1 Abstract Even though mitochondria possess their own genome and ribosomes, majority of mitochondrial proteins is encoded in the nucleus and translated by cytosolic ribosomes. Hence it was necessary to establish transport complexes allowing the import of proteins from the cytosol. These complexes are best described in yeast. However, we are encountering organisms lacking many of the subunits of these complexes with increasing frequency. Therefore, we are presenting the overview of the distribution of the subunits within eukaryotic organisms. We specifically take a closer look at parasitic protist Giardia intestinalis that is well known for its extreme reductions of the import complexes. There have been only few subunits identified so far. Porin Tom40, that is responsible for translocating all the incoming proteins across the outer mitochondrial membrane, has been identified despite the high divergence, while homolog of Sam50 hasn't been successfully identified yet. Sam50 is however believed to be necessary for insertion of Tom40 into the membrane. Vast part of this thesis is dedicated to this phenomenon that is highly uncommon and maybe unique among the eukaryotic organisms.

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Global industrialization was developed in response to both consumers and manufacturers demand for lower product prices and availability of goods and services. As a result, products are transported greater distances. Shipping constitutes the majority of costs in the export/import supply chain. Shippers and buyers commonly attempt to offset these costs by maximizing the capacity of ocean freight containers (cube or weight). Boxes (usually constructed of corrugated fiberboard) containing consumer grade products are commonly floor loaded into containers to maximize capacity. Boxes that are not floor loaded are likely to be unitized on pallets in containers. Beyond maximizing a container with cargo, a defined decision to determine which method of loading is most efficient in regard to cost and time does not exist. For this research, field studies were conducted and questionnaires were distributed to identify the variables that influence efficiency. A method to make an efficient decision was developed by incorporating the variables into a model. The model compares the overall export/import supply chain efficiency for boxes that are floor loaded to boxes that are unitized on pallets in containers. The recommended decision is determined by comparing the shipping and handling costs and the receiving dock door capability for the two loading methods. The results of this research reveal that floor loading boxes can provide a higher value per container due to increased capacity. Increased capacity by floor loading often reduces the number of containers needed to meet daily demand. However, since manual labor is utilized for the loading/unloading process, more time is required, which results in higher labor costs and restricted product throughput. Unitized boxes loaded in containers on pallets can limit container capacity, but allows for faster loading/unloading times (if no incompatibilities between product and pallet or pallet and/or material handling equipment exist), reduced labor costs, and the potential for increased product throughput. Importing boxes unitized on pallets commonly requires more containers to meet demand, but fewer receiving dock doors. Utilizing fewer dock doors allows otherwise occupied doors to be available to receive additional product. The decision to floor load or unitize exports/imports needs to be made on a SKU basis meeting daily demand, not only per container capacity. Labor cost, pallet cost, the magnitude of box variation between loading methods, and the ability of the receiver to process containers are all influencing factors in determining which loading method is most overall efficient. Given the current cost for containerized shipments and considering all costs, most consumer goods are more efficiently shipped floor loaded. When additional containers would be needed to meet demand for product unitized on pallets, floor loading will be more efficient. When there is only a small difference in box count between floor loading and palletizing, palletizing product will be more efficient. This will often occur when loads will meet container weight capacity before it reaches volume capacity. If the product is too heavy to move manually it will be palletized. / Ph. D.

