African monkey species are natural hosts of simian hemorrhagic fever virus (SHFV) and develop persistent, asymptomatic infections. SHFV was previously shown to also cause a rapid onset fatal hemorrhagic fever disease in macaques. Infection of macaques with a new isolate of SHFV from persistently infected baboon sera, that showed high nucleotide identity with the lab strain LVR, resulted in viremia, pro-inflammatory cytokine and tissue factor production, and symptoms of coagulation defects. Primary macrophages and myeloid dendritic cell cultures from disease-susceptible macaques efficiently replicated SHFV and produced pro-inflammatory cytokines, including IL-6 and TNF-α, as well as tissue factor. Cells from disease resistant baboons produced low virus yields and the immunomodulatory cytokine IL-10. IL-10 treatment of macaque cells decreased IL-6 levels but had no effect on TNF-α levels, tissue factor or virus production suggesting that IL-10 plays a role in modulating immunopathology in disease-resistant baboons but not in regulating the efficiency of virus replication. SHFV is a member of the family Arteriviridae. The SHFV genome encodes 8 minor structural proteins. Other arteriviruses encode 4 minor structural proteins. Amino acid sequence comparisons suggest that the four additional SHFV minor structural proteins resulted from gene duplication. A full-length infectious clone of SHFV was constructed and produced virus with replication kinetics comparable to the parental virus. Mutant infectious clones, each with the start codon of one of the minor structural proteins substituted, were analyzed. All eight SHFV proteins were required for infectious virus production. The SHFV nonstructural polyprotein is processed into the mature replicase proteins by several viral proteases including papain-like cysteine proteases (PLPs). Only one or two PLP domains are present in other arteriviruses but SHFV has three PLP domains. Analysis of in vitro proteolytic processing of C- and N-terminally tagged polyproteins indicated that the PLP in each of the three SHFV nsp1 proteins is active. However, the nsp1α protease is more similar to a cysteine protease than a PLP. Analysis of the subcellular localization of the three SHFV nsp1 proteins indicated they have divergent functions.

Computer-aided drug discovery involves the application of computer science and programming to solve chemical and biological problems. Specifically, the QSAR (Quantitative Structure Activity Relationships) methodology is used in drug development to provide a rational basis of drug synthesis, rather than a trial and error approach. Molecular dynamics (MD) studies focus on investigating the details of drug-target interactions to elucidate various biophysical characteristics of interest. Infectious diseases like Trypanosoma brucei rhodesiense (TBR) and P. falciparum (malaria) are responsible for millions of deaths annually around the globe. This necessitates an immediate need to design and develop new drugs that efficiently battle these diseases. As a part of the initiatives to improve drug efficacy QSAR studies accomplished the formulation of chemical hypothesis to assist development of drugs against TBR. Results show that CoMSIA 3D QSAR models, with a Pearson’s correlation coefficient of 0.95, predict a compound with meta nitrogens on the phenyl groups, in the combinatorial space based on a biphenyl-furan diamidine design template, to have higher activity against TBR relative to the existing compound set within the same space. Molecular dynamics study, conducted on a linear benzimidazole-biphenyl diamidine that has non-classical structural similarity to earlier known paradigms of minor groove binders, gave insights into the unique water mediated interactions between the DNA minor groove and this ligand. Earlier experiments suggested the interfacial water molecules near the terminal ends of the ligand to be responsible for the exceptianlly high binding constant of the ligand. Results from MD studies show two other modes of binding. The first conformation has a single water molecule with a residency time of 6ns (average) that is closer to the central part of the ligand, which stabilizes the structure in addition to the terminal water. The second conformation that was detected had the ligand completely away from the floor of the minor groove, and hydrogen bonded to the sugar oxygens.

