Cation distribution in manganese cobaltite spinels Co3−xMnxO4 (0 ≤ x ≤ 1) determined by thermal analysis

Thermogravimetric analysis was used in order to study the reduction in air of submicronic powders of Co3−x Mn x O4 spinels, with 0 ≤ x ≤ 1. For x = 0 (i.e. Co3O4), cation reduction occurred in a single step. It involved the CoIII ions at the octahedral sites, which were reduced to Co2+ on producing CoO. For 0 < x ≤ 1, the reduction occurred in two stages at increasing temperature with increasing amounts of manganese. The first step corresponded to the reduction of octahedral CoIII ions and the second was attributed to the reduction of octahedral Mn4+ ions to Mn3+. From the individual weight losses and the electrical neutrality of the lattice, the CoIII and Mn4+ ion concentrations were calculated. The distribution of cobalt and manganese ions present on each crystallographic site of the spinel was determined. In contrast to most previous studies that took into account either CoIII and Mn3+ or Co2+, CoIII and Mn4+ only, our thermal analysis study showed that Co2+/CoIII and Mn3+/Mn4+ pairs occupy the octahedral sites. These results were used to explain the resistivity measurements carried out on dense ceramics prepared from our powders sintered at low temperature (700–750 °C) in a Spark Plasma Sintering apparatus

Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.

CD4(+) T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i) that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+) cells, and (ii) that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+) compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+) T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p) and disappearance (d*) rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul) participated. CCR5-expression defined a CD4(+) subpopulation of predominantly CD45R0(+) memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+) vs CCR5(-); healthy controls; P<0.01). Conversely, CXCR4 expression defined CD4(+) T-cells (predominantly CD45RA(+) naive cells) with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+)CD45R0(+)CD4(+) memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05), naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9) or X4-tropic (n = 4). Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively). Our data are most consistent with models in which CD4(+) T-cell loss is primarily driven by non-specific immune activation

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

Detection of multiple respiratory pathogens during primary respiratory infection: nasal swab versus nasopharyngeal aspirate using real-time polymerase chain reaction

In this study, we present the multiple detection of respiratory viruses in infants during primary respiratory illness, investigate the sensitivity of nasal swabs and nasopharyngeal aspirates, and assess whether patient characteristics and viral load played a role in the sensitivity. Healthy infants were included at signs of first respiratory tract infection. Paired nasopharyngeal aspirates and nasal swabs were collected. Real-time polymerase chain reaction (PCR) was carried out for 11 respiratory pathogens. Paired nasopharyngeal aspirates and nasal swabs were collected in 98 infants. Rhinovirus (n = 67) and respiratory syncytial virus (n = 39) were the most frequently detected. Co-infection occurred in 48% (n = 45) of the infants. The sensitivity of the nasal swab was lower than the nasopharyngeal aspirate, in particular, for respiratory syncytial virus (51% vs. 100%) and rhinovirus (75% vs. 97%). The sensitivity of the nasal swab was strongly determined by the cycle threshold (CT) value (p < 0.001). The sensitivity of the swab for respiratory syncytial virus, but not rhinovirus, was 100% in children with severe symptoms (score ≥11). It is concluded that, for community-based studies and surveillance purposes, the nasal swab can be used, though the sensitivity is lower than the aspirate, in particular, for the detection of mild cases of respiratory syncytial virus (RSV) infection

Free edge effects study in laminated composites using Digital Image Correlation: effect of material and geometrical singularities

Composite materials are today used for various industrial applications. However, delamination on free edges, where stress gradients are strong, still remain a problem. In the aim of a better understanding of such phenomenons, Digital Image Correlation (DIC) measurements have been carried out on [(15n/-15n)2]s laminates under uniaxial tensile strain. Three different composites with different mechanical properties and microstructure have been tested as well as two samples geometries: flat and with ply drop. Experimental results show high shear strain concentrations near 15°/-15° interlaminar interfaces on free edges which depend on material mechanical properties and microstructure and increase in the vicinity of a geometrical singularity