As emissions of greenhouse gases has become one of our times most urgent issues, the policies implemented by governments in effort to reduce them are many and varied. In Sweden, a feebate system for vehicles was implemented in mid 2018. This paper attempts to answer the question whether or not the bonus-side (a subsidy for electric vehicles) of the policy will reduce emissions in a cost-efficient and fair way. The questions in answered by using material available to those who made the decision, and by looking at previous research and data. Mathematical examples of the cost, through the cost of the policy, of reduction is compared to EU ETS to evaluate cost-efficiency. The fairness aspect is reviewed by studying regional data. The conclusions are that the policy is neither cost-efficient nor is it free from interregional equity concerns. / Medan utsläppen av växthusgaser har kommit att bli vår tids största utmaningar försöker länder och myndigheter implementera en bred variation av styrmedel för att minska utsläppen. I Sverige, infördes ett s.k. feebate system för personbilar i mitten av 2018 och denna uppsats försöker besvara frågan om Bonusen (subvention av bl.a. elbilar) i styrmedlet kommer att reducera utsläpp på ett kostnadseffektivt vis samtidigt som det inte bidrar till negativa fördelningseffekter. Forskningsfrågan är besvarad genom att använda material som fanns tillgängligt när beslutet att införa styrmedlet fattades, genom att använda tidigare forskning samt statistik. Matematiska exempel över hur kostnaden, genom styrmedlet, för reduktionen blir jämfört med utsläppsrätter för att undersöka kostnadseffektivitet, och fördelningseffekterna är utvärderade genom studier av regional statistik. Slutsatserna är att styrmedlet varken är kostnadseffektivt eller utan negativa fördelningseffekter ur ett interregionalt perspektiv.

Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-10-24T17:02:58Z No. of bitstreams: 1 JULIANA_LORENZONI_ALTHOFF.pdf: 23099056 bytes, checksum: 2ebbb4db3683a55ddc1d12778cf36c64 (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-10-25T14:52:43Z (GMT) No. of bitstreams: 1 JULIANA_LORENZONI_ALTHOFF.pdf: 23099056 bytes, checksum: 2ebbb4db3683a55ddc1d12778cf36c64 (MD5) / Made available in DSpace on 2018-10-25T15:03:03Z (GMT). No. of bitstreams: 1 JULIANA_LORENZONI_ALTHOFF.pdf: 23099056 bytes, checksum: 2ebbb4db3683a55ddc1d12778cf36c64 (MD5) Previous issue date: 2009-03-23 / Background: The colon-rectal cancer is the third most frequent neoplasia in the western world with the highest mortality rates. The progression of normal colon tissue to invasiveness neoplasia is follow by several processes called carcinogenesis. Afterwards it converges to the cellular migration and metastasis of the tissue. The metabolic ways of the E26 (Ets) transcription factors, identified in a great variety of species, contributes in this process, by activating or repressing the DNA transcription. Specially, the prostate-derived Ets factor (PDEF) which prognosis and cancer colon-rectal relation action is not completely elucidating at the moment. Methods: A retrospective cohort of patients with pathologic stage I ? III colon-rectal cancer, diagnosed and treated in the same institution between 2002 and 2008, was study. Histological and clinical features as well as clinical outcomes and survival were reviewed. The tissue microarrays (TMA), immunohistochemical analysis and image capture quantification were carried out in representative blocks of tumor with antibodies for the detection of the PDEF expression and Ki-67. The endpoints were to determine the prevalence of the PDEF protein expression and its correlation with these population?s prognostic factors. Results: The sample was constituted 46 patients and the median follow-up was 23,2 months. There was a trend towards loss of PDEF protein expression according to the patients? clinical stage. PDEF expression values were 30,3%, 25,8% and 14,7% in stages I, II and III, respectively. There was not a significant correlation with the lost of PDEF protein expression and the clinical and pathological characteristics along with the proportion of Ki-67 proliferative marker and the patient?s global survival. Conclusions: These results suggest that the PDEF protein, member of the Ets family, act as a repression gene of cancer colon-rectal carcinogenesis. The PDEF expression analysis can be an interesting prognostic marker and a therapeutic target. New studies with more patients and a long follow-up are necessary to validate these results. / Base te?rica: O c?ncer colorretal ? a terceira neoplasia mais freq?ente no mundo ocidental com taxas de mortalidade ainda consideras altas. A progress?o do tecido epitelial do c?lon normal at? o est?gio de neoplasia invasiva ? acompanhada de uma s?rie de processos celulares chamados carcinog?nese que, ao fim, convergem para o potencial de migra??o celular e metastatiza??o. As vias metab?licas da fam?lia dos genes Ets (E26 - sequ?ncia espec?fica de transcri??o), identificada em uma grande diversidade de esp?cies, contribuem neste processo, ativando ou reprimindo transcri??es de DNA. Em especial o fator derivado prost?tico (PDEF) cujo progn?stico e mecanismo de a??o relacionado ao c?ncer colorretal, at? o momento, n?o est? claramente elucidado. M?todos: Uma coorte retrospectiva de pacientes com carcinoma colorretal est?gios de I a III, diagnosticados e tratados na mesma institui??o de 2002 a 2008, foi estudada. As caracter?sticas histol?gicas e cl?nicas, bem como os dados de evolu??o e a sobrevida foram revisados. A an?lise de imunoistoqu?mica com m?todo de matriz de amostras teciduais (TMA) e a quantifica??o por captura de imagem foram realizadas em blocos representativos do tumor com anticorpos para detec??o da express?o da prote?na PDEF e Ki-67. Os objetivos eram detectar a preval?ncia da express?o da prote?na PDEF e sua correla??o com fatores progn?sticos nesta popula??o. Resultados: A amostra foi constitu?da de 46 pacientes e tempo de seguimento mediano de 23,2 meses. Houve tend?ncia a perda da prote?na PDEF conforme o estadiamento dos pacientes sendo a express?o de 30,3%, 25,8% e 14,7% nos est?gio I, II e III, respectivamente, P=0,416. N?o encontrou-se associa??o significativa entre os achados cl?nico-patol?gicos, a dosagem do marcador de prolifera??o celular Ki-67 e a sobrevida global dos pacientes com a perda da express?o da prote?na PDEF. Conclus?es: Os resultados sugerem que a prote?na PDEF, membro da fam?lia Ets, atue como gene repressor da carcinog?nese do c?ncer colorretal. A an?lise de sua express?o pode se tornar um interessante marcador progn?stico e alvo terap?utico. S?o necess?rios novos estudos com amostras maiores e tempo de seguimento mais longo a fim de validar estes achados.

