Canted antiferromagnetism in phase-pure CuMnSb

We report the low-temperature properties of phase-pure single crystals of the half-Heusler compound CuMnSb grown by means of optical float-zoning. The magnetization, specific heat, electrical resistivity, and Hall effect of our single crystals exhibit an antiferromagnetic transition at $T_{\mathrm{N}} = 55~\mathrm{K}$ and a second anomaly at a temperature $T^{*} \approx 34~\mathrm{K}$. Powder and single-crystal neutron diffraction establish an ordered magnetic moment of $(3.9\pm0.1)~\mu_{\mathrm{B}}/\mathrm{f.u.}$, consistent with the effective moment inferred from the Curie-Weiss dependence of the susceptibility. Below $T_{\mathrm{N}}$, the Mn sublattice displays commensurate type-II antiferromagnetic order with propagation vectors and magnetic moments along $\langle111\rangle$ (magnetic space group $R[I]3c$). Surprisingly, below $T^{*}$, the moments tilt away from $\langle111\rangle$ by a finite angle $\delta \approx 11^{\circ}$, forming a canted antiferromagnetic structure without uniform magnetization consistent with magnetic space group $C[B]c$. Our results establish that type-II antiferromagnetism is not the zero-temperature magnetic ground state of CuMnSb as may be expected of the face-centered cubic Mn sublattice.Comment: 14 pages, 15 figure

In-silico insights on the prognostic potential of immune cell infiltration patterns in the breast lobular epithelium

Scattered inflammatory cells are commonly observed in mammary gland tissue, most likely in response to normal cell turnover by proliferation and apoptosis, or as part of immunosurveillance. In contrast, lymphocytic lobulitis (LLO) is a recurrent inflammation pattern, characterized by lymphoid cells infiltrating lobular structures, that has been associated with increased familial breast cancer risk and immune responses to clinically manifest cancer. The mechanisms and pathogenic implications related to the inflammatory microenvironment in breast tissue are still poorly understood. Currently, the definition of inflammation is mainly descriptive, not allowing a clear distinction of LLO from physiological immunological responses and its role in oncogenesis remains unclear. To gain insights into the prognostic potential of inflammation, we developed an agent-based model of immune and epithelial cell interactions in breast lobular epithelium. Physiological parameters were calibrated from breast tissue samples of women who underwent reduction mammoplasty due to orthopedic or cosmetic reasons. The model allowed to investigate the impact of menstrual cycle length and hormone status on inflammatory responses to cell turnover in the breast tissue. Our findings suggested that the immunological context, defined by the immune cell density, functional orientation and spatial distribution, contains prognostic information previously not captured by conventional diagnostic approaches. Several studies provided conclusive evidence that a delicate balance between mammary epithelial cell proliferation and apoptosis regulates homeostasis in the healthy breast tissue 1-7. After menarche, and in the absence of pregnancy, the adult female mammary gland is subjected to cyclic fluctuations depending on hormonal stimulation 1,8. In response to such systemic hormonal changes, the breast epithelium undergoes a tightly regulated sequence of cell proliferation and apoptosis during each ovarian/menstrual cycle 1-3. The peak of epithelial cell proliferation has been reported to occur during the luteal phase, suggesting a synergistic influence of steroid hormones, such as estrogen and progesterone 2-5. In turn, the peak of apoptotic activity would be expected in response to decreasing hormone levels towards the end of the menstrual cycle 2-5. However, recent histologic findings indicate that apoptosis reaches its maximum levels in the middle of the luteal phase, although there is also a peak at about the third day of the menstrual cycle 6,7. Experimental measurements of cell turnover, i.e. programmed cell death and proliferation, demonstrated that an imbalance between the mitotic and apoptotic activity might lead to malignant transformation of epithelial cells and tumorigenic processes 9-11. Indeed, excessive cell proliferation promotes accumulation of DNA damage due to insufficient timely repair and mutations 12,13. There is also recent evidence that hormones suppress effective DNA repair and alter DNA damage response (DDR) 13-15

A Graph-Based Digital Pathology Approach To Describe Lymphocyte Clustering Patterns After Renal Transplantation

