Kibble-Zurek Mechanism for Dynamical Ordering in a Driven Vortex System.

The Kibble-Zurek mechanism describes the formation of topological defects in systems crossing a continuous symmetry-breaking phase transition at a finite quench rate. While this mechanism has been extensively studied for equilibrium transitions, its applicability to nonequilibrium transitions has not yet been fully examined. Recent simulation has shown the applicability of the Kibble-Zurek mechanism to dynamical ordering transitions in particlelike assemblies, including superconducting vortices, driven over random disorder. Here, we experimentally study the configurational order of vortices in the course of dynamical ordering with various quench rates. We verify a power-law scaling of the defect density with the quench rate and an impulse-adiabatic crossover on the ordered side of the transition, which are key predictions of the Kibble-Zurek mechanism. Our results suggest the applicability of the Kibble-Zurek mechanism to other nonequilibrium phase transitions.

Quantum Criticality inside the Anomalous Metallic State of a Disordered Superconducting Thin Film.

The field-induced superconductor-insulator transition (SIT) in two-dimensional (2D) systems is a famous example of a quantum phase transition. However, an emergence of an anomalous metallic state induced by field has been a long-standing problem in 2D superconductors. While theories predicted that the emergence is attributed to strong phase fluctuations of the superconducting order parameter due to quantum fluctuations, usual resistance measurements have not probed them directly. Here, using Nernst effect measurements, we uncover superconducting fluctuations in the vicinity of the field-induced metallic state in an amorphous Mo_{x}Ge_{1-x} thin film. The field range where the vortex Nernst signals are detectable remains nonzero toward zero temperature, and it locates inside the metallic state defined by the magnetoresistance, indicating that the metallic state results from quantum vortex liquid (QVL) with phase fluctuations due to quantum fluctuations. Slow decay of transport entropy of vortices in the QVL with decreasing temperature suggests that the metallic state originates from broadening of a quantum critical point in SIT.

Orbital Selectivity in Scanning Tunneling Microscopy: Distance-Dependent Tunneling Process Observed in Iron Nitride.

In scanning tunneling microscopy, orbital selectivity of the tunneling process can make the topographic image dependent on a tip-surface distance. We have found reproducible dependence of the images on the distance for a monatomic layer of iron nitride formed on a Cu(001) surface. Observed atomic images systematically change between a regular dot array and a dimerized structure depending on the tip-surface distance, which turns out to be the only relevant parameter in the image variation. An accompanied change in the weight of Fe-3d local density of states to a tunneling background was detected in dI/dV spectra. These have been attributed to a shift in surface orbitals detected by the tip from the d states to the s/p states with increasing the tip-surface distance, consistent with an orbital assignment from first-principles calculations.

Evidence of second-order transition and critical scaling for the dynamical ordering transition in current-driven vortices.

Dynamical ordering from a disordered plastic flow to an anisotropically ordered smectic flow induced by a dc force has been studied in various many-particle systems, including vortices in type-II superconductors. However, it remains unclear whether the dynamical ordering is a true phase transition because of lack of suitable experimental methods. Here, we study the response of vortex flow to the transverse force using a cross-shaped amorphous Mo[Formula: see text]Ge[Formula: see text] film. From transverse current-voltage (force-velocity) characteristics under various longitudinal currents, we find a change of the transverse response in low voltage (velocity) regions from a nonlinear to linear behavior at a well-defined longitudinal current that marks the dynamical ordering transition. We also find the scaling collapse of the transverse current-voltage curves to a universal scaling function, providing evidence of the second-order transition for the dynamical ordering transition.

Critical behavior of nonequilibrium depinning transitions for vortices driven by current and vortex density.

We study the critical dynamics of vortices associated with dynamic disordering near the depinning transitions driven by dc force (dc current I) and vortex density (magnetic field B). Independent of the driving parameters, I and B, we observe the critical behavior of the depinning transitions, not only on the moving side, but also on the pinned side of the transition, which is the first convincing verification of the theoretical prediction. Relaxation times, [Formula: see text] and [Formula: see text], to reach either the moving or pinned state, plotted against I and B, respectively, exhibit a power-law divergence at the depinning thresholds. The critical exponents of both transitions are, within errors, identical to each other, which are in agreement with the values expected for an absorbing phase transition in the two-dimensional directed-percolation universality class. With an increase in B under constant I, the depinning transition at low B is replaced by the repinning transition at high B in the peak-effect regime. We find a trend that the critical exponents in the peak-effect regime are slightly smaller than those in the low-B regime and the theoretical one, which is attributed to the slight difference in the depinning mechanism in the peak-effect regime.

