Carcinoma-associated fibroblasts stimulate tumor progression of initiated human epithelium

The present study demonstrates that fibroblasts associated with carcinomas stimulate tumor progression of initiated nontumorigenic epithelial cells both in an in vivo tissue recombination system and in an in vitro coculture system. Human prostatic carcinoma-associated fibroblasts grown with initiated human prostatic epithelial cells dramatically stimulated growth and altered histology of the epithelial population. This effect was not detected when normal prostatic fibroblasts were grown with the initiated epithelial cells under the same experimental conditions. In contrast, carcinoma-associated fibroblasts did not affect growth of normal human prostatic epithelial cells under identical conditions. From these data, we conclude that in this human prostate cancer model, carcinoma-associated fibroblasts stimulate progression of tumorigenesis. Thus, carcinoma-associated fibroblasts can direct tumor progression of an initiated prostate epithelial cell

Deformation of Codimension-2 Surface and Horizon Thermodynamics

The deformation equation of a spacelike submanifold with an arbitrary codimension is given by a general construction without using local frames. In the case of codimension-1, this equation reduces to the evolution equation of the extrinsic curvature of a spacelike hypersurface. In the more interesting case of codimension-2, after selecting a local null frame, this deformation equation reduces to the well known (cross) focusing equations. We show how the thermodynamics of trapping horizons is related to these deformation equations in two different formalisms: with and without introducing quasilocal energy. In the formalism with the quasilocal energy, the Hawking mass in four dimension is generalized to higher dimension, and it is found that the deformation of this energy inside a marginal surface can be also decomposed into the contributions from matter fields and gravitational radiation as in the four dimension. In the formalism without the quasilocal energy, we generalize the definition of slowly evolving future outer trapping horizons proposed by Booth to past trapping horizons. The dynamics of the trapping horizons in FLRW universe is given as an example. Especially, the slowly evolving past trapping horizon in the FLRW universe has close relation to the scenario of slow-roll inflation. Up to the second order of the slowly evolving parameter in this generalization, the temperature (surface gravity) associated with the slowly evolving trapping horizon in the FLRW universe is essentially the same as the one defined by using the quasilocal energy.Comment: Latex, 61 pages, no figures; v2, type errors corrected; v3, references and comments are added, English is improved, to appear in JHE

Mass and Angular Momentum in General Relativity

We present an introduction to mass and angular momentum in General Relativity. After briefly reviewing energy-momentum for matter fields, first in the flat Minkowski case (Special Relativity) and then in curved spacetimes with or without symmetries, we focus on the discussion of energy-momentum for the gravitational field. We illustrate the difficulties rooted in the Equivalence Principle for defining a local energy-momentum density for the gravitational field. This leads to the understanding of gravitational energy-momentum and angular momentum as non-local observables that make sense, at best, for extended domains of spacetime. After introducing Komar quantities associated with spacetime symmetries, it is shown how total energy-momentum can be unambiguously defined for isolated systems, providing fundamental tests for the internal consistency of General Relativity as well as setting the conceptual basis for the understanding of energy loss by gravitational radiation. Finally, several attempts to formulate quasi-local notions of mass and angular momentum associated with extended but finite spacetime domains are presented, together with some illustrations of the relations between total and quasi-local quantities in the particular context of black hole spacetimes. This article is not intended to be a rigorous and exhaustive review of the subject, but rather an invitation to the topic for non-experts. In this sense we follow essentially the expositions in Szabados 2004, Gourgoulhon 2007, Poisson 2004 and Wald 84, and refer the reader interested in further developments to the existing literature, in particular to the excellent and comprehensive review by Szabados (2004).Comment: 41 pages. Notes based on the lecture given at the C.N.R.S. "School on Mass" (June 2008) in Orleans, France. To appear as proceedings in the book "Mass and Motion in General Relativity", eds. L. Blanchet, A. Spallicci and B. Whiting. Some comments and references added