This thesis is using the idea that climate change is a product of discourses. It puts focus on the knowledge creation of particular climate change governance. This thesis aims to identify the discursive articulations of carbon trading in the Czech EU ETS. Environmental discourses, informed by M. Foucaults governmentality concept, have an impact on how climate change is rendered governable. Discourse analysis of the Czech EU ETS uses governmentality lens to detect fields of visibility, technical aspects, forms of knowledge and formations of identities of the particular environmental discourse to uncover, how the EU ETS is translated into the national level and how does it hold together.

近年來世人注目的焦點已從金融風暴議題，轉向了地球暖化、氣候劇變等問題，世界環境變遷造成人類巨大的傷害，已是國際組織與各國政府施政重點。在1997年12月於日本召開UNFCCC COP3，通過旨在限制溫室氣體排放的京都議定書，其中排放交易是指已開發國家間的合作，普遍被認為最具有成本效率性。 近年全球對於環境保護意識已有大幅提升，各國降低碳排放之手段可區分為技術面以及經濟面。本文以後者為主要探討重點，亦即透過經濟手段以促進減碳科技廣泛的應用。減碳的技術同時具備外部性及公共財的特性，降低二氧化碳排放對環境之效益並無法排除他人享受，因此若碳價波動過度劇烈將影響企業減碳投資意願時，政府須介入管制碳價格。本文先探討究竟影響碳價波動的主因為何，以利後續研究碳權價格波動和價格管制間，權衡對減碳投資與減碳成效的影響。 研究結果顯示，歐洲地區如北歐、東歐及南歐夏日氣候差異大，以及歐洲地區處於溫帶氣候因素使得極熱變數對碳價波動影響不顯著，但不保證其它地區有相同結論；能源價格對碳權價格有重大之影響，尤其原油最為明顯；由於匯率會影響能源價格，因此連帶影響碳價；極寒氣候對碳價有顯著影響，其先影響能源之供需，間接影響碳價之波動；SP之落後期在phase 2有縮短之趨勢，即天然氣與煤炭間之價差對碳價影響越來越大；進行碳價格之實證分析必須區分第一階段及第二階段，否則會造成估計上之不準確。不僅能源價格本身對碳價會有直接之影響，影響能源價格之變數亦間接影響碳價之波動，如氣候以及匯率，先經由透過能源價格變動再傳導至碳權價格。

