Schizophrenia risk from complex variation of complement component 4

Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.

ISCR and their association with antibiotic resistance genes

A prevalência de bactérias resistentes a antibióticos em ambiente hospitalar tem vindo a tornar-se dramática e preocupante a nível mundial. Contudo, com a utilização inadequada de antibióticos em áreas tão diversas como a veterinária, a aquacultura e a agricultura, esta deixou de estar confinada ao ambiente hospitalar, sendo o ambiente um reservatório natural de microganismos resistentes a estes compostos. O conhecimento detalhado dos determinantes de resistência a antibióticos presentes nestes ambientes, sejam estes genes de resistência ou estruturas envolvidas na sua mobilização, é fundamental, não só do ponto de vista do conhecimento como para a eventual implementação de medidas de contenção da sua disseminação. Neste contexto, são necessários estudos que permitam conhecer o panorama mais realista da distribuição destes determinantes de resistência a antibióticos, quer no meio ambiente quer no ambiente clínico. Assim, constituiu objectivo principal deste trabalho contribuir para o conhecimento do panorama actual da prevalência e distribuição dos elementos ISCR, bem como de outros determinantes de resistência a antibióticos em espécies de Gram-negativo clinicamente relevantes (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii e Citrobacter freundii) recolhidas a partir de amostras de pacientes do Hospital Infante D. Pedro, EPE, Aveiro, Portugal, entre 2006 e 2008. Adicionalmente, foram também recolhidas bactérias de Gram-negativo do meio ambiente, a partir de amostras de águas e de vísceras de peixes, nas quais foram igualmente pesquisados os elementos acima referidos. À excepção dos isolados de E. coli e de Gramnegativo ambientais, todas as estirpes estudadas foram seleccionadas com base no seu perfil de multirresistência a antibióticos. Os resultados mostraram que em todas as espécies recolhidas no ambiente hospitalar foi detectada a presença de elementos ISCR, do tipo ISCR1 ou ISCR2. O elemento ISCR1, foi encontrado em isolados de E. coli, K. pneumoniae e C. freundii e o elemento ISCR2 em isolados de A. baumannii. Não foi detectada a presença de ISCRs nos isolados de Gram-negativo ambientais, o que sugere que a ocorrência dos mesmos é fortemente influenciada pela pressão selectiva exercida pelo ambiente em que os microrganismos se encontram. Genes qnr e integrões de classe 1 foram os determinantes de resistência mais frequentemente encontrados associados aos elementos ISCR1. Os vários determinantes de resistência foram encontrados em diferentes contextos genéticos e localizados em estruturas móveis, nomeadamente em plasmídeos. O elemento ISCR2 presente em isolados de A. baumannii encontra-se associado ao gene sul2 em todos os isolados, dentro de um mesmo contexto genético e com uma localização cromossomal. Contudo, o contexto genético encontrado nestes isolados é novo não tendo sido descrito até à data em outros microrganismos. O presente estudo constitui a primeira descrição de elementos ISCR intrinsecamente ligados a genes de resistência a antibióticos, em Portugal. Uma vez que estes elementos parecem ser responsáveis pela mobilização de um grande número de genes de resistência a antibióticos, a sua elevada incidência entre estirpes resistentes e multirresistentes, bem como a sua associação com genes de resistência é preocupante e requer vigilância.

Role of Automated Open Source Systems in the Intelligence Analysis of a High-Level Domain Expert

Design and Qualitative/Quantitative Analysis of Multi-Agent Spatial Simulation Library

Thesis (Master's)--University of Washington, 2012

'Incorrigibly Plural’: New Histories of Ulster and Northern Ireland’

Review article of Carson’s Army: The Ulster Volunteer Force, 1910–22. By Timothy Bowman. Manchester University Press, Manchester, 2007. 256 pp. ISBN 0719073715, £55. A History of the Northern Ireland Labour Party: Democratic Socialism and Sectarianism. By Aaron Edwards. Manchester University Press, Manchester, 2009. xiii + 240 pp. ISBN 0719078741, £60. Catholic Belfast and Nationalist Ireland in the Era of Joe Devlin 1871–1934. By A.C. Hepburn. Oxford University Press, Oxford, 2008. xix +307 pp. ISBN 019929884X, £55. The Big House in the North of Ireland: Land, Power and Social Elites, 1878–1960. By Olwen Purdue. University College Dublin Press, Dublin, 2009. xv + 297 pp. ISBN 978-1-906359-25-6, £24.

