Unexorcized ghost in DGP brane world

The braneworld model of Dvali-Gabadadze-Porrati realizes the self-accelerating universe. However, it is known that this cosmological solution contains a spin-2 ghost. We study the possibility of avoiding the appearance of the ghost by slightly modifying the model, introducing the second brane. First we consider a simple model without stabilization of the separation of the brane. By changing the separation between the branes, we find we can erase the spin-2 ghost. However, this can be done only at the expense of the appearance of a spin-0 ghost instead. We discuss why these two different types of ghosts are correlated. Then, we examine a model with stabilization of the brane separation. Even in this case, we find that the correlation between spin-0 and spin-2 ghosts remains. As a result we find we cannot avoid the appearance of ghost by two-branes model.Comment: 19 pages, 1 figur

Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer

Background: Defects in BRCA1, BRCA2, and other members of the homologous recombination pathway have potential therapeutic relevance when used to support agents that introduce or exploit double-stranded DNA breaks. This study examines the association between homologous recombination defects and genomic patterns of loss of heterozygosity (LOH). Methods: Ovarian tumours from two independent data sets were characterised for defects in BRCA1,BRCA2, and RAD51C, and LOH profiles were generated. Publically available data were downloaded for a third independent data set. The same analyses were performed on 57 cancer cell lines. Results: Loss of heterozygosity regions of intermediate size were observed more frequently in tumours with defective BRCA1 or BRCA2 (P=10−11). The homologous recombination deficiency (HRD) score was defined as the number of these regions observed in a tumour sample. The association between HRD score and BRCA deficiency was validated in two independent ovarian cancer data sets (P=10−5 and 10−29), and identified breast and pancreatic cell lines with BRCA defects. Conclusion: The HRD score appears capable of detecting homologous recombination defects regardless of aetiology or mechanism. This score could facilitate the use of PARP inhibitors and platinum in breast, ovarian, and other cancers

Computing earnings per share: unofficial accounting interpretations of APB Opinion no. 15

https://egrove.olemiss.edu/aicpa_guides/1601/thumbnail.jp

Resistance Mechanisms for the Bruton\u27s Tyrosine Kinase Inhibitor Ibrutinib

BACKGROUND Ibrutinib is an irreversible inhibitor of Bruton\u27s tyrosine kinase (BTK) and is effective in chronic lymphocytic leukemia (CLL). Resistance to irreversible kinase inhibitors and resistance associated with BTK inhibition have not been characterized. Although only a small proportion of patients have had a relapse during ibrutinib therapy, an understanding of resistance mechanisms is important. We evaluated patients with relapsed disease to identify mutations that may mediate ibrutinib resistance. METHODS We performed whole-exome sequencing at baseline and the time of relapse on samples from six patients with acquired resistance to ibrutinib therapy. We then performed functional analysis of identified mutations. In addition, we performed Ion Torrent sequencing for identified resistance mutations on samples from nine patients with prolonged lymphocytosis. RESULTS We identified a cysteine-to-serine mutation in BTK at the binding site of ibrutinib in five patients and identified three distinct mutations in PLC gamma 2 in two patients. Functional analysis showed that the C481S mutation of BTK results in a protein that is only reversibly inhibited by ibrutinib. The R665W and L845F mutations in PLC gamma 2 are both potentially gain-of-function mutations that lead to autonomous B-cell-receptor activity. These mutations were not found in any of the patients with prolonged lymphocytosis who were taking ibrutinib. CONCLUSIONS Resistance to the irreversible BTK inhibitor ibrutinib often involves mutation of a cysteine residue where ibrutinib binding occurs. This finding, combined with two additional mutations in PLC gamma 2 that are immediately downstream of BTK, underscores the importance of the B-cell-receptor pathway in the mechanism of action of ibrutinib in CLL

Urban seismic risk assessment using the Disruption Index: the case of the volcanic region of Mt. Etna (Italy)

This paper presents the ongoing activities for the assessment of the urban seismic risk at Mt. Etna volcano using the “Disruption Index” approach. We use updated information on the historic main seismicity, seismogenic faults and intensity attenuation that in a recent research project produced probabilistic seismic hazard maps and scenarios expressed in terms of macroseismic intensity. To apply the Disruption Index at Etna, we consider a probabilistic approach for seismic hazard evaluation based jointly on macroseismic fields and fault parameters. For information on the urban scale vulnerability, we use a GIS to organise data relating to buildings and network systems (e.g. typologies, schools, strategic structures, lifelines) related to the municipalities more exposed to seismic risk. The convolution of ground motion and vulnerability/ impact is based on a Monte Carlo simulation. We present here some preliminary results on the identification of nodes that are responsible for major disruption in urban systems.Co-financed by the EU - Civil Protection Financial Instrument, in the framework the European project ”Urban disaster Prevention Strategies using MAcroseismic Fields and FAult Sources (Acronym: UPStrat-MAFA, Grant Agreement N. 23031/2011/613486/SUB/A5). http://ec.europa.eu/echo/funding/cp_projects2011_en.htmPublishedLisbon - Portugal4.1. Metodologie sismologiche per l'ingegneria sismicaope

