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The ErbB2ΔEx16 splice variant is a major oncogenic driver in breast cancer that promotes a pro-metastatic tumor microenvironment.
Amplification and overexpression of erbB2/neu proto-oncogene is observed in 20-30% human breast cancer and is inversely correlated with the survival of the patient. Despite this, somatic activating mutations within erbB2 in human breast cancers are rare. However, we have previously reported that a splice isoform of erbB2, containing an in-frame deletion of exon 16 (herein referred to as ErbB2ΔEx16), results in oncogenic activation of erbB2 because of constitutive dimerization of the ErbB2 receptor. Here, we demonstrate that the ErbB2ΔEx16 is a major oncogenic driver in breast cancer that constitutively signals from the cell surface. We further show that inducible expression of the ErbB2ΔEx16 variant in mammary gland of transgenic mice results in the rapid development of metastatic multifocal mammary tumors. Genetic and biochemical characterization of the ErbB2ΔEx16-derived mammary tumors exhibit several unique features that distinguish this model from the conventional ErbB2 ones expressing the erbB2 proto-oncogene in mammary epithelium. Unlike the wild-type ErbB2-derived tumors that express luminal keratins, ErbB2ΔEx16-derived tumors exhibit high degree of intratumoral heterogeneity co-expressing both basal and luminal keratins. Consistent with these distinct pathological features, the ErbB2ΔEx16 tumors exhibit distinct signaling and gene expression profiles that correlate with activation of number of key transcription factors implicated in breast cancer metastasis and cancer stem cell renewal
A regularisation approach to causality theory for C^{1,1}Lorentzian metrics
We show that many standard results of Lorentzian causality theory remain valid if the regularity of the metric is reduced to C^{1,1}. Our approach is based on regularisations of the metric adapted to the causal structure
High Energy Gamma-Ray Emission From Blazars: EGRET Observations
We will present a summary of the observations of blazars by the Energetic
Gamma Ray Experiment Telescope (EGRET) on the Compton Gamma Ray Observatory
(CGRO). EGRET has detected high energy gamma-ray emission at energies greater
than 100 MeV from more that 50 blazars. These sources show inferred isotropic
luminosities as large as ergs s. One of the most
remarkable characteristics of the EGRET observations is that the gamma-ray
luminosity often dominates the bolometric power of the blazar. A few of the
blazars are seen to exhibit variability on very short time-scales of one day or
less. The combination of high luminosities and time variations seen in the
gamma-ray data indicate that gamma-rays are an important component of the
relativistic jet thought to characterize blazars. Currently most models for
blazars involve a beaming scenario. In leptonic models, where electrons are the
primary accelerated particles, gamma-ray emission is believed to be due to
inverse Compton scattering of low energy photons, although opinions differ as
to the source of the soft photons. Hardronic models involve secondary
production or photomeson production followed by pair cascades, and predict
associated neutrino production.Comment: 16 pages, 7 figures, style files included. Invited review paper in
"Observational Evidence for Black Holes in the Universe," 1999, ed. S. K.
Chakrabarti (Dordrecht: Kluwer), 215-23
On finite monoids of cellular automata.
For any group G and set A, a cellular automaton over G and A is a transformation τ:AG→AGτ:AG→AG defined via a finite neighbourhood S⊆GS⊆G (called a memory set of ττ) and a local function μ:AS→Aμ:AS→A. In this paper, we assume that G and A are both finite and study various algebraic properties of the finite monoid CA(G,A)CA(G,A) consisting of all cellular automata over G and A. Let ICA(G;A)ICA(G;A) be the group of invertible cellular automata over G and A. In the first part, using information on the conjugacy classes of subgroups of G, we give a detailed description of the structure of ICA(G;A)ICA(G;A) in terms of direct and wreath products. In the second part, we study generating sets of CA(G;A)CA(G;A). In particular, we prove that CA(G,A)CA(G,A) cannot be generated by cellular automata with small memory set, and, when G is finite abelian, we determine the minimal size of a set V⊆CA(G;A)V⊆CA(G;A) such that CA(G;A)=⟨ICA(G;A)∪V⟩CA(G;A)=⟨ICA(G;A)∪V⟩
Conformal weights in the Kerr/CFT correspondence
It has been conjectured that a near-extreme Kerr black hole is described by a
2d CFT. Previous work has shown that CFT operators dual to axisymmetric
gravitational perturbations have integer conformal weights. In this paper, we
study the analogous problem in 5d. We consider the most general near-extreme
vacuum black hole with two rotational symmetries. This includes Myers-Perry
black holes, black rings and Kaluza-Klein black holes. We find that operators
dual to gravitational (or electromagnetic or massless scalar field)
perturbations preserving both rotational symmetries have integer conformal
weights, the same for all black holes considered.Comment: 19 page
Non-small cell lung carcinoma in an adolescent manifested by acute paraplegia due to spinal metastases: a case report
