1,734,091 research outputs found
Abstract 1454: Estrogen receptor signaling in FTE of BRCA mutation carriers
No full textAbstract
Genetic and reproductive factors predicate epidemiological risk factors underlying epithelial ovarian cancer. The fallopian tube epithelia (FTE), the presumptive etiological site of high-grade serous ovarian cancer (HGSC), is a hormonal responsive tissue. Estrogen is known to promote cell proliferation and its metabolism produces reactive oxygen species that damage DNA and promote tumorigenesis. Estrogen receptor (ER) is rarely mutated, amplified or deleted in HGSC, yet only 10% of patients respond to anti-estrogen treatment, suggesting that intrinsic variables to the ER pathway contribute to this clinical outcome. TP53 mutations occur in almost 100% of HGSCs, indicating that mutated p53 supports a model as an early event in the pathogenesis of HGSC. We hypothesized that in the presence of dysfunctional p53, subsequent promiscuous binding of ER will yield aberrant signaling, ultimately significantly contributing to cellular transformation. Mutant p53 and ER co-localize in FTE cells, suggesting potential synergy. We established cell lines with p53 mutations and treated them with estradiol, an estrogen analog, to observe any changes in response. The genome binding sites of ER-regulated transcription factors were then identified and mapped by whole genome chromatin immunoprecipitation-deep sequencing (ChIP-Seq). The data generated will facilitate the development of gene signatures that will predict response to anti-estrogen therapy in serous ovarian cancer patients, and contribute to the discovery of biomarkers to more accurately identify patients who will benefit from hormonal therapies.
Citation Format: Leah V. Dodds, Omar L. Nelson, Ramlogan Sowamber, Andres Rodrigues, Victoria de Castro, Wendell Henry, Guillermo Morales, Brian Slomovitz, Patricia Shaw, Sophia H. George. Estrogen receptor signaling in FTE of BRCA mutation carriers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1454. doi:10.1158/1538-7445.AM2017-1454</jats:p
How Did I Get to Princess Margaret? (And How Did I Get Her to the World Wide Web?)
No full textThe paper explores the growing use of
tools from the arts and humanities for investigation
and dissemination of social science research.
Emerging spaces for knowledge transfer, such as
the World Wide Web, are explored as outlets for
"performative social science". Questions of ethnics
and questions of evaluation which emerge from
performative social science and the use of new
technologies are discussed. Contemporary thinking
in aesthetics is explored to answer questions
of evaluation. The use of the Internet for productions
is proposed as supporting the collective
elaboration of meaning supported by Relational
Aesthetics.
One solution to the ethical problem of performing
the narrations of others is the use of the writer's
own story as autoethnography. The author queries
autoethnography's tendency to tell "sad" stories and
proposes an amusing story, exemplified by "The
One about Princess Margaret" (see Appendix).
The conclusion is reached that the free and open
environment of the Internet sidelines the usual
tediousness of academic publishing and begins to
explore new answers to questions posed about
the evaluation and ethics of performative social
science
Würzburger Ratsprotokolle 1454–1465
No full textRezension von
Fuchs, Franz; Wagner, Ulrich (Hrsg.), Würzburger Ratsprotokolle 1454–1465
Würzburg : Gesellschaft für Fränkische Geschichte e.V., 201
Neuerscheinung: WÜRZBURGER RATSPROTOKOLLE 1454 – 1465
No full textGesellschaft für fränkische Geschichte e.V. Fränkische Urkundenbücher und Regestenwerke - Reihe III, Band 11 ISBN 978-3-86652-311-1 WÜRZBURGER RATSPROTOKOLLE 1454 – 1465 herausgegeben von Franz Fuchs und Ulrich Wagner bearbeitet von Antonia Bieber unter Mitwirkung von Stefan Petersen und Rainer Scharf 2017. Festeinband XIX und 731 Seiten, 11 Abbildungen VK 59,00 EUR Der vorliegende Band setzt die Reihe der Würzburger Ratsprotokolle für die Jahre 1454 bis 1465 fort. In den Protokolleinträg..
Hessisch-Lichtenau. Partie am Obertor, Turm erbaut 1454
No full textHESSISCH-LICHTENAU. PARTIE AM OBERTOR, TURM ERBAUT 1454
Hessisch-Lichtenau. Partie am Obertor, Turm erbaut 1454 ( -
Hunyadi János 1453 és 1455 közötti törökellenes politikája
No full textA magyar történészek mindenkor fontosnak tartották Hunyadi János életének és korának kutatását. Ennek ellenére mégsem mondhatjuk azt, hogy Hunyadi János korszakának teljes időintervallumával ugyanolyan alapossággal foglalkoztak volna. A magyar történetírás a mai napig adós maradt Hunyadi János 1453 és 1455 közötti törökellenes politikájának részletes vizsgálatával. Dolgozatomban ezen évek politikatörténeti és hadtörténeti eseményeire koncentrálok. A dolgozatom középpontja Hunyadi János 1454-es szerbiai hadjárata, amelyről megpróbálok részletes képet adni, és nemcsak annak eseménytörténetét kívánom feltárni, hanem logisztikai, hadsereg-ellátási, stratégiai kérdésekről is írok. Végezetül pedig rekonstruálom a kruseváci csatát, amelynek szemléltetésére térképeket készítettem.BKTörténelemMSc/M
Consolatorium timorate conscientie
No full textDe Italia illustrata opus : tum propter historia[rum] cognitionem, tum propter loco[rum] descriptionem valde necessariumA 335/141(2
Diverse Catalytic Reactions for the Stereoselective Synthesis of Cyclic Dinucleotide MK-1454
No full textAs
practitioners of organic chemistry strive to deliver efficient
syntheses of the most complex natural products and drug candidates,
further innovations in synthetic strategies are required to facilitate
their efficient construction. These aspirational breakthroughs often
go hand-in-hand with considerable reductions in cost and environmental
impact. Enzyme-catalyzed reactions have become an impressive and necessary
tool that offers benefits such as increased selectivity and waste
limitation. These benefits are amplified when enzymatic processes
are conducted in a cascade in combination with novel bond-forming
strategies. In this article, we report a highly diastereoselective
synthesis of MK-1454, a potent agonist of the stimulator of interferon
gene (STING) signaling pathway. The synthesis begins with the asymmetric
construction of two fluoride-bearing deoxynucleotides. The routes
were designed for maximum convergency and selectivity, relying on
the same benign electrophilic fluorinating reagent. From these complex
subunits, four enzymes are used to construct the two bridging thiophosphates
in a highly selective, high yielding cascade process. Critical to
the success of this reaction was a thorough understanding of the role
transition metals play in bond formation
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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