A quantitative investigation of the effect of a close-fitting superconducting shield on the coil-factor of a solenoid

Superconducting shields are commonly used to suppress external magnetic interference. We show, that an error of almost an order of magnitude can occur in the coil-factor in realistic configurations of the solenoid and the shield. The reason is that the coil-factor is determined by not only the geometry of the solenoid, but also the nearby magnetic environment. This has important consequences for many cryogenic experiments involving magnetic fields such as the determination of the parameters of Josephson junctions, as well as other superconducting devices. It is proposed to solve the problem by inserting a thin sheet of high-permeability material, and the result numerically tested.Comment: 3 pages, 4 figures, submitted to AP

Planar Josephson Tunnel Junctions in a Transverse Magnetic Field

Traditionally, since the discovery of the Josephson effect in 1962, the magnetic diffraction pattern of planar Josephson tunnel junctions has been recorded with the field applied in the plane of the junction. Here we discuss the static junction properties in a transverse magnetic field where demagnetization effects imposed by the junction geometry and configuration of the electrodes are important. Measurements of the critical current versus magnetic field in planar Nb-based high-quality junctions with different geometry, size and critical current density show that it is advantageous to use a transverse magnetic field rather than an in-plane field to suppress the Josephson tunnel current and Fiske resonances in practical applications.Comment: 5 pages, 2 figures, submitted to Journal of Applied Physic

Spontaneous Fluxon Production in Annular Josephson Tunnel Junctions in the Presence of a Magnetic Field

We report on the spontaneous production of fluxons in the presence of a symmetry-breaking magnetic field for annular Josephson tunnel junctions during a thermal quench. The dependence on field intensity $B$ of the probability $\bar{f_1}$ to trap a single defect during the N-S phase transition drastically depends on the sample circumferences. We show that the data can be understood in the framework of the Kibble-Zurek picture of spontaneous defect formation controlled by causal bounds.Comment: Submitted to Phys. Rev. B with 5 figures on Nov. 15, 200

Zurek-Kibble Mechanism for the Spontaneous Vortex Formation in Nb−Al/Alox/NbNb-Al/Al_{ox}/Nb Josephson Tunnel Junctions: New Theory and Experiment

New scaling behavior has been both predicted and observed in the spontaneous production of fluxons in quenched $Nb-Al/Al_{ox}/Nb$ annular Josephson tunnel junctions as a function of the quench time, $\tau_{Q}$. The probability $f_{1}$ to trap a single defect during the N-S phase transition clearly follows an allometric dependence on $\tau_{Q}$ with a scaling exponent $\sigma = 0.5$, as predicted from the Zurek-Kibble mechanism for {\it realistic} JTJs formed by strongly coupled superconductors. This definitive experiment replaces one reported by us earlier, in which an idealised model was used that predicted $\sigma = 0.25$, commensurate with the then much poorer data. Our experiment remains the only condensed matter experiment to date to have measured a scaling exponent with any reliability.Comment: Four pages, one figur

New Experiments for Spontaneous Vortex Formation in Josephson Tunnel Junctions

It has been argued by Zurek and Kibble that the likelihood of producing defects in a continuous phase transition depends in a characteristic way on the quench rate. In this paper we discuss an improved experiment for measuring the Zurek-Kibble scaling exponent $\sigma$ for the production of fluxons in annular symmetric Josephson Tunnel Junctions. We find $\sigma \simeq 0.5$. Further, we report accurate measurements of the junction gap voltage temperature dependence which allow for precise monitoring of the fast temperature variations during the quench.Comment: 12 pages, 5 figures, submitted to Phys. Rev.

