Phase Locking the Spin Precession in a Storage Ring.

This Letter reports the successful use of feedback from a spin polarization measurement to the revolution frequency of a 0.97 GeV/c bunched and polarized deuteron beam in the Cooler Synchrotron (COSY) storage ring in order to control both the precession rate (≈121 kHz) and the phase of the horizontal polarization component. Real time synchronization with a radio frequency (rf) solenoid made possible the rotation of the polarization out of the horizontal plane, yielding a demonstration of the feedback method to manipulate the polarization. In particular, the rotation rate shows a sinusoidal function of the horizontal polarization phase (relative to the rf solenoid), which was controlled to within a 1 standard deviation range of σ=0.21 rad. The minimum possible adjustment was 3.7 mHz out of a revolution frequency of 753 kHz, which changes the precession rate by 26 mrad/s. Such a capability meets a requirement for the use of storage rings to look for an intrinsic electric dipole moment of charged particles.

How to Reach a Thousand-Second in-Plane Polarization Lifetime with 0.97-GeV/c Deuterons in a Storage Ring.

We observe a deuteron beam polarization lifetime near 1000 s in the horizontal plane of a magnetic storage ring (COSY). This long spin coherence time is maintained through a combination of beam bunching, electron cooling, sextupole field corrections, and the suppression of collective effects through beam current limits. This record lifetime is required for a storage ring search for an intrinsic electric dipole moment on the deuteron at a statistical sensitivity level approaching 10^{-29} e cm.

New Method for a Continuous Determination of the Spin Tune in Storage Rings and Implications for Precision Experiments.

A new method to determine the spin tune is described and tested. In an ideal planar magnetic ring, the spin tune-defined as the number of spin precessions per turn-is given by ν(s)=γG (γ is the Lorentz factor, G the gyromagnetic anomaly). At 970 MeV/c, the deuteron spins coherently precess at a frequency of ≈120 kHz in the Cooler Synchrotron COSY. The spin tune is deduced from the up-down asymmetry of deuteron-carbon scattering. In a time interval of 2.6 s, the spin tune was determined with a precision of the order 10^{-8}, and to 1×10^{-10} for a continuous 100 s accelerator cycle. This renders the presented method a new precision tool for accelerator physics; controlling the spin motion of particles to high precision is mandatory, in particular, for the measurement of electric dipole moments of charged particles in a storage ring.

Observation of an "ABC" Effect in proton-proton collisions.

The cross section for inclusive multipion production in the pp-->ppX reaction was measured at COSY-ANKE at four beam energies, 0.8, 1.1, 1.4, and 2.0 GeV, for low excitation energy in the final pp system, such that the diproton quasiparticle is in the 1S0 state. At the three higher energies, the missing-mass M_{X} spectra show a strong enhancement at low M_{X}, corresponding to an Abashian-Booth-Crowe effect that moves steadily to larger values as the energy is increased. Despite the missing-mass structure looking very different at 0.8 GeV, the variation with M_{X} and beam energy are consistent with two-pion production being mediated through the excitation of two Delta(1232) isobars, coupled to S and D states of the initial pp system. There is no sign of any resonancelike structure in the energy dependence of the type recently observed for the pn-->dpi;{0}pi;{0} total cross section.

Observation of inverse diproton photodisintegration at intermediate energies.

The fundamental reaction pp-->{pp}_{s}gamma, where {pp}_{s} is a proton pair with low excitation energy, has been observed with the ANKE spectrometer at COSY-Jülich for proton beam energies of T_{p}=0.353, 0.500, and 0.550 GeV. This is equivalent to photodisintegration of a free 1S0 diproton for photon energies E_{gamma} approximately T_{p}/2. The differential cross sections measured for c.m. angles 0 degrees gammad is on the 10;{-3}-10;{-2} level. The increase of the pp-->{pp}_{s}gamma cross section with T_{p} might reflect the influence of the Delta(1232) excitation.