Introduction/ Background Renal transplantation (rTx) induces an adaptive immune response against foreign donor antigens mediated by lymphocytes of the recipient. Local accumulation of B- and T-cells is an important component of this response enabling and controlling immune cell interactions [1]. Combining digital microscopic images with network analysis [2][3] opens new perspectives to study the spa- tial dimension of lymphocyte clustering and to model their potential interactions.   Aims The aim of this study is to characterize the range of B- and T-lymphocytic infiltrates below the threshold of rejection defined by theBanffclassification [4][5] and to propose a mathematical description of immune cell clustering for use in systems medicine approaches.   Methods We established a workflow to comprehensively characterize lymphocyte clusters and compare their morphological features with organized structures such as secondary or tertiary lymphoid organs (TLO/SLO) [6]. 51 renal protocol and indication biopsies from 13 patients without evidence for severe rejection over 10 years were stained by CD3/CD20 duplex immunohisto- chemistry. Whole slide images (WSIs) were acquired to automatically detect biologically relevant regions of in- terest (ROIs) by means of density maps for lymphocytes (image analysis workflow illustrated in Fig. 1a). They are generated from single nuclei identification using an au- to-adaptive random forest pixelwise classifier (“nucleus container” module [7],Definiens,Germany). We imple- mented a graph-based tool in Java using individual cell coordinates to identify cell compartments (Fig. 1b) and applied it to each selected ROI. For this, a neighborhood graph is built by Delaunay triangulation and Euclidean distances. This analysis allows describing their specific clustering behavior based on features as described in [8]. The convex hull of the neighborhood graph allows a visualization of B- and T-cell compartments.   Results We identified B-cell rich compartments in about 55% of 150 ROIs in kidney tissue after successful transplantation (examples in Fig. 2). The B-cell compartments in rTx tended towards smaller overall size with on average about 90 cells in a B-cell cluster compared to more than 600 B-cells observed in mature TLOs and SLOs and they showed less prominent spatial organization (average degree on average 3.92 instead of 4.97; degree shows generally Poisson distribution as illustrated in Fig. 3A). Further, the graph analysis confirmed lower B-cell density (Fig. 3B displays the exponential character of the spatial B-cell distribution in a selected ROI), a different ratio between T- and B-cell compartments, and more frequent overlap between both regions than in mature lymphoid structures.   We conclude that the graph-based approach is feasible to distinguish relevant immune cell patterns in rTx and provides a useful mathematical description of neighborhood relationships between immune cells and their spatial organization. The workflow has the potential to improve throughput and robustness of immune cell evaluation for use in translational science

Graph-based description of tertiary lymphoid organs at single-cell level

Our aim is to complement observer-dependent approaches of immune cell evaluation in microscopy images with reproducible measures for spatial composition of lymphocytic infiltrates. Analyzing such patterns of inflammation is becoming increasingly important for therapeutic decisions, for example in transplantation medicine or cancer immunology. We developed a graph-based assessment of lymphocyte clustering in full whole slide images. Based on cell coordinates detected in the full image, a Delaunay triangulation and distance criteria are used to build neighborhood graphs. The composition of nodes and edges are used for classification, e.g. using a support vector machine. We describe the variability of these infiltrates on CD3/CD20 duplex staining in renal biopsies of long-term functioning allografts, in breast cancer cases, and in lung tissue of cystic fibrosis patients. The assessment includes automated cell detection, identification of regions of interest, and classification of lymphocytic clusters according to their degree of organization. We propose a neighborhood feature which considers the occurrence of edges with a certain type in the graph to distinguish between phenotypically different immune infiltrates. Our work addresses a medical need and provides a scalable framework that can be easily adjusted to the requirements of different research questions

Magnetic properties of the noncentrosymmetric tetragonal antiferromagnet EuPtSi3_3

