Influenza A is a single-stranded, multi-segmented, negative sense RNA virus of the family Orthomyxoviridae and is the causative agent of seasonal Influenza. Influenza viruses cause significant impacts on a global scale regarding public health and economics. Annual influenza virus infections in the United States account for over 200,000 hospitalizations, up to 49,000 deaths, and an $87.1 billion economic burden. Influenza A virus has caused several pandemics since the turn of the 20th century. The effects of Influenza on public health and economics, compounded with low efficacy of the annual vaccine and emerging antiviral resistance, brings to light the need for an effort to stem these impacts, prevent pandemics, and protect public health by developing novel treatments. This project proposes an alternative approach to combatting Influenza by targeting host factors hijacked during infection that, if inhibited, significantly impair viral RNA expression, but result in low host toxicity. The host factors we examined include RNA export factors (XpoT and Xpo5) and RNA helicases (UAP56 and URH49). We selected paralogs URH49 (DDX39A) and UAP56 (DDX39B) because previous studies suggest differing roles during infection, but we theorize that their high degree of sequence similarity, similar function, and association with many of the same cellular factors may allow them to substitute for one another if one is inhibited. CRISPR was considered as the primary method to evaluate the effect of knockout of these factors on viral RNA expression and host cell toxicity. CRISPR is an RNA-guided mechanism for gene editing and can be used to make null mutations in targeted host genes. However, CRISPR proved to be a significant challenge and, while we could not conclusively confirm whether the CRISPR plasmids were effective at targeting our genes of interest, our initial results were not promising and we did not pursue this approach further. As an alternative, host RNA export factors were evaluated using siRNA to knockdown the factor prior to influenza infection. RNA was analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The potential of inhibiting UAP56 or URH49 as a novel therapeutic target was determined using a visual assessment of cell death. We found that siRNA-mediated knockdown of XpoT and Xpo5 did not have any impact on viral RNA synthesis early during infection. siRNA against UAP56 and DDX39 (targets both UAP56 and URH49) resulted in significant impairment in viral RNA synthesis, confirming previously established work suggesting that UAP56 and URH49 have important roles during infection. Importantly, these helicases play an interferon (IFN) independent role to enhance viral replication, as indicated by analysis in IFN deficient VERO cells. A viability assay relying on trypan blue exclusion did not yield trustworthy results, so a visual assessment of cell death was done. The visual assessment confirms previously-established observations that Nxf1 siRNA treatments result in a high degree of cell death, indicating the toxic nature of Nxf1 inhibition. Cells treated with UAP56 or DDX39 siRNAs demonstrated little to no additional toxicity compared to the non-target control, suggesting they can be inhibited to serve as antiviral targets.

El objetivo base de la siguiente tesis, es que dentro del marco del Tratado de Libre Comercio Perú-Unión Europea, cuya importancia fue mayor después de su vigencia, es identificar a los factores determinantes en la exportación de higos frescos o secos, ya que actualmente estos tienen una mayor relevancia. Por tal motivo, se busca analizar dichos factores en la evolución de las exportaciones de higos con destino a los Países Bajos. Por consiguiente, se plantea la siguiente pregunta: ¿Cuál fue el factor determinante en la evolución de la exportación de higos frescos o secos con destino a los países bajos entre los años 2011-2017? Como respuesta tentativa se planteó la siguiente hipótesis general: El crecimiento de la participación de los competidores internacionales en el mercado de higo fue el factor más determinante en la evolución de las exportaciones de higos frescos o secos con destino a los países bajos entre los años 2011-2017. Aparte, también se plantearon hipótesis específicas. Por otra parte, también se plantean objetivos dentro de la presente tesis. Es por tal motivo, que las informaciones presentadas dentro de los capítulos de esta tesis buscan encontrar una solución a la pregunta de investigación. Asimismo, buscar validar las hipótesis y cumplir con los objetivos planteados. Para lo cual, se utilizó la metodología cualitativa y se elaboraron instrumentos como son las guías de entrevistas y el análisis de los datos recogidos de las diferentes instituciones. Asimismo, se realizaron entrevistas a expertos relacionados con el tema de investigación. / The basic objective of the following thesis is that within the framework of the Peru-European Union Free Trade Agreement, whose importance was greater after its validity, is to identify the determining factors in the export of fresh or dried figs, since currently these have a greater relevance. For this reason, we seek to analyze these factors in the evolution of fig exports to the Netherlands. In this sense, we seek to answer the question: What was the determining factor in the evolution of the export of fresh or dried figs destined to the Netherlands between the years 2011-2017? As a tentative response, the following general hypothesis was put forward: The growth of the participation of international competitors in the fig market was the most determining factor in the evolution of exports of fresh or dried figs to the lower countries between 2011 -2017. In addition, specific hypotheses were also raised. On the other hand, objectives are also proposed within this thesis. It is for this reason, that the information presented within the chapters of this thesis seek to give an answer to the research question. Also, seek to validate the hypotheses and meet the objectives set. For this purpose, the qualitative methodology was used and instruments such as the interview guides and the analysis of the data collected from the different institutions were elaborated. Likewise, interviews were conducted with experts related to the research topic. / Tesis

