Flavor SU(3) analysis of charmless B->PP decays

We perform a global fits to charmless $B \to PP$ decays which independently constrain the $(\bar\rho,\bar\eta)$ vertex of the unitarity triangle. The fitted amplitudes and phase are used to predict the branching ratios and CP asymmetries of all decay modes, including those of the $B_s$ system. Different schemes of SU(3) breaking in decay amplitude sizes are analyzed. The possibility of having a new physics contribution to $K \pi$ decays is also discussed.Comment: 3 pages, 2 figs. Talk given at EPS-HEP07 To appear in the proceedings, Reference adde

B -> K pi Puzzle and New Sources of CP Violation in Supersymmetry

The difference between the CP asymmetries of the $B^0 \to K^+ \pi^-$ and $B^+ \to K^+ \pi^0$ decays has been recently confirmed with an evidence larger than $5\sigma$'s. We discuss it as a possible signal of new physics associated with new (large) CP violation in the electroweak penguin contributions. We propose a supersymmetry breaking scheme where such new sources of CP violation occur in the flavor non-universal trilinear scalar couplings.Comment: 4 pages, 2 figure

Flavor SU(3) analysis of charmless B meson decays to two pseudoscalar mesons

Global fits to charmless B --> PP decays in the framework of flavor SU(3) symmetry are updated and improved without reference to the \sin2\beta measured from the charmonium decay modes. Fit results directly constrain the (\bar\rho,\bar\eta) vertex of the unitarity triangle, and are used to predict the branching ratios and CP asymmetries of all decay modes, including those of the B_s system. Different schemes of SU(3) breaking in decay amplitude sizes are analyzed. The major breaking effect between strangeness-conserving and strangeness-changing decays can be accounted for by including a ratio of decay constants in tree and color-suppressed amplitudes. The possibility of having a new physics contribution to K \pi decays is also examined from the data fitting point of view.Comment: 22 pages and 2 figures; some comments and references added; more references added, version to appear in journa

Charmless B→PPB \to PP decays using flavor SU(3) symmetry

The decays of $B$ mesons to a pair of charmless pseudoscalar ($P$) mesons are analyzed within a framework of flavor SU(3). Symmetry breaking is taken into account in tree ($T$) amplitudes through ratios of decay constants; exact SU(3) is assumed elsewhere. Acceptable fits to $B \to \pi \pi$ and $B \to K \pi$ branching ratios and CP asymmetries are obtained with tree, color-suppressed ($C$), penguin ($P$), and electroweak penguin ($P_{EW}$) amplitudes. Crucial additional terms for describing processes involving $\eta$ and $\eta'$ include a large flavor-singlet penguin amplitude ($S$) as proposed earlier and a penguin amplitude $P_{tu}$ associated with intermediate $t$ and $u$ quarks. For the $B^+ \to \pi^+ \eta'$ mode a term $S_{tu}$ associated with intermediate $t$ and $u$ quarks also may be needed. Values of the weak phase $\gamma$ are obtained consistent with an earlier analysis of $B \to VP$ decays, where $V$ denotes a vector meson, and with other analyses of CKM parameters.Comment: 26 pages, 1 figure. To be submitted to Phys. Rev. D. Reference update

Direct Phenotypical and Functional Dysregulation of Primary Human B Cells by Human Immunodeficiency Virus (HIV) Type 1 In Vitro

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) induces a general dysregulation of immune system. Dysregulation of B cell compartment is generally thought to be induced by HIV-related immune activation and lymphopenia. However, a direct influence of HIV-1 particles on B cells was recently proposed as the third pathway of B cells dysregulation. METHODS/PRINCIPAL FINDINGS: We evaluated the direct and specific consequences of HIV-1 contact on activation, survival, proliferation and phenotype of primary B cells in vitro. Moreover, we examined expression of activation-induced cytidine deaminase (AID) mRNA that is responsible for class switch recombination (CSR) and somatic hypermutation (SHM). Here, we report that changes observed in cellular proliferation, phenotypes and activation of B cells could be caused by direct contact between HIV-1 particles and primary B cells in vitro. Finally, direct HIV-1-derived B cells activation led to the increase of AID mRNA expression and its subsequent CSR function was detected in vitro. CONCLUSION/SIGNIFICANCE: We showed that HIV-1 could directly induce primary B cells dysregulation triggering phenotypical and functional abilities of B cells in vitro that could explain in some extent early B-cell abnormalities in HIV disease