Precision study of the eta3He system using the dp--> 3Heeta reaction.

The differential and total cross sections for the dp--> 3Heeta reaction have been measured in a high precision high statistics COSY-ANKE experiment near threshold using a continuous beam energy ramp up to an excess energy Q of 11.3 MeV with essentially 100% acceptance. The kinematics allowed the mean value of Q to be determined to about 9 keV. Evidence is found for the effects of higher partial waves for Q >or= 4 MeV. The very rapid rise of the total cross section to its maximum value within 0.5 MeV of threshold implies a very large eta3He scattering length and hence the presence of a quasibound state extremely close to threshold.

Precision measurement of the quasifree pn-->dvarphi reaction close to threshold.

The quasifree pn-->dvarphi reaction has been studied at the Cooler Synchrotron COSY-Jülich, using the internal proton beam incident on a deuterium cluster-jet target and detecting a fast deuteron in coincidence with the K+K- decay of the varphi meson. The energy dependence of the total and differential cross sections are extracted for excess energies up to 80 MeV by determining the Fermi momentum of the target neutron on an event-by-event basis. Though these cross sections are consistent with s-wave production, the kaon angular distributions show the presence of p waves at quite a low energy. Production on the neutron is found to be stronger than on the proton but not by as much as for the eta meson.

Measurement of the analyzing power in p-->d-->(p p)n with a fast forward 1S0 proton pair.

A measurement of the analyzing power A(y) of the p-->d--> (p p) + n reaction was carried out at the ANKE spectrometer at COSY at beam energies of 0.5 and 0.8 GeV by detection of a fast forward proton pair of small excitation energy E(pp) < 3 MeV. The S-wave dominance in the fast diproton is experimentally demonstrated in this reaction. While at T(p) = 0.8 GeV the measured analyzing power almost vanishes, it rises to nearly unity at T(p) = 0.5 GeV for neutrons emitted at theta(c.m.)(n) = 167 degrees. The results are compared with a model taking into account one-nucleon exchange, single scattering, and Delta(1232) excitation in the intermediate state. The model describes fairly well the unpolarized cross section obtained earlier and the analyzing power at 0.8 GeV; it fails to reproduce A(y) at 0.5 GeV.

A method to polarize stored antiprotons to a high degree.

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.

Indications for the presence of an atypical protease-activated receptor on rat platelets.

Activation of the protease-activated receptor (PAR)-1, one of four known PARs (PAR-1 to PAR-4), can be mimicked by thrombin receptor activating peptides (TRAPs) based on the PAR-1 tethered ligand. Interestingly, despite being activatable by thrombin, rodent platelets do not express PAR-1 and thus do not respond to PAR-1-derived TRAPs, indicating different activation mechanisms between human and rodent platelets. Using a rat platelet aggregation model, we determined that TRAPs based on the tethered ligand of PAR-1 fail to activate rat platelet aggregation at concentrations up to 1 mmol/l. In addition, TRAPs inhibit thrombin-mediated rat platelet aggregation, indicating the presence of a modified PAR-1 in this species. In order to determine characteristics of this putative receptor, we tested a panel of synthesized TRAPs based on the rat sequence (R) and human sequence (H) of the PAR-1 tethered ligand for their ability to inhibit thrombin-induced rat platelet aggregation. Peptides R1-9, R4-9, R4-10, and H4-10 inhibited rat platelet aggregation in response to alpha-thrombin [inhibitory concentration (IC) 50% 0.25-1.5 mmol/l]. None of these peptides blocked epinephrine-, collagen-, or arachidonic acid-induced platelet aggregation. Alanine substitution mapping of H4-10 indicated that both Leu4 and Arg5 are essential for inhibition. Inhibition of thrombin's catalytic activity required peptide concentrations tenfold higher than inhibition of platelet aggregation (IC50% 3-5 mmol/l). No prolongation of thrombin clotting time in response to TRAPs was detected at peptide concentrations up to 5 mmol/l. Our data suggest that (1) rat platelets express a PAR-1 subtype, (2) residues Leu4 and Arg5 of the tethered ligand peptide are required for binding to this new receptor, and (3) further analysis of peptide sequences might reveal a novel PAR-1 subtype.

