SuperB: a linear high-luminosity B Factory

This paper is based on the outcome of the activity that has taken place during the recent workshop on "SuperB in Italy" held in Frascati on November 11-12, 2005. The workshop was opened by a theoretical introduction of Marco Ciuchini and was structured in two working groups. One focused on the machine and the other on the detector and experimental issues. The present status on CP is mainly based on the results achieved by BaBar and Belle. Estabilishment of the indirect CP violation in B sector in 2001 and of the direct CP violation in 2004 thanks to the success of PEP-II and KEKB e+e- asymmetric B Factories operating at the center of mass energy corresponding to the mass of the Y(4s). With the two B Factories taking data, the Unitarity Triangle is now beginning to be overconstrained by improving the measurements of the sides and now also of the angles alpha, and gamma. We are also in presence of the very intriguing results about the measurements of sin(2 beta) in the time dependent analysis of decay channels via penguin loops, where b --> s sbar s and b --> s dbar d. Tau physics, in particular LFV search, as well as charm and ISR physics are important parts of the scientific program of a SuperB Factory. The physics case together with possible scenarios for the high luminosity SuperB Factory based on the concepts of the Linear Collider and the related experimental issues are discussed.Comment: 22 pages, 22 figures, INFN Roadmap Repor

Genetic Deletion of Sost or Pharmacological Inhibition of Sclerostin Prevent Multiple Myeloma-induced Bone Disease without Affecting Tumor Growth

Multiple myeloma (MM) causes lytic bone lesions due to increased bone resorption and concomitant marked suppression of bone formation. Sclerostin (Scl) levels, an osteocyte-derived inhibitor of Wnt/β-catenin signaling, are elevated in MM patient sera and are increased in osteocytes in MM-bearing mice. We show here that genetic deletion of Sost, the gene encoding Scl, prevented MM-induced bone disease in an immune-deficient mouse model of early MM, and that administration of anti-Scl antibody (Scl-Ab) increased bone mass and decreases osteolysis in immune-competent mice with established MM. Sost/Scl inhibition increased osteoblast numbers, stimulated new bone formation and decreased osteoclast number in MM-colonized bone. Further, Sost/Scl inhibition did not affect tumor growth in vivo or anti-myeloma drug efficacy in vitro. These results identify the osteocyte as a major contributor to the deleterious effects of MM in bone and osteocyte-derived Scl as a promising target for the treatment of established MM-induced bone disease. Further, Scl did not interfere with efficacy of chemotherapy for MM suggesting that combined treatment with anti-myeloma drugs and Scl-Ab should effectively control MM growth and bone disease, providing new avenues to effectively control MM and bone disease in patients with active MM

Recruitment, augmentation and apoptosis of rat osteoclasts in 1,25-(OH)2D3 response to short-term treatment with 1,25-dihydroxyvitamin D3in vivo

Background Although much is known about the regulation of osteoclast (OC) formation and activity, little is known about OC senescence. In particular, the fate of of OC seen after 1,25-(OH)2D3 administration in vivo is unclear. There is evidence that the normal fate of OC is to undergo apoptosis (programmed cell death). We have investigated the effect of short-term application of high dose 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on OC apoptosis in an experimental rat model. Methods OC recruitment, augmentation and apoptosis was visualised and quantitated by staining histochemically for tartrate resistant acid phosphatase (TRAP), double staining for TRAP/ED1 or TRAP/DAPI, in situ DNA fragmentation end labelling and histomorphometric analysis. Results Short-term treatment with high-dose 1,25-(OH)2D3 increased the recruitment of OC precursors in the bone marrow resulting in a short-lived increase in OC numbers. This was rapidly followed by an increase in the number of apoptotic OC and their subsequent removal. The response of OC to 1,25-(OH)2D3 treatment was dose and site dependent; higher doses producing stronger, more rapid responses and the response in the tibiae being consistently stronger and more rapid than in the vertebrae. Conclusions This study demonstrates that (1) after recruitment, OC are removed from the resorption site by apoptosis (2) the combined use of TRAP and ED1 can be used to identify OC and their precursors in vivo (3) double staining for TRAP and DAPI or in situ DNA fragmentation end labelling can be used to identify apoptotic OC in vivo

Brown dwarf census with the Dark Energy Survey year 3 data and the thin disc scale height of early L types

