Milieu-adopted in vitro and in vivo differentiation of mesenchymal tissues derived from different adult human CD34-negative progenitor cell clones

Adult mesenchymal stem cells with multilineage differentiation potentially exist in the bone marrow, but have also been isolated from the peripheral blood. The differentiation of stem cells after leaving their niches depends predominately on the local milieu and its new microenvironment, and is facilitated by soluble factors but also by the close cell-cell interaction in a three-dimensional tissue or organ system. We have isolated CD34-negative, mesenchymal stem cell lines from human bone marrow and peripheral blood and generated monoclonal cell populations after immortalization with the SV40 large T-antigen. The cultivation of those adult stem cell clones in an especially designed in vitro environment, including self-constructed glass capillaries with defined growth conditions, leads to the spontaneous establishment of pleomorphic three-dimensional cell aggregates ( spheroids) from the monoclonal cell population, which consist of cells with an osteoblast phenotype and areas of mineralization along with well-vascularized tissue areas. Modifications of the culture conditions favored areas of bone-like calcifications. After the transplantation of the at least partly mineralized human spheroids into different murine soft tissue sites but also a dorsal skinfold chamber, no further bone formation could be observed, but angiogenesis and neovessel formation prevailed instead, enabling the transplanted cells and cell aggregates to survive. This study provides evidence that even monoclonal adult human CD34-negative stem cells from the bone marrow as well as peripheral blood can potentially differentiate into different mesenchymal tissues depending on the local milieu and responding to the needs within the microenvironment. Copyright (C) 2005 S. Karger AG, Basel

Visualization of leukocyte transendothelial and interstitial migration using reflected light oblique transillumination in intravital video microscopy

Dynamic visualization of the intravascular events leading to the extravasation of leukocytes into tissues by intravital microscopy has significantly expanded our understanding of the underlying molecular processes. In contrast, the detailed observation of leukocyte transendothelial and interstitial migration in vivo has been hampered by the poor image contrast of cells within turbid media that is obtainable by conventional brightfield microscopy. Here we present a microscopic method, termed reflected light oblique transillumination microscopy, that makes use of the optical interference phenomena generated by oblique transillumination to visualize subtle gradients of refractive indices within tissues for enhanced image contrast. Using the mouse cremaster muscle, we demonstrate that this technique makes possible the reliable quantification of extravasated leukocytes as well as the characterization of morphological phenomena of leukocyte transendothelial and interstitial migration

A Parameter Study of Classical Be Star Disk Models Constrained by Optical Interferometry

We have computed theoretical models of circumstellar disks for the classical Be stars $\kappa$ Dra, $\beta$ Psc, and $\upsilon$ Cyg. Models were constructed using a non-LTE radiative transfer code developed by \citet{sig07} which incorporates a number of improvements over previous treatments of the disk thermal structure, including a realistic chemical composition. Our models are constrained by direct comparison with long baseline optical interferometric observations of the H$\alpha$ emitting regions and by contemporaneous H$\alpha$ line profiles. Detailed comparisons of our predictions with H$\alpha$ interferometry and spectroscopy place very tight constraints on the density distributions for these circumstellar disks.Comment: 10 figures,28 pages, accepted by Ap

AGI and the Knight-Darwin Law: why idealized AGI reproduction requires collaboration

Can an AGI create a more intelligent AGI? Under idealized assumptions, for a certain theoretical type of intelligence, our answer is: “Not without outside help”. This is a paper on the mathematical structure of AGI populations when parent AGIs create child AGIs. We argue that such populations satisfy a certain biological law. Motivated by observations of sexual reproduction in seemingly-asexual species, the Knight-Darwin Law states that it is impossible for one organism to asexually produce another, which asexually produces another, and so on forever: that any sequence of organisms (each one a child of the previous) must contain occasional multi-parent organisms, or must terminate. By proving that a certain measure (arguably an intelligence measure) decreases when an idealized parent AGI single-handedly creates a child AGI, we argue that a similar Law holds for AGIs

Atherosclerosis regression and TP receptor inhibition: effect of S18886 on plaque size and composition—a magnetic resonance imaging study

