Isolation of novel ribozymes that ligate AMP-activated RNA substrates

AbstractBackground: The protein enzymes RNA ligase and DNA ligase catalyze the ligation of nucleic acids via an adenosine-5′-5′-pyrophosphate ‘capped’ RNA or DNA intermediate. The activation of nucleic acid substrates by adenosine 5′-monophosphate (AMP) may be a vestige of ‘RNA world’ catalysis. AMP-activated ligation seems ideally suited for catalysis by ribozymes (RNA enzymes), because an RNA motif capable of tightly and specifically binding AMP has previously been isolated.Results: We used in vitro selection and directed evolution to explore the ability of ribozymes to catalyze the template-directed ligation of AMP-activated RNAs. We subjected a pool of 1015 RNA molecules, each consisting of long random sequences flanking a mutagenized adenosine triphosphate (ATP) aptamer, to ten rounds of in vitro selection, including three rounds involving mutagenic polymerase chain reaction. Selection was for the ligation of an oligonucleotide to the 5′-capped active pool RNA species. Many different ligase ribozymes were isolated; these ribozymes had rates of reaction up to 0.4 ligations per hour, corresponding to rate accelerations of ∼ 5 × 105 over the templated, but otherwise uncatalyzed, background reaction rate. Three characterized ribozymes catalyzed the formation of 3′-5′-phosphodiester bonds and were highly specific for activation by AMP at the ligation site.Conclusions: The existence of a new class of ligase ribozymes is consistent with the hypothesis that the unusual mechanism of the biological ligases resulted from a conservation of mechanism during an evolutionary replacement of a primordial ribozyme ligase by a more modern protein enzyme. The newly isolated ligase ribozymes may also provide a starting point for the isolation of ribozymes that catalyze the polymerization of AMP-activated oligonucleotides or mononucleotides, which might have been the prebiotic analogs of nucleoside triphosphates

Essential reflections versus minimal embeddings

This note addresses the following question. In a category C, with a full subcategory X which is reflective with each reflection morphism an embedding, and a C-object A: when does each X-object containing A contain the X-reflection of A? We prove, under mild hypotheses on C, the equivalence of (1) The reflection morphism for A is an essential embedding, (2) Any \u27minimal\u27 embedding of A in an X-object is the X-reflection of A, (3) \u27Always\u27 is the answer to the question above, (4) The reflection functor C → X carries embeddings of A to embeddings. We note that these conditions hold for every A, for every X, if, in C, every epic embedding is essential, or if C has the Amalgamation Property. Various examples are discussed. © 1985

Relaxation of Surface Profiles by Evaporation Dynamics

We present simulations of the relaxation towards equilibrium of one dimensional steps and sinusoidal grooves imprinted on a surface below its roughening transition. We use a generalization of the hypercube stacking model of Forrest and Tang, that allows for temperature dependent next-nearest-neighbor interactions. For the step geometry the results at T=0 agree well with the t^(1/4) prediction of continuum theory for the spreading of the step. In the case of periodic profiles we modify the mobility for the tips of the profile and find the approximate solution of the resulting free boundary problem to be in reasonable agreement with the T=0 simulations.Comment: 6 pages, Revtex, 5 Postscript figures, to appear in PRB 15, October 199

Beobachtungsstudien im Rahmen eines naturheilkundlichen Klinikverbunds :Teil III: Zwischenergebnisse der diagnosespezifischen Dokumentation Migräne in der Klinik für TraditionelleChinesische Medizin Kötzting

Objective: To evaluate the course of symtoms and quality of life of migraine patients after treatment with traditional Chinese medicine. Design: Prospective observational study with 12 months follow-up. Patients: 138 consecutive patients diagnosed by a neurologist to have migraine headaches. Intervention: Complex in-patient treatment with traditional Chinese medicine including acupuncture and Chinese drug therapy. Outcomes: Number of days with headaches per month, number, intensity and duration of migraine attacks, concomitant symptoms, quality of life, global assessment and days off work. Results: The number of days with headaches per month decreased from 9 (median) at baseline to 4 at discharge and was 3 at 12 months. Also, for the other outcomes a clear improvement was seen with a slight wash-out tendency in follow-up. Conclusion: The observed patients with long-lasting migraines had a marked benefit from an in-patient treatment with traditional Chinese medicine

