Thesis advisor: Junona Moroianu / Some non melanoma skin cancers (NMSC) have been associated with human papillomavirus (HPV) pathogenesis, like epidermodysplasia verruciformis (EV) and squamous cell carcinoma (SCC). EV is a genetically inherited skin disease that develops when the individuals are infected with cutaneous HPV types belonging to the β-genus, especially types 5 and 8. Transgenic mouse lineages expressing all early genes of cutaneous HPV8 develop papillomas, dysplasias and SCC after UV irradiation and this correlates with enhanced HPV8 oncogenes expression. We have previously discovered that the nuclear localization of mucosal HPV16 E7 and HPV11 E7 proteins is mediated by their zinc-binding domain via a Ran-dependent pathway and independent of nuclear import receptors and that a patch of hydrophobic residues within the zinc-binding domain of HPV16 E7 and HPV11 E7 proteins is responsible for their nuclear import via hydrophobic interactions with FG nucleoporins. Here we investigated the nucleocytoplasmic traffic of cutaneous HPV8 E7 protein using confocal microscopy to analyze the intracellular localization of EGFP-8E7, its subdomains and its mutants after transient transfections. We also investigated the nuclear import ability of GST-8E7, its subdomains and mutants using in vitro nuclear import assays in digitonin-permeabilized HeLa cells. In addition, we performed isolation assays to study the direct interaction between HPV8 E7 and two FG nucleoporins, Nup62 and Nup153 or the nuclear export receptor, CRM1. We found that the nuclear import of cutaneous HPV8 E7 is mediated by a nuclear localization signal (NLS) located within its zinc-binding domain. Furthermore, we determined that the hydrophobic residues within the 65LRLFV69 patch are responsible for the nuclear import and nuclear localization of HPV8 E7 via direct hydrophobic interactions with FG nucleoporins, Nup62 and Nup153, whereas the positively charged arginine 66 plays no significant role in the function of the NLS. In addition, we examined the nuclear export mechanism of cutaneous HPV8 E7 protein and showed that it has a leucine-rich nuclear export signal (NES) in its C-terminal domain that is recognized by the CRM1 nuclear export receptor. These studies are essential for understanding the nucleocytoplasmic traffic of cutaneous HPV8 E7 protein. / Thesis (PhD) — Boston College, 2014. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

Thesis advisor: Junona Moroianu / Human papillomaviruses (HPVs) have been estimated to be the most common sexually transmitted infection in the United States. In addition to condyloma accuminata, infection of the squamous basal epithelium by high-risk HPVs, notably type 16 (HPV16), has been shown to be the primary etiological agent in the majority of cervical carcinomas. The E7 major transforming protein of HPV16, along with E6, has been linked to tumorigenesis and malignancy. While the E7 protein itself possesses no enzymatic activity, its ability to bind a number of nuclear and cytoplasmic targets subverts a variety of cellular regulatory complexes and facilitates viral replication. Previous studies in the Moroianu Lab have shown the HPV16 E7 oncoprotein to translocate across the nuclear pore complex (NPC) in a facilitated manner dependent on a non-canonical, c-terminal, nuclear localization signal (cNLS) for import, and a consensus leucine-rich nuclear export sequence (NES) for export (28). While the leucine-rich NES has been characterized, a full examination of the cNLS has yet to be performed. Here we present evidence that the karyopherin independent nuclear import mediated by the cNLS of 16E7 is dependent on its c-terminal Zn binding domain. Furthermore, we demonstrate that nuclear import is mediated by the direct interaction of a small patch of hydrophobic residues, 65LRLCV69, with the FG domain of the central FG-nucleoporin Nup62. In addition, we examined a potential regulatory mechanism of 16E7 nucleocytoplasmic translocation. Previous work has shown that a serine conserved in the high-risk HPVs at position 71 is phosphorylated by an unknown kinase. Here we present evidence that while phosphorylation of S71 is not required for either 16E7 nuclear localization or nuclear export in HeLa cells, mimicking phosphorylation of the S71 residue results in a statistically significant shift in the distribution of localization phenotypes of the resultant cell population toward a larger percentage exhibiting more nuclear localization. These data suggest that nucleocytoplasmic transport of 16E7 is, at least in part, a regulated process. / Thesis (PhD) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

