Biochemical and pharmacological properties of SANORG 34006, a potent and long-acting synthetic pentasaccharide

SANORG 34006 is a new sulfated pentasaccharide obtained by chemical synthesis. It is an analog of the "synthetic pentasaccharide" (SR 90107/ ORG 31540) which represents the antithrombin (AT) binding site of heparin. SANORG 34006 showed a higher affinity to human AT than SR 90107/ORG 31540 (kd = 1.4 +/- 0.3 v 48 +/- 11 nmol/L), and it is a potent and selective catalyst of the inhibitory effect of AT on factor Xa (1,240 +/- 15 anti-factor Xa U/mg v 850 +/- 27 anti-factor Xa U/mg for SR 90107/ORG 31540). In vitro, SANORG 34006 inhibited thrombin generation occurring via both the extrinsic and intrinsic pathway. After intravenous (IV) or subcutaneous (SC) administration to rabbits, SANORG 34006 displayed a long-lasting anti-factor Xa activity and inhibition of thrombin generation (TG) ex vivo. SANORG 34006 was slowly eliminated after IV or SC administration to rats, rabbits, and baboons, showed exceptionally long half-lives (between 9.2 hours in rats and 61.9 hours in baboons), and revealed an SC bioavailability near 100%. SANORG 34006 displayed antithrombotic activity by virtue of its potentiation of the anti-factor Xa activity of AT. It strongly inhibited thrombus formation in experimental models of thromboplastin/stasis-induced venous thrombosis in rats (IV) and rabbits (SC) (ED50 values = 40.0 +/- 3.4 and 105.0 +/- 9.4 nmol/kg, respectively). The duration of its antithrombotic effects closely paralleled the ex vivo anti-factor Xa activity. SANORG 34006 enhanced rt-PA-induced thrombolysis and inhibited accretion of 125I-fibrinogen onto a preformed thrombus in the rabbit jugular vein suggesting that concomitant use of SANORG 34006 during rt-PA therapy might be helpful in facilitating thrombolysis and preventing fibrin accretion onto the thrombus under lysis. Contrary to standard heparin, SANORG 34006 did not enhance bleeding in a rabbit ear incision model at a dose that equals 10 times the antithrombotic ED50 in this species and, therefore, exhibited a favorable therapeutic index. We suggest that SANORG 34006 is a promising compound in the treatment and prevention of various thrombotic diseases.     

Marking student programs using graph similarity

We present a novel approach to the automated marking of student programming assignments. Our technique quantifies the structural similarity between unmarked student submissions and marked solutions, and is the basis by which we assign marks. This is accomplished through an efficient novel graph similarity measure (AssignSim). Our experiments show good correlation of assigned marks with that of a human marker.     

A visual digital library approach for time-oriented scientific primary data

Digital Library support for textual and certain types of non-textual documents has significantly advanced over the last years. While Digital Library support implies many aspects along the whole library workflow model, interactive and visual retrieval allowing effective query formulation and result presentation are important functions. Recently, new kinds of non-textual documents which merit Digital Library support, but yet cannot be fully accommodated by existing Digital Library technology, have come into focus. Scientific data, as produced for example, by scientific experimentation, simulation or observation, is such a document type. In this article we report on a concept and first implementation of Digital Library functionality for supporting visual retrieval and exploration in a specific important class of scientific primary data, namely, time-oriented research data. The approach is developed in an interdisciplinary effort by experts from the library, natural sciences, and visual analytics communities. In addition to presenting the concept and to discussing relevant challenges, we present results from a first implementation of our approach as applied on a real-world scientific primary data set. We also report from initial user feedback obtained during discussions with domain experts from the earth observation sciences, indicating the usefulness of our approach.     

