Large Phenotypic Enhancement of Structured Random RNA Pools.

Laboratory evolution of functional RNAs has applications in many areas of chemical and synthetic biology. In vitro selections critically depend on the presence of functional molecules, such as aptamers and ribozymes, in the starting sequence pools. For selection of novel functions the pools are typically transcribed from random-sequence DNA templates, yielding a highly diverse set of RNAs that contain a multitude of folds and biochemical activities. The phenotypic potential, the frequency of functional RNAs, is very low, requiring large complexity of starting pools, surpassing 1015 different sequences, to identify highly active isolates. Furthermore, the majority of random sequences is not structured and has a high propensity for aggregation; the in vitro selection process thus involves not just enrichment of functional RNAs, but also their purification from aggregation-prone "free-riders". We reasoned that purification of the nonaggregating, monomeric subpopulation of a random-sequence RNA pool will yield pools of folded, functional RNAs. We performed six rounds of selection for monomeric sequences and show that the enriched population is compactly folded. In vitro selections originating from various mixtures of the compact pool and a fully random pool showed that sequences from the compact pool always dominate the population once a biochemical activity is detectable. A head-to-head competition of the two pools starting from a low (5 × 1012) sequence diversity revealed that the phenotypic potential of the compact pool is about 1000-times higher than the fully random pool. A selection for folded and monomeric RNA pools thus greatly increases the frequency of functional RNAs from that seen in random-sequence pools, providing a facile experimental approach to isolation of highly active functional RNAs from low-diversity populations

Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease: an Interasma (Global Asthma Association - GAA) and World Allergy Organization (WAO) document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA) and Global Allergy and Asthma European Network (GA2LEN)

Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 μm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect the physician’s considerations of disease features, phenotype, and response to previous therapy

Measurement of the branching fraction for the decay KS --> pi e nu

We present a measurement of the branching ratio BR(KS --> pi e nu) performed using the KLOE detector. KS mesons are produced in the reaction e+ e- --> phi --> KS KL at the DAFNE collider. In a sample of about 5 million KS-tagged events we find 624 +- 30 semileptonic KS decays. Normalizing to the KS --> pi+ pi- count in the same data sample, we obtain BR(KS --> pi e nu) = (6.91 +- 0.37) 10^-4, in agreement with the Standard Model expectation.Comment: 9 pages, 5 Encapsulated Postscript figures. Submitted to Phys. Lett.

Measurement of hadronic cross section and preliminary results on the pion form factor using the radiative return at DAPHNE

In the fixed energy environment of the $e^{+}e^{-}$ collider DA$\Phi$NE, KLOE can measure the cross section of the process $e^{+}e^{-} \to$ hadrons as a function of the hadronic system energy using the radiative return. At energies below 1 GeV, $e^{+}e^{-} \to \rho \to \pi^{+}\pi^{-}$ is the dominating hadronic process. We report here on the status of the analysis for the e^{+}e^{-} \to \ppg channel, which allows to obtain a preliminary measurement of the pion form factor using an integrated luminosity of $\sim73 pb^{-1}$.Comment: Invited talk at the Seventh International Workshop on Tau Lepton Physics (TAU02-WE07), Santa Cruz, Ca, USA, Sept 2002, 9 pages, LaTeX, 9 eps figure

Study of the Decay phi --> eta pi0 gamma with the KLOE detector

In a sample of 5.3x10^7 phi-decays observed with the KLOE detector at the Frascati phi-factory Dafne we find 605 eta pi0 gamma events with eta --> gamma\gamma and 197 eta pi0 gamma events with eta --> pi+ pi- pi0. The decay phi --> eta pi0 gamma is dominated by the process phi --> a0 gamma. From a fit to the eta pi0 mass spectrum we find BR(phi --> ao(980) gamma)= (7.4 +- 0.7)x10^-5.Comment: 12 pages, 6 figures, submitted to Phys.Lett.

Measuring the hadronic cross section via radiative return

Recently it has been demonstrated that particle factories, such as DAPHNE and PEP-II, operating at fixed center-of-mass energies, are able to measure hadronic cross sections as a function of the hadronic system energy using the raditive return. This paper is an experimental overview of the progress in this aera. Preliminary results from KLOE for the process e+e- -> \rho \gamma -> \pi+\pi-\gamma and a fit to the pion form factor are presented. Some first results from the BABAR collaboration are also shown.Comment: Invited talk presented at RADCOR/Loops and Legs 2002, Kloster Banz/Germany, September 8-13 2002, 6 pages, 2 Figures; v1: references added, typos correcte