Catalyst-free vapour-solid technique for deposition of Bi2Te3 and Bi2Se3 nanowires/nanobelts with topological insulator properties.

We present a simple two-stage vapour-solid synthesis method for the growth of bismuth chalcogenide (Bi2Te3, Bi2Se3) topological insulator nanowires/nanobelts by using Bi2Se3 or Bi2Te3 powders as source materials. During the first stage of the synthesis process nanoplateteles, serving as "catalysts" for further nanowire/nanobelt growth, are formed. At a second stage of the synthesis, the introduction of a N2 flow at 35 Torr pressure in the chamber induces the formation of free standing nanowires/nanobelts. The synthesised nanostructures demonstrate a layered single-crystalline structure and Bi : Se and Bi : Te ratios 40 : 60 at% for both Bi2Se3 and Bi2Te3 nanowires/nanobelts. The presence of Shubnikov de Haas oscillations in the longitudinal magneto-resistance of the nanowires/nanobelts and their specific angular dependence confirms the existence of 2D topological surface states in the synthesised nanostructures.

Charge qubit coupled to an intense microwave electromagnetic field in a superconducting Nb device: evidence for photon-assisted quasiparticle tunneling.

We study a superconducting charge qubit coupled to an intensive electromagnetic field and probe changes in the resonance frequency of the formed dressed states. At large driving strengths, exceeding the qubit energy-level splitting, this reveals the well known Landau-Zener-Stückelberg interference structure of a longitudinally driven two-level system. For even stronger drives, we observe a significant change in the Landau-Zener-Stückelberg pattern and contrast. We attribute this to photon-assisted quasiparticle tunneling in the qubit. This results in the recovery of the qubit parity, eliminating effects of quasiparticle poisoning, and leads to an enhanced interferometric response. The interference pattern becomes robust to quasiparticle poisoning and has a good potential for accurate charge sensing.

Microwave response of superconducting YBa2Cu3O(7-δ) nanowire bridges sustaining the critical depairing current: evidence of Josephson-like behavior.

We have investigated the zero-field critical supercurrent of YBa(2)Cu(3)O(7-δ) bridges patterned from 50 nm thick films as a function of bridge width, ranging from 2 µm to 50 nm. The critical current density monotonically increases for decreasing bridge width even for widths smaller than the Pearl length. This behavior is accounted for by considering current crowding effects at the junction between the bridge and the wider electrodes. Comparison to numerical calculations of the current distributions in our bridge geometries of various widths yields a (local) critical current density at 4.2 K of 1.3×10(8) A/cm(2), the Ginzburg Landau depairing current density. The observation of up to 160 Shapiro-like steps in the current voltage characteristics under microwave irradiation substantiates the pristine character of our nanobridges with cross sections as small as 50×50 nm(2).

Fully gapped superconductivity in a nanometre-size YBa2Cu3O(7-δ) island enhanced by a magnetic field.

The symmetry of Cooper pairs is central to constructing a superconducting state. The demonstration of a d(x²-y²)-wave order parameter with nodes represented a breakthrough for high critical temperature superconductors (HTSs). However, despite this fundamental discovery, the origin of superconductivity remains elusive, raising the question of whether something is missing from the global picture. Deviations from d(x²-y²)-wave symmetry, such as an imaginary admixture d(x²-y²)+ is (or id(xy)), predict a ground state with unconventional properties exhibiting a full superconducting gap and time reversal symmetry breaking. The existence of such a state, until now highly controversial, can be proved by highly sensitive measurements of the excitation spectrum. Here, we present a spectroscopic technique based on an HTS nanoscale device that allows an unprecedented energy resolution thanks to Coulomb blockade effects, a regime practically inaccessible in these materials previously. We find that the energy required to add an extra electron depends on the parity (odd/even) of the excess electrons on the island and increases with magnetic field. This is inconsistent with a pure d(x²-y²)-wave symmetry and demonstrates a complex order parameter component that needs to be incorporated into any theoretical model of HTS.

Soft nanostructuring of YBCO Josephson junctions by phase separation.

