The minijets-in-a-jet statistical model and the RMS-flux correlation

The flux variability of blazars at very high energies does not have a clear origin. Flux variations on time scales down to the minute suggest that variability originates in the jet, where a relativistic boost can shorten the observed time scale, while the linear relation between the flux and its RMS or the skewness of the flux distribution suggests that the variability stems from multiplicative processes, which are associated in some models with the accretion disk. We study the RMS-flux relation and emphasize its link to Pareto distributions, characterized by a power-law probability density function. Such distributions are naturally generated within a minijets- in-a-jet statistical model, in which boosted emitting regions are isotropically oriented within the bulk relativistic flow of a jet. We prove that, within this model, the flux of a single minijet is proportional to its RMS. This relation still holds when considering a large number of emitting regions, for which the distribution of the total flux is skewed and could be interpreted as being log-normal. The minijets-in-a-jet statistical model reconciles the fast variations and the statistical properties of the flux of blazars at very high energies.Comment: 6 pages, 6 figures, accepted in A

New AGNs discovered by H.E.S.S

During the last year, six new Active Galactic Nuclei (AGN) have been discovered and studied by H.E.S.S. at Very High Energies (VHE). Some of these recent discoveries have been made thanks to new enhanced analysis methods and are presented at this conference for the first time. The three blazars 1ES 0414+009, SHBL J001355.9-185406 and 1RXS J101015.9-311909 have been targeted for observation due to their high levels of radio and X-ray fluxes, while the Fermi/LAT catalogue of bright sources triggered the observation of PKS 0447-439 and AP Librae. Additionally, the BL Lac 1ES 1312-423 was discovered in the field-of-view (FoV) of Centaurus A thanks to the large exposure dedicated by H.E.S.S. to this particularly interesting source. The newly-discovered sources are presented here and in three companion presentations at this conference.Comment: 8 pages, 3 figures, proceeding from the 25th Texas Symposium on Relativistic Astrophysics (Heidelberg, Germany, 2010

L-MTP-PE and zoledronic acid combination in osteosarcoma: pre-clinical evidence of positive therapeutic combination for clinical transfer

Osteosarcoma, the most frequent malignant primary bone tumor in pediatric patients is characterized by osteolysis promoting tumor growth. Lung metastasis is the major bad prognosis factor of this disease. Zoledronic Acid (ZA), a potent inhibitor of bone resorption is currently evaluated in phase III randomized studies in Europe for the treatment of osteosarcoma and Ewing sarcoma. The beneicial effect of the liposomal form of Muramyl-TriPeptide-Phosphatidyl Ethanolamine (L-mifamurtide, MEPACT®), an activator of macrophage populations has been demonstrated to eradicate lung metastatic foci in osteosarcoma. The objective of this study was to evaluate the potential therapeutic beneit and the safety of the ZA and L-mifamurtide combination in preclinical models of osteosarcoma, as a prerequisite before translation to patients. The effects of ZA (100 µg/kg) and L-mifamurtide (1 mg/kg) were investigated in vivo in xenogeneic and syngeneic mice models of osteosarcoma, at clinical (tumor proliferation, spontaneous lung metastases development), radiological (bone microarchitecture by microCT analysis), biological and histological levels. No interference between the two drugs could be observed on ZA-induced bone protection and on L-mifamurtide-induced inhibition of lung metastasis development. Unexpectedly, ZA and L-mifamurtide association induced an additional and in some cases synergistic inhibition of primary tumor progression. L-mifamurtide has no effect on tumor proliferation in vitro or in vivo, and macrophage population was not affected at the tumor site whatever the treatment. This study evidenced for the irst time a signiicant inhibition of primary osteosarcoma progression when both drugs are combined. This result constitutes a irst proof-of-principle for clinical application in osteosarcoma patients

Local control of intestinal stem cell homeostasis by enteroendocrine cells in the adult <i>Drosophila</i> midgut

Background: Enteroendocrine cells populate gastrointestinal tissues and are known to translate local cues into systemic responses through the release of hormones into the bloodstream.&lt;p&gt;&lt;/p&gt; Results: Here we report a novel function of enteroendocrine cells acting as local regulators of intestinal stem cell (ISC) proliferation through modulation of the mesenchymal stem cell niche in the &lt;i&gt;Drosophila&lt;/i&gt; midgut. This paracrine signaling acts to constrain ISC proliferation within the epithelial compartment. Mechanistically, midgut enteroendocrine cells secrete the neuroendocrine hormone Bursicon, which acts—beyond its known roles in development—as a paracrine factor on the visceral muscle (VM). Bursicon binding to its receptor, DLGR2, the ortholog of mammalian leucine-rich repeat-containing G protein-coupled receptors (LGR4-6), represses the production of the VM-derived EGF-like growth factor Vein through activation of cAMP.&lt;p&gt;&lt;/p&gt; Conclusions: We therefore identify a novel paradigm in the regulation of ISC quiescence involving the conserved ligand/receptor Bursicon/DLGR2 and a previously unrecognized tissue-intrinsic role of enteroendocrine cells.&lt;p&gt;&lt;/p&gt