2,202 research outputs found

    Rationality as the Rule of Reason

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    The demands of rationality are linked both to our subjective normative perspective (given that rationality is a person-level concept) and to objective reasons or favoring relations (given that rationality is non-contingently authoritative for us). In this paper, I propose a new way of reconciling the tension between these two aspects: roughly, what rationality requires of us is having the attitudes that correspond to our take on reasons in the light of our evidence, but only if it is competent. I show how this view can account for structural rationality on the assumption that intentions and beliefs as such involve competent perceptions of downstream reasons, and explore various implications of the account

    A Common Dominant TLR5 Stop Codon Polymorphism Abolishes Flagellin Signaling and Is Associated with Susceptibility to Legionnaires' Disease

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    Although Toll-like receptors (TLRs) are critical mediators of the immune response to pathogens, the influence of polymorphisms in this gene family on human susceptibility to infection is poorly understood. We demonstrated recently that TLR5 recognizes flagellin, a potent inflammatory stimulus present in the flagellar structure of many bacteria. Here, we show that a common stop codon polymorphism in the ligand-binding domain of TLR5 (TLR5392STOP) is unable to mediate flagellin signaling, acts in a dominant fashion, and is associated with susceptibility to pneumonia caused by Legionella pneumophila, a flagellated bacterium. We also show that flagellin is a principal stimulant of proinflammatory cytokine production in lung epithelial cells. Together, these observations suggest that TLR5392STOP increases human susceptibility to infection through an unusual dominant mechanism that compromises TLR5's essential role as a regulator of the lung epithelial innate immune response

    Measurement of Branching Fraction and Dalitz Distribution for B0->D(*)+/- K0 pi-/+ Decays

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    We present measurements of the branching fractions for the three-body decays B0 -> D(*)-/+ K0 pi^+/-andtheirresonantsubmodes and their resonant submodes B0 -> D(*)-/+ K*+/- using a sample of approximately 88 million BBbar pairs collected by the BABAR detector at the PEP-II asymmetric energy storage ring. We measure: B(B0->D-/+ K0 pi+/-)=(4.9 +/- 0.7(stat) +/- 0.5 (syst)) 10^{-4} B(B0->D*-/+ K0 pi+/-)=(3.0 +/- 0.7(stat) +/- 0.3 (syst)) 10^{-4} B(B0->D-/+ K*+/-)=(4.6 +/- 0.6(stat) +/- 0.5 (syst)) 10^{-4} B(B0->D*-/+ K*+/-)=(3.2 +/- 0.6(stat) +/- 0.3 (syst)) 10^{-4} From these measurements we determine the fractions of resonant events to be : f(B0-> D-/+ K*+/-) = 0.63 +/- 0.08(stat) +/- 0.04(syst) f(B0-> D*-/+ K*+/-) = 0.72 +/- 0.14(stat) +/- 0.05(syst)Comment: 7 pages, 3 figures submitted to Phys. Rev. Let

    Lignin biomarkers as tracers of mercury sources in lakes water column

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    This study presents the role of specific terrigenous organic compounds as important vectors of mercury (Hg) transported from watersheds to lakes of the Canadian boreal forest. In order to differentiate the autochthonous from the allochthonous organic matter (OM), lignin derived biomarker signatures [Lambda, S/V, C/V, P/(V ? S), 3,5-Bd/V and (Ad/Al)v] were used. Since lignin is exclusively produced by terrigenous plants, this approach can give a non equivocal picture of the watershed inputs to the lakes. Moreover, it allows a characterization of the source of OM and its state of degradation. The water column of six lakes from the Canadian Shield was sampled monthly between June and September 2005. Lake total dissolved Hg concentrations and Lambda were positively correlated, meaning that Hg and ligneous inputs are linked (dissolved OM r2 = 0.62, p\0.0001; particulate OM r2 = 0.76, p\0.0001). Ratios of P/(V ? S) and 3,5-Bd/V from both dissolved OM and particulate OM of the water column suggest an inverse relationship between the progressive state of pedogenesis and maturation of the OM in soil before entering the lake, and the Hg concentrations in the water column. No relation was found between Hg levels in the lakes and the watershed flora composition—angiosperm versus gymnosperm or woody versus non-woody compounds. This study has significant implications for watershed management of ecosystems since limiting fresh terrestrial OM inputs should reduce Hg inputs to the aquatic systems. This is particularly the case for largescale land-use impacts, such as deforestation, agriculture and urbanization, associated to large quantities of soil OM being transferred to aquatic systems

    Genomic characterisation of EΌ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene

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    The EΌ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we sequence spontaneously arising EΌ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. We identify frequent disruptive mutations in the PRC1-like component and BCL6-corepressor gene Bcor. Moreover, we find unexpected concomitant multigenic lesions involving Cdkn2a loss and other cancer genes including Nras, Kras and Bcor. These findings challenge the assumed two-hit model of EΌ-Myc lymphoma and demonstrate a functional in vivo role for Bcor in suppressing tumorigenesis.We acknowledge the following funding agencies: Leukaemia Foundation of Australia, Arrow Bone Marrow Transplant Foundation, National Health and Medical Research Council Australia, Cancer Council Victoria, Victorian Cancer Agency, Australian Cancer Research Foundation, Peter MacCallum Cancer Centre Foundation, National Institutes of Health

    Search for the W-exchange decays B0 --> Ds(*)- Ds(*)+

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    We report a search for the decays B0→Ds−Ds+B^{0} \to D_{s}^{-} D_{s}^{+}, B0→Ds∗−Ds+B^{0} \to D_{s}^{*-} D_{s}^{+}, B0→Ds∗−Ds∗+B^{0} \to D_{s}^{*-} D_{s}^{*+} in a sample of 232 million ΄(4S)\Upsilon(4S) decays to \BBb ~pairs collected with the \babar detector at the PEP-II asymmetric-energy e+e−e^+ e^- storage ring. We find no significant signal and set upper bounds for the branching fractions: B(B0→Ds−Ds+)<1.0×10−4,B(B0→Ds∗−Ds+)<1.3×10−4{\cal B}(B^{0} \to D_{s}^{-} D_{s}^{+}) < 1.0 \times 10^{-4}, {\cal B}(B^{0} \to D_{s}^{*-} D_{s}^{+}) < 1.3 \times 10^{-4} and B(B0→Ds∗−Ds∗+)<2.4×10−4{\cal B}(B^{0} \to D_{s}^{*-} D_{s}^{*+}) < 2.4 \times 10^{-4} at 90% confidence level.Comment: 8 pages, 2 figures, submitted to PRD-R

    Measurement of the B+ --> p pbar K+ Branching Fraction and Study of the Decay Dynamics

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    With a sample of 232x10^6 Upsilon(4S) --> BBbar events collected with the BaBar detector, we study the decay B+ --> p pbar K+ excluding charmonium decays to ppbar. We measure a branching fraction Br(B+ --> p pbar K+)=(6.7+/-0.5+/-0.4)x10^{-6}. An enhancement at low ppbar mass is observed and the Dalitz plot asymmetry suggests dominance of the penguin amplitude in this B decay. We search for a pentaquark candidate Theta*++ decaying into pK+ in the mass range 1.43 to 2.00 GeV/c2 and set limits on Br(B+ --> Theta*++pbar)xBr(Theta*++ --> pK+) at the 10^{-7} level.Comment: 8 pages, 7 postscript figures, submitted to Phys. Rev. D (Rapid Communications
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