We report a comprehensive study of single crystals of the noncentrosymmetric rare-earth compound EuPtSi$_3$ grown by the optical floating-zone technique. Measurements of the magnetization, ac susceptibility, and specific heat consistently establish antiferromagnetic order of localized Eu2+ moments below the Néel temperature T$_N$=17 K, followed by a second magnetic transition at T$_{N1}$=16 K. For a magnetic field along the easy [001] axis, the magnetic phase diagram is composed of these two phases. For fields applied in the magnetically hard basal plane, two additional phases emerge under magnetic field, where the in-plane anisotropy is weak with [100] being the hardest axis. At the phase transitions, the magnetic properties exhibit hysteresis and discrepancies between differential and ac susceptibility, suggesting slow reorientation processes of mesoscale magnetic textures. Consistently, powder and single-crystal neutron diffraction in zero field identify magnetic textures that are modulated on a length scale of the order of 100 Å, most likely in the form of Néel-type antiferromagnetic cycloids

In-silico insights on the prognostic potential of immune cell infiltration patterns in the breast lobular epithelium.

Scattered inflammatory cells are commonly observed in mammary gland tissue, most likely in response to normal cell turnover by proliferation and apoptosis, or as part of immunosurveillance. In contrast, lymphocytic lobulitis (LLO) is a recurrent inflammation pattern, characterized by lymphoid cells infiltrating lobular structures, that has been associated with increased familial breast cancer risk and immune responses to clinically manifest cancer. The mechanisms and pathogenic implications related to the inflammatory microenvironment in breast tissue are still poorly understood. Currently, the definition of inflammation is mainly descriptive, not allowing a clear distinction of LLO from physiological immunological responses and its role in oncogenesis remains unclear. To gain insights into the prognostic potential of inflammation, we developed an agent-based model of immune and epithelial cell interactions in breast lobular epithelium. Physiological parameters were calibrated from breast tissue samples of women who underwent reduction mammoplasty due to orthopedic or cosmetic reasons. The model allowed to investigate the impact of menstrual cycle length and hormone status on inflammatory responses to cell turnover in the breast tissue. Our findings suggested that the immunological context, defined by the immune cell density, functional orientation and spatial distribution, contains prognostic information previously not captured by conventional diagnostic approaches

Reduced laterality as a trait marker of Schizophrenia-evidence from structural and functional neuroimaging.

Laterality is a characteristic principle of the organization of the brain systems for language, and reduced hemispheric asymmetry has been considered a risk factor for schizophrenia. Here we sought support for the risk factor hypothesis by investigating whether reduced asymmetry of temporal lobe structure and function is also present in unaffected relatives. Sixteen schizophrenia patients, 16 age-matched first-degree relatives, and 15 healthy controls underwent high-resolution three-dimensional anatomical imaging and functional magnetic resonance imaging during auditory stimulation. Both the overall auditory cortex and planum temporale volumes and the lateralization to the left hemisphere were markedly reduced in patients. The decrease of lateralization correlated with increased severity of symptoms. In addition, both the overall functional activation in response to auditory stimulation and its asymmetry were reduced in the patients. Relatives had intermediate values between patients and controls on both structural and functional measures. This study provides added support for the idea that reduced hemispheric asymmetry is a biological risk factor for schizophrenia

Low-temperature structural investigations of the frustrated quantum antiferromagnets Cs2Cu(Cl4−xBrx){\mathrm{Cs}}_{2}\mathrm{Cu}\left({\mathrm{Cl}}_{4-x}{\mathrm{Br}}_{x}\right)

Powder x-ray diffraction (PXRD) and single-crystal neutron scattering were used to study in detail the structural properties of the Cs2Cu(Cl4−xBrx) series, good realizations of layered triangular antiferromagnets. Detailed temperature-dependent PXRD reveal a pronounced anisotropy of the thermal expansion for the three different crystal directions of the orthorhombic structure without any structural phase transition down to 20 K. Remarkably, the anisotropy of the thermal expansion varies for different x, leading to distinct changes of the geometry of the local Cu environment as a function of temperature and composition. The refinement of the atomic positions confirms that for x=1 and 2, the Br atoms occupy distinct halogen sites in the [CuX4] tetrahedra (X = Cl, Br). The precise structure data are used to calculate the magnetic exchange couplings using density functional methods for x=0. We observe a pronounced temperature dependence of the calculated magnetic exchange couplings, reflected in the strong sensitivity of the magnetic exchange couplings on structural details. These calculations are in good agreement with the experimentally established values for Cs2CuCl4 if one takes the low-temperature structure data as a starting point