Autoantibodies against low-density lipoprotein and atherogenic potential of blood.

Blood serum of ischaemic heart disease patients possesses an atherogenic potential which manifests itself in the accumulation of cholesterol in cultured smooth muscle cells of human aorta and in mouse peritoneal macrophages. Recently it was found that serum atherogenicity is associated with the presence in the blood of modified (desialylated) low-density lipoprotein (LDL) and of autoantibodies against LDL (anti-LDL). In the blood, anti-LDL and LDL form circulating immune complexes (CIC). Blood serum atherogenic potential is directly related to the content of LDL cholesterol or apolipoprotein B in CIC. The present study elucidates the effect of LDL and anti-LDL concentrations on the atherogenic properties of blood serum. After the addition of exogenic LDL, in certain atherogenic sera a significant increase in CIC cholesterol as well as the increase of serum atherogenic potential revealed in cell culture were registered. In these sera free anti-LDL capable of binding to exogenous LDL were detected. In other atherogenic sera and in all non-atherogenic sera, the LDL increase failed to be accompanied by any changes in the CIC cholesterol. In these sera no free anti-LDL were detected. The addition of exogenous anti-LDL into non-atherogenic sera was accompanied by 2.5-fold increase in CIC cholesterol and by the appearance of atherogenic properties in these sera. Affinity chromatography was used to remove anti-LDL from atherogenic sera. This removal was accompanied by 2.5- to 3-fold decrease in the CIC cholesterol up to the level characteristic of non-atherogenic serum of healthy donors. The removal of anti-LDL led to disappearance of serum atherogenic properties. From these data we assume that the CIC LDL level and, consequently, serum atherogenic potential is to a considerable degree determined by anti-LDL concentration in the serum.

[Effects of lovastatin therapy on the level of low density lipoproteins and atherogenic potential of serum in patients with ischemic heart disease and hypercholesterolemia]. / Vliianie terapii lovastatinom na uroven' lipoproteidov nizkoi plotnosti i aterogennyi potentsial syvorotki krovi bol'nykh ishemicheskoi bolezn'iu serdtsa s giperkholesterinemiei.

The serum atherogenic potential in patients with coronary heart disease (CHD) concurrent with hypercholesterolemia (LDL cholesterol more than 200 mg/dl), which is able to cause accumulation of intracellular cholesterol in cultured cells has been recently shown to be directly related to the level of total cholesterol and LDL cholesterol. The study was undertaken to examine how a lovastatin-induced decrease in LDL levels affects serum atherogenicity in patients with CHD and hypercholesterolemia. It was shown that the therapy of 22 patients with CHD and hypercholesterolemia led to a reduction in total and LDL cholesterol levels on an average by 24% and 32%, respectively. There were 3- and 1.5-2-fold decreases in circulatory immune complexes and the atherogenic potential, respectively. The findings suggest that the significant reduction in serum LDL cholesterol levels in patients with CHD concurrent with hypercholesterolemia who take hypolipidemic therapy is followed by a decrease in the atherogenic potential.

[Relations between the levels of lipoprotein-containing immune complexes and lipids in the blood of patients with ischemic heart disease]. / Vzaimosviaz' mezhdu urovnem lipoproteidsoderzhashchikh immunnykh kompleksov i urovnem lipidov v syvorotke krovi bol'nykh ishemicheskoi bolezn'iu serdtsa.

