X-ray Preionisation Powered by Accretion on the First Black Holes. II: Cosmological Simulations and Observational Signatures

We use cosmological simulations to study the X-ray ionisation and heating of the intergalactic medium by an early population of accreting black holes. By considering observational constraints from the X-ray background, we find an upper limit for the optical depth to Thompson scattering tau_e~0.17. The redshifted soft X-ray background from these early sources produces:(i) fully ionised atomic hydrogen in the low density intergalactic medium before redshift z~7 (consequently stellar reionisation is characterised by an instantaneous overlap phase of HII regions),(ii) a second HeII reionisation at z~3 and (iii) heats the intergalactic medium to near 10000 K at low redshifts. The typical luminosity in the soft X-ray band of the galaxies hosting the black holes is about one order of magnitude below the sensitivity limit of the Chandra deep field. About a thousand of these sources may be present per square arcmin of the sky, producing detectable fluctuations. Few rarer objects could be luminous enough to be visible in the Chandra deep field. XEUS and Con-X satellites will be able to detect more of these sources that, if radio loud, could be used to study the 21cm forest in absorption.A signature of an early X-ray preionisation is the production of secondary CMB anisotropies on small angular scales. We find that in these models the power spectrum of temperature fluctuations increases with decreasing angular scale (dT~16 muK at 1arcsec scales), while for stellar reionisation scenarios the power decreases on smaller scales. We also show that the redshifted 21 cm radiation from neutral hydrogen can be marginally detected in emission at redshifts 7<z<12. At a redshift of about z~30 a stronger and narrower (in redshift space) signal in absorption against the CMB, that is peculiar to these models,could be detectable.[abridged]Comment: 14 pages including 14 figures and 2 tables. Accepted for publication in MNRA

X-ray Preionisation Powered by Accretion on the First Black Holes. I: a Model for the WMAP Polarisation Measurement

We investigate the possibility that there is a first phase of partial ionisation due to X-rays produced by black hole accretion in small-mass galaxies at redshifts 7<z<20. This is followed by complete reionisation by stellar sources at z~7. This scenario is motivated by the large optical depth to Thompson scattering, tau_e=0.17, measured by WMAP. But it is also consistent with the observed Gunn-Peterson trough in the spectra of quasars at z~5-6. We use a semianalytic code to explore models with different black hole accretion histories and cosmological parameters.We find that ``preionisation'' by X-rays can increase the intergalactic medium (IGM) optical depth from tau_e~0.06 given by stellar sources only, to 0.1<tau_e<0.2, if a fraction of baryons 5x10^-5 is accreted onto seed black holes produced in the collapse of low metallicity, high mass stars before z~15. To be effective, preionisation requires a non-negligible star formation in the first small-mass galaxies in hich seed black holes are formed.The model predicts that dwarf spheroidal galaxies may host a mass in black holes that is 5-40% of their stellar mass. The redshifted X-ray background produced by this early epoch of black hole accretion constitutes about 5-10% of the X-ray background in the 2-50 keV bands and roughtly half of the currently estimated black hole mass density was formed at early times.Moreover, in most models, the photons from the redshifted background are sufficient to fully reionise HeII at redshift z~3 without any additional contribution from quasars at lower redshifts and the temperature of the mean density intergalactic medium remains close to 10^4 K down to redshift z~1.[abridged]Comment: MNRAS in press (ref: 2004, MNRAS, 352,547). 16 pages, including 10 figures and 3 table

Population III stars: hidden or disappeared ?

A PopIII/Pop II transition from massive to normal stars is predicted to occur when the metallicity of the star forming gas crosses the critical range Z_cr = 10^(-5 +/- 1) Z_sun. To investigate the cosmic implications of such process we use numerical simulations which follow the evolution, metal enrichment and energy deposition of both Pop III and Pop II stars. We find that: (i) due to inefficient heavy element transport by outflows and slow "genetic" transmission during hierarchical growth, large fluctuations around the average metallicity arise; as a result Pop III star formation continues down to z=2.5, but at a low peak rate of 10^-5 M_sun yr^-1 Mpc^-3 occurring at z~6 (about 10^-4 of the PopII one); (ii) Pop III star formation proceeds in a "inside-out" mode in which formation sites are progressively confined at the periphery of collapsed structures, where the low gas density and correspondingly long free-fall timescales result in a very inefficient astration. These conclusions strongly encourage deep searches for pristine star formation sites at moderate (2<z<5) redshifts where metal free stars are likely to be hidden.Comment: to appear in MNRA

C-KIT IS EXPRESSED IN SOFT TISSUE SARCOMA OF NEUROECTODERMIC ORIGIN AND ITS LIGAND PREVENTS APOPTOSIS OF NEOPLASTIC CELLS