Aims Endothelial dysfunction, platelet hyperactivity, and inflammation play a crucial role in atherogenesis. A growing body of evidence suggests that inhibition of the thromboxane A2 (TxA2 or TP) receptor may improve endothelial function and reduce the inflammatory component of atherosclerosis in addition to its demonstrated antiplatelet activity. Consequently, we sought to assess the effect of a novel TP receptor antagonist S18886, on atherosclerotic lesion progression and composition by serial non-invasive magnetic resonance imaging (MRI). Methods and results S18886 was compared with control in an experimental model of established aortic atherosclerosis in New Zealand White rabbits (n=10). The animals underwent MRI of the abdominal aorta at the time of randomization and at the end of treatment. Subsequently, animals were euthanized and specimens were stained for histopathology and immunohistochemistry with anti-α-actin antibodies for vascular smooth muscle cells (VSMC), anti-RAM-11 for macrophages, anti-caspase-3 for apoptotic cells, anti-MMP-1 for metalloproteinases, and anti-endothelin-1 (ET-1) as a marker of endothelial dysfunction. MRI analysis revealed a significant reduction in total vessel area (TVA) and vessel wall area (VWA) in the S18886 group (P<0.05). Immunostaining analysis showed a significant decrease in RAM-11, caspase-3, MMP-1, ET-1 and an increase in α-actin in the treated group (P<0.05 vs. control). Conclusion Inhibition of the TP receptor by S18886 causes a regression of advanced atherosclerotic plaques. In addition, the reduction in the markers for macrophages, apoptotic cells, metalloproteinases, and endothelin-1 and the increase in VSMC, suggests that S18886 may not only halt the progression of atherosclerosis, but also transform lesions towards a more stable phenotype. The possibility of combining antithrombotic and antiatherosclerotic activity by means of the administration of TP inhibitors deserves further investigation in a clinical settin

Validation of Kepler's Multiple Planet Candidates. II: Refined Statistical Framework and Descriptions of Systems of Special Interest

We extend the statistical analysis of Lissauer et al. (2012, ApJ 750, 112), which demonstrates that the overwhelming majority of Kepler candidate multiple transiting systems (multis) represent true transiting planets, and develop therefrom a procedure to validate large numbers of planet candidates in multis as bona fide exoplanets. We show that this statistical framework correctly estimates the abundance of false positives already identified around Kepler targets with multiple sets of transit-like signatures based on their abundance around targets with single sets of transit-like signatures. We estimate the number of multis that represent split systems of one or more planets orbiting each component of a binary star system. We use the high reliability rate for multis to validate more than one dozen particularly interesting multi-planet systems are validated in a companion paper by Rowe et al. (2014, ApJ, this issue). We note that few very short period (P < 1.6 days) planets orbit within multiple transiting planet systems and discuss possible reasons for their absence. There also appears to be a shortage of planets with periods exceeding a few months in multis

A critical assessment of the Self-Interaction Corrected Local Density Functional method and its algorithmic implementation

We calculate the electronic structure of several atoms and small molecules by direct minimization of the Self-Interaction Corrected Local Density Approximation (SIC-LDA) functional. To do this we first derive an expression for the gradient of this functional under the constraint that the orbitals be orthogonal and show that previously given expressions do not correctly incorporate this constraint. In our atomic calculations the SIC-LDA yields total energies, ionization energies and charge densities that are superior to results obtained with the Local Density Approximation (LDA). However, for molecules SIC-LDA gives bond lengths and reaction energies that are inferior to those obtained from LDA. The nonlocal BLYP functional, which we include as a representative GGA functional, outperforms both LDA and SIC-LDA for all ground state properties we considered.Comment: 14 pages, 5 figure

Constraining Disk Parameters of Be Stars using Narrowband H-alpha Interferometry with the NPOI

Interferometric observations of two well-known Be stars, gamma Cas and phi Per, were collected and analyzed to determine the spatial characteristics of their circumstellar regions. The observations were obtained using the Navy Prototype Optical Interferometer equipped with custom-made narrowband filters. The filters isolate the H-alpha emission line from the nearby continuum radiation, which results in an increased contrast between the interferometric signature due to the H-alpha-emitting circumstellar region and the central star. Because the narrowband filters do not significantly attenuate the continuum radiation at wavelengths 50 nm or more away from the line, the interferometric signal in the H-alpha channel is calibrated with respect to the continuum channels. The observations used in this study represent the highest spatial resolution measurements of the H-alpha-emitting regions of Be stars obtained to date. These observations allow us to demonstrate for the first time that the intensity distribution in the circumstellar region of a Be star cannot be represented by uniform disk or ring-like structures, whereas a Gaussian intensity distribution appears to be fully consistent with our observations.Comment: 23 pages, 14 figures, accepted for publication in A