An in vitro model of chronic wounding and its implication for age-related macular degeneration

Degeneration of the retinal pigment epithelium (RPE) plays a central role in age-related macular degeneration (AMD). Throughout life, RPE cells are challenged by a variety of cytotoxic stressors, some of which are cumulative with age and may ultimately contribute to drusen and lipofuscin accumulation. Stressors such as these continually damage RPE cells resulting in a state of chronic wounding. Current cell-based platforms that model a state of chronic RPE cell wounding are limited, and the RPE cellular response is not entirely understood. Here, we used the electric cell-substrate impedance sensing (ECIS) system to induce a state of acute or chronic wounding on differentiated human fetal RPE cells to analyze changes in the wound repair response. RPE cells surrounding the lesioned area employ both cell migration and proliferation to repair wounds but fail to reestablish their original cell morphology or density after repetitive wounding. Chronically wounded RPE cells develop phenotypic AMD characteristics such as loss of cuboidal morphology, enlarged size, and multinucleation. Transcriptomic analysis suggests a systemic misregulation of RPE cell functions in bystander cells, which are not directly adjacent to the wound. Genes associated with the major RPE cell functions (LRAT, MITF, RDH11) significantly downregulate after wounding, in addition to differential expression of genes associated with the cell cycle (CDK1, CDC6, CDC20), inflammation (IL-18, CCL2), and apoptosis (FAS). Interestingly, repetitive wounding resulted in prolonged misregulation of genes, including FAS, LRAT, and PEDF. The use of ECIS to induce wounding resulted in an over-representation of AMD-associated genes among those dysregulated genes, particularly genes associated with advanced AMD. This simple system provides a new model for further investigation of RPE cell wound response in AMD pathogenesis

On the Maximum Crossing Number

Research about crossings is typically about minimization. In this paper, we consider \emph{maximizing} the number of crossings over all possible ways to draw a given graph in the plane. Alpert et al. [Electron. J. Combin., 2009] conjectured that any graph has a \emph{convex} straight-line drawing, e.g., a drawing with vertices in convex position, that maximizes the number of edge crossings. We disprove this conjecture by constructing a planar graph on twelve vertices that allows a non-convex drawing with more crossings than any convex one. Bald et al. [Proc. COCOON, 2016] showed that it is NP-hard to compute the maximum number of crossings of a geometric graph and that the weighted geometric case is NP-hard to approximate. We strengthen these results by showing hardness of approximation even for the unweighted geometric case and prove that the unweighted topological case is NP-hard.Comment: 16 pages, 5 figure

Six topics on inscribable polytopes

Inscribability of polytopes is a classic subject but also a lively research area nowadays. We illustrate this with a selection of well-known results and recent developments on six particular topics related to inscribable polytopes. Along the way we collect a list of (new and old) open questions.Comment: 11 page

Polytopality and Cartesian products of graphs

We study the question of polytopality of graphs: when is a given graph the graph of a polytope? We first review the known necessary conditions for a graph to be polytopal, and we provide several families of graphs which satisfy all these conditions, but which nonetheless are not graphs of polytopes. Our main contribution concerns the polytopality of Cartesian products of non-polytopal graphs. On the one hand, we show that products of simple polytopes are the only simple polytopes whose graph is a product. On the other hand, we provide a general method to construct (non-simple) polytopal products whose factors are not polytopal.Comment: 21 pages, 10 figure

Theory of commensurable magnetic structures in holmium

The tendency for the period of the helically ordered moments in holmium to lock into values which are commensurable with the lattice is studied theoretically as a function of temperature and magnetic field. The commensurable effects are derived in the mean-field approximation from numerical calculations of the free energy of various commensurable structures, and the results are compared with the extensive experimental evidence collected during the last ten years on the magnetic structures in holmium. In general the stability of the different commensurable structures is found to be in accord with the experiments, except for the tau=5/18 structure observed a few degrees below T_N in a b-axis field. The trigonal coupling recently detected in holmium is found to be the interaction required to explain the increased stability of the tau=1/5 structure around 42 K, and of the tau=1/4 structure around 96 K, when a field is applied along the c-axis.Comment: REVTEX, 31 pages, 7 postscript figure

