Calls continually are made to provide economic assessments of research program achievements and efficiency. Yet little effort has been given to develop an assessment framework that would focus on the research discovery itself, treating the research manager as a producer and the research technology as a knowledge production function. The present dissertation develops such a framework and uses it, with a variety of analytical approaches, to evaluate a two-phase international aquacultural research program consisting of 55 distinct studies. A Bayesian knowledge measure is developed for this purpose, allowing close examination of each of two knowledge creation pathways ��� the extent of new findings (mean surprise) and the extent of uncertainty reduction (precision). Factors affecting each of these two pathways are estimated in decomposed form, their total effects on knowledge achievement then combined to form an aggregate knowledge production function. Team workload, education level, and scientist travel distance strongly affect knowledge creation as postulated, although exhibiting varying effect magnitudes and significances across the two program phases. A research study's analytical approach significantly affects its knowledge acquisition pathways, accounting partially for the newness of its scientific discoveries. Survey studies tend, in contrast, to have greater potential for new findings, but yield greater uncertainty than do experimental studies. In each of the two program phases, fish market trading and water quality are, in my output-elasticities-based approach, respectively the least productive topic area and research-outcome dimension. Asian researchers appear ��� compared to their colleagues in South America and Africa ��� to achieve the highest predictive precision but the least mean surprise, probably because of the greater maturity of their projects. In both program phases, estimated output elasticities imply increasing knowledge returns to scale, although the elasticities decline from 3.52 in Phase I to 1.07 in Phase II. The dual cost function approach provides indirect insight into the program manager���s investment decisions and to the returns to knowledge output, complementing the primal approach. In my cost-based approach, knowledge cost elasticities are below unity, estimated at 0.49 in Phase II and 0.37 in Phase I, consistent with the increasing returns to scale found in the output-elasticities-based approach. Given the increasing returns to scale estimated with both approaches, the aquacultural program appears to have a substantial incentive to enlarge its knowledge investments. Also consistent with duality, the least-output-productive fish-trade topic area, water-quality outcome, and Asian research are found in my cost analysis to be the most cost-consuming. The technical efficiencies of the aquacultural program's individual studies are also examined, relative to both one another and to their own potentially best practices. The examination is conducted using, successively, the Farrell input technical efficiency measure and the directional sum-distance measure. Results are consistent across these two efficiency instruments, confirming the conclusions about output and cost elasticities in the previous chapters and providing a completeness to the overall research evaluation. / Graduation date: 2013 / Access restricted to the OSU Community at author's request from Dec. 27, 2012 - Dec. 27, 2014

This project updated the California State University, San Bernardino's Office of Technology Transfer and Commercialization's Solicitation Management System (SMS) software, used to facilitate the processing of grant proposal solicitations. The SMS software update improved the interface so that it is more user-friendly, increased the processing speed, and added additional functions necessary to comply with new requirements. The software was rewritten using the Spring and Hibernate frameworks.

Learning exercises containing chemical calculations are necessary for complex understanding of some parts of chemical curriculum. This diploma thesis deals with creation and evaluation of worksheets containing multicomponent learning tasks closely connected to reality for pupils of elementary and high school. The theoretical part consists of the summary of present valid Czech curricular documents, mainly parts focused on chemical calculations and sustainable development. The main part of this thesis is creation of worksheets containing multicomponent learning tasks focused on different topics of chemistry which were chosen according to Framework Education Programmes. Created worksheets were verified and evaluated at high school. Based on evaluations of worksheets action research focused on problems during solving chemical calculations was conducted on elementary school.

