New organogermanium substrates for palladium-catalyzed cross-coupling reactions. Application of organogermanes towards the synthesis of carbon-5 modified uridine analogues

The diverse biological properties exhibited by uridine analogues modified at carbon-5 of the uracil base have attracted special interest to the development of efficient methodologies for their synthesis. This study aimed to evaluate the possible application of vinyl tris(trimethylsilyl)germanes in the synthesis of conjugated 5-modified uridine analogues via Pd-catalyzed cross-coupling reactions. The stereoselective synthesis of 5-[(2-tris(trimethylsilyl)germyl)ethenyl]uridine derivatives was achieved by the radical-mediated hydrogermylation of the protected 5-alkynyluridine precursors with tris(trimethylsilyl)germane [(TMS)3GeH]. The hydrogermylation with Ph3GeH afforded in addition to the expected 5-vinylgermane, novel 5-(2-triphenylgermyl)acetyl derivatives. Also, the treatment with Me3GeH provided access to 5-vinylgermane uridine analogues with potential biological applications. Since the Pd-catalyzed cross-coupling of organogermanes has received much less attention than the couplings involving organostannanes and organosilanes, we were prompted to develop novel organogermane precursors suitable for transfer of aryl and/or alkenyl groups. The allyl(phenyl)germanes were found to transfer allyl groups to aryl iodides in the presence of sodium hydroxide or tetrabutylammonium fluoride (TBAF) via a Heck arylation mechanism. On the other hand, the treatment of allyl(phenyl)germanes with tetracyanoethylene (TCNE) effectively cleaved the Ge-C(allyl) bonds and promoted the transfer of the phenyl groups upon fluoride activation in toluene. It was discovered that the trichlorophenyl,- dichlorodiphenyl,- and chlorotriphenylgermanes undergo Pd-catalyzed cross-couplings with aryl bromides and iodides in the presence of TBAF in toluene with addition of the measured amount of water. One chloride ligand on the Ge center allows efficient activation by fluoride to promote transfer of one, two or three phenyl groups from the organogermane precursors. The methodology shows that organogermanes can render a coupling efficiency comparable to the more established stannane and silane counterparts. Our coupling methodology (TBAF/moist toluene) was also found to promote the transfer of multiple phenyl groups from analogous chloro(phenyl)silanes and stannanes.

New Organogermanium Substrates for Palladium-Catalyzed Cross-Coupling Reactions. Application of Organogermanes towards the Synthesis of Carbon-5 Modified Uridine Analogues

The diverse biological properties exhibited by uridine analogues modified at carbon-5 of the uracil base have attracted special interest to the development of efficient methodologies for their synthesis. This study aimed to evaluate the possible application of vinyl tris(trimethylsilyl)germanes in the synthesis of conjugated 5-modified uridine analogues via Pd-catalyzed cross-coupling reactions. The stereoselective synthesis of 5-[(2-tris(trimethylsilyl)germyl)ethenyl]uridine derivatives was achieved by the radical-mediated hydrogermylation of the protected 5-alkynyluridine precursors with tris(trimethylsilyl)germane [(TMS)3GeH]. The hydrogermylation with Ph3GeH afforded in addition to the expected 5-vinylgermane, novel 5-(2-triphenylgermyl)acetyl derivatives. Also, the treatment with Me3GeH provided access to 5-vinylgermane uridine analogues with potential biological applications. Since the Pd-catalyzed cross-coupling of organogermanes has received much less attention than the couplings involving organostannanes and organosilanes, we were prompted to develop novel organogermane precursors suitable for transfer of aryl and/or alkenyl groups. The allyl(phenyl)germanes were found to transfer allyl groups to aryl iodides in the presence of sodium hydroxide or tetrabutylammonium fluoride (TBAF) via a Heck arylation mechanism. On the other hand, the treatment of allyl(phenyl)germanes with tetracyanoethylene (TCNE) effectively cleaved the Ge-C(allyl) bonds and promoted the transfer of the phenyl groups upon fluoride activation in toluene. It was discovered that the trichlorophenyl,- dichlorodiphenyl,- and chlorotriphenylgermanes undergo Pd-catalyzed cross-couplings with aryl bromides and iodides in the presence of TBAF in toluene with addition of the measured amount of water. One chloride ligand on the Ge center allows efficient activation by fluoride to promote transfer of one, two or three phenyl groups from the organogermane precursors. The methodology shows that organogermanes can render a coupling efficiency comparable to the more established stannane and silane counterparts. Our coupling methodology (TBAF/moist toluene) was also found to promote the transfer of multiple phenyl groups from analogous chloro(phenyl)silanes and stannanes.

