Can the Type-IIB axion prevent Pre-big Bang inflation?

We look at the possibility of superinflationary behavior in a class of anisotropic Type-IIB superstring cosmologies in the context of Pre-big Bang scenario and find that there exists a rather narrow range of parameters for which these models inflate. We then show that, although in general this behavior is left untouched by the introduction of a Ramond-Ramond axion field through a SL(2,R) rotation, there exists a particular class of axions for which inflation disappears completely. Asymptotic past initial conditions are briefly discussed, and some speculations on the possible extension of Pre-big Bang ideas to gravitational collapse are presented.Comment: harvmac, epsf. 3 figures include

Large N limit of Extremal Non-supersymmetric Black Holes

The large N limit of extremal non-supersymmetric Type-I five-dimensional string black holes is studied from the point of view of D-branes. We find that the agreement between the D-brane and the black-hole picture is due to an asymptotic restoration of supersymmetry in the large $N$ limit in which both pictures are compared. In that limit Type-I string perturbation theory is effectively embedded into a Type-IIB perturbation theory with unbroken supersymmetric charges whose presence guarantees the non-renormalization of mass and entropy as the effective couplings are increased. In this vein, we also study the near-horizon geometry of the Type-I black hole using D5-brane probes to find that the low energy effective action for the probe is identical to the corresponding one in the auxiliary Type-IIB theory in the large N limit.Comment: 25 pages, harvmac, typos corrected and references adde

Open String Thermodynamics and D-Branes

We study the thermodynamics of open superstrings in the presence of $p$-dimensional D-branes. We get some finite temperature dualities relating the one-loop canonical free energy of open strings to the self-energy of D-branes at dual temperature. For the open bosonic string the inverse dual temperature is, as expected, the dual length under T-duality, $4\pi^{2}\alpha^{'}/\beta$. On the contrary, for the $SO(N)$, type-I superstring the dual temperature is given by $\beta$-duality, $2\pi^{2}\alpha^{'}/\beta$. We also study the emergence of the Hagedorn singularity in the dual description as triggered by the coupling of the D-brane to unphysical tachyons as well as the high temperature limit.Comment: 16 pages, harvmac (b), epsf, 2 figures included. Minor changes; discussion in section 4 has been expanded and two footnotes and a reference adde

Quantum Corrections in Two-Dimensional Non-Supersymmetric Heterotic Strings

We study quantum corrections for a family of 24 non-supersymmetric heterotic strings in two dimensions. We compute their genus two cosmological constant using the hyperelliptic formalism and the genus one two-point functions for the massless states. From here we get the mass corrections to the states in the massless sector and discuss the role of the infrared divergences that appear in the computation. We also study some tree-level aspects of these theories and find that they are classified not only by the corresponding Niemeier lattice but also by their {\it hidden} right-moving gauge symmetry.Comment: Minor changes. The discussion on the infrared divergences has been expanded and typos have been corrected. Final version to be published in Nucl. Phys. B. 40 pages. LaTeX, epsf. 4 Postscript figures in uuencoded fil

M-theory resolution of four-dimensional cosmological singularities via U-duality

We consider cosmological solutions of string and M-theory compactified to four dimensions by giving a general prescription to construct four-dimensional modular cosmologies with two commuting Killing vectors from vacuum solutions. By lifting these solutions to higher dimensions we analyze the existence of cosmological singularities and find that, in the case of non-closed Friedmann-Robertson-Walker universes, singularities can be removed from the higher-dimensional model when only one of the extra dimensions is time-varying. By studying the moduli space of compactifications of M-theory resulting in homogeneous cosmologies in four dimensions we show that U-duality transformations map singular cosmologies into non-singular ones.Comment: 21 pages, harvmac. No figures. Minor changes. Typos corrected, a footnote added in Sec. 3 and two words added to the title. Final version to appear in Nuclear Physics

Epigenetic footprint enables molecular risk stratification of hepatoblastoma with clinical implications

Background & aims: Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Herein, we aimed to uncover the mechanisms of HB pathobiology and to identify new biomarkers and therapeutic targets in a move towards precision medicine for patients with advanced HB. Methods: We performed a comprehensive genomic, transcriptomic and epigenomic characterization of 159 clinically annotated samples from 113 patients with HB, using high-throughput technologies. Results: We discovered a widespread epigenetic footprint of HB that includes hyperediting of the tumor suppressor BLCAP concomitant with a genome-wide dysregulation of RNA editing and the overexpression of mainly non-coding genes of the oncogenic 14q32 DLK1-DIO3 locus. By unsupervised analysis, we identified 2 epigenomic clusters (Epi-CA, Epi-CB) with distinct degrees of DNA hypomethylation and CpG island hypermethylation that are associated with the C1/C2/C2B transcriptomic subtypes. Based on these findings, we defined the first molecular risk stratification of HB (MRS-HB), which encompasses 3 main prognostic categories and improves the current clinical risk stratification approach. The MRS-3 category (28%), defined by strong 14q32 locus expression and Epi-CB methylation features, was characterized by CTNNB1 and NFE2L2 mutations, a progenitor-like phenotype and clinical aggressiveness. Finally, we identified choline kinase alpha as a promising therapeutic target for intermediate and high-risk HBs, as its inhibition in HB cell lines and patient-derived xenografts strongly abrogated tumor growth. Conclusions: These findings provide a detailed insight into the molecular features of HB and could be used to improve current clinical stratification approaches and to develop treatments for patients with HB. Lay summary: Hepatoblastoma is a rare childhood liver cancer that has been understudied. We have used cutting-edge technologies to expand our molecular knowledge of this cancer. Our biological findings can be used to improve clinical management and pave the way for the development of novel therapies for this cancer