<p>Vid sin tillkomst är de flesta företag små. Av den anledning kan man anta att det, inom företaget, finns en huvudsaklig beslutsfattare som i slutändan står för de allra viktigaste besluten. Denna person borde således vara den som avgör huruvida ett företag ska initiera export, det vill säga han eller hon fattar det första internationaliseringsbeslutet. Beslutsfattarens entreprenörsdrag blir därför intressanta, då en person med sådan karaktär i större utsträckning torde sträva efter, söka och svara på exportstimuli.</p><p>I denna uppsats undersöks beslutsfattarens inverkan på internationaliseringsprocessen i ett mindre svenskt producerande företag utifrån sju parametrar genom en fallstudie. Av dessa sju är tre parametrar sammanfattade i <em>psykologiska faktorer</em> vilka kopplas till beslutsfattarens riskvillighet, attityd och ambition. Tre ytterligare parametrar är de <em>icke-psykologiska</em> vilka utgörs av kunskap, ålder och erfarenheter. Den sista parametern är <em>aktiviteter</em> vilken avser företagets engagemang.</p><p>Samtliga parametrar, undantag ålder, har visat sig stå i relation till beslut om internationalisering. <em>Aktiviteter</em> har visat sig särskilt viktig då dessa framförallt skapat organisatoriska och ekonomiska förutsättningar för expansion. Detta tillsammans med en, hos beslutsfattaren, positiv inställning till handel med utlandet och en ambition att växa är starkt korrelerade med initiering av exportverksamhet. Att dessa parametrar varit viktiga i internationaliseringen för vårt fallstudieföretag är tydligt men deras enskilda inverkan är dock svårare att uttala sig om.</p><p> </p>

This thesis describes the natural variation and influence of aspen harvesting on stream chemical concentration and flow-weighted export from catchments typical of the Western Boreal Plain, Alberta, Canada. The catchment stream discharge and stream chemical concentrations presented are taken from a subset of a five-year paired catchment (2005-2010) HEAD2 NSERC-CRD study. Nutrients, major anions, major cations and two minor ions were monitored from second-order streams draining a 18.3 sq km reference catchment (R1) and compared to a 9.9 sq km experimental catchment (H1) for two years of pre-harvesting (2005-2006) and two years of sequential harvesting (2007-2008). Preliminary analyses showed that non-harvest high flows had a total average instantaneous export greater than 10 times that of low flows. In addition, summer storms and beaver dam breakages had stream export equivalent to or greater than spring melt. Intensive upland aspen harvesting showed no significant differences in major cation and anion export post-harvest with the exception of increased sulfate. / Ecology

Proper mRNA nuclear export is essential for harmonious growth and maintenance of a cell. An effective weapon influenza virus employs to hijack a host cell is its ability to inhibit such export. Exactly how influenza virus achieves this inhibition is not fully known. Here, we demonstrate that upon infection, influenza virus degrades two nucleopore proteins (Nup98 and Nup96), which play a key role in mRNA nuclear export. Also, a main virulence factor of influenza virus (non-structural protein 1, NS1) binds directly to NXF1 and E1B-AP5, two key constituents of the mRNA export pathway (NXF1/NXT pathway) responsible for exporting bulk (~70%) mRNA from the nucleus. By increasing the expression levels of members of the NXF1/NXT pathway, we were able to reverse NS1-mediated inhibition of gene expression. On the other hand, by decreasing the levels of members of the NXF1/NXT pathway, we demonstrated that host cells become more sensitive to influenza virus infection and produce more viral particles. These results demonstrate undiscovered influenza-mediated host interactions that may be used to medicinally inhibit influenza virus. To this end, high-throughput screens were designed to identify small molecule antagonists of both NS1-mediated inhibition of gene expression and influenza virus-mediated cell death. Seventy-one compounds were identified, and the most potent molecule (named compound #8) was examined further. We found that compound #8 releases influenza virus-mediated mRNA nuclear export blockage and decreased viral replication and viral gene expression. Thus, the bulk mRNA nuclear export machinery is vital to antiviral response, and compound #8 enhances its ability to fight the cytopathic effects of NS1 and influenza virus. In conclusion, our data demonstrate that the mRNA export machinery is disrupted by influenza virus, and that this machinery also facilitates an antiviral function. We have also shown that these two events can be manipulated chemically to attenuate the negative effect of the virus and enhance the positive antiviral effect of the mRNA export machinery, thereby providing a powerful, new strategy against the ever-present, global threat of influenza virus.