Serum accumulation of a creatinine oxidative metabolite (NZ-419: 5-hydroxy-1- methylhydatoin) as an intrinsic antioxidant in diabetic patients with or without chronic kidney disease.

AIMS: In mammals, creatinine (Cr) is catabolized by a dual oxidative pathway via 5-hydroxy-1-methylhydantoin or 5-hydroxycreatinine. The former, an intrinsic antioxidant, termed NZ-419, has been reported to prevent the progression of chronic renal failure in animal models. However, its clinical intrinsic serum level has not yet been reported. METHODS: We analyzed serum NZ-419 levels in diabetic and nondiabetic patients with or without Stage 3 - 5 chronic kidney disease (CKD). RESULTS: The levels of NZ-419 in diabetic patients with (88.1 ± 17.2 µg/dl, p < 0.001) or without (31.5 ± 2.4 µg/dl, p < 0.05) Stage 3 - 5 CKD were significantly higher than in nondiabetic normal controls (9.0 ± 5.6 µg/dl). The molar ratio data showed NZ-419/Cr was significantly higher in both diabetic patients with (p < 0.01) or without Stage 3 - 5 CKD (p < 0.001) compared to nondiabetic normal controls. No further increase occurred with increasing severity of renal failure. Furthermore, nondiabetic patients with or without Stage 3 - 5 CKD did not show significantly different molar ratio values than controls but had significantly higher values of NZ-419 levels (p < 0.001). CONCLUSIONS: Overproduction and decreased clearance played a major role in the increased NZ-419 levels we observed in the patients with diabetes and Stage 3 - 5 CKD, respectively. The existence of chronic renal failure did not further enhance this overproduction.

Critical behavior of density-driven and shear-driven reversible-irreversible transitions in cyclically sheared vortices.

Random assemblies of particles subjected to cyclic shear undergo a reversible-irreversible transition (RIT) with increasing a shear amplitude d or particle density n, while the latter type of RIT has not been verified experimentally. Here, we measure the time-dependent velocity of cyclically sheared vortices and observe the critical behavior of RIT driven by vortex density B as well as d. At the critical point of each RIT, [Formula: see text] and [Formula: see text], the relaxation time [Formula: see text] to reach the steady state shows a power-law divergence. The critical exponent for B-driven RIT is in agreement with that for d-driven RIT and both types of RIT fall into the same universality class as the absorbing transition in the two-dimensional directed-percolation universality class. As d is decreased to the average intervortex spacing in the reversible regime, [Formula: see text] shows a significant drop, indicating a transition or crossover from a loop-reversible state with vortex-vortex collisions to a collisionless point-reversible state. In either regime, [Formula: see text] exhibits a power-law divergence at the same [Formula: see text] with nearly the same exponent.

Critical behavior near the reversible-irreversible transition in periodically driven vortices under random local shear.

When many-particle (vortex) assemblies with disordered distribution are subjected to a periodic shear with a small amplitude [Formula: see text], the particles gradually self-organize to avoid next collisions and transform into an organized configuration. We can detect it from the time-dependent voltage [Formula: see text] (average velocity) that increases towards a steady-state value. For small [Formula: see text], the particles settle into a reversible state where all the particles return to their initial position after each shear cycle, while they reach an irreversible state for [Formula: see text] above a threshold [Formula: see text]. Here, we investigate the general phenomenon of a reversible-irreversible transition (RIT) using periodically driven vortices in a strip-shaped amorphous film with random pinning that causes local shear, as a function of [Formula: see text]. By measuring [Formula: see text], we observe a critical behavior of RIT, not only on the irreversible side, but also on the reversible side of the transition, which is the first under random local shear. The relaxation time [Formula: see text] to reach either the reversible or irreversible state shows a power-law divergence at [Formula: see text]. The critical exponent is determined with higher accuracy and is, within errors, in agreement with the value expected for an absorbing phase transition in the two-dimensional directed-percolation universality class. As [Formula: see text] is decreased down to the intervortex spacing in the reversible regime, [Formula: see text] deviates downward from the power-law relation, reflecting the suppression of intervortex collisions. We also suggest the possibility of a narrow smectic-flow regime, which is predicted to intervene between fully reversible and irreversible flow.

Vortex rectenna powered by environmental fluctuations.

A rectenna, standing for a rectifying antenna, is an apparatus which generates d.c. electricity from electric fluctuations. It is expected to realize wireless power transmission as well as energy harvesting from environmental radio waves. To realize such rectification, devices that are made up of internal atomic asymmetry such as an asymmetric junction have been necessary so far. Here we report a material that spontaneously generates electricity by rectifying environmental fluctuations without using atomic asymmetry. The sample is a common superconductor without lowered crystalline symmetry, but, just by putting it in an asymmetric magnetic environment, it turns into a rectifier and starts generating electricity. Superconducting vortex strings only annihilate and nucleate at surfaces, and this allows the bulk electrons to feel surface fluctuations in an asymmetric environment: a vortex rectenna. The rectification and generation can be switched on and off with only a slight change in temperature or external magnetic fields.

The metabolism of 1-methylhydantoin via 5-hydroxy-1-methylhydantoin in mammals.

The metabolic pathway of 1-methylhydantoin (2) via 5-hydroxy-1-methylhydantoin (3), methylparabanic acid (4) and N5-methyloxaluric acid (5) proved to be a major and general one in mammals. Hence the formation of (3), which has not been detected in normal tissue, is likely to be indirect in inflamed tissue, probably depending on the arising formation of (2) from creatinine (1).

A protein kinase C-beta-selective inhibitor ameliorates neural dysfunction in streptozotocin-induced diabetic rats.

Increased protein kinase C (PKC) activity has been implicated in the pathogenesis of diabetic retinopathy and nephropathy. However, the role of PKC in diabetic neuropathy remains unclear. The present study was conducted to compare the effect of PKC inhibition by a PKC-beta-selective inhibitor, LY333531 (LY), on diabetic nerve dysfunction with that of an aldose reductase inhibitor, NZ-314 (NZ). Streptozotocin-induced diabetic rats were treated with or without LY and/or NZ for 4 weeks, and motor nerve conduction velocity (MNCV), coefficient of variation of R-R interval (CVR-R), sciatic nerve blood flow (SNBF), peak latencies of oscillatory potentials on electroretinogram, PKC activities in membranous and cytosolic fractions of sciatic nerves, and polyol contents in the tail nerves were measured. Untreated diabetic rats demonstrated delayed MNCV, decreased CVR-R, reduced SNBF, and prolonged peak latencies of oscillatory potentials. Treatment with LY as well as NZ prevented all these deficits in diabetic rats. There were no significant differences in PKC activities in membranous or cytosolic fractions of sciatic nerves between normal and diabetic rats. Treatment with neither LY nor NZ altered PKC activities. Nerve myo-inositol depletion in diabetic rats was ameliorated not only by NZ, but also by LY. These observations suggest that inhibition of PKC-beta by LY may have a beneficial effect in preventing the development of diabetic nerve dysfunction, and that this effect may be mediated through its action on the endoneurial micro-vasculature.

Highly selective aldose reductase inhibitors. 1. 3-(Arylalkyl)-2,4,5-trioxoimidazolidine-1-acetic acids.

A series of 3-(arylalkyl)-2,4,5-trioxoimidazolidine-1-acetic acids (1) was prepared and tested for aldose reductase (AR) and aldehyde reductase (ALR) inhibitory activities. These compounds showed strong inhibitory activity against AR without significant inhibitory activity for ALR. The ratio of IC50(ALR)/IC50(AR) was > 1000 in some compounds. On the basis of pharmacological tests such as the recovery of reduced motor nerve conduction velocity and toxicological profile, 3-(3-nitrobenzyl)-2,4,5-trioxoimidazolidine-1-acetic acid (NZ-314) was selected as the candidate for clinical development.

Effect of neurotropin on the binding of high molecular weight kininogen and Hageman factor to human umbilical vein endothelial cells and the autoactivation of bound Hageman factor.

