11,900 research outputs found

    Retrieve and Refine: Improved Sequence Generation Models For Dialogue

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    Sequence generation models for dialogue are known to have several problems: they tend to produce short, generic sentences that are uninformative and unengaging. Retrieval models on the other hand can surface interesting responses, but are restricted to the given retrieval set leading to erroneous replies that cannot be tuned to the specific context. In this work we develop a model that combines the two approaches to avoid both their deficiencies: first retrieve a response and then refine it -- the final sequence generator treating the retrieval as additional context. We show on the recent CONVAI2 challenge task our approach produces responses superior to both standard retrieval and generation models in human evaluations

    Alloreactive cytotoxic T lymphocytes generated in the presence of viral- derived peptides show exquisite peptide and MHC specificity

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    The nature of alloreactivity to MHC molecules has been enigmatic, primarily because of the observation that allogeneic responses are considerably stronger than syngeneic responses. To better determine the specificity potential of allogeneic responses, we have generated alloreactive CTL specific for exogenous, viral-derived peptide ligands. This approach allowed us to critically evaluate both the peptide- and MHC-specificity of these alloreactive T cells. Exploiting the accessibility of the H-2Ld class I molecule for exogenous peptide ligands, alloreactive CTL were generated that are specific for either murine cytomegalovirus (MCMV) or lymphocytic choriomeningitis virus (LCMV) peptides bound by Ld alloantigens. Peptide specificity was initially observed in bulk cultures of alloreactive CTL only when tested on peptide-sensitized T2.Ld target cells that have defective presentation of endogenous peptides. Subsequent cloning of bulk alloreactive CTL lines generated to MCMV yielded CTL clones that had exquisitely specific MCMV peptide recognition requirement. All of the MCMV/Ld alloreactive CTL clones were also exquisitely MHC-specific in that none of the CTL clones lysed targets expressing MCMV/Lq complexes, even though Lq differs from Ld by only six amino acid residues and Lq also binds the MCMV peptide. This observation clearly demonstrates that alloreactive CTL are capable of the same degree of specificity for target cell recognition as are syngeneic CTL in MHC-restricted responses

    Overdiagnosis and overtreatment of breast cancer: Overdiagnosis in randomised controlled trials of breast cancer screening

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    Data from randomised controlled trials of mammographic screening can be used to determine the extent of any overdiagnosis, as soon as either a time equivalent to the lead-time has elapsed after the final screen, or the control arm has been offered screening. This paper reviews those randomised trials for which breast cancer incidence data are available. In recent trials in which the control group has not been offered screening, an excess incidence of breast cancer remains after many years of follow-up. In those trials in which the control arm has been offered screening, although there is a possible shift from invasive to in situ disease, there is no evidence of overdiagnosis as a result of incident screens

    On the generalized Bykovskii presentation of Steinberg modules

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    We study presentations of the virtual dualizing modules of special linear groups of number rings, the Steinberg modules. Bykovskii gave a presentation for the Steinberg modules of the integers, and our main result is a generalization of this presentation to the Gaussian integers and the Eisenstein integers. We also show that this generalization does not give a presentation for the Steinberg modules of several Euclidean number rings.Comment: Minor revisions based on referee's comments. Accepted for publication at IMR

    NMR Chemical Shifts of Trace Impurities: Common Laboratory Solvents, Organics, and Gases in Deuterated Solvents Relevant to the Organometallic Chemist

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    Tables of ^1H and ^(13)C NMR chemical shifts have been compiled for common organic compounds often used as reagents or found as products or contaminants in deuterated organic solvents. Building upon the work of Gottlieb, Kotlyar, and Nudelman in the Journal of Organic Chemistry, signals for common impurities are now reported in additional NMR solvents (tetrahydrofuran-d_8, toluene-d_8, dichloromethane-d_2, chlorobenzene-d_5, and 2,2,2-trifluoroethanol-d_3) which are frequently used in organometallic laboratories. Chemical shifts for other organics which are often used as reagents or internal standards or are found as products in organometallic chemistry are also reported for all the listed solvents

    Asteroseismological constraints on the pulsating planetary nebula nucleus (PG1159-type) RX J2117.1+3412

