526 research outputs found
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 nuclear energy density functional formalism
The present document focuses on the theoretical foundations of the nuclear
energy density functional (EDF) method. As such, it does not aim at reviewing
the status of the field, at covering all possible ramifications of the approach
or at presenting recent achievements and applications. The objective is to
provide a modern account of the nuclear EDF formalism that is at variance with
traditional presentations that rely, at one point or another, on a {\it
Hamiltonian-based} picture. The latter is not general enough to encompass what
the nuclear EDF method represents as of today. Specifically, the traditional
Hamiltonian-based picture does not allow one to grasp the difficulties
associated with the fact that currently available parametrizations of the
energy kernel at play in the method do not derive from a genuine
Hamilton operator, would the latter be effective. The method is formulated from
the outset through the most general multi-reference, i.e. beyond mean-field,
implementation such that the single-reference, i.e. "mean-field", derives as a
particular case. As such, a key point of the presentation provided here is to
demonstrate that the multi-reference EDF method can indeed be formulated in a
{\it mathematically} meaningful fashion even if does {\it not} derive
from a genuine Hamilton operator. In particular, the restoration of symmetries
can be entirely formulated without making {\it any} reference to a projected
state, i.e. within a genuine EDF framework. However, and as is illustrated in
the present document, a mathematically meaningful formulation does not
guarantee that the formalism is sound from a {\it physical} standpoint. The
price at which the latter can be enforced as well in the future is eventually
alluded to.Comment: 64 pages, 8 figures, submitted to Euroschool Lecture Notes in Physics
Vol.IV, Christoph Scheidenberger and Marek Pfutzner editor
HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.
The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders
- …