Conformally rescaled spacetimes and Hawking radiation

We study various derivations of Hawking radiation in conformally rescaled metrics. We focus on two important properties, the location of the horizon under a conformal transformation and its associated temperature. We find that the production of Hawking radiation cannot be associated in all cases to the trapping horizon because its location is not invariant under a conformal transformation. We also find evidence that the temperature of the Hawking radiation should transform simply under a conformal transformation, being invariant for asymptotic observers in the limit that the conformal transformation factor is unity at their location.Comment: 22 pages, version submitted to journa

Isolated and dynamical horizons and their applications

Over the past three decades, black holes have played an important role in quantum gravity, mathematical physics, numerical relativity and gravitational wave phenomenology. However, conceptual settings and mathematical models used to discuss them have varied considerably from one area to another. Over the last five years a new, quasi-local framework was introduced to analyze diverse facets of black holes in a unified manner. In this framework, evolving black holes are modeled by dynamical horizons and black holes in equilibrium by isolated horizons. We review basic properties of these horizons and summarize applications to mathematical physics, numerical relativity and quantum gravity. This paradigm has led to significant generalizations of several results in black hole physics. Specifically, it has introduced a more physical setting for black hole thermodynamics and for black hole entropy calculations in quantum gravity; suggested a phenomenological model for hairy black holes; provided novel techniques to extract physics from numerical simulations; and led to new laws governing the dynamics of black holes in exact general relativity.Comment: 77 pages, 12 figures. Typos and references correcte

The Heartbleed bug : insecurity repackaged, rebranded and resold

The emergence of a post-industrial information economy shaped by and around networked communication technology has presented new opportunities for identity theft. In particular, the accidental leakage or deliberate harvesting of information, via either hacking or social engineering, is an omnipresent threat to a large number of commercial organisations and state agencies who manage digital databases and sociotechnical forms of data. Throughout the twenty-first century the global media have reported on a series of data breaches fuelling amongst the public an anxiety concerning the safety and security of their personal and financial data. With concern outpacing reliable information a reassurance gap has emerged between the public's expectations and the state's ability to provide safety and security online. This disparity presents a significant opportunity for a commercial computer crime control industry who has sought to position itself as being able to offer consumer citizens the antidotes for such ills. This paper considers how neoliberal discourses of cybercrime control are packaged, branded and sold, through an examination of the social construction of the Heartbleed bug. It demonstrates how security company Codenomicon masterfully communicated the vulnerability, the product of a simple coding error, through its name, a logo and an accompanying website, in turn, shaping news coverage across the mainstream media and beyond

Particle creation rate for dynamical black holes

We present the particle creation probability rate around a general black hole as an outcome of quantum fluctuations. Using the uncertainty principle for these fluctuation, we derive a new ultraviolet frequency cutoff for the radiation spectrum of a dynamical black hole. Using this frequency cutoff, we define the probability creation rate function for such black holes. We consider a dynamical Vaidya model, and calculate the probability creation rate for this case when its horizon is in a slowly evolving phase. Our results show that one can expect the usual Hawking radiation emission process in the case of a dynamical black hole when it has a slowly evolving horizon. Moreover, calculating the probability rate for a dynamical black hole gives a measure of when Hawking radiation can be killed off by an incoming flux of matter or radiation. Our result strictly suggests that we have to revise the Hawking radiation expectation for primordial black holes that have grown substantially since they were created in the early universe. We also infer that this frequency cut off can be a parameter that shows the primordial black hole growth at the emission moment.Comment: 10 pages, 1 figure. The paper was rewritten in more clear presentation and one more appendix is adde

Identification of stromally expressed molecules in the prostate by tag-profiling of cancer-associated fibroblasts, normal fibroblasts and fetal prostate.

