211 research outputs found

    Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape.

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    Human astroviruses (HAstV) are understudied positive-strand RNA viruses that cause gastroenteritis mostly in children and the elderly. Three clades of astroviruses, classic, MLB-type and VA-type have been reported in humans. One limitation towards a better understanding of these viruses has been the lack of a physiologically relevant cell culture model that supports growth of all clades of HAstV. Herein, we demonstrate infection of HAstV strains belonging to all three clades in epithelium-only human intestinal enteroids (HIE) isolated from biopsy-derived intestinal crypts. A detailed investigation of infection of VA1, a member of the non-canonical HAstV-VA/HMO clade, showed robust replication in HIE derived from different patients and from different intestinal regions independent of the cellular differentiation status. Flow cytometry and immunofluorescence analysis revealed that VA1 infects several cell types, including intestinal progenitor cells and mature enterocytes, in HIE cultures. RNA profiling of VA1-infected HIE uncovered that the host response to infection is dominated by interferon (IFN)-mediated innate immune responses. A comparison of the antiviral host response in non-transformed HIE and transformed human colon carcinoma Caco-2 cells highlighted significant differences between these cells, including an increased magnitude of the response in HIE. Additional studies confirmed the sensitivity of VA1 to exogenous IFNs, and indicated that the endogenous IFN response of HIE to curtail the growth of strains from all three clades. Genotypic variation in the permissiveness of different HIE lines to HAstV could be overcome by pharmacologic inhibition of JAK/STAT signaling. Collectively, our data identify HIE as a universal infection model for HAstV and an improved model of the intestinal epithelium to investigate enteric virus-host interactions

    Search for CP Violation in the Decay Z -> b (b bar) g

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    About three million hadronic decays of the Z collected by ALEPH in the years 1991-1994 are used to search for anomalous CP violation beyond the Standard Model in the decay Z -> b \bar{b} g. The study is performed by analyzing angular correlations between the two quarks and the gluon in three-jet events and by measuring the differential two-jet rate. No signal of CP violation is found. For the combinations of anomalous CP violating couplings, h^b=h^AbgVbh^VbgAb{\hat{h}}_b = {\hat{h}}_{Ab}g_{Vb}-{\hat{h}}_{Vb}g_{Ab} and hb=h^Vb2+h^Ab2h^{\ast}_b = \sqrt{\hat{h}_{Vb}^{2}+\hat{h}_{Ab}^{2}}, limits of \hat{h}_b < 0.59and and h^{\ast}_{b} < 3.02$ are given at 95\% CL.Comment: 8 pages, 1 postscript figure, uses here.sty, epsfig.st

    Measurement of the tau lepton lifetime

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    Observation of charmless hadronic B decays

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    Four candidates for charmless hadronic B decay are observed in a data sample of four million hadronic Z decays recorded by the ALEPH detector at LEP. The probability that these events come from background sources is estimated to be less than 10(-6). The average branching of weakly decaying B hadrons (a mixture of B-d(0), B-s(0) and Lambda(b) weighted by their production The average branching ratio of weakly decaying B hadrons (a mixture of B-d(0) cross sections and lifetimes, here denoted B) into two long-lived charged hadrons (pions, kaons or protons) is measured to be Br(B-->h(+)h(-))=(1.7(-0.7)(+1.0)+/-0.2)x10(-5). The relative branching fraction Br(B-d(s)(0)-->pi(+)pi(-)(K-))/Br(B-d(s)(0)-->h(+)h(-)) is measured to be 1.0(-0.3-0.1)(+0.0+0.0). In addition, branching ratio upper limits are obtained for a variety of exclusive charmless hadronic two-body decays of B hadrons

    Limit on Bs0B^0_s oscillation using a jet charge method

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    A lower limit is set on the B_{s}^{0} meson oscillation parameter \Delta m_{s} using data collected from 1991 to 1994 by the ALEPH detector. Events with a high transverse momentum lepton and a reconstructed secondary vertex are used. The high transverse momentum leptons are produced mainly by b hadron decays, and the sign of the lepton indicates the particle/antiparticle final state in decays of neutral B mesons. The initial state is determined by a jet charge technique using both sides of the event. A maximum likelihood method is used to set a lower limit of \, \Delta m_{s}. The 95\% confidence level lower limit on \Delta m_s ranges between 5.2 and 6.5(\hbar/c^{2})~ps^{-1} when the fraction of b quarks from Z^0 decays that form B_{s}^{0} mesons is varied from 8\% to 16\%. Assuming that the B_{s}^{0} fraction is 12\%, the lower limit would be \Delta m_{s} 6.1(\hbar/c^{2})~ps^{-1} at 95\% confidence level. For x_s = \Delta m_s \, \tau_{B_s}, this limit also gives x_s 8.8 using the B_{s}^{0} lifetime of \tau_{B_s} = 1.55 \pm 0.11~ps and shifting the central value of \tau_{B_s} down by 1\sigma

    Measurement of the Bs0^0_s lifetime and production rate with Dsl+^-_s l^+ combinations in Z decays

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    The lifetime of the \bs meson is measured in approximately 3 million hadronic Z decays accumulated using the ALEPH detector at LEP from 1991 to 1994. Seven different \ds decay modes were reconstructed and combined with an opposite sign lepton as evidence of semileptonic \bs decays. Two hundred and eight \dsl candidates satisfy selection criteria designed to ensure precise proper time reconstruction and yield a measured \bs lifetime of \mbox{\result .} Using a larger, less constrained sample of events, the product branching ratio is measured to be \mbox{\pbrresult

    Measurement of Lambda polarization from Z decays

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    Measurement of the tau lepton lifetime

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    Search for excited leptons at 130-140 GeV

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    Search for supersymmetric particles in e+ee^+e^- collisions at centre-of-mass energies of 130 and 136 GeV

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