602 research outputs found

    Contribution of an alveolar cell of origin to the high-grade malignant phenotype of pregnancy-associated breast cancer.

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    Pregnancy-associated breast cancers (PABCs) are tumors diagnosed during pregnancy or up to 5 years following parturition, and are usually high-grade, connective tissue-rich, and estrogen receptor (ER)/progesterone receptor-negative. Little is known about the cellular origin of PABCs or the mechanisms by which PABCs are initiated. Using the RCAS retrovirus to deliver the ErbB2 oncogene into the mammary epithelium of our previously reported MMTV-tva transgenic mice, we detected high-grade, poorly differentiated, stroma-rich and ER-negative tumors during pregnancy and lactation. These high-grade and stroma-rich tumors were less frequent in involuted mice or in age-matched nulliparous mice. More importantly, by generating a WAP-tva transgenic line for expression of ErbB2 selectively in WAP(+) mammary alveolar cells, we found that tumors had similar morphological phenotypes (high grade, poorly differentiated, stroma-rich and ER-negative), irrespective of the time since pregnancy and even in the absence of pregnancy. These data suggest that PABCs arise preferentially from an alveolar cell population that expands during pregnancy and lactation. This somatic mouse model may also be useful for preclinical testing of new prophylactic and therapeutic strategies against PABC

    Firm-level evidence for the language investment effect on SME exporters

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    Both analysis of international trade and the knowledge resource theory of the firm imply that language skills should play a vital role in exporting. This may be apparent to large multinationals with sites in many different linguistic locations, but we show it is less obvious to smaller companies. With data on the language used by each of a large sample of European small and medium sized enterprises in their export markets we test and estimate the effects of language assets on language performance in export markets and on export sales. Controlling for the possibility that language skills may be acquired by exporting, we find a very substantial export return to linguistic expertise, indicative of unexploited gains from investment in languages. There is also evidence of greater under-investment in language skills in English-speaking Europe, which we show can be a prediction of Konya’s (2006) trade model

    The strength and persistence of entrepreneurial cultures

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    The twentieth century United States provides a natural experiment to measure the strength and persistence of entrepreneurial cultures. Assuming immigrants bear the cultures of their birth place, comparison of revealed entrepreneurial propensities of US immigrant groups in 1910 and 2000 reflected these backgrounds. According to this test North-western Europe, where modern economic growth is widely held to have originated, did not host unusually strong entrepreneurial cultures. Instead such cultures were carried by persons originating from Greece, Turkey and Italy, together with Jews. The rise of widespread female entrepreneurship provides additional evidence by showing that this trait systematically responded less strongly, but in the same way, to cultural background as did male entrepreneurship

    Expression of PIK3CA mutant E545K in the mammary gland induces heterogeneous tumors but is less potent than mutant H1047R.

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    The phosphoinositide 3-kinase (PI3K) signaling cascade is a key mediator of cellular growth, survival and metabolism and is frequently subverted in human cancer. The gene encoding for the alpha catalytic subunit of PI3K (PIK3CA) is mutated and/or amplified in ∼30% of breast cancers. Mutations in either the kinase domain (H1047R) or the helical domain (E545K) are most common and result in a constitutively active enzyme with oncogenic capacity. PIK3CA(H1047R) was previously demonstrated to induce tumors in transgenic mouse models; however, it was not known whether overexpression of PIK3CA(E545K) is sufficient to induce mammary tumors and whether tumor initiation by these two types of mutants differs. Here, we demonstrate that expression of PIK3CA(E545K) in the mouse mammary gland induces heterogenous mammary carcinomas but with a longer latency than PIK3CA(H1047R)-expressing mice. Our results suggest that the helical domain mutant PIK3CA(E545K) is a less potent inducer of mammary tumors due to less efficient activation of downstream Akt signaling

    Voice, plumage and natural history of Anthony's Nightjar (Caprimulgus anthonyi)

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    This is the published version. Copyright Central Ornithology Publication Offic

