Gravitational Waves from the First Stars

We consider the stochastic background of gravitational waves produced by an early generation of Population III stars coupled with a normal mode of star formation at lower redshift. The computation is performed in the framework of hierarchical structure formation and is based on cosmic star formation histories constrained to reproduce the observed star formation rate at redshift z \la 6, the observed chemical abundances in damped Lyman alpha absorbers and in the intergalactic medium, and to allow for an early reionization of the Universe at $z\sim 10-20$ as indicated by the first year results released by WMAP. We find that the normal mode of star formation produces a gravitational wave background which peaks at 300-500 Hz and is within LIGO III sensitivity. The Population III component peaks at lower frequencies (30-100 Hz depending on the model), and could be detected by LIGO III as well as the planned BBO and DECIGO interferometers.Comment: 16 pages, 8 figure

Cosmic Star Formation, Reionization, and Constraints on Global Chemical Evolution

Motivated by the WMAP results indicating an early epoch of reionization, we consider alternative cosmic star formation models which are capable of reionizing the early intergalactic medium. We develop models which include an early burst of massive stars (with several possible mass ranges) combined with standard star formation. We compute the stellar ionizing flux of photons and we track the nucleosynthetic yields for several elements: D, He4, C, N, O, Si, S, Fe, Zn. We compute the subsequent chemical evolution as a function of redshift, both in the intergalactic medium and in the interstellar medium of forming galaxies, starting with the primordial objects which are responsible for the reionization. We apply constraints from the observed abundances in the Lyman alpha forest and in Damped Lyman alpha clouds in conjunction with the ability of the models to produce the required degree of reionization. We also consider possible constraints associated with the observations of the two extremely metal-poor stars HE 0107-5240 and CS22949-037. We confirm that an early top-heavy stellar component is required, as a standard star formation model is unable to reionize the early Universe and reproduce the abundances of the very metal-poor halo stars. A bimodal (or top-heavy) IMF (40 - 100 M_\odot) is our preferred scenario compared to the extreme mass range (\ga 100 M_\odot) often assumed to be responsible for the early stages of reionization. A mode of even more extreme stellar masses in the range (\ge 270 M_\odot) has also been considered. All massive stars in this mode collapse entirely into black holes, and as a consequence, chemical evolution and reionization are de-correlated. [Abstract abbreviated.]Comment: 45 pages, 18 eps figures, as accepted in Ap

Hierarchical Growth and Cosmic Star Formation: Enrichment, Outflows and Supernova Rates

The cosmic star formation histories are evaluated for different minimum masses of the initial halo structures, with allowance for realistic gas outflows. With a minimum halo mass of 10^{7} - 10^{8} M_odot and a moderate outflow efficiency, we reproduce both the current baryon fraction and the early chemical enrichment of the IGM. The intensity of the formation rate of ``normal'' stars is also well constrained by the observations: it has to be dominated by star formation in elliptical galaxies, except perhaps at very low redshift. The fraction of baryons in stars is predicted as are also the type Ia and II supernova event rates. Comparison with SN observations in the redshift range z=0-2 allows us to set strong constraints on the time delay of type Ia supernovae (a total delay of \sim 4 Gyr is required to fit the data), the lower end of the mass range of the progenitors (2 - 8 M_odot) and the fraction of white dwarfs that reproduce the type Ia supernova (about 1 per cent). The intensity in the initial starburst of zero metallicity stars below 270 M_\odot must be limited in order to avoid premature overenrichment of the IGM. Only about 10 - 20 % of the metals present in the IGM at z = 0 have been produced by population III stars at very high z. The remaining 80 - 90 % are ejected later by galaxies forming normal stars, with a maximum outflow efficiency occurring at a redshift of about 5. We conclude that 10^{-3} of the mass in baryons must lie in first massive stars in order to produce enough ionizing photons to allow early reionization of the IGM by z \sim 15.Comment: 51 pages, 23 eps figure

Breast cancer incidence using administrative data: correction with sensitivity and specificity.

International audienceOBJECTIVE: To estimate breast cancer incidence in the general population using a method that corrects for lack of sensitivity and specificity in the identification of incident breast cancer in inpatient claims data. STUDY DESIGN AND SETTINGS: Two-phase study: phase 1 to identify incident cases in claims data, and phase 2 to estimate sensitivity and specificity in a subset of the population. Two algorithms (1: principal diagnosis; 2: principal diagnosis+specific surgery procedures) were used to identify incident cases in claims of women aged 20 years or older, living in a French district covered by a cancer registry. Sensitivity and specificity were estimated in one district and used to correct incident cases identified. RESULTS: The sensitivity and specificity for algorithms 1 and 2 were 69.0% and 99.89%, and 64.4% and 99.93%, respectively. In contrast to specificity, the sensitivity for both algorithms was lower for women younger than 40 years and older than 65 years. Cases reported by cancer registries were closer to cases identified with algorithm 2 (-3.2% to +20.1%) and to corrected numbers with algorithm 1 (-1% to +15%). CONCLUSION: To obtain reliable estimates of breast cancer incidence in the general population, sensitivity and specificity, which reflect medical and coding practice variations, are necessary

A screen for suppressors of gross chromosomal rearrangements identifies a conserved role for PLP in preventing DNA lesions.

Genome instability is a hallmark of cancer cells. One class of genome aberrations prevalent in tumor cells is termed gross chromosomal rearrangements (GCRs). GCRs comprise chromosome translocations, amplifications, inversions, deletion of whole chromosome arms, and interstitial deletions. Here, we report the results of a genome-wide screen in Saccharomyces cerevisiae aimed at identifying novel suppressors of GCR formation. The most potent novel GCR suppressor identified is BUD16, the gene coding for yeast pyridoxal kinase (Pdxk), a key enzyme in the metabolism of pyridoxal 5' phosphate (PLP), the biologically active form of vitamin B6. We show that Pdxk potently suppresses GCR events by curtailing the appearance of DNA lesions during the cell cycle. We also show that pharmacological inhibition of Pdxk in human cells leads to the production of DSBs and activation of the DNA damage checkpoint. Finally, our evidence suggests that PLP deficiency threatens genome integrity, most likely via its role in dTMP biosynthesis, as Pdxk-deficient cells accumulate uracil in their nuclear DNA and are sensitive to inhibition of ribonucleotide reductase. Since Pdxk links diet to genome stability, our work supports the hypothesis that dietary micronutrients reduce cancer risk by curtailing the accumulation of DNA damage and suggests that micronutrient depletion could be part of a defense mechanism against hyperproliferation

Major West Indies MRSA clones in human beings: do they travel with their hosts?

International audienceBACKGROUND: Descriptions of the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) have seldom been produced in the Caribbean, which is a major tourism destination. MATERIALS AND METHODS: Using DNA microarrays and spa typing, we characterized 85 MRSA isolates from human skin and soft-tissue infections from five different islands. RESULTS: In the French West Indies (n = 72), the most frequently isolated clones were the same clones that are specifically isolated from mainland France [Lyon (n = 35) and Geraldine (n = 11) clones], whereas the clones that were most frequently isolated from the other islands (n = 13) corresponded with clones that have a worldwide endemic spread [Vienna/Hungarian/Brazilian (n = 5), Panton Valentine leukocidin-positive USA300 (n = 4), New York/Japan (n = 2), and pediatric (n = 1) clones]. CONCLUSION: The distribution of the major MRSA clones in the French (Guadeloupe and Martinique) and non-French West Indies (Jamaica, Trinidad, and Tobago) is different, and the clones most closely resemble those found in the home countries of the travelers who visit the islands most frequently. The distribution might be affected by tourist migration, which is specific to each island

PD-1 mediates functional exhaustion of activated NK cells in patients with Kaposi sarcoma

International audienceProgrammed Death-1 (PD-1), an inhibitory receptor expressed by activated lymphocytes, is involved in regulating T-and B-cell responses. PD-1 and its ligands are exploited by a variety of cancers to facilitate tumor escape through PD-1-mediated functional exhaustion of effector T cells. Here, we report that PD-1 is upregulated on Natural Killer (NK) cells from patients with Kaposi sarcoma (KS). PD-1 was expressed in a sub-population of activated, mature CD56(dim)CD16(pos) NK cells with otherwise normal expression of NK surface receptors. PD-1(pos) NK cells from KS patients were hyporesponsive ex vivo following direct triggering of NKp30, NKp46 or CD16 activating receptors, or short stimulation with NK cell targets. PD-1(pos) NK cells failed to degranulate and release IFN gamma, but exogenous IL-2 or IL-15 restored this defect. That PD-1 contributed to NK cell functional impairment and was not simply a marker of dysfunctional NK cells was confirmed in PD-1-transduced NKL cells. In vitro, PD-1 was induced at the surface of healthy control NK cells upon prolonged contact with cells expressing activating ligands, i. e. a condition mimicking persistent stimulation by tumor cells. Thus, PD-1 appears to plays a critical role in mediating NK cell exhaustion. The existence of this negative checkpoint fine-tuning NK activation highlights the possibility that manipulation of the PD-1 pathway may be a strategy for circumventing tumor escape not only from the T cell-, but also the NK-cell mediated immune surveillance

Enediynes Bearing Polyfluoroaryl Sulfoxide as New Antiproliferative Agents with Dual Targeting of Microtubules and DNA

International audienceA novel series of enediynes possessing pentafluorophenylsulfoxide have been developed. The innovative compounds possess antiproliferative activity against a broad panel of human cancer cells originating from breast, blood, lung, kidney, colon, prostate, pancreas or skin with IC 50 ranging from 0.6 to 3.4 µM. The antiproliferative activity of enediynes in darkness is associated to their ability to compromise microtubule network. In addition, exposure to UV leads to double-stranded DNA cleavage caused by the newly synthesized molecules reducing further their IC 50 in nanomolar range against human tumor cells, including chemo-resistant pancreatic cancer cells. Taken together, the examined data demonstrate that enediynes possessing pentafluorosulfoxide are promising molecules in the cancer therapy