Topologically Enforced Bifurcations in Superconducting Circuits.

The relationship of topological insulators and superconductors and the field of nonlinear dynamics is widely unexplored. To address this subject, we adopt the linear coupling geometry of the Su-Schrieffer-Heeger model, a paradigmatic example for a topological insulator, and render it nonlinearly in the context of superconducting circuits. As a consequence, the system exhibits topologically enforced bifurcations as a function of the topological control parameter, which finally gives rise to chaotic dynamics, separating phases that exhibit clear topological features.

Semiclassical bifurcations and topological phase transitions in a one-dimensional lattice of coupled Lipkin-Meshkov-Glick models.

In this work we study a one-dimensional lattice of Lipkin-Meshkov-Glick models with alternating couplings between nearest-neighbors sites, which resembles the Su-Schrieffer-Heeger model. Typical properties of the underlying models are present in our semiclassical-topological hybrid system, allowing us to investigate an interplay between semiclassical bifurcations at mean-field level and topological phases. Our results show that bifurcations of the energy landscape lead to diverse ordered quantum phases. Furthermore, the study of the quantum fluctuations around the mean-field solution reveals the existence of nontrivial topological phases. These are characterized by the emergence of localized states at the edges of a chain with free open-boundary conditions.

Topological Instabilities in ac-Driven Bosonic Systems.

Under nonequilibrium conditions, bosonic modes can become dynamically unstable with an exponentially growing occupation. On the other hand, topological band structures give rise to symmetry protected midgap states. In this Letter, we investigate the interplay of instability and topology. Thereby, we establish a general relation between topology and instability under ac driving. We apply our findings to create dynamical instabilities which are strongly localized at the boundaries of a finite-size system. As these localized instabilities are protected by symmetry, they can be considered as topological instabilities.

The biochemical effects of extracellular Zn(2+) and other metal ions are severely affected by their speciation in cell culture media.

Investigations of physiological and toxicological effects of metal ions are frequently based on in vitro cell culture systems, in which cells are incubated with these ions in specialized culture media, instead of their physiological environment. This allows for targeted examination on the cellular or even molecular level. However, it disregards one important aspect, the different metal ion speciation under these conditions. This study explores the role of culture conditions in investigations with zinc ions (Zn(2+)). Their concentration is buffered by several orders of magnitude by fetal calf serum. Due to the complexity of serum and its many zinc-binding components, zinc speciation in culture media cannot be completely predicted. Still, the primary effect is due to the main Zn(2+)-binding protein albumin. Buffering reduces the free Zn(2+) concentration, thereby diminishing its biological effects, such as cytotoxicity and the impact on protein phosphorylation. This is not limited to Zn(2+), but is also observed with Ag(+), Cu(2+), Pb(2+), Cd(2+), Hg(2+), and Ni(2+). Usually, the serum content of culture media, and thereby their metal buffering capacity, is only a fraction of that in the physiological cellular environment. This leads to systematic over-estimation of the effects of extracellular metal ions when standard cell culture conditions are used as model systems for assessing potential in vivo effects.

ac-Driven quantum phase transition in the Lipkin-Meshkov-Glick model.

We establish a set of nonequilibrium quantum phase transitions in the Lipkin-Meshkov-Glick model under monochromatic modulation of the interparticle interaction. We show that the external driving induces a rich phase diagram that characterizes the multistability in the system. Interestingly, the number of stable configurations can be tuned by increasing the amplitude of the driving field. Furthermore, by studying the quantum evolution, we demonstrate that the system exhibits a set of quantum phases that correspond to dynamically stabilized states.

Assessment of the performance of the Ames II assay: a collaborative study with 19 coded compounds.