An α-disconnected space has no proper monic preimage

AbstractAll spaces are compact Hausdorff. α is an uncountable cardinal or the symbol ∞. A continuous map τ:X→Y is called an α-SpFi morphism if τ-1(G) is dense in X whenever G is a dense α-cozero set of Y. We thus have a category α-SpFi (spaces with the α-filter) which, like any category, has its monomorphisms; these need not be one-to-one. For general α, we cannot say what the α-SpFi monics are, but we show, and R.G. Woods showed, that ∞-SpFi monic means range-irreducible. The main theorem here is: X has no proper α-SpFi monic preimage if and only if X is α-disconnected. This generalizes (by putting in α = ∞) the well-known fact: X has no proper irreducible preimage if and only if X is extremally disconnected. If, in our theorem, we restrict to Boolean spaces and apply Stone duality, we have the theorem of R. Lagrange, that in Boolean α-algebras, epimorphisms are surjective.The theory of spaces with filters has a lot of connections with ordered algebra—Boolean algebras of course, but also lattice-ordered groups and frames. This paper is a contribution to the development of this topological theory

Extensions of l-homomorphisms

It is shown that, in abelian l-groups, each morphism to a complete vector lattice extends over any majorizing embedding. This extends a result of the first author for Archimedean f-algebras with identity, and the recent Luxemburg-Schep theorem for vector lattices, and solves a problem of Conrad and McAlister. The proof presented here differs substantially from the Luxem- burg-Schep proof. Ours uses the Yosida representation and Gleason’s theorem on topological projectivity—this is novel, and seems relatively economical and transparent. The l-group theorem is shown to imply, and with some modestly categorical machinery, to be implied by, certain similar statements in subcategories of l-groups. © 1982 Rocky Mountain Mathematics Consortium

Beobachtungsstudien im Rahmen eines naturheilkundlichen Klinikverbunds :Teil II: Detaillierte Ergebnisse der Klinik für Traditionelle ChinesischeMedizin Kötzting

Objective: To collect information on patients, interventions and outcomes in a hospital for traditional Chinese medicine in Germany. Design: Prospective observational study with 12 months followup. Patients: All 667 consecutive patients admitted for in-patient treatment in the hospital between December 1994 and July 1995 were documented. The follow-up rate after 12 months was 65.8%. Outcome Measures: Sociodemographic data, diagnoses, duration of complaints, type and frequency of diagnostic and therapeutic interventions, intensity of complaints, assessment of the therapeutic success and quality of life. Results: About two thirds of the patients suffered from chronic pain syndromes (the most frequent single diagnoses were migraine, lumbago, and neck pain/headaches). 72.3% of the patients were female; the median duration since the onset of the disease was 7 years. Almost all patients received acupuncture and treatment with traditional Chinese drugs. 50.3% assessed the therapeutic success as good or very good at discharge; after 12 months this rate was 55.6%. Both intensity of main complaints and psychic and physical aspects of quality of life improved after treatment. After 12 months the improvement was less distinct but still significant. Conclusions: The in-patient treatment provided a clear benefit to the patients. Without a valid comparison with an alternative treatment little can be concluded about comparative effectiveness and efficiency of a treatment in the hospital for traditional Chinese medicine

Topological Constraints at the Theta Point: Closed Loops at Two Loops

We map the problem of self-avoiding random walks in a Theta solvent with a chemical potential for writhe to the three-dimensional symmetric U(N)-Chern-Simons theory as N goes to 0. We find a new scaling regime of topologically constrained polymers, with critical exponents that depend on the chemical potential for writhe, which gives way to a fluctuation-induced first-order transition.Comment: 5 pages, RevTeX, typo

Fast and Accurate Camera Covariance Computation for Large 3D Reconstruction

Estimating uncertainty of camera parameters computed in Structure from Motion (SfM) is an important tool for evaluating the quality of the reconstruction and guiding the reconstruction process. Yet, the quality of the estimated parameters of large reconstructions has been rarely evaluated due to the computational challenges. We present a new algorithm which employs the sparsity of the uncertainty propagation and speeds the computation up about ten times \wrt previous approaches. Our computation is accurate and does not use any approximations. We can compute uncertainties of thousands of cameras in tens of seconds on a standard PC. We also demonstrate that our approach can be effectively used for reconstructions of any size by applying it to smaller sub-reconstructions.Comment: ECCV 201