Lennart Stenberg. / Includes bibliographical references (p. 58-60). / Supported by the Swedish Board for Technical Development.

Alice H. Amsden adn Takashi Hikino. / Includes bibliographical references (p. 59-67).

Blotterkrossed is a twelve-minute work for wind ensemble which elaborates on a compositional system known as the Circle of 12 Tones, originally developed by Ron Jarzombek and used to compose music performed by death metal supergroup Blotted Science. Jarzombek’s system presents an intuitive method of selecting pitch-class segments from twelve-tone aggregates. These individual segments are articulated until the aggregate structure is completed. At that point, a new permutation of the aggregate is initiated. This method is compositionally attractive as it is somewhat open-ended and unordered, but the absence of deeper pitch relations projects a certain lack of musical coherence. In order to add a deeper level of structural integrity to this system, a method is utilized which structurally relates multiple forms of the initial row, in effect creating four distinct subsets of the ordered aggregate collection, each one related by transposition and/or inversion. The result is a palate of hundreds of pseudo-serialized aggregate permutations. In Blotterkrossed, each one of these aggregate “row forms” is used as the basis of respectively independent sections of the piece. The sonority of each row form evokes distinct character changes to better aurally convey the transformation from one row form to the next.

Despite improvements in chemotherapy and radical surgical debulking, peritoneal carcinomatosis (PC) remains among the most common causes of death for abdominal cancers. Immunotherapies have demonstrated efficacy in selected solid malignancies but their potential in PC is poorly explored. Here I report that intraperitoneal injection of an infected cell vaccine (ICV), consisting of autologous tumor cells infected ex-vivo with an oncolytic Maraba MG1 virus expressing interleukin-12 (IL-12), promotes the migration of activated natural killer (NK) cells to the peritoneal cavity in response to the secretion of interferon gamma-induced protein-10 (IP-10) from dendritic cells. This recruitment of cytotoxic, IFNγ-secreting NK cells is associated with a dramatic reduction in tumor burden and improved survival in a colon cancer model of PC. Even in mice with bulky PC (tumors >8 mm), a complete radiological response was demonstrated within 8-14 weeks, associated with 100% long-term survival. Importantly, these results were recapitulated in human lymphocytes exposed to human tumor cell lines infected with MG1-IL12. Finally, I demonstrate that MG1-IL12-ICV generates an effective CD4 and CD8 T cell response in mice following prophylactic immunization associated with the maturation of peritoneal dendritic cells and enrichment of tumor-specific peritoneal T cells. The research presented in this thesis suggests that an MG1-IL12-ICV is a promising therapy that could provide benefit to the thousands of patients diagnosed with PC each year.

Informe de Seminario para optar al grado de Licenciado en Historia / Seminario de grado: “Historia, Mujeres y Sociedad”