Towards the prediction of essential genes by integration of network topology, cellular localization and biological process information

<p>Abstract</p> <p>Background</p> <p>The identification of essential genes is important for the understanding of the minimal requirements for cellular life and for practical purposes, such as drug design. However, the experimental techniques for essential genes discovery are labor-intensive and time-consuming. Considering these experimental constraints, a computational approach capable of accurately predicting essential genes would be of great value. We therefore present here a machine learning-based computational approach relying on network topological features, cellular localization and biological process information for prediction of essential genes.</p> <p>Results</p> <p>We constructed a decision tree-based meta-classifier and trained it on datasets with individual and grouped attributes-network topological features, cellular compartments and biological processes-to generate various predictors of essential genes. We showed that the predictors with better performances are those generated by datasets with integrated attributes. Using the predictor with all attributes, i.e., network topological features, cellular compartments and biological processes, we obtained the best predictor of essential genes that was then used to classify yeast genes with unknown essentiality status. Finally, we generated decision trees by training the J48 algorithm on datasets with all network topological features, cellular localization and biological process information to discover cellular rules for essentiality. We found that the number of protein physical interactions, the nuclear localization of proteins and the number of regulating transcription factors are the most important factors determining gene essentiality.</p> <p>Conclusion</p> <p>We were able to demonstrate that network topological features, cellular localization and biological process information are reliable predictors of essential genes. Moreover, by constructing decision trees based on these data, we could discover cellular rules governing essentiality.</p

The Saccharomyces cerevisiae Histone Chaperone Rtt106 Mediates the Cell Cycle Recruitment of SWI/SNF and RSC to the HIR-Dependent Histone Genes

In Saccharomyces cerevisiae, three out of the four histone gene pairs (HTA1-HTB1, HHT1-HHF1, and HHT2-HHF2) are regulated by the HIR co-repressor complex. The histone chaperone Rtt106 has recently been shown to be present at these histone gene loci throughout the cell cycle in a HIR- and Asf1-dependent manner and involved in their transcriptional repression. The SWI/SNF and RSC chromatin remodeling complexes are both recruited to the HIR-dependent histone genes; SWI/SNF is required for their activation in S phase, whereas RSC is implicated in their repression outside of S phase. Even though their presence at the histone genes is dependent on the HIR complex, their specific recruitment has not been well characterized. In this study we focused on characterizing the role played by the histone chaperone Rtt106 in the cell cycle-dependent recruitment of SWI/SNF and RSC complexes to the histone genes.Using GST pull-down and co-immunoprecipitation assays, we showed that Rtt106 physically interacts with both the SWI/SNF and RSC complexes in vitro and in vivo. We then investigated the function of this interaction with respect to the recruitment of these complexes to HIR-dependent histone genes. Using chromatin immunoprecipitation assays (ChIP), we found that Rtt106 is important for the recruitment of both SWI/SNF and RSC complexes to the HIR-dependent histone genes. Furthermore, using synchronized cell cultures, we showed by ChIP assays that the Rtt106-dependent SWI/SNF recruitment to these histone gene loci is cell cycle regulated and restricted to late G1 phase just before the peak of histone gene expression in S phase.Overall, these data strongly suggest that the interaction between the histone chaperone Rtt106 and both the SWI/SNF and RSC chromatin remodeling complexes is important for the cell cycle regulated recruitment of these two complexes to the HIR-dependent histone genes

