintaining the peak reaction force at a prescribed limit. The underlying design for thickness distribution follows a uniform mutual potential energy density under a dynamic impact event. Nonlinear explicit finite element code LS-DYNA is used to simulate tubular structures under crash loading. Biologically inspired hybrid cellular automaton (HCA) method is used to drive the design process. Results are demonstrated on long straight and S-rail tubes subject to oblique loading, achieving progressive crushing in most cases.

Indiana University-Purdue University Indianapolis (IUPUI) / Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that has proven to be an important signaling molecule both as an extracellular primary messenger and as an intracellular second messenger. Extracellular S1P acts through a family of five S1P receptors, S1PR1-5, all of which are G protein-coupled receptors associated with different G proteins. Previous work from our laboratory shows that externally applied S1P increases the excitability of small-diameter sensory neurons by enhancing the action potential firing. The increased neuronal excitability is mediated primarily, but not exclusively, through S1PR1. This raises the question as to which other S1PRs mediate the enhanced excitability in sensory neurons. To address this question, the expression of different S1PR subtypes in small-diameter sensory neurons was examined by single-cell quantitative PCR. The results show that sensory neurons express the mRNAs for all five S1PRs, with S1PR1 mRNA level significantly greater than the other subtypes. To investigate the functional contribution of other S1PRs in augmenting excitability, sensory neurons were treated with a pool of three individual siRNAs targeted to S1PR1, R2 and R3. This treatment prevented S1P from augmenting excitability, indicating that S1PR1, R2 and/or R3 are essential in mediating S1P-induced sensitization. To study the role of S1PR2 in S1P-induced sensitization, JTE-013, a selective antagonist at S1PR2, was used. Surprisingly, JTE-013 by itself enhanced neuronal excitability. Alternatively, sensory neurons were pretreated with FTY720, which is an agonist at S1PR1/R3/R4/R5 and presumably downregulates these receptors. FTY720 pretreatment prevented S1P from increasing neuronal excitability, suggesting that S1PR2 does not mediate the S1P-induced sensitization. To test the hypothesis that S1PR1 and R3 mediate S1P-induced sensitization, sensory neurons were pretreated with specific antagonists for S1PR1 and R3, or with siRNAs targeted to S1PR1 and R3. Both treatments blocked the capacity of S1P to enhance neuronal excitability. Therefore my results demonstrate that the enhanced excitability produced by S1P is mediated by S1PR1 and/or S1PR3. Additionally, my results indicate that S1P/S1PR1 elevates neuronal excitability through the activation of mitogen-activated protein kinase kinase. The data from antagonism at S1PR1 to regulate neuronal excitability provides insight into the importance of S1P/S1PR1 axis in modulating pain signal transduction.

Diese Dissertation aus der Sparte der Reflexiven Bibliometrie erforscht die Rückwirkungen der Verwendung von quantitativen Indikatoren in der Wissenschaftsevaluation auf die Wissensproduktion und Forschungsqualität in der Astronomie. Eine qualitative Analyse der strukturellen Bedingungen der akamdeischen Astronomie anhand des Rational Choice Frameworks führen zur Beobachtung eines "Evaluation Gap" zwischen dem, was Indikatoren messen und dem, was Forscher unter Forschungsqualität verstehen. Die Analyse offenbart weiters einen Balanceakt, in dem Astronomen zwischen Publikationsdruck und Forschungsintegrität Kompromisse finden. Weiterführende quantitative Untersuchungen unter Einbezug von Organisational Culture Theories und Self-Determination Theory zeigen, dass kontrollierte Formen von Motivation zu einem erhöhten Publikationsdruck und wissenschaftlichem Fehlverhalten führen, während autonome Formen von Motivation das Gegenteil bewirken. Schließlich skizziert die Arbeit Wege zur Transformation der Forschungskultur hin zu mehr Vielfalt und Partizipation, einschließlich der Einführung offener Wissensmanagement-Infrastrukturen und kontinuierlicher, reflexiver Evaluationsprozesse. / This dissertation from the field of Reflexive Bibliometrics, investigates the constitutive effects of utilizing quantitative metrics in research evaluation on knowledge production and research quality in astronomy. Embedded in the Rational Choice Framework to analyze the structural conditions within academic astronomy, a qualitative analysis reveals an "Evaluation Gap" between what metrics measure and researchers' perceptions of research quality. Furthermore, the analysis unveils a balancing act where astronomers navigate compromises between publication pressures and research integrity. Subsequent quantitative analyses, incorporating Organizational Culture Theories and Self-Determination Theory, demonstrate that controlled forms of motivation exacerbate publication pressure and scientific misconduct, while autonomous motivations yield contrasting effects. Lastly, the study outlines pathways towards transforming research culture towards greater diversity and participation, including the adoption of open knowledge management infrastructures and continuous, reflexive evaluation processes.