Les facteurs de transcription FLI-1 et SPI-1/PU.1 appartiennent à la famille ETS et reconnaissent le même motif sur l'ADN GGAA. Leur activation est observée de manière récurrente dans les érythroleucémies murines induites par le virus de Friend. Ces observations suggèrent un rôle crucial de ces deux facteurs dans la transformation de la lignée érythrocytaire potentiellement par la dérégulation de gènes cibles communs. Mon travail de thèse a consisté à tester la contribution de ces deux facteurs au phénotype des cellules érythroleucémiques et à rechercher les gènes cibles directs communs.Nous avons pu montrer que FLI-1 et SPI-1/PU.1 ont des contributions additives au phénotype des cellules érythroleucémiques surexprimant les deux facteurs. Par une approche transcriptomique, nous avons identifié une grande proportion de gènes cibles directs communs à FLI-1 et à SPI-1/PU.1 impliqués dans différentes étapes de la biogenèse des ribosomes. La déplétion de ces facteurs induit une réduction de la biogenèse des ribosomes qui n'induit pas de stress ribosomique stabilisant p53. Néanmoins, nous avons mis en évidence une contribution spécifique de RPL11, un médiateur essentiel du stress ribosomique, à la différenciation des cellules érythroleucémiques induites par l'absence de ces facteurs.Nous avons mené en parallèle l'inventaire par ChIP-Seq des sites de recrutement de FLI-1 et de SPI-1/PU.1 sur le génome entier de 3 lignées érythroleucémiques indépendantes. Cette stratégie nous a permis de montrer que les régions de recrutement communes sont la conséquence de la proximité de consensus spécifiques et distincts et du recrutement de FLI-1 et de SPI-1/PU.1 sur leur propre consensus.

<p>The genus <i>Arnica</i> (Asteraceae) was investigated for phylogenetic relationships and sesquiterpene lactone (STL) content with the aims to trace the evolutionary history of the genus and to investigate possible congruencies between DNA sequence data, secondary chemistry, and biological activity. </p><p>Complex evolutionary patterns in <i>Arnica</i> are evident from phylogenetic analyses of chloroplast regions (the <i>rpl16</i> and <i>rps16</i> introns and the <i>psbA–trnH</i>, <i>ycf4–cemA</i>, and <i>trnT–L</i> spacers), nuclear ribosomal regions (the internal and external transcribed spacers) and the nuclear low-copy DNA region coding for the second largest subunit of RNA polymerase II (<i>RPB2</i>) between exons 17 and 23. Polymorphism was detected in nuclear ribosomal and low-copy regions<i>,</i> likely caused by polyploidy and agamospermy. Lineage sorting and/or hybridization is a possible explanation for incongruencies between topologies of the different DNA regions. None of the five subgenera in <i>Arnica</i> constitute a monophyletic group according to any of our analyses. </p><p>Sesquiterpene lactone profiles were compared to nuclear ribosomal DNA data using phylogenetic inference and principal component analysis for 33 accessions of 16 species. Clusters supported by both STL chemistry and ribosomal DNA sequence data consist of multiple accessions of the same species (e.g.<i> A montana </i>and<i> A. longifolia</i>), indicating that these species are well defined both genetically and chemically, based on our sampling. Support for subspecies classification of <i>A. chamissonis</i> and <i>A. parryi</i> was found in chemical data. For the first time STLs are reported from subtribe Madiinae, sister to Arniciinae.</p><p>Anti-inflammatory properties, as measured by inhibition of human neutrophil elastase release from neutrophils and inhibition of the binding of transcription factor NF-κB to DNA, were investigated for extracts of 12 <i>Arnica</i> species. <i>Arnica montana</i>, <i>A. chamissonis</i> and <i>A. longifolia</i> accessions show high inhibitory effects in both bioassays. Generally, species with a more diverse STL chemistry also possess the strongest inhibitory activity in the bioassays.</p>

