Structure properties of 226{}^{226}Th and 256,258,260{}^{256,258,260}Fm fission fragments: mean field analysis with the Gogny force

The constrained Hartree-Fock-Bogoliubov method is used with the Gogny interaction D1S to calculate potential energy surfaces of fissioning nuclei ${}^{226}$Th and ${}^{256,258,260}$Fm up to very large deformations. The constraints employed are the mass quadrupole and octupole moments. In this subspace of collective coordinates, many scission configurations are identified ranging from symmetric to highly asymmetric fragmentations. Corresponding fragment properties at scission are derived yielding fragment deformations, deformation energies, energy partitioning, neutron binding energies at scission, neutron multiplicities, charge polarization and total fragment kinetic energies.Comment: 15 pages, 23 figures, accepted for publication in Phys. Rev. C (2007

Heralding two- and four-photon path entanglement on chip

Generating quantum entanglement is not only an important scientific endeavor, but will be essential to realizing quantum-enhanced technologies, in particular, quantum-enhanced measurements with precision beyond classical limits. We investigate the heralded generation of multiphoton entanglement for quantum metrology using a reconfigurable integrated waveguide device in which projective measurement of auxiliary photons heralds the generation of path-entangled states. We use four and six-photon inputs, to analyze the heralding process of two- and four-photon NOON states-a superposition of N photons in two paths, capable of enabling phase supersensitive measurements at the Heisenberg limit. Realistic devices will include imperfections; as part of the heralded state preparation, we demonstrate phase superresolution within our chip with a state that is more robust to photon loss

Einstein-Weyl structures and Bianchi metrics

We analyse in a systematic way the (non-)compact four dimensional Einstein-Weyl spaces equipped with a Bianchi metric. We show that Einstein-Weyl structures with a Class A Bianchi metric have a conformal scalar curvature of constant sign on the manifold. Moreover, we prove that most of them are conformally Einstein or conformally K\"ahler ; in the non-exact Einstein-Weyl case with a Bianchi metric of the type $VII_0, VIII$ or $IX$, we show that the distance may be taken in a diagonal form and we obtain its explicit 4-parameters expression. This extends our previous analysis, limited to the diagonal, K\"ahler Bianchi $IX$ case.Comment: Latex file, 12 pages, a minor modification, accepted for publication in Class. Quant. Gra

Cryo-EM reconstructions of inhibitor-bound SMG1 kinase reveal an autoinhibitory state dependent on SMG8

The PI3K-related kinase (PIKK) SMG1 monitors the progression of metazoan nonsense-mediated mRNA decay (NMD) by phosphorylating the RNA helicase UPF1. Previous work has shown that the activity of SMG1 is impaired by small molecule inhibitors, is reduced by the SMG1 interactors SMG8 and SMG9, and is downregulated by the so-called SMG1 insertion domain. However, the molecular basis for this complex regulatory network has remained elusive. Here, we present cryo-electron microscopy reconstructions of human SMG1-9 and SMG1-8-9 complexes bound to either a SMG1 inhibitor or a non-hydrolyzable ATP analog at overall resolutions ranging from 2.8 to 3.6 angstrom. These structures reveal the basis with which a small molecule inhibitor preferentially targets SMG1 over other PIKKs. By comparison with our previously reported substrate-bound structure (Langer et al.,2020), we show that the SMG1 insertion domain can exert an autoinhibitory function by directly blocking the substrate-binding path as well as overall access to the SMG1 kinase active site. Together with biochemical analysis, our data indicate that SMG1 autoinhibition is stabilized by the presence of SMG8. Our results explain the specific inhibition of SMG1 by an ATP-competitive small molecule, provide insights into regulation of its kinase activity within the NMD pathway, and expand the understanding of PIKK regulatory mechanisms in general.Acknowledgements: Daniel Bollschweiler and Tillman Schäfer at the MPIB cryo-EM facility for help with EM data collection and Barbara Steigenberger and Elisabeth Weyher at MPIB biochemistry core facility for carrying out mass spectrometry

Structure of substrate-bound SMG1-8-9 kinase complex reveals molecular basis for phosphorylation specificity

PI3K-related kinases (PIKKs) are large Serine/Threonine (Ser/Thr)-protein kinases central to the regulation of many fundamental cellular processes. PIKK family member SMG1 orchestrates progression of an RNA quality control pathway, termed nonsense-mediated mRNA decay (NMD), by phosphorylating the NMD factor UPF1. Phosphorylation of UPF1 occurs in its unstructured N- and C-terminal regions at Serine/Threonine-Glutamine (SQ) motifs. How SMG1 and other PIKKs specifically recognize SQ motifs has remained unclear. Here, we present a cryo-electron microscopy (cryo-EM) reconstruction of a human SMG1-8-9 kinase complex bound to a UPF1 phosphorylation site at an overall resolution of 2.9 angstrom. This structure provides the first snapshot of a human PIKK with a substrate-bound active site. Together with biochemical assays, it rationalizes how SMG1 and perhaps other PIKKs specifically phosphorylate Ser/Thr-containing motifs with a glutamine residue at position +1 and a hydrophobic residue at position -1, thus elucidating the molecular basis for phosphorylation site recognition