An androgen receptor mutation in the MDA-MB-453 cell line model of molecular apocrine breast cancer compromises receptor activity

Recent evidence indicates that the estrogen receptor-a-negative, androgen receptor (AR)- positive molecular apocrine subtype of breast cancer is driven by AR signaling. The MDA-MB-453 cell line is the prototypical model of this breast cancer subtype; its proliferation is stimulated by androgens such as 5a-dihydrotestosterone (DHT) but inhibited by the progestin medroxyprogesterone acetate (MPA) via AR-mediated mechanisms. We report here that the AR gene in MDAMB- 453 cells contains a G-T transversion in exon 7, resulting in a receptor variant with a glutamine to histidine substitution at amino acid 865 (Q865H) in the ligand binding domain. Compared with wild-type AR, the Q865H variant exhibited reduced sensitivity to DHT and MPA in transactivation assays in MDA-MB-453 and PC-3 cells but did not respond to non-androgenic ligands or receptor antagonists. Ligand binding, molecular modeling, mammalian two-hybrid and immunoblot assays revealed effects of the Q865H mutation on ligand dissociation, AR intramolecular interactions, and receptor stability. Microarray expression profiling demonstrated that DHT and MPA regulate distinct transcriptional programs in MDA-MB-453 cells. Gene Set Enrichment Analysis revealed that DHT- but not MPA-regulated genes were associated with estrogen-responsive transcriptomes from MCF-7 cells and the Wnt signaling pathway. These findings suggest that the divergent proliferative responses of MDA-MB-453 cells to DHT and MPA result from the different genetic programs elicited by these two ligands through the AR-Q865H variant. This work highlights the necessity to characterize additional models of molecular apocrine breast cancer to determine the precise role of AR signaling in this breast cancer subtype. Endocrine-Related Cancer (2012) 19 599–613

Sovereignty, song and 'The Sapphires' (Wayne Blair 2012)

With its foregrounding of the political issue of the denial of Aboriginal Australian sovereignty by British invaders in its big budget, mainstream narrative, 'The Sapphires' (Wayne Blair 2012) is shown to be another example of a "fourth formation" (Starrs 2012) in Moore and Muecke's 1985 model. Blair's feel-good movie features an all-Aboriginal Australian troupe of singers, The Sapphires, who undertake a journey of self-discovery whereby they learn the importance of choosing the protest songs of black Soul over the white coloniser's "whining" Country and Western songs and this is historically contextualised with a discussion of Aboriginal Australians and popular radio. Furthermore, this paper argues the iconic 'Welcome to Country' is twice subverted to reinforce this theme, firstly in the Cummeragunja pub and secondly in war-torn Vietnam. Finally, the prediction is made that a "fifth formation", in which seeking recognition of Aboriginal Australian sovereignty is no longer the goal because it has become the ongoing reality, will soon be the project of Australian film-makers as they celebrate this long overdue societal shift.

The nest and eggs of Wayne's warbler (Dendroica Virens Waynei) taken near Mount Pleasant, S.C.

This document contains information on the nest and eggs of the bird, Wayne’s Warbler, taken near Mount Pleasant, South Carolina.

Remesas y desarrollo económico. Un análisis empírico del caso mexicano

El objetivo de este trabajo es contribuir a identificar el efecto de las remesas que envían los emigrantes a sus comunidades de origen en México. Del mismo modo, se estudia el efecto que la participación de la mujer tiene en este proceso. La fuente de información es el Consejo Nacional de Población de México CONAPO y contiene variables a nivel estatal y municipal para el año 2000. La base de datos contiene índices de desarrollo humano, intensidad migratoria y remesas para los 2443 municipios mexicanos. La evidencia empírica sugiere que las remesas tienen un impacto positivo sobre los niveles de desarrollo de las comunidades receptoras. No obstante, la relación entre remesas y desarrollo es no lineal. Adicionalmente, se en contró que el efecto positivo que tienen las remesas sobre el desarrollo es más alto cuando la cabeza de familia de los hogares receptores es mujer.

