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

Operations on integral lifts of K(n)

This very rough sketch is a sequel to arXiv:1808.08587; it presents evidence that operations on lifts of the functors K(n) to cohomology theories with values in modules over valuation rings of local number fields, indexed by Lubin-Tate groups of such fields, are extensions of the groups of automorphisms of the indexing group laws, by the exterior algebras on the normal bundle to the orbits of the group laws in the space of lifts.Comment: \S 2.0 hopefully less cryptic. To appear in the proceedings of the 2015 Nagoya conference honoring T Ohkawa. Comments very welcome

Determining the Statistical Significance of Observed Frequencies of Short DNA Motifs in a Genome

Until recently over 90 percent of the DNA in the human genome was considered junk DNA, with no known function. However, this non-coding DNA is now known to harbor elements that perform important functions in gene regulation. In particular, there is currently much interest in the search for short DNA motifs collectively known as cis-regulatory elements. Most studies attempt to identify these elements by means of cross-species comparisons. We have approached the problem of finding cis-regulatory elements by searching for conserved DNA motifs within genomes. This requires searching for DNA motifs that are repeated in the genomes either more or less frequently than expected by random chance. However, the usual chi-squared test cannot be used to test for the statistical significance of any observed frequency since overlapping regions of the genome are checked for DNA motif matches. We present here a statistical measure that has been developed to quantify the expectation and variance of the frequency of a given DNA motif in a given target sequence that may contain overlapping regions

Determining the Statistical Significance of Observed Frequencies of Short DNA Motifs in a Genome

Until recently over 90 percent of the DNA in the human genome was considered junk DNA, with no known function. However, this non-coding DNA is now known to harbor elements that perform important functions in gene regulation. In particular, there is currently much interest in the search for short DNA motifs collectively known as cis-regulatory elements. Most studies attempt to identify these elements by means of cross-species comparisons. We have approached the problem of finding cis-regulatory elements by searching for conserved DNA motifs within genomes. This requires searching for DNA motifs that are repeated in the genomes either more or less frequently than expected by random chance. However, the usual chi-squared test cannot be used to test for the statistical significance of any observed frequency since overlapping regions of the genome are checked for DNA motif matches. We present here a statistical measure that has been developed to quantify the expectation and variance of the frequency of a given DNA motif in a given target sequence that may contain overlapping regions

HARP/ACSIS: A submillimetre spectral imaging system on the James Clerk Maxwell Telescope

This paper describes a new Heterodyne Array Receiver Programme (HARP) and Auto-Correlation Spectral Imaging System (ACSIS) that have recently been installed and commissioned on the James Clerk Maxwell Telescope (JCMT). The 16-element focal-plane array receiver, operating in the submillimetre from 325 to 375 GHz, offers high (three-dimensional) mapping speeds, along with significant improvements over single-detector counterparts in calibration and image quality. Receiver temperatures are $\sim$120 K across the whole band and system temperatures of $\sim$300K are reached routinely under good weather conditions. The system includes a single-sideband filter so these are SSB figures. Used in conjunction with ACSIS, the system can produce large-scale maps rapidly, in one or more frequency settings, at high spatial and spectral resolution. Fully-sampled maps of size 1 square degree can be observed in under 1 hour. The scientific need for array receivers arises from the requirement for programmes to study samples of objects of statistically significant size, in large-scale unbiased surveys of galactic and extra-galactic regions. Along with morphological information, the new spectral imaging system can be used to study the physical and chemical properties of regions of interest. Its three-dimensional imaging capabilities are critical for research into turbulence and dynamics. In addition, HARP/ACSIS will provide highly complementary science programmes to wide-field continuum studies, and produce the essential preparatory work for submillimetre interferometers such as the SMA and ALMA.Comment: MNRAS Accepted 2009 July 2. 18 pages, 25 figures and 6 table

Excision for simplicial sheaves on the Stein site and Gromov's Oka principle

A complex manifold $X$ satisfies the Oka-Grauert property if the inclusion \Cal O(S,X) \hookrightarrow \Cal C(S,X) is a weak equivalence for every Stein manifold $S$, where the spaces of holomorphic and continuous maps from $S$ to $X$ are given the compact-open topology. Gromov's Oka principle states that if $X$ has a spray, then it has the Oka-Grauert property. The purpose of this paper is to investigate the Oka-Grauert property using homotopical algebra. We embed the category of complex manifolds into the model category of simplicial sheaves on the site of Stein manifolds. Our main result is that the Oka-Grauert property is equivalent to $X$ representing a finite homotopy sheaf on the Stein site. This expresses the Oka-Grauert property in purely holomorphic terms, without reference to continuous maps.Comment: Version 3 contains a few very minor improvement

