Decoding of epigenetic and metabolic events driving immune diversion of myeloid cells in cancer

Cancers induce \u2018emergency\u2019 hematopoiesis and expansion of myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM), immunosuppressive and tumor-promoting cell populations, correlated with poor prognosis and resistance to chemo-immunotherapies. Molecular characterization of these cells offers new potential therapeutic opportunities. Previously, we showed that nuclear accumulation of p50 NF-kB transcription factor in TAM regulates expression of anti-inflammatory, pro-tumoral genes. Monocytic MDSC share myeloid progenitor and immunosuppressive properties with TAM. Here, we described how p50 NF-kB mediates the protumor functions of M-MDSC. Indeed, during cancer-related inflammation, chronic production of PGE2 induces nuclear p50 accumulation in M-MDSC, epigenetically reprogramming the response to IFN\u3b3 towards an immunosuppressive phenotype. Myeloid-specific deletion of p50 or antagonists of PGE2 receptors restore the antitumor inflammatory response to IFN\u3b3 of MMDSC. Recently, we identified that RORC1/ROR\u3b3 drives cancer-related myelopoiesis. ROR\u3b3 is a nuclear receptor co-activated by cholesterol-related molecules (eg. oxysterols). Of note, hypercholesterolemia predisposes to cancer and induces expansion of immature monocytes. Hence, we hypothesized an interplay between cholesterol metabolism and ROR\u3b3-driven myelopoiesis. Noteworthy, while tumor bearers (mice and humans) displayed increased levels of LDL-cholesterol, diet-induced hypercholesterolemia promotes metastasis and expansion of immunosuppressive M-MDSC and TAM. ROR\u3b3 deficiency prevents hypercholesterolemia-induced myelopoiesis disabling metastasis formation. Collectively, we identified p50 NF-kB as key driver of immunosuppressive M-MDSC in response to tumor-derived PGE2, and we underlined that ROR\u3b3 induces emergency myelopoiesis remarkably in dyslipidemic conditions. Hence, inhibitors of PGE2/p50 NF-kB and of cholesterol/ROR\u3b3 axis could be useful in the improvement of anticancer therapy

Nuclear re-interaction effects in quasi-elastic neutrino nucleus scattering

The quasi-elastic neutrino-nucleus cross section has been calculated by using a Fermi gas model corrected to consider the re-scattering between the emitted nucleon and the rest nucleus. As an example of the relevance of this effect we show results for the muon production cross section on 16O target.Comment: 7 pages, 4 Postscript figures, Contribution to NuInt01 Workshop, KEK, Tsukuba, Japa

Identification of Showers with Cores Outside the ARGO-YBJ Detector

In any EAS array, the rejection of events with shower cores outside the detector boundaries is of great importance. A large difference between the true and the reconstructed shower core positions may lead to a systematic miscalculation of some shower characteristics. Moreover, an accurate determination of the shower core position for selected internal events is important to reconstruct the primary direction using conical fits to the shower front, improving the detector angular resolution, or to performe an efficient gamma/hadron discrimination. In this paper we present a procedure able to identify and reject showers with cores outside the ARGO-YBJ carpet boundaries. A comparison of the results for gamma and proton induced showers is reported.Comment: 4 pages, to be published in the Proceedings of the 28th International Cosmic Ray Conference (Tsukuba, Japan 2003

Expected sensitivity of ARGO-YBJ to detect point gamma-ray sources

ARGO-YBJ is a full coverage air shower detector currently under construction at the Yangbajing Laboratory (4300 m a.s.l., Tibet, China). First data obtained with a subset of the apparatus will be available in summer 2003 while the full detector operation is expected in 2005. One of the main aims of ARGO-YBJ is the observation of gamma-ray sources, at an energy threshold of a few hundreds GeV. In this paper we present the expected sensitivity to detect point gamma ray sources, with particular attention to the Crab Nebula. According to our simulations a Crab-like signal could be detected in one year of operation with a statistical significance of 10 standard deviations, without any gamma/hadron discrimination.Comment: 4 pages, 2 Postscript figure

Final state interaction effects in neutrino-nucleus quasielastic scattering

We consider the charged-current quasielastic scattering of muon neutrinos on an Oxygen 16 target, described within a relativistic shell model and, for comparison, the relativistic Fermi gas. Final state interactions are described in the distorted wave impulse approximation, using both a relativistic mean field potential and a relativistic optical potential, with and without imaginary part. We present results for inclusive cross sections at fixed neutrino energies in the range $E_\nu =$ 200 MeV - 1 GeV, showing that final state interaction effects can remain sizable even at large energies.Comment: 4 pages, 4 figures; poster session of the Third International Workshop on Neutrino-Nucleus Interactions in the Few GeV Region (NuInt04), Gran Sasso (Italy), March 17-21, 2004; to appear in the proceeding

Solid Lipid Nanoparticles: Technological Developments and in Vivo Techniques to Evaluate Their Interaction with the Skin

This chapter provides informations about the non-invasive bioengineering techniques to study the SLN distribution and interaction on the ski

Biotechnology can Improve a Traditional Product as Table Olives

Table olives are fermented vegetables very popular in the world and especially in the Mediterranean countries. Five main styles (Spanish or Sevillian, Castelvetrano, Siciliano, Californian, and Greek) are diffused to produce commercial products, beside several traditional styles. Although the main preparation methods of table olives are known for a long time, they are not yet optimized systems, and each of them is characterized by advantages and disadvantages. The use of NaOH for green olive debittering is responsible for the elimination of many aroma compounds and nutritionally important molecules. High volumes of heavily contaminated wastewaters are produced during olive processing. Spontaneous fermentation processes used to ferment black or green olives are difficult either to monitor or control. Microbial starters, selected for specific bio/technological and safety traits, can be useful to (i) improve the table olives organoleptic characteristics, (ii) control the fermentation process and significantly reduce the time to obtain a final product, (iii) monitor the correct evolution of the process, (iv) ensure the maintenance and/or improvement of nutritional and healthy features of the product, (v) protect table olives from undesired spoilage and pathogenic microorganisms, (vi) produce table olives as a carrier of microorganisms with probiotics characters, and (vii) enhance product stability and shelf life