Cell surface saccharides are involved in a variety of essential biological events. Fluorescent sensors for saccharides can be used for detection, diagnosis, analysis and monitoring of pathological processes. The boronic acid functional group is known to bind strongly and reversibly to compounds with diol groups, which are commonly found on saccharides. Sensors that have been developed for the purpose of saccharide recognition have shown great potential. However, they are very hydrophobic and this lack of essential water-solubility makes them useful in biological applications. The first section of this dissertation details the process of developing water-soluble saccharide sensors that change fluorescent properties upon binding to saccharides. The second section of the dissertation focuses on the development of DNA-minor groove binders as antiparasitical agents. Parasitical diseases comprise some of the world’s largest health problems and yet current medication and treatments for these parasitical diseases are often difficult to administer, costly to the patients, and have disruptive side effects. Worse yet, these parasites are developing drug resistance, thus creating an urgent need for new treatments. Dicationic molecules constitute a class of antimicrobial drug candidates that possess high activity against various parasites. The second section details the development of a series of di-cationic agents that were then screened in in vitro activities against parasitical species.

Tellurium is one of the rarest metals in the earth’s crust. Increased demand for cadmium telluride photovoltaic cells along with an opaque pricing and quantity-reporting system, have recently caused high price volatility and a speculative bubble in the tellurium market, resulting in overstocking and depressed prices. In a longer perspective this may be a threat to cadmium telluride photovoltaics as a power-generating technology. This master thesis compares how actors may perceive news innovation in the opaque tellurium market compared to the more transparent molybdenum market. A quantitative analysis of industry news reporting on the two metals, combined with a SVAR impulse response analysis, helps me determine which actors and factors exert most influence on spot market prices. In the opaque tellurium market, relatively unreliable proxies of supply and demand are most frequent in the news reporting while having a big impact on prices, whereas the transparent molybdenum market uses more reliable variables – such as futures prices – and transparent supply information, whilst also relying on a frequent stream of dependable proxies to scope market sentiments. My findings lead me to recommend policy makers to implement measures to increase market transparency, which may be accomplished by extending the data-sharing regime of the REACH database to minor metal markets. Attempting to limit speculation in minor metal markets is perhaps too blunt a tool to fix an inherent problem of a free exchange-pricing mechanism. / Tellur är en av de mest sällsynta metallerna på Jorden. Ökad efterfrågan av kadmiumtelluridsolpaneler har nyligen orsakat stor volatilitet på tellurmarknaden. Ett opakt prissättnings-och kvantitetsrapporteringssystem har bidragit till att en prisbubbla bildats och spruckit, vilket resulterat i att marknadsaktörer köpt på sig stora lager till höga priser som de sedan inte kunnat sälja vidare. I ett längre perspektiv kan detta innebära begränsningar vid tillverkning av solcellsteknologi baserad på kadmiumtellurid, då ett volatilt pris kan göra nya tellurgruvprojekt alltför riskabla. Denna masteruppsats jämför hur en typisk marknadsaktör kan reagera på prisinnovationer i den opaka tellurmarkanden och den mer transparenta molybdenmarknaden. Metoden består av en kvantitativ analys av facknyheter rörande de två metallerna, varifrån variabler väljs till en SVAR modell med impuls-responsanalys. Urvalet av variabler är få och volatila på den opaka tellurmarknaden, medan den mer transparenta molybdenmarknaden har ett större utbud av variabler som kännetecknas av god transparens och relativ förutsägbarhet. Mina slutsatser leder mig till att rekommendera beslutsfattare att vidta åtgärder för att öka tellurmarknadens transparens genom EU-samarbetet, förslagsvis genom att göra anonymiserad data från REACH databasen tillgänglig för allmänheten. Samtidigt avråder jag från åtgärder som syftar till att minska spekulation, då implementering av en sådan policy kan bli både dyr och komplicerad.

