Overexpression of an activated REL mutant enhances the transformed state of the human B-lymphoma BJAB cell line and alters its gene expression profile

The human REL proto-oncogene encodes a transcription factor in the nuclear factor (NF)-kappaB family. Overexpression of REL is acutely transforming in chicken lymphoid cells, but has not been shown to transform any mammalian lymphoid cell type. In this report, we show that overexpression of a highly transforming mutant of REL (RELDeltaTAD1) increases the oncogenic properties of the human B-cell lymphoma BJAB cell line, as shown by increased colony formation in soft agar, tumor formation in SCID (severe combined immunodeficient) mice, and adhesion. BJAB-RELDeltaTAD1 cells also show decreased activation of caspase in response to doxorubicin. BJAB-RELDeltaTAD1 cells have increased levels of active nuclear REL protein as determined by immunofluorescence, subcellular fractionation and electrophoretic mobility shift assay. Overexpression of RELDeltaTAD1 in BJAB cells has transformed the gene expression profile of BJAB cells from that of a germinal center B-cell subtype of diffuse large B-cell lymphoma (DLBCL) (GCB-DLBCL) to that of an activated B-cell subtype (ABC-DLBCL), as evidenced by increased expression of many ABC-defining mRNAs. Upregulated genes in BJAB-RELDeltaTAD1 cells include several NF-kappaB targets that encode proteins previously implicated in B-cell development or oncogenesis, including BCL2, IRF4, CD40 and VCAM1. The cell system we describe here may be valuable for further characterizing the molecular details of REL-induced lymphoma in humans.P42 ES007381 - NIEHS NIH HHS; R01 CA047763 - NCI NIH HHS; CA047763 - NCI NIH HHS; R01 CA047763-20 - NCI NIH HHS; P42 ES007381-140019 - NIEHS NIH HHS; 5 P42 ES07381 - NIEHS NIH HHS; P42 ES007381-150019 - NIEHS NIH HHS; R01 CA047763-19 - NCI NIH HH

The energy production rate & the generation spectrum of UHECRs

We derive simple analytic expressions for the flux and spectrum of ultra-high energy cosmic-rays (UHECRs) predicted in models where the CRs are protons produced by extra-Galactic sources. For a power-law scaling of the CR production rate with redshift and energy, d\dot{n} /dE\propto E^-\alpha (1+z)^m, our results are accurate at high energy, E>10^18.7 eV, to better than 15%, providing a simple and straightforward method for inferring d\dot{n}/dE from the observed flux at E. We show that current measurements of the UHECR spectrum, including the latest Auger data, imply E^2d\dot{n}/dE(z=0)=(0.45\pm0.15)(\alpha-1) 10^44 erg Mpc^-3 yr^-1 at E<10^19.5 eV with \alpha roughly confined to 2\lesseq\alpha<2.7. The uncertainty is dominated by the systematic and statistic errors in the experimental determination of individual CR event energy, (\Delta E/E)_{sys} (\Delta E/E)_{stat} ~20%. At lower energy, d\dot{n}/dE is uncertain due to the unknown Galactic contribution. Simple models in which \alpha\simeq 2 and the transition from Galactic to extra-Galactic sources takes place at the "ankle", E ~10^19 eV, are consistent with the data. Models in which the transition occurs at lower energies require a high degree of fine tuning and a steep spectrum, \alpha\simeq 2.7, which is disfavored by the data. We point out that in the absence of accurate composition measurements, the (all particle) energy spectrum alone cannot be used to infer the detailed spectral shapes of the Galactic and extra-Galactic contributions.Comment: 9 pages, 11 figures, minor revision

Well-posedness of Hydrodynamics on the Moving Elastic Surface

The dynamics of a membrane is a coupled system comprising a moving elastic surface and an incompressible membrane fluid. We will consider a reduced elastic surface model, which involves the evolution equations of the moving surface, the dynamic equations of the two-dimensional fluid, and the incompressible equation, all of which operate within a curved geometry. In this paper, we prove the local existence and uniqueness of the solution to the reduced elastic surface model by reformulating the model into a new system in the isothermal coordinates. One major difficulty is that of constructing an appropriate iterative scheme such that the limit system is consistent with the original system.Comment: The introduction is rewritte

Gamma-Ray Bursts: The Underlying Model

A pedagogical derivation is presented of the ``fireball'' model of gamma-ray bursts, according to which the observable effects are due to the dissipation of the kinetic energy of a relativistically expanding wind, a ``fireball.'' The main open questions are emphasized, and key afterglow observations, that provide support for this model, are briefly discussed. The relativistic outflow is, most likely, driven by the accretion of a fraction of a solar mass onto a newly born (few) solar mass black hole. The observed radiation is produced once the plasma has expanded to a scale much larger than that of the underlying ``engine,'' and is therefore largely independent of the details of the progenitor, whose gravitational collapse leads to fireball formation. Several progenitor scenarios, and the prospects for discrimination among them using future observations, are discussed. The production in gamma- ray burst fireballs of high energy protons and neutrinos, and the implications of burst neutrino detection by kilometer-scale telescopes under construction, are briefly discussed.Comment: In "Supernovae and Gamma Ray Bursters", ed. K. W. Weiler, Lecture Notes in Physics, Springer-Verlag (in press); 26 pages, 2 figure

