Current patterns and magnetic impurities in time-reversal breaking superconductor

We study the impurity effect in the time reversal symmetry (${\cal T}$) breaking superconductor based on the Bogoliubov-de Gennes (BdG) equations. In ${\cal T}$-violating superconductors, spontaneous currents are induced around the impurity. The current patterns around the impurity reflect the structures of the Cooper pairs. We investigate impurity problem numerically for two kinds of ${\cal T}$ violating superconductors $(p_{x}\pm {\rm i}p_{y}$ and $d+{\rm i}s)$ and investigate the currents around the impurity. We also study the effects of the magnetic impurity in p-wave ($p_{x}\pm {\rm i}p_{y}$) superconductor, especially in view of the zero-energy crossing of energy levels related to the phase transition of the ground state.Comment: 18 page

Fast Particle Effects on the Internal Kink, Fishbone and Alfven Modes

The issues of linear stability of low frequency perturbative and nonperturbative modes in advanced tokamak regimes are addressed based on recent developments in theory, computational methods, and progress in experiments. Perturbative codes NOVA and ORBIT are used to calculate the effects of TAEs on fast particle population in spherical tokamak NSTX. Nonperturbative analysis of chirping frequency modes in experiments on TFTR and JT-60U is presented using the kinetic code HINST, which identified such modes as a separate branch of Alfven modes - resonance TAE (R-TAE). Internal kink mode stability in the presence of fast particles is studied using the NOVA code and hybrid kinetic-MHD nonlinear code M3D

Analysis of Alfven eigenmodes destabilization by energetic particles in TJ-II using a Landau-closure model

Alfven Eigenmodes (AE) can be destabilized by energetic particles in neutral beam injection (NBI) heated plasmas through inverse Landau damping and couplings with gap modes in the shear Alfven continua. We describe the linear evolution of the poloidal flux and the toroidal component of the vorticity in a full 3D system using the reduced MHD equations, density and parallel velocity moments for the energetic particles as well as the geodesic acoustic wave dynamics. A closure relation adds the Landau damping and resonant destabilization effects in the model. We apply the model to study the Alfven modes stability in TJ-II, performing a parametric analysis in a range of realistic values of energetic particle beta (beta(f)), ratios of thermal/Alfven velocities (V-th/V-A0), energetic particle density profiles and toroidal modes (n) including toroidal and helical couplings. The study predicts a large helical coupling between different toroidal modes and the destabilization of helical Alfven eigenmodes (HAE) with frequencies similar to the AE activity measured in TJ-II, between 50-400 kHz. The analysis has also revealed the destabilization of GAE (global Alfven eigenmodes), TAE (toroidal Alfven eigenmodes) and EPM (energetic particle modes). For the modes considered here, optimized TJ-II operations require a t profile in the range of [0.845, 0.979] to stabilize AEs in the inner and middle plasma. AEs in the plasma periphery cannot be fully stabilized, although for a configuration with t = [0.945, 1.079], only n = 7, 11, 15 AE are unstable with a growth rate 4 times smaller compared to the standard t = [1.54, 1.68] case and a frequency of 100 kHz. We reproduce the frequency sweeping evolution of the AE frequency observed in TJ-II as the t profile is varied. The AE frequency sweeping is caused by consecutive changes of the instability dominant modes between different helical families.This material based on work is supported both by the U.S. Department of Energy, Office of Science, under Contract DE-AC05-00OR22725 with UT-Battelle, LLC. This research was sponsored in part by the Ministerio of Economia y Competitividad of Spain under project no. ENE2015-68265-P. We also want to acknowledge Alexander Melnikov and the TJ-II group at CIEMAT for providing us the initial VMEC equilibria and useful discussions regarding the experimental phenomena

Validation of pharmacodynamic assays to evaluate the clinical efficacy of an antisense compound (AEG 35156) targeted to the X-linked inhibitor of apoptosis protein XIAP

The inhibitor of apoptosis protein, XIAP, is frequently overexpressed in chemoresistant human tumours. An antisense oligonucleotide (AEG 35156/GEM 640) that targets XIAP has recently entered phase I trials in the UK. Method validation data are presented on three pharmacodynamic assays that will be utilised during this trial. Quantitative RT-PCR was based on a Taqman assay and was confirmed to be specific for XIAP. Assay linearity extended over four orders of magnitude. MDA-MB-231/U6-E1 cells and clone X-G4 stably expressing an RNAi vector against XIAP were chosen as high and low XIAP expression quality controls (QCs). Within-day and between-day coefficients of variation (CVs) in precision for cycle threshold (CT) and delta CT values (employing GAPDH and beta 2 microglobulin as housekeepers) were always less than 10%. A Western blotting technique was validated using a GST–XIAP fusion protein as a standard and HeLa cells and SF268 (human glioblastoma) cells as high and low XIAP expression QCs. Specificity of the final choice of antibody for XIAP was evaluated by analysing a panel of cell lines including clone X-G4. The assay was linear over a 29-fold range of protein concentration and between-day precision was 29% for the low QC and 23% for the high QC when normalised to GAPDH. XIAP protein was also shown to be stable at −80°C for at least 60 days. M30-Apoptosense™ plasma Elisa detects a caspase-cleaved fragment of cytokeratin 18 (CK18), believed to be a surrogate marker for tumour cell apoptosis. Generation of an independent QC was achieved through the treatment of X-G4 cells with staurosporine and collection of media. Measurements on assay precision and kit-to-kit QC were always less than 10%. The M30 antigen (CK18-Asp396) was stable for 3 months at −80°C, while at 37°C it had a half-life of 80–100 h in healthy volunteer plasma. Results from the phase I trial are eagerly awaited

The interaction of Wnt-11 and signalling cascades in prostate cancer

Prostate cancer (PCa) is the second most common cancer among the male population. Conventional therapies target androgen signalling, which drives tumour growth; however, they provide limited survival benefits for patients. It is essential, therefore, to develop a more specific biomarker than the current gold standard, PSA testing. The Wnt signalling pathway induces expression of target genes through cell surface receptors. A non-canonical member of this family, Wnt-11, is evolutionarily highly conserved and is normally expressed by various cells in the developing embryo, as well as in the heart, liver and skeletal muscle of adult humans. We comprehensively review several cell signalling pathways to explain how they interact with Wnt-11, demonstrating its use as a potential biomarker for PCa. Several studies have shown that the expression of Wnt-11 is associated with gastric, renal and colorectal adenocarcinomas and PCa. Moreover, Wnt-11 affects extracellular matrix composition and cytoskeletal rearrangement, and it is required for proliferation and/or survival during cell differentiation. It was found that PCa cell lines express high levels of Wnt-11, which allows differentiation of the epithelial prostate tumour cells to neuron-like (NE) cells. The NE cells produce additional factors that can cause regression after treatment. Accumulating evidence shows that Wnt-11 could be a potential biomarker in diagnosing PCa. Many studies have shown both non-canonical and canonical Wnts interact with several signalling cascades such as PKC, JNK, NF-κB, Rho, PKA and PI3K. In particular, evidence demonstrates Wnt-11 is involved in the progression of PCa, thus it could have the potential to become both a specific disease marker and an important therapeutic target

Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and induces apoptosis by blocking NCAM expression

<p>Abstract</p> <p>Background</p> <p>Cimetidine, a histamine type-2 receptor antagonist, has been reported to inhibit the growth of glandular tumors such as colorectal cancer, however the mechanism of action underlying this effect is unknown. Adenoid cystic carcinoma is well known as a malignant salivary gland tumor which preferentially invades neural tissues. We demonstrated previously that human salivary gland tumor (HSG) cells spontaneously express neural cell adhesion molecule (NCAM), that HSG cell proliferation may be controlled via a homophilic (NCAM-NCAM) binding mechanism and that NCAM may be associated with perineural invasion by malignant salivary gland tumors. We further demonstrated that cimetidine inhibited NCAM expression and induced apoptosis in HSG cells. Here, we investigated the effects of cimetidine on growth and perineural/neural invasion of salivary gland tumor cells.</p> <p>Methods</p> <p>In this study, we have examined the effect of cimetidine on cancer cell adhesion to neural cells <it>in vitro</it>, one of the critical steps of cancer invasion and metastasis. We have also used an <it>in vivo </it>carcinogenesis model to confirm the effect of cimetidine.</p> <p>Results</p> <p>We have demonstrated for the first time that cimetidine can block the adhesion of HSG cells to neural cell monolayers and that it can also induce significant apoptosis in the tumor mass in a nude mouse model. We also demonstrated that these apoptotic effects of cimetidine might occur through down-regulation of the cell surface expression of NCAM on HSG cells. Cimetidine-mediated down-regulation of NCAM involved suppression of the nuclear translocation of NF-κB, a transcriptional activator of NCAM gene expression.</p> <p>Conclusion</p> <p>These findings suggest that growth and perineural/neural invasion of salivary gland tumors can be blocked by administration of cimetidine via induction of apoptosis and in which NCAM plays a role.</p