Probing the Symmetry Energy with the Spectral Pion Ratio.

Many neutron star properties, such as the proton fraction, reflect the symmetry energy contributions to the equation of state that dominate when neutron and proton densities differ strongly. To constrain these contributions at suprasaturation densities, we measure the spectra of charged pions produced by colliding rare isotope tin (Sn) beams with isotopically enriched Sn targets. Using ratios of the charged pion spectra measured at high transverse momenta, we deduce the slope of the symmetry energy to be 42

The influence of rapid growth in broilers on florfenicol pharmacokinetics - allometric modelling of the pharmacokinetic and haemodynamic parameters.

1. The aim of this study was to determine if the pharmacokinetics (PK) of florfenicol (FF) undergo age-dependent changes in broilers. Since drug elimination depends on cardiovascular functions, a haemodynamic study was performed in parallel. 2. Broilers of 0.68, 1.27, 2.45 and 5.13 kg were administered FF in a single intravenous dose of 30 mg/kg body weight. Plasma drug concentrations were determined using high-performance liquid chromatography and PK parameters were calculated using a non-compartmental model. Echocardiography was used to measure haemodynamic functions. 3. During growth, the area under the drug concentration-time curve (AUCinf) increased from 25.7 ± 2.9 to 39.0 ± 8.0 mg h/l. Total body clearance (ClB) gradually decreased from 1.19 ± 0.14 to 0.80 ± 0.15 l/h/kg. Elimination half-life increased from 0.73 ± 0.08 to 1.07 ± 0.07 h, whereas volume of distribution (Vss) remained unchanged. Haemodynamic measurements revealed an increase in cardiac output, from 495 ± 65 to 1303 ± 306 ml/min, in the respective body weight groups. 4. Allometric models for PK and haemodynamic parameters were developed and validated. All models proved to be statistically significant; however, only models for ClB and Vss met stringent validation criteria. Model for ClB was used to calculate an optimal dose for a given age group that provides uniform AUCinf. 5. Age-dependent change in FF kinetics may cause variability in therapeutic response under clinical conditions. A novel approach to the dosing protocol was proposed as a means of optimising therapeutic efficacy.

Elevated percentage of HLA-DR⁺ and ICAM-1⁺ conjunctival epithelial cells in active Graves' orbitopathy.

BACKGROUND: To evaluate if conjunctival epithelial cells' expression of HLA-DR and ICAM-1 could be helpful as early topical markers of inflammation in Graves' orbitopathy (GO). METHODS: The ocular examination evaluated a clinical activity score (CAS) by assessment of clinical features, (e.g., eyelid or conjunctival inflammation, lid width, lid closure, proptosis, ocular motility). Conjunctival epithelial cell specimens for flow-cytometric evaluations of ICAM-I and HLADR expression were collected by impression cytology from ten eyes with active GO (CAS ≥ 4 and duration ≤ 12 months), from 15 eyes with Graves' disease (GD) without active GO (CAS 0-2) and from 15 normal specimens without any ocular disorders. RESULTS: The percentage of HLA-DR + conjunctival epithelial cells was significantly elevated in patients with active GO comparing to GD without active GO and healthy controls, 10.7 % (8.5-17.7) and 7.78 % (3.92-10.1) (p < 0.05) vs. control 4.89 % (3.5-5.5) (p < 0.005), respectively. The expression of ICAM - 1+ conjunctival epithelial cells was greater only in patients with GO vs. controls, 5.5 % (4.8-7.03) and 1.46 % (0.69-2.51) (p < 0.005), respectively. CONCLUSION: The percentage of HLA-DR⁺ and ICAM-1⁺ conjunctival epithelial cells in patients with the active GO may serve as a topical inflammation marker in Graves' orbitopathy.

Nuclear multifragmentation time scale and fluctuations of the largest fragment size.

Distributions of the largest fragment charge, Zmax, in multifragmentation reactions around the Fermi energy can be decomposed into a sum of a Gaussian and a Gumbel distribution, whereas at much higher or lower energies one or the other distribution is asymptotically dominant. We demonstrate the same generic behavior for the largest cluster size in critical aggregation models for small systems, in or out of equilibrium, around the critical point. By analogy with the time-dependent irreversible aggregation model, we infer that Zmax distributions are characteristic of the multifragmentation time scale, which is largely determined by the onset of radial expansion in this energy range.