The genus Arnica (Asteraceae) was investigated for phylogenetic relationships and sesquiterpene lactone (STL) content with the aims to trace the evolutionary history of the genus and to investigate possible congruencies between DNA sequence data, secondary chemistry, and biological activity. Complex evolutionary patterns in Arnica are evident from phylogenetic analyses of chloroplast regions (the rpl16 and rps16 introns and the psbA–trnH, ycf4–cemA, and trnT–L spacers), nuclear ribosomal regions (the internal and external transcribed spacers) and the nuclear low-copy DNA region coding for the second largest subunit of RNA polymerase II (RPB2) between exons 17 and 23. Polymorphism was detected in nuclear ribosomal and low-copy regions, likely caused by polyploidy and agamospermy. Lineage sorting and/or hybridization is a possible explanation for incongruencies between topologies of the different DNA regions. None of the five subgenera in Arnica constitute a monophyletic group according to any of our analyses. Sesquiterpene lactone profiles were compared to nuclear ribosomal DNA data using phylogenetic inference and principal component analysis for 33 accessions of 16 species. Clusters supported by both STL chemistry and ribosomal DNA sequence data consist of multiple accessions of the same species (e.g. A montana and A. longifolia), indicating that these species are well defined both genetically and chemically, based on our sampling. Support for subspecies classification of A. chamissonis and A. parryi was found in chemical data. For the first time STLs are reported from subtribe Madiinae, sister to Arniciinae. Anti-inflammatory properties, as measured by inhibition of human neutrophil elastase release from neutrophils and inhibition of the binding of transcription factor NF-κB to DNA, were investigated for extracts of 12 Arnica species. Arnica montana, A. chamissonis and A. longifolia accessions show high inhibitory effects in both bioassays. Generally, species with a more diverse STL chemistry also possess the strongest inhibitory activity in the bioassays.

In Sweden, close to 10 000 men are annually diagnosed with prostate cancer (PCa) and approximately 2400 men die of their disease each year. Today there is no reliable marker that can separate patients who will have an aggressive type of disease that requires treatment, from patients who will have a more indolent clinical course and can be left untreated. This further leads to the current problem of over treatment of men with PCa. Hence, there is an urgent need for reliable prognostic markers that can be used at time of diagnosis. With the discovery of recurrent gene rearrangements in PCa, most commonly ERG rearrangements, hope came that this aberration could play a role in diagnosis and/or prognosis of the disease. The aim of this thesis was to investigate the clinical implication of ERG rearrangements in the management of PCa. The work in this thesis supports the findings from previous studies, suggesting that the ERG rearrangement is a sign of a more aggressive type of cancer. The major findings are that in multifocal PCa, the ERG rearranged cancer foci are more prone to metastatic dissemination compared to foci without the ERG rearrangement and that patients harboring the ERG rearrangement have a faster disease progression leading up to earlier start of hormonal treatment. Furthermore, the results add an additional level of complexity in a subset of PCa tumors that harbor multiple gene rearrangements on the cellular level. The result also show that the newly available ERG antibody is highly predictive of ERG rearrangement and is appropriate to use when faced with limitations in tissue amounts. The findings in this thesis indicate that the ERG rearrangement has a potential role in the clinical management of PCa but further studies arerequired.