Small grid embeddings of 3-polytopes

We introduce an algorithm that embeds a given 3-connected planar graph as a convex 3-polytope with integer coordinates. The size of the coordinates is bounded by $O(2^{7.55n})=O(188^{n})$. If the graph contains a triangle we can bound the integer coordinates by $O(2^{4.82n})$. If the graph contains a quadrilateral we can bound the integer coordinates by $O(2^{5.46n})$. The crucial part of the algorithm is to find a convex plane embedding whose edges can be weighted such that the sum of the weighted edges, seen as vectors, cancel at every point. It is well known that this can be guaranteed for the interior vertices by applying a technique of Tutte. We show how to extend Tutte's ideas to construct a plane embedding where the weighted vector sums cancel also on the vertices of the boundary face

Additional experimental evidence for a solar influence on nuclear decay rates

Additional experimental evidence is presented in support of the recent hypothesis that a possible solar influence could explain fluctuations observed in the measured decay rates of some isotopes. These data were obtained during routine weekly calibrations of an instrument used for radiological safety at The Ohio State University Research Reactor using Cl-36. The detector system used was based on a Geiger-Mueller gas detector, which is a robust detector system with very low susceptibility to environmental changes. A clear annual variation is evident in the data, with a maximum relative count rate observed in January/February, and a minimum relative count rate observed in July/August, for seven successive years from July 2005 to June 2011. This annual variation is not likely to have arisen from changes in the detector surroundings, as we show here.Comment: 8 pages, 6 figure

Brachionus rotundiformis tschugunoff, 1921 from the brachionus plicatilis species complex (Rotifera: Monogononta): A new record from galápagos archipelago, Ecuador

The presence of the rotifer species Brachionus rotundiformis from the B. plicatilis species complex in Lake Arcturo, a saline lake in the Genovesa Island of the Galápagos Islands, is here reported. This is the first record of the species for the rotifer fauna of Ecuador as well as of the species complex to the Galápagos Islands. This finding is consistent with the idea of high dispersion capacity, and of cosmopolitan distribution of this species complex. Because Genovesa Island is uninhabited, passive transport by wind currents and zoochory by migrant birds seem to emerge as the most plausible factors in this process of colonization. Integrative studies on the morphological variations, genetic, molecular, and ecological aspects are still required to further understand the process of dispersion and the ecology of this member of the B. plicatilis species complex in this remote and isolated locality, and the exact taxonomical position of the island’s population to the other members of the complex.</p

Persistent Spin Currents in Helimagnets

We demonstrate that weak external magnetic fields generate dissipationless spin currents in the ground state of systems with spiral magnetic order. Our conclusions are based on phenomenological considerations and on microscopic mean-field theory calculations for an illustrative toy model. We speculate on possible applications of this effect in spintronic devices.Comment: 9 pages, 6 figures, updated version as published, Journal referenc

Maintaining Disorder: Some Technical and Aesthetic Issues Involved in the Performance of Ligeti’s E´ tudes for Piano

This article examines some of the particular questions and associated strategies concerning matters of rhythm, perceived metre, notation, accentuation, line, physical approach to the keyboard, pedalling, and more in the performance of Ligeti’s Études for piano. I relate these issues to those encountered in earlier repertoire, including works of Schumann, Liszt, Stravinsky, Prokofiev, Bartók and Blacher, and argue that particular approaches and attitudes to both technical and musical matters in the context of these Études can fundamentally affect the concept of the music. A particular focus is upon issues of continuity and discontinuity, and the ‘situation’ of these works within particular pianistic and other traditions by virtue of the approach taken to performance