126 research outputs found

    The role of orphan nuclear receptor DAX-1 (NR0B1) in human breast cancer cells: expression, proliferation and metastasis

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    The orphan nuclear hormone receptor DAX-1 (Dosage Sensitive Sex Reversal, Adrenal Hypoplasia Congenita on the X Chromosome, gene 1) plays an important role in the development of adrenal and gonadal tissues and functions as a global negative-regulator of steroidogenesis. In addition, it is known to be involved in several diseases including some cancers. Herein, we describe our examination of the role of DAX-1 in breast cancer, specifically its influence on proliferation and metastasis and its expression during progressive stages of disease. In an effort to understand how DAX-1 influences breast cancer cell proliferation and metastasis, we used MCF7 breast cancer cells and MCF10A normal breast cells and manipulated their DAX-1 expression to increase DAX-1 expression by adenovirus infection in MCF7 cells, or knockdown expression of DAX-1 through the use of RNAi in MCF10A cells. We found a trend toward increased cell proliferation when DAX-1 expression was knocked down, and decreased proliferation when DAX-1 is overexpressed. In addition, we looked at the influence of DAX-1 on breast cancer cell proliferation when the estrogen receptor a (ERa) activity is inhibited by the antagonist, Fulvestrant. To gain a better understanding of the transcriptional role of DAX-1 in breast cancer, we utilized PCR arrays to analyze changes in gene expression in the presence of DAX-1. We identified several genes with roles in breast cancer, estrogen receptor signaling and metastasis whose expression was significantly influenced by overexpression of DAX-1 in MCF7 cells. To investigate expression of DAX-1 through progressive stages of disease we utilized IHC and bioinformatics techniques. We found DAX-1 to be expressed more frequently and at higher levels at earlier stages of breast cancers and at very low levels regardless of stage in hormone receptor-positive (ER and PR) patients. Through these studies, we hypothesize that DAX-1 has the potential to be utilized clinically as biomarker for predicting disease progression and for tailoring more personalized treatment plans. There may even be a role for DAX-1 as a possible therapeutic for later stage or hormone receptor-positive patients

    Den dionysiske theôria

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    Fagfilosofien forholder seg med stor usikkerhet til Aristoteles’ theôria-begrep. I alminnelighet oppfattes det som uttrykk for en høyeste form av filosofisk tankevirksomhet. En dypere forståelse av antikkens religiøse erfaringsverden kan imidlertid bringe oss til en klarere forståelse. Mye kan nemlig tyde på at Arisoteles med theôria refererte til mysteriekultenes idealiserte ekstase, som antikken bare motvillig lar oss skimte konturene av

    Undervisning med digitale verktøy, medier og ressurser - En kvalitativ intervjuundersøkelse om hva utvalgte lærere ved to norske barneskoler vektlegger i sin undervisningspraksis i forhold til utvikling av elevers grunnleggende digitale ferdigheter