Elliptic flow of charged particles in Pb-Pb collisions at 2.76 TeV

We report the first measurement of charged particle elliptic flow in Pb-Pb collisions at 2.76 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurement is performed in the central pseudorapidity region (|$\eta$|<0.8) and transverse momentum range 0.2< $p_{\rm T}$< 5.0 GeV/$c$. The elliptic flow signal v$_2$, measured using the 4-particle correlation method, averaged over transverse momentum and pseudorapidity is 0.087 $\pm$ 0.002 (stat) $\pm$ 0.004 (syst) in the 40-50% centrality class. The differential elliptic flow v$_2(p_{\rm T})$ reaches a maximum of 0.2 near $p_{\rm T}$ = 3 GeV/$c$. Compared to RHIC Au-Au collisions at 200 GeV, the elliptic flow increases by about 30%. Some hydrodynamic model predictions which include viscous corrections are in agreement with the observed increase.Comment: 10 pages, 4 captioned figures, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/389

Identification of the TeV Gamma-ray Source ARGO J2031+4157 with the Cygnus Cocoon

The extended TeV gamma-ray source ARGO J2031+4157 (or MGRO J2031+41) is positionally consistent with the Cygnus Cocoon discovered by $Fermi$-LAT at GeV energies in the Cygnus superbubble. Reanalyzing the ARGO-YBJ data collected from November 2007 to January 2013, the angular extension and energy spectrum of ARGO J2031+4157 are evaluated. After subtracting the contribution of the overlapping TeV sources, the ARGO-YBJ excess map is fitted with a two-dimensional Gaussian function in a square region of $10^{\circ}\times 10^{\circ}$, finding a source extension $\sigma_{ext}$= 1$^{\circ}$.8$\pm$0$^{\circ}$.5. The observed differential energy spectrum is $dN/dE =(2.5\pm0.4) \times 10^{-11}(E/1 TeV)^{-2.6\pm0.3}$ photons cm$^{-2}$ s$^{-1}$ TeV$^{-1}$, in the energy range 0.2-10 TeV. The angular extension is consistent with that of the Cygnus Cocoon as measured by $Fermi$-LAT, and the spectrum also shows a good connection with the one measured in the 1-100 GeV energy range. These features suggest to identify ARGO J2031+4157 as the counterpart of the Cygnus Cocoon at TeV energies. The Cygnus Cocoon, located in the star-forming region of Cygnus X, is interpreted as a cocoon of freshly accelerated cosmic rays related to the Cygnus superbubble. The spectral similarity with Supernova Remnants indicates that the particle acceleration inside a superbubble is similar to that in a SNR. The spectral measurements from 1 GeV to 10 TeV allows for the first time to determine the possible spectrum slope of the underlying particle distribution. A hadronic model is adopted to explain the spectral energy distribution.Comment: 16 pages, 3 figures, has been accepted by ApJ for publicatio

Evaluation of preindustrial to present-day black carbon and its albedo forcing from ACCMIP (Atmospheric Chemistry and Climate Model Intercomparison Project)

As part of the Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP), we evaluate the historical black carbon (BC) aerosols simulated by 8 ACCMIP models against observations including 12 ice core records, long-term surface mass concentrations and recent Arctic BC snowpack measurements. We also estimate BC albedo forcing by performing additional simulations using offline models with prescribed meteorology from 1996–2000. We evaluated the vertical profile of BC snow concentrations from these offline simulations using the recent BC snowpack measurements. Despite using the same BC emissions, the global BC burden differs by approximately a factor of 3 among models due to differences in aerosol removal parameterizations and simulated meteorology: 34 Gg to 103 Gg in 1850 and 82 Gg to 315 Gg in 2000. However, the global BC burden from preindustrial to present-day increases by 2.5–3 times with little variation among models, roughly matching the 2.5-fold increase in total BC emissions during the same period. We find a large divergence among models at both Northern Hemisphere (NH) and Southern Hemisphere (SH) high latitude regions for BC burden and at SH high latitude regions for deposition fluxes. The ACCMIP simulations match the observed BC surface mass concentrations well in Europe and North America except at Jungfraujoch and Ispra. However, the models fail to predict the Arctic BC seasonality due to severe underestimations during winter and spring. The simulated vertically resolved BC snow concentrations are, on average, within a factor of 2–3 of the BC snowpack measurements except for Greenland and the Arctic Ocean. For the ice core evaluation, models tend to capture both the observed temporal trends and the magnitudes well at Greenland sites. However, models fail to predict the decreasing trend of BC depositions/ice-core concentrations from the 1950s to the 1970s in most Tibetan Plateau ice cores. The distinct temporal trend at the Tibetan Plateau ice cores indicates a strong influence from Western Europe, but the modeled BC increases in that period are consistent with the emission changes in Eastern Europe, the Middle East, South and East Asia. At the Alps site, the simulated BC suggests a strong influence from Europe, which agrees with the Alps ice core observations. Models successfully simulate higher BC concentrations observed at Zuoqiupu during the non-monsoon season than monsoon season, but models underpredict BC in both seasons. Despite a large divergence in BC deposition at two Antarctic ice core sites, models are able to capture the relative increase from preindustrial to present-day seen in the ice cores. In 2000 relative to 1850, globally annually averaged BC surface albedo forcing from the offline simulations ranges from 0.014 to 0.019 W m−2 among the ACCMIP models. Comparing offline and online BC albedo forcings computed by some of the same models, we find that the global annual mean can vary by up to a factor of two because of different aerosol models or different BC-snow parameterizations and snow cover. The spatial distributions of the offline BC albedo forcing in 2000 show especially high BC forcing (i.e. over 0.1 W m−2) over Manchuria, Karakoram, and most of the Former USSR. Models predict the highest global annual mean BC forcing in 1980 rather than 2000, mostly driven by the high fossil fuel and biofuel emissions in the Former USSR in 1980