A novel model of tumour formation in NF1

Neurofibromatosis type 1 (NF1) is a common genetic disorder that predisposes to the development of heterogeneous tumours of Schwann cell origin, termed neurofibromas. Neurofibromas are thought to arise from a combination of genetic events – loss of the Ras-GAP neurofibromin in the Schwann cell lineage – and microenvironmental cues. Schwann cells are specialised cells that ensheath and myelinate the axons in the peripheral nervous system (PNS). In the adult they are present in a quiescent state, however following damage to the PNS they have a remarkable ability to regenerate. Distal to the site of injury, Schwann cells dedifferentiate to a progenitor-like state, in which they contribute to nerve repair by recruiting a robust inflammatory response and helping axons return to their targets. Work from our laboratory has shown that activation of the Ras/Raf/ERK pathway plays a central role in driving the switch in Schwann cell state from a fully differentiated to a proliferating, “progenitor-like” cell. Crucially, neurofibromas resemble injured nerves in that they are composed of a mixture of inflammatory cells and Schwann cells that are found dedifferentiated and dissociated from axons, suggesting that deregulation of Ras/ERK may trigger tumourigenic events. In this thesis I present work on how the Ras/Raf/ERK pathway may be regulated in Schwann cells. I show that the phosphatase MKP3 may be involved in controlling the levels of ERK activity in Schwann cells during differentiation and following nerve injury. I also describe a new model for neurofibroma formation. Using transgenic mice I show that Nf1 loss in adult, myelinating Schwann cells has no effect on peripheral nerves and does not induce tumourigenesis. However, when coupled with an injury, the mice developed tumours at a high frequency. Furthermore, I show that in the absence of Nf1, ERK signalling is deregulated upon injury, implicating this pathway in the tumour formation. This may have therapeutic relevance, which is currently being tested in our animal model. In addition, we observed that tumours only arise at the wound site, despite Schwann cells dedifferentiating along the length of the nerve. This strongly implies that the microenvironment is a crucial player in the outcome of Nf1 loss and reveals this new animal model as a promising system to further dissect molecular events involved in tumourigenesis

U-Pb dating of the Paimán Granite, Sierra de Paimán, Chilecito, La Rioja

Se da a conocer los resultados de la datación U-Pb convencional en circones del Granito Paimán, uno de los componentes del flanco oriental del Sistema de Famatina. Fueron analizadas cinco fracciones de cristales de circón de un granito porfiroide, característico de la unidad. Los resultados son coherentes entre sí y proveen una edad de 477,6 ± 4,1 Ma, que ubican la edad de cristalización y emplazamiento en el Ordovícico Temprano. La datación corrobora su asignación a la fase magmática oclóyica y específicamente al cinturón famatiniano. El análisis del presente y otros datos U-Pb previos de otras rocas graníticas del cinturón famatiniano entre los 28º y 33º S, permiten delimitar un estrecho lapso (alrededor de 20 Ma) de actividad ígnea, sin poderse determinar ninguna polaridad en la producción del magmatismo.Conventional U-Pb zircon ages for the Paimán Granite are presented. The magmatic unit crops out in the eastern border of the Famatina range. Five zircon fractions were analysed from a coarse porphyritic granitoid, the major component in the Paimán-Chilecito area. Results are concordant for the five fractions and the mean 206Pb/238U age of 477.6 ± 4.1 Ma is Early Ordovician. This age confirms that the Paimán Granite is part of the Ocloyic magmatic phase and Famatinian belt. The present age together with the previous U-Pb ages from granitoids of the Famatinian belt between 28º and 33º S suggest that the magmatic activity occurred over a short time span of about 20 Ma, following no noticeable internal polarity within the belt.Centro de Investigaciones Geológica

