Evidence of multiple ethanol pools in the brain: an in vivo proton magnetization transfer study

Studies of isolated cell membranes and animal brain extracts have shown that ethanol (EtOH) partitions into cell membranes. We tested the hypothesis that EtOH in the living brain after EtOH administration exists in two or more pools: a free, mobile pool of EtOH and one or more EtOH pools that are restricted in their molecular mobility, possibly because of association with membranes. In vivo brain proton magnetic resonance spectroscopy (1H MRS) routinely detects the methyl protons of the mobile EtOH pool but does not detect motionally restricted EtOH. We used in vivo brain 1H MRS in rat brain (n = 11) after intraperitoneal EtOH administration to measure the signal intensity of methyl EtOH protons in the presence and absence of off-resonance saturation. Off-resonance saturation resulted in a 33 +/- 4% decrease of the EtOH methyl proton signal. We interpret this signal reduction as a magnetization transfer effect. It is consistent with the existence of an MRS-invisible EtOH pool with restricted molecular mobility, which is in exchange with the free EtOH pool. Off-resonance saturation at the water frequency resulted in an even larger decrease of the EtOH methyl signal, consistent with water molecules being in close proximity to EtOH molecules at the restricted motion site(s). These results provide support for the hypothesis that partial MRS-invisibility of brain EtOH is at least to some extent caused by the presence of a (MRS-invisible) pool of motionally restricted EtOH. They also strongly suggest that water suppression, routinely used in in vivo 1H MRS, may reduce the observable EtOH methyl signal intensity through a magnetization transfer mechanism. These studies may provide both a mechanism of, and a means to investigate the alterations of EtOH MRS visibility observed in heavy drinkers.     

Determination of rate and equilibrium constants for some typical biochemical reactions

Three types of typical biological reactions are considered. Their kinetic curves plotted in the semilogarithmic scale are approximated well by two lines intercepting at different angles and may be described with the systems of differential equations. The latters are resolved as a complex system of transcendental irrational equations interconnecting the reagent concentrations, time and rate constants. A new method for numerical solution of such equations is suggested which permits determining the exact rate constants on the basis of either theoretical or experimental kinetic curves.     

The effect of magnetization transfer in meniscal fibrocartilage

Magnetic resonance imaging of the knee was performed in 28 patients (ages 15-72 years), using a 1.5-T unit. Volume gradient echo (3D GRASS) acquisition with and without presaturation off-resonance RF pulse was used to evaluate magnetization transfer (MT) effects, determined by placing regions of interest on muscle, fat, hyaline, and fibrocartilage; the percent change in signal intensity was calculated and compared using a paired two-sample t test. An in vitro study of the normal meniscus from a cadaver containing a scalpel cut extending to an articular surface was performed to observe the relative improvement in contrast in the presence of a small meniscal defect. MR imaging of the specimen was performed using an Omega CSI 2.0-T system (General Electric Medical Systems, Fremont, CA). Analysis of clinical images resulted in signal loss, compared to that of the identically timed and tuned non-MT images of 47 +/- 5, 8 +/- 5, 49 +/- 5, and 57 +/- 7% for muscle, fat, articular cartilage and fibrocartilage, respectively. Application of MT improved the depiction of the artificially introduced meniscal defect. Meniscal fibrocartilage demonstrates significant MT effect after application of off-resonance RF presaturation, which may improve visualization of meniscal defects.     

Magnetic relaxation contrast agents in magnetization transfer imaging

RATIONALE AND OBJECTIVES: The effects of magnetic relaxation agents are explored in the context of magnetization transfer pulse sequences using cross-linked protein gels as modeled tissue systems. METHODS: Magnetization transfer pulse sequences were used to study contrast agents that are designed to bind to rotationally immobilized protein targets. RESULTS: The dynamic range available from contrast agents, used in conjunction with magnetization transfer pulse sequences, is comparable with or better than that based on spin-echo imaging sequences with short repetition times. Furthermore, useful changes in the intensity of water resonances may be achieved by using this combined approach even though the paramagnetic metal center may not have a free coordination position in the chelate complex for water molecule exchange. CONCLUSIONS: The inclusion of magnetization transfer acquisition protocols in the context of magnetic imaging with contrast agents presents new opportunities for control of the information content of the image and for new classes of contrast agent structure and delivery.     

Rate of reduction of ore-carbon composites: Part I. Determination of intrinsic rate constants

A process for ironmaking was proposed consisting of the combination of a rotary hearth furnace and a bath smelter employing wood charcoal as reductant and energy source. This article examines reactions in composites of iron oxides and carbon at elevated temperatures in conditions developed to minimize the influence of mass and heat transfer to the overall rates. A combined reaction model considering the steps of carbon oxidation and reduction of the iron oxides was developed allowing the measurement of rate constants for carbon oxidation and wustite reduction to be used in a comprehensive pellet model developed in Part II of the current article. This analysis showed that wustite reduction can have a significant effect on the overall rate of reduction in composites at high temperatures or in the presence of large excess of carbon. Rate constants measured for graphite showed that graphite is as reactive as wood charcoal, possibly due to the catalysis of graphite or its higher temperature dependence. The poisoning of carbon surfaces by CO is less significant than anticipated from works of previous authors.     

