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.

Zugl.: München, Univ. der Bundeswehr, Diss., 2009

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The cobalt-catalysed oxidative cyclisation of 5-hydroxy alkenes has been demonstrated to be a powerful synthetic tool for the formation of trans-THFs with excellent diastereoselectivity. This thesis describes the utilisation of this methodology in the synthesis of the FG fragment of pectenotoxin-4, allowing the scope of the reaction to be further explored. Introduction: This section introduces the pectenotoxins, a family of structurally complex closed-chain polyether macrolides with promising biological activities. The isolation, structural elucidation, and biological properties of the pectenotoxins are reviewed, along with a summary of previous syntheses towards the FG fragment of pectenotoxin-4. In addition, the cobalt-catalysed oxidative cyclisation of 5-hydroxy alkenes and its application in synthesis is discussed. Results and Discussion: An outline of the synthetic strategy employed in this project and details of the novel retrosynthesis of the C31-C40 fragment of pectenotoxin-4 is described. The synthetic studies carried out towards the synthesis of the FG fragment of pectenotoxin-4 are discussed in detail, with the exploitation of a cobalt-catalysed oxidative cyclisation as the key step to form the trans-THF F-ring. Overall, the FG fragment, which contains six stereogenic centres, was achieved in 18 total synthetic steps (13 longest linear sequence).

Lentiviruses can infect non-dividing cells, and various cellular nuclear transport proteins provide crucial functions for lentiviral nuclear entry and integration. Genome-wide small interfering RNA screens previously identified nuclear pore complex component nucleoporin 153 (NUP153) as being important for infection by human immunodeficiency virus type 1 (HIV-1). We found that HIV-1 infection of NUP153 depleted cells resulted in normal levels of reverse transcription, a moderate reduction of 2-long terminal repeat circles, and a relatively large reduction in integrated proviruses, consistent with a role for NUP153 during nuclear entry of the HIV-1 pre-integration complex. We ascertained the capsid (CA) to be the major viral determinant for NUP153 dependence during infection, and accordingly observed a direct interaction between the CA N-terminal domain and the phenylalanine-glycine (FG)-repeat enriched NUP153 C-terminal domain (NUP153C). NUP153C fused to the effector domains of the rhesus Trim5alpha restriction factor (Trim-NUP153C) potently restricted HIV-1, providing an intracellular readout for the NUP153C-CA interaction during retroviral infection. Primate lentiviruses and equine infectious anemia virus (EIAV) bound NUP153C under these conditions, results that correlated with direct binding between purified recombinant proteins in vitro. These binding phenotypes moreover correlated with the requirement for endogenous NUP153 function during infection. Mutagenesis experiments identified NUP153C and CA residues important for binding, and different FG motifs within NUP153C mediated binding to HIV-1 versus EIAV CA proteins. HIV-1 CA binding mapped to residues that line a common alpha helix 3/4 hydrophobic pocket that also mediates binding to the small molecule PF-3450074 (PF74) inhibitor and cleavage and polyadenylation specific factor 6 (CPSF6) protein, with Asn57 (Asp58 in EIAV) playing a particularly important role. PF74 and CPSF6 each competed with NUP153C for binding to HIV-1 CA, and significantly higher concentrations of PF74 were needed to inhibit HIV-1 infection in the face of Trim-NUP153C expression or NUP153 knockdown. Correlation between CA mutant viral cell cycle and NUP153 dependencies moreover indicated that the NUP153C-CA interaction underlies the ability of HIV-1 to infect non-dividing cells. We propose that HIV-1 CA binds NUP153 FG motifs to affect viral nuclear import, serving as a novel example of viral hijacking of a fundamental cellular process.

