Chlorination and oxidation of heparin and hyaluronan by hypochlorous acid and hypochlorite anions: effect of sulfate groups on reaction pathways and kinetics.

Hypochlorous acid (HOCl), produced in inflammatory conditions by the enzyme myeloperoxidase, and its anion hypochlorite (OCl(-)) exist in vivo at almost equal concentrations. Their reactions with hyaluronan and heparin (as a model for sulfated glycosaminoglycans in the extracellular matrix) have been studied as a function of pH. The major product in these reactions is the chloramide derivative of the glycosaminoglycans. Spectral, chloramide yield, and kinetic measurements show sharply contrasting behavior of heparin and hyaluronan and the data allow the calculation of second-order rate constants for the reactions of both HOCl and OCl(-) for all reaction pathways leading to the formation of chloramides and also oxidation products. By comparison with hyaluronan, it can be demonstrated that both N-sulfate and O-sulfate groups in heparin influence the proportions of these pathways in this glycosaminoglycan. Evidence is also given for further oxidation pathways involving a reaction of HOCl with the chloramide product of hyaluronan but not with heparin. The significance of these results for the mechanisms of inflammation, particularly for fragmentation of extracellular matrix glycosaminoglycans, is discussed

On pairwise distances and median score of three genomes under DCJ

In comparative genomics, the rearrangement distance between two genomes (equal the minimal number of genome rearrangements required to transform them into a single genome) is often used for measuring their evolutionary remoteness. Generalization of this measure to three genomes is known as the median score (while a resulting genome is called median genome). In contrast to the rearrangement distance between two genomes which can be computed in linear time, computing the median score for three genomes is NP-hard. This inspires a quest for simpler and faster approximations for the median score, the most natural of which appears to be the halved sum of pairwise distances which in fact represents a lower bound for the median score. In this work, we study relationship and interplay of pairwise distances between three genomes and their median score under the model of Double-Cut-and-Join (DCJ) rearrangements. Most remarkably we show that while a rearrangement may change the sum of pairwise distances by at most 2 (and thus change the lower bound by at most 1), even the most "powerful" rearrangements in this respect that increase the lower bound by 1 (by moving one genome farther away from each of the other two genomes), which we call strong, do not necessarily affect the median score. This observation implies that the two measures are not as well-correlated as one's intuition may suggest. We further prove that the median score attains the lower bound exactly on the triples of genomes that can be obtained from a single genome with strong rearrangements. While the sum of pairwise distances with the factor 2/3 represents an upper bound for the median score, its tightness remains unclear. Nonetheless, we show that the difference of the median score and its lower bound is not bounded by a constant.Comment: Proceedings of the 10-th Annual RECOMB Satellite Workshop on Comparative Genomics (RECOMB-CG), 2012. (to appear

Beyond Node Degree: Evaluating AS Topology Models

This is the accepted version of 'Beyond Node Degree: Evaluating AS Topology Models', archived originally at arXiv:0807.2023v1 [cs.NI] 13 July 2008.Many models have been proposed to generate Internet Autonomous System (AS) topologies, most of which make structural assumptions about the AS graph. In this paper we compare AS topology generation models with several observed AS topologies. In contrast to most previous works, we avoid making assumptions about which topological properties are important to characterize the AS topology. Our analysis shows that, although matching degree-based properties, the existing AS topology generation models fail to capture the complexity of the local interconnection structure between ASs. Furthermore, we use BGP data from multiple vantage points to show that additional measurement locations significantly affect local structure properties, such as clustering and node centrality. Degree-based properties, however, are not notably affected by additional measurements locations. These observations are particularly valid in the core. The shortcomings of AS topology generation models stems from an underestimation of the complexity of the connectivity in the core caused by inappropriate use of BGP data

Preserving Liveness Guarantees from Synchronous Communication to Asynchronous Unstructured Low-Level Languages

In the implementation of abstract synchronous communication in asynchronous unstructured low-level languages, e.g. using shared variables, the preservation of safety and especially liveness properties is a hitherto open problem due to inherently different abstraction levels. Our approach to overcome this problem is threefold: First, we present our notion of handshake refinement with which we formally prove the correctness of the implementation relation of a handshake protocol. Second, we verify the soundness of our handshake refinement, i.e., all safety and liveness properties are preserved to the lower level. Third, we apply our handshake refinement to show the correctness of all implementations that realize the abstract synchronous communication with the handshake protocol. To this end, we employ an exemplary language with asynchronous shared variable communication. Our approach is scalable and closes the verification gap between different abstraction levels of communication

Information-Theoretic Active Learning for Content-Based Image Retrieval

We propose Information-Theoretic Active Learning (ITAL), a novel batch-mode active learning method for binary classification, and apply it for acquiring meaningful user feedback in the context of content-based image retrieval. Instead of combining different heuristics such as uncertainty, diversity, or density, our method is based on maximizing the mutual information between the predicted relevance of the images and the expected user feedback regarding the selected batch. We propose suitable approximations to this computationally demanding problem and also integrate an explicit model of user behavior that accounts for possible incorrect labels and unnameable instances. Furthermore, our approach does not only take the structure of the data but also the expected model output change caused by the user feedback into account. In contrast to other methods, ITAL turns out to be highly flexible and provides state-of-the-art performance across various datasets, such as MIRFLICKR and ImageNet.Comment: GCPR 2018 paper (14 pages text + 2 pages references + 6 pages appendix

Stereolithographic (SLA) 3D printing of oral modified-release dosage forms.

