Effect of varying material anisotropy on critical current anistropy in vicinal YBa2_2Cu3_3O7−δ_{7-\delta} thin films

The high $T_{c}$ cuprate superconductors are noted for their anisotropic layered structure, certain of these materials indeed tend toward the limit of a Lawrence-Doniach superconductor. However, YBa$_2$Cu$_3$O$_{7-\delta}$ has a smaller anisotropy than would be expected from its interlayer spacing. This is due to the cuprate chains in the structure. To investigate the influence of the chain oxygen on transport properties critical current versus applied field angle measurements were performed on fully oxygenated and de-oxygenated YBa$_2$Cu$_3$O$_{7-\delta}$ thin films and optimally oxygenated Y$_{0.75}$Ca$_{0.2}$Ba$_2$Cu$_3$O$_{7-\delta}$ thin films. The films were grown on 10$^{\circ}$ mis-cut SrTiO$_3$ substrates to enable the intrinsic vortex channelling effect to be observed. The form of the vortex channelling minimum observed in field angle dependent critical current studies on the films was seen to depend on film oxygenation. The vortex channelling effect is dependent on a angular dependent cross-over to a string-pancake flux line lattice. The results obtained appear to be consistent with the prediction of Blatter et al. [Rev. Mod. Phys., 66 (4): 1125 (1994)] that increased superconducting anisotropy leads to the kinked string-pancake lattice existing over a smaller angular range.Comment: To be submitted to AP

Cell-specific synaptic plasticity induced by network oscillations

Gamma rhythms are known to contribute to the process of memory encoding. However, little is known about the underlying mechanisms at the molecular, cellular and network levels. Using local field potential recording in awake behaving mice and concomitant field potential and whole-cell recordings in slice preparations we found that gamma rhythms lead to activity-dependent modification of hippocampal networks, including alterations in sharp wave- ripple complexes. Network plasticity, expressed as long-lasting increases in sharp wave-associated synaptic currents, exhibits enhanced excitatory synaptic strength in pyramidal cells that is induced postsynaptically and depends on metabotropic glutamate receptor-5 activation. In sharp contrast, alteration of inhibitory synaptic strength is independent of postsynaptic activation and less pronounced. Further, we found a cell type-specific, directionally biased synaptic plasticity of two major types of GABAergic cells, parvalbumin- and cholecystokinin-expressing interneurons. Thus, we propose that gamma frequency oscillations represent a network state that introduces long-lasting synaptic plasticity in a cell-specific manner

Cross-Over between universality classes in a magnetically disordered metallic wire

In this article we present numerical results of conduction in a disordered quasi-1D wire in the possible presence of magnetic impurities. Our analysis leads us to the study of universal properties in different conduction regimes such as the localized and metallic ones. In particular, we analyse the cross-over between universality classes occurring when the strength of magnetic disorder is increased. For this purpose, we use a numerical Landauer approach, and derive the scattering matrix of the wire from electron's Green's function.Comment: Final version, accepted for publication in New Journ. of Physics, 27 pages, 28 figures. Replaces the earlier shorter preprint arXiv:0910.427

Counting defects with the two-point correlator

We study how topological defects manifest themselves in the equal-time two-point field correlator. We consider a scalar field with Z_2 symmetry in 1, 2 and 3 spatial dimensions, allowing for kinks, domain lines and domain walls, respectively. Using numerical lattice simulations, we find that in any number of dimensions, the correlator in momentum space is to a very good approximation the product of two factors, one describing the spatial distribution of the defects and the other describing the defect shape. When the defects are produced by the Kibble mechanism, the former has a universal form as a function of k/n, which we determine numerically. This signature makes it possible to determine the kink density from the field correlator without having to resort to the Gaussian approximation. This is essential when studying field dynamics with methods relying only on correlators (Schwinger-Dyson, 2PI).Comment: 11 pages, 7 figures

Highly Efficient Elimination of Colorectal Tumor-Initiating Cells by an EpCAM/CD3-Bispecific Antibody Engaging Human T Cells

With their resistance to genotoxic and anti-proliferative drugs and potential to grow tumors and metastases from very few cells, cancer stem or tumor-initiating cells (TICs) are a severe limitation for the treatment of cancer by conventional therapies. Here, we explored whether human T cells that are redirected via an EpCAM/CD3-bispecific antibody called MT110 can lyse colorectal TICs and prevent tumor growth from TICs. MT110 recognizes EpCAM, a cell adhesion molecule expressed on TICs from diverse human carcinoma, which was recently shown to promote tumor growth through engagement of elements of the wnt pathway. MT110 was highly potent in mediating complete redirected lysis of KRAS-, PI3 kinase- and BRAF-mutated colorectal TICs, as demonstrated in a soft agar assay. In immunodeficient mice, MT110 prevented growth of tumors from a 5,000-fold excess of a minimally tumorigenic TIC dose. T cells engaged by MT110 may provide a potent therapeutic means to eradicate TICs and bulk tumor cells derived thereof

Interleukin 22 serum levels are associated with radiographic progression in rheumatoid arthritis

To study the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA)

Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.

Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants

Tyrosine Sulfation of Native Mouse Psgl-1 Is Required for Optimal Leukocyte Rolling on P-Selectin In Vivo

We recently demonstrated that tyrosine sulfation is an important contributor to monocyte recruitment and retention in a mouse model of atherosclerosis. P-selectin glycoprotein ligand-1 (Psgl-1) is tyrosine-sulfated in mouse monocyte/macrophages and its interaction with P-selectin is important in monocyte recruitment in atherosclerosis. However, whether tyrosine sulfation is required for the P-selectin binding function of mouse Psgl-1 is unknown. Here we test the function of native Psgl-1 expressed in leukocytes lacking endogenous tyrosylprotein sulfotransferase (TPST) activity.Psgl-1 function was assessed by examining P-selectin dependent leukocyte rolling in post-capillary venules of C57BL6 mice transplanted with hematopoietic progenitors from wild type (WT → B6) or Tpst1;Tpst2 double knockout mice (Tpst DKO → B6) which lack TPST activity. We observed that rolling flux fractions were lower and leukocyte rolling velocities were higher in Tpst DKO → B6 venules compared to WT → B6 venules. Similar results were observed on immobilized P-selectin in vitro. Finally, Tpst DKO leukocytes bound less P-selectin than wild type leukocytes despite equivalent surface expression of Psgl-1.These findings provide direct and convincing evidence that tyrosine sulfation is required for optimal function of mouse Psgl-1 in vivo and suggests that tyrosine sulfation of Psgl-1 contributes to the development of atherosclerosis