<p>Abstract</p> <p>Introduction</p> <p>Bronchial carcinomas in childhood and adolescence are extremely rare; only individual cases have been reported previously.</p> <p>Case presentation</p> <p>We report on a 16-year-old Caucasian German boy with non-small cell lung carcinoma (squamous cell non-small cell lung carcinoma) stage IV, T4N2M1, without epidermal growth factor receptor overexpression and/or mutation or k-ras mutation. He presented with paraplegia due to spinal metastases of the bronchial carcinoma. No familial predisposition or toxin exposure was identified. Treatment following adult protocols consisted of surgical intervention for spinal metastases, first-line cisplatinum and gemcitabine, irradiation and second-line docetaxel. After a transient response our patient experienced disease progression and died about 10 months later.</p> <p>Conclusion</p> <p>Response and survival in our 16-year-old patient were similar to adult patients with stage IV non-small cell lung carcinoma.</p
A rocky planet transiting a nearby low-mass star
M-dwarf stars -- hydrogen-burning stars that are smaller than 60 per cent of
the size of the Sun -- are the most common class of star in our Galaxy and
outnumber Sun-like stars by a ratio of 12:1. Recent results have shown that M
dwarfs host Earth-sized planets in great numbers: the average number of M-dwarf
planets that are between 0.5 to 1.5 times the size of Earth is at least 1.4 per
star. The nearest such planets known to transit their star are 39 parsecs away,
too distant for detailed follow-up observations to measure the planetary masses
or to study their atmospheres. Here we report observations of GJ 1132b, a
planet with a size of 1.2 Earth radii that is transiting a small star 12
parsecs away. Our Doppler mass measurement of GJ 1132b yields a density
consistent with an Earth-like bulk composition, similar to the compositions of
the six known exoplanets with masses less than six times that of the Earth and
precisely measured densities. Receiving 19 times more stellar radiation than
the Earth, the planet is too hot to be habitable but is cool enough to support
a substantial atmosphere, one that has probably been considerably depleted of
hydrogen. Because the host star is nearby and only 21 per cent the radius of
the Sun, existing and upcoming telescopes will be able to observe the
composition and dynamics of the planetary atmosphere.Comment: Published in Nature on 12 November 2015, available at
http://dx.doi.org/10.1038/nature15762. This is the authors' version of the
manuscrip
The centrosome and spindle as a ribonucleoprotein complex
Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Chromosome Research 19 (2011): 367-376, doi:10.1007/s10577-011-9186-7.The presence of nucleic acids in centrosomes and the spindle have been proposed,
observed, and reported since the 1950s. Why did the subject remain, perhaps even until
today, such a controversial issue? The explanation is manifold, and includes legitimate
concern over contamination from other cellular compartments in biochemical
preparations. With a typically high background of cytoplasmic ribosomes, even
microscopic images of stained intact cells could be difficult to interpret. Also, evidence
for RNA and DNA in centrosomes accumulated for approximately 40 years but was
interspersed with contradictory studies, primarily regarding the presence of DNA
(reviewed in Johnson and Rosenbaum, 1991; Marshall and Rosenbaum, 2000). Perhaps
less tangible but still a likely cause for lingering controversy is that the presence of
nucleic acids in the spindle or centrosomes will require us to look differently at these
structures from a functional, and more to the point, evolutionary standpoint.This work was supported by grants from the NIH (GM088503) and NSF (MCB0843092)
to MCA
Binary and Millisecond Pulsars at the New Millennium
We review the properties and applications of binary and millisecond pulsars.
Our knowledge of these exciting objects has greatly increased in recent years,
mainly due to successful surveys which have brought the known pulsar population
to over 1300. There are now 56 binary and millisecond pulsars in the Galactic
disk and a further 47 in globular clusters. This review is concerned primarily
with the results and spin-offs from these surveys which are of particular
interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living
Reviews in Relativity (http://www.livingreviews.org
Was Wright Right? The Canonical Genetic Code is an Empirical Example of an Adaptive Peak in Nature; Deviant Genetic Codes Evolved Using Adaptive Bridges
The canonical genetic code is on a sub-optimal adaptive peak with respect to its ability to minimize errors, and is close to, but not quite, optimal. This is demonstrated by the near-total adjacency of synonymous codons, the similarity of adjacent codons, and comparisons of frequency of amino acid usage with number of codons in the code for each amino acid. As a rare empirical example of an adaptive peak in nature, it shows adaptive peaks are real, not merely theoretical. The evolution of deviant genetic codes illustrates how populations move from a lower to a higher adaptive peak. This is done by the use of “adaptive bridges,” neutral pathways that cross over maladaptive valleys by virtue of masking of the phenotypic expression of some maladaptive aspects in the genotype. This appears to be the general mechanism by which populations travel from one adaptive peak to another. There are multiple routes a population can follow to cross from one adaptive peak to another. These routes vary in the probability that they will be used, and this probability is determined by the number and nature of the mutations that happen along each of the routes. A modification of the depiction of adaptive landscapes showing genetic distances and probabilities of travel along their multiple possible routes would throw light on this important concept
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