The sera from most patients with coronary heart disease concurrent with angiographically documented coronary atherosclerosis were found to contain apolipoprotein B (Apo B), neither apolipoprotein E (Apo E) nor apolipoprotein AI (Apo AI) in the circulating immune complexes precipitated by polyethylene glycol-6000 (PEG). Low density lipoproteins are the major components of cholesterol-containing immune complexes precipitated by PEG. A correlation was established between the serum levels of total cholesterol (r = 0,74; p less than 0.01), and low density lipoprotein (LDL) cholesterol (r = 0.77; p less than 0.01) in patients with coronary heart disease and cholesterol in LDL-containing No relationship was found in healthy individuals. The in vitro increase in LDL levels in most patients with coronary heart disease concurrent with coronary atherosclerosis was not followed by an elevation in LDL-containing immune complexes.

[Desialylated low density lipoproteins--atherogenic lipoproteins occurring in blood of patients with coronary atherosclerosis]. / Desialirovannye lipoproteidy nizkoi plotnosti--aterogennye lipoproteidy, obnaruzhennye v krovibol'nykh koronarnym aterosklerozom.

We have recently established that LDL of most patients with coronary atherosclerosis differ from the LDL of most healthy subjects by the ability to cause primary atherosclerotic changes, i.e. the accumulation of intracellular cholesterol in the cells of smooth muscle origin cultured from unaffected intima of human aorta. We assumed that patients LDL is modified lipoprotein differing from native LDL by chemical composition. It has been established in the present study that patients LDL has a substantially lower content of sialic acid as compared with the LDL of healthy subjects. Desialylation of native LDL of healthy subjects with neuraminidase makes them atherogenic, therefore, capable of causing the accumulation of intracellular cholesterol similarly to patients LDL.

Low density lipoprotein-containing circulating immune complexes and coronary atherosclerosis.

Blood serum of most patients with coronary heart disease (CHD) caused a 2- to 5-fold increase in the lipid content of smooth muscle cells cultured from unaffected human aortic intima, i.e., possessed an atherogenic potential manifested in culture. Treatment of the CHD patients' serum with 2.5% polyethylene glycol 6000 removed the circulating immune complexes. The serum subjected to this treatment lost its atherogenic properties, i.e., failed to increase the content of lipids in cultured cells. Incubation of smooth muscle cells derived from human aortic intima with circulating immune complexes isolated from an atherogenic patient's serum caused a 1.5- to 3-fold rise in the intracellular cholesterol. Circulating immune complexes contained apolipoprotein B (apo B), but not apolipoproteins A1 and E. The apo B content strongly correlated with the total cholesterol content. The cholesterol/apo B ratio of the complexes was characteristic of low density lipoproteins (LDL), but not of very low density lipoproteins or intermediate density lipoproteins. The composition of the main lipid classes in these complexes was similar to that in LDL. Blood sera of most (90%) CHD patients was characterized by a high cholesterol and apolipoprotein B content in circulating immune complexes. The ability of these sera to induce lipid accumulation in cultured cells directly correlated with the cholesterol and apolipoprotein B level of circulating immune complexes (r = 0.91). These findings suggest that the atherogenic potential of CHD patients' blood serum is due to LDL-containing immune complexes.

Correlation between cholesterol content in circulating immune complexes and atherogenic properties of CHD patients' serum manifested in cell culture.

Blood serum of most patients with coronary heart disease (CHD) caused a 2-5-fold increase in the total cholesterol content of smooth muscle cells cultured from unaffected human aortic intima, i.e. possessed an atherogenic potential manifested in culture. Removal of immunoglobulins G and M from an atherogenic serum brought about a fall in its atherogenic potential. The serum deficient in immunoglobulins A retained its ability to induce the cholesterol accumulation in cells. Treatment of the CHD patients' serum with 2.5% polyethylene glycol 6000 removed the circulating immune complexes. The serum subjected to this treatment lost its atherogenicity, i.e. failed to increase the cholesterol content in cultured cells. Incubation of smooth muscle cells derived from human aortic intima with circulating immune complexes isolated from an atherogenic patients' serum caused a 1.5-3-fold rise in the intracellular cholesterol. Blood sera of most (89%) CHD patients was characterized by a high cholesterol content in circulating immune complexes. More than 75% of healthy subjects and patients without stenosis of coronary arteries had low level of cholesterol in immune complexes. Blood sera atherogenicity manifested in culture directly correlated with the cholesterol level of circulating immune complexes (r = 0.90). These findings suggest that the atherogenicity of CHD patients blood serum is due to cholesterol-containing immune complexes.