The aim of this work was to evaluate the suitability of stereolithography (SLA) to fabricate drug-loaded tablets with modified-release characteristics. The SLA printer creates solid objects by using a laser beam to photopolymerise monomers. In this work polyethylene glycol diacrylate (PEGDA) was used as a monomer and diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide was used as a photo-initiator. 4-aminosalicylic acid (4-ASA) and paracetamol (acetaminophen) were selected as model drugs. Tablets were successfully printed and formulations with different properties were fabricated by adding polyethylene glycol 300 (PEG 300) to the printing solution. The loading of paracetamol and 4-ASA in the printed tablets was 5.69% and 5.40% respectively. In a realistic dynamic dissolution simulation of the gastrointestinal tract, drug release from the tablets was dependent on the composition of the formulations, but independent of dissolution pH. In conclusion SLA 3DP technology allows the manufacture of drug loaded tablets with specific extended-release profiles. In the future this technology could become a manufacturing technology for the elaboration of oral dosage forms, for industrial production or even for personalised dose

Stability, Structure and Scale: Improvements in Multi-modal Vessel Extraction for SEEG Trajectory Planning

Purpose Brain vessels are among the most critical landmarks that need to be assessed for mitigating surgical risks in stereo-electroencephalography (SEEG) implantation. Intracranial haemorrhage is the most common complication associated with implantation, carrying signi cant associated morbidity. SEEG planning is done pre-operatively to identify avascular trajectories for the electrodes. In current practice, neurosurgeons have no assistance in the planning of electrode trajectories. There is great interest in developing computer assisted planning systems that can optimise the safety pro le of electrode trajectories, maximising the distance to critical structures. This paper presents a method that integrates the concepts of scale, neighbourhood structure and feature stability with the aim of improving robustness and accuracy of vessel extraction within a SEEG planning system. Methods The developed method accounts for scale and vicinity of a voxel by formulating the problem within a multi-scale tensor voting framework. Feature stability is achieved through a similarity measure that evaluates the multi-modal consistency in vesselness responses. The proposed measurement allows the combination of multiple images modalities into a single image that is used within the planning system to visualise critical vessels. Results Twelve paired datasets from two image modalities available within the planning system were used for evaluation. The mean Dice similarity coe cient was 0.89 ± 0.04, representing a statistically signi cantly improvement when compared to a semi-automated single human rater, single-modality segmentation protocol used in clinical practice (0.80 ±0.03). Conclusions Multi-modal vessel extraction is superior to semi-automated single-modality segmentation, indicating the possibility of safer SEEG planning, with reduced patient morbidity

Quadratic Word Equations with Length Constraints, Counter Systems, and Presburger Arithmetic with Divisibility

Word equations are a crucial element in the theoretical foundation of constraint solving over strings, which have received a lot of attention in recent years. A word equation relates two words over string variables and constants. Its solution amounts to a function mapping variables to constant strings that equate the left and right hand sides of the equation. While the problem of solving word equations is decidable, the decidability of the problem of solving a word equation with a length constraint (i.e., a constraint relating the lengths of words in the word equation) has remained a long-standing open problem. In this paper, we focus on the subclass of quadratic word equations, i.e., in which each variable occurs at most twice. We first show that the length abstractions of solutions to quadratic word equations are in general not Presburger-definable. We then describe a class of counter systems with Presburger transition relations which capture the length abstraction of a quadratic word equation with regular constraints. We provide an encoding of the effect of a simple loop of the counter systems in the theory of existential Presburger Arithmetic with divisibility (PAD). Since PAD is decidable, we get a decision procedure for quadratic words equations with length constraints for which the associated counter system is \emph{flat} (i.e., all nodes belong to at most one cycle). We show a decidability result (in fact, also an NP algorithm with a PAD oracle) for a recently proposed NP-complete fragment of word equations called regular-oriented word equations, together with length constraints. Decidability holds when the constraints are additionally extended with regular constraints with a 1-weak control structure.Comment: 18 page

Influence of Geometry on the Drug Release Profiles of Stereolithographic (SLA) 3D-Printed Tablets

Additive manufacturing (3D printing) permits the fabrication of tablets in shapes unattainable by powder compaction, and so the effects of geometry on drug release behavior is easily assessed. Here, tablets (printlets) comprising of paracetamol dispersed in polyethylene glycol were printed using stereolithographic 3D printing. A number of geometric shapes were produced (cube, disc, pyramid, sphere and torus) with either constant surface area (SA) or constant surface area/volume ratio (SA/V). Dissolution testing showed that printlets with constant SA/V ratio released drug at the same rate, while those with constant SA released drug at different rates. A series of tori with increasing SA/V ratio (from 0.5 to 2.4) were printed, and it was found that dissolution rate increased as the SA/V ratio increased. The data show that printlets can be fabricated in multiple shapes and that dissolution performance can be maintained if the SA/V ratio is constant or that dissolution performance of printlets can be fine-tuned by varying SA/V ratio. The results suggest that 3D printing is therefore a suitable manufacturing method for personalized dosage forms