U-Pb dating of the Paimán Granite, Sierra de Paimán, Chilecito, La Rioja

Se da a conocer los resultados de la datación U-Pb convencional en circones del Granito Paimán, uno de los componentes del flanco oriental del Sistema de Famatina. Fueron analizadas cinco fracciones de cristales de circón de un granito porfiroide, característico de la unidad. Los resultados son coherentes entre sí y proveen una edad de 477,6 ± 4,1 Ma, que ubican la edad de cristalización y emplazamiento en el Ordovícico Temprano. La datación corrobora su asignación a la fase magmática oclóyica y específicamente al cinturón famatiniano. El análisis del presente y otros datos U-Pb previos de otras rocas graníticas del cinturón famatiniano entre los 28º y 33º S, permiten delimitar un estrecho lapso (alrededor de 20 Ma) de actividad ígnea, sin poderse determinar ninguna polaridad en la producción del magmatismo.Conventional U-Pb zircon ages for the Paimán Granite are presented. The magmatic unit crops out in the eastern border of the Famatina range. Five zircon fractions were analysed from a coarse porphyritic granitoid, the major component in the Paimán-Chilecito area. Results are concordant for the five fractions and the mean 206Pb/238U age of 477.6 ± 4.1 Ma is Early Ordovician. This age confirms that the Paimán Granite is part of the Ocloyic magmatic phase and Famatinian belt. The present age together with the previous U-Pb ages from granitoids of the Famatinian belt between 28º and 33º S suggest that the magmatic activity occurred over a short time span of about 20 Ma, following no noticeable internal polarity within the belt.Centro de Investigaciones Geológica

U-Pb dating of the Paimán Granite, Sierra de Paimán, Chilecito, La Rioja

Se da a conocer los resultados de la datación U-Pb convencional en circones del Granito Paimán, uno de los componentes del flanco oriental del Sistema de Famatina. Fueron analizadas cinco fracciones de cristales de circón de un granito porfiroide, característico de la unidad. Los resultados son coherentes entre sí y proveen una edad de 477,6 ± 4,1 Ma, que ubican la edad de cristalización y emplazamiento en el Ordovícico Temprano. La datación corrobora su asignación a la fase magmática oclóyica y específicamente al cinturón famatiniano. El análisis del presente y otros datos U-Pb previos de otras rocas graníticas del cinturón famatiniano entre los 28º y 33º S, permiten delimitar un estrecho lapso (alrededor de 20 Ma) de actividad ígnea, sin poderse determinar ninguna polaridad en la producción del magmatismo.Conventional U-Pb zircon ages for the Paimán Granite are presented. The magmatic unit crops out in the eastern border of the Famatina range. Five zircon fractions were analysed from a coarse porphyritic granitoid, the major component in the Paimán-Chilecito area. Results are concordant for the five fractions and the mean 206Pb/238U age of 477.6 ± 4.1 Ma is Early Ordovician. This age confirms that the Paimán Granite is part of the Ocloyic magmatic phase and Famatinian belt. The present age together with the previous U-Pb ages from granitoids of the Famatinian belt between 28º and 33º S suggest that the magmatic activity occurred over a short time span of about 20 Ma, following no noticeable internal polarity within the belt.Centro de Investigaciones Geológica

Distinct incubation for homologous in vitro spermatozoa binding on swine oocytes subjected to different storage conditions

AbstractThe sperm in vitro binding assay in homologous oocytes can be used to estimate the boar fertility potential, but its usefulness may be limited by laboratorial structure and oocytes availability. This study aimed at determining the effect of distinct methods of oocytes conditioning and incubation media for the in vitro penetration (IVP) test. Oocytes used in the IVP test were: fresh and conditioned in PBS (T1); cooled and conditioned in PBS at 5°C for 48h (T2); or stored in ovaries frozen at −20°C (T3). For each treatment, two incubation media were tested at 39°C for 6h: modified TRIS buffer medium (mTBM); or Beltsville Thawing Solution (BTS) extender. The responses of interest were: IVP and polyspermy rates; and the number of penetrating spermatozoa per oocyte. All responses observed with incubation in BTS were inferior to those observed with incubation in mTBM (P<0.0001). When incubation was done in mTBM, none of the responses differed across treatments (P>0.05). However, when incubation was in BTS, all the three responses were superior for T1 than for T2 and T3 (P<0.05). Thus, the IVP test may be conducted with ovaries either cooled or recovered from frozen ovaries with results similar to those observed with fresh oocytes, if incubation is done in mTBM

Solving Fuzzy Job-Shop Scheduling Problems with a Multiobjective Optimizer

International audienceIn real-world manufacturing environments, it is common to face a job-shop scheduling problem (JSP) with uncertainty. Among different sources of uncertainty, processing times uncertainty is the most common. In this paper, we investigate the use of a multiobjective genetic algorithm to address JSPs with uncertain durations. Uncertain durations in a JSP are expressed by means of triangular fuzzy numbers (TFNs). Instead of using expected values as in other work, we consider all vertices of the TFN representing the overall completion time. As a consequence, the proposed approach tries to obtain a schedule that optimizes the three component scheduling problems (corresponding to the lowest, most probable, and largest durations) all at the same time. In order to verify the quality of solutions found by the proposed approach, an experimental study was carried out across different benchmark instances. In all experiments, comparisons with previous approaches that are based on a single-objective genetic algorithm were also performed

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters