Targeting self-renewal pathways in myeloid malignancies

A fundamental property of hematopoietic stem cells (HSCs) is the ability to self-renew. This is a complex process involving multiple signal transduction cascades which control the fine balance between self-renewal and differentiation through transcriptional networks. Key activators/regulators of self-renewal include chemokines, cytokines and morphogens which are expressed in the bone marrow niche, either in a paracrine or autocrine fashion, and modulate stem cell behaviour. Increasing evidence suggests that the downstream signaling pathways induced by these ligands converge at multiple levels providing a degree of redundancy in steady state hematopoiesis. Here we will focus on how these pathways cross-talk to regulate HSC self-renewal highlighting potential therapeutic windows which could be targeted to prevent leukemic stem cell self-renewal in myeloid malignancies

Σ−p\Sigma^- p emission rates in K−K^- absorptions at rest on 6^6Li, 7^7Li, 9^{9}Be, 13^{13}C and 16^{16}O

An experimental study of the $K^-_{stop}A\rightarrow \Sigma^- p A'$ reaction on $A=^6$Li, $^7$Li, $^9$Be, $^{13}$C and $^{16}$O $p$-shell nuclei is presented. The data were collected by the FINUDA spectrometer operating at the DA$\Phi$NE $\phi$-factory (LNF-INFN, Italy). Emission rates for the reaction in the mentioned nuclei are measured and compared with the few existing data. The spectra of several observables are discussed; indications of Quasi-Free absorptions by a $(np)$ pair embedded in the $A$ nucleus can be obtained from the study of the missing mass distributions.Comment: Version accepted by PR

A study of the proton spectra following the capture of K−K^- in 6^6Li and 12^{12}C with FINUDA

Momenta spectra of protons emitted following the capture of $K^-$ in $^6$Li and $^{12}$C have been measured with 1% resolution. The $^{12}$C spectrum is smooth whereas for $^6$Li a well defined peak appears at about 500 MeV/$c$. The first observation of a structure in this region was identified as a strange tribaryon or, possibly, a $\bar K$-nuclear state. The peak is correlated with a $\pi^-$ coming from $\Sigma^-$ decay in flight, selected by setting momenta larger than 275 MeV/$c$. The $\Sigma^-$ could be produced, together with a 500 MeV/$c$ proton, by the capture of a $K^-$ in a deuteron-cluster substructure of the $^6$Li nucleus. The capture rate for such a reaction is (1.62\pm 0.23_{stat} ^{+0.71}_{-0.44}(sys))%/K^-_{stop}, in agreement with the existing observations on $^4$He targets and with the hypothesis that the $^6$Li nucleus can be interpreted as a $(d+\alpha)$ cluster.Comment: 21 pages, 10 figures. Accepted for publication in NP

Production of Λ6^{6}_{\Lambda}H and Λ7^{7}_{\Lambda}H with the (Kstop−^{-}_{stop},π+\pi^+) reaction

The production of neutron rich $\Lambda$-hypernuclei via the ($K^-_stop$,$\pi^+$) reaction has been studied using data collected with the FINUDA spectrometer at the DA$\Phi$NE $\phi$-factory (LNF). The analysis of the inclusive $\pi^+$ momentum spectra is presented and an upper limit for the production of $^6_\Lambda$H and $^7_\Lambda$H from $^6$Li and $^7$Li, is assessed for the first time.Comment: 11 pages, 3 figures. Accepted for publication in PL

Correlated Λd\Lambda d pairs from the Kstop−A→ΛdA′K^{-}_{stop} A \to \Lambda d A' reaction

Correlated $\Lambda d$ pairs emitted after the absorption of negative kaons at rest $K^{-}_{stop}A\to \Lambda d A'$ in light nuclei $^6Li$ and $^{12}C$ are studied. $\Lambda$-hyperons and deuterons are found to be preferentially emitted in opposite directions. The $\Lambda d$ invariant mass spectrum of $^6Li$ shows a bump whose mass is 3251$\pm$6 MeV/c$^2$. The bump mass (binding energy), width and yield are reported. The appearance of a bump is discussed in the realm of the [$\bar{K}3N$] clustering process in nuclei. The experiment was performed with the FINUDA spectrometer at DA$\Phi$NE (LNF).Comment: 13 pages, 5 figures, accepted for publication in Phys. Lett.

Proton spectra from Non-Mesonic Weak Decay of p-shell Lambda-Hypernuclei and evidence for the two-nucleon induced process

New spectra from the FINUDA experiment of the Non Mesonic Weak Decay (NMWD) proton kinetic energy for 9(Lambda)Be, 11(Lambda)B, 12(Lambda)C, 13(Lambda)C, 15 (Lambda)N and 16(Lambda)O are presented and discussed along with the published data on 5(Lambda)He and 7(Lambda)Li. Exploiting the large mass number range and the low energy threshold (15 MeV) for the proton detection of FINUDA, an evaluation of both Final State Interactions (FSI) and the two nucleon induced NMWD contributions to the decay process has been done. Based on this evaluation, a linear dependence of FSI on the hypernuclear mass number A is found and for the two nucleon stimulated decay rate the experimental value of Gamma2/Gammap=0.43+-0.25 is determined for the first time. A value for the two nucleon stimulated decay rate to the total decay rate Gamma2/GammaNMWD=0.24+-0.10 is also extracted.Comment: 11 pages and 2 figure

Hypernuclear spectroscopy with K−^- at rest on 7^7Li, 9^9Be, 13^{13}C and 16^{16}O

The FINUDA experiment collected data to study the production of hypernuclei on different nuclear targets. The hypernucleus formation occurred through the strangeness-exchange reaction $K^-_{stop} + \; ^AZ \rightarrow \; ^A_{\Lambda}Z + \pi^-$. From the analysis of the momentum of the emerging $\pi^-$, binding energies and formation probabilities of $^7_{\Lambda}$Li, $^9_{\Lambda}$Be, $^{13}_{\Lambda}$C and $^{16}_{\Lambda}$O have been measured and are here presented. The behavior of the formation probability as a function of the atomic mass number A is also discussed.Comment: Accepted for publication in PL

Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets

This document is the Technical Design Report covering the two large spectrometer magnets of the PANDA detector set-up. It shows the conceptual design of the magnets and their anticipated performance. It precedes the tender and procurement of the magnets and, hence, is subject to possible modifications arising during this process.Comment: 10 pages, 14MB, accepted by FAIR STI in May 2009, editors: Inti Lehmann (chair), Andrea Bersani, Yuri Lobanov, Jost Luehning, Jerzy Smyrski, Technical Coordiantor: Lars Schmitt, Bernd Lewandowski (deputy), Spokespersons: Ulrich Wiedner, Paola Gianotti (deputy