Introdução. A paracoccidioidomicose (PCM) é uma micose sistêmica crônica, endêmica na América Latina, principalmente Brasil, sendo a oitava causa de morte entre as doenças infecciosas crônicas recorrentes. A PCM infecção é caracterizada por uma resposta Th1, a forma aguda por um perfil misto da resposta Th2/Th9, enquanto na forma crônica caracteriza-se pelo perfil Th17/Th22. A ocorrência e gravidade da PCM humana podem também estar associadas a fatores genéticos como os polimorfismos dos genes de citocinas. Objetivos. 1. Descrever a frequência dos polimorfismos de (SNPs) IFNG +874 T/A, IL12B 3\' UTR +1188 A/C e IL12RB1 11014 A/G no éxon 7 em pacientes e controles; 2. Investigar a associação entre esses polimorfismos e as diferentes formas clínicas da micose; 3. Verificar se há associação entre esses polimorfismos e a secreção das citocinas IFN-y, IL-12p40 e IL-12p70. Materiais e Métodos. 143 pacientes com PCM foram incluídos (40 com a forma aguda, 100 com a forma crônica multifocal e 17 unifocal). Critérios de inclusão: ter doença ativa (DA) comprovada por exame micológico ou histopatológico positivo ou presença de anticorpos anti-Paracoccidioides brasiliensis (>= 1/32 por contraimunoeletroforese) ou ter doença curada/tratada (CT) quando comprovada anteriormente pelos critérios de DA e atualmente com títulos de anticorpos estáveis e <= 4 em dois períodos com intervalo >= 6 meses. Analisaram-se os SNPs IFNG pela técnica de PCR-ARMS (\"Polymerase Chain Reaction - Amplification Refractory Mutational System\"), IL12B e IL12RB1 por RFLP (\"PCR-Restriction Fragment Lenght Polymorphism\"). Para a dosagem de citocinas foram utilizadas as técnicas de ELISA (n=29) e CBA (\"Cytometric Bead Array\"; n= 18), sendo considerados estatisticamente significantes, os valores de p < 0,05 para os testes de x2 e o teste de Kruskal-Wallis, com pós-teste de Dunn. Resultados. O genótipo AA do SNP IL12RB1 foi mais frequente na forma crônica multifocal e o genótipo AG, na forma unifocal masculina (p= 0,048). À análise desta forma clínica entre ambos os sexos, o genótipo AG foi também mais frequente no sexo masculino (p= 0,009). Segundo a etnia, foi demonstrada diferença estatisticamente significante nas frequências dos genótipos e alelos dos SNPs IFNG e IL12RB1 (p < 0,05). Em relação às formas clínicas da PCM, houve similaridade nas frequências dos genótipos e alelos dos SNPs estudados. Quanto aos níveis das citocinas, para os SNPs IFNG, IL12B e IL12RB1, maiores níveis de secreção de citocinas, frente a PHA, foram registrados nos grupos CT e CO em relação ao DA, sugerindo relação com a evolução da doença e com a imunossupressão já descrita na doença ativa. Conclusão. Não houve associação entre os SNPs IFNG, IL12B e IL12RB1 e as diferentes formas da doença quando todos os pacientes foram analisados; no sexo masculino, sugere-se que o genótipo AA esteja associado à doença crônica mais disseminada (IL12RB1). Houve diferença significante entre as etnias nos SNPs IFNG e IL12RB1, sugerindo-se a ampliação do número de pacientes em determinadas etnias e na forma clínica unifocal para melhor compreensão dessas associações / Introduction. Paracoccidioidomycosis (PCM) is a systemic chronic mycosis, endemic in Latin America, mainly in Brazil where it is the eighth cause of death among chronic recurrent infectious diseases. PCM infection is characterized by the Th1 immune response, the acute form, by a mixed Th2/Th9 profile, while the chronic form is characterized by Th17/Th22 profile. The occurrence and severity of human PCM can also be associated with genetic factors such as polymorphisms on genes of cytokines. Objectives. 1. To describe the frequencies of the single nucleotide polymorphisms (SNPs) IFNG +874 T/A, IL12B 3\'UTR +1188 A/C and IL12RB1 11014 A/G on exon 7, on patients with PCM and non-PCM controls; 2. To investigate the association between those SNPs and the different clinical forms of PCM. 3. To verify the possible association between those SNPs and the secretion of the cytokines IFN-?, IL-12p40 and IL12p70. Materials and Methods. 143 patients with PCM were included (40 with acute form, 100 with multifocal chronic form and 17 unifocal). Inclusion criteria: active disease (DA) proved by fungal identification on direct microscopy/histopathology or culture, or presence of antibodies antiParacoccidioides brasiliensis ( >= 1/32 by counterimmunoelectrophoresis) or cured/treated disease (CT) when previously proved by criteria of DA and present stable antibodies titles =6 months in between. The SNP IFNG was analyzed by PCR-ARMS (Polymerase Chain Reaction - Amplification Refractory Mutational System) and the SNPs IL12B and IL12RB1 by PCR-RFLP (PCR-Restriction Fragment Length Polymorphism). The levels of cytokines were detected by ELISA (n= 29) and CBA (Cytometric Bead Array; n= 18) and values of p < 0.05 for ?2 test and Kruskal-Wallis\' test, with Dunn\'s post-test were considered statistically significant. Results. The AA genotype of SNP IL12RB1 was the most frequent in the multifocal chronic form while the AG was more frequent in men with the unifocal chronic form of PCM (p = 0.048). On this clinical form in the comparison between genres, the AG genotype was also more frequent in men (p= 0.009). On ethnicity, it was demonstrated statistical difference between the frequencies of genotypes and alleles of SNPs IFNG and IL12RB1 (p < 0.05). In the comparison between the clinical forms of PCM, the frequencies of genotypes and alleles of the evaluated SNPs were similar. On the levels of cytokines, for SNPs IFNG, IL12B and IL12RB1, increased levels of cytokines were observed with PHA on the CT and CO groups compared with DA, suggesting a connection with the evolution of the disease and the previously described immunosuppression during active disease. Conclusion. There was no association between the SNPs IFNG, IL12B and IL12RB1 and the different forms of PCM when all patients were analyzed; among men, it is suggested that the AA genotype of IL12RB1 is associated with a more disseminated chronic disease. There was a significant difference between the ethnicities on SNPs IFNG and IL12RB1, being the latter also associated with the chronic form in men. The increase in the number of patients in certain ethnic groups and in the unifocal clinical form of PCM might help the better understanding of these associations

No description available.

