Influenza virus A circulates in birds and mammals and causes severe infectious disease that affects from 3 to 5 million people each year. There are two classes of anti-influenza drugs currently available: neuraminidase and M2 channel inhibitors. However, increasing resistance against these two types of inhibitors along with the potential emergence of new viral strains and unpredictability of pandemic outbreaks emphasize an unmet need for new types of inhibitors. RNA-dependent influenza polymerase serves as a novel promising target for the development of anti-influenza medications. The aim of this master thesis is to develop in vitro high-throughput assays for screening of compounds targeting influenza RNA polymerase, particularly, its cap binding and endonuclease domains. For cap-binding domain the screening is based on DIANA (DNA-linked Inhibitor ANtibody Assay) method that was recently developed in our laboratory; for endonuclease domain, the method is based on AlphaScreen technology. For the purposes of the methods development, recombinant cap binding domain of PB2 subunit and N-terminal endonuclease domain of PA subunit of influenza polymerase were expressed with appropriate fusion tags and purified using affinity and gel permeation chromatography. The probes for the screening assays were...

This study has examined the ten most shorted shares belonging to the Swedish Stockholm Stock Exchange's Large Cap list, by following randomly selected financial institutions that have chosen to take short positions. The purpose of the study is to investigate whether it is possible for short sellers to generate an excess return compared to the index OMXS30GI. The theory is mostly about short selling in general, efficient market hypothesis, behavioral finance, opponents of short selling, technical analysis of an index and the theory also includes previous research regarding short selling. The method used is based on collected secondary data from different databases. Via the secondary data, we have artificially followed randomly selected financial institutions that have glossed over and done the same as them to see if it can generate an excess return. In this study we will not take the cost associated with short selling into account which normally would be costs as margin interest, stock borrowing costs and commissions to brokers. The results show that it is possible for short sellers to generate an excess return that outperforms index OMXS30GI. We can also conclude that short sellers follow a pattern that indicates that they do not act in a way to destroy market efficiency and we can question whether the market is efficient or not.

Price trends on the Swedish housing market has risen sharply in recent decades and is at the moment up to the highest price level ever. The sharp price movements have opened up for discussion about a possible housing bubble. To prevent this the Riksbank can change the repo rate, which in turn aects the lenders' lending rates. Finansinspektionen introduced in autumn 2010, a mortgage cap which means that the house will be mortgaged to a maximum of 85 percent of its market value. The purpose of this was to cool the housing market and prevent the unsustainable development of household debt. The purpose of this study is to examine in particular the repo rates and the mortgage caps eect on house prices in Sweden. Although other variables that aect supply and demand in the housing market from a macroeconomic perspective will be included in the model, such as GDP, unemployment and the nancial crisis of 2008. This study has been done by using a quantitative analysis, consisting of time series analysis. The results conrm all the investigated variables expected impact on house prices. As for the repo rate and the mortgage cap the results showed that these have a negative eect on house prices in Sweden. / Prisutvecklingen pa den Svenska bostadsmarknaden har stigit kraftigt under de senaste decennierna och ar just nu uppe i den hogsta prisnivan nagonsin. Den kraftiga prisutvecklingen har oppnat for diskussion om en eventuell bostadsbubbla. For att motverka detta kan Riksbanken andra reporantan som i sin tur paverkar kreditgivarnas utlaningsranta. Finansinspektionen inforde under hosten 2010 ett bolanetak som innebar att bostaden hogst ska belanas till 85 procent av marknadsvardet. Detta for att kyla bostadsmarknaden och motverka den ohallbara utvecklingen av hushallens skuldsattning. Syftet med denna studie ar att framforallt undersoka reporantans och bolanetakets eekt pa smahuspriser i Sverige. Aven andra variabler som paverkar utbudet och efterfragan pa bostadsmarknaden ur ett makroekonomiskt perspektiv kommer att inga i modellen, till exempel BNP, arbetsloshet och nanskrisen 2008. Detta genomfors med hjalp av en kvantitativ analys, bestaende av tidsserieanalys. Resultatet bekraftar alla undersokta variablers vantade eekter pa smahuspriser. Vad galler reporantan och bolanetaket sa visade resultatet pa att dessa har negativ eekt pa smahuspriser i Sverige.

