Accumulation of driver and passenger mutations during tumor progression

Major efforts to sequence cancer genomes are now occurring throughout the world. Though the emerging data from these studies are illuminating, their reconciliation with epidemiologic and clinical observations poses a major challenge. In the current study, we provide a novel mathematical model that begins to address this challenge. We model tumors as a discrete time branching process that starts with a single driver mutation and proceeds as each new driver mutation leads to a slightly increased rate of clonal expansion. Using the model, we observe tremendous variation in the rate of tumor development - providing an understanding of the heterogeneity in tumor sizes and development times that have been observed by epidemiologists and clinicians. Furthermore, the model provides a simple formula for the number of driver mutations as a function of the total number of mutations in the tumor. Finally, when applied to recent experimental data, the model allows us to calculate, for the first time, the actual selective advantage provided by typical somatic mutations in human tumors in situ. This selective advantage is surprisingly small, 0.005 +- 0.0005, and has major implications for experimental cancer research

Parity Violation in Neutron Resonances in 107,109Ag

Parity nonconservation (PNC) was studied in p-wave resonances in Ag by measuring the helicity dependence of the neutron total cross section. Transmission measurements on natural Ag were performed in the energy range 32 to 422 eV with the time-of-flight method at the Manuel Lujan Neutron Scattering Center at Los Alamos National Laboratory. A total of 15 p-wave neutron resonances were studied in 107Ag and ninep-wave resonances in 109Ag. Statistically significant asymmetries were observed for eight resonances in 107Ag and for four resonances in109Ag. An analysis treating the PNC matrix elements as random variables yields a weak spreading width of Γw=(2.67-1.21+2.65)×10-7 eV for107Ag and Γw=(1.30-0.74+2.49)×10-7 eV for 109Ag

Parity Violation in Neutron Resonances in 115In

Parity nonconservation (PNC) was studied in p-wave resonances in indium by measuring the helicity dependence of the neutron total cross section in the neutron energy range 6.0–316 eV with the time-of-flight method at LANSCE. A total of 36 p-wave neutron resonances were studied in 115In, and statistically significant asymmetries were observed for nine cases. An analysis treating the PNC matrix elements as random variables yields a weak matrix element of M=(0.67-0.12+0.16) meV and a weak spreading width of Γw=(1.30-0.43+0.76)×10-7 eV

Centrality dependence of the expansion dynamics in Pb-Pb collisions at 158 A GeV/c

Two-particle correlation functions of negatively charged hadrons from Pb-Pb collisions at 158 GeV/c per nucleon have been measured by the WA97 experiment at the CERN SPS. A Coulomb correction procedure that assumes an expanding source has been implemented. Within the framework of an expanding thermalized source model the size and dynamical state of the collision fireball at freeze-out have been reconstructed as a function of the centrality of the collision. Less central collisions exhibit a different dynamics than central ones: both transverse and longitudinal expansion velocities are slower, the expansion duration is shorter and the system freezes out showing smaller dimensions and higher temperature.Comment: 22 pages, 11 figures, Te

Trim17, novel E3 ubiquitin-ligase, initiates neuronal apoptosis

Accumulating data indicate that the ubiquitin-proteasome system controls apoptosis by regulating the level and the function of key regulatory proteins. In this study, we identified Trim17, a member of the TRIM/RBCC protein family, as one of the critical E3 ubiquitin ligases involved in the control of neuronal apoptosis upstream of mitochondria. We show that expression of Trim17 is increased both at the mRNA and protein level in several in vitro models of transcription-dependent neuronal apoptosis. Expression of Trim17 is controlled by the PI3K/Akt/GSK3 pathway in cerebellar granule neurons (CGN). Moreover, the Trim17 protein is expressed in vivo, in apoptotic neurons that naturally die during post-natal cerebellar development. Overexpression of active Trim17 in primary CGN was sufficient to induce the intrinsic pathway of apoptosis in survival conditions. This pro-apoptotic effect was abolished in Bax(-/-) neurons and depended on the E3 activity of Trim17 conferred by its RING domain. Furthermore, knock-down of endogenous Trim17 and overexpression of dominant-negative mutants of Trim17 blocked trophic factor withdrawal-induced apoptosis both in CGN and in sympathetic neurons. Collectively, our data are the first to assign a cellular function to Trim17 by showing that its E3 activity is both necessary and sufficient for the initiation of neuronal apoptosis. Cell Death and Differentiation (2010) 17, 1928-1941; doi: 10.1038/cdd.2010.73; published online 18 June 201

Strangeness enhancements at central rapidity in 40 A GeV/c Pb-Pb collisions

Results are presented on neutral kaon, hyperon and antihyperon production in Pb-Pb and p-Be interactions at 40 GeV/c per nucleon. The enhancement pattern follows the same hierarchy as seen in the higher energy data - the enhancement increases with the strangeness content of the hyperons and with the centrality of collision. The centrality dependence of the Pb-Pb yields and enhancements is steeper at 40 than at 158 A GeV/c. The energy dependence of strangeness enhancements at mid-rapidity is discussed.Comment: 15 pages, 10 figures and 3 tables. Presented at International Conference on Strangeness in Quark Matter (SQM2009), Buzios, Rio de Janeiro, Brazil, 27 Sept - 2 Oct 2009. Submitted to J.Phys.G: Nucl.Part.Phys, one reference adde

Rapidity distributions around mid-rapidity of strange particles in Pb-Pb collisions at 158 AA GeV/c

The production at central rapidity of K0s, Lambda, Xi and Omega particles in Pb-Pb collisions at 158 A GeV/c has been measured by the NA57 experiment over a centrality range corresponding to the most central 53% of the inelastic Pb-Pb cross section. In this paper we present the rapidity distribution of each particle in the central rapidity unit as a function of the event centrality. The distributions are analyzed based on hydrodynamical models of the collisions.Comment: 15 pages, 10 figure

New results from the NA57 experiment

We report results from the experiment NA57 at CERN SPS on hyperon production at midrapidity in Pb-Pb collisions at 158 $A$ GeV/$c$ and 40 $A$ GeV/$c$. $\Lambda$, $\Xi$ and $\Omega$ yields are compared with those from the STAR experiment at the higher energy of the BNL RHIC. $\Lambda$, $\Xi$, $\Omega$\ and preliminary $K_S^0$ transverse mass spectra are presented and interpreted within the framework of a hydro-dynamical blast wave model.Comment: 8 pages, 3 figures, contribution to the proceedings of The XXXVIIIth Rencontres de Moriond "QCD and High Energy Hadronic Interactions

Expansion dynamics of Pb-Pb collisions at 40 A GeV/c viewed by negatively charged hadrons

In this paper we present results on transverse mass spectra and Hanbury-Brown and Twiss correlation functions of negatively charged hadrons, which are expected to be mostly negative pions, measured in Pb-Pb collisions at 40 A GeV/c beam momentum. Based on these data, the collision dynamics and the space-time extent of the system at the thermal freeze-out are studied over a centrality range corresponding to the most central 53% of the Pb--Pb inelastic cross section. Comparisons with freeze-out conditions of strange particles and HBT results from other experiments are discussed.Comment: 29 pages, 18 figure

Results on hyperon production from the NA57 experiment

Recent results on hyperon production in Pb--Pb collisions from the NA57 experiment are reported. Strangeness enhancement and the transverse mass spectra properties at 158 GeV per nucleon are described.Comment: submitted to Acta Phys. Hung. A (Heavy Ion Physics