310 research outputs found
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
Reconfiguration of Cliques in a Graph
We study reconfiguration problems for cliques in a graph, which determine
whether there exists a sequence of cliques that transforms a given clique into
another one in a step-by-step fashion. As one step of a transformation, we
consider three different types of rules, which are defined and studied in
reconfiguration problems for independent sets. We first prove that all the
three rules are equivalent in cliques. We then show that the problems are
PSPACE-complete for perfect graphs, while we give polynomial-time algorithms
for several classes of graphs, such as even-hole-free graphs and cographs. In
particular, the shortest variant, which computes the shortest length of a
desired sequence, can be solved in polynomial time for chordal graphs,
bipartite graphs, planar graphs, and bounded treewidth graphs
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
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
Inhibition of transcription leads to rewiring of locus-specific chromatin proteomes
Transcription of a chromatin template involves the concerted interaction of many different proteins and protein complexes. Analyses of specific factors showed that these interactions change during stress and upon developmental switches. However, how the binding of multiple factors at any given locus is coordinated has been technically challenging to investigate. Here we used Epi-Decoder in yeast to systematically decode, at one transcribed locus, the chromatin binding changes of hundreds of proteins in parallel upon perturbation of transcription. By taking advantage of improved Epi-Decoder libraries, we observed broad rewiring of local chromatin proteomes following chemical inhibition of RNA polymerase. Rapid reduction of RNA polymerase II binding was accompanied by reduced binding of many other core transcription proteins and gain of chromatin remodelers. In quiescent cells, where strong transcriptional repression is induced by physiological signals, eviction of the core transcriptional machinery was accompanied by the appearance of quiescent cell-specific repressors and rewiring of the interactions of protein-folding factors and metabolic enzymes. These results show that Epi-Decoder provides a powerful strategy for capturing the temporal binding dynamics of multiple chromatin proteins under varying conditions and cell states. The systematic and comprehensive delineation of dynamic local chromatin proteomes will greatly aid in uncovering protein-protein relationships and protein functions at the chromatin template.Chemical Immunolog
Feedback Vertex Sets in Tournaments
We study combinatorial and algorithmic questions around minimal feedback
vertex sets in tournament graphs.
On the combinatorial side, we derive strong upper and lower bounds on the
maximum number of minimal feedback vertex sets in an n-vertex tournament. We
prove that every tournament on n vertices has at most 1.6740^n minimal feedback
vertex sets, and that there is an infinite family of tournaments, all having at
least 1.5448^n minimal feedback vertex sets. This improves and extends the
bounds of Moon (1971).
On the algorithmic side, we design the first polynomial space algorithm that
enumerates the minimal feedback vertex sets of a tournament with polynomial
delay. The combination of our results yields the fastest known algorithm for
finding a minimum size feedback vertex set in a tournament
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
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
Status report KfK contribution to the development of DEMO-relevant test blankets for NET/ITER. Part 2: BOT helium cooled solid breeder blanket. Vol. 1: Summary
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