Who Was Elizabeth Hanson? Book reveals the secret circumstances surrounding the death of the CIA's rising star

Book by Washington Post reporter reveals the secret circumstances surrounding the death of rising CIA star Elizabeth Hanson ’02.

Síndrome de John Wayne: o gestor, o discurso e a crise

Apresentar os elementos constitutivos essenciais e descrever as dinâmicas interativas básicas constituintes da "Síndrome de John Wayne" - SJW- são os objetivos primários deste trabalho. A SJW é um estilo de gestão e perfil de gestor marcados por uma concepção de sucesso que cega o indivíduo para as peculiaridades dos períodos de crises organizacionais. Baseando-se em fórmulas e procedimentos que lhe garantiram o sucesso em tempos de bonança, o portador da SJW nas crises desenvolve ações cujas conseqüências, em geral, agravam ainda mais esse período de exceção. Por outro lado, a pesquisa pretende também demonstrar que a SJW é atributo individual não só tolerado, como desejado pelas companhias em tempos de bonança, pois está em harmonia com formas organizacionais de um tecido social que enfatiza a projeção pessoal, sob os auspícios da fama e da celebridade, como sinônimo de sucesso. Assim, a SJW evoca o desejo desse gestor de ser um herói. Ele almeja ser um herói nos moldes do ideal heróico "épico", mas o século XXI flerta com a celebridade, sendo o ato heróico celebrado um dos recursos pará atingir essa condição

CMS physics technical design report, volume II: Physics performance

CMS is a general purpose experiment, designed to study the physics of pp collisions at 14 TeV at the Large Hadron Collider ( LHC). It currently involves more than 2000 physicists from more than 150 institutes and 37 countries. The LHC will provide extraordinary opportunities for particle physics based on its unprecedented collision energy and luminosity when it begins operation in 2007. The principal aim of this report is to present the strategy of CMS to explore the rich physics programme offered by the LHC. This volume demonstrates the physics capability of the CMS experiment. The prime goals of CMS are to explore physics at the TeV scale and to study the mechanism of electroweak symmetry breaking - through the discovery of the Higgs particle or otherwise. To carry out this task, CMS must be prepared to search for new particles, such as the Higgs boson or supersymmetric partners of the Standard Model particles, from the start- up of the LHC since new physics at the TeV scale may manifest itself with modest data samples of the order of a few fb(-1) or less. The analysis tools that have been developed are applied to study in great detail and with all the methodology of performing an analysis on CMS data specific benchmark processes upon which to gauge the performance of CMS. These processes cover several Higgs boson decay channels, the production and decay of new particles such as Z' and supersymmetric particles, B-s production and processes in heavy ion collisions. The simulation of these benchmark processes includes subtle effects such as possible detector miscalibration and misalignment. Besides these benchmark processes, the physics reach of CMS is studied for a large number of signatures arising in the Standard Model and also in theories beyond the Standard Model for integrated luminosities ranging from 1 fb(-1) to 30 fb(-1). The Standard Model processes include QCD, B-physics, diffraction, detailed studies of the top quark properties, and electroweak physics topics such as the W and Z(0) boson properties. The production and decay of the Higgs particle is studied for many observable decays, and the precision with which the Higgs boson properties can be derived is determined. About ten different supersymmetry benchmark points are analysed using full simulation. The CMS discovery reach is evaluated in the SUSY parameter space covering a large variety of decay signatures. Furthermore, the discovery reach for a plethora of alternative models for new physics is explored, notably extra dimensions, new vector boson high mass states, little Higgs models, technicolour and others. Methods to discriminate between models have been investigated. This report is organized as follows. Chapter 1, the Introduction, describes the context of this document. Chapters 2-6 describe examples of full analyses, with photons, electrons, muons, jets, missing E-T, B-mesons and tau's, and for quarkonia in heavy ion collisions. Chapters 7-15 describe the physics reach for Standard Model processes, Higgs discovery and searches for new physics beyond the Standard Model.

Search for narrow resonances in dilepton mass spectra in pp collisions at root s=7 TeV CMS Collaboration

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)