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Neoplastic transformation of porcine mammary epithelial cells in vitro and tumor formation in vivo.
BackgroundThe mammary glands of pigs share many functional and morphological similarities with the breasts of humans, raising the potential of their utility for research into the mechanisms underlying normal mammary function and breast carcinogenesis. Here we sought to establish a model for the efficient manipulation and transformation of porcine mammary epithelial cells (pMEC) in vitro and tumor growth in vivo.MethodsWe utilized a vector encoding the red florescent protein tdTomato to transduce populations of pMEC from Yorkshire -Hampshire crossbred female pigs in vitro and in vivo. Populations of primary pMEC were then separated by FACS using markers to distinguish epithelial cells (CD140a-) from stromal cells (CD140a+), with or without further enrichment for basal and luminal progenitor cells (CD49f+). These separated pMEC populations were transduced by lentivirus encoding murine polyomavirus T antigens (Tag) and tdTomato and engrafted to orthotopic or ectopic sites in immunodeficient NOD.Cg-Prkdc (scid) Il2rg (tm1Wjl) /SzJ (NSG) mice.ResultsWe demonstrated that lentivirus effectively transduces pMEC in vitro and in vivo. We further established that lentivirus can be used for oncogenic-transformation of pMEC ex vivo for generating mammary tumors in vivo. Oncogenic transformation was confirmed in vitro by anchorage-independent growth, increased cell proliferation, and expression of CDKN2A, cyclin A2 and p53 alongside decreased phosphorylation of Rb. Moreover, Tag-transformed CD140a- and CD140a-CD49f + pMECs developed site-specific tumors of differing histopathologies in vivo.ConclusionsHerein we establish a model for the transduction and oncogenic transformation of pMEC. This is the first report describing a porcine model of mammary epithelial cell tumorigenesis that can be applied to the study of human breast cancers
Neoplastic transformation of porcine mammary epithelial cells in vitro and tumor formation in vivo
BACKGROUND: The mammary glands of pigs share many functional and morphological similarities with the breasts of humans, raising the potential of their utility for research into the mechanisms underlying normal mammary function and breast carcinogenesis. Here we sought to establish a model for the efficient manipulation and transformation of porcine mammary epithelial cells (pMEC) in vitro and tumor growth in vivo. METHODS: We utilized a vector encoding the red florescent protein tdTomato to transduce populations of pMEC from Yorkshire –Hampshire crossbred female pigs in vitro and in vivo. Populations of primary pMEC were then separated by FACS using markers to distinguish epithelial cells (CD140a-) from stromal cells (CD140a+), with or without further enrichment for basal and luminal progenitor cells (CD49f+). These separated pMEC populations were transduced by lentivirus encoding murine polyomavirus T antigens (Tag) and tdTomato and engrafted to orthotopic or ectopic sites in immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ (NSG) mice. RESULTS: We demonstrated that lentivirus effectively transduces pMEC in vitro and in vivo. We further established that lentivirus can be used for oncogenic-transformation of pMEC ex vivo for generating mammary tumors in vivo. Oncogenic transformation was confirmed in vitro by anchorage-independent growth, increased cell proliferation, and expression of CDKN2A, cyclin A2 and p53 alongside decreased phosphorylation of Rb. Moreover, Tag-transformed CD140a- and CD140a-CD49f + pMECs developed site-specific tumors of differing histopathologies in vivo. CONCLUSIONS: Herein we establish a model for the transduction and oncogenic transformation of pMEC. This is the first report describing a porcine model of mammary epithelial cell tumorigenesis that can be applied to the study of human breast cancers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1572-7) contains supplementary material, which is available to authorized users
Observation of Target Electron Momentum Effects in Single-Arm M\o ller Polarimetry
In 1992, L.G. Levchuk noted that the asymmetries measured in M\o ller
scattering polarimeters could be significantly affected by the intrinsic
momenta of the target electrons. This effect is largest in devices with very
small acceptance or very high resolution in laboratory scattering angle. We use
a high resolution polarimeter in the linac of the polarized SLAC Linear
Collider to study this effect. We observe that the inclusion of the effect
