80 research outputs found
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 of the probability
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 Josephson Tunnel Junctions: New Theory and Experiment
New scaling behavior has been both predicted and observed in the spontaneous
production of fluxons in quenched annular Josephson tunnel
junctions as a function of the quench time, . The probability
to trap a single defect during the N-S phase transition clearly follows an
allometric dependence on with a scaling exponent , 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
, 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 for the production of fluxons in
annular symmetric Josephson Tunnel Junctions. We find .
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
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