[Low density lipoproteins isolated from the blood of patients with ischemic heart disease induce accumulation of lipids in human aortic intima cells]. / Lipoproteiny nizkoi plotnosti, vydelennye iz krovi bol'nykh ishemicheskoi bolezn'iu serdtsa, vyzyvaiut nakoplenie lipidov v intimal'nykh kletkakh aorty cheloveka.

Very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) were isolated from the blood of healthy subjects and CHD patients. LDL from the blood of healthy individuals did not raise the intracellular lipid values within 24 h of cultivation. During intracellular lipid values within 24 h of cultivation. During the same incubation period. LDL obtained from the blood of CHD patients caused a 2- to 5-fold rise in cholesterol esters as well as a 1.5- to 3-fold rise in free cholesterol and triglycerides, while the intracellular phospholipid levels remained unchanged. In one of the three cases, the ability to raise the intracellular level of cholesterol esters was demonstrated by VLDL (500 micrograms/ml) derived from CHD patients blood. HDL did not affect the lipid levels in smooth muscle cells cultured from unaffected intima. The obtained data suggests that circulating LDL and, possibly, VLDL in the blood of CHD patients are capable of inducing the accumulation of fat in vascular wall cells.

[Cholesterol-containing circulating immune complexes--a component of the blood serum in patients with ischemic heart disease that determines its atherogenic properties]. / Kholesterinsoderzhashchie tsirkuliruiushchie immunnye kompleksy-- komponent syvorotki krovi bo'lnykh ishemicheskoi bolez'niu serdtsa obuslovlivaiushchii ee aterogennos't.

In most patients with coronary heart disease (CHD) and angiographically documented stenosed 1-3 coronary arteries, serum contained cholesterol (C) in the circulating immune complexes (CIC), cholesterol levels in these complexes being directly related to serum atherogenicity, i.e. to their ability to cause a 2-5-fold accumulation of lipids in cultured smooth muscle cells (SMC) of the uninvolved human aortic intima (r = 0.91). Removal of IgG and IgM from the patients' sera led to a 75 and 37% decrease, respectively, in their atherogenic properties displayed in cultured SMC. Much more decrease in the atherogenic potential of the sera was seen in 2.5% polyethylene glycol-induced precipitation of CIC. At the same time, incubation of human aortic intimal SMC with CIC isolated from the atherogenic sera from CHD patients caused a 1.5-3-fold increase in intracellular C levels. It was suggested that CIC cholesterol was a determinant of atherogenicity of the sera from patients with coronary atherosclerosis.

[Atherogenic properties of sera from patients with ischemic heart disease demonstrated in vitro]. / Aterogennye svoistva syvorotok bol'nykh ishemicheskoi bolezn'iu serdtsa, proiavliaiushchiesia in vitro.

The sera of coronary patients with angiographically-documented stenosis of 1 to 3 coronary arteries caused a two-to-fivefold accumulation of intracellular cholesterol in intact human aortic intimal cell culture. This property, qualified as "atherogenic", was exhibited by the sera of 90% of the coronary patients examined (97 males and females, aged 29 to 55 years). Only 20% of normal subjects revealed atherogenic properties in cell cultures. The capacity of the sera to accumulate intracellular cholesterol was unrelated to the levels of total cholesterol, high density lipoprotein cholesterol, apo-B or apo-AI, taken separately, but showed a weak correlation to the apo-B/apo-AI ratio. The sera of coronary patients caused lipid accumulation in human aortic medial smooth-muscle cells and blood mononuclear cells, in human and mouse peritoneal macrophages, but never in human aortic or umbilical vein endothelial cells, nor human embryo fibroblasts.