Morita base change in Hopf-cyclic (co)homology

In this paper, we establish the invariance of cyclic (co)homology of left Hopf algebroids under the change of Morita equivalent base algebras. The classical result on Morita invariance for cyclic homology of associative algebras appears as a special example of this theory. In our main application we consider the Morita equivalence between the algebra of complex-valued smooth functions on the classical 2-torus and the coordinate algebra of the noncommutative 2-torus with rational parameter. We then construct a Morita base change left Hopf algebroid over this noncommutative 2-torus and show that its cyclic (co)homology can be computed by means of the homology of the Lie algebroid of vector fields on the classical 2-torus.Comment: Final version to appear in Lett. Math. Phy

Modeling variability of the lactation curves of cows in automated milking systems

Historically, cow selection criteria were developed for conventional milking systems that have regular milking intervals (MI). However, in automatic milking systems (AMS), there is variability in MI within and between cows. These sources of variability provide an opportunity to identify cows with high daily milk yield (DY) and long MI. An extended MI (longer than 16 h in pasture-based systems) has a negative effect on DY. Cows that tolerate extended MI and maintain high DY can be considered more efficient than cows with low DY and long MI, or with high DY but short MI, thereby improving robotic system use. Knowledge of the behavior and parameters of lactation curves of cows in AMS could help farmers to identify cows with a specific lactational phenotype. The objective of this study was to identify individual cows with high DY and long MI within herds, which could reflect increased tolerance to milk accumulation under AMS. A database containing records for 773,483 milking events for one year (July 2016–June 2017) from 4 pasture-based AMS farms was used. Lactation curves within each herd were fitted using several mixed models including fixed effects for the parameters of the lactation curve and random cow effects. Predicted curves of average DY according to parity (multiparous and primiparous) were obtained. The best linear unbiased prediction of the random cow effect allowed us to categorize lactations as having either high or low milk production. The median MI of each lactation was then used to categorize cows as having either short or long MI. Daily yield at the peak of lactation, days to peak and 305-d cumulative milk production were used to compare the effect of DY and MI categories, as well as the DY × MI interaction. Milk production by multiparous and primiparous cows with high DY and long MI was between 35 and 45% higher than that of the low DY and short MI. From all lactations analyzed, the incidence of animals with high DY and long MI across farms was 7.5%. We have identified and quantified a new, AMS-specific, phenotype (the combination of a relatively higher DY with relatively longer MI) with potential to increase use of AMS units. Identifying more efficient animals should help generate new approaches for differential management and for selecting cows in AMS.Fil: Masía, Fernando. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Lyons, N. A.. Intensive Livestock Industries; AustraliaFil: Piccardi, Mónica Belén. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Departamento de Desarrollo Rural. Área de Estadística y Biometría; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Balzarini, Monica Graciela. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Departamento de Desarrollo Rural. Área de Estadística y Biometría; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Hovey, R. C.. University of California at Davis; Estados UnidosFil: Garcia, S. C.. University of Sydney; Australi

Rotation Measure Synthesis of Galactic Polarized Emission with the DRAO 26-m Telescope

Radio polarimetry at decimetre wavelengths is the principal source of information on the Galactic magnetic field. The diffuse polarized emission is strongly influenced by Faraday rotation in the magneto-ionic medium and rotation measure is the prime quantity of interest, implying that all Stokes parameters must be measured over wide frequency bands with many frequency channels. The DRAO 26-m Telescope has been equipped with a wideband feed, a polarization transducer to deliver both hands of circular polarization, and a receiver, all operating from 1277 to 1762 MHz. Half-power beamwidth is between 40 and 30 arcminutes. A digital FPGA spectrometer, based on commercially available components, produces all Stokes parameters in 2048 frequency channels over a 485-MHz bandwidth. Signals are digitized to 8 bits and a Fast Fourier Transform is applied to each data stream. Stokes parameters are then generated in each frequency channel. This instrument is in use at DRAO for a Northern sky polarization survey. Observations consist of scans up and down the Meridian at a drive rate of 0.9 degree per minute to give complete coverage of the sky between declinations -30 degree and 90 degree. This paper presents a complete description of the receiver and data acquisition system. Only a small fraction of the frequency band of operation is allocated for radio astronomy, and about 20 percent of the data are lost to interference. The first 8 percent of data from the survey are used for a proof-of-concept study, which has led to the first application of Rotation Measure Synthesis to the diffuse Galactic emission obtained with a single-antenna telescope. We find rotation measure values for the diffuse emission as high as approximately 100 rad per square metre, much higher than recorded in earlier work.Comment: Accepted for publication in The Astronomical Journa