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This study is among the first to provide insight into the assessment of the Swedish central bank’s (Riksbank) three unconventional monetary policies (UMPs) and their influence on Swedish commercial banks. The three UMPs include forward guidance (FG), quantitative easing (QE) and negative interest rate policy (repo rate). Riksbank introduced the UMPs in order to revive inflation and support Sweden’s economic recovery. The banks’ ability to certainly forecast their operations is highly dependent on the communication availed by the Riksbank on its expected future monetary policies through FG. QE is paramount because this is when commercial banks sell government bonds to the Riksbank. Repo rate determines interest rates set by banks. Four indicators (uncertainty, government bond yields, bank interest rates, borrowing and lending) were used in this study to investigate the perception of the commercial banks on the three UMPs. There are limited studies on Swedish banks’ perception of the UMPs which leaves a research gap in this area.Previous studies indicate that dominant banks in terms of asset shares and deposits are more sensitive to monetary policy shocks. The four dominant commercial banks studied include: Nordea, Handelsbanken, Swedbank and Skandinaviska Enskilda Banken. This thesis considers the evidence of the results from previous empirical studies. Empirical material for this study was collected through semi-structured interviews from respondents by the Riksbank and the four commercial banks. A deductive approach was used to interpret the information collected.Our results presents various perceptions of the dominant commercial banks on the three UMPs in relation to the four indicators. Some commercial banks perceived the increased transparency and clarity during the increased FG to have reduced their uncertainty. Other banks perceived that FG had increased their uncertainty. They questioned the credibility of the FG since they could not predict Riksbank’s monetary policies with the FG availed. In regards to the perception of QE on uncertainty, an increased signalling channel during QE implementation had resulted in a decline of their uncertainty since they were experiencing a surplus of liquidity in the banking sector. However, they stated other factors that increased market volatility during QE. The increased market volatility during QE increased their uncertainty. The four commercial banks agreed that the demand for government bonds increased while the yields of the government bonds declined. They perceived these changes to have been influenced by QE. The commercial banks’ lending, deposit and interbank interest rates have declined systematically correlating the trend of the declining repo rate. The four banks experienced a decline in their average net interest income, an improved flow of credit through higher lending volumes and stable lending margins to households and firms. Commercial banks perceived these changes to have resulted from the declining market interest rates because of the negative repo rate.Riksbank can use this study to assess the effectiveness of its UMPs on commercial banks based on the perception of the employees from these respective banks. This study discusses implications of the findings for commercial banks and the Riksbank, as well as academics in the realm of implementations and influences of UMPs.

The high temperature adsorption of oxygen and the room temperature adsorption of CO on the Pt3Sn(111) and Pt3Sn(110) surfaces have been investigated by scanning tunneling microscopy (STM), low-energy electron diffraction (LEED), and Auger electron spectroscopy (AES). Beforehand the structure of the clean surfaces has been reviewed. After exposure to several 1000 L O2 at sample temperatures of about 750 K on both Pt3Sn(111) and (110) an ultra-thin Sn-O surface layer is formed. For the (111) X-ray photoelectron spectroscopy (XPS) indicates that this layer does not yet exhibit oxide properties. STM topographs of the Sn-O phase show on both surfaces meshes of highly corrugated protrusions commensurate with the substrate. In the case of the (111), after additional thermal annealing with STM and LEED a (4 × 4) reconstruction is observed, that is due to a (2 × 2) supermesh of depressions in the p(2 × 2) mesh of protrusions. This structure is similar to findings reported for the oxidation of Sn/Pt(111) surface alloys. X-ray photoelectron diffraction (XPD) measurements in comparison with simulations yield a tentative model for the (111) Sn-O layer. On the Pt3Sn(110) surface after oxygen exposure a c(2 × 2) hexagonal grid of protrusions with regard to the (2 × 1) substrate is observed with STM and LEED. STM reveals the existence of domains due to two equivalent positions of the Sn-O layer relative to the substrate. The domain boundaries zigzag around the [1-10] direction. The Sn-O layer can on both surfaces be removed by thermal annealing to more than 1050 K. After CO adsorption at room temperature on both Pt3Sn(111) and (110) adsorbate structures are observable with the STM. On the (111) two different types of structures are found: ordered patches of protrusions and unordered clusters. These structures are seen only on (√3 × √3)R30° substrate regions, not on p(2 × 2) regions. Surprisingly on the (110) the CO molecules mostly arrange in dimers. For both (111) and (110) saturation coverage is already reached at about 30% of a closed monolayer. The CO can be desorbed by slightly heating the samples to about 400 K. STM topographs show that on both surfaces CO adsorbes in Pt sites, not on Sn. It was possible to observe the CO adsorption on the (110) directly live with the STM. The observed adsorption processes hint to a dimer formation mechanism where a preadsorbed monomer and a CO molecule form the gas phase or a precursor phase stick together. When on partially Sn-O phase covered Pt3Sn(111) and (110) surfaces CO is adsorbed at room temperature, the respective structures coexist. Neither is CO observed on the Sn-O phase nor does a reaction between CO and O occur.