Assessing the impact of business group diversification on the internationalization of their affiliates: The case of Latin American firms

This dissertation explored the capacity of business group diversification to generate value to their affiliates in an institutional environment characterized by the adoption of structural pro-market reforms. In particular, the three empirical essays explored the impact of business group diversification on the internationalization process of their affiliates. ^ The first essay examined the direct effect of business group diversification on firm performance and its moderating effect on the multinationality-performance relationship. It further explored whether such moderating effect varies depending upon whether the focal affiliate is a manufacturing or service firm. The findings suggested that the benefits of business group diversification on firm performance have a threshold, that those benefits are significant at earlier stages of internationalization and that these benefits are stronger for service firms. ^ The second essay studied the capacity of business group diversification to ameliorate the negative effects of the added complexity faced by its affiliates when they internationalized. The essay explored this capacity in different dimensions of international complexity. The results indicated that business group diversification effectively ameliorated the effects of the added international complexity. This positive effect is stronger in the institutional voids rather than the societal complexity dimension. In the former dimension, diversified business groups can use both their non-market resources and previous experience to ameliorate the effects of complexity on firm performance. ^ The last essay explored whether the benefits of business group diversification on the scope-performance relationship varies depending on the level of development of the network of subsidiaries and the region of operation of the focal firm. The results suggested that the benefits of business group diversification are location bound within the region but that they are not related to the level of development of the targeted countries. ^ The three essays use longitudinal analyses on a sample of Latin American firms to test the hypotheses. While the first essay used multilevel models and fix effects models, the last two essays used exclusively fix effects models to assess the impact of business group diversification. In conclusion, this dissertation aimed to explain the capacity of business group diversification to generate value under conditions of institutional change.^

Essays on the political economy of the Dominican reform process

This dissertation provides an analytical framework to study the political economy of policy reform in the Dominican Republic during the nineties. Based on a country study, I develop two theoretical models that replicate the mechanisms of policy approval in developing countries with weak democracies. The first model considers a pro-reform President who submits a tariff bill to an anti-reform Congress dominated by the opposition party. In between, two opposing lobbies try to get their favored policy approved. Lobbies act as Stackelberg leaders vis a vis a weak President. The behavior of the Congress is determined exogenously while the lobbies act strategically pursuing the approval of the reform bill and indirectly affecting the President's decision. I show that in such a setting external agents like the Press play an important role in the decision-making process of the political actors. ^ The second model presents a similar framework. However, the President, who is a Stackelberg leader, is allowed only two choices, total reform or status-quo. I show how a lobby reacts to an increase in its rival's or its own size. These reactions depend on the President's level of commitment to the reform. Finally, I discuss the effect of variations in the size of the lobbies on the President's choice. The model suitably explains real events that took place in the Dominican Republic in the mid-nineties. ^

Essays on the political economy of the dominican reform process

This dissertation provides an analytical framework to study the political economy of policy reform in the Dominican Republic during the nineties. Based on a country study, I develop two theoretical models that replicate the mechanisms of policy approval in developing countries with weak democracies. The first model considers a pro-reform President who submits a tariff bill to an anti-reform Congress dominated by the opposition party. In between, two opposing lobbies try to get their favored policy approved. Lobbies act as Stackelberg leaders vis a vis a weak President. The behavior of the Congress is determined exogenously while the lobbies act strategically pursuing the approval of the reform bill and indirectly affecting the President's decision. I show that in such a setting external agents like the Press play an important role in the decision-making process of the political actors. The second model presents a similar framework. However, the President, who is a Stackelberg leader, is allowed only two choices, total reform or status-quo. I show how a lobby reacts to an increase in its rival's or its own size. These reactions depend on the President's level of commitment to the reform. Finally, I discuss the effect of variations in the size of the lobbies on the President's choice. The model suitably explains real events that took place in the Dominican Republic in the mid-nineties.