Indiana University-Purdue University Indianapolis (IUPUI) / Protein-protein interactions play a crucial role in a wide range of biological processes. Research on the design and synthesis of small molecules to modulate these proteinprotein interactions can lead to new targets and drugs to modulate their function. In Chapter one, we discuss the design and synthesis of small molecules to probe a proteinprotein interaction in a voltage-gated Ca2+ channel. Virtual screening identified a compound (BTT-3) that contained a 3,4-dihydro-3,4’-pyrazole core. This compound had modest biological activity when tested in a fluorescence polarization (FP) assay. The synthetic route to BTT-3 consisted of six steps. In addition, analogs of BTT-3 were made for a structure-activity study to establish the importance of a carboxylate moiety. We also synthesized a biotinylated benzophenone photo-affinity probe and linked it to BTT-3 to identify additional protein targets of the compound. In Chapter two, small-molecule antagonists targeting uPA-uPAR protein-protein interaction are presented. A total of 500 commercially-available compounds were previously identified by virtual screening and tested by a FP assay. Three classes of compounds were found with biological activity. The first class of compounds contains pyrrolidone core structures represented by IPR- 1110, the second class has a novel pyrrolo[3,4-c]pyrazole ring system, represented by xv IPR-1283 and the last series had compounds with a 1,2-disubstituted 1,2- dihydropyrrolo[3,4-b]indol-3(4H)-one core structure, represented by IPR-540. Each of these three compounds were synthesized and assessed by FP and ELISA assays. A binding mode of IPR-1110 with uPA was subsequently proposed. Based on this binding mode, another 61 IPR-1110 derivatives were synthesized by us to illustrate the SAR activity. Analogs of the other two series were also synthesized.

Indiana University-Purdue University Indianapolis (IUPUI) / Purpose: Script concordance tests (SCTs) are assessments purported to measure clinical data interpretation. The aims of this research were to (1) test the psychometric properties of SCT items, (2) directly examine the construct validity of SCTs, and (3) explore the concurrent validity of six SCT scoring methods while also considering validity at the item difficulty and item type levels. Methods: SCT scores from a problem solving SCT (SCT-PS; n=522) and emergency medicine SCT (SCT-EM; n=1040) were used to investigate the aims of this research. An item analysis was conducted to optimize the SCT datasets, to categorize items into levels of difficulty and type, and to test for gender biases. A confirmatory factor analysis tested whether SCT scores conformed to a theorized unidimensional factor structure. Exploratory factor analyses examined the effects of six SCT scoring methods on construct validity. The concurrent validity of each scoring method was also tested via a one-way multivariate analysis of variance (MANOVA) and Pearson’s product moment correlations. Repeated measures analysis of variance (ANOVA) and one-way ANOVA tested the discriminatory power of the SCTs according to item difficulty and type. Results: Item analysis identified no gender biases. A combination of moderate model-fit indices and poor factor loadings from the confirmatory factor analysis suggested that the SCTs under investigation did not conform to a unidimensional factor structure. Exploratory factor analyses of six different scoring methods repeatedly revealed weak factor loadings, and extracted factors consistently explained only a small portion of the total variance. Results of the concurrent validity study showed that all six scoring methods discriminated between medical training levels in spite of lower reliability coefficients on 3-point scoring methods. In addition, examinees as MS4s significantly (p<0.001) outperformed their MS2 SCT scores in all difficulty categories. Cross-sectional analysis of SCT-EM data reported significant differences (p<0.001) between experienced EM physicians, EM residents, and MS4s at each level of difficulty. When considering item type, diagnostic and therapeutic items differentiated between all three training levels, while investigational items could not readily distinguish between MS4s and EM residents. Conclusions: The results of this research contest the assertion that SCTs measure a single common construct. These findings raise questions about the latent constructs measured by SCTs and challenge the overall utility of SCT scores. The outcomes of the concurrent validity study provide evidence that multiple scoring methods reasonably differentiate between medical training levels. Concurrent validity was also observed when considering item difficulty and item type.

