Mechanisms of Copper-Dependent Notochord Formation in Zebrafish

The interplay of genes and nutrition during early development profoundly impacts fetal outcome. Copper is an essential nutrient required for the redox activity of many enzymes, and recent work in our laboratory has elucidated the phenotype of copper deficiency in zebrafish, which includes a strikingly distorted notochord. The studies described here establish the specific genetic etiology of this distortion and reveal a number of gene-gene and gene-nutrient interactions critical to notochord morphogenesis. We first demonstrate that the notochord distortion observed in copper-deficient zebrafish results from lysyl oxidase cuproenzyme inhibition. Four lysyl oxidase family members are expressed throughout the developing zebrafish notochord, including loxl1 and loxl5b. Morpholino antisense experiments reveal that knockdown of loxl1 results in notochord distortion and also demonstrate overlapping roles for loxl1 and loxl5b in notochord formation. Furthermore, partial knockdown of either loxl1 or loxl5b sensitizes embryos to notochord distortion when combined with reduced copper availability, and any of these treatments alone sensitizes embryos to notochord distortion after partial disruption of the gene encoding a lysyl oxidase substrate, col2a1. To elucidate additional gene-nutrient interactions involved in notochord formation, we conducted a forward genetic screen for mutants that exhibit increased notochord distortion after partial lysyl oxidase inhibition. This screen was facilitated by the identification of a novel, highly potent lysyl oxidase inhibitor, 2-mercaptopyridine-N-oxide, and yielded a mutant with defects in notochord and vascular morphogenesis, puff daddygw1. Subsequent work demonstrated that the puff daddygw1 phenotype results from loss of zebrafish fibrillin-2. Importantly, the notochords of puff daddygw1 mutants are strikingly sensitized to distortion under conditions of suboptimal copper nutrition that do not affect wild-type embryos. This sensitization is also observed in a published notochord mutant, gulliverm208, and we demonstrate that the gulliverm208 phenotype arises from a missense mutation in the alpha 1 chain of type VIII collagen. Taken together, these studies demonstrate essential roles for copper and multiple extracellular matrix components in late notochord formation and suggest that nutritional status should be interpreted within the polymorphic genetic context of the developing embryo

Rectangular Layouts and Contact Graphs

Contact graphs of isothetic rectangles unify many concepts from applications including VLSI and architectural design, computational geometry, and GIS. Minimizing the area of their corresponding {\em rectangular layouts} is a key problem. We study the area-optimization problem and show that it is NP-hard to find a minimum-area rectangular layout of a given contact graph. We present O(n)-time algorithms that construct $O(n^2)$-area rectangular layouts for general contact graphs and $O(n\log n)$-area rectangular layouts for trees. (For trees, this is an $O(\log n)$-approximation algorithm.) We also present an infinite family of graphs (rsp., trees) that require $\Omega(n^2)$ (rsp., $\Omega(n\log n)$) area. We derive these results by presenting a new characterization of graphs that admit rectangular layouts using the related concept of {\em rectangular duals}. A corollary to our results relates the class of graphs that admit rectangular layouts to {\em rectangle of influence drawings}.Comment: 28 pages, 13 figures, 55 references, 1 appendi

A Coloring Algorithm for Disambiguating Graph and Map Drawings

Drawings of non-planar graphs always result in edge crossings. When there are many edges crossing at small angles, it is often difficult to follow these edges, because of the multiple visual paths resulted from the crossings that slow down eye movements. In this paper we propose an algorithm that disambiguates the edges with automatic selection of distinctive colors. Our proposed algorithm computes a near optimal color assignment of a dual collision graph, using a novel branch-and-bound procedure applied to a space decomposition of the color gamut. We give examples demonstrating the effectiveness of this approach in clarifying drawings of real world graphs and maps

Using Link Cuts to Attack Internet Routing

Attacks on the routing system, with the goal of diverting traffic past an enemy-controlled point for purposes of eavesdropping or connection-hijacking, have long been known. In principle, at least, these attacks can be countered by use of appropriate authentication techniques. We demonstrate a new attack, based on link-cutting, that cannot be countered in this fashion. Armed with a topology map and a list of already-compromised links and routers, an attacker can calculate which links to disable, in order to force selected traffic to pass the compromised elements. The calculations necessary to launch this attack are quite efficient; in our implementation, most runs took less than half a second, on databases of several hundred nodes. We also suggest a number of work-arounds, including one based on using intrusion detection systems to modify routing metrics

Timber resources of the Missouri Prairie region

Cover title.Includes bibliographical references

A Sparse Stress Model

Force-directed layout methods constitute the most common approach to draw general graphs. Among them, stress minimization produces layouts of comparatively high quality but also imposes comparatively high computational demands. We propose a speed-up method based on the aggregation of terms in the objective function. It is akin to aggregate repulsion from far-away nodes during spring embedding but transfers the idea from the layout space into a preprocessing phase. An initial experimental study informs a method to select representatives, and subsequent more extensive experiments indicate that our method yields better approximations of minimum-stress layouts in less time than related methods.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016

Node overlap removal by growing a tree

Node overlap removal is a necessary step in many scenarios including laying out a graph, or visualizing a tag cloud. Our contribution is a new overlap removal algorithm that iteratively builds a Minimum Spanning Tree on a Delaunay triangulation of the node centers and removes the node overlaps by ”growing” the tree. The algorithm is simple to implement yet produces high quality layouts. According to our experiments it runs several times faster than the current state-of-the-art methods

Timber resources of Missouri's northwestern Ozarks

Caption title."Agricultural Experiment Station and U.S.D.A. Forest Service Cooperating"--Cover."This bulletin reports on Missouri Agricultural Experiment Station Research Project 399, Forest Survey"--Page 2