Towards the formation of a sustainable South Florida: An analysis of conflict resolution and consensus building in the South Florida Everglades Ecosystem Restoration Initiative

This dissertation examines the sociological process of conflict resolution and consensus building in South Florida Everglades Ecosystem Restoration through what I define as a Network Management Coordinative Interstitial Group (NetMIG). The process of conflict resolution can be summarized as the participation of interested and affected parties (stakeholders) in a forum of negotiation. I study the case of the Governor's Commission for a Sustainable South Florida (GCSSF) that was established to reduce social conflict. Such conflict originated from environmental disputes about the Everglades and was manifested in the form of gridlock among regulatory (government) agencies, Indian tribes, as well as agricultural, environmental conservationist and urban development interests. The purpose of the participatory forum is to reduce conflicts of interest and to achieve consensus, with the ultimate goal of restoration of the original Everglades ecosystem, while cultivating the economic and cultural bases of the communities in the area. Further, the forum aim to formulate consensus through envisioning a common sustainable community by providing means to achieve a balance between human and natural systems. ^ Data were gathered using participant observation and document analysis techniques to conduct a theoretically based analysis of the role of the Network Management Coordinative Interstitial Group (NetMIG). I use conflict resolution theory, environmental conflict theory, stakeholder analysis, systems theory, differentiation and social change theory, and strategic management and planning theory. ^ The purpose of this study is to substantiate the role of the Governor's Commission for a Sustainable South Florida (GCSSF) as a consortium of organizations in an effort to resolve conflict rather than an ethnographic study of this organization. Environmental restoration of the Everglades is a vehicle for recognizing the significance of a Network Management Coordinative Interstitial Group (NetMIG), namely the Governor's Commission for a Sustainable South Florida (GCSSF), as a structural mechanism for stakeholder participation in the process of social conflict resolution through the creation of new cultural paradigms for a sustainable community. ^

The men behind the market: Merchants, the Atlantic slave trade, and the shaping of South Carolina plantation society, 1700–1756

The purpose of this dissertation is to examine the role played by merchants in the shaping of South Carolina plantation society in its early stages of development. In 1700 South Carolina was on the fringes of the British Empire. By mid-century the colony had become an integral part of the British Atlantic system. This dissertation addresses merchants' activity in the shaping of plantation society through their involvement in the Atlantic slave trade. Records of the British and South Carolina governments, and petitions from merchants on both sides of the Atlantic have been extremely valuable in understanding the complex and rapidly changing political affiliations of merchants on both sides of the Atlantic. These sources are valuable to this study since they illustrate the merchants' strategy of utilizing government policies to acquire the absolute best terms of trade. Records such as wills and inventories yielded valuable information on merchants' economic portfolios and provided valuable insight into their personal lives. The data shows that the integration of Colonial South Carolina into the global economy can be attributed to its merchant class, who actively sought out business opportunities in the global economy while working within the framework of British mercantilism.

Essays on the political economy of trade policy and economic *development

This dissertation studies the political economy of trade policy in a developing country, namely Turkey, under different economic and political regimes. The research analyzes the effects of these different regimes on the import structure, the trade policy and the industrialization process in Turkey and derives implications for aggregate welfare. ^ In the second chapter, the effects of trade liberalization policies on import demand are examined. Using disaggregated industry-level data, import demand elasticities for various sectors have been computed, analyzed under different economic regimes, and compared with those of developed countries. The results are statistically significant and reliable, and conform to the predictions of economic theory. Estimation of these elasticities is also a necessary ingredient for the third chapter of the dissertation. ^ The third chapter examines the predictions of the state-of-the-art “Protection For Sale” model of Grossman and Helpman (1994). Employing advanced econometric methods and a unique data set, strong support is found for the fundamental predictions of the model in the context of Turkey. Specifically, the government is found to attach a much higher weight to social welfare than to political contributions. This weight is higher under the democratic regime than under the dictatorship, a result potentially of interest to all researchers in the area of political economy. ^ The fourth chapter looks at the effects of industry concentration and import price shocks on protection, promotion and the choice of policy instruments in Turkey. In this context, it examines and finds support for the predictions of some well-known models in the literature. ^