We have developed a new method to fabricate biepitaxial YBa2 Cu3 O7-δ (YBCO) Josephson junctions at the nanoscale, allowing junctions widths down to 100 nm and simultaneously avoiding the typical damage in grain boundary interfaces due to conventional patterning procedures. By using the competition between the superconducting YBCO and the insulating Y2 BaCuO5 phases during film growth, we formed nanometer sized grain boundary junctions in the insulating Y2 BaCuO5 matrix as confirmed by high-resolution transmission electron microscopy. Electrical transport measurements give clear indications that we are close to probing the intrinsic properties of the grain boundaries.

Interplay between static and dynamic properties of semifluxons in YBa2Cu3O(7-delta) 0-pi Josephson junctions.

We have investigated the static and dynamic properties of long YBa2Cu3O(7-delta) 0-pi Josephson junctions and compared them with those of conventional 0 junctions. Scanning SQUID microscope imaging has revealed the presence of a semifluxon at the phase discontinuity point in 0-pi Josephson junctions. Zero field steps have been detected in the current-voltage characteristics of all junctions. Comparison with simulation allows us to attribute these steps to fluxons traveling in the junction for conventional 0 junctions and to fluxon-semifluxon interactions in the case of 0-pi Josephson junctions.

Collapse of thermal activation in moderately damped Josephson junctions.

We study switching current statistics in moderately damped Nb-InAs-Nb and intrinsic Bi2Sr2CaCu2O8+delta) Josephson junctions. A paradoxical collapse of thermal activation with increasing temperature is reported and explained by the interplay of two conflicting consequences of thermal fluctuations, which can both assist in premature escape and help in retrapping back into the stationary state. We analyze the influence of dissipation on the thermal escape by tuning damping with a gate voltage, magnetic field, temperature, and an in situ capacitor.

Macroscopic quantum tunneling in d-wave YBa2Cu3O7-delta Josephson junctions.

The escape rate from the zero voltage state in a superconducting Josephson junction (JJ) is determined by the temperature, but it saturates at low temperature due to macroscopic quantum tunneling (MQT). Complications due to d-wave symmetry in a high temperature superconductor, like low energy quasiparticles and an unconventional current-phase relation, may influence the escape rate. We report, for the first time to our knowledge, the observation of MQT in a YBa(2)Cu(3)O(7-delta) grain boundary biepitaxial JJ. This proves that dissipation can be significantly reduced by a proper junction configuration, which is of significance for quantum coherence.

Does radiotherapy affect the outcome of the comet assay?

This study was designed to assess possible effects of fractionated radiotherapy (5 or 10 fractions at 2 Gy per fraction) on the DNA repair capacity of lymphocytes, as measured by the comet assay. 50 patients with various tumour types were chosen. They had received no chemotherapy during the 6 months prior to radiotherapy and did not receive cortisone. 10 ml of heparinized blood was collected before radiotherapy, after 5 fractions and after 10 fractions. Lymphocytes were isolated and analysed using the comet assay. On average, no effect on DNA repair capacity was observed that could be attributed to radiotherapy. On an individual basis, there were a few patients who showed a comparatively pronounced variability in their response to radiotherapy (three patients with a relative coefficient of variability of more than 30%). There was some indication of a weak correlation between poor repair capacity and severe side effects in normal tissue. We also found that alcohol in particular, and smoking to some extent, may impair repair capacity during radiotherapy. Age, gender, field size, medication and tumour entity showed no effect on repair capacity.

BRCA1 and BRCA2 heterozygosity and repair of X-ray-induced DNA damage.

PURPOSE: Up to 90% of hereditary breast cancer cases are linked to germ-line mutations in one of the two copies of the BRCA1 or BRCA2 genes. Brca1 and Brca2 proteins are both involved in the cellular defence against DNA damage, although the precise function of the proteins is still not known. Some studies on a small number of samples as well as the present pilot study also suggested that BRCA1 heterozygosity may lead to impaired repair of ionizing-radiation-induced DNA double-strand breaks. The purpose of the study was to test in a larger family-matched study whether carriers of BRCA1 or BRCA2 mutations have an increased sensitivity to ionizing radiation. MATERIALS AND METHODS: In a blind study, the effect of different germ-line mutations in one allele of the BRCA1 or BRCA2 gene on the ability to repair X-ray-induced DNA breaks was investigated. Fibroblasts and lymphocytes were taken from heterozygotic individuals (BRCA1+ /- and BRCA2+ /-) with different mutations and from relatives proven to be non-carriers of the BRCA mutations. Rejoining of DNA breaks was analysed by pulsed-field gel electrophoresis (for fibroblasts) or the comet assay (for lymphocytes). RESULTS: Significant interindividual differences were found in the capacities of the fibroblasts and lymphocytes to rejoin DNA breaks induced by X-radiation. However, these differences were not related to heterozygosity in BRCA1 or BRCA2. CONCLUSIONS: Cells from carriers of mutations in one allele of the BRCA1 or BRCA2 genes have no gross defects in their ability to rejoin radiation-induced DNA breaks. Hence, these carriers may not be at risk of developing excess normal tissue reactions after radiotherapy consistent with data from recent clinical studies.