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    Masteroppgave pedagogikk- Universitetet i Agder, 2015Denne masteroppgaven omhandler undervisning med digitale, verktøy, medier og ressurser i barneskolen. Den undersøker hva utvalgte lærere fra småskole- og mellomtrinnet vektlegger i sin undervisningspraksis i forhold til utvikling av elevers grunnleggende digitale ferdigheter. Læreplanverket for Kunnskapsløftet (Kunnskapsdepartementet, 2006) fremhever grunnleggende ferdigheter som en vesentlig faktor for elevers læring og utvikling i skole- og arbeidsliv. Digitale ferdigheter er én av fem grunnleggende ferdighetsområder, og det forventes at lærere integrerer arbeid med å utvikle disse i alle fag. Tross satsing på IKT i norsk skole, viser forskning til at undervisningspraksisen ikke er målrettet nok (Erstad, 2012). Undersøkelsen Monitor skole 2013 (Hatlevik, Egeberg, Gudmundsdottir, Loftsgarden & Loi, 2013) viser samtidig til at det er store variasjoner i norske læreres digitale undervisningspraksis. Masteroppgaven er en kvalitativ studie som undersøker et utvalg læreres perspektiver på sin egen digitale undervisningspraksis. Den bidrar til å fremvise hva som blir vektlagt av lærerne og kan dermed forklare hva som ligger bak varierte digitale undervisningspraksiser. Masteroppgaven har en praksisnær og didaktisk tilnærming til studieobjektet, og den belyser temaet digital undervisningspraksis med utgangspunkt i læreres perspektiver. På bakgrunn av to fokusgruppeintervju med forskjellige barneskolelærere ble det gjennomført en innholdsmessig dataanalyse. Dataanalysen førte frem til fire kategorier som representerte hovedinnholdet i intervjuene, og disse kategoriene ble knyttet opp til didaktisk relasjonstenkning. Det ble videre utviklet en forklaringsmodell som antyder at de utvalgte lærerne i denne undersøkelsen vektlegger enkelte didaktiske faktorer mer enn andre. Faktorene som vektlegges innebærer elever og læreres forutsetninger, læringsaktiviteter og arbeidsformer, tilrettelegging for integrering av tilgjengelige digitale redskaper i undervisningen og institusjonelle rammefaktorer. Det fremkom ingen direkte vektlegging av mål og innhold i de digitale undervisningspraksisene som ble diskutert i intervjusamtalene. Det kan bygge opp under forskningen som viser at ikke alle lærere i norsk skole arbeider tilstrekkelig målrettet med utvikling av elevers grunnleggende digitale ferdigheter. Didaktisk relasjonstenking ble presentert av Bjørndal og Lieberg (1978) i Nye veier i didaktikken. Et sitat fra boken kan derimot forklare hvorfor det fremstår som at mål og innhold ikke ble vektlagt av lærerne i særlig grad i denne undersøkelsen. 3 ”I vel tilrettelagt undervisning vil således mål, innhold og læringsaktiviteter smelte sammen i en høyere enhet. Undervisningsmål og innhold kan med andre ord bare ”forstås” eller oppleves gjennom bestemte læringsaktiviteter.” (ibid., s.114-115) Studiens begrensning ligger i at digitale læringsaktiviteter ikke var studieobjektet og ble dermed ikke analysert. Masteroppgaven er et bidrag til å belyse i hvilken grad det fortsatt er behov for forskning på digital undervisning i norsk skole. Den er også en oppfordring til å studere digitale arbeidsmåter i større grad

    Economic Performance of 11 Cheddar Cheese Manufacturing Plants in Northeast and North Central Regions

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    A.E. Res. 87-

    'Inventions and adventures': the work of the Stevenson engineering firm in Scotland, c. 1830 - c. 1890

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    This thesis examines the work of the nineteenth-century Stevenson civil engineering firm to argue that civil engineering should be approached geographically both because it takes place in and is shaped by particular spaces, but also because the result of such work reshapes space and the relationship between places. Geographers have extensively analysed the ways in which humans have worked to alter environments, but relatively little attention has been paid to engineering as a socially and geographically transformative process, to the technical questions and to the engineering professionals whose work brought about such change. This thesis analyses engineers as social and technical agents of environmental change, rather than viewing their role as the simple implementation of directives developed elsewhere and by others. It combines insights from the history and historical geography of science, environmental history and the history of technology to make a case for the relevance of an historical geography of engineering. The thesis explores these issues through the work of the Stevenson family. The Stevensons were an Edinburgh-based and internationally-renowned firm of engineers who specialised in the construction of coastal infrastructure. The start and end dates of the thesis indicate, broadly, the careers of David and Thomas Stevenson, who jointly managed the family firm under the name D. & T. Stevenson between 1850 and 1886. The empirical basis for this thesis draws upon the detailed analysis of the firm’s archival records: technical publications, project reports, diaries, correspondence, maps, plans and diagrams. The work of the Stevensons—their engineering epistemologies, practices, and professional identities— are examined through four diverse projects undertaken by the firm in the nineteenth century. These projects are: the training of new engineers; surveying and designing improvement works for the rivers Tay and Clyde; the implementation of a coastal sound-based fog signal network; and the failed attempt to expand Wick harbour through the construction of a breakwater. These projects highlight the range of activities undertaken by nineteenth-century engineers and illustrate the ‘making’ of engineers and the work they did by highlighting training and learning, surveying, maintenance, testing, evaluation, repair and the explanation of failure. With reference to these projects and by drawing upon relevant contextual material, the thesis examines the conceptualisation of geographical space and natural forces in engineering, the relationship between science and engineering, the nature of expertise and notions of engineering judgement, and the role of family, legacy and reputation in securing professional credibility and status. This approach challenges older historiographical traditions which portrayed engineers as individual geniuses. The thesis instead understands engineering to be a combination of specialist knowledge and tacit skill and situates engineers within their social and institutional networks of power and authority. In pointing out that some engineering works failed, the thesis challenges the tendency in histories of engineering works to focus on success. It makes the case for an historical geography of engineering as a way of understanding engineering as an activity, a status and as processes which changed human-environment relations

    Una mirada comprensiva a la gestión de la Migración de Retorno en Colombia desde una Perspectiva Transnacional

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    This article’s objectives are: First, to identify the policy and care programs orientation promoted by the Colombian State in return migration matter, in order to establish who are their target. Second, to present a critical approach to the basic orientation -economist and instrumental- of this measures, according to the return migration transnational perspective, which proposes to recognize that some migrants and their descendants are influenced by continuous links with their origin countries or by social networks that cross national borders. The information collection had a qualitative approach, such as documentary review and semi-structured interviews. From there it was concluded that it is necessary to continue working, from the academy and political scenarios, in the compilation of a law that unify disseminated decrees, and that assume from a structural institutional perspective, the approach to the phenomenon and its treatment.Los objetivos de este artículo son, primero, identificar la orientación de la política y los programas de atención a través de los cuales el Estado colombiano ha configurado el soporte discursivo frente a la migración de retorno, con el fin de establecer hacia quiénes se ha enfocado este; segundo, presentar una aproximación crítica a la orientación básica -economicista e instrumental- sobre la que se sustentan dichas medidas de conformidad con lo establecido desde la perspectiva transnacional de la migración de retorno, la cual propone reconocer que algunos migrantes y sus descendientes son influenciados por continuos vínculos con los países de origen que sobrepasan las fronteras nacionales. Mediante un enfoque cualitativo se hizo uso de estrategias de recolección de información como la revisión documental y las entrevistas semiestructuradas, a partir de las cuales se concluyó que es necesario continuar trabajando desde la academia y los escenarios políticos en la compilación de una ley que recoja lo que está estipulado de forma diseminada en decretos, y de esta manera lograr asumir desde una perspectiva institucional el abordaje del fenómeno y el tratamiento del mismo

    Synthesis and asymmetric hydrogenation of (3E)-1-benzyl-3-[(2-oxopyridin-1(2H)-yl)methylidene]piperidine-2,6-dione

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    The synthesis of (3E)-1-benzyl-3-[(2-oxopyridin-1(2H)-yl)methylidene]piperidine-2,6-dione 4 from N-benzylglutarimide was achieved in three steps. The asymmetric hydrogenation of 4 gave either the product of partial reduction (10) or full reduction (13), depending on the catalyst which was employed, in high ee in each case. Attempts at asymmetric transfer hydrogenation (ATH) of 4 resulted in formation of a racemic product

    A gated ion source for time-of-flight spectroscopy

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    A gated ion source using tetrode geometry and having 100% gating efficiency for all ion species is described. Static transfer characteristics and gating characteristics are presented, and the effect of other charge states on the space charge limited current of a given ion species is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33836/1/0000094.pd

    Data for Synthesis and reduction reactions of pyridones and 5-acyl-2-methoxypyridines

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    The synthesis of a series of pyridones, from their 2-hydroxypyridine or 2-methoxypyridine precursors, is described, along with studies into their reductions to saturated heterocycles. A number of 5-acylpyridones were prepared and were evaluated as substrates for asymmetric transfer hydrogenation prior to conversion to saturated heterocycles. The enantioselective reduction of 5-acetyl-1-benzylpyrimidine-2,4(1H,3H)-dione is also described
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