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    We present asteroseismological inferences on RX J2117.1+3412, the hottest known pulsating PG1159 star. Our results are based on full PG1159 evolutionary models recently presented by Miller Bertolami & Althaus (2006). We performed extensive computations of adiabatic g-mode pulsation periods on PG1159 evolutionary models with stellar masses ranging from 0.530 to 0.741 Mo. PG1159 stellar models are extracted from the complete evolution of progenitor stars started from the ZAMS, through the thermally pulsing AGB and born-again phases to the domain of the PG 1159 stars. We constrained the stellar mass of RX J2117.1+3412 by comparing the observed period spacing with the asymptotic period spacing and with the average of the computed period spacings. We also employed the individual observed periods to find a representative seismological model. We derive a stellar mass of 0.56-0.57 Mo from the period spacing data alone. In addition, we found a best-fit model representative for RX J2117.1+3412 with an effective temperature of 163,400 K, a stellar mass of 0.565 Mo, and a surface gravity log g= 6.61. The derived stellar luminosity and radius are log(L/Lo)= 3.36 and log(R/Ro)= -1.23, respectively, and the He-rich envelope thickness is Menv= 0.02 Mo. We derive a seismic distance of 452 pc and a linear size of the planetary nebula of 1.72 pc. These inferences seem to solve the discrepancy between the RX J2117.1+3412 evolutionary timescale and the size of the nebula. All of the seismological tools we use concur to the conclusion that RX J2117.1+3412 must have a stellar mass of 0.565 Mo much in agreement with recent asteroseismology studies and in clear conflict with the predictions of spectroscopy plus evolutionary tracks.Comment: 10 pages, 6 figures, 2 tables. Accepted for publication in Astronomy and Astrophysics. Erratum available as a separate fil

    Analytic shock-fronted solutions to a reaction-diffusion equation with negative diffusivity

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    Reaction-diffusion equations (RDEs) model the spatiotemporal evolution of a density field u(x⃗,t)u(\vec{x},t) according to diffusion and net local changes. Usually, the diffusivity is positive for all values of uu, which causes the density to disperse. However, RDEs with negative diffusivity can model aggregation, which is the preferred behaviour in some circumstances. In this paper, we consider a nonlinear RDE with quadratic diffusivity D(u)=(u−a)(u−b)D(u) = (u - a)(u - b) that is negative for u∈(a,b)u\in(a,b). We use a non-classical symmetry to construct analytic receding time-dependent, colliding wave, and receding travelling wave solutions. These solutions are initially multi-valued, and we convert them to single-valued solutions by inserting a shock. We examine properties of these analytic solutions including their Stefan-like boundary condition, and perform a phase plane analysis. We also investigate the spectral stability of the u=0u = 0 and u=1u=1 constant solutions, and prove for certain aa and bb that receding travelling waves are spectrally stable. Additionally, we introduce an new shock condition where the diffusivity and flux are continuous across the shock. For diffusivity symmetric about the midpoint of its zeros, this condition recovers the well-known equal-area rule, but for non-symmetric diffusivity it results in a different shock position.Comment: 35 pages, 10 figure

    X-ray crystallographic structure of a complex between a synthetic protease of human immunodeficiency virus 1 and a substrate-based hydroxyethylamine inhibitor

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    The structure of a crystal complex of the chemically synthesized protease of human immunodeficiency virus 1 with a heptapeptide-derived inhibitor bound in the active site has been determined. The sequence of the inhibitor JG-365 is Ac-Ser-Leu-Asn-Phe-ψ[CH(OH)CH_2N]-Pro-Ile-Val-OMe; the K_i is 0.24 nM. The hydroxyethylamine moiety, in place of the normal scissile bond of the substrate, is believed to mimic a tetrahedral reaction intermediate. The structure of the complex has been refined to an R factor of 0.146 at 2.4-Å resolution by using restrained least squares with rms deviations in bond lengths of 0.02 Å and bond angles of 4. The bound inhibitor diastereomer has the S configuration at the hydroxyethylamine chiral carbon, and the hydroxyl group is positioned between the active site aspartate carboxyl groups within hydrogen bonding distance. Comparison of this structure with a reduced peptide bond inhibitor-protease complex indicates that these contacts confer the exceptional binding strength of JG-365
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