During development, mice with mutations of stem cell factor (SCF) or its receptor c-kit exhibit defects in melanogenesis, as well as hematopoiesis and gonadogenesis. Consequently, accumulating evidence suggests that the c-kit/SCF system plays a crucial role in all of these processes and in tumors which derive from them. Especially in neuroblastoma (infant tumors of neuroectoderm crest derivation such as melano-cytes) it would appear that an autocrine loop exists between c-kit and SCF, and that the functional block of the c-kit receptors with monoclonal antibodies (MoAbs) results in a significant decrease in cellular proliferation. We studied the expression and role of c-kit and SCF in cell lines of soft tissue sarcoma of neuroectodermic origin, such as Ewing’s sar-coma (ES) and peripheral neuro-ectodermal tumors (PNET). Using flow cytometry with MoAb CD117 PE, c-kit expressio

The transition from population III to population II-I star formation

We present results from the first cosmological simulations which study the onset of primordial, metal-free (population III), cosmic star formation and the transition to the present-day, metal-rich star formation (population II-I), including molecular (H$_2$, HD, etc.) evolution, tracing the injection of metals by supernov{\ae} into the surrounding intergalactic medium and following the change in the initial stellar mass function (IMF) according to the metallicity of the corresponding stellar population. Our investigation addresses the role of a wide variety of parameters (critical metallicity for the transition, IMF slope and range, SN/pair-instability SN metal yields, star formation threshold, resolution, etc.) on the metal-enrichment history and the associated transition in the star formation mode. All simulations present common trends. Metal enrichment is very patchy, with rare, unpolluted regions surviving at all redshifts, inducing the simultaneous presence of metal-free and metal-rich star formation regimes. As a result of the rapid pollution within high-density regions due to the first SN/pair-instability SN, local metallicity is quickly boosted above the critical metallicity for the transition. The population III regime lasts for a very short period during the first stages of star formation ($\sim 10^7\,\rm yr$), and its average contribution to the total star formation rate density drops rapidly below $\sim 10^{-3}-10^{-2}$

Long-term natural history data in Duchenne muscular dystrophy ambulant patients with mutations amenable to skip exons 44, 45, 51 and 53

The aim of this international collaborative effort was to report 36-month longitudinal changes using the 6MWT in ambulant patients affected by Duchenne muscular dystrophy amenable to skip exons 44, 45, 51 or 53

Addition of 5-fluorouracil to doxorubicin-paclitaxel sequence increases caspase-dependent apoptosis in breast cancer cell lines

INTRODUCTION: The aim of the study was to evaluate the activity of a combination of doxorubicin (Dox), paclitaxel (Pacl) and 5-fluorouracil (5-FU), to define the most effective schedule, and to investigate the mechanisms of action in human breast cancer cells. METHODS: The study was performed on MCF-7 and BRC-230 cell lines. The cytotoxic activity was evaluated by sulphorhodamine B assay and the type of drug interaction was assessed by the median effect principle. Cell cycle perturbation and apoptosis were evaluated by flow cytometry, and apoptosis-related marker (p53, bcl-2, bax, p21), caspase and thymidylate synthase (TS) expression were assessed by western blot. RESULTS: 5-FU, used as a single agent, exerted a low cytotoxic activity in both cell lines. The Dox→Pacl sequence produced a synergistic cytocidal effect and enhanced the efficacy of subsequent exposure to 5-FU in both cell lines. Specifically, the Dox→Pacl sequence blocked cells in the G2-M phase, and the addition of 5-FU forced the cells to progress through the cell cycle or killed them. Furthermore, Dox→Pacl pretreatment produced a significant reduction in basal TS expression in both cell lines, probably favoring the increase in 5-FU activity. The sequence Dox→Pacl→48-h washout→5-FU produced a synergistic and highly schedule-dependent interaction (combination index < 1), resulting in an induction of apoptosis in both experimental models regardless of hormonal, p53, bcl-2 or bax status. Apoptosis in MCF-7 cells was induced through caspase-9 activation and anti-apoptosis-inducing factor hyperexpression. In the BRC-230 cell line, the apoptotic process was triggered only by a caspase-dependent mechanism. In particular, at the end of the three-drug treatment, caspase-8 activation triggered downstream executioner caspase-3 and, to a lesser degree, caspase-7. CONCLUSION: In our experimental models, characterized by different biomolecular profiles representing the different biology of human breast cancers, the schedule Dox→Pacl→48-h washout→5-FU was highly active and schedule-dependent and has recently been used to plan a phase I/II clinical protocol