Heterogeneity in 2-deoxy-D-glucose-induced modifications in energetics and radiation responses of human tumor cell lines.

PURPOSE: The glucose analog and glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has been shown to differentially enhance the radiation damage in tumor cells by inhibiting the postirradiation repair processes. The present study was undertaken to examine the relationship between 2-DG-induced modification of energy metabolism and cellular radioresponses and to identify the most relevant parameter(s) for predicting the tumor response to the combined treatment of radiation + 2-DG. METHODS AND MATERIALS: Six human tumor cell lines (glioma: BMG-1 and U-87, squamous cell carcinoma: 4451 and 4197, and melanoma: MeWo and Be-11) were investigated. Cells were exposed to 2 Gy of Co-60 gamma-rays or 250 kVP X-rays and maintained under liquid-holding conditions 2-4 h to facilitate repair. 2-DG (5 mM, equimolar with glucose) that was added at the time of irradiation was present during the liquid holding. Glucose utilization, lactate production (enzymatic assays), and adenine nucleotides (high performance liquid chromatography and capillary isotachophoresis) were investigated as parameters of energy metabolism. Induction and repair of DNA damage (comet assay), cytogenetic damage (micronuclei formation), and cell death (macrocolony assay) were analyzed as parameters of radiation response. RESULTS: The glucose consumption and lactate production of glioma cell lines (BMG-1 and U-87) were nearly 2-fold higher than the squamous carcinoma cell lines (4197 and 4451). The ATP content varied from 3.0 to 6.5 femto moles/cell among these lines, whereas the energy charge (0.86-0.90) did not show much variation. Presence of 2-DG inhibited the rate of glucose usage and glycolysis by 30-40% in glioma cell lines and by 15-20% in squamous carcinoma lines, while ATP levels reduced by nearly 40% in all the four cell lines. ATP:ADP ratios decreased to a greater extent ( approximately 40%) in glioma cells than in squamous carcinoma 4451 and MeWo cells; in contrast, presence of 2-DG reduced ADP:AMP ratios by 3-fold in the squamous carcinoma 4451, whereas an increase was noted in the glioma cell line BMG-1. 2-DG significantly reduced the initial rates of DNA repair in all cells, resulting in an excess residual damage after 2 h of repair in BMG-1, U-87, and 4451 cell lines, whereas no significant differences could be observed in the other cell lines. Recovery from potentially lethal damage was also significantly inhibited in BMG-1 cells. 2-DG increased the radiation-induced micronuclei formation in the melanoma line (MeWo) by nearly 60%, while a moderate (25-40%) increase was observed in the glioma cell lines (BMG-1 and U-87). Presence of 2-DG during liquid holding (4 h) enhanced the radiation-induced cell death by nearly 40% in both the glioma cell lines, while significant effects were not observed in others. CONCLUSIONS: The modifications in energetics and radiation responses by 2-DG vary considerably among different human tumor cell lines, and the relationships between energy metabolism and various radiobiologic parameters are complex in nature. The 2-DG-induced modification of radiation response does not strictly correlate with changes in the levels of ATP. However, a significant enhancement of the radiation damage by 2-DG was observed in cells with high rates of glucose usage and glycolysis, which appear to be the two most important factors determining the tumor response to the combined treatment of 2-DG + radiation therapy.

Radiation sensitivity of lymphocytes from healthy individuals and cancer patients as measured by the comet assay.

