Discovering Restricted Regular Expressions with Interleaving

Discovering a concise schema from given XML documents is an important problem in XML applications. In this paper, we focus on the problem of learning an unordered schema from a given set of XML examples, which is actually a problem of learning a restricted regular expression with interleaving using positive example strings. Schemas with interleaving could present meaningful knowledge that cannot be disclosed by previous inference techniques. Moreover, inference of the minimal schema with interleaving is challenging. The problem of finding a minimal schema with interleaving is shown to be NP-hard. Therefore, we develop an approximation algorithm and a heuristic solution to tackle the problem using techniques different from known inference algorithms. We do experiments on real-world data sets to demonstrate the effectiveness of our approaches. Our heuristic algorithm is shown to produce results that are very close to optimal.Comment: 12 page

Mod/Resc Parsimony Inference

We address in this paper a new computational biology problem that aims at understanding a mechanism that could potentially be used to genetically manipulate natural insect populations infected by inherited, intra-cellular parasitic bacteria. In this problem, that we denote by \textsc{Mod/Resc Parsimony Inference}, we are given a boolean matrix and the goal is to find two other boolean matrices with a minimum number of columns such that an appropriately defined operation on these matrices gives back the input. We show that this is formally equivalent to the \textsc{Bipartite Biclique Edge Cover} problem and derive some complexity results for our problem using this equivalence. We provide a new, fixed-parameter tractability approach for solving both that slightly improves upon a previously published algorithm for the \textsc{Bipartite Biclique Edge Cover}. Finally, we present experimental results where we applied some of our techniques to a real-life data set.Comment: 11 pages, 3 figure

Chiral three-nucleon forces and bound excited states in neutron-rich oxygen isotopes

We study the spectra of neutron-rich oxygen isotopes based on chiral two- and three-nucleon interactions. First, we benchmark our many-body approach by comparing ground-state energies to coupled-cluster results for the same two-nucleon interaction, with overall good agreement. We then calculate bound excited states in 21,22,23O, focusing on the role of three-nucleon forces, in the standard sd shell and an extended sdf7/2p3/2 valence space. Chiral three-nucleon forces provide important one- and two-body contributions between valence neutrons. We find that both these contributions and an extended valence space are necessary to reproduce key signatures of novel shell evolution, such as the N = 14 magic number and the low-lying states in 21O and 23O, which are too compressed with two-nucleon interactions only. For the extended space calculations, this presents first work based on nuclear forces without adjustments. Future work is needed and open questions are discussed.Comment: 6 pages, 4 figures, published versio

Foot-and-mouth disease virus genome replication is unaffected by inhibition of type III phosphatidylinositol-4-kinases

Foot-and-mouth disease virus (FMDV) causes economically-damaging infections of cloven-hooved animals, with outbreaks resulting in large financial losses to the agricultural industry. Due to the highly contagious nature of FMDV, research with infectious virus is restricted to a limited number of key facilities worldwide. FMDV subgenomic replicons are therefore important tools for the study of viral translation and genome replication. The type III phosphatidylinositol-4-kinases (PI4K) are a family of enzymes that play a key role in the production of replication complexes (viral factories) of a number of positive-sense RNA viruses and represents a potential target for novel pan-viral therapeutics. Here, we have investigated whether type III PI4Ks also play a role in the FMDV lifecycle, using a combination of FMDV subgenomic replicons and bicistronic IRES-containing reporter plasmids. We have demonstrated that replication of the FMDV replicon was unaffected by inhibitors of either PI4KIIIα or PI4KIIIβ. However, PIK93, an inhibitor previously demonstrated to target PI4KIIIβ, did inhibit IRES-mediated protein translation. Consistent with this, cells transfected with FMDV replicons did not exhibit elevated levels of PI4P lipids. These results are therefore supportive of the hypothesis that FMDV genome replication does not require type III PI4K activity and does not activate these kinases

Glycan shifting on hepatitis C virus (HCV) E2 glycoprotein is a mechanism for escape from broadly neutralizing antibodies

Hepatitis C virus (HCV) infection is a major cause of liver disease and hepatocellular carcinoma. Glycan shielding has been proposed to be a mechanism by which HCV masks broadly neutralizing epitopes on its viral glycoproteins. However, the role of altered glycosylation in HCV resistance to broadly neutralizing antibodies is not fully understood. Here, we have generated potent HCV neutralizing antibodies hu5B3.v3 and MRCT10.v362 that, similar to the previously described AP33 and HCV1, bind to a highly conserved linear epitope on E2. We utilize a combination of in vitro resistance selections using the cell culture infectious HCV and structural analyses to identify mechanisms of HCV resistance to hu5B3.v3 and MRCT10.v362. Ultra deep sequencing from in vitro HCV resistance selection studies identified resistance mutations at asparagine N417 (N417S, N417T and N417G) as early as 5 days post treatment. Comparison of the glycosylation status of soluble versions of the E2 glycoprotein containing the respective resistance mutations revealed a glycosylation shift from N417 to N415 in the N417S and N417T E2 proteins. The N417G E2 variant was glycosylated neither at residue 415 nor at residue 417 and remained sensitive to MRCT10.v362. Structural analyses of the E2 epitope bound to hu5B3.v3 Fab and MRCT10.v362 Fab using X-ray crystallography confirmed that residue N415 is buried within the antibody–peptide interface. Thus, in addition to previously described mutations at N415 that abrogate the β-hairpin structure of this E2 linear epitope, we identify a second escape mechanism, termed glycan shifting, that decreases the efficacy of broadly neutralizing HCV antibodies

The Chromatin Remodeler SPLAYED Regulates Specific Stress Signaling Pathways

Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks

Positioning of subdomain IIId and apical loop of domain II of the hepatitis C IRES on the human 40S ribosome

The 5′-untranslated region of the hepatitis C virus (HCV) RNA contains a highly structured motif called IRES (Internal Ribosome Entry Site) responsible for the cap-independent initiation of the viral RNA translation. At first, the IRES binds to the 40S subunit without any initiation factors so that the initiation AUG codon falls into the P site. Here using an original site-directed cross-linking strategy, we identified 40S subunit components neighboring subdomain IIId, which is critical for HCV IRES binding to the subunit, and apical loop of domain II, which was suggested to contact the 40S subunit from data on cryo-electron microscopy of ribosomal complexes containing the HCV IRES. HCV IRES derivatives that bear a photoactivatable group at nucleotide A275 or at G263 in subdomain IIId cross-link to ribosomal proteins S3a, S14 and S16, and HCV IRES derivatized at the C83 in the apex of domain II cross-link to proteins S14 and S16