Bradykinin is generated by activation of the plasma kallikrein-kinin (K-K) cascade and contributes to the symptoms of allergic reactions and the perception of pain. Neurotropin is a biological material obtained from inflamed rabbit skin inoculated with vaccinia virus, which is widely used clinically in Japan as an effective agent for these disorders. Factor XII (FXII) and high molecular weight kininogen (HK), two critical constituents of the plasma K-K cascade, bind to endothelial cells, and bound FXII is autoactivated in the presence of zinc ions. We have investigated the effects of Neurotropin on the interactions of FXII and HK with endothelial cells. Neurotropin inhibited the binding of both proteins to cultured human umbilical vein endothelial cells (HUVEC) and inhibited autoactivation of FXII upon HUVEC in a concentration-dependent manner. These data suggest that the ameliorating effects of Neurotropin in allergic disorders and pain syndromes may be related to this ability to inhibit activation of the K-K cascade and, consequently, the formation of bradykinin.

First isolation of gamma-L-glutamyl-gamma-aminobutyric acid from bovine brains.

We had obtained some immunohistochemical indications which suggested that peptide(s) containing GABA at the C-terminal could exist in specific neurons in brains. We therefore sought such GABA conjugate(s) by isolating an acidic GABA-dipeptide from bovine brains and determined its structure as gamma-L-glutamyl-gamma-aminobutyric acid (gamma-L-Glu-gamma Abu:GluGABA). Its gamma-linkage was determined by a mass-spectrometric (B/E linked scan SIMS) analysis; its chirality was established by a chiral column HPLC technique. This peptide is the first acidic GABA-peptide recognized in brain and the first brain peptide containing GABA at the C-terminal.

Gamma-glutamyltaurine has potent and long-lasting antiepileptic action as demonstrated by intra-amygdaloid injection in amygdala-kindled rats.

Intra-amygdaloid injections of gamma-glutamyltaurine, a recently identified brain dipeptide, strongly suppressed seizures in amygdala-kindled rats stimulated with intensities 10 or 50 microA above the generalized seizure triggering threshold (mean 82 microA). The suppressive effect persisted as long as 3 days. Taurine had relatively weak suppressive effects. Thus gamma-glutamyltaurine seems much more potent than taurine in the suppression of epileptic seizures when injected directly into the kindling site.

The role of protein kinase C in the increased generation in isolated rat hepatocytes of the hydroxyl radical by puromycin aminonucleoside.

Puromycin aminonucleoside (PAN) has been known to induce proteinuria. The increased generation of reactive oxygen species (ROS) has been implicated in this toxicity of PAN. We have reported that PAN increases the synthesis of methylguanidine (MG) and creatol which are the products of the reaction of creatinine and the hydroxyl radical in isolated rat hepatocytes. However, the mechanism for the increased ROS induced by PAN is still unclear. In this paper, we investigate the role of protein kinase C (PKC) on the PAN induced reactive oxygen generation in isolated rat hepatocytes. Isolated hepatocytes were incubated in Krebs-Henseleit bicarbonate buffer containing 3% BSA, 16.6 mM creatinine and tested reagents. MG and creatol were determined by high-performance liquid chromatography using 9,10-phenanthrenequinone for the post-labeling. PAN increased MG and creatol synthesis in isolated rat hepatocytes by 60%. 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), a PKC inhibitor, at 10 and 100 microM significantly inhibited MG and creatol synthesis with or without PAN. The inhibition rate is dose dependent from 10 to 100 microM. H1004, a reagent used as control for H-7, did not affect (at 10 microM) or increased little (at 100 microM) the synthesis of MG and creatol. Ro31-8425, a potent PKC inhibitor, significantly inhibited (at 10 microM) MG synthesis in the presence of PAN. PKC in the membrane fraction, a marker of PKC activation, increased over the initial concentration by a factor of 1.65-fold at 60 min incubation and 2.16-fold at 120 min with PAN, while it changed little without PAN. These results indicate that PAN activates PKC resulting in increased hydroxyl radical generation in isolated rat hepatocytes.

Synthesis of creatol, a hydroxyl radical adduct of creatinine and its increase by puromycin aminonucleoside in isolated rat hepatocytes.

Creatol is a hydroxyl radical adduct of creatinine and the precursor of methylguanidine (MG), a uremic toxin. We investigate the synthesis of creatol and MG from creatinine and the effect of substances that affect the hydroxyl radical in isolated rat hepatocytes. In the presence of increasing concentrations of creatinine, rising level of creatol were found after 2 h incubation in Krebs-Henseleit bicarbonate buffer. However, further increase of creatol was not observed after 4 and 6h incubations. On the other hand, MG after 2 h incubation achieved a level of about 50% that of creatol and increased depending on both the creatinine concentration and the incubation period. DMSO, a hydroxyl radical scavenger decreased the generation of creatol and MG by about 50% at 2.5 mM and the inhibition depended on DMSO concentration. Puromycin amino-nucleoside (PAN) increased both by about 170%. These findings demonstrated that hepatocytes synthesize creatol prior to MG and are inhibited by a hydroxyl] radical scavenger. They also show that PAN increased hydroxyl radical generation in tissue cells.

