There is growing interest in sex differences and RAS components. However, whether gender influences cardiac angiotensin I-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity ...is still unknown. In the present work, we determined the relationship between ACE and ACE2 activity, left ventricular function and gender in spontaneously hypertensive rats (SHRs).
Twelve-week-old female (F) and male (M) SHRs were divided into 2 experimental groups (n = 7 in each group): sham (S) and gonadectomized (G). Fifty days after gonadectomy, we measured positive and negative first derivatives (dP/dt maximum left ventricle (LV) and dP/dt minimum LV, respectively), hypertrophy (morphometric analysis) and ACE and ACE2 catalytic activity (fluorimetrically). Expression of calcium handling proteins was measured by western blot. Male rats exhibited higher cardiac ACE and ACE2 activity as well as hypertrophy compared to female rats. Orchiectomy decreased the activity of these enzymes and hypertrophy, while ovariectomy increased hypertrophy and ACE2, but did not change ACE activity. For cardiac function, the male sham group had a lower +dP/dt than the female sham group. After gonadectomy, the +dP/dt increased in males and reduced in females. The male sham group had a lower -dP/dt than the female group. After gonadectomy, the -dP/dt increased in the male and decreased in the female groups when compared to the sham group. No difference was observed among the groups in SERCA2a protein expression. Gonadectomy increased protein expression of PLB (phospholamban) and the PLB to SERCA2a ratio in female rats, but did not change in male rats.
Ovariectomy leads to increased cardiac hypertrophy, ACE2 activity, PLB expression and PLB to SERCA2a ratio, and worsening of hemodynamic variables, whereas in males the removal of testosterone has the opposite effects on RAS components.
Experiments were performed at the CERN SPS with 120 GeV/c stored proton beams to assess the possibility of beam halo collimation assisted by bent crystals. A bent crystal was used to deflect ...horizontally by an angle of about 170 μrad the beam halo protons in channeling states directing them into a 60 cm long tungsten absorber. The halo loss rate due to nuclear inelastic interactions of protons in the aligned crystal was up to five times smaller than for its amorphous orientation. Channeled fractions, (75±4)% and (85±5)% for the two tested silicon crystals, were measured by intercepting the deflected beam with another collimator located between the crystals and the absorber. The pixel detector (MEDIPIX) installed in a Roman pot inside the beam pipe was used to obtain visual images of the deflected beam.
Polarized antiprotons can be produced in a storage ring by spin-dependent interaction in a purely electron-polarized hydrogen gas target. The polarizing process is based on spin transfer from the ...polarized electrons of the target atoms to the orbiting antiprotons. After spin filtering for about two beam lifetimes at energies T approximately equal 40-170 MeV using a dedicated large acceptance ring, the antiproton beam polarization would reach P=0.2-0.4. Polarized antiprotons would open new and unique research opportunities for spin-physics experiments in p(-) p interactions.
A study of crystal assisted collimation has been continued at the CERN SPS for different energies of stored beams using 120 GeV/c and 270 GeV/c protons and Pb ions with 270 GeV/c per charge. A bent ...silicon crystal used as a primary collimator deflected halo particles using channeling and directing them into the tungsten absorber. A strong correlation of the beam losses in the crystal and off-momentum halo intensity measured in the first high dispersion (HD) area downstream was observed. In channeling conditions, the beam loss rate induced by inelastic interactions of particles with nuclei is significantly reduced in comparison with the non-oriented crystal. A maximal reduction of beam losses in the crystal larger than 20 was observed with 270 GeV/c protons. The off-momentum halo intensity measured in the HD area was also strongly reduced in channeling conditions. The reduction coefficient was larger than 7 for the case of Pb ions. A strong loss reduction was also detected in regions of the SPS ring far from the collimation area. It was shown by simulations that the miscut angle between the crystal surface and its crystallographic planes doubled the beam losses in the aligned crystal.
New experiments on crystal assisted collimation have been carried out at the CERN SPS with stored beams of 120 GeV/c protons and Pb ions. Bent silicon crystals of 2 mm long with about 170 μrad bend ...angle and a small residual torsion were used as primary collimators. In channeling conditions, the beam loss rate induced by inelastic interactions of particles with the crystal nuclei is minimal. The loss reduction was about 6 for protons and about 3 for Pb ions. Lower reduction value for Pb ions can be explained by their considerably larger ionization losses in the crystal. In one of the crystals, the measured fraction of the Pb ion beam halo deflected in channeling conditions was 74%, a value very close to that for protons. The intensity of the off-momentum halo leaking out from the collimation station was measured in the first high dispersion area downstream. The particle population in the shadow of the secondary collimator–absorber was considerably smaller in channeling conditions than for amorphous orientations of the crystal. The corresponding reduction was in the range of 2–5 for both protons and Pb ions.
