Optimal limits on f_{NL}^{local} from WMAP 5-year data

We have applied the optimal estimator for f_{NL}^{local} to the 5 year WMAP data. Marginalizing over the amplitude of foreground templates we get -4 < f_{NL}^{local} < 80 at 95% CL. Error bars of previous (sub-optimal) analyses are roughly 40% larger than these. The probability that a Gaussian simulation, analyzed using our estimator, gives a result larger in magnitude than the one we find is 7%. Our pipeline gives consistent results when applied to the three and five year WMAP data releases and agrees well with the results from our own sub-optimal pipeline. We find no evidence of any residual foreground contamination.Comment: [v1] 21 pages, 7 figures. [v2] minor changes matching published versio

Prostaglandin E(2) in a TLR3- and 7/8-agonist-based DC maturation cocktail generates mature, cytokine-producing, migratory DCs but impairs antigen cross-presentation to CD8(+) T cells

Mature dendritic cells (DCs) represent cellular adjuvants for optimal antigen presentation in cancer vaccines. Recently, a combination of prostaglandin E(2) (PGE(2)) with Toll-like receptor agonists (TLR-P) was proposed as a new standard to generate superior cytokine-producing DCs with high migratory capacity. Here, we compare TLR-P DCs with conventional DCs matured only with the proinflammatory cytokines TNFα and IL-1ß (CDCs), focussing on the interaction of resulting DCs with CD8(+) T-cells. TLR-P matured DCs showed elevated expression of activation markers such as CD80 and CD83 compared to CDCs, together with a significantly higher migration capacity. Secretion of IL-6, IL-8, IL-10, and IL-12 was highest after 16 h in TLR-P DCs, and only TLR-P DCs secreted active IL-12p70. TLR-P DCs as well as CDCs successfully primed multifunctional CD8(+) T-cells from naïve precursors specific for the peptide antigens Melan-A, NLGN4X, and PTP with comparable priming efficacy and T-cell receptor avidity. CD8(+) T-cells primed by TLR-P DCs showed significantly elevated expression of the integrin VLA-4 and a trend for higher T-cell numbers after expansion. In contrast, TLR-P DCs displayed a substantially reduced capability to cross-present CMVpp65 protein antigen to pp65-specific T cells, an effect that was dose-dependent on PGE(2) during DC maturation and reproducible with several responder T-cell lines. In conclusion, TLR-P matured DCs might be optimal presenters of antigens not requiring processing such as short peptides. However, PGE(2) seems less favorable for maturation of DCs intended to process and cross-present more complex vaccine antigens such as lysates, proteins or long peptides

Improved constraints on the expansion rate of the Universe up to z~1.1 from the spectroscopic evolution of cosmic chronometers

We present new improved constraints on the Hubble parameter H(z) in the redshift range 0.15 < z < 1.1, obtained from the differential spectroscopic evolution of early-type galaxies as a function of redshift. We extract a large sample of early-type galaxies (\sim11000) from several spectroscopic surveys, spanning almost 8 billion years of cosmic lookback time (0.15 < z < 1.42). We select the most massive, red elliptical galaxies, passively evolving and without signature of ongoing star formation. Those galaxies can be used as standard cosmic chronometers, as firstly proposed by Jimenez & Loeb (2002), whose differential age evolution as a function of cosmic time directly probes H(z). We analyze the 4000 {\AA} break (D4000) as a function of redshift, use stellar population synthesis models to theoretically calibrate the dependence of the differential age evolution on the differential D4000, and estimate the Hubble parameter taking into account both statistical and systematical errors. We provide 8 new measurements of H(z) (see Tab. 4), and determine its change in H(z) to a precision of 5-12% mapping homogeneously the redshift range up to z \sim 1.1; for the first time, we place a constraint on H(z) at z \neq 0 with a precision comparable with the one achieved for the Hubble constant (about 5-6% at z \sim 0.2), and covered a redshift range (0.5 < z < 0.8) which is crucial to distinguish many different quintessence cosmologies. These measurements have been tested to best match a \Lambda CDM model, clearly providing a statistically robust indication that the Universe is undergoing an accelerated expansion. This method shows the potentiality to open a new avenue in constrain a variety of alternative cosmologies, especially when future surveys (e.g. Euclid) will open the possibility to extend it up to z \sim 2.Comment: 34 pages, 15 figures, 6 tables, published in JCAP. It is a companion to Moresco et al. (2012b, http://arxiv.org/abs/1201.6658) and Jimenez et al. (2012, http://arxiv.org/abs/1201.3608). The H(z) data can be downloaded at http://www.physics-astronomy.unibo.it/en/research/areas/astrophysics/cosmology-with-cosmic-chronometer

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

A 6% measurement of the Hubble parameter at z~0.45 : direct evidence of the epoch of cosmic re-acceleration

