Partial-Wave Amplitudes and Resonances in pbar + p -> pi + pi

Partial wave amplitudes have been extracted from accurate data on pbar + p -> pi + pi by a method which incorporates the theoretical constraints of analyticity and crossing symmetry. The resulting solution gives a good fit to the annihilation data and is also consistent with the wealth of information in the crossed channel pi + N -> pi + N. The partial wave amplitudes show evidence for resonances in all partial waves with J < 6, at least one of which, a J = 0+ state, (and possibly another with J = 1-) is unlikely to have a simple quark-antiquark structure.Comment: 17 pages, Revtex, 21 postscript figure

The Dwarf Novae During Quiescence

We present a synthetic spectral analysis of nearly the entire FUV IUE archive of spectra of DNe in or near quiescence. We have examined all of the systems for which S/N permitted an analysis. The study includes 53 systems of all DN subtypes both above and below the period gap. The spectra were uniformly analyzed using synthetic spectral codes for optically thick accretion disks and stellar photospheres along with the best-available distance measurements or estimates. We present newly determined approximate WD temperatures or upper limits and estimated accretion rates. The average temperature of WDs in DNe below the period gap is ~18,000K. For WDs in DNe above the period gap, the average WD temperature is ~26,000K. There is a flux component, in addition to a WD photosphere, which contributes >60% of the flux in the FUV in 53% of the quiescent DNe in this study. We find that for 41% of the DNe in our sample, a WD photosphere provides >60% of the FUV flux. Accretion rates estimated from the FUV alone for the sample of DNe during quiescence ranged from 10^-12 Msun/yr to 10^-10 Msun/yr.The additional flux component is almost certainly not an optically thick accretion disk since, according to the disk instability model, the disk should be optically thin and too cool during DN quiescence to be a significant FUV continuum emitter. Among the candidates for the second component of FUV light are the quiescent inner disk, a hot equatorial accretion belt, and a hot rotating ring. The implications of our study for disk accretion physics and CV evolution are discussed.Comment: 36 pages, 3 tables, 8 figures, final accepted version of manuscrip

Annexin A2 Binds RNA and Reduces the Frameshifting Efficiency of Infectious Bronchitis Virus

Annexin A2 (ANXA2) is a protein implicated in diverse cellular functions, including exocytosis, DNA synthesis and cell proliferation. It was recently proposed to be involved in RNA metabolism because it was shown to associate with some cellular mRNA. Here, we identified ANXA2 as a RNA binding protein (RBP) that binds IBV (Infectious Bronchitis Virus) pseudoknot RNA. We first confirmed the binding of ANXA2 to IBV pseudoknot RNA by ultraviolet crosslinking and showed its binding to RNA pseudoknot with ANXA2 protein in vitro and in the cells. Since the RNA pseudoknot located in the frameshifting region of IBV was used as bait for cellular RBPs, we tested whether ANXA2 could regulate the frameshfting of IBV pseudoknot RNA by dual luciferase assay. Overexpression of ANXA2 significantly reduced the frameshifting efficiency from IBV pseudoknot RNA and knockdown of the protein strikingly increased the frameshifting efficiency. The results suggest that ANXA2 is a cellular RBP that can modulate the frameshifting efficiency of viral RNA, enabling it to act as an anti-viral cellular protein, and hinting at roles in RNA metabolism for other cellular mRNAs

Measurement of the pbar p -> Ks Ks Reaction from 0.6 to 1.9 GeV/c

The pbar p -> Ks Ks -> 4pi+/- cross section was measured at incident antiproton momenta between 0.6 and 1.9 GeV/c using the CERN Low Energy Antiproton Ring (LEAR). This investigation was part of a systematic study of in-flight antiproton-proton annihilations into two-neutral-meson final states in a search for hadronic resonances. A coarse scan of the pbar p -> Ks Ks cross section as a function of center-of-mass energy between 1.964 and 2.395 GeV/c^2 and a fine scan of the region surrounding the Xi(2220) are presented. Upper limits on the product branching ratio BR(Xi -> pbar p)BR(Xi -> Ks Ks) are determined for a wide range of mass and width assumptions based on the non-observation of the Xi(2220). A rise in the pbar p -> Ks Ks cross section is observed near 2.15 GeV/c^2, which is consistent with the f2(2150) resonance.Comment: 11 pages, Latex, to be published in Phys Rev D (Oct 97

Altered Thymic Function during Interferon Therapy in HCV-Infected Patients

Interferon alpha (IFNα) therapy, despite good efficacy in curing HCV infection, leads to major side effects, in particular inducement of a strong peripheral T-cell lymphocytopenia. We here analyze the early consequences of IFNα therapy on both thymic function and peripheral T-cell homeostasis in patients in the acute or chronic phase of HCV-infection as well as in HIV/HCV co-infected patients. The evolution of T-cell subsets and T-cell homeostasis were estimated by flow cytometry while thymic function was measured through quantification of T-cell receptor excision circles (TREC) and estimation of intrathymic precursor T-cell proliferation during the first four months following the initiation of IFNα therapy. Beginning with the first month of therapy, a profound lymphocytopenia was observed for all T-cell subsets, including naïve T-cells and recent thymic emigrants (RTE), associated with inhibition of intrathymic precursor T-cell proliferation. Interleukin (IL)-7 plasma concentration rapidly dropped while lymphocytopenia progressed. This was neither a consequence of higher consumption of the cytokine nor due to its neutralization by soluble CD127. Decrease in IL-7 plasma concentration under IFNα therapy correlated with the decline in HCV viral load, thymic activity and RTE concentration in blood. These data demonstrate that IFNα-based therapy rapidly impacts on thymopoiesis and, consequently, perturbs T-cell homeostasis. Such a side effect might be detrimental for the continuation of IFNα therapy and may lead to an increased level of infectious risk, in particular in HIV/HCV co-infected patients. Altogether, this study suggests the therapeutic potential of IL-7 in the maintenance of peripheral T-cell homeostasis in IFNα-treated patients