The stromal microenvironment has key roles in prostate development and cancer, and cancer-associated fibroblasts (CAFs) stimulate tumourigenesis via several mechanisms including the expression of pro-tumourigenic factors. Mesenchyme (embryonic stroma) controls prostate organogenesis, and in some circumstances can re-differentiate prostate tumours. We have applied next-generation Tag profiling to fetal human prostate, normal human prostate fibroblasts (NPFs) and CAFs to identify molecules expressed in prostatic stroma. Comparison of gene expression profiles of a patient-matched pair of NPFs vs CAFs identified 671 transcripts that were enriched in CAFs and 356 transcripts whose levels were decreased, relative to NPFs. Gene ontology analysis revealed that CAF-enriched transcripts were associated with prostate morphogenesis and CAF-depleted transcripts were associated with cell cycle. We selected mRNAs to follow-up by comparison of our data sets with published prostate cancer fibroblast microarray profiles as well as by focusing on transcripts encoding secreted and peripheral membrane proteins, as well as mesenchymal transcripts identified in a previous study from our group. We confirmed differential transcript expression between CAFs and NPFs using QrtPCR, and defined protein localization using immunohistochemistry in fetal prostate, adult prostate and prostate cancer. We demonstrated that ASPN, CAV1, CFH, CTSK, DCN, FBLN1, FHL1, FN, NKTR, OGN, PARVA, S100A6, SPARC, STC1 and ZEB1 proteins showed specific and varied expression patterns in fetal human prostate and in prostate cancer. Colocalization studies suggested that some stromally expressed molecules were also expressed in subsets of tumour epithelia, indicating that they may be novel markers of EMT. Additionally, two molecules (ASPN and STC1) marked overlapping and distinct subregions of stroma associated with tumour epithelia and may represent new CAF markers

Gravitational collapse with tachyon field and barotropic fluid

A particular class of space-time, with a tachyon field, \phi, and a barotropic fluid constituting the matter content, is considered herein as a model for gravitational collapse. For simplicity, the tachyon potential is assumed to be of inverse square form i.e., V(\phi) \sim \phi^{-2}. Our purpose, by making use of the specific kinematical features of the tachyon, which are rather different from a standard scalar field, is to establish the several types of asymptotic behavior that our matter content induces. Employing a dynamical system analysis, complemented by a thorough numerical study, we find classical solutions corresponding to a naked singularity or a black hole formation. In particular, there is a subset where the fluid and tachyon participate in an interesting tracking behaviour, depending sensitively on the initial conditions for the energy densities of the tachyon field and barotropic fluid. Two other classes of solutions are present, corresponding respectively, to either a tachyon or a barotropic fluid regime. Which of these emerges as dominant, will depend on the choice of the barotropic parameter, \gamma. Furthermore, these collapsing scenarios both have as final state the formation of a black hole.Comment: 18 pages, 7 figures. v3: minor changes. Final version to appear in GR

Regulation of Epithelial Branching Morphogenesis and Cancer Cell Growth of the Prostate by Wnt Signaling

Although Wnt signaling has been shown to be important for embryonic morphogenesis and cancer pathogenesis of several tissues, its role in prostatic development and tumorigenesis is not well understood. Here we show that Wnt signaling regulated prostatic epithelial branching morphogenesis and luminal epithelial cell differentiation in developing rat prostate organ cultures. Specifically, Wnt signaling regulated the proliferation of prostate epithelial progenitor cells. Assessment of the expression levels of a Wnt pathway transcriptional target gene, Axin2, showed that the Wnt pathway was activated in the developing prostate, but was down-regulated in the adult. Castration resulted in an upregulation of Axin2 whereas androgen replacement resulted in a down regulation of Axin2. Such dynamic changes of Wnt activity was also confirmed in a BAT-gal transgenic mouse line in which β-galactosidase reporter is expressed under the control of β-catenin/T cell factor responsive elements. Furthermore, we evaluated the role of Wnt signaling in prostate tumorigenesis. Axin2 expression was found upregulated in the majority of human prostate cancer cell lines examined. Moreover, addition of a Wnt pathway inhibitor, Dickkopf 1 (DKK1), into the culture medium significantly inhibited prostate cancer cell growth and migration. These findings suggest that Wnt signaling regulates prostatic epithelial ductal branching morphogenesis by influencing cell proliferation, and highlights a role for Wnt pathway activation in prostatic cancer progression