Angle-dependent Magnetoresistance of an Ordered Bose Glass of Vortices in YBa2_{2}Cu3_{3}O7−δ_{7-\delta} Thin Films with a Periodic Pinning~Lattice

The competition between intrinsic disorder in superconducting YBa$_{2}$Cu$_{3}$O$_{7-\delta}$ (YBCO) thin films and an ultradense triangular lattice of cylindrical pinning centers spaced at 30 nm intervals results in an ordered Bose glass phase of vortices. The samples were created by scanning the focused beam of a helium-ion microscope over the surface of the YBCO thin film to form columns of point defects where superconductivity was locally suppressed. The voltage-current isotherms reveal critical behavior and scale in the vicinity of the second-order glass transition. The latter exhibits a distinct peak in melting temperature ($T_g$) vs. applied magnetic field ($B_a$) at the magnetic commensurability field, along with a sharp rise in the lifetimes of glassy fluctuations. Angle-dependent magnetoresistance measurements in constant-Lorentz-force geometry unveil a strong increase in anisotropy compared to a pristine reference film where the density of vortices matches that of the columnar defects. The pinning is therefore, dominated by the magnetic-field component parallel to the columnar defects, exposing its one-dimensional character. These results support the idea of an ordered Bose glass phase.Comment: 9 pages, 4 figure

Ordered Bose Glass of Vortices in Superconducting YBa2_{2}Cu3_{3}O7−δ_{7-\delta} Thin Films with a Periodic Pin Lattice Created by Focused Helium Ion Irradiation

The defect-rich morphology of YBa$_{2}$Cu$_{3}$O$_{7-\delta}$ (YBCO) thin films leads to a glass-like arrangement of Abrikosov vortices which causes the resistance to disappear in vanishing current densities. This vortex glass consists of entangled vortex lines and is identified by a characteristic scaling of the voltage-current isotherms. Randomly distributed columnar defects stratify the vortex lines and lead to a Bose glass. Here, we report on the observation of an ordered Bose glass in a YBCO thin film with a hexagonal array of columnar defects with 30 nm spacings. The periodic pinning landscape was engineered by a focused beam of 30 keV He$^+$ ions in a helium-ion microscope.Comment: 10 pages, 4 figure

Comprehensive multimodality characterization of hemodynamically significant and non-significant coronary lesions using invasive and noninvasive measures

Background There is limited knowledge about morphological molecular-imaging-derived parameters to further characterize hemodynamically relevant coronary lesions. Objective The aim of this study was to describe and differentiate specific parameters between hemodynamically significant and non-significant coronary lesions using various invasive and non-invasive measures. Methods This clinical study analyzed patients with symptoms suggestive of coronary artery disease (CAD) who underwent native T1-weighted CMR and gadofosveset-enhanced CMR as well as invasive coronary angiography. OCT of the culprit vessel to determine the plaque type was performed in a subset of patients. Functional relevance of all lesions was examined using quantitative flow reserve (QFR-angiography). Hemodynamically significant lesions were defined as lesions with a QFR <0.8. Signal intensity (contrast-to-noise ratios; CNRs) on native T1-weighted CMR and gadofosveset-enhanced CMR was defined as a measure for intraplaque hemorrhage and endothelial permeability, respectively. Results Overall 29 coronary segments from 14 patients were examined. Segments containing lesions with a QFR 0.8; n = 19) (5.32 (4.47–7.02) vs. 2.42 (1.04–5.11); p = 0.042). No differences in signal enhancement were seen on native T1-weighted CMR (2.2 (0.68–6.75) vs. 2.09 (0.91–6.57), p = 0.412). 66.7% (4 out of 6) of all vulnerable plaque and 33.3% (2 out of 6) of all non-vulnerable plaque (fibroatheroma) as assessed by OCT were hemodynamically significant lesions. Conclusion The findings of this pilot study suggest that signal enhancement on albumin-binding probe-enhanced CMR but not on T1-weighted CMR is associated with hemodynamically relevant coronary lesion

Aberrant Expression of and Cell Death Induction by Engagement of the MHC-II Chaperone CD74 in Anaplastic Large Cell Lymphoma (ALCL)

SIMPLE SUMMARY: Anaplastic large cell lymphoma (ALCL) is a lymphoid malignancy considered to be derived from T cells. Currently, two types of systemic ALCL are distinguished: anaplastic lymphoma kinase (ALK)-positive and ALK-negative ALCL. Although ALK(+) and ALK(−) ALCL differ at the genomic and molecular levels, various key biological and molecular features are highly similar between both entities. We have developed the concept that both ALCL entities share a common principle of pathogenesis. In support of this concept, we here describe a common deregulation of CD74, which is usually not expressed in T cells, in ALCL. Ligation of CD74 induces cell death of ALCL cells in various conditions, and an anti-CD74-directed antibody-drug conjugate efficiently kills ALCL cell lines. Furthermore, we reveal expression of the proto-oncogene and known CD74 interaction partner MET in a fraction of ALCL cases. These data give insights into ALCL pathogenesis and might help to develop new treatment strategies for ALCL. ABSTRACT: In 50–60% of cases, systemic anaplastic large cell lymphoma (ALCL) is characterized by the t(2;5)(p23;q35) or one of its variants, considered to be causative for anaplastic lymphoma kinase (ALK)-positive (ALK(+)) ALCL. Key pathogenic events in ALK-negative (ALK(−)) ALCL are less well defined. We have previously shown that deregulation of oncogenic genes surrounding the chromosomal breakpoints on 2p and 5q is a unifying feature of both ALK(+) and ALK(−) ALCL and predisposes for occurrence of t(2;5). Here, we report that the invariant chain of the MHC-II complex CD74 or li, which is encoded on 5q32, can act as signaling molecule, and whose expression in lymphoid cells is usually restricted to B cells, is aberrantly expressed in T cell-derived ALCL. Accordingly, ALCL shows an altered DNA methylation pattern of the CD74 locus compared to benign T cells. Functionally, CD74 ligation induces cell death of ALCL cells. Furthermore, CD74 engagement enhances the cytotoxic effects of conventional chemotherapeutics in ALCL cell lines, as well as the action of the ALK-inhibitor crizotinib in ALK(+) ALCL or of CD95 death-receptor signaling in ALK(−) ALCL. Additionally, a subset of ALCL cases expresses the proto-oncogene MET, which can form signaling complexes together with CD74. Finally, we demonstrate that the CD74-targeting antibody-drug conjugate STRO-001 efficiently and specifically kills CD74-positive ALCL cell lines in vitro. Taken together, these findings enabled us to demonstrate aberrant CD74-expression in ALCL cells, which might serve as tool for the development of new treatment strategies for this lymphoma entity

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder