High-precision Studies of the 3^{\bf{3}}He(e,e′^{\bf{\prime}}p) Reaction at the Quasielastic Peak

Precision studies of the reaction $^{3}$He(e,e$^\prime$p) using the three-spectrometer facility at the Mainz microtron MAMI are presented. All data are for quasielastic kinematics at $|\vec{q} | =685$ MeV/c. Absolute cross sections were measured at three electron kinematics. For the measured missing momenta range from 10 to 165 MeV/c, no strength is observed for missing energies higher than 20 MeV. Distorted momentum distributions were extracted for the two-body breakup and the continuum. The longitudinal and transverse behavior was studied by measuring the cross section for three photon polarizations. The longitudinal and transverse nature of the cross sections is well described by a currently accepted and widely used prescription of the off-shell electron-nucleon cross-section. The results are compared to modern three-body calculations and to previous data.Comment: 4 pages, 3 figures. Submitted for publication in Phys. Rev. Let

Measurement of the 12C(e,e'p)11B Two-Body Breakup Reaction at High Missing Momentum Values

The five-fold differential cross section for the 12C(e,e'p)11B reaction was determined over a missing momentum range of 200-400 MeV/c, in a kinematics regime with Bjorken x > 1 and Q2 = 2.0 (GeV/c)2. A comparison of the results and theoretical models and previous lower missing momentum data is shown. The theoretical calculations agree well with the data up to a missing momentum value of 325 MeV/c and then diverge for larger missing momenta. The extracted distorted momentum distribution is shown to be consistent with previous data and extends the range of available data up to 400 MeV/c.Comment: 12 pages, 1 table and 3 figures for submission to Journal Physics

Pharmacokinetics of acute tryptophan depletion using a gelatin-based protein in male and female Wistar rats

The essential amino acid tryptophan is the precursor of the neurotransmitter serotonin. By depleting the body of tryptophan, brain tryptophan and serotonin levels are temporarily reduced. In this paper, several experiments are described in which dose and treatment effects of acute tryptophan depletion (ATD) using a gelatin-based protein–carbohydrate mixture were studied in male and female Wistar rats. Two or three doses of tryptophan depleting mixture resulted in 65–70% depletion after 2–4 h in males. ATD effects were similar in females, although females may return to baseline levels faster. Treatment effects after four consecutive days of ATD were similar to the effects of 1 day of treatment. Object recognition memory was impaired 2, 4, and 6 h after the first of two doses of ATD, suggesting that the central effects occurred rapidly and continued at least 6 h, in spite of decreasing treatment effects on plasma tryptophan levels at that time point. The method of acute tryptophan depletion described here can be used to study the relationship between serotonin and behaviour in both male and female rats

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

One-year safety and efficacy of mitapivat in sickle cell disease:follow-up results of a phase 2, open-label study

Targeting the primary pathogenic event of sickle cell disease (SCD), the polymerization of sickle hemoglobin (HbS), may prevent downstream clinical events. Mitapivat, an oral pyruvate kinase (PK) activator, has therapeutic potential by increasing adenosine triphosphate (ATP) and decreasing 2,3-diphosphoglycerate (2,3-DPG), a glycolytic red blood cell (RBC) intermediate. In the previously reported 8-week dose-finding period of this phase 2, investigator-initiated, open-label study, mitapivat was well tolerated and showed efficacy in SCD. Here, the 1-year fixed-dose extension period is reported in which 9 of 10 included patients (90%) aged ≥16 years with SCD (HbSS, HbS/β0, or HbS/β+) continued with mitapivat. Mostly mild treatment-emergent adverse events (AEs) (most commonly, transaminase increase and headache) were still reported. Apart from the reported nontreatment-related serious AE (SAE) of a urinary tract infection in the dose-finding period, 1 nontreatment-related SAE occurred in the fixed-dose extension period in a patient who died of massive pulmonary embolism due to COVID-19. Importantly, sustained improvement in Hb level (mean increase, 1.1 ± 0.7 g/dL; P = .0014) was seen, which was accompanied by decreases in markers of hemolysis. In addition, the annualized rate of vaso-occlusive events reduced significantly from a historic baseline of 1.33 ± 1.32 to 0.64 ± 0.87 (P = .0489) when combining the dose-finding period and fixed-dose extension period. Cellularly, the ATP:2,3-DPG ratio and Hb-oxygen affinity significantly increased and RBC sickling (point of sickling) nonsignificantly reduced. Overall, this study demonstrated 1-year safety and efficacy of treatment with mitapivat in SCD, supporting further evaluation in ongoing phase 2/3 study (RISE UP, NCT05031780). This trial was registered at https://www.clinicaltrialsregister.eu/as NL8517 and EudraCT 2019-003438-18.</p