Experiment K-6-22. Growth hormone regulation, synthesis and secretion in microgravity. Part 1: Somatotroph physiology. Part 2: Immunohistochemical analysis of hypothalamic hormones. Part 3: Plasma analysis

The objectives of the 1887 mission were: (1) to determine if the results of the SL-3 pituitary gland experiment (1) were repeatable; and (2) to determine what effect a longer mission would have on the rat pituitary gland growth hormone (GH) system. In the 1887 experiment two issues were considered especially important. First, it was recognized that cells prepared from individual rat pituitary glands should be considered separately so that the data from the 5 glands could be analyzed in a statistically meaningful way. Second, results of the SL-3 flight involving the hollow fiber implant and HPLC GH-variant experiments suggested that the biological activity of the hormone had been negatively affected by flight. The results of the 1887 experiment documented the wisdom of addressing both issues in the protocol. Thus, the reduction in secretory capacity of flight cells during subsequent extended cell culture on Earth was documented statistically, and thereby established the validity of the SL-3 result. The results of both flight experiments thus support the contention that there is a secretory lesion in pituitary GH cells of flight animals. The primary objective of both missions was a clear definition of the effect of spaceflight on the GH cell system. There can no longer be any reasonable doubt that this system is affected in microgravity. One explanation for the reason(s) underlying the better known effects of spaceflight on organisms, viz. changes in bone, muscle and immune systems may very well rest with such changes in bGH. In spite of the fact that rats in the Cosmos 1887 flight were on Earth for two days after flight, the data show that the GH system had still not recovered from the effects of flight. Many questions remain. One of the more important concerns the GRF responsiveness of somatotrophs after flight. This will be tested in an upcoming experiment

Formation number of confined vortex rings

This paper investigates the formation number of vortex rings generated by a piston-cylinder mechanism in a confined tube. We use Direct Numerical Simulations (DNS) of axisymmetric confined vortex rings to study the influence of different parameters on the separation (or pinch-off) of the vortex ring from the trailing jet. It is shown that the structure of the vortex ring at pinch-off depends on the type of injection program (pulse dominated by either positive or negative acceleration ramps) and the confinement ratio D w /D , where D w is the inner diameter of the tube and D the diameter of the cylinder). For low confinement ratios ( D w /D ≤ 2), a vortex of opposite sign generated at the lateral wall strongly interacts with the vortex ring and the pinch-off is not clearly observed. The pinch-off is observed and analysed for confinement ratios D w /D ≥ 2 . 5. DNS data are used to estimate the value of the formation time, which is the time necessary for the vortex generator to inject the same amount of circulation as carried by the detached vortex ring. The confined vortex ring at pinch-off is described by the model suggested by Danaila, Kaplanski and Sazhin [A model for confined vortex rings with elliptical core vorticity distribution, Journal of Fluid Mechanics, 811 :67-94, 2017]. This model allows us to take into account the influence of the lateral wall and the elliptical shape of the vortex core. The value of the formation time is predicted using this model and the slug-flow model

The differential-algebraic and bi-Hamiltonian integrability analysis of the Riemann type hierarchy revisited

A differential-algebraic approach to studying the Lax type integrability of the generalized Riemann type hydrodynamic hierarchy is revisited, its new Lax type representation and Poisson structures constructed in exact form. The related bi-Hamiltonian integrability and compatible Poissonian structures of the generalized Riemann type hierarchy are also discussed.Comment: 18 page

Differential-Algebraic Integrability Analysis of the Generalized Riemann Type and Korteweg-de Vries Hydrodynamical Equations

A differential-algebraic approach to studying the Lax type integrability of the generalized Riemann type hydrodynamic equations at N = 3; 4 is devised. The approach is also applied to studying the Lax type integrability of the well known Korteweg-de Vries dynamical system.Comment: 11 page

Neuronatin: A New Inflammation Gene Expressed on the Aortic Endothelium of Diabetic Mice

OBJECTIVE—Identification of arterial genes and pathways altered in obesity and diabetes

Ligand-Receptor Interactions

The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the interest of biologists to the kinetic and mechanical properties of cell membrane receptors. The aim of this review is to give a description of these advances that benefitted from a largely multidisciplinar approach

Tumor-Like Stem Cells Derived from Human Keloid Are Governed by the Inflammatory Niche Driven by IL-17/IL-6 Axis

Alterations in the stem cell niche are likely to contribute to tumorigenesis; however, the concept of niche promoted benign tumor growth remains to be explored. Here we use keloid, an exuberant fibroproliferative dermal growth unique to human skin, as a model to characterize benign tumor-like stem cells and delineate the role of their "pathological" niche in the development of the benign tumor.Subclonal assay, flow cytometric and multipotent differentiation analyses demonstrate that keloid contains a new population of stem cells, named keloid derived precursor cells (KPCs), which exhibit clonogenicity, self-renewal, distinct embryonic and mesenchymal stem cell surface markers, and multipotent differentiation. KPCs display elevated telomerase activity and an inherently upregulated proliferation capability as compared to their peripheral normal skin counterparts. A robust elevation of IL-6 and IL-17 expression in keloid is confirmed by cytokine array, western blot and ELISA analyses. The altered biological functions are tightly regulated by the inflammatory niche mediated by an autocrine/paracrine cytokine IL-17/IL-6 axis. Utilizing KPCs transplanted subcutaneously in immunocompromised mice we generate for the first time a human keloid-like tumor model that is driven by the in vivo inflammatory niche and allows testing of the anti-tumor therapeutic effect of antibodies targeting distinct niche components, specifically IL-6 and IL-17.These findings support our hypothesis that the altered niche in keloids, predominantly inflammatory, contributes to the acquirement of a benign tumor-like stem cell phenotype of KPCs characterized by the uncontrolled self-renewal and increased proliferation, supporting the rationale for in vivo modification of the "pathological" stem cell niche as a novel therapy for keloid and other mesenchymal benign tumors