27 pages, 18 figuresIn this paper we present a catalogue of 11 745 brown dwarfs with spectral types ranging from L0 to T9, photometrically classified using data from the Dark Energy Survey (DES) year 3 release matched to the Vista Hemisphere Survey (VHS) DR3 and Wide-field Infrared Survey Explorer (WISE) data, covering ≈2400 deg2 up to iAB = 22. The classification method follows the same phototype method previously applied to SDSS-UKIDSS-WISE data. The most significant difference comes from the use of DES data instead of SDSS, which allow us to classify almost an order of magnitude more brown dwarfs than any previous search and reaching distances beyond 400 pc for the earliest types. Next, we also present and validate the GalmodBD simulation, which produces brown dwarf number counts as a function of structural parameters with realistic photometric properties of a given survey. We use this simulation to estimate the completeness and purity of our photometric LT catalogue down to iAB = 22, as well as to compare to the observed number of LT types. We put constraints on the thin disc scale height for the early L (L0–L3) population to be around 450 pc, in agreement with previous findings. For completeness, we also publish in a separate table a catalogue of 20 863 M dwarfs that passed our colour cut with spectral types greater than M6. Both the LT and the late M catalogues are found at DES release page https://des.ncsa.illinois.edu/releases/other/y3-mlt.Peer reviewedFinal Published versio

The Discovery Potential of a Super B Factory

The Proceedings of the 2003 SLAC Workshops on flavor physics with a high luminosity asymmetric e+e- collider. The sensitivity of flavor physics to physics beyond the Standard Model is addressed in detail, in the context of the improvement of experimental measurements and theoretical calculations.Comment: 476 pages. Printed copies may be obtained by request to [email protected] . arXiv admin note: v2 appears to be identical to v

Bidirectional Notch signaling and osteocyte-derived factors in the bone marrow microenvironment promote tumor cell proliferation and bone destruction in multiple myeloma

In multiple myeloma, an overabundance of monoclonal plasma cells in the bone marrow induces localized osteolytic lesions that rarely heal due to increased bone resorption and suppressed bone formation. Matrix-embedded osteocytes comprise more than 95% of bone cells and are major regulators of osteoclast and osteoblast activity, but their contribution to multiple myeloma growth and bone disease is unknown. Here, we report that osteocytes in a mouse model of human MM physically interact with multiple myeloma cells in vivo, undergo caspase-3-dependent apoptosis, and express higher RANKL (TNFSF11) and sclerostin levels than osteocytes in control mice. Mechanistic studies revealed that osteocyte apoptosis was initiated by multiple myeloma cell-mediated activation of Notch signaling and was further amplified by multiple myeloma cell-secreted TNF. The induction of apoptosis increased osteocytic Rankl expression, the osteocytic Rankl/Opg (TNFRSF11B) ratio, and the ability of osteocytes to attract osteoclast precursors to induce local bone resorption. Furthermore, osteocytes in contact with multiple myeloma cells expressed high levels of Sost/sclerostin, leading to a reduction in Wnt signaling and subsequent inhibition of osteoblast differentiation. Importantly, direct contact between osteocytes and multiple myeloma cells reciprocally activated Notch signaling and increased Notch receptor expression, particularly Notch3 and 4, stimulating multiple myeloma cell growth. These studies reveal a previously unknown role for bidirectional Notch signaling that enhances MM growth and bone disease, suggesting that targeting osteocyte-multiple myeloma cell interactions through specific Notch receptor blockade may represent a promising treatment strategy in multiple myeloma

Astrometric calibration and performance of the Dark Energy Camera

We characterize the ability of the Dark Energy Camera (DECam) to perform relative astrometry across its 500~Mpix, 3 deg^2 science field of view, and across 4 years of operation. This is done using internal comparisons of ~4x10^7 measurements of high-S/N stellar images obtained in repeat visits to fields of moderate stellar density, with the telescope dithered to move the sources around the array. An empirical astrometric model includes terms for: optical distortions; stray electric fields in the CCD detectors; chromatic terms in the instrumental and atmospheric optics; shifts in CCD relative positions of up to ~10 um when the DECam temperature cycles; and low-order distortions to each exposure from changes in atmospheric refraction and telescope alignment. Errors in this astrometric model are dominated by stochastic variations with typical amplitudes of 10-30 mas (in a 30 s exposure) and 5-10 arcmin coherence length, plausibly attributed to Kolmogorov-spectrum atmospheric turbulence. The size of these atmospheric distortions is not closely related to the seeing. Given an astrometric reference catalog at density ~0.7 arcmin^{-2}, e.g. from Gaia, the typical atmospheric distortions can be interpolated to 7 mas RMS accuracy (for 30 s exposures) with 1 arcmin coherence length for residual errors. Remaining detectable error contributors are 2-4 mas RMS from unmodelled stray electric fields in the devices, and another 2-4 mas RMS from focal plane shifts between camera thermal cycles. Thus the astrometric solution for a single DECam exposure is accurate to 3-6 mas (0.02 pixels, or 300 nm) on the focal plane, plus the stochastic atmospheric distortion.Comment: Submitted to PAS