Antiproton-Hydrogen annihilation at sub-kelvin temperatures

The main properties of the interaction of ultra low-energy antiprotons ($E\le10^{-6}$ a.u.) with atomic hydrogen are established. They include the elastic and inelastic cross sections and Protonium (Pn) formation spectrum. The inverse Auger process ($Pn+e \to H+\bar{p}$) is taken into account in the framework of an unitary coupled-channels model. The annihilation cross-section is found to be several times smaller than the predictions made by the black sphere absorption models. A family of $\bar{p}H$ nearthreshold metastable states is predicited. The dependence of Protonium formation probability on the position of such nearthreshold S-matrix singularities is analysed. An estimation for the $H\bar{H}$ annihilation cross section is obtained.Comment: latex.tar.gz file, 22 pages, 9 figure

Highly specific gene silencing in a monocot species by artificial microRNAs derived from chimeric MIRNA precursors

[EN] Artificial microRNAs (amiRNAs) are used for selective gene silencing in plants. However, current methods to produce amiRNA constructs for silencing transcripts in monocot species are not suitable for simple, cost-effective and large-scale synthesis. Here, a series of expression vectors based on Oryza sativa MIR390 (OsMIR390) precursor was developed for high-throughput cloning and high expression of amiRNAs in monocots. Four different amiRNA sequences designed to target specifically endogenous genes and expressed from OsMIR390-based vectors were validated in transgenic Brachypodium distachyon plants. Surprisingly, amiRNAs accumulated to higher levels and were processed more accurately when expressed from chimeric OsMIR390-based precursors that include distal stem-loop sequences from Arabidopsis thaliana MIR390a (AtMIR390a). In all cases, transgenic plants displayed the predicted phenotypes induced by target gene repression, and accumulated high levels of amiRNAs and low levels of the corresponding target transcripts. Genome-wide transcriptome profiling combined with 5¿-RLM-RACE analysis in transgenic plants confirmed that amiRNAs were highly specific.We thank Goretti Nguyen, Robyn Stevens, Jacob Mreen, Fangfang Ma and Madison Schniers for invaluable technical assistance, and Zacchery R. Smith for his initial contribution to develop the pH7WG2B-OsMIR390-B/c vector. Noah Fahlgren was supported by a USDA AFRI NIFA Postdoctoral Fellowship (MOW-2012-01361). This work was supported by grants from the National Science Foundation (MCB-1231726, MCB-1330562) and National Institutes of Health (AI043288) to James C. Carrington, and from the Department of Energy (DOE DE-SC0006627) to Todd C. Mockler.Carbonell, A.; Fahlgren, N.; Mitchell, S.; Cox, KLJ.; Reilly, KC.; Mockler, TC.; Carrington, JC. (2015). Highly specific gene silencing in a monocot species by artificial microRNAs derived from chimeric MIRNA precursors. The Plant Journal. 82(6):1061-1075. https://doi.org/10.1111/tpj.12835S10611075826Addo-Quaye, C., Eshoo, T. W., Bartel, D. P., & Axtell, M. J. (2008). Endogenous siRNA and miRNA Targets Identified by Sequencing of the Arabidopsis Degradome. Current Biology, 18(10), 758-762. doi:10.1016/j.cub.2008.04.042Alvarez, J. P., Pekker, I., Goldshmidt, A., Blum, E., Amsellem, Z., & Eshed, Y. (2006). Endogenous and Synthetic MicroRNAs Stimulate Simultaneous, Efficient, and Localized Regulation of Multiple Targets in Diverse Species. The Plant Cell, 18(5), 