Die Untersuchung erläutert und vergleicht die Ausgestaltung der Werberegulierung in Deutschland und Großbritannien. Während in Deutschland mit dem Gesetz gegen unlauteren Wettbewerb (UWG) ein zentrales Regelwerk existiert, sind in Großbritannien drei Rechtsmassen von Bedeutung, nämlich das dem Konkurrentenschutz dienende common law, verschiedene Verbraucherschutzgesetze strafrechtlicher Ausgestaltung und die freiwillige Werbeselbstkontrolle. Der Schwerpunkt der Untersuchung liegt auf dem Vergleich der Werbekontrolle durch das deutsche Wettbewerbsrecht einerseits und die britische Werbeselbstregulierung andererseits. Letztere stellt aufgrund der Lückenhaftigkeit staatlicher Rechtssetzung die bedeutendste Form der Werberegulierung in Großbritannien dar und gilt gemeinhin als weltweit effektivstes und anspruchsvollstes Selbstkontrollsystem. Diese grundlegend verschiedenen Regelungsansätze lassen einen Vergleich in besonderem Maße ergiebig erscheinen. Auch stellt sich mit Blick auf die Bestrebungen im europäischen Einigungsprozess, das Recht des unlauteren Wettbewerbs europaweit anzugleichen, zuletzt durch Erlass der Richtlinie 2005/29/EG über unlautere Geschäftspraktiken im binnenmarktinternen Geschäftsverkehr zwischen Unternehmern und Verbrauchern, die Frage nach der Vorzugswürdigkeit eines der beiden Ansätze. Im ersten Teil der Untersuchung folgt nach einer geschlossenen Gesamtdarstellung der Funktionsweise des Systems der britischen Werberegulierung eine integrierte Vergleichsbetrachtung der Werbekontrollsysteme Deutschlands und Großbritanniens. Der zweite Teil behandelt anhand von Fallgruppen typischer Problembereiche der Werbung in einem integrierten Vergleich den materiellen Regelungsgehalt der jeweiligen Regulierungsvorschriften, wie er sich in der Entscheidungspraxis deutscher Gerichte und der britischen Entscheidungsorgane darstellt. Eine Schlussbetrachtung nimmt eine zusammenfassende Bewertung der in beiden Teilen gefundenen Ergebnisse vor.

Current multifactor valuation pricing models use size (measured by market capitalization) of a firm as one factor to determine the value of a security. The problem with current standard models was that none of them could explain the value of a security consistently and accurately based on current factors and in particular the size factor. The purpose of this quantitative study using existing time-series data over a 10-year period from 2006 to 2015 was to examine the impact of size factor on the realized rate of return of financial securities, while controlling for the impact of market rate of return. There are currently many valuation models but there is no 2-factor model or a model that uses a size factor that includes mid-cap sized securities. The research questions examined mid-cap sized securities for the size factor in a 2-factor model to determine the accuracy of predicting financial returns compared to the current standard Fama-French 3-factor model. The main theoretical framework that guided the study was the efficient market hypothesis that postulates that the price of a stock reflects all relevant available information. Data were collected for historical returns of 15 individual firms and portfolios of securities based on size. Multiple regression analysis methodology was used to examine the impact of size factor on the realized rate of return of financial securities, while controlling for the impact of market rate of return in the modified 2-factor model that included mid-caps. The results of the study indicate that size is a statistically significant factor in a 2-factor model that included mid-caps. The positive social impact of this study is that it could provide greater confidence in financial markets by providing a fair and equitable means of investment and flow of capital for a robust economy.

The office market in central Stockholm has since the financial crises in ‘08 showed remarkablegrowth and the current conditions are compared to the once under the previous crises. Thecommercial real estate market has had a substantial role in the last crises, as it is sensitive to cyclesand has high indebtedness. The study aimed to evaluate the market today by comparing it withforemostly the crises in Sweden in the 90s and dotcom-era, but also the great recession in’08.Further, the perception of the market actors was analysed. The methodology was qualitative, as sixprofessionals have been interviewed representing property companies, consultancy firms, bank,and institutional owners. The result shows more differences than similarities to the past crises, inboth macro and micro level. Furthermore, consensus had an optimistic view of the future and thereal estate market. Central Stockholm office market can be regarded as more professional andstable. However, there are uncertainties which were not present during the crises, such ascoworking, market-financing and low-interest rate. The study suggests that the factor causing thenext crisis is something the market does not know. / Kontorsmarknaden i centrala Stockholm har sedan finanskrisen 2008 visat en stark tillväxt och denuvarande förhållandena har jämförts med de som rådde under tidigare kriser. Kommersiellafastighetsmarknaden har haft en betydande roll i de senaste kriserna, eftersom den är känslig motcykler och har hög skuldsättning. Studien syftade till att jämföra marknaden idag med främstkriserna i Sverige på 90-talet och dotcom, men också den stora finanskrisen 2008. Dessutomanalyseras marknadsaktörernas uppfattning om riskerna för en kris i dagens kontorsmarknad.Metoden var kvalitativ då sex professionella intervjuades som representerade fastighetsbolag,konsultföretag, banker och institutionella ägare. Resultatet visar fler skillnader än likheterna medkriserna på både makro och mikronivå. Vidare hade konsensus en optimistisk syn på marknadensframtid. Centrala Stockholm kan betraktas som mer professionell och stabil. Det finns emellertidosäkerheter som inte var närvarande under kriserna, till exempel coworking, marknadsfinansieringoch de låg räntorna. Studien tyder på att faktorn som kommer orsaka nästa kris är något okänt förmarknaden idag.

