\v{C}ech-Delaunay gradient flow and homology inference for self-maps

We call a continuous self-map that reveals itself through a discrete set of point-value pairs a sampled dynamical system. Capturing the available information with chain maps on Delaunay complexes, we use persistent homology to quantify the evidence of recurrent behavior. We establish a sampling theorem to recover the eigenspace of the endomorphism on homology induced by the self-map. Using a combinatorial gradient flow arising from the discrete Morse theory for \v{C}ech and Delaunay complexes, we construct a chain map to transform the problem from the natural but expensive \v{C}ech complexes to the computationally efficient Delaunay triangulations. The fast chain map algorithm has applications beyond dynamical systems.Comment: 22 pages, 8 figure

In Silico and Experimental ADAM17 Kinetic Modeling as Basis for Future Screening System for Modulators

Understanding the mechanisms of modulators’ action on enzymes is crucial for optimizing and designing pharmaceutical substances. The acute inflammatory response, in particular, is regu lated mainly by a disintegrin and metalloproteinase (ADAM) 17. ADAM17 processes several disease mediators such as TNFα and APP, releasing their soluble ectodomains (shedding). A malfunction of this process leads to a disturbed inflammatory response. Chemical protease inhibitors such as TAPI-1 were used in the past to inhibit ADAM17 proteolytic activity. However, due to ADAM170 s broad expression and activity profile, the development of active-site-directed ADAM17 inhibitor was discontinued. New ‘exosite’ (secondary substrate binding site) inhibitors with substrate selectivity raised the hope of a substrate-selective modulation as a promising approach for inflammatory disease therapy. This work aimed to develop a high-throughput screen for potential ADAM17 modula tors as therapeutic drugs. By combining experimental and in silico methods (structural modeling and docking), we modeled the kinetics of ADAM17 inhibitor. The results explain ADAM17 inhibi tion mechanisms and give a methodology for studying selective inhibition towards the design of pharmaceutical substances with higher selectivity

Gluon Saturation Effects at the Nuclear Surface: Inelastic Cross Section of Proton-Nucleus at Ultra High Energy Cosmic Ray domain

Considering the high-energy limit of the QCD gluon distribution inside a nucleus, we calculate the proton-nucleus total inelastic cross section using a simplified dipole model. We show that, if gluon saturation occurs in the nuclear surface region, the total cross section of proton-nucleus collisions increases more rapidly as a function of the incident energy compared to that of a Glauber-type estimate. We discuss the implications of this with respect to recent ultra-high-energy cosmic ray experiments.Comment: Published in Nuclear Physics A, 29 pages, 5 figures, 1 tabl

Gluon Saturation Effects in Relativistic U+U Collisions

We examine entropy production in relativistic U+U collisions on the basis of a Color Glass Condensate (CGC) type picture as implemented in the Kharzeev-Levin-Nardi model (KLN). In this framework, we find that the peak entropy density produced in tip-on-tip U+U collisions is about 30% greater than that seen in central Au+Au collisions. Although the resulting difference in the produced charged particle multiplicity between tip-on-tip and side-on-side collisions is smaller than that predicted by previous Glauber model estimates, it is still large enough to allow for experimental discrimination between average orientations of the uranium nuclei. We also point out that in the saturation/CGC approach the collision geometry plays a more important role than previously believed, and that the observed centrality dependence of the produced particle multiplicity per participant in Au+Au collisions can be qualitatively reproduced even without running coupling effects.Comment: 7 pages, including 8 figure

Zur regionalen Konzentration von Innovationspotentialen in Deutschland : Studie im Auftrag des BMBF

Wo liegen Deutschlands regionale und sektorale Innovationsschwerpunkte

Podoplanin immunopositive lymphatic vessels at the implant interface in a rat model of osteoporotic fractures

Insertion of bone substitution materials accelerates healing of osteoporotic fractures. Biodegradable materials are preferred for application in osteoporotic patients to avoid a second surgery for implant replacement. Degraded implant fragments are often absorbed by macrophages that are removed from the fracture side via passage through veins or lymphatic vessels. We investigated if lymphatic vessels occur in osteoporotic bone defects and whether they are regulated by the use of different materials. To address this issue osteoporosis was induced in rats using the classical method of bilateral ovariectomy and additional calcium and vitamin deficient diet. In addition, wedge-shaped defects of 3, 4, or 5 mm were generated in the distal metaphyseal area of femur via osteotomy. The 4 mm defects were subsequently used for implantation studies where bone substitution materials of calcium phosphate cement, composites of collagen and silica, and iron foams with interconnecting pores were inserted. Different materials were partly additionally functionalized by strontium or bisphosphonate whose positive effects in osteoporosis treatment are well known. The lymphatic vessels were identified by immunohistochemistry using an antibody against podoplanin. Podoplanin immunopositive lymphatic vessels were detected in the granulation tissue filling the fracture gap, surrounding the implant and growing into the iron foam through its interconnected pores. Significant more lymphatic capillaries were counted at the implant interface of composite, strontium and bisphosphonate functionalized iron foam. A significant increase was also observed in the number of lymphatics situated in the pores of strontium coated iron foam. In conclusion, our results indicate the occurrence of lymphatic vessels in osteoporotic bone. Our results show that lymphatic vessels are localized at the implant interface and in the fracture gap where they might be involved in the removal of lymphocytes, macrophages, debris and the implants degradation products. Therefore the lymphatic vessels are involved in implant integration and fracture healing

Flow cytometric measurement of STAT5 phosphorylation in cytomegalovirus-stimulated T cells

Cytomegalovirus (CMV)-specific T cells expand with CMV reactivation and are probably prerequisite for control and protection. Given the critical role STAT5A phosphorylation (pSTAT5A) in T cell proliferation, this study presents a simple and sensitive flow cytometric-based pSTAT5A assay to quickly identify CMV-specific T cell proliferation. We determined pSTAT5A in T cells treated with CMV-specific peptide mix (pp65 + IE1 peptides) from 20 healthy adult subjects and three immunodeficient patients with CARMIL-2 mutation. After stimulation, the percentage of pSTAT5A+ T cells in CMV-seropositive (CMV+) subjects significantly increased from 3.0% ± 1.9% (unstimulated) to 11.4% ± 5.9% (stimulated) for 24 h. After 7 days of stimulation, the percentage of expanded T cells amounted to 26% ± 17.2%. Conversely, the percentage of pSTAT5A+ T cells and T cell proliferation from CMV-seronegative (CMV−) subjects hardly changed (from 3.0% ± 1.3% to 3.7% ± 1.8% and from 4.3% ± 2.1% to 5.7% ± 1.7%, respectively). We analyzed the correlation between the percentage of pSTAT5A+ T cells versus (1) CMV-IgG concentrations versus (2) the percentage of expanded T cells and versus (3) the percentage of initial CMV-specific T cells. In immunodeficient patients with CARMIL-2 mutation, CMV-specific pSTAT5A and T cell proliferation were completely deficient. In conclusion, flow cytometric-based pSTAT5A assay represents an appropriate tool to quickly identify CMV-specific T cell proliferation and helps to understand dysfunctions in controlling other pathogens. Flow cytometric-based pSTAT5A assay may be a useful test in clinical practice and merits further validation in large studies