    Implementation of an Online Database for Chemical Propulsion Systems

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    The Johns Hopkins University, Chemical Propulsion Information Analysis Center (CPIAC) has been working closely with NASA Goddard Space Flight Center (GSFC); NASA Marshall Space Flight Center (MSFC); the University of Alabama at Huntsville (UAH); The Johns Hopkins University, Applied Physics Laboratory (APL); and NASA Jet Propulsion Laboratory (JPL) to capture satellite and spacecraft propulsion system information for an online database tool. The Spacecraft Chemical Propulsion Database (SCPD) is a new online central repository containing general and detailed system and component information on a variety of spacecraft propulsion systems. This paper only uses data that have been approved for public release with unlimited distribution. The data, supporting documentation, and ability to produce reports on demand, enable a researcher using SCPD to compare spacecraft easily, generate information for trade studies and mass estimates, and learn from the experiences of others through what has already been done. This paper outlines the layout and advantages of SCPD, including a simple example application with a few chemical propulsion systems from various NASA spacecraft

    Operationalising closure in a colonial context: the association of accountants in East Africa 1949-1963

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    The migration of British accounting professionals to both settler and non-settler colonies in the late nineteenth and early twentieth centuries bequeathed an enduring legacy for the professionalisation process in these countries. This study sets out to trace the rise of professional accountancy in colonial Kenya, a racially diversified and hierarchical colonial society where non-whites were marginalized and the minority white population ruled. Drawing from archival sources and some oral history data, the study traces the formation and operation of a colonial professional body, the Association of Accountants in East Africa (AAEA), comprised mainly of British expatriate accountants. In particular, it shows how traditional, formal closure devices, such as the restrictive use of designations, examinations and training requirements and the registration of accountants were employed by AAEA in its attempts to exclude unqualified practitioners and control the market for accounting services in the colony. It also presents evidence that attests to the use of more informal closure devices, taking advantage of the socio-cultural conditions specific to this colony, to exclude on the basis of race

    Vacuum Pyrolysis and Related ISRU Techniques

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    A number of ISRU-related techniques have been developed at NASA Goddard Space Flight Center. The focus of the team has been on development of the vacuum pyrolysis technique for the production of oxygen from the lunar regolith. However, a number of related techniques have also been developed, including solar concentration, solar heating of regolith, resistive heating of regolith, sintering, regolith boiling, process modeling, parts manufacturing, and instrumentation development. An initial prototype system was developed to vaporize regolith simulants using a approx. l square meter Fresnel lens. This system was successfully used to vaporize quantities of approx. lg, and both mass spectroscopy of the gasses produced and Scanning Electron Microscopy (SEM) of the slag were done to show that oxygen was produced. Subsequent tests have demonstrated the use of a larger system With a 3.8m diameter reflective mirror to vaporize the regolith. These results and modeling of the vacuum pyrolysis reaction have indicated that the vaporization of the oxides in the regolith will occur at lower temperature for stronger vacuums. The chemical modeling was validated by testing of a resistive heating system that vaporized quantities of approx. 10g of MLS-1A. This system was also used to demonstrate the sintering of regolith simulants at reduced temperatures in high vacuum. This reduction in the required temperature prompted the development of a small-scale resistive heating system for application as a scientific instrument as well as a proof-of principle experiment for oxygen production

    Increased bit rate direct modulation AMO-OFDM transmission by optical injection using monolithically integrated lasers

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    Experimental and simulation work, presented in this letter, demonstrates for the first time how the monolithic integration of two single-mode lasers in a master-slave configuration, can substantially increase the achievable bit rate of a direct modulation adaptively modulated optical orthogonal frequency-division multiplexing (AMO-OFDM) system. The Levin-Campello algorithm is applied to select the OFDM bit and power loading scheme used for each system configuration. Improvement in terms of data throughput due to injection is measured for several transmission distances with the improvement in performance presented in terms of error vector magnitude per OFDM subcarrier
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