Thesis advisor: Junona Moroianu / The E7 protein of low risk HPV11 has been shown to interact with multiple proteins, including pRb, in both the cytoplasm and the nucleus. High risk HPV16 E7 and low risk HPV11 E7 share a novel nuclear import pathway independent of karyopherins but dependent on the GTPase Ran (Angeline, et al., 2003; Knapp, et al., 2009; Piccioli, et al., 2010). We continued to analyze the nucleocytoplasmic transport of HPV11 E7 in vivo through transfection assays in HeLa cells with EGFP-HPV11 E7 wild type and mutant fusion constructs. We found that nuclear localization of HPV11 E7 is mediated by a nuclear localization signal located in the C-terminal domain which contains a unique zinc-binding domain. Mutations of cysteine residues that interfered with zinc-binding clearly disrupted the nuclear localization of the EGFP-11cE7 and EGFP-11E7 mutants. These data suggest that the integrity of the zinc-binding domain is essential for the nuclear localization of HPV11 E7. In addition, we discovered that HPV11 E7 has a leucine-rich C-terminal nuclear export signal (NES) (76IRQLQDLLL84) mediating the nuclear export of HPV11 E7 in a CRM1-dependent manner. / Thesis (BS) — Boston College, 2011. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Biology Honors Program. / Discipline: Biology.

O objetivo do estudo foi estimar os impactos do tempo dos procedimentos portuários sobre as exportações brasileiras. O trabalho utiliza uma base de dados inovadora com dados de exportações municipais, com distinção do porto utilizado, país de destino e com produtos desagregados de acordo com o sistema harmonizado em 4 dígitos para o período de 2010 a 2012. Uma equação gravitacional em diferenças foi estimada pelo método de efeitos fixos utilizando as exportações municipais relativas (volume e número de setores exportadores) contra medidas de tempo em horas dos procedimentos portuários e outras variáveis de controle. Os resultados da análise descritiva indicam a presença de um gargalo no escoamento da produção brasileira para o mercado internacional, e apontam para a necessidade de investimentos que ampliem a capacidade portuária, reduzindo as ineficiências que geram elevadas porcentagens do tempo de inoperância nos portos brasileiros. Os resultados das estimações indicam que, de modo geral, cada hora adicional na condução dos procedimentos portuários representam custos para os exportadores brasileiros, que podem estar se refletindo em perda da competitividade dos produtos nacionais no exterior. Segundo as estimações realizadas, cada hora adicional de estadia no porto mediano é equivalente a uma redução do volume total das exportações municipais em cerca de 1%. Além disso, uma redução de 10% no tempo de estadia relativo do navio no porto pode aumentar o número de categorias de produtos exportados entre 0,3% e 0,9%. / The purpose of this study was to estimate the impacts of the port procedures time on Brazilian exports. The study uses an innovative database with municipal exports, with distinction over the port used, country of destination, and with disaggregated products according to the harmonized system in 4 digits for the period from 2010 to 2012. A difference gravity equation was estimated by the fixed effect method using the relative municipal exports (volume and the number of exporter sectors) against time measured in hours of the port procedures and other control variables. The results of descriptive analysis indicate the presence of a bottleneck in the flow of Brazilian production for the international market, and point to the need for investments that increase port capacity, reducing the inefficiencies that generate high ineffectiveness time percentages in Brazilian ports. The estimation results indicate that, in general, each additional hour in the conduction of the port procedures represent costs to the Brazilian exporters. Those costs may be reflected in loss of competitiveness of the domestic products abroad. According to the estimates made, each additional hour of the ship stay in the median port is equivalent to a reduction of the municipal exports in around 1%. Besides that, a reduction of 10% in time of stay for a ship in port can increase the number of exported product categories between 0.3% and 0.9%.

