657,918 research outputs found

    On the uniform one-dimensional fragment

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    The uniform one-dimensional fragment of first-order logic, U1, is a recently introduced formalism that extends two-variable logic in a natural way to contexts with relations of all arities. We survey properties of U1 and investigate its relationship to description logics designed to accommodate higher arity relations, with particular attention given to DLR_reg. We also define a description logic version of a variant of U1 and prove a range of new results concerning the expressivity of U1 and related logics

    Conditional U1 gene silencing in Toxoplasma gondii

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    The functional characterisation of essential genes in apicomplexan parasites, such as Toxoplasma gondii or Plasmodium falciparum, relies on conditional mutagenesis systems. Here we present a novel strategy based on U1 snRNP-mediated gene silencing. U1 snRNP is critical in pre-mRNA splicing by defining the exon-intron boundaries. When a U1 recognition site is placed into the 3’-terminal exon or adjacent to the termination codon, pre-mRNA is cleaved at the 3’-end and degraded, leading to an efficient knockdown of the gene of interest (GOI). Here we describe a simple method that combines endogenous tagging with DiCre-mediated positioning of U1 recognition sites adjacent to the termination codon of the GOI which leads to a conditional knockdown of the GOI upon rapamycin-induction. Specific knockdown mutants of the reporter gene GFP and several endogenous genes of T. gondii including the clathrin heavy chain gene 1 (chc1), the vacuolar protein sorting gene 26 (vps26), and the dynamin-related protein C gene (drpC) were silenced using this approach and demonstrate the potential of this technology. We also discuss advantages and disadvantages of this method in comparison to other technologies in more detail

    Molecular principles underlying dual RNA specificity in the Drosophila SNF protein

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    The first RNA recognition motif of the Drosophila SNF protein is an example of an RNA binding protein with multi-specificity. It binds different RNA hairpin loops in spliceosomal U1 or U2 small nuclear RNAs, and only in the latter case requires the auxiliary U2A′ protein. Here we investigate its functions by crystal structures of SNF alone and bound to U1 stem-loop II, U2A′ or U2 stem-loop IV and U2A′, SNF dynamics from NMR spectroscopy, and structure-guided mutagenesis in binding studies. We find that different loop-closing base pairs and a nucleotide exchange at the tips of the loops contribute to differential SNF affinity for the RNAs. U2A′ immobilizes SNF and RNA residues to restore U2 stem-loop IV binding affinity, while U1 stem-loop II binding does not require such adjustments. Our findings show how U2A′ can modulate RNA specificity of SNF without changing SNF conformation or relying on direct RNA contacts

    On the Consequences of the Detection of an Interstellar Asteroid

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    The arrival of the robustly hyperbolic asteroid A/2017 U1 has potentially interesting ramifications for the planet-formation process. Although extrapolations from a sample size of one are necessarily uncertain, order-of-magnitude estimates suggest that the Galaxy contains a substantial mass in similar bodies. We argue that despite its lack of Coma, A/2017 U1 likely contained a significant mass fraction of volatile components, and we argue that its presence can be used to infer a potentially large population of as-yet undetected Neptune-like extrasolar planets.Comment: Submitted to Research Notes of the AA

    Undecidability of a weak version of MSO+U

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    We prove the undecidability of MSO on ω-words extended with the second-order predicate U1(X) which says that the distance between consecutive positions in a set X⊆N is unbounded. This is achieved by showing that adding U1 to MSO gives a logic with the same expressive power as MSO+U, a logic on ω-words with undecidable satisfiability. As a corollary, we prove that MSO on ω-words becomes undecidable if allowing to quantify over sets of positions that are ultimately periodic, i.e., sets X such that for some positive integer p, ultimately either both or none of positions x and x+p belong to X

    A search variability in the UV spectrum of Pi Aquarii and Fe 3 shell lines of Be stars

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    Several short U1 and U2 observations of Be stars are obtained with the Copernicus satellite. Pi Aquarii (B1 IV-Ve) is observed with the U1 and U2 spectrometers. These scans are compared with earlier observations. Variations in the strengths and profiles of selected shell and photospheric features are examined. In order to study possible changes in the temperature of the circumstellar envelope, features covering a wide range in ionization are observed. Included in the observing program are lines of O VI, N V, Si IV, Si III, S III, Fe III, and N I

    Upregulation of Functional Kv11.1a Isoform Expression by Modified U1 Small Nuclear RNA

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    The KCNH2 or human ether-a go-go-related gene (hERG) encodes the Kv11.1 potassium channel that conducts the rapidly activating delayed rectifier potassium current in the heart. The expression of Kv11.1 C-terminal isoforms is directed by the alternative splicing and polyadenylation of intron 9. Splicing of intron 9 leads to the formation of a functional, full-length Kv11.1a isoform and polyadenylation of intron 9 results in the production of a non-functional, C-terminally truncated Kv11.1a-USO isoform. The relative expression of Kv11.1a and Kv11.1a-USO plays an important role in regulating Kv11.1 channel function. In the heart, only one-third of KCNH2 pre-mRNA is processed to Kv11.1a due to the weak 5′ splice site of intron 9. We previously showed that the weak 5′ splice site is caused by sequence deviation from the consensus, and that mutations toward the consensus sequence increased the efficiency of intron 9 splicing. It is well established that 5′ splice sites are recognized by complementary base-paring with U1 small nuclear RNA (U1 snRNA). In this study, we modified the sequence of U1 snRNA to increase its complementarity to the 5′ splice site of KCNH2 intron 9 and observed a significant increase in the efficiency of intron 9 splicing. RNase protection assay and western blot analysis showed that modified U1 snRNA increased the expression of the functional Kv11.1a isoform and concomitantly decreased the expression of the non-functional Kv11.1a-USO isoform. In patch-clamp experiments, modified U1 snRNA significantly increased Kv11.1 current. Our findings suggest that relative expression of Kv11.1 C-terminal isoforms can be regulated by modified U1 snRNA

    LHC Missing-Transverse-Energy Constraints on Models with Universal Extra Dimensions

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    We consider the performance of the ATLAS and CMS searches for events with missing transverse energy, which were originally motivated by supersymmetry, in constraining extensions of the Standard Model based on extra dimensions, in which the mass differences between recurrences at the same level are generically smaller than the mass hierarchies in typical supersymmetric models. We consider first a toy model with pair-production of a single vector-like quark U1 decaying into a spin-zero stable particle A1 and jet, exploring the sensitivity of the CMS alphaT and ATLAS meff analysis to U1 mass and the U1-A1 mass difference. For this purpose we use versions of the Delphes generic detector simulation with CMS and ATLAS cards, which have been shown to reproduce the published results of CMS and ATLAS searches for supersymmetry. We then explore the sensitivity of these searches to a specific model with two universal extra dimensions, whose signal is dominated by the pair production of quark recurrences, including searches with leptons. We find that the LHC searches have greater sensitivity to this more realistic model, due partly to the contributions of signatures with leptons, and partly to events with large missing transverse energy generated by the decays of higher-level Kaluza-Klein recurrences. We find that the CMS alphaT analysis with ~5/fb of data at 7 TeV excludes a recurrence scale of 600 GeV at a confidence level above 99%, increasing to 99.9% when combined with the CMS single-lepton search, whereas a recurrence scale of 700 GeV is disfavoured at the 72% confidence level.Comment: 29 pages, 11 figures, 5 tables, references adde
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