Sex hormones modulate the action of both cytokines and the renin-angiotensin system. However, the effects of angiotensin I-converting enzyme (ACE) on the proinflammatory and anti-inflammatory ...cytokine levels in male and female spontaneously hypertensive rats (SHR) are unclear. We determined the relationship between ACE activity, cytokine levels and sex differences in SHR. Female (F) and male (M) SHR were divided into 4 experimental groups each (n = 7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage), castrated + vehicle, and castrated + enalapril. Treatment began 21 days after castration and continued for 30 days. Serum cytokine levels (ELISA) and ACE activity (fluorimetry) were measured. Male rats exhibited a higher serum ACE activity than female rats. Castration reduced serum ACE in males but did not affect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV = 16.4 ± 1.1 pg/mL; MSV = 12.8 ± 1.2 pg/mL), TNF-α (FSV = 16.6 ± 1.2 pg/mL; MSV = 12.8 ± 1 pg/mL) and IL-6 (FSV = 10.3 ± 0.2 pg/mL; MSV = 7.2 ± 0.2 pg/mL) levels were higher in females than in males. Ovariectomy reduced all cytokine levels and orchiectomy reduced IL-6 but increased IL-10 concentrations in males. Castration eliminated the differences in all inflammatory cytokine levels (IL-6 and TNF-α) between males and females. Enalapril increased IL-10 in all groups and reduced IL-6 in SV rats. In conclusion, serum ACE inhibition by enalapril eliminated the sexual dimorphisms of cytokine levels in SV animals, which suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive effects.
Deflection due to planar channeling and volume reflection in short bent silicon crystals was observed for the first time for 150 GeV/c negative particles, π− mesons, at one of the secondary beams of ...the CERN SPS. The deflection efficiency was about 30% for channeling and higher than 80% for volume reflection. Volume reflection occurs, in spite of the attractive character of the forces acting between the particles and the crystal planes, in a wide angular range of the crystal orientations determined by the crystal bend angle.
In ideal two-stage collimation systems, the secondary collimator–absorber should have its length sufficient to exclude practically the exit of halo particles with large impact parameters. In the UA9 ...experiments on the crystal assisted collimation of the SPS beam a 60 cm long tungsten bar is used as a secondary collimator–absorber which is insufficient for the full absorption of the halo protons. Multi-turn simulation studies of the collimation allowed to select the position for the beam loss monitor downstream the collimation area where the contribution of particles deflected by the crystal in channeling regime but emerging from the secondary collimator–absorber is considerably reduced. This allowed observation of a strong leakage reduction of halo protons from the SPS beam collimation area, thereby approaching the case with an ideal absorber.
Channeling is the confinement of the trajectory of a charged particle in a crystalline solid. Positively charged particles channeled between crystal planes oscillate with a certain oscillation ...length, which depends on particle energy. A crystal whose thickness is half the oscillation length for planar channeling may act as a mirror for charged particles. If the incident angle of the particle trajectory with the crystal plane is less than the critical angle for channeling, under-barrier particles undergo half an oscillation and exit the crystal with the reversal of their transverse momentum, i.e., the particles are “mirrored” by the crystal planes. Unlike the traditional scheme relying on millimeter-long curved crystals, particle mirroring enables beam steering in high-energy accelerators via interactions with micrometer-thin straight crystal. The main advantage of mirroring is the interaction with a minimal amount of material along the beam, thereby decreasing unwanted incoherent nuclear interactions. The effectiveness of the mirror effect for ultrarelativistic positive particles has been experimentally proven at external lines of CERN-SPS. The mirroring effect in a 26.5-μm-thick Si crystal has been studied in the experiment with a narrow beam of 400 GeV/c protons at the CERN-SPS. The reflection efficiency for a quasi-parallel beam is larger than 80%.
The possibility for optimization of crystal assisted collimation has been studied at the CERN SPS for stored beams of protons and Pb ions with 270 GeV/c per unit charge. A bent silicon crystal used ...as a primary collimator deflects halo particles in the channeling regime, directing them into a tungsten absorber. In channeling conditions a strong reduction of off-momentum particle numbers produced in the crystal and absorber, which form collimation leakage, has been observed in the first high dispersion (HD) area downstream. The present study shows that the collimation leakage is minimal for some values of the absorber offset relative to the crystal. The optimal offset value is larger for Pb ions because of their considerably larger ionization losses in the crystal, which cause large increases of particle betatron oscillation amplitudes. The optimal absorber offset allows obtaining maximal efficiency of crystal-assisted collimation.