"24" Wind Ensemble, Campus Band, Concert Band, Symphonic Band, March 11, 2008

Concert program for '24' Wind Ensemble, Campus Band, Concert Band, Symphonic Band, March 11, 2008

The Wind Ensemble, December 4, 1991

Concert Program for The Wind Ensemble, December 4, 1991

From T cell “exhaustion” to anti-cancer immunity

The immune system has the potential to protect from malignant diseases for extended periods of time. Unfortunately, spontaneous immune responses are often inefficient. Significant effort is required to develop reliable, broadly applicable immunotherapies for cancer patients. A major innovation was transplantation with hematopoietic stem cells from genetically distinct donors for patients with hematologic malignancies. In this setting, donor T cells induce long-term remission by keeping cancer cells in check through powerful allogeneic graft-versus-leukemia effects. More recently, a long awaited breakthrough for patients with solid tissue cancers was achieved, by means of therapeutic blockade of T cell inhibitory receptors. In untreated cancer patients, T cells are dysfunctional and remain in a state of T cell "exhaustion". Nonetheless, they often retain a high potential for successful defense against cancer, indicating that many T cells are not entirely and irreversibly exhausted but can be mobilized to become highly functional. Novel antibody therapies that block inhibitory receptors can lead to strong activation of anti-tumor T cells, mediating clinically significant anti-cancer immunity for many years. Here we review these new treatments and the current knowledge on tumor antigen-specific T cells.

Réception de M. Herrick à l'Hôtel de Ville, 26/7/20, M. Herrick [signe le livre d'or] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 60228

26/7/20, à l'Hôtel de Ville [de Paris], réception de M. Myron T. Herrick : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 60224

Teachers' perspectives on the implementation of expectations-based curricula /

This qualitative study examines teachers' experiences implementing new standardized curricula in Ontario schools. This new curricula contained several policy changes and an expectations based format which directed what knowledge and skills students were to demonstrate in each subject. This level of specificity of subject-content served to control teachers in relation to curricula; however, data suggested that at the same time, teachers had enormous flexibility in terms of pedagogy. Four secondary teachers who were implementing a Grade 10 course in the 2000-2001 school year participated in the study. The qualitative framework supported the researcher's emphasis on examining the participants' perspectives on the implementation of expectation-based curricula. Data collected included transcripts from interviews conducted with teacher participants and a representative of the Ontario Ministry of Education and Training, field notes, and a research journal. Many of the factors often cited in the literature as influencing implementation practices were found to have affected the participants' experiences of curriculum implementation: time, professional development, and teachers' beliefs, particularly concerning students. In addition, the format of the policy documents proved to both control and free teachers during the implementation process. Participants believed that the number of specific expectations did not provide them an opportunity to add content to the curriculum; at the same time, teachers also noted that the general format of the policy document allowed them to direct instruction to match students' needs and their own teaching preferences. Alignment between teachers' beliefs about education and their understanding of the new curriculum affected the ways in which many participants adapted during the implementation process.

Mr. Pickering's speech in the Senate of the United States, on the resolution offered by Mr. Hillhouse to repeal the several acts laying an embargo, November 30, 1808. --

Caption title.

Studies in the mass spectra of perfluoroaromatic derivatives of phosphorus and some selected transition metals

The mass spectra and fragmentation of a variety of fluoroaromatic compounds of Group V and some selected transition elements are discussed in some detail, aided by data from metastable defocussed experiments. Results of ,studies on the coupling reaction using unstable organotitanium chloride intermediate species are reported. The preparation of some 5-substituted octafluorodibenzophospho1es is also discussed. Rearrangements under electron bombardment resulting in the loss of heteroatom-fluoride fragments are discussed in the light of presently accepted mechanisms for these processes as are rearrangements observed in compounds involving thionophosphoryl bonds ( p=s ).

Towards a just community: an examination of the development of cultural citizenship rights in Canada from a communitarian perspective

The notion of citizenship, while a basic human right, has come under scrutiny. It was once assumed a liberal inspired regime of citizenship rights would reign as the primary ideological perspective in the Western world, however this has not been the case. Numerous competing paradigms have questioned the premise upon which liberal guarantees of citizenship rights are based. In particular, communitarianism has subjected liberal rights discourse to a closer examination. Communitarian theory holds that universalist principles negate any articulation of community and its internal diversity, such as cultural citizenship. It is this understanding of citizenship that has taken hold in Canada. The Canadian political experience illustrates a number of attributes associated with communitarian thought. It is a collectivist society that articulates a notion of the common good, acknowledges the internal diversity of its citizens and possesses a highly developed deliberative democratic process. To this end, Canada can be described as being more communitarian than liberal in nature in the process it has adopted to address citizenship rights. However, the type of commuIiitarianism displayed in Canada differs from the political models examined by such scholars as Michael Sandel, Iris Marion Young or Will Kymlicka. Cultural citizenship rights are fluid and malleable in Canada. While no clear guarantees of citizenship rights exist, there is a common commitment by Canadians to engage in a fair, open and inclusive deliberative process. This model is unique to Canada; it cannot be exported in that it is a product of Canadian political culture. As a result, the contemporary demands of cultural citizenship are dealt with effectively and democratically in Canada in that the proper mechanisms for public deliberation exist.