Nineteen coded chemicals were tested in an international collaborative study for their mutagenic activity. The assay system employed was the Ames II Mutagenicity Assay, using the tester strains TA98 and TAMix (TA7001-7006). The test compounds were selected from a published study with a large data set from the standard Ames plate-incorporation test. The following test compounds including matched pairs were investigated: cyclophoshamide, 2-naphthylamine, benzo(a)pyrene, pyrene, 2-acetylaminofluorene, 4,4'-methylene-bis(2-chloroaniline), 9,10-dimethylanthracene, anthracene, 4-nitroquinoline-N-oxide, diphenylnitrosamine, urethane, isopropyl-N(3-chlorophenyl)carbamate, benzidine, 3,3'-5,5'-tetramethylbenzidine, azoxybenzene, 3-aminotriazole, diethylstilbestrol, sucrose and methionine. The results of both assay systems were compared, and the inter-laboratory consistency of the Ames II test was assessed. Of the eight mutagens selected, six were correctly identified with the Ames II assay by all laboratories, one compound was judged positive by five of six investigators and one by four of six laboratories. All seven non-mutagenic samples were consistently negative in the Ames II assay. Of the four chemicals that gave inconsistent results in the traditional Ames test, three were uniformly classified as either positive or negative in the present study, whereas one compound gave equivocal results. A comparison of the test outcome of the different investigators resulted in an inter-laboratory consistency of 89.5%. Owing to the high concordance between the two test systems, and the low inter-laboratory variability in the Ames II assay results, the Ames II is an effective screening alternative to the standard Ames test, requiring less test material and labor.

The testing of chemicals in the Syrian hamster embryo (SHE) cell transformation assay for assessment of carcinogenic potential.

The Syrian hamster embryo (SHE) cell transformation assay was used to test 28 chemical substances for their ability to induce morphologically transformed colonies. The purpose was to determine how well the assay method could be transferred from an experienced laboratory by including 18 chemicals previously evaluated and 10 new chemicals. Technical training was obtained in the experienced lab prior to testing. The assay was conducted at pH 6.7, a treatment period of 7 days was used, and single experiments were performed for each chemical. With this limited testing, 78% concordance with rodent bioassay results was obtained, and this high concordance would have increased if small, but statistically negative responses from single trials were overturned by positive data from repeat trials. Similarly, the results were highly concordant (90%) with the experienced lab results; only 2 chemical evaluations were discordant, and the use of repeat experiments would likely have eliminated these apparent disagreements. Thus, with appropriate training, the pH 6.7 SHE assay was successfully and reliably transferred.

The daily dietary intake of ochratoxin a - Results of a duplicate portion study with Bavarian schoolchildren.

The daily dietary intakes of ochratoxin A (OTA) were estimated for 28 school-children at the age of seven and eight years using duplicate portions of the total diets collected on three successive days. For most children and collection days the dietary OTA intakes were below the PTDI-value of 5 ng/kg bw/day. The mean dietary intake was 1.52 ng/kg bw/day for all children. According to sex the mean intakes were 1.21 ng/kg bw/day for boys and 1.83 ng/kg bw/day for girls.

Degradation of ochratoxin a and b by the white rot funguspleurotus ostreatus.

Degradation of ochratoxin A (OTA) and B (OTB) by three selected fungi during solid state fermentation of barley contaminated with ochratoxins was compared. In presence of the soil fungusRhizopus japonicus and the white rot fungusPanerochaete chrysosporium more than 60 % of the mycotoxins remained stable, while in the white rot fungusPleurotus ostreatus only 23 % of the initial OTA and 3 % of OTB were detected after a four weeks incubation period. Kinetic studies on mycotoxin degradation byPI ostreatus demonstrated formation of ochratoxin α and presumably ochratoxin ß as intermediate products, what indicates that hydrolysis is the first step in OTA and OTB degradation followed by further degradation of the intermediates.

Transformation of mutagenic aromatic amines into non-mutagenic species by alkyl substituents. Part I. Alkylation ortho to the amino function.

Alkyl-substituted derivatives of 2-aminonaphthalene (2-AN) 1, 2-aminofluorene (2-AF) 6 and 4-aminobiphenyl (4-ABP) 11 were synthesized and the mutagenic activity of these compounds determined in Salmonella typhimurium strains TA98 and TA100 with and without S9 mix. In the case of the ortho-substituted 4-aminobiphenyls 12-15 (3-alkyl=ethyl, iso-propyl, n-butyl, tert-butyl) the substituent with the strongest steric demand (3-tert-butyl) shows the strongest influence on the decrease of mutagenicity if compared with the parent compound. In the series of the bis-ortho-disubstituted compounds 16-18 (3,5-dimethyl-, 3,5-diethyl- and 3,5-diisopropyl-4-aminobiphenyl) generation of non-mutagenic species occurs already with the introduction of two ethyl groups. For the 4-aminobiphenyl derivatives 12-15 and 16-18, as well as for the 1-alkylated 2-aminofluorenes 7-10 and the 1-alkylated 2-aminonaphthalenes 2-5 a smaller mutagenicity was observed if compared with predicted mutagenicities as calculated by the QSAR equations of Debnath et al. (Environ. Mol. Mutagen. 19 (1992) 37). The largest differences resulted in the cases of the tert-butyl substituted compounds. Only with smaller alkyl groups like ethyl the QSAR predictions and the experimentally determined mutagenicities come close to each other. Thus, these results show that appropriate alkyl substitution reduces (eliminates) mutagenicity, secondly, it is necessary to introduce steric parameters to predict the mutagenicity of such compounds correctly.

[Not Available]. / Nachweis von Zearalenon-4-ß-D-Glucopyranosid in Weizen.

Maize (Zea mays) cell cultures were used for the production of zearalenone-4-ß-D-glucopyranoside as standard compound. Wheat samples were extracted with acetonitrile: water, applied to a florisil column and eluted with methanol:ethyl acetate. For determination and quantification of zearalenone-4-ß-D-glucopyranoside and zearalenone a LC-MS method was developed. A concentration of 10 µg/kg zearalenone-4-ß-D-glucopyranoside and zearalenone was detectable. The recovery rates were calculated to be 69% and 89% at a concentration level of 100 µg/kg for zearalenone-4-ß-D-glucopyranoside and zearalenone, respectively.24 Bavarian wheat samples from harvest 1999 were analyzed. Zearalenone was present in 22 out of 24 field samples, the levels ranged from 11-860 µg/kg. Zearalenone-4-ß-D-glucopyranoside was found in 10 out of the zearalenone positive samples (42%) at levels ranging from 17 to 104 µg/kg. The amounts of zearalenone-4-ß-D-glucopyranoside were correlated to those of zearalenone (r2=0,86; b=0,10).

Effects of caffeine and paracetamol alone or in combination with acetylsalicylic acid on prostaglandin E(2) synthesis in rat microglial cells.

Paracetamol has mild analgesic and antipyretic properties and is, along with acetylsalicylic acid, one of the most popular "over the counter" analgesic agents. However, the mechanism underlying its clinical effects is unknown. Another drug whose mechanism of action is unknown is caffeine, which is often used in combination with other analgesics, augmenting their effect. We investigated the inhibitory effect of paracetamol and caffeine on lipopolysaccharide (LPS)-induced cyclooxygenase (COX)- and prostaglandin (PG)E(2)-synthesis in primary rat microglial cells and compared it with the effect of acetylsalicylic acid, salicylic acid, and dipyrone. Furthermore, combinations of these drugs were used to investigate a possible synergistic inhibitory effect on PGE(2)-synthesis. Both paracetamol (IC(50)=7.45 microM) and caffeine (IC(50)=42.5 microM) dose-dependently inhibited microglial PGE(2) synthesis. In combination with acetylsalicylic acid (IC(50)=3.12 microM), both substances augmented the inhibitory effect of acetylsalicylic acid on LPS-induced PGE(2)-synthesis. Whereas paracetamol inhibited only COX enzyme activity, caffeine also inhibited COX-2 protein synthesis. These results are compatible with the view that the clinical activity of paracetamol and caffeine is due to inhibition of COX. Furthermore, these results may help explain the clinical experience of an adjuvant analgesic effect of caffeine and paracetamol when combined with acetylsalicylic acid.

In vitro micronucleus assay with Chinese hamster V79 cells - results of a collaborative study with in situ exposure to 26 chemical substances.

A collaborative study with 10 participating laboratories was conducted to evaluate a test protocol for the performance of the in vitro micronucleus (MN) test using the V79 cell line with one treatment and one sampling time only. A total of 26 coded substances were tested in this study for MN-inducing properties. Three substances were tested by all 10 laboratories and 23 substances were tested by three or four laboratories in parallel. Six aneugenic, 7 clastogenic and 6 non-genotoxic chemicals were uniformly recognised as such by all laboratories. Three chemicals were tested uniformly negative by three laboratories although also clastogenic properties have been reported for these substances. Another set of three clastogenic substances showed inconsistent results and one non-clastogenic substance was found to be positive by one out of three laboratories. Within the study, the applicability of the determination of a proliferation index (PI) as an internal cytotoxicity parameter in comparison with the determination of the mitotic index (MI) was also evaluated. Both parameters were found to be useful for the interpretation of the MN test result with regard to the control of cell cycle kinetics and the mode of action for MN induction. The MN test in vitro was found to be easy to perform and its results were mainly in accordance with results from chromosomal aberration tests in vitro.