Indiana University-Purdue University Indianapolis (IUPUI) / Dicalcium phosphate dihydrate (DCPD) cements have been used for bone repair due to its excellent biocompatibility and resorbability. However, DCPD cements are typically weak and brittle. To overcome these limitations, the sodium citrate used as a setting regulator and the coating of poly-L-lactide acid (PLLA) technique have been proposed in this study. The first purpose of this thesis is to develop composite PLLA/DCPD scaffolds with enhanced toughness by PLLA coating. The second purpose is to examine the biocompatibility of the scaffolds. The final purpose is to investigate the degradation behaviors of DCPD and PLLA/DCPD scaffolds. In this experiment, DCPD cements were synthesized from monocalcium phosphate monohydrate (MCPM) and 𝛽-tricalcium phosphate (𝛽 –TCP) by using deionized water and sodium citrate as liquid components. The samples were prepared with powder to liquid ratio (P/L) at 1.00, 1.25 and 1.50. To fabricate the PLLA/DCPD composite samples, DCPD samples were coated with 5 % PLLA. The samples were characterized mechanical properties, such as porosity, diametral tensile strength, and fracture energy. The mechanical properties of DCPD scaffolds with and without PLLA coating after the in vitro static degradation (day 1, week1, 4, and 6) and in vitro dynamic degradation (day 1, week 1, 2, 4, 6, and 8) were investigated by measuring their weight loss, fracture energy, and pH of phosphate buffer solution. In addition, the dog bone marrow stromal stem cells (dBMSCs) adhesion on DCPD and PLLA/DCPD composite samples were examined by scanning electron microscopy. The cell proliferation and differentiation in the medium conditioned with DCPD and PLLA/DCPD composite samples were studied by XTT (2,3-Bis(2-methoxy-4- nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt), and alkaline phosphatase (ALP) assay, respectively. The addition of sodium citrate and PLLA coating played a crucial role in improving the mechanical properties of the samples by increasing the diametral tensile strength from 0.50 ± 0.15 MPa to 2.70 ± 0.54 MPa and increasing the fracture energy from 0.76 ± 0.18 N-mm to 12.67 ± 4.97 N-mm. The DCPD and PLLA/DCPD composite samples were compatible with dBMSCs and the cells were able to proliferate and differentiate in the conditioned medium. The degradation rate of DCPD and PLLA/DCPD samples were not significant different (p > 0.05). However, the DCPD and PLLA/DCPD composite samples those used sodium citrate as a liquid component was found to degrade faster than the groups that use deionized water as liquid component

Indiana University-Purdue University Indianapolis (IUPUI) / Mammary ductal epithelial cell growth is controlled by microenvironmental signals in serum under both normal physiological settings and during breast cancer progression. Importantly, the effects of several of these microenvironmental signals are mediated by the activities of the tumor suppressor protein kinases of the Hippo pathway. Canonically, Hippo protein kinases inhibit cellular growth through the phosphorylation and inactivation of the oncogenic transcriptional co-activator Yes-Associated Protein (YAP). This study defines an alternative mechanism whereby Hippo protein kinases induce growth arrest via the phosphorylation of the long isoform of Angiomotin (Amot130). Specifically, serum starvation is found to activate the Hippo protein kinase, Large Tumor Suppressor (LATS), which phosphorylates the adapter protein Amot130 at serine-175. Importantly, wild-type Amot130 potently inhibits mammary epithelial cell growth, unlike the Amot130 serine-175 to alanine mutant, which cannot be phosphorylated at this residue. The growth-arrested phenotype of Amot130 is likely a result of its mechanistic response to LATS signaling. Specifically, LATS activity promotes the association of Amot130 with the ubiquitin ligase Atrophin-1 Interacting Protein 4 (AIP4). As a consequence, the Amot130-AIP4 complex amplifies LATS tumor suppressive signaling by stabilizing LATS protein steady state levels via preventing AIP4-targeted degradation of LATS. Additionally, AIP4 binding to Amot130 leads to the ubiquitination and stabilization of Amot130. In turn, the Amot130-AIP4 complex signals the ubiquitination and degradation of YAP. This inhibition of YAP activity by Amot130 requires both AIP4 and the ability of Amot130 to be phosphorylated by LATS. Together, these findings significantly modify the current view that the phosphorylation of YAP by Hippo protein kinases is sufficient for YAP inhibition and cellular growth arrest. Based upon these results, the inhibition of cellular growth in the absence of serum more accurately involves the stabilization of Amot130 and LATS, which together inhibit YAP activity and mammary epithelial cell growth.

Indiana University-Purdue University Indianapolis (IUPUI) / In medical research, data analysis often requires complex statistical methods where no closed-form solutions are available. Under such circumstances, Monte Carlo (MC) methods have found many applications. In this dissertation, we proposed several novel statistical models where MC methods are utilized. For the first part, we focused on semicompeting risks data in which a non-terminal event was subject to dependent censoring by a terminal event. Based on an illness-death multistate survival model, we proposed flexible random effects models. Further, we extended our model to the setting of joint modeling where both semicompeting risks data and repeated marker data are simultaneously analyzed. Since the proposed methods involve high-dimensional integrations, Bayesian Monte Carlo Markov Chain (MCMC) methods were utilized for estimation. The use of Bayesian methods also facilitates the prediction of individual patient outcomes. The proposed methods were demonstrated in both simulation and case studies. For the second part, we focused on re-randomization test, which is a nonparametric method that makes inferences solely based on the randomization procedure used in clinical trials. With this type of inference, Monte Carlo method is often used for generating null distributions on the treatment difference. However, an issue was recently discovered when subjects in a clinical trial were randomized with unbalanced treatment allocation to two treatments according to the minimization algorithm, a randomization procedure frequently used in practice. The null distribution of the re-randomization test statistics was found not to be centered at zero, which comprised power of the test. In this dissertation, we investigated the property of the re-randomization test and proposed a weighted re-randomization method to overcome this issue. The proposed method was demonstrated through extensive simulation studies.