Analysis of on- and off-resonance magnetization transfer techniques

PURPOSE: To quantitatively assess all gamma-ray induced chromosomal changes confined to one human chromosome using fluorescence microscopy and in situ hybridization with a fluorescently labeled human chromosome specific nucleic acid probe. METHODS AND MATERIALS: Synchronized human-hamster hybrid cells containing human chromosome 11 were obtained by a modified mitotic shake-off procedure. G1 phase cells (> 95%) were irradiated with 137Cs gamma rays (0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, and 10.0 Gy) at a dose rate of 1.1 Gy/min and mitotic cells collected 16-20 h later; chromosomal spreads were prepared, denatured, and hybridized with a fluorescein-tagged nucleic acid probe against total human DNA. Chromosomes were examined by fluorescence microscopy and all categories of change involving the human chromosome 11 as target, recorded. RESULTS: Overall, of the 3104 human-hamster hybrid cells examined, 82.1% were euploid, of which 88.6% contained one copy of human chromosome 11, 6.2% contained two copies, and 5.2% contained 0 copies. This is compatible with mitotic nondisjunction in a small fraction of cells. Of the remaining 17.9% of cells, 85.2% were tetraploid cells with two copies of human chromosome 11. For all aberrations involving human chromosome 11 there was a linear relationship between yield and absorbed dose of 0.1 aberrations per chromosome per Gy. The yield of dicentrics, translocations, and terminal deletions that involve one lesion on the human chromosome was linear, while the yield of interstitial deletions that arise from two interacting lesions on the human chromosome was curvilinear. The frequencies of dicentrics and translocations were about equal, while there was a high (40-60%) incidence of incomplete exchanges between human and hamster chromosomes. CONCLUSIONS: Fluorescent in situ hybridization (FISH) procedures allow for the efficient detection of a broad range of induced changes in target chromosomes. Symmetrical exchanges induced in G1 (translocations) were readily scored and found to equate with the complementary asymmetrical exchanges (dicentrics). That is, nonlethal stable changes, which might be of concern in carcinogenic processes, complement lethal, unstable changes. Interstitial deletions that may contribute to the loss of antioncogenes as well as to lethality are also readily detected with enhanced levels detected at higher doses. The high level of induced terminal deletions and of incomplete dicentrics and translocations indicate a partial failure of interaction between lesions induced in human and hamster DNA, and suggest that such interspecies interactions lack the fidelity of intraspecies DNA lesion interactions. This suggests caution in the use of such model systems as indicators of human cell responsiveness.     

Determination of real-time oxygen transfer rate based on an electrochemical method

The interfacial oxygen transfer rate is one of the main factors to control the composition of alloys.The commonly employed method of studying the interfacial ox...     

Determination of the rate of superoxide generation from biological systems by spin trapping: use of rapid oxygen depletion to measure the decay rate of spin adducts

A method was developed to measure the superoxide generation rate from biological systems using the spin trapping method. Kinetic treatment of the decay rate of the superoxide adduct of 5,5-dimethylpyrroline N-oxide (DMPO) revealed that the EPR signal intensity of the system is proportional to the superoxide generation rate. Rapid depletion of oxygen in the sample was utilized to terminate superoxide generation so that the decay rate of the DMPO superoxide adduct (DMPO-OOH) could be determined. For this decay measurement, a controlled atmosphere EPR cavity was developed and was used with an open-air sample cell. Superoxide generation rates determined with this method for stimulated neutrophils and for the hypoxanthine-xanthine oxidase system were comparable to those obtained with the cytochrome c reduction method. This method is specifically applicable to the system in which dissolved oxygen supplied from the gas phase is utilized as a source of superoxide.     

A "parallel plate" electrostatic model for bimolecular rate constants applied to electron transfer proteins

A "parallel plate" model describing the electrostatic potential energy of protein-protein interactions is presented that provides an analytical representation of the effect of ionic strength on a biomolecular rate constant. The model takes into account the asymmetric distribution of charge on the surface of the protein and localized charges at the site of electron transfer that are modeled as elements of a parallel plate condenser. Both monopolar and dipolar interactions are included. Examples of simple (monophasic) and complex (biphasic) ionic strength dependencies obtained from experiments with several electron transfer protein systems are presented, all of which can be accommodated by the model. The simple cases do not require the use of both monopolar and dipolar terms (i.e., they can be fit well by either alone). The biphasic dependencies can be fit only by using dipolar and monopolar terms of opposite sign, which is physically unreasonable for the molecules considered. Alternatively, the high ionic strength portion of the complex dependencies can be fit using either the monopolar term alone or the complete equation; this assumes a model in which such behavior is a consequence of electron transfer mechanisms involving changes in orientation or site of reaction as the ionic strength is varied. Based on these analyses, we conclude that the principal applications of the model presented here are to provide information about the structural properties of intermediate electron transfer complexes and to quantify comparisons between related proteins or site-specific mutants. We also conclude that the relative contributions of monopolar and dipolar effects to protein electron transfer kinetics cannot be evaluated from experimental data by present approximations.     