Strategic positioning of Taiwan in the outsourcing market: Evidence from information technology services and electronic manufacturing outsourcing to China

In outsourcing relationships with China, the Electronic Manufacturing (EM) and Information Technology Services (ITS) industry in Taiwan may possess such advantages as the continuing growth of its production value, complete manufacturing supply chain, low production cost and a large-scale Chinese market, and language and culture similarity compared to outsourcing to other countries. Nevertheless, the Council for Economic Planning and Development of Executive Yuan (CEPD) found that Taiwan's IT services outsourcing to China is subject to certain constraints and might not be as successful as the EM outsourcing (Aggarwal, 2003; CEPD, 2004a; CIER, 2003; Einhorn and Kriplani, 2003; Kumar and Zhu, 2006; Li and Gao, 2003; MIC, 2006). Some studies examined this issue, but failed to (1) provide statistical evidence about lower prevalence rates of IT services outsourcing, and (2) clearly explain the lower prevalence rates of IT services outsourcing by identifying similarities and differences between both types of outsourcing contexts. This research seeks to fill that gap and possibly provide potential strategic guidelines to ITS firms in Taiwan. This study adopts Transaction Cost Economics (TCE) as the theoretical basis. The basic premise is that different types of outsourcing activities may incur differing transaction costs and realize varying degrees of outsourcing success due to differential attributes of the transactions in the outsourcing process. Using primary data gathered from questionnaire surveys of ninety two firms, the results from exploratory analysis and binary logistic regression indicated that (1) when outsourcing to China, Taiwanese firms' ITS outsourcing tends to have higher level of asset specificity, uncertainty and technical skills relative to EM outsourcing, and these features indirectly reduce firms' outsourcing prevalence rates via their direct positive impacts on transaction costs; (2) Taiwanese firms' ITS outsourcing tends to have lower level of transaction structurability relative to EM outsourcing, and this feature indirectly increases firms' outsourcing prevalence rates via its direct negative impacts on transaction costs; (3) frequency does influence firms' transaction costs in ITS outsourcing positively, but does not bring impacts into their outsourcing prevalence rates, (4) relatedness does influence firms' transaction costs positively and prevalence rates negatively in ITS outsourcing, but its impacts on the prevalence rates are not caused by the mediation effects of transaction costs, and (5) firm size of outsourcing provider does not affect firms' transaction costs, but does affect their outsourcing prevalence rates in ITS outsourcing directly and positively. Using primary data gathered from face-to-face interviews of executives from seven firms, the results from inductive analysis indicated that (1) IT services outsourcing has lower prevalence rates than EM outsourcing, and (2) this result is mainly attributed to Taiwan's core competence in manufacturing and management and higher overall transaction costs of IT services outsourcing. Specifically, there is not much difference between both types of outsourcing context in the transaction characteristics of reputation and most aspects of overall comparison. Although there are some differences in the feature of firm size of the outsourcing provider, the difference doesn't cause apparent impacts on firms' overall transaction costs. The medium or above medium difference in the transaction characteristics of asset specificity, uncertainty, frequency, technical skills, transaction structurability, and relatedness has caused higher overall transaction costs for IT services outsourcing. This higher cost might cause lower prevalence rates for ITS outsourcing relative to EM outsourcing. Overall, the interview results are consistent with the statistical analyses and provide support to my expectation that in outsourcing to China, Taiwan's electronic manufacturing firms do have lower prevalence rates of IT services outsourcing relative to EM outsourcing due to higher transaction costs caused by certain attributes. To solve this problem, firms' management should aim at identifying alternative strategies and strive to reduce their overall transaction costs of IT services outsourcing by initiating appropriate strategies which fit their environment and needs.