Di(isononyl) phthalate (DINP) and di(isodecyl) phthalate (DIDP) are not mutagenic.

Recently there have been reports of liver and kidney tumors in rodents following long-term exposure to di(isononyl) phthalate (DINP). Mechanistic studies suggested that the liver tumors were a consequence of peroxisomal proliferation, whereas the kidney tumors (found only in male rats) were associated with induction of alpha(2u)-globulin. Because both peroxisomal proliferation and alpha(2u)-globulin are considered to be non-genotoxic carcinogenic processes, it seemed appropriate to investigate the genotoxic potential of DINP. Additional studies were also conducted on di(isodecyl) phthalate (DIDP), a structurally related substance that also induces peroxisomal proliferation, although it has not been tested in a carcinogenicity bioassay. The DINP was tested in Salmonella, in vitro cytogenetics and mouse micronucleus assays, whereas DIDP was evaluated in a mouse micronucleus test. All of these tests produced negative results, i.e. neither phthalate was mutagenic in any of the test systems. These data are consistent with results of other published and unpublished genotoxicity tests and provide support for the hypothesis that the liver and kidney tumors induced by DINP were the result of non-genotoxic processes.

The use of touch for a patient experiencing laryngospasm.

This article is based on a course work assignment for the Welsh National Board Certificate Level Module in Operating Department Practice (Recovery Branch). The article uses a critical incident reflective approach to explore the issues of using touch in caring for a patient, experiencing laryngospasm following a general anaesthetic. A literature review will explain the mechanisms of laryngospasm and will discuss the use of different forms of touch. Conclusions and recommendations will be drawn from the issues discussed.

Lead hydro sodalite [Pb2(OH)(H2O)3]2[Al3Si3O12]2: synthesis and structure determination by combining X-ray rietveld refinement, 1H MAS NMR FTIR and XANES spectroscopy.

Ion exchange of the sodium hydro sodalites [Na3(H2O)4]2-[Al3Si3O12]2 [Na4(H3O2)]2[Al3Si3O12]2 and [Na4(OH)]2[Al3Si3O12]2 with aqueous Pb(NO3)2 solutions yielded, whichever reactant sodalite phase was used, the same lead hydro sodalite, [Pb2(OH)-(H2O)3]2[Al3Si3O12]2. Thus, in the case of the non-basic reactant [Na3(H2O)4]2-[Al3Si3O12]2 an overexchange occurs with respect to the number of nonframework cationic charges. Rietveld structure refinement of the lead hydro sodalite based on powder X-ray diffraction data (cubic, a = 9.070 A, room temperature, space group P43n) revealed that the two lead cations within each polyhedral sodalite cage form an orientationally disordered dinuclear [Pb2(micro-OH)(micro-H2O)(H2O)2]3+ complex. Due to additional lead framework oxygen bonds the coordination environment of each metal cation (CN 3+3) is approximately spherical, and clearly the lead 6s electron lone pair is stereochemically inactive. This is also suggested by the absence of a small peak at 13.025 keV, attributed in other Pb2+-O compounds to an electronic 2p-6s transition, in the PbL3 edge XANES spectrum. 1H MAS NMR and FTIR spectra show that the hydrogen atoms of the aqua hydroxo complex (which could not be determined in the Rietveld analysis) are involved in hydrogen bonds of various strengths.

Is American PGA tour more competitive than European tour? Reply to Jiménez and Fierro-Hernández.

Analysis of the 1998 European PGA tour yielded four statistically significant differences between the shot-making skills of the top 10 and bottom 10 money winners. Analysis of the 1995 American PGA tour indicated only two skills significantly higher among the 10 top-ranked money winners. The results suggest the American PGA tour may be more competitive.

Strategies for extracting NMR parameters from 23Na MAS, DOR and MQMAS spectra. A case study for Na4P2O7.

