A Measurement of the Interference Structure Function, R_LT, for the 12C(e,e'p) reaction in the Quasielastic Region

The coincidence cross-section and the interference structure function, R_LT, were measured for the 12C(e,e'p) 11B reaction at quasielastic kinematics and central momentum transfer of q=400 MeV/c. The measurement was at an opening angle of theta_pq=11 degrees, covering a range in missing energy of E_m = 0 to 65 MeV. The R_LT structure function is found to be consistent with zero for E_m > 50 MeV, confirming an earlier study which indicated that R_L vanishes in this region. The integrated strengths of the p- and s-shell are compared with a Distorted Wave Impulse Approximation calculation. The s-shell strength and shape are compared with a Hartree Fock-Random Phase Approximation calculation. The DWIA calculation overestimates the cross sections for p- and s-shell proton knockout as expected, but surprisingly agrees with the extracted R_LT value for both shells. The HF-RPA calculation describes the data more consistently, which may be due to the inclusion of 2-body currents in this calculation.Comment: 8 Pages LaTex, 5 postscript figures. Submitted to Phys. Rev.

First measurements of the ^16O(e,e'pn)^14N reaction

This paper reports on the first measurement of the ^16O(e,e'pn)^14N reaction. Data were measured in kinematics centred on a super-parallel geometry at energy and momentum transfers of 215 MeV and 316 MeV/c. The experimental resolution was sufficient to distinguish groups of states in the residual nucleus but not good enough to separate individual states. The data show a strong dependence on missing momentum and this dependence appears to be different for two groups of states in the residual nucleus. Theoretical calculations of the reaction using the Pavia code do not reproduce the shape or the magnitude of the data.Comment: 10 pages, 11 figures, 2 tables, Accepted for publication in EPJ

Investigation of the Exclusive 3He(e,e'pp)n Reaction

Cross sections for the 3He(e,e'pp)n reaction were measured over a wide range of energy and three- momentum transfer. At a momentum transfer q=375 MeV/c, data were taken at transferred energies omega ranging from 170 to 290 MeV. At omega=220 MeV, measurements were performed at three q values (305, 375, and 445 MeV/c). The results are presented as a function of the neutron momentum in the final-state, as a function of the energy and momentum transfer, and as a function of the relative momentum of the two-proton system. The data at neutron momenta below 100 MeV/c, obtained for two values of the momentum transfer at omega=220 MeV, are well described by the results of continuum-Faddeev calculations. These calculations indicate that the cross section in this domain is dominated by direct two-proton emission induced by a one-body hadronic current. Cross section distributions determined as a function of the relative momentum of the two protons are fairly well reproduced by continuum-Faddeev calculations based on various realistic nucleon-nucleon potential models. At higher neutron momentum and at higher energy transfer, deviations between data and calculations are observed that may be due to contributions of isobar currents.Comment: 14 pages, 1 table, 17 figure

MIG and the Regulatory Cytokines IL-10 and TGF-β1 Correlate with Malaria Vaccine Immunogenicity and Efficacy

Malaria remains one of the world's greatest killers and a vaccine is urgently required. There are no established correlates of protection against malaria either for natural immunity to the disease or for immunity conferred by candidate malaria vaccines. The RTS,S/AS02A vaccine offers significant partial efficacy against malaria

Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

MDM2-Driven Ubiquitination Rapidly Removes p53 from Its Cognate Promoters

MDM2 is the principal antagonist of the tumor suppressor p53. p53 binds to its cognate DNA element within promoters and activates the transcription of adjacent genes. These target genes include MDM2. Upon induction by p53, the MDM2 protein binds and ubiquitinates p53, triggering its proteasomal degradation and providing negative feedback. This raises the question whether MDM2 can also remove p53 from its target promoters, and whether this also involves ubiquitination. In the present paper, we employ the MDM2-targeted small molecule Nutlin-3a (Nutlin) to disrupt the interaction of MDM2 and p53 in three different cancer cell lines: SJSA-1 (osteosarcoma), 93T449 (liposarcoma; both carrying amplified MDM2), and MCF7 (breast adenocarcinoma). Remarkably, removing Nutlin from the culture medium for less than five minutes not only triggered p53 ubiquitination, but also dissociated most p53 from its chromatin binding sites, as revealed by chromatin immunoprecipitation. This also resulted in reduced p53-responsive transcription, and it occurred much earlier than the degradation of p53 by the proteasome, arguing that MDM2 removes p53 from promoters prior to and thus independent of degradation. Accordingly, the short-term pharmacological inhibition of the proteasome did not alter the removal of p53 from promoters by Nutlin washout. However, when the proteasome inhibitor was applied for several hours, depleting non-conjugated ubiquitin prior to eliminating Nutlin, this compromised the removal of DNA-bound p53, as did an E1 ubiquitin ligase inhibitor. This suggests that the ubiquitination of p53 by MDM2 is necessary for its clearance from promoters. Depleting the MDM2 cofactor MDM4 in SJSA cells did not alter the velocity by that p53 was removed from promoters upon Nutlin washout. We conclude that MDM2 antagonizes p53 not only by covering its transactivation domain and by destabilization, but also by the rapid, ubiquitin-dependent termination of p53–chromatin interactions