Thymic nurse cells. Lymphoepithelial cell complexes in murine thymuses: morphological and serological characterization

We describe a new cellular component of normal mouse thymuses, which is isolated by fractionated trypsin dissociation of minced thymus tissue followed by repeated unit gravity sedimentation. These cells are of unusually large size, with diameters of 30 μm and more. They represent cellular complexes of single large cells filled with high numbers of lymphoid cells. The majority of the engulfed lymphoid cells is not only fully intact, as judged by morphological criteria, but, moreover, includes a high proportion of mitotic figures. Electron microscopic investigations reveal the epithelial character of the large thymic nurse cells (TNC). The peripherally situated cytoplasmic tonofilament streams, and characteristic vacuoles filled with coarse, unidentified material, closely resemble cytoplasmic organelles found in the cortical reticuloepithelial cells described in situ. The internalized lymphocytes are located within caveolae lined by plasma membranes. These TNC caveolae are completely sequestered, and have lost any communication with the extracellular space, as demonstrated by the inability of an electrondense marker, cationized ferritin, to diffuse into the perilymphocytic clefts. The structural interactions between the membranes of the engulfed thymocytes with the surrounding TNC caveolar membranes were investigated both in ultrathin sections and in freeze-etch preparates. Two distinct contact types between both membranes were discerned: (a) complete, close contact along the entire lymphocyte circumference, and (b) more frequently, contact restricted to discrete, localized areas. Judging from their size and distribution, the localized contacts could correspond particle aggregates of freeze-etch preparates, which morphologically resemble certain stages of gap junction. Furthermore, we regularly found square arrays of particles of uniform size, which so far have been thought to be typical for cell membranes actively engaged in ion exchange. Tight junction-like particle arrays, which were present on TNC outer membranes, and probably represented disrupted contacts between adjacent TNC in the intact tissue, could not be found on caveolar or lymphocyte membranes. Finally, one of the most conspicuous specializations of the TNC caveolar membrane were membrane invaginations, which were arranged mainly in groups, and which probably reflect endo- or exocytotoxic events. We investigated the surface antigen phenotype of TNC by indirect immunofluorescence, with monoclonal antibodies against determinants of H-2- complex subregions as well as against lymphocyte differentiation markers. Semiquantification was reached with flow cytofluorimetry, followed by morphological control by fluorescence microscopy. The surface antigen formula of TNC is: Ig(-), Thy-l(-), H-2K(++), I-A (++), I-E/C(+), H-D(++), Ly-1(-), Ly-2(-), Qat-4(-), Qat-5(-), and peanut agglutinin (PNA)(-). Thymic macrophages, which were identified by double fluorescence, with rhodamine- coupled zymosan as a phagocytosis marker, were serologically identical with TNC. Free thymocytes, in contrast, had the following antigen formula: Ig(-), Thy-1(++), H-2K(+/-), I-A(-), I-E/C(-), H-2D(+/-), Ly-1(+/-), Ly-2(+), Qat- 4(-), Qat-5(-), and PNA(+). The unprecedented finding of high numbers of dividing thymocytes sojourning within thymic epithelial cells, and the particular specializations of the TNC caveolar membranes surrounding these engulfed thymocytes is the basis of a hypothesis that postulates that an intraepithelial differentiation cycle is one essential step in, intrathymic T lymphocyte generation

Design and Validation of a Bifunctional Ligand Display System for Receptor Targeting

AbstractHere we developed a bacteriophage display particle designed to serve as a bifunctional entity that can target tumors while delivering an agent. We engineered a chimera phage vector containing a pIII-displayed αv integrins-targeting moiety and a pVIII-displayed streptavidin binding adaptor moiety. By using the chimeric phage particle, targeting of αv integrins on cells in culture and tumor-related blood vessels was shown through different applications, including luminescent quantum dots localization, surface plasmon resonance-based binding detection, and an in vivo tumor model. The strategy validated here will accelerate the discovery and characterization of receptor-ligand binding events in high throughput, and cell-specific delivery of diagnostics or therapeutics to organs of choice without the need for chemical conjugation

Методы повышения эффективности работы газотурбинных установок

Объект исследования: газотурбинная установка. Цель работы: аналитический обзор современных направлений повышения эффективности работы ГТУ, сравнительный расчет простой и регенеративной ГТУ при заданных равных условиях. Для достижения поставленной цели рассмотрены следующие задачи: проведение литературного обзора современных направлений повышения эффективности работы газотурбинных установок; сравнительный тепловой расчет простой и регенеративной ГТУ при заданных равных условиях; Определение сметной стоимости работ по монтажу регенератора; анализ вредныхThe object of the study: gas turbine plant. The purpose of the work: analytical review of modern directions of increasing the efficiency of GTP operation, comparative calculation of simple and regenerative GTP under given equal conditions. To achieve this goal, the following tasks are considered: conducting a literature review of modern technologies to increase the efficiency of gas turbine plants; comparative heat calculation of simple and regenerative gas turbine plant (efficiency, specific fuel consumption, heat rate) for given equal conditions; determination of the estimated cost of

A Novel Monoclonal Antibody to Secreted Frizzled-Related Protein 2 Inhibits Tumor Growth

Secreted frizzled related protein 2 (SFRP2) is overexpressed in human angiosarcoma and breast cancer, and stimulates angiogenesis via activation of the calcineurin/ NFATc3 pathway. There are conflicting reports in the literature as to whether SFRP2 is an antagonist or agonist of ß-catenin. The aims of these studies were to assess the effects of SFRP2 antagonism on tumor growth and Wnt-signaling, and to evaluate whether SFRP2 is a viable therapeutic target. The anti-angiogenic and anti-tumor properties of SFRP2 monoclonal antibody (mAb) were assessed using in vitro proliferation, migration, and tube formation assays; and in vivo angiosarcoma and triple negative breast cancer models. Wnt-signaling was assessed in endothelial and tumor cells treated with SFRP2 mAb using Western blotting. Pharmacokinetic (PK) and biodistribution data were generated in tumor-bearing and non-tumor bearing mice. SFRP2 mAb was shown to induce anti-tumor and anti-angiogenic effects in vitro, and inhibit activation of ß-catenin and NFATc3 in endothelial and tumor cells. Treatment of SVR angiosarcoma allografts in nude mice with the SFRP2 mAb decreased tumor volume by 58% compared to control (p=0.004). Treatment of MDA-MB-231 breast carcinoma xenografts with SFRP2 mAb decreased tumor volume by 52% (p=0.03) compared to control, while bevacizumab did not significantly reduce tumor volume. Pharmacokinetic studies show the antibody is long circulating in the blood and preferentially accumulates in SFRP2-positive tumors. In conclusion, antagonizing SFRP2 inhibits activation of ß-catenin and NFATc3 in endothelial and tumor cells, and is a novel therapeutic approach to inhibiting angiosarcoma and triple negative breast cancer

Overview of the PALM model system 6.0

In this paper, we describe the PALM model system 6.0. PALM (formerly an abbreviation for Parallelized Largeeddy Simulation Model and now an independent name) is a Fortran-based code and has been applied for studying a variety of atmospheric and oceanic boundary layers for about 20 years. The model is optimized for use on massively parallel computer architectures. This is a follow-up paper to the PALM 4.0 model description in Maronga et al. (2015). During the last years, PALM has been significantly improved and now offers a variety of new components. In particular, much effort was made to enhance the model with components needed for applications in urban environments, like fully interactive land surface and radiation schemes, chemistry, and an indoor model. This paper serves as an overview paper of the PALM 6.0 model system and we describe its current model core. The individual components for urban applications, case studies, validation runs, and issues with suitable input data are presented and discussed in a series of companion papers in this special issue

Comparison of Synchrotron X-Ray Microanalysis With Electron and Proton Microscopy for Individual Particle Analysis

This paper is concerned with the evaluation of the use of synchrotron/radiation induced x-ray fluorescences ({mu}-SRXRF) as implemented at two existing X-ray microprobes for the analysis of individual particles. As representative environmental particulates, National Institutes of Science and Technology (NIST) K227, K309, K441 and K961 glass microspheres were analyzed using two types of X-ray micro probes: the white light microprobe at beamline X26A of the monochromatic (15 keV) X-ray microprobe at station 7.6 of the SRS. For reference, the particles were also analyzed with microanalytical techniques more commonly employed for individual particles analysis such as EPMA and micro-PIXE