Lymphocytes of healthy volunteers (n = 24) and of tumour patients (n = 30, 18 of whom had experienced severe side-effects) were irradiated with x-rays in vitro. DNA damage was analysed after 0.25-2 Gy and DNA repair after 2 Gy, and quantification of both endpoints was done by the comet assay. The individual differences in radiation-induced DNA damage as well as in the repair kinetics were observed to be striking for both healthy donors and tumour patients. After a repair time of 3 h, following 2 Gy x-irradiation, some of the healthy volunteers showed no residual DNA damage at all in their lymphocytes, whereas others revealed about 30%. There was no indication that our results were affected by either age, gender or smoking habits. Slow repair kinetics and high amounts of residual damage were characteristic for many but not all tumour patients who had experienced severe side-effects in their normal tissues during or after radiotherapy (n = 18). Our conclusion is that those individuals showing poor DNA repair characteristics in the lymphocytes following in vitro irradiation, have a high probability of being radiosensitive. The opposite conclusion is not necessarily true: if repair is effective, this does not mean that the individual is radioresistant, because factors other than impaired repair may cause radiosensitivity.

Effects of theophylline on exercise indices in a patient with chronotropic incompetence.

Several investigators have documented the successful use of oral sustained-release theophylline in treating symptomatic bradycardia and sick sinus syndrome. This paper reports a case of chronotropic incompetence in which specific exercise indices, including the chronotropic response index, were used to measure the therapeutic efficacy of theophylline.

DNA excision repair and DNA damage-induced apoptosis are linked to Poly(ADP-ribosyl)ation but have different requirements for p53.

Poly(ADP-ribose) polymerase (PARP) is a DNA binding zinc finger protein that catalyzes the transfer of ADP-ribose residues from NAD(+) to itself and different chromatin constituents, forming branched ADP-ribose polymers. The enzymatic activity of PARP is induced upon DNA damage and the PARP protein is cleaved during apoptosis, which suggested a role of PARP in DNA repair and DNA damage-induced cell death. We have generated transgenic mice that lack PARP activity in thymocytes owing to the targeted expression of a dominant negative form of PARP. In the presence of single-strand DNA breaks, the absence of PARP activity correlated with a strongly increased rate of apoptosis compared to cells with intact PARP activity. We found that blockage of PARP activity leads to a drastic increase of p53 expression and activity after DNA damage and correlates with an accelerated onset of Bax expression. DNA repair is almost completely blocked in PARP-deficient thymocytes regardless of p53 status. We found the same increased susceptibility to apoptosis in PARP null mice, a similar inhibition of DNA repair kinetics, and the same upregulation of p53 in response to DNA damage. Thus, based on two different experimental in vivo models, we identify a direct, p53-independent, functional connection between poly(ADP-ribosyl)ation and the DNA excision repair machinery. Furthermore, we propose a p53-dependent link between PARP activity and DNA damage-induced cell death.

Automated comet assay analysis.

BACKGROUND: Recently the "comet assay" or "single-cell gel electrophoresis assay" has been established as a sensitive method for the detection of DNA damage and repair. Most of the software now available to quantify various parameters for DNA damage requires the interaction of a human observer. In this report, we describe an automated analysis system that is based on self-developed software and hardware and needs minimal human interaction. METHODS: The image analysis is divided into two parts: 1) automatic cell recognition and comet classification and 2) quantification of desired comet parameters. Image preprocessing, segmentation, and feature classification were developed with algorithms based on mathematical morphology. To enhance evaluation speed, we have introduced parallel processing of data under the Windows NT operating system (Microsoft Corporation, Redmond, WA). Use of an analogue real-time autofocus unit (Böcker et al.: Phys Med Biol 1997;42:1981-1992) allows for faster analysis. RESULTS: Our recognition software shows a sensitivity of 95.2% and a specificity of 92.7% when tested on test samples from routine work with DNA damage by low-dose radiation (0-2 Gy). The parallel hardware and software concept enables us to analyze 100 comets on one slide in less than 15 min. CONCLUSIONS: A comparison of measurements made on the same samples by manual and automated analysis systems revealed that there are no significant differences. The slope of the dose-response curves and the repair kinetics are very similar and demonstrate that automatic comet assay analysis is possible.

Neurochemical substrates and neuroanatomical generators of the event-related P300.