L'exploitation de l'énergie éolienne loin des côtes, bien qu'abondante, dépend du transport de puissance en Courant Continu Haute Tension (HVDC) qui nécessite une sous-station placée sur une plateforme dédiée. Cette plate-forme offshore étant volumineuse, son cout d'installation est élevé et sa mise en œuvre est compliquée. Cette thèse s'intéresse à une topologie de ferme éolienne offshore DC qui transporte son énergie vers l'onshore sans utiliser de sous-station offshore. Ce type de Ferme Eolienne est appelé Ferme Eolienne Série Parallèle (SPWF). Il est composé de plusieurs grappes d'éoliennes interconnectées en série, de sorte que cette interconnexion engendre directement un niveau de tension adapté à la tension du réseau HVDC. Cependant, la connexion en série implique que la tension de chacune d'entre elle n'est plus constante. Un déséquilibré de production d'énergie conduit à des variations des tensions en sortie des éoliennes. Ces variations de tension peuvent engendrer des surtensions aux bornes d'une éolienne dans la grappe et l’endommagé. Une stratégie permettant de limiter la surtension d'éolienne est proposée et développée. Cette stratégie est d'abord validée dans un contexte de connexion point à point avec la prise en compte de la transmission HVDC basée sur des câbles DC et un Convertisseur Modulaire Multiniveaux (MMC) permettant de la connecté au réseau onshore. Dans un second temps, la ferme SPWF est intégrée dans des systèmes DC multi-terminaux (MTDC). Les résultats de simulation démontrent la faisabilité de la stratégie et montrent qu'aucune réduction de puissance n'est alors nécessaire pour limiter les tensions en sortie des éoliennes. / The massive exploitation of far offshore wind energy relies heavily on the High Voltage Direct Current (HVDC) transmission system, in which dedicated offshore substations for converting power from AC into DC are necessary. However, the bulky offshore platform is costly and its installation is complicated. This thesis aims to contribute to the study of a pure DC offshore wind farm topology which exports its energy to onshore without using an offshore centralized power conversion substation. The examined wind farm topology is called Series Parallel Wind Farm (SPWF), which comprises several clusters of wind turbines connected in series, so that the output converters of the wind turbines step up the voltage to a higher level for direct power transmission. However, due to this distinctive feature, unbalanced power production of wind turbines leads to output voltage variation of wind turbines, which is harmful to the wind turbines. The work carried out in this thesis begins with the identification of the basic elements to constitute the SPWF. Afterwards, the operation of the SPWF is explained and its overvoltage characteristic is described and emphasized. An overvoltage limitation control strategy is developed, which requires an active participation of the onshore converter. Hence, the onshore Multilevel Modular Converter (MMC) as well as the HVDC cables models are examined. The control strategy is applied to both Point-to-Point (P2P) HVDC transmission system and Multi-Terminal DC (MTDC) systems. The results validate the feasibility of the proposed strategy, and demonstrate its advantage of no power curtailment requirement to limit the wind turbines output voltage.

Alcoholics Anonymous (AA) is the world’s largest and most recognisable recovery ‘program’, and central to its philosophy is the 12 Step Program. AA is a global organisation of 2.2 million members worldwide (AAWS, 2001), with a reported 3,600 weekly meetings in the United Kingdom (AAWS, 2011). AA has made many claims in their literature about the program’s effectiveness (AAWS, 2001: 84). Alcoholism is associated with a number of very serious health and social problems, including involvement in crime (Finney 2004; Fitzpatrick, 2010; Alcohol Reduction Strategy 2003). As fiscal pressure mounts, groups such as AA will be of interest to policy makers. Through an analysis of interviews with twenty long-term abstinent members of Alcoholics Anonymous, the thesis seeks to explain the effects of participation in AA’s therapeutic practices. Evidence from the literature on AA, revealed three concepts key to understanding participation in AA: Motivation to Engage (MtE), Structured Social Engagement (SSE), and Personal Agency (PA). A hypothetical model of AA-mediated behavioural change, constituted by these elements, was constructed and the findings supported this putative model. Further analysis revealed the coping strategies members of AA employed that ensured engagement with AA during stressful life events that threatened abstinence. The model was adapted to incorporate the temporal effects of long-term engagement with AA. Elements of Maruna’s (2001: 73) Condemnation Script resonated in the narratives of AA members. Contra Maruna’s analysis, AA members accepted ‘condemnation script’, but these were not negative, limiting beliefs. AA’s therapeutic practices structure, a coherent sense of self, one that supports cessation from negative patterns of drinking. The data exposed the sustained usage of AA’s discourse in the narrative accounts given. This finding extends Borkman’s (1976) Experiential Knowledge thesis, a language of ‘truth’ based on personal experience. The ‘linguistic echoes’ embedded in each narrative, suggests that a person uses AA’s discourse to ‘scaffold’ their recovery. This thesis provides an explanation of AA’s therapeutic practices of how adherence to AA’s principles, cognitively restructures the individual towards mastering self-control. AA’s philosophy and the following empirical evidence asserts abstinence as pre-requisite for recovery from alcohol dependence.

No description available.