The development of small-molecules which target nucleic acids, more specifically the minor groove of DNA, in a sequence specific manner and control gene expression are currently being investigated as potential therapeutic compounds for the treatment of various diseases, including cancer, as well as viral and bacterial infections. The naturally occurring compounds netropsin and distamycin have been shown to demonstrate antitumor and antibacterial properties. Currently, there are synthetic efforts to create pyrrole and imidazole-containing polyamide derivatives of netropsin and distamycin that show potential as medicinal agents. Synthetic pyrrole and imidazole-containing polyamides are potentially useful for targeting and modulating the expression of genes, including those associated with cancer cell growth. The key challenges that must be overcome to realize this goal of using synthetic polyamides in the treatment of disease are the development of polyamides with low molar mass so the molecules can readily diffuse into cells and concentrate in the nucleus. In addition, the molecules must have appreciable water solubility, bind DNA sequence specifically, and with high affinity. As part of a systematic study within the authors’ laboratory, our goal is to develop polyamides which can be synthesized readily yet possess excellent sequence specificity, stronger binding affinity, high solubility in biological media and enhanced cell penetration and nuclear localization properties. There is a need to develop a library of modified polyamides which target DNA and exhibit improved biological properties. The present study is a systematic examination of the binding properties of various modified synthetic polyamide compounds. The synthetic polyamide derivatives presented have more potential as therapeutic candidates over other synthetic polyamides because of their increased water solubility, smaller molecular weights, and molecular design, thus, allowing them to penetrate into cells and localize in the nucleus.

Bolivia, as the poorest country in South America, can gain a lot from international trade. It is an important factor for a country to build prosperity and gain economic growth and thereby reach a higher standard of living. But for a company to succeed in the international market is a demanding task. Both internal and external factors that influence a company’s competence need to be taken into consideration. This Master Thesis deals with two Bolivian wooden door producers’ possibilities to export to the Swedish market. The demand of tropical wood products is expected to increase and the Bolivian wood industry has been identified as an export industry of the future. Another thing in favor for the Bolivian export is the fact that the country is number one in the world when it comes to sustainable management of forest resources. This gives the companies the possibility to offer an environmentally friendly and unique product and thereby create competitive advantages. There are though areas that need improvement. One of the most important improvement areas for both of the companies is marketing and understanding what the customers needs. They need to keep the costumer in focus in all of their activities and learn how to promote their products advantages. The facts that both the studied companies have earlier experience in export and a high level of motivation support the possibility to succeed in this matter. But, these factors are not enough for the studied companies to succeed in export. The result of this study also shows that the instable situation in the country results in financial problems and lack of trust. Therefore the companies must focus on building trust to attract new customers and investors. This should be done by keeping an even level of quality, fulfilling promises and finding ways to reduce the risk for potential investors. The trend towards more individual and exclusive doors in the Swedish market results in the recommendation to focus on offering a niche product in the middle-price segment. It is also recommended for the Bolivian companies to use some kind of representative to reach the market. A good alternative is to work as a supplier to a door producing partner and help them widen their assortment and in turn get someone present in the market that can work close to the customers.

The variety of principal minors of nxn symmetric matrices, denoted Zn, can be described naturally as a projection from the Lagrangian Grassmannian. Moreover, Zn is invariant under the action of a group G C GL(2n) isomorphic to (SL(2)xn) x Sn. One may use this symmetry to study the defining ideal of Zn as a G-module via a coupling of classical representation theory and geometry. The need for the equations in the defining ideal comes from applications in matrix theory, probability theory, spectral graph theory and statistical physics. I describe an irreducible G-module of degree 4 polynomials called the hyperdeterminantal module (which is constructed as the span of the G-orbit of Cayley's hyperdeterminant of format 2 x 2 x 2) and show that it that cuts out Zn set theoretically. This result solves the set-theoretic version of a conjecture of Holtz and Sturmfels and gives a collection of necessary and sufficient conditions for when it is possible for a given vector of length 2n to be the principal minors of a symmetric n x n matrix. In addition to solving the Holtz and Sturmfels conjecture, I study Zn as a prototypical G-variety. As a result, I exhibit the use of and further develop techniques from classical representation theory and geometry for studying G-varieties.

Anatolia has been the cradle of many different cultures throughout history. One of these was the Celts who migrated from Europe to Anatolia in the 3rd century BC and had various impacts on the settlement pattern of the region called Galatia after their arrival. Therefore in Anatolia urbanization history we know them as Galatians. The main statement of this thesis is that, cultural identity is not a static, inherent quality, but a dynamic and contigent aspect of the existence of people. Therefore cultural identity should be regarded as a pattern continuum. In thisd study, in order to predict the Galatian settlement pattern until thr Roman dominance in the late 1st century BC in Anatolia, European Celtic settlement pattern has been reviewed as well as archaeolgical evidence and the Celtic language. The Hallstatt and the following La Tene periods in European history have been investigated since La Tene period is isochronic with Galatians in Anatolia. From the archaeological evidence in Europe, it is clear that the Celts established defended settlements, mastered the art of iron working and mining, and traded with the classical world. In previous literature, Anatolia Celts/Galatians have been regarded as nomads who were involved mostly in warfare. However, the location of their forts and village-like settlements along the ancient trade routes implies that they were settled people who were engaged in production and trading activities as well, similar to La Tene in Europe. Settlement types and their distribution pattern, linguistic and archaeological evidence investigated in this thesis verify that Celtic cultural identity in the history of Europe and Anatolia should be regarded as a pattern continuum.

This thesis is an examination of the role of architectural benefaction of the local elite on the urbanization of the Greek cities of Asia Minor in the Roman Imperial period, and its impact on the social status of the benefactor. While providing a theoretical framework for the nature of benefaction in antiquity and the pattern of architectural renewal of the Anatolian cities under the Roman influence, the thesis focuses on a single case study / the Hellenistic City Gate of Perge which was restored by Plancia Magna during the reign of Hadrian. After its renovation, the gate became an indispensible part of the urban activities of Perge and a source of pride for both the city and its donor. Hence, this study constitutes an attempt to investigate the involvement of Plancia Magna&rsquo / s architectural patronage within the Roman urbanization of Perge and also the transformation of the public persona of Plancia Magna in the center of the male-dominated Roman society.

The study presents the results of an experimental and analytical investigation aimed at examining the lateral stability of rectangular reinforced concrete slender beams. In the experimental part of the investigation, a total of eleven reinforced concrete beams having a depth to width ratio between 10.20 and 12.45 and a length to width ratio between 96 and 156 were tested. Beam thickness, depth and unbraced length were 1.5 to 3.0 in., 18 to 44 in., and 12 to 39.75 ft, respectively. Each beam was subjected to a single concentrated load applied at midspan by means of a gravity load simulator that allowed the load to always remain vertical when the section displaces out of plane. The loading mechanism minimized the lateral translational and rotational restraints at the load application point to simulate the nature of gravity load. Each beam was simply-supported in and out of plane at the ends. The supports allowed warping deformations, yet prevented twisting rotations at the beam ends. In the analytical part of the study, a formula was developed for determining the critical loads of lateral torsional buckling of rectangular reinforced concrete beams free from initial geometric imperfections. The influences of shrinkage cracking and inelastic stress-strain properties of concrete and the contribution of longitudinal reinforcement to the lateral stability are accounted for in the critical load formula. The experiments showed that the limit load of a concrete beam with initial geometric imperfections can be significantly lower than the critical load corresponding to its geometrically perfect configuration. Accordingly, a second formula was developed for the estimation of limit loads of reinforced concrete beams with initial lateral imperfections, by introducing the destabilizing effect of sweep to the critical load formula. The experimental results were compared to the proposed analytical solution and to various lateral torsional buckling solutions in the literature. The formulation proposed in the present study was found to agree well with the experimental results. The incorporation of the geometric and material nonlinearities into the formula makes the proposed solution superior to the previous lateral torsional buckling solutions for rectangular reinforced concrete beams.