The present review focuses on the current knowledge of the neurochemical processes and neuronal structures involved in the generation of P300. The increasing knowledge in this area facilitates the physiological interpretation of P300 findings as well as the link between P300 research and other research findings in biological psychiatry. Concerning the question of neurochemical substrates, the glutamatergic, GABAergic, cholinergic, noradrenergic, dopaminergic and serotonergic influences on P300 are reviewed. The knowledge of the generating structures of P300 is summarized from intracranial studies, magnetoencephalographic investigations, lesion and animal studies.

Optimization and standardization of the "comet assay" for analyzing the repair of DNA damage in cells.

BACKGROUND: The "comet assay" has become an interesting and a very useful tool for the analysis of the induction and amount of DNA damage in single cells thus offering the opportunity to measure the effectiveness of DNA repair. On the basis of the Ostling and Johanson protocol we have developed a modified method with increased sensitivity and high reproducibility. MATERIAL AND METHODS: Human tumor cells or isolated human peripheral blood lymphocytes were analyzed in the experiments. The amount of DNA damage and the effectiveness of DNA repair was measured after X-irradiation using the "comet assay" technique. RESULTS: In this presentation the influences of different methodological factors like agarose concentration, buffer pH, electrophoresis time, electric field strength on the applicability of the "comet assay" are described in detail and optimum conditions for "comet assay" experiments have been evaluated. Additionally the authors will show a comparison of different fluorescent DNA dyes pointing out their advantages or disadvantages for "comet" analysis. The usefulness of this technique and its capabilities are exemplified by showing DNA repair kinetics of human lymphocytes of different healthy or radiosensitive donors after in-vitro irradiation with 2 Gy X-rays. CONCLUSIONS: This paper presents data on the optimization and standardization of the original "comet assay" leading to an extremely fast and practicable protocol in the field of single cell gel electrophoresis. After irradiation with 0.1 Gy an increase in the amount of DNA damage can be measured with high statistical significance and the DNA repair capacity of individual cells after X-ray doses of 2 Gy can be analyzed with high reproducibility. The results comparing DNA repair capacities of different donors point out that the "comet assay" may have the potential for the estimation of individual radiosensitivity.

Stability of the mismatch negativity under different stimulus and attention conditions.

OBJECTIVE: Mismatch negativities (MMN) elicited by frequency and duration changes in a sequence of repetitive tones were recorded in test and retest sessions from 45 subjects. METHODS: Tones presented with a stimulus onset asynchrony (SOA) of 0.5 s were to be ignored while attention had no instructed focus in one group and was directed to an active visual vigilance task in a second group of subjects. RESULTS: MMN amplitude was larger for duration deviants, the focus of attention had no systematic effect. Individual replicability of the MMN amplitudes was generally better when duration deviants were used. In addition, directing attention to the visual task increased the retest reliability of the duration deviance MMN. In this condition, the test-retest correlation coefficients were above 0.8 at all frontal scalp sites (0.87 at F4). CONCLUSIONS: The study shows that the deviant type as well as the attentional condition may have substantial effects on the stability and replicability of MMN potentials. The choice of the appropriate task condition is essential for using the MMN in group comparisons and as a diagnostic tool in individual cases.

Late auditory evoked potentials (P300) do not discriminate between subgroups of alcohol-dependent patients defined by family history and antisocial personality traits.

Alcohol dependent patients with a family history of alcoholism and with antisocial personality traits were supposed to have frontal brain dysfunction. Late evoked potentials may be useful to discriminate these patients from patients without family history or antisocial behavior. We investigated 56 abstinent patients hypothesizing that four subgroups of abstinent alcoholics with regard to family history (FHP: family history positive, FHN: family history negative) and antisocial behavior (ASP: antisocial traits present, ASN: antisocial traits not present) would exhibit differences in P300, particularly when recorded by frontal electrodes. FHP/ASP patients were expected to show the lowest P300 amplitudes in frontal electrode sites. Beside single electrode recordings, a new method in analyzing P300 scalp data by dipole source analysis (BESA: Brain electric signal analysis) was used. No difference in the P300 values was observed between the FHP/FHN and ASP/ASN groups. Similar results were found by analyzing ASP/ASN and FHP/FHN groups separately. The findings of single electrode recordings were consistent with BESA-dipole results. In conclusion, auditory P300 had a low discriminative power with regards to subgroups of inpatient alcoholics defined by family history and antisocial personality traits. Reasons for the negative findings in this study are discussed.