Introduction: The trade relationship between the European Union (EU) and African coun-tries based on regional groupings, under the framework of Economic Partnership Agree-ment(EPAs) came to play in most countries in January 2008. It replaces the preferential trade treatment granted by the EU under the Lomé convention and Cotonou agreement which allowed African, Carribean and Pacific countries(ACP) greater access to EU markets as a means of leveraging African exports, and encouraging the competitiveness of African economies in the global economy. Method: This work explores basically secondary data sources on EU trade with regional blocs in Africa over the course of the last 27 years. Special attention is given to thematic concerns in the area of intra-regional trade, balance of trade as well as market share. Graphically presentations are utilized in certain instances across the work to serve illustra-tive purposes and to highlight trends established. Conclusion: The study uncovers compelling evidence suggestive of imbalances in trade be-tween the EU and her trading partners in Africa. It is anticipated that these imbalances could shrink export benefits for the African countries concerned. There is reason to be-lieve that problems associated with implementation of EPA‟s, deriving from the distinct development context of the various countries concerned will hamper their development prospects. As it is at the moment, it is quite obvious that these countries will have to live with the consequences of these agreements and strive to cope with new economic realities that seem clearly difficult to reverse.

Vid sin tillkomst är de flesta företag små. Av den anledning kan man anta att det, inom företaget, finns en huvudsaklig beslutsfattare som i slutändan står för de allra viktigaste besluten. Denna person borde således vara den som avgör huruvida ett företag ska initiera export, det vill säga han eller hon fattar det första internationaliseringsbeslutet. Beslutsfattarens entreprenörsdrag blir därför intressanta, då en person med sådan karaktär i större utsträckning torde sträva efter, söka och svara på exportstimuli. I denna uppsats undersöks beslutsfattarens inverkan på internationaliseringsprocessen i ett mindre svenskt producerande företag utifrån sju parametrar genom en fallstudie. Av dessa sju är tre parametrar sammanfattade i psykologiska faktorer vilka kopplas till beslutsfattarens riskvillighet, attityd och ambition. Tre ytterligare parametrar är de icke-psykologiska vilka utgörs av kunskap, ålder och erfarenheter. Den sista parametern är aktiviteter vilken avser företagets engagemang. Samtliga parametrar, undantag ålder, har visat sig stå i relation till beslut om internationalisering. Aktiviteter har visat sig särskilt viktig då dessa framförallt skapat organisatoriska och ekonomiska förutsättningar för expansion. Detta tillsammans med en, hos beslutsfattaren, positiv inställning till handel med utlandet och en ambition att växa är starkt korrelerade med initiering av exportverksamhet. Att dessa parametrar varit viktiga i internationaliseringen för vårt fallstudieföretag är tydligt men deras enskilda inverkan är dock svårare att uttala sig om.

Given the present situation of environmental problems, clean technologies or cleantech is considered a way of reaching global sustainability and at the same time also seen as an engine of economic growth and fulfilling commitments to social and environmental welfare. Under this background, Swedish cleantech sector have not achieved that much commercial success yet that they are supposed to be while maintaining a reputation of top technological innovative country. The Swedish cleantech sector is dominated by small medium-sized firms (SMEs) and often limited to resources at their disposition. Thus, the Swedish government has designed various policies and export support programs to promote this sector but somehow firms could not reach up to them. Hence, it has become necessary to study the Swedish cleantech firms in order to analyze the existing gap. The purpose of this study is to run an investigation about individual cleantech firms and analyze how they are experiencing Swedish governmental export support programs. On the other hand, this study has also tried to find out what firms really expect from these programs so that it will help to reduce the gap. Based on the study of four cases and one independent interview, the study has shown two different scenarios. In one hand, micro level SMEs specially which are in initial phase of their internationalization process cannot reach up to governmental export support programs due to high acquiring cost and inflexible pre-requirements. On the other hand, small level SMEs which are in mature phase of their internationalization process have faced completely reverse experience than initial phase micro firms but not satisfied with the provided service quality. The study has also revealed that firms with relatively new technology face problems to get support from governmental agencies due to uncertain market performance. The study has further showed, this is not always the high acquiring cost and inflexible conditions, participation in governmental export support programs is also depend on firm’s owns mindset and their business strategy. So, in order to reduce the gap between Swedish governmental export support programs and cleantech firms’ expectations, the studied firms have suggested to implement a proper business model that fits into each type of firms’ needs based on their position in the internationalization process, create a separate institution or agency and Science Park that only deals with cleantech firms issues, and co-operation among the different state cleantech firms and the universities.

Det finns idag över 40 000 registrerade små och medelstora bolag i Sverige, varav cirka 25 procent exporterar. Värdet av all Sveriges export uppgår till nästan hälften av Sveriges BNP, vilket innebär att Sverige är mycket beroende av sin exportverksamhet. När ett företag ska utvidga sin verksamhet och ta sig in på utländska marknader kan man inte lita på att man kan arbeta som på hemmamarknaden längre. En exportmarknad skiljer sig ofta åt från hemmamarknaden, och företagen behöver kunskap för att kunna utföra en lyckad export. Tidigare forskning har uppmärksammat tre kunskapstyper som alla är kritiska för att ett företag ska kunna internationaliseras på ett lyckat sätt. Dessa tre kunskaptyper är teknologisk kunskap, marknadskunskap samt internationaliseringskunskap. Denna uppsats ämnar undersöka hur dessa kunskapstyper utvecklas av företag som exporterar. En flerfallsstudie på sex svenska exporterande företag har utförts med semi-strukturerade intervjuer med nyckelpersoner på varje företag. Uppsatsen visar att ett företags teknologiska kunskap är kritisk för att företaget ska kunna exportera på ett lyckat sätt. Behovet av marknadskunskap blir högre ju längre bort från hemmamarknaden företaget exporterar. Slutligen så ökar företagets erhållna internationaliseringskunskap ju fler marknader som företaget exporterar till.

Plant cells contain multiple mobile Golgi bodies. Golgi bodies receive cargo from specialized subdomains of the endoplasmic reticulum (ER), so-called ER export sites (ERES). How ERES operate in plant cells is largely uncharacterized. <p>In mammals and yeast, the commonly recognized ER-to-Golgi transport model asserts that protein transport between these two organelles is mediated by vesicles. Formation of these vesicles is interceded by COPII and COPI coat complexes. COPII coat proteins assemble at ERES. The minimal components of the COPII coat comprise the following proteins: the GTPase Sar1, and two large heterodimeric complexes, Sec23/24 and Sec13/31. COPII vesicles are responsible for forward (anterograde) protein traffic from the ER to the Golgi apparatus. Proteins are constantly recycled from the Golgi back to the ER through a conserved backward (retrograde) pathway mediated by COPI coat proteins. Fusion of the anterograde and retrograde carriers with target membranes is mediated by a subset of specialized proteins called soluble N-ethyl maleimide sensitive factor attachment protein receptors (SNAREs). Studies conducted in mammalian and yeast systems also concluded that ER-to-Golgi SNARE proteins and membrane cargo proteins are concentrated into COPII vesicles through a direct interaction and binding with the pre-budding complex Sec23/24-Sar1. <p>The COPII component distribution and their biological function in plant cells are largely uncharacterized. Therefore, through the study of the COPII protein Sec24, this work aimed (i) to investigate where and how protein transport between ER and Golgi occurs in plant cells, and (ii) to establish the importance of the anterograde and retrograde transport equilibrium in regulating the ER protein export. To do so, live cell imaging of a fluorescent protein fusion of Sec24 was used and the dynamics of this protein chimaera were followed in tobacco leaf epidermal cells. The imaging investigations were complemented by mutagenesis studies and biochemical analyses. <p>The obtained results indicate that in plant cells Sec24 is localized at specific regions of the ER that represent mobile units continuously joined to the Golgi apparatus. From this study the importance of the balance between the anterograde and retrograde transport in protein ER export has also emerged. I have shown in fact, that blockage of the retrograde pathway using Arf1 mutants and COPI chemical inhibitor determines the collapse of the anterograde protein trafficking from the ER to the Golgi. Moreover, this study has shown that Sec24 is capable of an interaction with the SNAREs Sed5 and Sec22. This is a forward step in our understanding of the role of Sec24 in the mechanism of cargo selection and recruitment.