Modulated Scale-free Network in the Euclidean Space

A random network is grown by introducing at unit rate randomly selected nodes on the Euclidean space. A node is randomly connected to its $i$-th predecessor of degree $k_i$ with a directed link of length $\ell$ using a probability proportional to $k_i \ell^{\alpha}$. Our numerical study indicates that the network is Scale-free for all values of $\alpha > \alpha_c$ and the degree distribution decays stretched exponentially for the other values of $\alpha$. The link length distribution follows a power law: $D(\ell) \sim \ell^{\delta}$ where $\delta$ is calculated exactly for the whole range of values of $\alpha$.Comment: 4 pages, 4 figures. To be published in Physical Review

Anisotropy at the end of the cosmic ray spectrum?

The starburst galaxies M82 and NGC253 have been proposed as the primary sources of cosmic rays with energies above $10^{18.7}$ eV. For energies \agt 10^{20.3} eV the model predicts strong anisotropies. We calculate the probabilities that the latter can be due to chance occurrence. For the highest energy cosmic ray events in this energy region, we find that the observed directionality has less than 1% probability of occurring due to random fluctuations. Moreover, during the first 5 years of operation at Auger, the observation of even half the predicted anisotropy has a probability of less than $10^{-5}$ to occur by chance fluctuation. Thus, this model can be subject to test at very small cost to the Auger priors budget and, whatever the outcome of that test, valuable information on the Galactic magnetic field will be obtained.Comment: Final version to be published in Physical Review

Randall-Sundrum black holes and strange stars

It has recently been suggested that the existence of bare strange stars is incompatible with low scale gravity scenarios. It has been claimed that in such models, high energy neutrinos incident on the surface of a bare strange star would lead to catastrophic black hole growth. We point out that for the flat large extra dimensional case, the parts of parameter space which give rise to such growth are ruled out by other methods. We then go on to show in detail how black holes evolve in the the Randall-Sundrum two brane scenario where the extra dimensions are curved. We find that catastrophic black hole growth does not occur in this situation either. We also present some general expressions for the growth of five dimensional black holes in dense media.Comment: 16 pages, more numerics has lead to different path to same conclusion. Accepted in PR

Relic neutrino masses and the highest energy cosmic rays

We consider the possibility that a large fraction of the ultrahigh energy cosmic rays are decay products of Z bosons which were produced in the scattering of ultrahigh energy cosmic neutrinos on cosmological relic neutrinos. We compare the observed ultrahigh energy cosmic ray spectrum with the one predicted in the above Z-burst scenario and determine the required mass of the heaviest relic neutrino as well as the necessary ultrahigh energy cosmic neutrino flux via a maximum likelihood analysis. We show that the value of the neutrino mass obtained in this way is fairly robust against variations in presently unknown quantities, like the amount of neutrino clustering, the universal radio background, and the extragalactic magnetic field, within their anticipated uncertainties. Much stronger systematics arises from different possible assumptions about the diffuse background of ordinary cosmic rays from unresolved astrophysical sources. In the most plausible case that these ordinary cosmic rays are protons of extragalactic origin, one is lead to a required neutrino mass in the range 0.08 eV - 1.3 eV at the 68 % confidence level. This range narrows down considerably if a particular universal radio background is assumed, e.g. to 0.08 eV - 0.40 eV for a large one. The required flux of ultrahigh energy cosmic neutrinos near the resonant energy should be detected in the near future by AMANDA, RICE, and the Pierre Auger Observatory, otherwise the Z-burst scenario will be ruled out.Comment: 19 pages, 22 figures, REVTeX

Ultra-High Energy Neutrino Fluxes and Their Constraints

Applying our recently developed propagation code we review extragalactic neutrino fluxes above 10^{14} eV in various scenarios and how they are constrained by current data. We specifically identify scenarios in which the cosmogenic neutrino flux, produced by pion production of ultra high energy cosmic rays outside their sources, is considerably higher than the "Waxman-Bahcall bound". This is easy to achieve for sources with hard injection spectra and luminosities that were higher in the past. Such fluxes would significantly increase the chances to detect ultra-high energy neutrinos with experiments currently under construction or in the proposal stage.Comment: 11 pages, 15 figures, version published in Phys.Rev.

Extragalactic Sources for Ultra High Energy Cosmic Ray Nuclei

In this article we examine the hypothesis that the highest energy cosmic rays are complex nuclei from extragalactic sources. Under reasonable physical assumptions, we show that the nearby metally rich starburst galaxies (M82 and NGC 253) can produce all the events observed above the ankle. This requires diffusion of particles below $10^{20}$ eV in extragalactic magnetic fields $B \approx 15$ nG. Above $10^{19}$ eV, the model predicts the presence of significant fluxes of medium mass and heavy nuclei with small rate of change of composition. Notwithstanding, the most salient feature of the starburst-hypothesis is a slight anisotropy induced by iron debris just before the spectrum-cutoff.Comment: To appear in Phys. Rev. D, reference adde