Effects of miRNA-15 and miRNA-16 expression replacement in chronic lymphocytic leukemia : implication for therapy

This work was supported by: Associazione Italiana Ricerca sul Cancro (AIRC) Grant 5 x mille n.9980, (to M.F., F.M. A. N., P.T. and M.N.) ; AIRC I.G. n. 14326 (to M.F.), n.10136 and 16722 (A.N.), n.15426 (to F.F.). AIRC and Fondazione CaRiCal co-financed Multi Unit Regional Grant 2014 n.16695 (to F.M.). Italian Ministry of Health 5x1000 funds (to S.Z. and F.F). A.G R. was supported by Associazione Italiana contro le Leucemie-Linfomi-Mielomi (AIL) Cosenza - Fondazione Amelia Scorza (FAS). S.M. C.M., M.C., L.E., S.B. were supported by AIRC.Peer reviewedPostprin

PREDICTING THE DATE OF FIRST CATCH OF THE CORN EARWORM, HELICOVERPA ZEA, IN CENTRAL U.S.

This paper develops predictive (or correlative) models for the date of first catch of the com earworm, Helicoverpa zea, as a basis for identifying biotic and abiotic factors that influence dispersal and migration. Data described in Goodenough et al. (1988, J. Econ. Entomol.) on the catch of H. zea gathered at over 150 sites predominantly in the central U.S. from 1983 to 1986 are analyzed. The dependent variables, Y1 and Y2, are date of first meaningful catch and date when cumulative catch exceeds 5, respectively; the independent variables are latitude, longitude and elevation of the site. Outstanding among the findings are the following : 1) There is no statistical evidence based on all the data that the slopes of the simple linear regression models of Y2 on latitude differ among the four years. The common slope estimate is 8.11 days/degree, the intercepts differ by as many as 16 days, and the combined model has r2 = 0.69. 2) There is no statistical evidence based on the data in the central U.S. that the partial slopes of the multiple regression models of Y2 on latitude and longitude differ among the four years. The common partial slope estimates are 7.36 and -1.27 days/degree, the intercepts differ by as many as 17 days, and the combined model has R 2= 0.69. Second order terms are not significant . 3) An exploratory analysis using GIS mapping software suggests that elevation is also a significant predictor variable. The suggestion is confirmed in multiple regression models for both Y1 and Y22= 0.71 and 0.72 respectively. The intercepts differ by as many as 20 and 17 days, respectively, over the four years . These results imply that the time of fi!\u27st appearance at any location in the central U.S. could be predicted once the date of first appearance in South Texas is ascertained. They also demonstrate the utility of analyzing residuals using GIS mapping software. Research is in progress to investigate other possible predictor variables including soil moisture, soil temperature and precipitation

Sensor development and readout prototyping for the STAR Pixel detector

The STAR experiment at the Relativistic Heavy Ion Collider (RHIC) is designing a new vertex detector. The purpose of this upgrade detector is to provide high resolution pointing to allow for the direct topological reconstruction of heavy flavor decays such as the D{sup 0} by finding vertices displaced from the collision vertex by greater than 60 microns. We are using Monolithic Active Pixel Sensor (MAPS) as the sensor technology and have a coupled sensor development and readout system plan that leads to a final detector with a <200 {micro}s integration time, 400 M pixels and a coverage of -1 < {eta} < 1. We present our coupled sensor and readout development plan and the status of the prototyping work that has been accomplished

Dielectron Cross Section Measurements in Nucleus-Nucleus Reactions at 1.0 A GeV

We present measured dielectron production cross sections for Ca+Ca, C+C, He+Ca, and d+Ca reactions at 1.0 A GeV. Statistical uncertainties and systematic effects are smaller than in previous DLS nucleus-nucleus data. For pair mass < 0.35 GeV/c2 : 1) the Ca+Ca cross section is larger than the previous DLS measurement and current model results, 2) the mass spectra suggest large contributions from pi0 and eta Dalitz decays, and 3) dsigma/dM is proportional to ApAt. For M > 0.5 GeV/c2 the Ca+Ca to C+C cross section ratio is significantly larger than the ratio of ApAt values.Comment: Submitted to Physical Review Letters. Further analysis information will be posted on our web pages -- http://macdls.lbl.gov Figure 1 has been redrawn to make more legible. Text modified to support redrawn figur

Current gene panels account for nearly all homologous recombination repair-associated multiple-case breast cancer families

It was hypothesized that variants in underexplored homologous recombination repair (HR) genes could explain unsolved multiple-case breast cancer (BC) families. We investigated HR deficiency (HRD)-associated mutational signatures and second hits in tumor DNA from familial BC cases. No candidates genes were associated with HRD in 38 probands previously tested negative with gene panels. We conclude it is unlikely that unknown HRD-associated genes explain a large fraction of unsolved familial BC

Integrative genomic analysis of trisomy 12 abnormality in B-cell chronic lymphocytic leukemia

Background: Flow cytometry allows specific assessment of the expression of ZAP-70, a promising new prognostic factor in B-cell chronic lymphocytic leukemia (B-CLL), but suffers from a lack of multicenter standardization. Design and Methods: An optimized method for direct detection of ZAP-70 in flow cytometry was tested in a multicenter fashion. Adapted for frozen cells, this method includes a normalization step by addition of B cells from a pool of peripheral blood mononuclear cells collected from normal donors. ZAP-70 expression levels were assessed for 153 patients with typical B-cell chronic lymphocytic leukemia chronic lymphocytic leukemia. Results were expressed as the ratio of ZAP-70 mean fluorescence intensity between B-CLL cells and normal B cells. Results: The statistically optimized cut-off of ZAP-70 positivity was a ratio of 1.4. Concordance between ZAP-70 and CD38 expression was 67%. Concordance between the mutational status of IgVH genes and ZAP-70 or CD38 expression was 87% and 65%, respectively. ZAP-70 was significantly expressed in 28%, 54% and 61% of patients with Binet stages A, B and C B-cell chronic lymphocytic leukemia, respectively (p=0.008). The absence of ZAP-70 expression was associated with isolated del(13q14), a cytogenetic abnormality with a good prognosis, while most patients with the del(17p13) poor prognosis cytogenetic marker expressed ZAP-70 (p&lt;10-5). ZAP-70 expression was not related to the other poor prognosis cytogenetic abnormality del(11q22.3) nor to trisomy 12. Conclusions: This new technique provides highly reliable results well correlated with the mutational status of IgVH genes, CD38 expression, Binet stage and cytogenetic abnormalities. This robust discriminative technique appears of particular interest for routine diagnosis and assessment of ZAP-70 expression in large, prospective, multicenter therapeutic trials

Inclusive Dielectron Cross Sections in p+p and p+d Interactions at Beam Energies from 1.04 to 4.88 GeV

Measurements of dielectron production in p+p and p+d collisions with beam kinetic energies from 1.04 to 4.88 GeV are presented. The differential cross section is presented as a function of invariant pair mass, transverse momentum, and rapidity. The shapes of the mass spectra and their evolution with beam energy provide information about the relative importance of the various dielectron production mechanisms in this energy regime. The p+d to p+p ratio of the dielectron yield is also presented as a function of invariant pair mass, transverse momentum, and rapidity. The shapes of the transverse momentum and rapidity spectra from the p+d and p+p systems are found to be similar to one another for each of the beam energies studied. The beam energy dependence of the integrated cross sections is also presented.Comment: 15 pages and 16 figure