Correct understanding of passive force behavior is particularly key to lateral evaluations of bridges because plastic deformation of soil backfill is vital to dissipation of earthquake energy and thermally-induced stresses in abutments. Only recently have studies investigated the effects of skew on passive force. Numerical modeling and a handful of skewed abutment tests performed in sand backfill have found reduced passive force with increasing skew, but previous to this study no skewed tests had been performed in gravel or Geosynthetic Reinforced Soil (GRS) backfills. The goal of this study was to better understand passive force behavior in non-skewed and skewed abutments with gravel and GRS backfills. Prior to this study, passive pressures in a GRS integrated approach had not been investigated. Gravel backfills also lack extensive passive force tests.Large-scale testing was performed with non-skewed and 30° skewed abutment configurations. Two tests were performed at each skew angle, one with unconfined gravel backfill and one with GRS backfill, for a total of four tests. The test abutment backwall was 11 ft (3.35 m) wide, non-skewed, and 5.5 ft (1.68 m) high and loaded laterally into the backfill. However, due to actuator loading constraints, all tests except the non-skewed unconfined gravel test were performed to a backfill height of 3.5 ft (1.07 m). The passive force results for the unconfined gravel test was scaled to a 3.5 ft (1.07 m) height for comparison.Test results in both sets of backfills confirmed previous findings that there is significant reduction in passive force with skewed abutment configurations. The reduction factor was 0.58 for the gravel backfill and 0.63 for the GRS backfill, compared to the predicted reduction factor of 0.53 for a 30° skew. These results are within the scatter of previous skewed testing, but could indicate that slightly higher reduction factors may be applicable for gravel backfills. Both backfills exhibited greater passive strength than sand backfills due to increased internal friction angle and unit weight. The GRS backfill had reduced initial stiffness and only reached 79% to 87% of the passive force developed by the unreinforced gravel backfill. This reduction was considered to be a result of reduced interface friction due to the geotextile. Additionally, the GRS behaved more linearly than unreinforced soil. This backfill elasticity is favorable in the GRS-Integrated Bridge System (GRS-IBS) abutment configuration because it allows thermal movement without developing excessive induced stresses in the bridge superstructure.

The effects of seismic forces and thermal expansion on bridge performance necessitate an accurate understanding of the relationship between passive force and backwall deflection. In past case studies, skewed bridges exhibited significantly more damage than non-skewed bridges. These findings prompted studies involving numerical modeling, lab-scale tests, and large-scale tests that each showed a dramatic reduction in passive force with increased skew. Using these results, a correlation was developed between peak passive force and backwall skew angle. The majority of these tests had length to height ratios of 2.0; however, for several abutments in the field, the length to height ratio might be considerably higher than 2.0. This change in geometry could potentially affect the validity of the previously found passive force reduction correlation. To explore this issue, laterally loaded, large-scale pile cap tests were performed with densely compacted sand at a length of 11 ft (3.35 m) and a height of 3 ft (0.91 m), resulting in a length to height ratio of 3.7. The backwall interface was adjusted to fit three various skew angles including: 0°, 15° and 30°. The behavior of both the pile cap and adjacent soil backfill were monitored under these conditions. The peak passive force for the 15° and 30° tests were found to be 71% and 45%, respectively, of the peak passive force for the 0° skew test. These findings are relatively consistent with previously performed tests. Passive forces peaked at deflections between 2% and 5% of the backwall height, decreasing with skew angle. All skews exhibited a log spiral failure plane that transitioned into a linear plane. These results also agreed with previously reported values for large-scale passive force-deflection tests. Rotation of the pile cap was detected in the direction opposite to the skew. Higher pressures were found to be on both corners of the pile cap than in the middle portion, as is suggested by the elastic theory.

Plaque rupture with superimposed thrombosis is the primary cause of acute coronary syndromes of unstable angina, myocardial infarction and sudden death. Although intensive studies in the past decade have shed light on the mechanism that causes unstable atheroma, none has directly addressed the clinical observation that most myocardial infarction (MI) patients have moderate stenoses (less than 50%). Considering the important role the arterial wall compliance and pulsitile blood flow play in atheroma rupture, fluid-structure interaction (FSI) phenomenon has been of interest in recent studies. In this thesis, the impact is investigated numerically of coupled blood flow and structural dynamics on coronary plaque rupture. The objective is to determine a unique index that can be used to characterize plaque rupture potential. The FSI index, developed in this study for the first time derives from the theory of buckling of thin-walled cylinder subjected to radial pressure. Several FSI indices are first defined by normalizing the predicted hemodynamic endothelial shear stress by the structural stresses, specifically, by the maximum principal stress (giving the ratio ), and the Von Mises stress (giving the ratio ). The predicted at the location of maximum (i.e { }) denoted , is then chosen to characterize plaque rupture through systematic investigation of a variety of plaque characteristics and simulated patient conditions. The conditions investigated include varying stenosis levels ranging from 20% to 70%, blood pressure drop ranging from 3125 Pa/m to 9375 Pa/m, fibrous cap thickness ranging from to , lipid pool location ranging from the leading to the trailing edge of plaque, lipid pool volume relative to stenosis volume ranging from 24% to 80%, Calcium volume relative to stenosis volume ranging from 24% to 80% and arterial remodeling. The predicted varies with the stenosis severity and indicates that the plaques investigated are prone to rupture at approximately 40-45% stenosis levels. It predicts that high pressure significantly lowers the threshold stenosis rate for plaque rupture. In addition, the plaque potential to rupture increases for relatively thin fibrous cap, lipid core located near the leading plaque shoulder, and dramatically for relative lipid pool volume above 60%. However, calcium deposit has marginal effect on plaque rupture. Overall, the predicted results are consistent with clinical observations, indicating that the has the potential to characterize plaque rupture when properly established. In the appendix, the unsteady flow in a collapsible tube model of a diseased artery is solved analytically. The novelty of our approach is that the set of governing equations is reduced to a single integro-differential equation in the transient state. The equation was solved using the finite difference method to obtain the pressure and compliant wall behavior. The analytical approach is less computer-intensive than solving the full set of governing equations. The predicted membrane deflection is quite large at low inlet velocity, suggesting possible approach to breakdown in equilibrium. As the transmural pressure increases with wall deflection, bulges appear at the ends of the membrane indicating critical stage of stability, consistent with previous studies. An increase in wall thickness reduces the wall deflection and ultimately results in its collapse. The collapse is due to breakdown in the balance of wall governing equation. An increase in internal pressure is required to maintain membrane stability.

Skewed bridges have exhibited poorer performance during lateral earthquake loading in comparison to non-skewed bridges (Apirakvorapinit et al. 2012; Elnashai et al. 2010). Results from numerical modeling by Shamsabadi et al. (2006), small-scale laboratory tests by Rollins and Jessee (2012), and several large-scale tests performed by Rollins et al. at Brigham Young University (Franke 2013; Marsh 2013; Palmer 2013; Smith 2014; Frederickson 2015) led to the proposal of a reduction curve used to determine a passive force skew reduction factor depending on abutment skew angle (Shamsabadi and Rollins 2014). In all previous tests, a uniform longitudinal load has been applied to the simulated bridge abutment. During seismic events, however, it is unlikely that bridge abutments would experience pure longitudinal loading. Rather, an inclined loading situation would be expected, causing rotation of the abutment backwall into the backfill. In this study, a large-scale test was performed where inclined loading was applied to a 30° skewed bridge abutment with sand backfill and compared to a baseline test with uniform loading and a non-skewed abutment. The impact of rotational force on the passive resistance of the backfill and the skew adjust factor was then evaluated. It was determined that inclined loading does not have a significant effect on the passive force skew reduction factor. However, the reduction factor was somewhat higher than predicted by the proposed reduction curve from Shamsabadi and Rollins 2014. This can be explained by a reduction in the effective skew angle caused by the friction between the side walls and the back wall. The inclined loading did not change the amount of movement required to mobilize passive resistance with ultimate passive force developing for displacements equal to 3 to 6% of the wall height. The rotation of the pile cap due to inclined loading produced higher earth pressure on the obtuse side of the skew wedge, as was expected.These findings largely resolve the concern that inclined loading situations during an earthquake may render the proposed passive force skew reduction curve invalid. We suggest that the proposed reduction curve remains accurate during inclined loading and should be implemented in current codes and practices to properly account for skew angle in bridge design.