The market value implications of pension asset allocation

Pension funds have been part of the private sector since the 1850's. Defined Benefit pension plans [DB], where a company promises to make regular contributions to investment accounts held for participating employees in order to pay a promised lifelong annuity, are significant capital markets participants, amounting to 2.3 trillion dollars in 2010 (Federal Reserve Board, 2013). In 2006, Statement of Financial Accounting Standards No.158 (SFAS 158), Employers' Accounting for Defined Benefit Pension and Other Postemployment Plans, shifted information concerning funding status and pension asset/liability composition from disclosure in the footnotes to recognition in the financial statements. I add to the literature by being the first to examine the effect of recent pension reform during the financial crisis of 2008-09. This dissertation is comprised of three related essays. In my first essay, I investigate whether investors assign different pricing multiples to the various classes of pension assets when valuing firms. The pricing multiples on all classes of assets are significantly different from each other, but only investments in bonds and equities were value-relevant during the recent financial crisis. Consistent with investors viewing pension liabilities as liabilities of the firm, the pricing multiples on pension liabilities are significantly larger than those on non-pension liabilities. The only pension costs significantly associated with firm value are actual rate of return and interest expense. In my second essay, I investigate the role of accruals in predicting future cash flows, extending the Barth et al. (2001a) model of the accrual process. Using market value of equity as a proxy for cash flows, the results of this study suggest that aggregate accounting amounts mask how the components of earnings affect investors' ability to predict future cash flows. Disaggregating pension earnings components and accruals results in an increase in predictive power. During the 2008-2009 financial crisis, however, investors placed a greater (and negative) weight on the incremental information contained in the individual components of accruals. The inferences are robust to alternative specifications of accruals. Finally, in my third essay I investigate how investors view under-funded plans. On average, investors: view deficits arising from under-funded plans as belonging to the firm; reward firms with fully or over-funded pension plans; and encourage those funds with unfunded pension plans to become funded. Investors also encourage conservative pension asset allocations to mitigate firm risk, and smaller firms are perceived as being better able to handle the risk associated with underfunded plans. During the financial crisis of 2008-2009 underfunded status had a lower negative association with market value. In all three models, there are significant differences in pre- and post- SFAS 158 periods. These results are robust to various scenarios of the timing of the financial crisis and an alternative measure of funding.

Towards the prediction of mutations in genomic sequences

Bio-systems are inherently complex information processing systems. Furthermore, physiological complexities of biological systems limit the formation of a hypothesis in terms of behavior and the ability to test hypothesis. More importantly the identification and classification of mutation in patients are centric topics in today's cancer research. Next generation sequencing (NGS) technologies can provide genome-wide coverage at a single nucleotide resolution and at reasonable speed and cost. The unprecedented molecular characterization provided by NGS offers the potential for an individualized approach to treatment. These advances in cancer genomics have enabled scientists to interrogate cancer-specific genomic variants and compare them with the normal variants in the same patient. Analysis of this data provides a catalog of somatic variants, present in tumor genome but not in the normal tissue DNA. In this dissertation, we present a new computational framework to the problem of predicting the number of mutations on a chromosome for a certain patient, which is a fundamental problem in clinical and research fields. We begin this dissertation with the development of a framework system that is capable of utilizing published data from a longitudinal study of patients with acute myeloid leukemia (AML), who's DNA from both normal as well as malignant tissues was subjected to NGS analysis at various points in time. By processing the sequencing data at the time of cancer diagnosis using the components of our framework, we tested it by predicting the genomic regions to be mutated at the time of relapse and, later, by comparing our results with the actual regions that showed mutations (discovered at relapse time). We demonstrate that this coupling of the algorithm pipeline can drastically improve the predictive abilities of searching a reliable molecular signature. Arguably, the most important result of our research is its superior performance to other methods like Radial Basis Function Network, Sequential Minimal Optimization, and Gaussian Process. In the final part of this dissertation, we present a detailed significance, stability and statistical analysis of our model. A performance comparison of the results are presented. This work clearly lays a good foundation for future research for other types of cancer.^