1134-1151. doi:10.1105/tpc.105.040725Arikit, S., Zhai, J., & Meyers, B. C. (2013). Biogenesis and function of rice small RNAs from non-coding RNA precursors. Current Opinion in Plant Biology, 16(2), 170-179. doi:10.1016/j.pbi.2013.01.006Axtell, M. J. (2013). Classification and Comparison of Small RNAs from Plants. Annual Review of Plant Biology, 64(1), 137-159. doi:10.1146/annurev-arplant-050312-120043Axtell, M. J., Jan, C., Rajagopalan, R., & Bartel, D. P. (2006). A Two-Hit Trigger for siRNA Biogenesis in Plants. Cell, 127(3), 565-577. doi:10.1016/j.cell.2006.09.032Bartel, D. P. (2004). MicroRNAs. Cell, 116(2), 281-297. doi:10.1016/s0092-8674(04)00045-5Bernard, P., & Couturier, M. (1992). Cell killing by the F plasmid CcdB protein involves poisoning of DNA-topoisomerase II complexes. Journal of Molecular Biology, 226(3), 735-745. doi:10.1016/0022-2836(92)90629-xBologna, N. G., & Voinnet, O. (2014). The Diversity, Biogenesis, and Activities of Endogenous Silencing Small RNAs in Arabidopsis. Annual Review of Plant Biology, 65(1), 473-503. doi:10.1146/annurev-arplant-050213-035728Bouvier d’Yvoire, M., Bouchabke-Coussa, O., Voorend, W., Antelme, S., Cézard, L., Legée, F., … Sibout, R. (2012). Disrupting thecinnamyl alcohol dehydrogenase 1gene (BdCAD1) leads to altered lignification and improved saccharification inBrachypodium distachyon. The Plant Journal, 73(3), 496-508. doi:10.1111/tpj.12053Butardo, V. M., Fitzgerald, M. A., Bird, A. R., Gidley, M. J., Flanagan, B. M., Larroque, O., … Rahman, S. (2011). Impact of down-regulation of starch branching enzyme IIb in rice by artificial microRNA- and hairpin RNA-mediated RNA silencing. Journal of Experimental Botany, 62(14), 4927-4941. doi:10.1093/jxb/err188Carbonell, A., Fahlgren, N., Garcia-Ruiz, H., Gilbert, K. B., Montgomery, T. A., Nguyen, T., … Carrington, J. C. (2012). Functional Analysis of Three Arabidopsis ARGONAUTES Using Slicer-Defective Mutants  . The Plant Cell, 24(9), 3613-3629. doi:10.1105/tpc.112.099945Carbonell, A., Takeda, A., Fahlgren, N., Johnson, S. C., Cuperus, J. T., & Carrington, J. C. (2014). New Generation of Artificial MicroRNA and Synthetic Trans-Acting Small Interfering RNA Vectors for Efficient Gene Silencing in Arabidopsis. Plant Physiology, 165(1), 15-29. doi:10.1104/pp.113.234989Chen, H., Jiang, S., Zheng, J., & Lin, Y. (2012). Improving panicle exsertion of rice cytoplasmic male sterile line by combination of artificial microRNA and artificial target mimic. Plant Biotechnology Journal, 11(3), 336-343. doi:10.1111/pbi.12019Chen, M., Wei, X., Shao, G., Tang, S., Luo, J., & Hu, P. (2012). Fragrance of the rice grain achieved via artificial microRNA-induced down-regulation ofOsBADH2. Plant Breeding, 131(5), 584-590. doi:10.1111/j.1439-0523.2012.01989.xCuperus, J. T., Carbonell, A., Fahlgren, N., Garcia-Ruiz, H., Burke, R. T., Takeda, A., … Carrington, J. C. (2010). Unique functionality of 22-nt miRNAs in triggering RDR6-dependent siRNA biogenesis from target transcripts in Arabidopsis. Nature Structural & Molecular Biology, 17(8), 997-1003. doi:10.1038/nsmb.1866Cuperus, J. T., Fahlgren, N., & Carrington, J. C. (2011). Evolution and Functional Diversification of MIRNA Genes. The Plant Cell, 23(2), 431-442. doi:10.1105/tpc.110.082784Endo, Y., Iwakawa, H., & Tomari, Y. (2013). Arabidopsis ARGONAUTE7 selects miR390 through multiple checkpoints during RISC assembly. EMBO reports, 14(7), 652-658. doi:10.1038/embor.2013.73Fahlgren, N., & Carrington, J. C. (2009). miRNA Target Prediction in Plants. Plant MicroRNAs, 51-57. doi:10.1007/978-1-60327-005-2_4Felippes, F. F., & Weigel, D. (2009). Triggering the formation of tasiRNAs in Arabidopsis thaliana  : the role of microRNA miR173. EMBO reports, 10(3), 264-270. doi:10.1038/embor.2008.247Gilbert, K., Fahlgren, N., Kasschau, K., Chapman, E., Carrington, J., & Carbonell, A. (2014). Preparation of Multiplexed Small RNA Libraries from Plants. BIO-PROTOCOL, 4(21). doi:10.21769/bioprotoc.1275Guo, Y., Han, Y., Ma, J., Wang, H., Sang, X., & Li, M. (2014). Undesired Small RNAs Originate from an Artificial microRNA Precursor in Transgenic Petunia (Petunia hybrida). PLoS ONE, 9(6), e98783. doi:10.1371/journal.pone.0098783He, G., Zhu, X., Elling, A. A., Chen, L., Wang, X., Guo, L., … Deng, X.-W. (2010). Global Epigenetic and Transcriptional Trends among Two Rice Subspecies and Their Reciprocal Hybrids. The Plant Cell, 22(1), 17-33. doi:10.1105/tpc.109.072041Heisel, S. E., Zhang, Y., Allen, E., Guo, L., Reynolds, T. L., Yang, X., … Roberts, J. K. (2008). Characterization of Unique Small RNA Populations from Rice Grain. PLoS ONE, 3(8), e2871. doi:10.1371/journal.pone.0002871Johnson, C., Kasprzewska, A., Tennessen, K., Fernandes, J., Nan, G.-L., Walbot, V., … Bowman, L. H. (2009). Clusters and superclusters of phased small RNAs in the developing inflorescence of rice. Genome Research, 19(8), 1429-1440. doi:10.1101/gr.089854.108Karimi, M., Inzé, D., & Depicker, A. (2002). GATEWAY™ vectors for Agrobacterium-mediated plant transformation. Trends in Plant Science, 7(5), 193-195. doi:10.1016/s1360-1385(02)02251-3Kozomara, A., & Griffiths-Jones, S. (2013). miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Research, 42(D1), D68-D73. doi:10.1093/nar/gkt1181Liang, G., He, H., Li, Y., & Yu, D. (2012). A new strategy for construction of artificial miRNA vectors in Arabidopsis. Planta, 235(6), 1421-1429. doi:10.1007/s00425-012-1610-5Liu, Q., Wang, F., & Axtell, M. J. (2014). Analysis of Complementarity Requirements for Plant MicroRNA Targeting Using a Nicotiana benthamiana Quantitative Transient Assay  . The Plant Cell, 26(2), 741-753. doi:10.1105/tpc.113.120972Mi, S., Cai, T., Hu, Y., Chen, Y., Hodges, E., Ni, F., … Qi, Y. (2008). Sorting of Small RNAs into Arabidopsis Argonaute Complexes Is Directed by the 5′ Terminal Nucleotide. Cell, 133(1), 116-127. doi:10.1016/j.cell.2008.02.034Montgomery, T. A., Howell, M. D., Cuperus, J. T., Li, D., Hansen, J. E., Alexander, A. L., … Carrington, J. C. (2008). Specificity of ARGONAUTE7-miR390 Interaction and Dual Functionality in TAS3 Trans-Acting siRNA Formation. Cell, 133(1), 128-141. doi:10.1016/j.cell.2008.02.033Ossowski, S., Schwab, R., & Weigel, D. (2008). Gene silencing in plants using artificial microRNAs and other small RNAs. The Plant Journal, 53(4), 674-690. doi:10.1111/j.1365-313x.2007.03328.xOster, U., Tanaka, R., Tanaka, A., & Rüdiger, W. (2000). Cloning and functional expression of the gene encoding the key enzyme for chlorophyll b biosynthesis (CAO) from Arabidopsis thaliana. The Plant Journal, 21(3), 305-310. doi:10.1046/j.1365-313x.2000.00672.xPhilippar, K., Geis, T., Ilkavets, I., Oster, U., Schwenkert, S., Meurer, J., & Soll, J. (2007). Chloroplast biogenesis: The use of mutants to study the etioplast-chloroplast transition. Proceedings of the National Academy of Sciences, 104(2), 678-683. doi:10.1073/pnas.0610062104Rapaport, F., Khanin, R., Liang, Y., Pirun, M., Krek, A., Zumbo, P., … Betel, D. (2013). Comprehensive evaluation of differential gene expression analysis methods for RNA-seq data. Genome Biology, 14(9), R95. doi:10.1186/gb-2013-14-9-r95Schwab, R., Ossowski, S., Riester, M., Warthmann, N., & Weigel, D. (2006). Highly Specific Gene Silencing by Artificial MicroRNAs inArabidopsis. The Plant Cell, 18(5), 1121-1133. doi:10.1105/tpc.105.039834Takeda, A., Iwasaki, S., Watanabe, T., Utsumi, M., & Watanabe, Y. (2008). The Mechanism Selecting the Guide Strand from Small RNA Duplexes is Different Among Argonaute Proteins. Plant and Cell Physiology, 49(4), 493-500. doi:10.1093/pcp/pcn043Tanaka, A., Ito, H., Tanaka, R., Tanaka, N. K., Yoshida, K., & Okada, K. (1998). Chlorophyll a oxygenase (CAO) is involved in chlorophyll b formation from chlorophyll a. Proceedings of the National Academy of Sciences, 95(21), 12719-12723. doi:10.1073/pnas.95.21.12719Thole, V., Peraldi, A., Worland, B., Nicholson, P., Doonan, J. H., & Vain, P. (2011). T-DNA mutagenesis in Brachypodium distachyon. Journal of Experimental Botany, 63(2), 567-576. doi:10.1093/jxb/err333Tiwari, M., Sharma, D., & Trivedi, P. K. (2014). Artificial microRNA mediated gene silencing in plants: progress and perspectives. Plant Molecular Biology, 86(1-2), 1-18. doi:10.1007/s11103-014-0224-7Trabucco, G. M., Matos, D. A., Lee, S. J., Saathoff, A. J., Priest, H. D., Mockler, T. C., … Hazen, S. P. (2013). Functional characterization of cinnamyl alcohol dehydrogenase and caffeic acid O-methyltransferase in Brachypodium distachyon. BMC Biotechnology, 13(1). doi:10.1186/1472-6750-13-61Vogel, J., & Hill, T. (2007). High-efficiency Agrobacterium-mediated transformation of Brachypodium distachyon inbred line Bd21-3. Plant Cell Reports, 27(3), 471-478. doi:10.1007/s00299-007-0472-yWang, L., Si, Y., Dedow, L. K., Shao, Y., Liu, P., & Brutnell, T. P. (2011). A Low-Cost Library Construction Protocol and Data Analysis Pipeline for Illumina-Based Strand-Specific Multiplex RNA-Seq. PLoS ONE, 6(10), e26426. doi:10.1371/journal.pone.0026426Warthmann, N., Chen, H., Ossowski, S., Weigel, D., & Hervé, P. (2008). Highly Specific Gene Silencing by Artificial miRNAs in Rice. PLoS ONE, 3(3), e1829. doi:10.1371/journal.pone.0001829Zeng, L.-R., Qu, S., Bordeos, A., Yang, C., Baraoidan, M., Yan, H., … Wang, G.-L. (2004). Spotted leaf11, a Negative Regulator of Plant Cell Death and Defense, Encodes a U-Box/Armadillo Repeat Protein Endowed with E3 Ubiquitin Ligase Activityw⃞. The Plant Cell, 16(10), 2795-2808. doi:10.1105/tpc.104.025171Zhang, X., Niu, D., Carbonell, A., Wang, A., Lee, A., Tun, V., … Jin, H. (2014). ARGONAUTE PIWI domain and microRNA duplex structure regulate small RNA sorting in Arabidopsis. Nature Communications, 5(1). doi:10.1038/ncomms6468Zhou, X., Sunkar, R., Jin, H., Zhu, J.-K., & Zhang, W. (2008). Genome-wide identification and analysis of small RNAs originated from natural antisense transcripts in Oryza sativa. Genome Research, 19(1), 70-78. doi:10.1101/gr.084806.108Zhu, Q.-H., Spriggs, A., Matthew, L., Fan, L., Kennedy, G., Gubler, F., & Helliwell, C. (2008). A diverse set of microRNAs and microRNA-like small RNAs in developing rice grains. Genome Research, 18(9), 1456-1465. doi:10.1101/gr.075572.107Zhu, H., Hu, F., Wang, R., Zhou, X., Sze, S.-H., Liou, L. W., … Zhang, X. (2011). Arabidopsis Argonaute10 Specifically Sequesters miR166/165 to Regulate Shoot Apical Meristem Development. Cell, 145(2), 242-256. doi:10.1016/j.cell.2011.03.024Zhu, J.-Y., Sae-Seaw, J., & Wang, Z.-Y. (2013). Brassinosteroid signalling. Development, 140(8), 1615-1620. doi:10.1242/dev.06059