Syftet med denna studie var att undersöka vilken betydelse Systembolagets har haft för fem småskaliga vinimportörer i Sverige under coronapandemin. Studien ville även undersöka hur coronapandemin påverkat vinimportörernas försäljning samt vilka lärdomar vinimportörerna tar med sig av coronapandemin i sitt framtida arbete.  Studien genomfördes genom kvalitativ metod i form av semistrukturerade intervjuer med fem småskaliga vinimportörer i Sverige. Syftet med intervjuerna var att lyfta de småskaliga vinimportörernas berättelser om hur de hanterat coronapandemin. Det empiriska materialet analyserades genom tematisk analys och resulterade i två teman – Vinimportörernas föreställning om Systembolaget och Passionen hos vinimportörer.  Resultatet visade att Systembolaget haft en stor betydelse i småskaliga vinimportörers hantering av coronapandemin. Importörerna som aktivt skiftat sin försäljning från restaurang till Systembolaget har kunnat rädda företagens ekonomi trots en kraftig minskad restaurangförsäljning. Vinimportörerna lärdomar av pandemin var en ökad krismedvetenhet, ett värde i att snabbt justera sin affärsmodell och att sprida riskerna i verksamheten. Genom att ha kunskap om processen av vinförsäljning till Systembolaget samt en förmåga att snabbt justera sin försäljning från restaurang till Systembolaget, föreslår studiens författare att småskaliga vinimportörer vara bättre förberedda inför framtida pandemier. / The purpose of this study was to investigate the importance of Systembolaget for five small-scale wine importers in Sweden during the corona pandemic. The study also wanted to examine how the corona pandemic has affected the wine importers sales and their learnings from the corona pandemic.  The study was conducted using a qualitative method in the form of semi-structured interviews with five small-scale wine importers in Sweden. The purpose of the interviews was to highlight the small-scale wine importer’s stories of how they handled the corona pandemic. The empirical data was analyzed through thematic analysis and resulted in two themes – The wine importers perception of Systembolaget and the passion of wine importers.  The results show that Systembolaget had great importance in the small-scale wine importers’ handling of the corona pandemic. The importers who actively shifted their sales from restaurants to Systembolaget had been able to save their companies’ financial results despite a reduction in restaurant sales. The wine importers learnings from the pandemic were an increased crisis awareness, the value of quickly adjusting their business model and spreading the risks in their business. By having knowledge of the process of wine sales to Systembolaget and an ability to quickly adjust their sales from restaurants to Systembolaget, the study’s authors suggest that small-scale wine importers can be better prepared for future pandemics.

The work deals with the topic of portability of test questions and creating a program unit for on-line testing. It mentions standards used for data exchange among e-learning systems and describes formats used for import and export of test questions. On the basis of gained knowledge a concept and subsequently a complex program unit for on-line testing of students were created, which matches the requirements for work with test questions, test management and evaluation and the possibility of exchanging questions with other systems.

Thesis advisor: Junona Moroianu / In this study we investigated the hydrophobic interactions between HPV11 E7 and the FG regions of Nup62N through transfection assays with EGFP-11E7 fusion plasmids in HeLa cells and binding assays with GST-Nup62N immobilized on Glutathione-Sepharose beads. We found that EGFP-11cE7 binds to Nup62N. This suggests a possible mechanism for the nuclear import of HPV11 E7 through direct hydrophobic interactions between its carboxy-terminus and the FG region of Nup62. The interaction between HPV11 E7 and CRM1 nuclear export receptor was also examined using similar methods. Binding between these proteins suggest that nuclear export of 11E7 is mediated by CRM1 binding to its leucine-rich nuclear export signal (NES). / Thesis (BS) — Boston College, 2013. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: College Honors Program. / Discipline: Biology.

Thesis advisor: Georg Strasser / Exchange Rate Pass Through (ERPT) is the percentage change in a destination country’s import price given a percentage change in the exchange rate. A complete ERPT occurs when import price decreases by the same percentage as the depreciation of the exporting country’s currency and vice versa. In this paper I analyze ERPT in large and small open economies, and hypothesize that as destination economy size gets larger, ERPT will decrease. Reasons I provide to support this hypothesis are: the import share of exporters in destination economies, the demand elasticity that foreign exporters face, and the proportion of consumer demand to world demand that the foreign exporter faces. I find, with statistical significance, that ERPT decreases as the destination economy size increases. The main reason attributed to this inverse relationship is the import share of foreign exporters in destination economies. As import share of the foreign exporter increases, ERPT increases within those destination economies. Since foreign exporters have a higher chance of establishing a large import share in small economies than in large economies, they have a better chance of passing through exchange rate changes into destination country prices. / Thesis (BA) — Boston College, 2011. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Economics Honors Program. / Discipline: Economics.

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.