The SπRIT time projection chamber.

The Superconducting Analyzer for MUlti-particles from RAdioIsotope (SAMURAI) Pion-Reconstruction and Ion-Tracker Time Projection Chamber (SπRIT TPC) was designed to enable measurements of heavy ion collisions with the SAMURAI spectrometer at the RIKEN radioactive isotope beam factory and provides constraints on the equation of state of neutron-rich nuclear matter. The SπRIT TPC has a 50.5 cm drift length and an 86.4 × 134.4 cm2 pad plane with 12 096 pads that are equipped with the generic electronics for TPCs. The SπRIT TPC allows for an excellent reconstruction of particles and provides isotopic resolution for pions and other light charged particles across a wide range of energy losses and momenta. The details of the SπRIT TPC are presented, along with discussion of the TPC performance based on cosmic rays and charged particles emitted in heavy ion collisions.

Comparison of the relative synthesis of the proteins of the 50S ribosomal subunit in growing and valine-deprived HeLa cells.

Quantitative studies of the synthesis of the ribosomal proteins of the 50S ribosomal subunit have been made with growing versus valine-deprived HeLa cells. The synthesis of total cell protein and 50S subunits was also compared between the growing and nongrowing cells. It was found that between 12 and 20 hr of valine deprivation the net synthesis of 50S subunits drops to approximately 8% of that in control cells while the over-all synthesis of 50S subunit ribosomal proteins declines to approximately 12% of that in the controls. However, the synthesis rates for each of two particular 50S subunit proteins decline to approximately 8% of the rates in the growing cells, indicating that the synthesis of one of these proteins may be rate limiting for 50S subunit biosynthesis in valine-deprived HeLa cells. Other evidence indicates that the regulation of synthesis of the ribosomal proteins in valine deprivation depends on control at the level of transcription or translation rather than being a function of the relative valine content of these proteins.

Modulation of lymphocyte subsets and humoral immune response by florfenicol administered to sheep red blood cell-immunized broiler chickens.

Florfenicol is a broad-spectrum bacteriostatic antibiotic commonly used for the treatment of systemic infections in farm animals. The aim of this study was to determine the effect of florfenicol on the percentage of T lymphocytes (CD3+, CD4+, CD8+, TCRgd+ cells) and B lymphocytes (Bu-1+ cells) and on total serum anti - sheep red blood cell (SRBC) haemagglutinin titer in the peripheral blood of SRBC-immunized broiler chickens. The study included three groups of broiler chickens differentiated by weight (0.5, 1.2, 2.4 kg). Florfenicol was administered orally at a dose of 30 mg/kg. The drug was administered eight times at 24 h intervals. The chickens were immunized with SRBC 24 h after administration of the third dose of florfenicol. Florfenicol increased the percentage of CD3+ blood lymphocytes with a corresponding decrease in the percentage of B lymphocytes in birds weighing 0.5 and 2.4 kg. Florfenicol reduced the production of total anti SRBC-haemagglutinins on day 5 after antigen injection in all three body weight groups of the broiler chickens. In conclusion, florfenicol exerted a modulating effect on the immune response of the birds and this should be taken into consideration when using this antibiotic for certain indications.

HSP binding and mitochondrial localization of p53 protein in human HT1080 and mouse C3H10T1/2 cell lines.

In normal cells, the tumor suppressor actions of p53 protein are mediated by specific DNA binding and protein-protein interactions within the nucleus. Mutant p53 proteins, however, often assume an aberrant conformation devoid of tumor suppressor activity and newly capable of binding to the cognate or inducible HSP70. Recent reports from our laboratory and others show that additional unknown proteins may also complex with mutant p53. In this study, we characterize p53:HSP complexes and their subcellular location in the transformed cell lines, human HT1080 and murine C3H10T1/2, which both contain aberrant p53 conformers. Immunoprecipitation and SDS-PAGE of p53 from whole cell lysates revealed the additional presence of a broad 70 kDa band and a 90 kDa band in both lines, while p53 isolated from nuclear lysates was free from other proteins. 2D-PAGE was used to isolate and identify HSP members from cytoplasmic and nuclear lysates by immunoprecipitation, Western blotting and protein sequencing. Anti-p53 immune complexes from cytoplasmic lysates contained not only HSC70 but also GRP75, GRP78 and a weakly basic 90 kDa protein, which may be related to HSP90. The inducible form of HSP70 was not complexed to p53 protein, even though expressed in these cells. Analysis of anti-HSP70, anti-GRP75 and anti-HSP90 immune complexes suggests that HSP members exist as performed complexes in the cytoplasm, but not the nucleus. The presence of the mitochondrial and endoplasmic reticular chaperones, GRP75 and GRP78, in p53:HSP complexes suggested that p53 might be found in these cytoplasmic organelles which was confirmed in mitochondria by biochemical and immunoelectron microscopic evidence. These studies suggest that newly identified members of p53:HSP complexes represent components of a chaperone program which affects the subcellular distribution of p53 protein in these transformed lines.

Bioelectrorheological model of the cell. 8. Cellular deformation under prolonged and recurrent shear stress.

The influence of a prolonged and recurrent shear stress created by a periodic electric field on the mechanical properties of Neurospora crassa cells was investigated. Conditions were found under which modifications of cellular structures responding to stress become irreversible, and plastic flow of the viscoelastic structural elements is observed. The symmetry of the response of the cell under stress application and relaxation was lost, when compared to the reference conditions. To interpret the results a general rheological model was proposed. As previously described (Pawlowski et al., 1997), the existence of the three hypothetical supramolecular regions of the membrane (F, S and O) was suggested. Rheological parameters for the above regions were calculated. Theoretical functions were satisfactorily fitted to the experimental results.

Bioelectrorheological model of the cell. 7. Cellular deformation in the presence of cytochalasin B.

The influence of cytochalasin B on the mechanical properties of Neurospora crassa cells subjected to a periodic electric field was investigated. Shear and extensional deformations were considered and studied separately. Conditions were found under which shear deformations become irreversible. Rheological models helped in the interpretation of the results in terms of the different response to the shear stress of the three hypothetical supramolecular regions of the membrane-skeleton network (F, S and 0). Rheological parameters for the above regions related to the proposed models were calculated. The models were satisfactorily fitted to the experimental results. The influence of cytochalasin B on the course of extensional deformation of cells was investigated and characterized semiquantitatively.

Isotopic dependence of the nuclear caloric curve.

The A/Z dependence of projectile fragmentation at relativistic energies has been studied with the ALADIN forward spectrometer at SIS. A stable beam of (124)Sn and radioactive beams of (124)La and (107)Sn at 600 MeV per nucleon have been used in order to explore a wide range of isotopic compositions. Chemical freeze-out temperatures are found to be nearly invariant with respect to the A/Z of the produced spectator sources, consistent with predictions for expanded systems. Small Coulomb effects (DeltaT approximately 0.6 MeV) appear for residue production near the onset of multifragmentation.

Coincidence measurement of residues and light particles in the reaction 56Fe+p at 1 GeV per nucleon with the spallation reactions setup SPALADIN.

The spallation of 56Fe in collisions with hydrogen at 1A GeV has been studied in inverse kinematics with the large-aperture setup SPALADIN at GSI. Coincidences of residues with low-center-of-mass kinetic energy light particles and fragments have been measured allowing the decomposition of the total reaction cross section into the different possible deexcitation channels. Detailed information on the evolution of these deexcitation channels with excitation energy has also been obtained. The comparison of the data with predictions of several deexcitation models coupled to the INCL4 intranuclear cascade model shows that only GEMINI can reasonably account for the bulk of collected results, indicating that in a light system with no compression and little angular momentum, multifragmentation might not be necessary to explain the data.

Pharmacokinetics of florfenicol, thiamphenicol, and chloramphenicol in turkeys.