Two Host Factors Regulate Persistence of H7a-Specific T Cells Injected in Tumor-Bearing Mice

BACKGROUND: Injection of CD8 T cells primed against immunodominant minor histocompatibility antigens (MiHA) such as H7(a) can eradicate leukemia and solid tumors. To understand why MiHA-targeted T cells have such a potent antitumor effect it is essential to evaluate their in vivo behavior. In the present work, we therefore addressed two specific questions: what is the proliferative dynamics of H7(a)-specifc T cells in tumors, and do H7(a)-specific T cells persist long-term after adoptive transfer? METHODOLOGY/PRINCIPAL FINDINGS: By day 3 after adoptive transfer, we observed a selective infiltration of melanomas by anti-H7(a) T cells. Over the next five days, anti-H7(a) T cells expanded massively in the tumor but not in the spleen. Thus, by day 8 after injection, anti-H7(a) T cells in the tumor had undergone more cell divisions than those in the spleen. These data strongly suggest that anti-H7(a) T cells proliferate preferentially and extensively in the tumors. We also found that two host factors regulated long-term persistence of anti-H7(a) memory T cells: thymic function and expression of H7(a) by host cells. On day 100, anti-H7(a) memory T cells were abundant in euthymic H7(a)-negative (B10.H7(b)) mice, present in low numbers in thymectomized H7(a)-positive (B10) hosts, and undetectable in euthymic H7(a)-positive recipients. CONCLUSIONS/SIGNIFICANCE: Although in general the tumor environment is not propitious to T-cell invasion and expansion, the present work shows that this limitation may be overcome by adoptive transfer of primed CD8 T cells targeted to an immunodominant MiHA (here H7(a)). At least in some cases, prolonged persistence of adoptively transferred T cells may be valuable for prevention of late cancer relapse in adoptive hosts. Our findings therefore suggest that it may be advantageous to target MiHAs with a restricted tissue distribution in order to promote persistence of memory T cells and thereby minimize the risk of cancer recurrence

Exploring RNA Structural Codes with SHAPE Chemistry

RNA is the central conduit for gene expression. This role depends on an ability to encode information at two levels: in its linear sequence and in the complex structures RNA can form by folding back on itself. Understanding the global structure-function interrelationships mediated by RNA remains a great challenge in molecular and structural biology. In this Account, we discuss evolving work in our laboratory focused on creating facile, generic, quantitative, accurate, and highly informative approaches for understanding RNA structure in biologically important environments. The core innovation derives from our discovery that the nucleophilic reactivity of the ribose 2'-hydroxyl in RNA is gated by local nucleotide flexibility. The 2'-hydroxyl is reactive at conformationally flexible positions but is unreactive at nucleotides constrained by base pairing. Sites of modification in RNA can be detected efficiently either using primer extension or by protection from exoribonucleolytic degradation. This technology is now called SHAPE, for selective 2'-hydroxyl acylation analyzed by primer extension (or protection from exoribonuclease). SHAPE reactivities are largely independent of nucleotide identity but correlate closely with model-free measurements of molecular order. The simple SHAPE reaction is thus a robust, nucleotide-resolution, biophysical measurement of RNA structure. SHAPE can be used to provide an experimental correction to RNA folding algorithms and, in favorable cases, yield kilobase-scale secondary structure predictions with high accuracies. SHAPE chemistry is based on very simple reactive carbonyl centers that can be varied to yield slow- and fast-reacting reagents. Differential SHAPE reactivities can be used to detect specific RNA positions with slow local nucleotide dynamics. These positions, which are often in the C2'-endo conformation, have the potential to function as molecular timers that regulate RNA folding and function. In addition, fast-reacting SHAPE reagents can be used to visualize RNA structural biogenesis and RNA-protein assembly reactions in one second snapshots in very straightforward experiments. The application of SHAPE to challenging problems in biology has revealed surprises in well-studied systems. New regions have been identified that are likely to have critical functional roles on the basis of their high levels of RNA structure. For example, SHAPE analysis of large RNAs, such as authentic viral RNA genomes, suggests that RNA structure organizes regulatory motifs and regulates splicing, protein folding, genome recombination, and ribonucleoprotein assembly. SHAPE has also revealed limitations to the hierarchical model for RNA folding. Continued development and application of SHAPE technologies will advance our understanding of the many ways in which the genetic code is expressed through the underlying structure of RNA

The MATCH Corpus: A Corpus of Older and Younger Users' Interactions With Spoken Dialogue Systems.

We present the MATCH corpus, a unique data set of 447 dialogues in which 26 older and 24 younger adults interact with nine different spoken dialogue systems. The systems varied in the number of options presented and the confirmation strategy used. The corpus also contains information about the users’ cognitive abilities and detailed usability assessments of each dialogue system. The corpus, which was collected using a Wizard-of-Oz methodology, has been fully transcribed and annotated with dialogue acts and ‘‘Information State Update’’ (ISU) representations of dialogue context. Dialogue act and ISU annotations were performed semi-automatically. In addition to describing the corpus collection and annotation, we present a quantitative analysis of the interaction behaviour of older and younger users and discuss further applications of the corpus. We expect that the corpus will provide a key resource for modelling older people’s interaction with spoken dialogue systems