On the number of higher order Delaunay triangulations

Higher order Delaunay triangulations are a generalization of the Delaunay triangulation that provides a class of well-shaped triangulations, over which extra criteria can be optimized. A triangulation is order-k Delaunay if the circumcircle of each triangle of the triangulation contains at most k points. In this paper we study lower and upper bounds on the number of higher order Delaunay triangulations, as well as their expected number for randomly distributed points. We show that arbitrarily large point sets can have a single higher order Delaunay triangulation, even for large orders, whereas for first order Delaunay triangulations, the maximum number is 2ⁿ⁻³. Next we show that uniformly distributed points have an expected number of at least 2^{ρ₁n(1+o(1))} first order Delaunay triangulations, where ρ₁ is an analytically defined constant (ρ₁≈0.525785), and for k>1, the expected number of order-k Delaunay triangulations (which are not order-i for any i<k) is at least 2^{ρ_kn(1+o(1))}, where ρ_k can be calculated numerically.     

In vivo interactive visualization of four-dimensional blood flow patterns

In this paper we give an overview over a series of experiments to visualize and measure flow fields in the human vascular system with respect to their diagnostic capabilities. The experiments utilize a selection of GPU-based sparse and dense flow visualization algorithms to show the diagnostic opportunities for volumetric cardiovascular phase contrast magnetic resonance imaging data sets. Besides classical hardware accelerated particle and line-based approaches, an extensible tublet-based visualization, a four-dimensional volumetric line integral convolution and a new two-dimensional cutting plane tool for three-dimensional velocity data sets have been implemented. To evaluate the results, several hearts of human subjects have been investigated and a flow phantom was built to artificially simulate distinctive flow features. Our results demonstrate that we are able to provide an interactive tool for cardiovascular diagnostics with complementary hardware accelerated visualizations. Electronic Supplementary Material  The online version of this article () contains supplementary material, which is available to authorized users.

On packing shortest cycles in graphs

We study the problems to find a maximum packing of shortest edge-disjoint cycles in a graph of given girth g (g-ESCP) and its vertex-disjoint analogue g-VSCP. In the case g=3, Caprara and Rizzi (2001) have shown that g-ESCP can be solved in polynomial time for graphs with maximum degree 4, but is APX-hard for graphs with maximum degree 5, while g-VSCP can be solved in polynomial time for graphs with maximum degree 3, but is APX-hard for graphs with maximum degree 4. For g∈{4,5}, we show that both problems allow polynomial time algorithms for instances with maximum degree 3, but are APX-hard for instances with maximum degree 4. For each g?6, both problems are APX-hard already for graphs with maximum degree 3.     

Exact Algorithms for <Emphasis Type="Italic">L</Emphasis>(2,1)-Labeling of Graphs

The notion of distance constrained graph labelings, motivated by the Frequency Assignment Problem, reads as follows: A mapping from the vertex set of a graph G=(V,E) into an interval of integers {0,…,k} is an L(2,1)-labeling of G of span k if any two adjacent vertices are mapped onto integers that are at least 2 apart, and every two vertices with a common neighbor are mapped onto distinct integers. It is known that for any fixed k≥4, deciding the existence of such a labeling is an NP-complete problem. We present exact exponential time algorithms that are faster than the naive O ^*((k+1) ⁿ ) algorithm that would try all possible mappings. The improvement is best seen in the first NP-complete case of k=4, where the running time of our algorithm is O(1.3006 ⁿ ). Furthermore we show that dynamic programming can be used to establish an O(3.8730 ⁿ ) algorithm to compute an optimal L(2,1)-labeling.     

Bandwidth on AT-free graphs

We study the classical Bandwidth problem from the viewpoint of parametrised algorithms. Given a graph G=(V,E) and a positive integer k, the Bandwidth problem asks whether there exists a bijective function β:{1,…,∣V∣}→V such that for every edge uv∈E, ∣β⁻¹(u)−β⁻¹(v)∣≤k. It is known that under standard complexity assumptions, no algorithm for Bandwidth with running time of the form f(k)n^O(1) exists, even when the input is restricted to trees. We initiate the search for classes of graphs where such algorithms do exist. We present an algorithm with running time n⋅2^O(klogk) for Bandwidth on AT-free graphs, a well-studied graph class that contains interval, permutation, and cocomparability graphs. Our result is the first non-trivial algorithm that shows fixed-parameter tractability of Bandwidth on a graph class on which the problem remains NP-complete.