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).

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.

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.

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.

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.

P300 subcomponents reflect different aspects of psychopathology in schizophrenia.

BACKGROUND: The aim of the study was to investigate abnormalities of P300 subcomponents in schizophrenic patients as well as relationships between these subcomponents and positive versus negative schizophrenic symptoms. METHODS: Nineteen schizophrenic patients and 19 healthy controls were tested with an auditory event-related potential oddball paradigm designed to elicit the P300. The P300 data were analyzed by separating P300 subcomponents with a recently developed dipole source model. RESULTS: Compared to healthy controls, schizophrenic patients showed reduced P300 amplitudes of the temporo-basal dipoles, corresponding mainly to P3b. Positive symptoms of the Positive and Negative Syndrome Scale correlated positively with the temporo-basal but not with temporo-superior dipole P300 activities, whereas negative symptoms correlated positively with the temporo-superior but not with temporo-basal dipole activities. CONCLUSIONS: The P300 subcomponents separated with the dipole model are affected in a different manner by positive versus negative symptoms. Furthermore, the positive correlation between the severity of psychopathology and the P300 amplitudes of the different dipole activities appears to be a state-dependent effect, which has to be separated from the P300 amplitude reduction as a trait marker in schizophrenic patients.

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.

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.

Comet assay studies of radiation-induced DNA damage and repair in various tumour cell lines.

We used the 'comet assay' to compare the amount of radiation-induced DNA damage in three tumour cell lines (MeWo, PECA 4451 and PECA 4197) and the extent of DNA repair in two of these lines (MeWo and PECA 4197). Tumour cells were irradiated with X-rays (0.1-10 Gy), embedded in agarose on slides, lysed with sodium dodecyl sulphate and exposed to an electric field. DNA migrated within the agarose and formed comets whose length depended on the amount of DNA damage. When the cells were incubated at 37 degrees C for various time intervals before electrophoresis started, the comets shrank in the course of time, indicating repair of DNA damage. All three cell lines showed the same extent of DNA damage after radiation exposure, despite the fact that in the colony-forming assay MeWo and PECA 4451 were much more sensitive to radiation exposure than PECA 4197. The repair characteristics, however, were markedly different for MeWo and PECA 4197 cells. PECA 4197 cells showed a much faster restoration of the original shape of the cell nucleus than MeWo cells.

Image analysis of comet assay measurements.

In the last decade the 'comet assay' or 'single cell gel electrophoresis assay' has been established as a sensitive method for the detection of DNA damage and the measurement of its recovery. The results published in the literature have often been obtained with different methods for comet structure measurement. In most cases these data are not comparable with each other. Even when using similar systems for the analysis, it is difficult to obtain matching data. This presentation will describe some technical aspects of our measurement equipment and evaluation software. It focuses on necessary experimental conditions to minimize errors in obtaining such data. The software developed here allows the rapid analysis of the microscopic samples (< 2 s per image). The image analysis was designed with respect to the morphological shapes of comet cells, which were investigated with a confocal laser microscope. The system is built with standard components which are commercially available. As a measure of the amount of DNA damage the ratio of fluorescence intensity was used inside the comet tail and the fluorescence intensity of the comet head. Other parameters such as DNA content, comet area, head radius, tail length and tail moment are also determined. The reproducibility of the system has been evaluated in several experiments over a period of 5 years.

Comet assay study of DNA damage and repair of tumour cells following boron neutron capture irradiation with fast d(14) + Be neutrons.

We compared the amount of radiation-induced DNA damage and the extent of DNA repair in human melanoma cells (MeWo) using the 'comet assay' after neutron, boron neutron capture and X-irradiation. Using a colony-forming assay it was shown earlier that lethal effects in tumour cells treated with fast neutrons may be increased by the neutron capture reaction 10B(n, alpha)7Li. The effectiveness of boron neutron capture in killing tumour cells depends on the number of 10B atoms delivered to the tumour, the subcellular distribution of 10B and the thermal neutron fluence at the side of the tumour. Using the 'comet assay' the DNA damage of fast neutrons (mean energy 5.8 MeV) was shown to be significantly greater than for the same absorbed dose of X-rays. The presence of 600 ppm 10B (boric acid H5 10BO3) in the cell medium during irradiation with d(14) + Be neutrons in a phantom enhances the DNA damage by 20% compared with neutron irradiation alone. After DNA damage induction by neutrons and neutron capture of boron, the DNA repair capacity of the MeWo cells is significantly reduced in comparison with X-irradiation resulting in proportionally more residual DNA damage after 180 min of repair time.

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.

Dipole source analysis of P300 component of the auditory evoked potential: a methodological advance?

A dipole model of the P300 component of the auditory evoked potential was developed with the aim of separating the overlapping P300 subcomponents and assessing the reliability of P300 dipole parameters compared with other methods such as principal component analysis (PCA). P300 was recorded within an auditory oddball paradigm in 57 healthy subjects. Dipole source analysis was performed with Brain Electrical Source Analysis (BESA). With a temporo-basal and a temporo-superior dipole per hemisphere, most of the variance of scalp-recorded P300 activity can be explained. When dipole source analysis is used, the test-retest reliability of P300-amplitude measurements is enhanced as compared with PCA or single channel analysis. The P300 activity of the temporo-basal dipoles and that of the temporo-superior dipoles differ in several respects (e.g. latency, correlations with age) and thus appear to reflect functionally different neuronal processes. In spite of problems in the interpretation of dipole locations, it is concluded that dipole source analysis enhances both the reliability and physiological validity of P300 parameters.

Breakage of an embolized intravascular catheter fragment: a complication of nonsurgical transvenous retrieval.

The use of permanently implantable central venous catheters may be complicated by catheter fracture and embolism. Nonsurgical retrieval of embolized catheter fragments is well established, and complications are rarely noted. We report a case in which the retrieval technique led to further fracture of a silicone rubber (Silastic) catheter and embolization to the lung. Silastic catheters may be prone to this complication, and appropriate caution during recovery of such catheter fragments is recommended.

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.

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.

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.

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.