MM, LP and AC acknowledge financial contributions by grants ASI/INAF I/023/12/0 and PRIN MIUR 2010-2011 "The dark Universe and the cosmic evolution of baryons: from current surveys to Euclid". RJ and LV thank the Royal Society for financial support and the ICIC at Imperial College for hospitality while this work was being completed. LV is supported by the European Research Council under the European Community's Seventh Framework Programme FP7-IDEAS-Phys.LSS 240117. Funding for this work was partially provided by the Spanish MINECO under projects AYA2014-58747-P and MDM-2014-0369 of ICCUB (Unidad de Excelencia "Maria de Maeztu") Funding for SDSS-III has been provided by the Alfred P. Sloan Foundation, the Participating Institutions, the National Science Foundation, and the U.S. Department of Energy Office of Science.Deriving the expansion history of the Universe is a major goal of modern cosmology. To date, the most accurate measurements have been obtained with Type Ia Supernovae (SNe) and Baryon Acoustic Oscillations (BAO), providing evidence for the existence of a transition epoch at which the expansion rate changes from decelerated to accelerated. However, these results have been obtained within the framework of specific cosmological models that must be implicitly or explicitly assumed in the measurement. It is therefore crucial to obtain measurements of the accelerated expansion of the Universe independently of assumptions on cosmological models. Here we exploit the unprecedented statistics provided by the Baryon Oscillation Spectroscopic Survey (BOSS, [1-3]) Data Release 9 to provide new constraints on the Hubble parameter H(z) using the cosmic chronometers approach. We extract a sample of more than 130000 of the most massive and passively evolving galaxies, obtaining five new cosmology-independent H(z) measurements in the redshift range 0.3 < z < 0.5, with an accuracy of ~11–16% incorporating both statistical and systematic errors. Once combined, these measurements yield a 6% accuracy constraint of H(z = 0.4293) = 91.8 ± 5.3 km/s/Mpc. The new data are crucial to provide the first cosmology-independent determination of the transition redshift at high statistical significance, measuring zt = 0.4 ± 0.1, and to significantly disfavor the null hypothesis of no transition between decelerated and accelerated expansion at 99.9% confidence level. This analysis highlights the wide potential of the cosmic chronometers approach: it permits to derive constraints on the expansion history of the Universe with results competitive with standard probes, and most importantly, being the estimates independent of the cosmological model, it can constrain cosmologies beyond—and including—the ΛCDM model.PostprintPeer reviewe

Incidence of subsequent malignancies after total body irradiation-based allogeneic HSCT in children with ALL - long-term follow-up from the prospective ALL-SCT 2003 trial

Total body irradiation (TBI)-based conditioning is associated with superior leukemia-free survival in children with ALL undergoing HSCT. However, the risk for subsequent malignant neoplasms (SMN) remains a significant concern. We analyzed 705 pediatric patients enrolled in the prospective ALL-SCT-BFM-2003 trial and its subsequent registry. Patients >2 years received conditioning with TBI 12 Gy/etoposide (n = 558) and children ≤2 years of age or with contraindications for TBI received busulfan/cyclophosphamide/etoposide (n = 110). The 5- and 10-year cumulative incidence of SMN was 0.02 ± 0.01 and 0.13 ± 0.03, respectively. In total, 39 SMN (34 solid tumors, 5 MDS/AML) were diagnosed in 33 patients at a median of 5.8 years (1.7-13.4), exclusively in the TBI group. Of 33 affected patients, 21 (64%) are alive at a median follow-up of 5.1 years (0-9.9) after diagnosis of their first SMN. In univariate analysis, neither age at HSCT, donor type, acute GVHD, chronic GVHD, nor CMV constituted a significant risk factor for SMN. The only significant risk factor was TBI versus non-TBI based conditioning. This analysis confirms and quantifies the increased risk of SMN in children with ALL after conditioning with TBI. Future strategies to avoid TBI will need careful tailoring within prospective, controlled studies to prevent unfavorable outcomes

Dust in Supernovae and Supernova Remnants I : Formation Scenarios

Supernovae are considered as prime sources of dust in space. Observations of local supernovae over the past couple of decades have detected the presence of dust in supernova ejecta. The reddening of the high redshift quasars also indicate the presence of large masses of dust in early galaxies. Considering the top heavy IMF in the early galaxies, supernovae are assumed to be the major contributor to these large amounts of dust. However, the composition and morphology of dust grains formed in a supernova ejecta is yet to be understood with clarity. Moreover, the dust masses inferred from observations in mid-infrared and submillimeter wavelength regimes differ by two orders of magnitude or more. Therefore, the mechanism responsible for the synthesis of molecules and dust in such environments plays a crucial role in studying the evolution of cosmic dust in galaxies. This review summarises our current knowledge of dust formation in supernova ejecta and tries to quantify the role of supernovae as dust producers in a galaxy.Peer reviewe

Immunotherapy with the trifunctional anti-CD20 x anti-CD3 antibody FBTA05 (Lymphomun) in paediatric high-risk patients with recurrent CD20-positive B cell malignancies.

Summary: Children with B cell malignancies refractory to standard therapy are known to have a poor prognosis and very limited treatment options. Here, we report on the treatment and follow-up of ten patients diagnosed with relapsed or refractory mature B-cell Non Hodgkin Lymphoma (B-NHL), Burkitt leukaemia (B-AL) or pre B-acute lymphoblastic leukaemia (pre B-ALL). All children were treated with FBTA05 (now designated Lymphomun), an anti-CD3 x anti-CD20 trifunctional bispecific antibody (trAb) in compassionate use. Within individual treatment schedules, Lymphomun was applied (a) after allogeneic stem cell transplantation (allo-SCT, n = 6) to induce sustained long-term remission, or (b) stand alone prior to subsequent chemotherapy to eradicate residual disease before allo-SCT (n = 4). Nine of ten children displayed a clinical response: three stable diseases (SD), one partial remission (PR) and five induced or sustained complete remissions (CR). Five of these nine responders died during follow-up. The other patients still maintain CR with a current overall survival of 874-1424 days (median: 1150 days). In conclusion, despite the dismal clinical prognosis of children refractory to standard therapy, immunotherapy with Lymphomun resulted in a favourable clinical outcome in this cohort of refractory paediatric patients