! BACKGROUND: Exposure to Environmental Tobacco Smoke (ETS) is elevating blood levels of inflammatory mediators and chemoattractants which seem to play an important role in the development of several diseases (e.g. Chronic Obstructive Pulmonary Disease). First evidences showed that men and women might differ in their proneness for these diseases. The aim of this study was to investigate whether there are effects of ETS during pregnancy on inflammatory cytokines in cord blood and in mother’s blood and if there are any differences between male and female newborns. METHODS: Within the LiNA (Lifestyle and environmental factors and their influence on Newborn Allergy Risk) study, whole blood samples of 460 mother-child pairs were analyzed for the concentrations of IL-6, IL-8, IL-10, IL-12, IL-4, IL-5, INF-gamma, TNF-alpha and MCP-1 using cytrometic bead asseys. The association between ETS exposure and cytokines was calculated using the Mann-Whitney-U-test and adjusted with a multiple regression model for parental atopy, parental education status and cat ownership. The exposure assessment is based on questionnaire data on smoking behaviour of the parents and measurement of indoor benzene concentration. RESULTS: Female newborn, being exposed in utero to 10 cigarettes a day or more, had significantly higher blood concentrations of IL-8, IL-6 and MCP-1 whereas there have been no elevations in male newborn being exposed to the same amount of cigarettes. Furthermore a significantly decreased amount of INF-gamma was found in cord blood of male newborns but not in female newborns. General increasing levels of TNF-alpha in cord blood where found for daily smoke exposure without relating it to the exact number of cigarettes. CONCLUSION: The data of this study refer to gender-specific differences in the susceptibility to ETS exposure. The induction of inflammatory signals in cord blood in response to cigarette smoke exposure is stronger in female than in male newborn. / Die vorliegende Arbeit ist Teil einer umweltepidemiologischen Kohortenstudie (LiNA), in der der Einfluss von Umwelt- und Lebensbedingungen auf die Entwicklung von Immunsystem und Allergien bei Neugeborenen unter Einbezug der vorgeburtlichen Zeit untersucht wird. In welchem Maße sich eine Rauchbelastung während der Schwangerschaft auf die Zytokinmuster der Neugeborenen im Nabelschnurblut auswirkt und inwiefern dies mit dem Zytokinmuster der Mutter korreliert, sollte das Ziel dieser Dissertation sein. Dafür wurden Daten von insgesamt 629 Mutter-Kind-Paaren erhoben, Zytokin- und Chemokinbestimmungen, sowie die des Gesamt-IgE aus den Blutproben der 34. SSW und denen der Nabelschnur vorgenommen. Interessanterweise konnten geschlechterspezifische Unterschiede im Zytokinspektrum der Neugeborenen gefunden werden. Bei den weiblichen Neugeborenen zeigte sich eine deutliche Erhöhung proinflammatorischer Marker, wenn deren Mütter dem Rauch von mehr als 10 Zigaretten pro Tag ausgesetzt waren. Dieser Anstieg war weder im Blut der männlichen Neugeborenen noch im Blut der Schwangeren in der 34. SSW zu beobachten. Zusätzlich konnte beobachtet werden, dass auch einzig die männlichen Neugeborenen stark negativ mit ihrer IFN-gamma-Produktion auf die passive Rauchbelastung reagieren. Die mit dieser Arbeit ermittelten Daten, dass das Immunsystem beim Neugeborenen geschlechterspezifisch unterschiedlich auf Tabakrauch zu reagieren scheint, sind erstmals in der Literatur zu finden. Die Erforschung des Immunsystems und dessen Beteiligung an zahlreichen Erkrankungen, besonders den chronisch Inflammatorischen, ist durchaus relevant im medizinischen Alltag. Diese Arbeit trägt einen weiteren Baustein dazu bei und gibt Anstoß für weitere Studien.

Human epithelium-specific ETS transcription factor-1 (ESE-1), which is also known as E74-like factor-3 (Elf3) in mice, is strongly expressed in lung during fetal development and in certain lung cancers. The primary goal of the work presented in this thesis was to investigate whether ESE-1 is involved in regeneration of the injured lung epithelium by administering naphthalene to both wild-type (Elf3 +/+) and Elf3-deficient (Elf3 -/-) mice. However, optimal conditions for proper utilization of the naphthalene-induced lung injury model must first be established. Therefore, dose-response studies were initially conducted by administering three different doses of naphthalene to both male and female mice, as described in chapter 2. Although it is shown that the extent of naphthalene-induced Clara cell injury is dose-dependent in both male and female mice, female mice are more sensitive to naphthalene-induced injury than male mice independent of the dose. Furthermore, it is also demonstrated that these gender-dependent differences in naphthalene injury can subsequently influence downstream lung repair kinetics. In light of these findings, lung regeneration was examined in both sexes of both Elf3 +/+ and Elf3 -/- mice. As reported in chapter 3, the kinetics of bronchiolar epithelial cell proliferation and differentiation is delayed considerably in Elf3 -/- mice following naphthalene injury. Moreover, expression of transforming growth factor-beta type II receptor, which is a well-known transcriptional target gene of ESE-1 and is involved in the induction of epithelial cell differentiation, is significantly lower in the bronchiolar airway epithelium of Elf3 -/- mice as compared to Elf3 +/+ mice under steady-state conditions and during repair of naphthalene-induced damage. Collectively, these findings occur to a similar extent in both sexes of both Elf3 +/+ and Elf3 -/- mice, and suggest that ESE-1 plays an important role in regulating the kinetics of airway epithelial regeneration after acute lung injury.