Channel Coupling in A(e⃗,e′N⃗)BA(\vec{e},e' \vec{N})B 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 $^{16}$O are presented for 200 and 433 MeV ejectile energies, corresponding to proposed experiments at MAMI and TJNAF, and for $^{12}$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, $p_m > 300$ 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 $Q^2 \gtrsim 0.5 (GeV/c)^2$ 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