The Notch pathway drives the ability of the bone marrow niche to promote RNA editing in multiple myeloma

Multiple myeloma (MM) is the second most frequently diagnosed hematological malignancy, and despite all the therapeutic advances it remains incurable due to the development of drug resistance. Recently, RNA editing has emerged as one of the important mechanisms that determines expression variability and therefore may be involved in the development of resistance to standard therapy. This process is mediated by adenosine deaminase acting on RNA (ADAR) enzymes that convert adenosines to inosines (A-->I editing) in double-stranded RNA (dsRNA) substrates. We hypothesize that ADAR1 activation in MM cells may be promoted by the normal cells of the bone marrow (BM) niche through the release of pro-tumor factor controlled by the oncogenic Notch pathway. Indeed, Notch is known to be hyperactivated in myeloma and it is crucial for the pathologic crosstalk between tumor cells and the surrounding BM microenvironment. Aim of this work was to investigate how the Notch pathway contributes to the ability of the BM microenvironment stromal cells on their ability to boost RNA editing and drug resistance in MM, in order to provide the rationale for a Notch-directed therapy that may allow to inhibit the progression of this disease

Phenomenology of Supersymmetric Theories with and without R-Parity

We review supersymmetry models with and without R-parity. After briefly describing the Minimal Supersymetric Standard Model and its particle content we move to models where R-parity is broken, either spontaneously or explicitly. In this last case we consider the situation where R-parity is broken via bilinear terms in the superpotential. The radiative breaking of these models is described in the context of $b$--$\tau$ and $b$--$\tau$--$t$ unification. Finally we review the phenomenology of these R-parity violating models.Comment: 9 pages, 5 Figures in Postscript. Talk given at the EuroConference on Frontiers in Particle Astrophysics and Cosmology, San Feliu de Guixols, Spain, 30 September - 5 October, 200

Lepton Flavor Violating Processes and Muon g-2 in Minimal Supersymmetric SO(10) Model

In the recently proposed minimal supersymmetric SO(10) model, the neutrino Dirac Yukawa coupling matrix, together with all the other fermion mass matrices, is completely determined once free parameters in the model are appropriately fixed so as to accommodate the recent neutrino oscillation data. Using this unambiguous neutrino Dirac Yukawa couplings, we calculate the lepton flavor violating (LFV) processes and the muon g-2 assuming the minimal supergravity scenario. The resultant rates of the LFV processes are found to be large enough to well exceed the proposed future experimental bound, while the magnitude of the muon g-2 can be within the recent result by Brookhaven E821 experiment. Furthermore, we find that there exists a parameter region which can simultaneously realize the neutralino cold dark matter abundance consistent with the recent WMAP data.Comment: 18 pages, 10 figures. The version to be published in Phys. Rev.

Composite quarks and leptons in higher space-time dimensions

A new approach towards the composite structure of quarks and leptons in the context of the higher dimensional unified theories is proposed. Owing to the certain strong dynamics, much like an ordinary QCD, every possible vectorlike multiplets of composites appear in higher dimensional bulk space-time, however, through a proper Sherk-Schwarz compactification only chiral set of composite quarks and leptons survive as the massless states in four dimensions. In this scenario restrictions related with the 't Hooft's anomaly matching condition are turned out to be avoided and, as a result, the composite models look rather simple and economic. We demonstrate our approach by an explicit construction of model of preons and their composites unified in the supersymmetric SU(5) GUT in five space-time dimensions. The model predicts exactly three families of the composite quarks and leptons being the triplets of the chiral horizontal symmetry SU(3)_h which automatically appears in the composite spectrum when going to ordinary four dimensions.Comment: 13 pages, tcilatex, no figures, v2 - misprints correcte

Model Independent Higgs Boson Mass Limits at LEP

We derive model-independent constraints on Higgs mass and couplings from associated signals for higher masses, accessible at LEP2. This work is motivated by the fact that, in many extensions of the standard model, the Higgs boson can have substantial "invisible" decay modes, for example, into light or massless weakly interacting Goldstone bosons associated to the spontaneous violation of lepton number below the weak scale.Comment: FTUV/93-19, 13 pag + 2 figures(not included but available upon request), Late

Charged lepton Flavor Violation in Supersymmetry with Bilinear R-Parity Violation

The simplest unified extension of the Minimal Supersymmetric Standard Model with bi-linear R-parity violation naturally predicts a hierarchical neutrino mass spectrum, suitable to explain atmospheric and solar neutrino fluxes. We study whether the individual violation of the lepton numbers L_{e,mu,tau} in the charged sector can lead to measurable rates for BR(mu->e gamma)and $BR(tau-> mu gamma). We find that some of the R-parity violating terms that are compatible with the observed atmospheric neutrino oscillations could lead to rates for mu->e gamma measurable in projected experiments. However, the Delta m^2_{12} obtained for those parameters is too high to be compatible with the solar neutrino data, excluding therefore the possibility of having measurable rates for mu->e gamma in the model.Comment: 29 pages, 8 figures. Constraint from solar neutrino data included, conclusions changed respect v

A scheme with two large extra dimensions confronted with neutrino physics

We investigate a particle physics model in a six-dimensional spacetime, where two extra dimensions form a torus. Particles with Standard Model charges are confined by interactions with a scalar field to four four-dimensional branes, two vortices accommodating ordinary type fermions and two antivortices accommodating mirror fermions. We investigate the phenomenological implications of this multibrane structure by confronting the model with neutrino physics data.Comment: LATEX, 24 pages, 9 figures, minor changes in the tex