The 23Na magic-angle spinning (MAS), double rotation (DOR) and multiple-quantum magic-angle spinning (MQMAS) NMR spectra of anhydrous sodium pyrophosphate, Na4P2O7, measured at five different Larmor frequencies (nuL) ranging from 105.8 MHz (corresponding to 400 MHz 1H frequency) to 211.6 MHz (800 MHz) are analysed and the complete set of NMR parameters (C(qcc), etaQ and delta(iso)) of the four crystallographically inequivalent sodium sites were determined with high accuracy. Different approaches of spectra evaluation are discussed and their results are compared. The most reliable results are obtained from a combined evaluation of five DOR and three MQMAS spectra but also from two DOR and one MAS spectra or even from a single MQMAS spectrum all data can be derived. It is shown that Na4P2O7 may serve as a useful reference material for experimental set-up and reliability tests of the various NMR experiments.

Genotoxic bifunctional aldehydes produce specific images in the comet assay.

Seven genotoxic aldehydes (acrolein, chloroacetaldehyde, crotonaldehyde, formaldehyde, glutardialdehyde, glyoxal, and methylacrolein) have been studied in vitro using the alkaline version of the comet assay (or single cell microgel electrophoresis assay) in freshly isolated rat hepatocytes. Chloroacetaldehyde, glyoxal and methylacrolein treatment resulted in an elevated tail moment (TM), used as indicator for an DNA damaging activity and formation of comet like structures. In addition, this treatment also caused characteristic DNA spot images with small, highly condensed areas within the otherwise circular DNA spots. These were not seen in solvent and N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated control cells. Treatment of hepatocytes with acrolein, crotonaldehyde, formaldehyde and glutardialdehyde resulted in an TM which did not differ from those of control values although 86-95% of the cells showed characteristic changes of their DNA spot images. The condensed areas are probably the consequence of the known DNA and protein crosslinking activities of these bifunctional aldehydes. It is suggested that using the alkaline comet assay both TM (or overall comet length) as well as changes in the DNA spot image should be evaluated.

Differential inhibition of cyclooxygenases-1 and -2 by meloxicam and its 4'-isomer.

OBJECTIVE AND DESIGN: Two structurally related compounds, meloxicam (Mel) and its structural 4'-isomer (4'-Mel), were compared to examine the role of a slightly different chemical structure on cyclooxygenase (COX) selectivity in in vitro and in vivo experimental models. MATERIAL OR SUBJECTS: In vitro studies were performed using human whole blood obtained from healthy volunteers, in vivo studies were performed in rats. TREATMENT: A concentration-response curve was obtained in the whole blood assay for Mel, 4'-Mel, indomethacin, piroxicam and diclofenac. These were used to calculate the respective IC50 values of either prostaglandin E2 (PGE2) or thromboxane B2 (TxB2). Similarly, a dose-response curve was obtained for Mel, 4'-Mel and piroxicam when measuring in vivo prostaglandin production, anti-inflammatory activity and gastric tolerance to determine the dose resulting in a 50% reduction of the each parameter. METHODS: COX selectivity was investigated in vitro using a human whole blood assay. PGE2 synthesis in vivo was measured in inflammatory exudate, in the stomach and kidneys of rats. Anti-inflammatory effects were measured in an adjuvant arthritis model and gastric tolerance was tested in an ulcerogenicity model in vivo in rats. RESULTS: In the human whole blood assay, the ratio of IC50 values for COX-1 vs. COX-2 inhibition was 13 for Mel and 1.8 for 4'-Mel. In inflammatory exudate in rats, Mel and 4'-Mel inhibited PGE2 synthesis to a similar extent, ID50 values approximately 0.3 mg/kg. In contrast, Mel was a weaker inhibitor of PG synthesis than 4'-Mel in the rat stomach and in the rat kidney. Paw swelling was reduced by 50% with 0.1 and 0.2 mg/kg for Mel and 4'-Mel, respectively, in the rat adjuvant arthritis model. Gastric tolerance (UD50) was 2.4 mg/kg for Mel and 0.4 mg/kg for 4'-Mel. CONCLUSIONS: These data demonstrate that the in vitro and in vivo pharmacological profile of meloxicam is structurally dependent and that minor structural changes can lead to significant differences in the selectivity for COX-1 and COX-2 in vitro and to different profiles in vivo suggesting different therapeutic potential.