On isovector meson exchange currents in the Bethe-Salpeter approach

We investigate the nonrelativistic reduction of the Bethe-Salpeter amplitude for the deuteron electrodisintegration near threshold energies. To this end, two assumptions have been used in the calculations: 1) the static approximation and 2) the one iteration approximation. Within these assumptions it is possible to recover the nonrelativistic result including a systematic extension to relativistic corrections. We find that the so-called pair current term can be constructed from the $P$-wave contribution of the deuteron Bethe-Salpeter amplitude. The form factor that enters into the calculation of the pair current is constrained by the manifestly gauge independent matrix elements.Comment: 15 pages, incl. 3 figures, to be published Phys. Rev.

Cost effectiveness of palivizumab in Spain: an analysis using observational data

Objectives: To assess the cost effectiveness of palivizumab for prevention of severe respiratory syncytial virus (RSV) disease in high-risk infants in Spain, incorporating country-specific observational hospitalisation data. Methods: An existing decision tree model, designed using data from a large international clinical trial of palivizumab versus no prophylaxis, was updated to include Spanish observational hospitalisation data. The analysis was performed for preterm children born at or before 32 weeks gestational age, who are at high risk of developing severe RSV disease requiring hospitalisation. Data sources included published literature, official price/tariff lists and national population statistics. The primary perspective of the study was that of the Spanish National Health Service in 2006. Results: The base-case analysis included the direct medical costs associated with palivizumab prophylaxis and hospital care for RSV infections. Use of palivizumab produces an undiscounted incremental cost-effectiveness ratio (ICER) of €6,142 per quality-adjusted life-year (QALY), and a discounted ICER of €12,814/QALY. Conclusion: Palivizumab provides a cost-effective method of prophylaxis against severe RSV disease requiring hospitalisation among preterm infants in Spain

The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

Immunoprophylaxis of respiratory syncytial virus: global experience

Respiratory syncytial virus (RSV) infects nearly all children by age 2 years, and it causes considerable illness and death in certain high-risk pediatric populations. Historically, treatment for RSV has been symptomatic, and developing a safe and effective vaccine has been a challenge. Therefore, research efforts have turned to passive immunization as the best option to control RSV. Palivizumab, a genetically engineered humanized monoclonal antibody, has been shown to reduce RSV-related hospitalizations significantly, with few adverse effects. It was approved for use in high-risk children in the USA in 1998 and in Europe in 1999; it is now approved for use in more than 45 countries. The efficacy and safety of palivizumab continue to be supported by both clinical trial and outcomes data

A meta-analysis of the effect of antibody therapy for the prevention of severe respiratory syncytial virus infection