Effect of heterogeneous microstructure on magnetization reversal mechanism of hot-deformed Nd-Fe-B magnets

The hot-deformed(HD) Nd-Fe-B magnets show heterogeneous microstructure composed of coarse and fine grain regions. It is significant to fully understand the influence of this complex microstructure on the magnetization reversal process which can give the guidance for the enhancement of the magnetic properties. In this paper, the heterogeneous microstructure of the(HD) Nd-Fe-B magnets were characterized from the morphology, size, macro-texture and micro-structure. In addition, the magnetization reversal process of the HD Nd-Fe-B magnets was systematically analyzed by magnetic measurement, insitu domain evolution observation and micromagnetic simulation. The results indicate that the HD NdFe-B magnets mainly consist of fine grain regions(FGRs) and coarse grain regions(CGRs). The FGRs show plate-like grains with fine grain size and strong c-axis texture, while the CGRs show equiaxial grains with large grain size and weak c-axis texture. In particular, it is worth noting that the texture in homogeneity exists not only between FGRs and CGRs, but also inside both the FGRs and CGRs. The dominant coercivity mechanism of the HD Nd-Fe-B magnets is domain wall pinning. Also, the experimental analysis shows that the reverse domain is formed and expanded in the CGRs at low reverse applied field, while the reverse domain occurs in the FGRs at higher reverse applied field. The micromagnetic simulation results also confirm the above magnetization reversal process. In addition, micromagnetic simulation results also show that the orientation of the grains also affects the pinning strength, besides the grain size.     

Correlation of volumetric magnetization transfer imaging with clinical data in MS

We examined the relations between quantitative volumetric estimates of cerebral lesion load based on magnetization transfer imaging (MTI), clinical data, and measures of neuropsychological function in 44 patients with clinically diagnosed MS. In this population we assessed the correlation between several volumetric MTI measures, measures of neurologic function (Kurtzke Expanded Disability Status Scale and Ambulation Index), and disease duration using Spearman's correlation coefficient. Patients were classified on the basis of neuropsychological test performance as severely impaired, moderately impaired, and normal. We assessed differences between these groups with respect to MTI results using the Kruskal-Wallis test. MTI measures corrected for brain volume were found to correlate with disease duration (p < 0.01) and showed suggestive correlations with measures of neurologic impairment (p < 0.05). Individual neuropsychological tests correlated with MTI measures corrected and not corrected for brain volume (p < 0.001). An MTI measure not corrected for brain volume differed (p < 0.05) between severely impaired, moderately impaired, and normal patients. These preliminary results suggest that volumetric MTI analysis provides new measures that reflect more accurately the global lesion load in the brain of MS patients, and they may serve as a method to study the natural course of the disease and as an outcome measure to evaluate the effect of drugs.     

Measurement of spin-lattice relaxation times and kinetic rate constants in rat muscle using progressive partial saturation and steady-state saturation transfer

The determination of neomycin sulfate by liquid chromatography using a column packed with a poly(styrenedivinylbenzene) co-polymer and pulsed electrochemical detection on a gold electrode is described. The mobile phase consisted of an aqueous solution containing 70 g/l of sodium sulfate, 1.4 g/l of sodium 1-octanesulfonate and 50 ml/l of a 0.2 M phosphate buffer (pH 3.0). Sodium hydroxide was added post-column. The influence of the different chromatographic parameters on the separation was investigated. The method shows good linearity and repeatability and is stability indicating. A number of commercial samples was analyzed using this method and the results were compared with results obtained with the European Pharmacopoeia method and a previously described thin-layer chromatographic method.     

Estimating the rate constants in a two-compartment stochastic model

A procedure is described for estimating the rate constants of a two-compartment stochastic model for which the covariance structure over time of the observations is known. The proposed estimation procedure, by incorporating the known (as a function of the parameters to be estimated) covariance structure of the observations, produces regular best asymptotically normal (RBAN) estimators for the parameters. In addition, the construction of approximate confidence intervals and regions for the parameters is made possible by identification of the asymptotic covariance matrix of the estimators. The explicit form of the inverse of the covariance matrix, which is required in the estimation procedure, is presented. The procedure is illustrated by application to real as well as simulated data, and a comparison is made to the widely used nonlinear least squares procedure, which does not account for correlations over time.     

Electron transfer and proton pumping in cytochrome oxidase

This article presents an outlook on the structure and function of terminal oxidases, the respiratory enzymes which catalyze the reduction of dioxygen to water in aerobic organisms. The structure of the redox active metals, their interactions with the protein matrix, and their role in electron transfer ligand binding and proton pumping are briefly reviewed.     

离散时间异质多智能体系统的一致性控制

针对由一阶智能体和二阶智能体组成的离散异质多智能体系统,研究其一致性问题.设计无通信时延和具有有界通信时延时的分布式一致性协议,通过将系统转化为自治的离散时间线性时不变系统,运用矩阵理论和代数图论方法,分析得到系统实现一致性的充分条件.获得的充分条件与采样周期、控制参数和系统的拓扑结构有关.证明了系统的一致性不受有界通信时延影响.数值仿真结果验证了理论结果的正确性.