Indiana University-Purdue University Indianapolis (IUPUI) / 17-β estradiol (E2) exerts protective effects in hypoxia-induced pulmonary hypertension (HPH) via endothelial cell estrogen receptor (ER)-dependent mechanisms. However, the effects of hypoxia on ER expression in the pulmonary-right ventricle (RV) axis remain unknown. Based on previous data suggesting a role of ER-β in mediating E2 protection, we hypothesized that hypoxia selectively up-regulates ER-β in the lung and pulmonary endothelial cells. In our Male Sprague-Dawley rat model, chronic hypoxia exposure (10% FiO2) resulted in a robust HPH phenotype associated with significant increases in ER- β but not ER-α protein in the lung via western blotting. More importantly, this hypoxia-induced ER-β increase was not replicated in the RV, left ventricle (LV) or in the liver. Hence, hypoxia-induced ER-β up-regulation appears to be lung-specific. Ex vivo, hypoxia exposure time-dependently up-regulated ER-β but not ER-α in cultured primary rat pulmonary artery endothelial cells (RPAECs) exposed to hypoxia (1% O2) for 4, 24 or 72h. Furthermore, the hypoxia induced ER-β protein abundance, while not accompanied by increases in its own transcript, was associated with ER-β nuclear translocation, suggesting increase in activity as well as post-transcriptional up-regulation of ER-β. Indeed, the requirement for ER-β activation was indicated in hypoxic ER-βKO mice where administration of E2 failed to inhibit hypoxia-induced pro-proliferative ERK1/2 signaling. Interestingly, HIF-1α accumulation was noted in lung tissue of hypoxic ER-βKO mice; consistent with previously reported negative feedback of ER-β on HIF-1α protein and transcriptional activation. In RAPECs, HIF-1 stabilization and overexpression did not replicate the effects of ER- β up-regulation seen in gas hypoxia; suggestive that HIF-1α is not sufficient for ER-β up- regulation. Similarly, HIF-1 inhibition with chetomin did not result in ER-β down-regulation. HIF-1α knockdown in RPAECs in hypoxic conditions is currently being investigated. Hypoxia increases ER- β, but not ER-α in the lung and lung vascular cells. Interpreted in context of beneficial effects of E2 on hypoxic PA and RV remodeling, our data suggest a protective role for ER-β in HPH. The mechanisms by which hypoxia increases ER-β appears to be post-transcriptional and HIF-1α independent. Elucidating hypoxia-related ER-β signaling pathways in PAECs may reveal novel therapeutic targets in HPH.

Indiana University-Purdue University Indianapolis (IUPUI) / Text mining is a process of extraction of knowledge from unstructured text documents. We have huge volumes of text documents in digital form. It is impossible to manually extract knowledge from these vast texts. Hence, text mining is used to find useful information from text through the identification and exploration of interesting patterns. The objective of this thesis in text mining area is to find compact but high quality frequent patterns from text documents related to neuroscience field. We try to prove that interactive sampling algorithm is efficient in terms of time when compared with exhaustive methods like FP Growth using RapidMiner tool. Instead of mining all frequent patterns, all of which may not be interesting to user, interactive method to mine only desired and interesting patterns is far better approach in terms of utilization of resources. This is especially observed with large number of keywords. In interactive patterns mining, a user gives feedback on whether a pattern is interesting or not. Using Markov Chain Monte Carlo (MCMC) sampling method, frequent patterns are generated in an interactive way. Thesis discusses extraction of patterns between the keywords related to some of the common disorders in neuroscience in an interactive way. PubMed database and keywords related to schizophrenia and alcoholism are used as inputs. This thesis reveals many associations between the different terms, which are otherwise difficult to understand by reading articles or journals manually. Graphviz tool is used to visualize associations.

Indiana University-Purdue University Indianapolis (IUPUI) / RNA polymerase II (RNAPII) is regulated by multiple modifications to the C-terminal domain (CTD) of the largest subunit, Rpb1. This study has focused on the relationship between hyperphosphorylation of the CTD and RNAPII turnover and proteolytic degradation as well as post-translational modifications of the globular core of RNAPII. Following tandem affinity purification, western blot analysis showed that MG132 treated RTR1 ERG6 deletion yeast cells have accumulation of total RNAPII and in particular, the hyperphosphorylated form of the protein complex. In addition, proteomic studies using MuDPIT have revealed increased interaction between proteins of the ubiquitin-proteasome degradation system in the mutant MG132 treated yeast cells as well as potential ubiquitin and phosphorylation sites in RNAPII subunits, Rpb6 and Rpb1, respectively. A novel Rpb1 phosphorylation site, T1471-P, is located in the linker region between the CTD and globular domain of Rpb1 and will be the focus of future studies to determine biological significance of this post-translational modification.