Thesis advisor: James E. Anderson / Thesis advisor: Rosen Valchev / The effect of uncertainty on firms' behavior and on the macroeconomy is generally negative in the literature. Extensive research has also demonstrated that financial frictions limit the extent of firms' activities and growth prospects. In the first two chapters of this dissertation, I study both empirically and theoretically how a specific type of uncertainty, exchange rate uncertainty, interacts with financial frictions to affect the behavior of exporting firms. In line with the existing literature, I find in the first chapter that exports of manufacturing sectors in which firms are more financially constrained decrease by more in times of high uncertainty. Having more tangible capital, which can potentially be used as collateral, makes the effect of uncertainty less negative, especially im sectors where firms are large. Relying more on external financing, on the other hand, makes the effect more negative and affects sectors with small firms more. Current theoretical models have little to say about the effect of uncertainty on heterogeneous firms. To address this issue, I introduce in the second chapter a model of financially-constrained heterogeneous exporting firms in which credit conditions depend on the degree of exchange rate uncertainty. Firms in different sectors face different types of financial constraints, and are therefore differently affected by uncertainty. I use the calibrated model to evaluate potential policies that could be implemented to alleviate the negative effect of exchange rate uncertainty on exports. The uncovered interest parity puzzle is the empirical finding that countries with higher risk-free interest rates tend to see their currencies appreciate in the short run. Typical two-country macroeconomic models instead predict that high interest-rate currencies depreciate, with arbitrage opportunities eliminating profitable carry trade strategies. The international finance literature responded to this puzzle by providing several alternative theoretical models able to explain the puzzle. In the third chapter of this dissertation, I study how the predictions of two of these alternative models - the habit model of Verdelhan (2010) and the distorted belief model of Gourinchas and Tornell (2004) - are affected when re-cast in a standard dynamic stochastic general equilibrium framework. I investigate how the mechanisms rely on specific parameter values in order to find under which conditions, if any, they can explain the UIP puzzle. In addition, I obtain business cycle moments from model simulations and compare them to the moments obtained from a standard two-country DSGE model and from the data. My results show that for the first model, the habit model, the UIP results disappear under realistic calibrations. For the second model, the distorted beliefs model, UIP properties remain under some calibrations. In addition, business cycle predictions remain close to empirical evidence. / Thesis (PhD) — Boston College, 2019. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Economics.

Summary in Chinese. / Thesis (M.B.A.)--Chinese University of Hong Kong. / Bibliography: leaves 81.

Chiu Chung Wai. / Summary in Chinese on endpapers. / Thesis (M.B.A.)--Chinese University of Hong Kong. / Bibliography: leaves 86-87.

Wat Cheong Huen. / Thesis (M.B.A.)--Chinese University of Hong Kong. / Bibliography: leaves [170]-171.

This thesis examines the British Joint Intelligence Bureau (JIB), which, between its creation in 1946 and its end in 1964, gathered, collated and processed topographic, economic, scientific, and atomic intelligence. It did so on an inter-service, national level. The thesis examines the creation of the organisation, in the aftermath of the Second World War, exploring what factors and which people supported the creation of the new agency. It then moves on to examine the work of the JIB in several of its key fields of work, namely topography, economics and monitoring the threat from Soviet nuclear forces, before examining some of the JIB’s international connections and how these contributed to its work. It concludes with an examination of how the JIB begat the Defence Intelligence Staff (DIS). It argues that the creation of the JIB was an appropriate response to the need to centralise and retrench in the intelligence machinery after the War, but that the organisation, in essence, represented a compromise between those who wanted to fully centralise military (and military-relevant) intelligence and those who wished to preserve service independence. Over the course of its existence it made important contributions to several key areas of policy – including mapping the Soviet Union for nuclear strike planning, the economic containment of the USSR, as well as China and North Korea during the Korean War, and in monitoring the production of Soviet bombers and missiles – before becoming a central component of the new DIS.

Tato diplomová práce se zabývá zhodnocením marketingové strategie společnosti Emco při vstupu na zahraniční trhy. Společnost Emco je známá jako výrobce cereálních produktů a distributor značkových zahraničních potravin. Tato práce v krátkosti představuje firmu Emco a podává charakteristiku trhu cereálních výrobků. Těžiště práce spočívá ve zhodnocení marketingové strategie, resp. marketingového mixu firmy. V návaznosti na marketingovou strategii následují kapitoly zabývající se marketingovým výzkumem, strategickým plánováním a SWOT analýzou.