Crossline levels in serum and erythrocyte membrane proteins from patients with diabetic nephropathy.

Crossline is one of the structurally defined adducts of advanced glycation endproducts (AGEs) which has both a crosslink and fluorescence similar to AGE-protein in vivo. Crossline was measured in serum and erythrocyte membrane proteins (EMP) from 52 type 2 diabetic patients using a specific enzyme-linked immunosorbent assay system. Serum and EMP crossline levels in the diabetic patients were significantly higher than those in normal control. The patients with advanced diabetic nephropathy (serum creatinine levels of more than 1.2 mg/dl) had markedly elevated serum crossline levels compared to those with moderate diabetic nephropathy (clinical proteinuria) (180. 7+/-51.7 vs. 71.8+/-18.4 pmol/ml; P<0.01). On the other hand, there were no significant differences in EMP crossline levels between the two. EMP crossline levels in the patients with moderate diabetic nephropathy (8.8+/-2.9 pmol/mg protein) and those with advanced diabetic nephropathy (9.7+/-3.0 pmol/mg protein) were significantly higher than those without clinical proteinuria (6.4+/-1.9 pmol/mg protein; P<0.01). The present study demonstrated that EMP crossline levels were associated with the presence of nephropathy in patients with type 2 diabetes mellitus. Serum crossline levels were significantly influenced by remaining renal function. The measurement of crossline from a blood sample could provide us with important information for the study of clinical evaluation and pathogenesis of diabetic complications.

Neurotropin induces antinociceptive effect by enhancing descending pain inhibitory systems involving 5-HT3 and noradrenergic alpha2 receptors in spinal dorsal horn.

Neurotropin, a non-protein extract from the inflamed skin of rabbits inoculated with vaccinia virus, has been clinically used as an analgesic drug in Japan. Its analgesic effect has been demonstrated by reduced mechano-nociception in hyperalgesic rats exposed to SART-stress (a repeated cold stress) for 5 days. In order to clarify the mechanism of the analgesic effect of neurotropin at the spinal cord level, we examined the effects of several neurotransmitter receptor antagonists given by intrathecal (i.t.) injection on the antinociceptive effect of intraperitoneally (i.p.) injected neurotropin [100 and 200 Neurotropin Unit (NU)/kg]. The analgesic effect of neurotropin was significantly inhibited not only by methysergide (100 nmol/rat, i.t.), a non-selective antagonist against serotonin (5-HT), but also MDL 72222 (30 nmol/rat, i.t.), a selective 5-HT3 antagonist, but not influenced by ketanserin (100 nmol/rat, i.t.), a 5-HT2A antagonist. The antinociceptive effect of neurotropin (200 NU/kg, i. p.) was significantly inhibited also by yohimbine (30 nmol/rat, i.t.), a noradrenergic alpha2 antagonist. However, the analgesic effect of neurotropin (100 and 200 NU/kg, i.p.) was not influenced by naloxone (30 nmol/rat, i.t.), an opioid antagonist. These results suggest that the mechanism of the antinociceptive effect of neurotropin is via enhancement of endogenous descending pain inhibitory pathways of the serotonergic and noradrenergic systems, especially involving 5-HT3 and noradrenergic alpha2 receptors in spinal dorsal horn in which these neurons terminate. No influence of opioid receptors at the spinal cord level is indicated.

Effects of creatinine, creatol and methylguanidine on renal function.

Creatinine (Cr), creatol or methylguanidine (MG) was administered intraperitoneally to normal rats, and several renal function parameters were examined in an attempt to clarify the pathology under the various conditions. The glomerular filtration rate, renal plasma flow and renal blood flow after administration of Cr remained virtually unchanged when compared to those in the control group. In contrast, administration of creatol induced a significant decrease in these renal functions. Further decreases in the renal functions were observed in the rats given MG. However, the level of serum MG was extraordinarily high in the rats given creatol or MG. The toxic effects are discussed on the basis of the above results.