Stochastic and epistemic uncertainty propagation in LCA

Purpose: When performing uncertainty propagation, most LCA practitioners choose to represent uncertainties by single probability distributions and to propagate them using stochastic methods. However the selection of single probability distributions appears often arbitrary when faced with scarce information or expert judgement (epistemic uncertainty). Possibility theory has been developed over the last decades to address this problem. The objective of this study is to present a methodology that combines probability and possibility theories to represent stochastic and epistemic uncertainties in a consistent manner and apply it to LCA. A case study is used to show the uncertainty propagation performed with the proposed method and compare it to propagation performed using probability and possibility theories alone. Methods: Basic knowledge on the probability theory is first recalled, followed by a detailed description of hal-00811827, version 1- 11 Apr 2013 epistemic uncertainty representation using fuzzy intervals. The propagation methods used are the Monte Carlo analysis for probability distribution and an optimisation on alpha-cuts for fuzzy intervals. The proposed method (noted IRS) generalizes the process of random sampling to probability distributions as well as fuzzy intervals, thus making the simultaneous use of both representations possible

Single-cell analysis identifies cellular markers of the HIV permissive cell.

Cellular permissiveness to HIV infection is highly heterogeneous across individuals. Heterogeneity is also found across CD4+ T cells from the same individual, where only a fraction of cells gets infected. To explore the basis of permissiveness, we performed single-cell RNA-seq analysis of non-infected CD4+ T cells from high and low permissive individuals. Transcriptional heterogeneity translated in a continuum of cell states, driven by T-cell receptor-mediated cell activation and was strongly linked to permissiveness. Proteins expressed at the cell surface and displaying the highest correlation with T cell activation were tested as biomarkers of cellular permissiveness to HIV. FACS sorting using antibodies against several biomarkers of permissiveness led to an increase of HIV cellular infection rates. Top candidate biomarkers included CD25, a canonical activation marker. The combination of CD25 high expression with other candidate biomarkers led to the identification of CD298, CD63 and CD317 as the best biomarkers for permissiveness. CD25highCD298highCD63highCD317high cell population showed an enrichment of HIV-infection of up to 28 fold as compared to the unsorted cell population. The purified hyper-permissive cell subpopulation was characterized by a downregulation of interferon-induced genes and several known restriction factors. Single-cell RNA-seq analysis coupled with functional characterization of cell biomarkers provides signatures of the "HIV-permissive cell"

B_s -> phi rho^0 and B_s -> phi pi^0 as a handle on isospin-violating New Physics

The 2.5 sigma discrepancy between theory and experiment observed in the difference A_CP(B^- --> pi^0 K^-)-A_CP(Bbar^0 --> pi^+ K^-) can be explained by a new electroweak penguin amplitude. Motivated by this result, we analyse the purely isospin-violating decays B_s --> phi rho^0 and B_s --> phi pi^0, which are dominated by electroweak penguins, and show that in presence of a new electroweak penguin amplitude their branching ratio can be enhanced by up to an order of magnitude, without violating any constraints from other hadronic B decays. This makes them very interesting modes for LHCb and future B factories. We perform both a model-independent analysis and a study within realistic New Physics models such as a modified-Z^0-penguin scenario, a model with an additional Z' boson and the MSSM. In the latter cases the new amplitude can be correlated with other flavour phenomena, such as semileptonic B decays and B_s-Bbar_s mixing, which impose stringent constraints on the enhancement of the two B_s decays. In particular we find that, contrary to claims in the literature, electroweak penguins in the MSSM can reduce the discrepancy in the B --> pi K modes only marginally. As byproducts we update the SM predictions to Br(Bbar_s --> phi pi^0)=1.6^{+1.1}_{-0.3}*10^{-7} and Br(Bbar_s --> phi rho^0)=4.4^{+2.7}_{-0.7}*10^{-7} and perform a state-of-the-art analysis of B --> pi K amplitudes in QCD factorisation.Comment: 56 pages, 12 figures, Journal version. Some typos corrected and references added; improved treatment of the MSSM analysis including chirally enhanced corrections. Conclusion unchange