Static Properties of Small Josephson Tunnel Junctions in a Transverse Magnetic Field

The magnetic field distribution in the barrier of small planar Josephson tunnel junctions is numerically simulated in the case when an external magnetic field is applied perpendicular to the barrier plane. The simulations allow for heuristic analytical solutions for the Josephson static phase profile from which the dependence of the maximum Josephson current on the applied field amplitude is derived. The most common geometrical configurations are considered and, when possible, the theoretical findings are compared with the experimental data.Comment: Submitted to JAP with 24 pages and 14 figure

Integrating Factor Analysis and a Transgenic Mouse Model to Reveal a Peripheral Blood Predictor of Breast Tumors

Abstract Background Transgenic mouse tumor models have the advantage of facilitating controlled in vivo oncogenic perturbations in a common genetic background. This provides an idealized context for generating transcriptome-based diagnostic models while minimizing the inherent noisiness of high-throughput technologies. However, the question remains whether models developed in such a setting are suitable prototypes for useful human diagnostics. We show that latent factor modeling of the peripheral blood transcriptome in a mouse model of breast cancer provides the basis for using computational methods to link a mouse model to a prototype human diagnostic based on a common underlying biological response to the presence of a tumor. Methods We used gene expression data from mouse peripheral blood cell (PBC) samples to identify significantly differentially expressed genes using supervised classification and sparse ANOVA. We employed these transcriptome data as the starting point for developing a breast tumor predictor from human peripheral blood mononuclear cells (PBMCs) by using a factor modeling approach. Results The predictor distinguished breast cancer patients from healthy individuals in a cohort of patients independent from that used to build the factors and train the model with 89% sensitivity, 100% specificity and an area under the curve (AUC) of 0.97 using Youden's J-statistic to objectively select the model's classification threshold. Both permutation testing of the model and evaluating the model strategy by swapping the training and validation sets highlight its stability. Conclusions We describe a human breast tumor predictor based on the gene expression of mouse PBCs. This strategy overcomes many of the limitations of earlier studies by using the model system to reduce noise and identify transcripts associated with the presence of a breast tumor over other potentially confounding factors. Our results serve as a proof-of-concept for using an animal model to develop a blood-based diagnostic, and it establishes an experimental framework for identifying predictors of solid tumors, not only in the context of breast cancer, but also in other types of cancer.</p

Identification of germline alterations of the mad homology 2 domain of SMAD3 and SMAD4 from the Ontario site of the breast cancer family registry (CFR)

Abstract Introduction A common feature of neoplastic cells is that mutations in SMADs can contribute to the loss of sensitivity to the anti-tumor effects of transforming growth factor-β (TGF-β). However, germline mutation analysis of SMAD3 and SMAD4, the principle substrates of the TGF-β signaling pathway, has not yet been conducted in breast cancer. Thus, it is currently unknown whether germline SMAD3 and SMAD4 mutations are involved in breast cancer predisposition. Methods We performed mutation analysis of the highly conserved mad-homology 2 (MH2) domains for both genes in genomic DNA from 408 non-BRCA1/BRCA2 breast cancer cases and 710 population controls recruited by the Ontario site of the breast cancer family registry (CFR) using denaturing high-performance liquid chromatography (DHPLC) and direct DNA sequencing. The results were interpreted in several ways. First, we adapted nucleotide diversity analysis to quantitatively assess whether the frequency of alterations differ between the two genes. Next, in silico tools were used to predict variants' effect on domain function and mRNA splicing. Finally, 37 cases or controls harboring alterations were tested for aberrant splicing using reverse-transcription polymerase chain reaction (PCR) and real-time PCR statistical comparison of germline expressions by non-parametric Mann-Whitney test of independent samples. Results We identified 27 variants including 2 novel SMAD4 coding variants c.1350G > A (p.Gln450Gln), and c.1701A > G (p.Ile525Val). There were no inactivating mutations even though c.1350G > A was predicted to affect exonic splicing enhancers. However, several additional findings were of note: 1) nucleotide diversity estimate for SMAD3 but not SMAD4 indicated that coding variants of the MH2 domain were more infrequent than expected; 2) in breast cancer cases SMAD3 was significantly over-expressed relative to controls (P A was associated with elevated germline expression (> 5-fold); 3) separate analysis using tissue expression data showed statistically significant over-expression of SMAD3 and SMAD4 in breast carcinomas. Conclusions This study shows that inactivating germline alterations in SMAD3 and SMAD4 are rare, suggesting a limited role in driving tumorigenesis. Nevertheless, aberrant germline expressions of SMAD3 and SMAD4 may be more common in breast cancer than previously suspected and offer novel insight into their roles in predisposition and/or progression of breast cancer

Randomised comparison of provisional side branch stenting versus a two-stent strategy for treatment of true coronary bifurcation lesions involving a large side branch: the Nordic-Baltic Bifurcation Study IV

Background It is still uncertain whether coronary bifurcations with lesions involving a large side branch (SB) should be treated by stenting the main vessel and provisional stenting of the SB (simple) or by routine two-stent techniques (complex). We aimed to compare clinical outcome after treatment of lesions in large bifurcations by simple or complex stent implantation.Methods The study was a randomised, superiority trial. Enrolment required a SB >= 2.75 mm, >= 50% diameter stenosis in both vessels, and allowed SB lesion length up to 15 mm. The primary endpoint was a composite of cardiac death, non-procedural myocardial infarction and target lesion revascularisation at 6 months. Two-year clinical follow-up was included in this primary reporting due to lower than expected event rates.Results A total of 450 patients were assigned to simple stenting (n = 221) or complex stenting (n=229) in 14 Nordic and Baltic centres. Two-year follow-up was available in 218 (98.6%) and 228 (99.5%) patients, respectively. The primary endpoint of major adverse cardiac events (MACE) at 6 months was 5.5% vs 2.2% (risk differences 3.2%, 95% CI -0.2 to 6.8, p=0.07) and at 2 years 12.9% vs 8.4% (HR 0.63, 95% CI 0.35 to 1.13, p = 0.12) after simple versus complex treatment. In the subgroup treated by newer generation drug-eluting stents, MACE was 12.0% vs 5.6% (HR 0.45, 95% CI 0.17 to 1.17, p = 0.10) after simple versus complex treatment.Conclusion In the treatment of bifurcation lesions involving a large SB with ostial stenosis, routine two-stent techniques did not improve outcome significantly compared with treatment by the simpler main vessel stenting technique after 2 years

Transcriptome Profiling of Whole Blood Cells Identifies PLEK2 and C1QB in Human Melanoma

Developing analytical methodologies to identify biomarkers in easily accessible body fluids is highly valuable for the early diagnosis and management of cancer patients. Peripheral whole blood is a "nucleic acid-rich" and "inflammatory cell-rich" information reservoir and represents systemic processes altered by the presence of cancer cells.We conducted transcriptome profiling of whole blood cells from melanoma patients. To overcome challenges associated with blood-based transcriptome analysis, we used a PAXgene™ tube and NuGEN Ovation™ globin reduction system. The combined use of these systems in microarray resulted in the identification of 78 unique genes differentially expressed in the blood of melanoma patients. Of these, 68 genes were further analyzed by quantitative reverse transcriptase PCR using blood samples from 45 newly diagnosed melanoma patients (stage I to IV) and 50 healthy control individuals. Thirty-nine genes were verified to be differentially expressed in blood samples from melanoma patients. A stepwise logit analysis selected eighteen 2-gene signatures that distinguish melanoma from healthy controls. Of these, a 2-gene signature consisting of PLEK2 and C1QB led to the best result that correctly classified 93.3% melanoma patients and 90% healthy controls. Both genes were upregulated in blood samples of melanoma patients from all stages. Further analysis using blood fractionation showed that CD45(-) and CD45(+) populations were responsible for the altered expression levels of PLEK2 and C1QB, respectively.The current study provides the first analysis of whole blood-based transcriptome biomarkers for malignant melanoma. The expression of PLEK2, the strongest gene to classify melanoma patients, in CD45(-) subsets illustrates the importance of analyzing whole blood cells for biomarker studies. The study suggests that transcriptome profiling of blood cells could be used for both early detection of melanoma and monitoring of patients for residual disease