Indiana University-Purdue University Indianapolis (IUPUI) / The substantial interpersonal and economic costs of depression make it imperative to better understand the predictors and moderators of depressive symptoms. The ability to use social support protects people from depressive symptoms, but individuals high in attachment avoidance tend not to use others as sources of support. Research has found that attachment avoidance is related to depressive symptoms in some samples but not in others (Mikulincer & Shaver, 2007; Shea, 2011). Thus, there appear to be factors that moderate the relationship between attachment avoidance and depressive symptoms. The present study examined if cognitive abilities that facilitate effective emotion regulation strategies moderate the relationship between attachment avoidance and depressive symptoms. Using a sample of college students, attachment avoidance, cognitive abilities, depressive symptoms, and other indices of psychological distress and well-being were measured and examined for evidence of moderation via hierarchical linear regression. The hypothesis that cognitive abilities moderate the relationship between attachment avoidance and depressive symptoms was not supported (ΔR2 = 0.02, p = .68). Factors contributing to the null findings are discussed and conceptual and methodological suggestions are offered for future research.

Indiana University-Purdue University Indianapolis (IUPUI) / Cellular membranes contain a staggering diversity of lipids. The lipids are heterogeneously distr ibuted to create regions, or domains, whose physical properties differ from the bulk membrane and play an essential role in modulating the function of resident proteins. Many basic questions pertaining to the formation of these lateral assemblies remain. T his research employs model membranes of well - defined composition to focus on the potential role of polyunsaturated fatty acids (PUFAs) and their interaction with cholesterol (chol) in restructuring the membrane environment. Omega - 3 (n - 3) PUFAs are the main bioactive components of fish oil, whose consumption alleviates a variety of health problems by a molecular mechanism that is unclear. We hypothesize that the incorporation of PUFAs into membrane lipids and the effect they have on molecular organization may be, in part, responsible. Chol is a major constituent in the plasma membrane of mammals. It determines the arrangement and collective properties of neighboring lipids, driving the formation of domains via differential affinity for different lipids . T he m olecular organization of 1 -[ 2 H 31 ]palmitoyl -2- eicosapentaenoylphosphatidylcholine (PEPC - d 31 ) and 1 -[ 2 H 31 ]palmitoyl -2- docosahexaenoylphosphatidylcholine (PDPC -d 31 ) in membran es with sphingomyelin (SM) and chol (1:1:1 mol) was compared by solid - state 2 H NMR spectroscopy. Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids are the two major n - 3 PUFAs found in fish oil, while PEPC -d 31 and PDPC -d 31 are phospholipids containing the respective PUFAs at the sn - 2 position and a perdeuterated palmitic acid a t the sn - 1 position . Analysis of s pectra recorded as a function of temperature indicate s that in both cases, formation of PUFA - rich (less ordered) and SM - rich (more ordered) domains occurred. A surprisingly substantial proportion of PUFA was found to infil trate the more ordered domain. There was almost twice as much DHA (65%) as EPA (30%) . The implication is that n - 3 PUFA s can incorporate into lipid rafts, which are domains enriched in SM and chol in the plasma membrane, and potentially disrupt the activity of signaling proteins that reside therein. DHA, furthermore, may be the more potent component of fish oil. PUFA - chol interactions were also examined through affinity measurements. A novel method utilizing electron paramagnetic resonance (EPR) was develope d, to monitor the partitioning of a spin - labeled analog of chol , 3β - doxyl - 5α - cholestane (chlstn), between large unilamellar vesicles (LUVs) and met hyl - β - cyclodextrin (mβCD). The EPR spectra for chlstn in the two environments are distinguishable due to the substantial differences in tumbling rates , allowing the population distribution ratio to be determined by spectral simulation. Advantages of this approach include speed of implementation and a vo idance of potential artifact s associated with physical separation of LUV and mβCD . Additionally, in a check of the method, t he relative partition coefficients between lipids measured for the spin label analog agree with values obtained for chol by isothermal titration calorimetry (ITC). Results from LUV with different composition confirmed a hierarchy of decreased sterol affinity for phospholipids with increasing acyl chain unsaturation , PDPC possessing half the affinity of the corresponding monounsaturated phospholipid. Taken together, the results of these studies on model membranes demonstrate the potential for PUFA - driven alteration of the architecture of biomembranes, a mechanism through which human health may be impacted.