The pharmacokinetics of florfenicol (FF), thiamphenicol (TP) and chloramphenicol (CP) after single intravenous (i.v.) or oral (p.o.) administration was studied in an independent cross-over study in broiler turkeys. All the fenicol antibiotics were administered at a dose of 30 mg/kg b.w. and their concentrations in plasma samples were assayed using the same validated high-performance liquid chromatography method. Pharmacokinetic parameters were calculated by a noncompartmental method. The kinetic profiles of the compounds were compared with the results of the structure-activity relationship. According to the proposed mathematical description, no differences in plasma clearance values for the studied antibiotics were observed. The mean residence time values of FF, TF, and CP after i.v. injection were 3.37+/-0.63, 2.43+/-0.29, and 2.12+/-0.21 h, respectively. The mean values of Varea for FF (1.39+/-0.31 L/kg) and TP (1.31+/-0.19 L/kg) were similar, but significantly different from that of CP (1.04+/-0.12 L/kg). The bioavailabilities of FF, TP, and CP after oral administration were 82%, 69%, and 45%, respectively. Differences in the bioavailability values of the compared fenicol antibiotics correspond to the ratio of the apolar/polar surface areas of their particles.

Mechanisms involved in the relaxing effect of midazolam on coronary arteries.

BACKGROUND AND OBJECTIVE: Hypotension, especially in elderly and hypovolaemic patients, is frequently associated with intravenous midazolam administration. The mechanisms are not completely understood. This study was designed to investigate the mechanisms involved in the relaxing effect of midazolam on coronary arteries. METHODS: The substance was studied in isolated porcine coronary artery rings precontracted by either potassium chloride or prostaglandin F2alpha. RESULTS: Midazolam caused vasodilatation in a concentration-dependent manner. Relaxation was more pronounced in prostaglandin F2alpha precontracted segments than in those treated with potassium chloride (P < 0.001). Vasodilatation was unaffected by Nomega-nitro-L-arginine, indomethacin and glibenclamide. Tetraethylammonium chloride, an inhibitor of the BK(Ca) K+ channel (a high conductance Ca(2+)-sensitive K+ channel), dose dependently attenuated the vasodilating effect of midazolam (P < 0.01). CONCLUSIONS: Hyperpolarization of the smooth muscle cell in the vessel wall, elicited by the activation the BK(Ca) K+ channel, may contribute to the vasorelaxing effect of midazolam.

Differential effect of hypertonic initiation block on the synthesis of collagen chains by cultured chick embryo cells.

The major type of collagen synthesized by fibroblasts or bone cells, type I collagen, consists of two chains normally found in a 2:1 ratio designated alpha 1(I)2 alpha 2(I) or more simply alpha 1(I)2 alpha 2. I have analyzed the relative synthesis of type I chains in these cells under conditions which reduce the initiation of protein synthesis. It was found that in bone cells, which make a large amount of collagen, the alpha 1(I):alpha 2 ratio is unaltered whereas in fibroblasts, which make smaller amounts of collagen, the alpha 2 chain is particularly sensitive to these same conditions. Examination of the collagen secreted into the medium, under these same conditions, also revealed an altered chain ratio from cells making low amounts of collagen.

Effect of 5-bromodeoxyuridine on the appearance of cytoplasmic poly-A containing RNA.

Cytoplasmic poly-A containing RNA, synthesized by cultured chick embryo cells, was examined during growth in 5-bromodeoxyuridine. The kinetics of 3H-adenosine incorporation into this species of RNA, when compared to the rest of the cytoplasmic RNA, and to control cells, indicates that the rate of synthesis of this RNA is slower in BrdU treated cells. An examination of the rate at which a steady state distribution of radioactivity, between the poly-A segment and non-poly-A portion of poly-A containing RNA is reached also indicated that this species is synthesized at a lower rate in BrdU treated cells.

Bioelectrorheological model of the cell. 2. Analysis of creep and its experimental verification.

The electrorheological model of the cell proposed in Part 1 of this work was used to analyze changes in time of the shape of a cell acted on by a constant-amplitude external alternating electric field, with lossiness of the media taken into account. Shear stress in the cell membrane was determined. This model was then subjected to preliminary experimental verification using Neurospora crassa (slime) spheroplasts subjected to an external alternating electric field of constant frequency (3 MHz) and varying magnitude for different periods of time. Reversible viscoelastic cell deformation and fatigue (stiffening) of the material were observed. A satisfactory fit of the experimental data to Burgers' rheological model was found, and the values of the elastic moduli E1 = 9 X 10(2) N/m2, E2 = 2 X 10(2) N/m2 and viscosities eta 1 = 8 X 10(4) Ns/m2; eta 2 = 7 X 10(3) Ns/m2 were evaluated.