Abstract Background The primary objective of this meta-analytic study was to determine the impact of RSV-IGIV and palivizumab on risk of respiratory syncytial virus (RSV)-related hospitalization. Secondary objectives were to determine if antibody therapy decreases the risk of RSV infection, intensive care admission, mechanical ventilation, and mortality in high risk infant populations. Methods We performed searches of electronic data bases from 1966 to April 2009. Inclusion and exclusion criteria were defined a priori. Inclusion criteria were as follows: 1) There was randomization between polyclonal or monoclonal antibodies and placebo or no therapy, and 2) Polyclonal or monoclonal antibodies were given as prophylaxis. Results Of the six included studies, three utilized RSV-IGIV (total of 533 randomized to treatment groups) and three utilized palivizumab (total of 1,663 randomized to treatment groups). The absolute risk of hospitalization in the control arms was 12% and overall RR for all 2,196 children who received one of the antibody products was 0.53 (95% CI 0.43, 0.66), P < 0.00001. When looking only at the children who received palivizumab, the RR for hospitalization was 0.50 (95% CI 0.38, 0.66), P < 0.00001. For the children receiving RSV-IGIV, the RR for hospitalization was 0.59 (95% CI 0.42, 0.83, P < 0.002). The use of palivizumab resulted in a significant decrease in admission to the ICU (RR 0.29 (95% CI 0.14, 0.59; P = 0.0007). There was no significant reduction in the risk of mechanical ventilation or mortality with the use of antibody prophylaxis. Infants born at less than 35 weeks gestational age, and those with chronic lung and congenital heart disease all had a significant reduction in the risk of RSV hospitalization with children born under 35 weeks gestational age showing a trend towards the greatest benefit. Conclusion Both palivizumab and RSV-IGIV decrease the incidence of RSV hospitalization and ICU admission and their effect appears to be qualitatively similarly. There was neither a statistically significant reduction in the incidence of mechanical ventilation nor in all cause mortality. This meta-analysis separately quantifies the impact of RSV-IGIV and palivizumab on various measures of severe RSV disease and builds upon a previous study that was only able to examine the pooled effect of all antibody products together

Respiratory syncytial virus infection is associated with an altered innate immunity and a heightened pro-inflammatory response in the lungs of preterm lambs

<p>Abstract</p> <p>Introduction</p> <p>Factors explaining the greater susceptibility of preterm infants to severe lower respiratory infections with respiratory syncytial virus (RSV) remain poorly understood. Fetal/newborn lambs are increasingly appreciated as a model to study key elements of RSV infection in newborn infants due to similarities in lung alveolar development, immune response, and susceptibility to RSV. Previously, our laboratory demonstrated that preterm lambs had elevated viral antigen and developed more severe lesions compared to full-term lambs at seven days post-infection. Here, we compared the pathogenesis and immunological response to RSV infection in lungs of preterm and full-term lambs.</p> <p>Methods</p> <p>Lambs were delivered preterm by Caesarian section or full-term by natural birth, then inoculated with bovine RSV (bRSV) via the intratracheal route. Seven days post-infection, lungs were collected for evaluation of cytokine production, histopathology and cellular infiltration.</p> <p>Results</p> <p>Compared to full-term lambs, lungs of preterm lambs had a heightened pro-inflammatory response after infection, with significantly increased MCP-1, MIP-1α, IFN-γ, TNF-α and PD-L1 mRNA. RSV infection in the preterm lung was characterized by increased epithelial thickening and periodic acid-Schiff staining, indicative of glycogen retention. Nitric oxide levels were decreased in lungs of infected preterm lambs compared to full-term lambs, indicating alternative macrophage activation. Although infection induced significant neutrophil recruitment into the lungs of preterm lambs, neutrophils produced less myeloperoxidase than those of full-term lambs, suggesting decreased functional activation.</p> <p>Conclusions</p> <p>Taken together, our data suggest that increased RSV load and inadequate immune response may contribute to the enhanced disease severity observed in the lungs of preterm lambs.</p