alters the measured beam polarization by -14% of itself and produces a result
that is consistent with measurements from a Compton polarimeter. Additionally,
the inclusion of the effect is necessary to correctly simulate the observed
shape of the two-body elastic scattering peak.Comment: 29 pages, uuencoded gzip-compressed postscript (351 kb). Uncompressed
postscript file (898 kb) available to DECNET users as
SLC::USER_DISK_SLC1:[MORRIS]levpre.p
Hadron multiplicities in e+e- annihilation with heavy primary quarks
The multiple hadron production in the events induced by the heavy primary
quarks in annihilation is reconsidered with account of corrected
experimental data. New value for the multiplicity in events is
presented on the basis of pQCD estimates.Comment: 16 pages, 6 figures. Version accepted for publication in EPJ
Hydrogen penetration into titanium from environment in different states
In this paper, the accumulation of hydrogen in titanium from media of different aggregate states is considered, since the accumulation of hydrogen in structural and functional materials, which ultimately can lead to the destruction of structures, essentially depends on the environments in which these structures operate. Obtained: electrolytic and plasma saturation is characterized by hydrogen entrapment by low-temperature traps with weak binding energy (point defects and their complexes, vacancies and their complexes, etc. The method of Siwerst is characterized by capture of high-temperature traps (microcracks of microcracks, intergranular boundaries, etc.)
Mobility of thorium ions in liquid xenon
We present a measurement of the Th ion mobility in LXe at 163.0 K and
0.9 bar. The result obtained, 0.2400.011 (stat) 0.011 (syst)
cm/(kV-s), is compared with a popular model of ion transport.Comment: 6.5 pages,
Observation of single collisionally cooled trapped ions in a buffer gas
Individual Ba ions are trapped in a gas-filled linear ion trap and observed
with a high signal-to-noise ratio by resonance fluorescence. Single-ion storage
times of ~5 min (~1 min) are achieved using He (Ar) as a buffer gas at
pressures in the range 8e-5 - 4e-3 torr. Trap dynamics in buffer gases are
experimentally studied in the simple case of single ions. In particular, the
cooling effects of light gases such as He and Ar and the destabilizing
properties of heavier gases such as Xe are studied. A simple model is offered
to explain the observed phenomenology.Comment: 5 pages, 4 figures, accepted for publication in Phys. Rev. A. Minor
text and figure change
Towards environmentally sustainable human behaviour: targeting non-conscious and conscious processes for effective and acceptable policies.
Meeting climate change targets to limit global warming to 2°C requires rapid and large reductions in demand for products that most contribute to greenhouse gas (GHG) emissions. These include production of bulk materials (e.g. steel and cement), energy supply (e.g. fossil fuels) and animal source foods (particularly ruminants and their products). Effective strategies to meet these targets require transformative changes in supply as well as demand, involving changes in economic, political and legal systems at local, national and international levels, building on evidence from many disciplines. This paper outlines contributions from behavioural science in reducing demand. Grounded in dual-process models of human behaviour (involving non-conscious and conscious processes) this paper considers first why interventions aimed at changing population values towards the environment are usually insufficient or unnecessary for reducing demand although they may be important in increasing public acceptability of policies that could reduce demand. It then outlines two sets of evidence from behavioural science towards effective systems-based strategies, to identify interventions likely to be effective at: (i) reducing demand for products that contribute most to GHG emissions, mainly targeting non-conscious processes and (ii) increasing public acceptability for policy changes to enable these interventions, targeting conscious processes.This article is part of the themed issue 'Material demand reduction'
Search for nucleon decays with EXO-200
A search for instability of nucleons bound in Xe nuclei is reported
with 223 kgyr exposure of Xe in the EXO-200 experiment. Lifetime
limits of 3.3 and 1.9 yrs are established for
nucleon decay to Sb and Te, respectively. These are the most
stringent to date, exceeding the prior decay limits by a factor of 9 and 7,
respectively
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