15 research outputs found
Channel Coupling in Reactions
The sensitivity of momentum distributions, recoil polarization observables,
and response functions for nucleon knockout by polarized electrons to channel
coupling in final-state interactions is investigated using a model in which
both the distorting and the coupling potentials are constructed by folding
density-dependent effective interactions with nuclear transition densities.
Calculations for O are presented for 200 and 433 MeV ejectile energies,
corresponding to proposed experiments at MAMI and TJNAF, and for C at 70
and 270 MeV, corresponding to experiments at NIKHEF and MIT-Bates. The relative
importance of charge exchange decreases as the ejectile energy increases, but
remains significant for 200 MeV. Both proton and neutron knockout cross
sections for large recoil momenta, MeV/c, are substantially
affected by inelastic couplings even at 433 MeV. Significant effects on the
cross section for neutron knockout are also predicted at smaller recoil
momenta, especially for low energies. Polarization transfer for proton knockout
is insensitive to channel coupling, even for fairly low ejectile energies, but
polarization transfer for neutron knockout retains nonnegligible sensitivity to
channel coupling for energies up to about 200 MeV. The present results suggest
that possible medium modifications of neutron and proton electromagnetic form
factors for can be studied using recoil
polarization with relatively little sensitivity due to final state
interactions.Comment: Substantially revised version accepted by Phys. Rev. C; shortened to
49 pages including 21 figure
Bi-allelic variants in TONSL cause SPONASTRIME dysplasia and a spectrum of skeletal dysplasia phenotypes
SPONASTRIME dysplasia is an autosomal-recessive spondyloepimetaphyseal dysplasia characterized by spine (spondylar) abnormalities, midface hypoplasia with a depressed nasal bridge, metaphyseal striations, and disproportionate short stature. Scoliosis, coxa vara, childhood cataracts, short dental roots, and hypogammaglobulinemia have also been reported in this disorder. Although an autosomal-recessive inheritance pattern has been hypothesized, pathogenic variants in a specific gene have not been discovered in individuals with SPONASTRIME dysplasia. Here, we identified bi-allelic variants in TONSL, which encodes the Tonsoku-like DNA repair protein, in nine subjects (from eight families) with SPONASTRIME dysplasia, and four subjects (from three families) with short stature of varied severity and spondylometaphyseal dysplasia with or without immunologic and hematologic abnormalities, but no definitive metaphyseal striations at diagnosis. The finding of early embryonic lethality in a Tonsl-/- murine model and the discovery of reduced length, spinal abnormalities, reduced numbers of neutrophils, and early lethality in a tonsl-/- zebrafish model both support the hypomorphic nature of the identified TONSL variants. Moreover, functional studies revealed increased amounts of spontaneous replication fork stalling and chromosomal aberrations, as well as fewer camptothecin (CPT)-induced RAD51 foci in subject-derived cell lines. Importantly, these cellular defects were rescued upon re-expression of wild-type (WT) TONSL; this rescue is consistent with the hypothesis that hypomorphic TONSL variants are pathogenic. Overall, our studies in humans, mice, zebrafish, and subject-derived cell lines confirm that pathogenic variants in TONSL impair DNA replication and homologous recombination-dependent repair processes, and they lead to a spectrum of skeletal dysplasia phenotypes with numerous extra-skeletal manifestations