Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain

Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) inhibitors induces strong antihyperalgesic effect during inflammatory pain. In this study we observed low level of DPP4 mRNA in the rat spinal dorsal horn in physiological conditions, which did not change significantly either in carrageenan-induced inflammatory or partial nerve ligation-generated neuropathic states. In naive animals, microglia and astrocytes expressed DPP4 protein with one and two orders of magnitude higher than neurons, respectively. DPP4 significantly increased in astrocytes during inflammation and in microglia in neuropathy. Intrathecal application of two DPP4 inhibitors tripeptide isoleucin-prolin-isoleucin (IPI) and the antidiabetic drug vildagliptin resulted in robust opioid-dependent antihyperalgesic effect during inflammation, and milder but significant opioid-independent antihyperalgesic action in the neuropathic model. The opioid-mediated antihyperalgesic effect of IPI was exclusively related to mu-opioid receptors, while vildagliptin affected mainly delta-receptor activity, although mu- and kappa-receptors were also involved. None of the inhibitors influenced allodynia. Our results suggest pathology and glia-type specific changes of DPP4 activity in the spinal cord, which contribute to the development and maintenance of hyperalgesia and interact with endogenous opioid systems

Heuristically Driven Front Propagation for Geodesic Paths Extraction

In this paper we present a simple modification of the Fast Marching algorithm to speed up the computation using a heuristic. This modification leads to an algorithm that is similar in spirit to the A* algorithm used in artificial intelligence. Using a heuristic allows to extract geodesics from a single source to a single goal very quickly and with a low memory requirement. Any application that needs to compute a lot of geodesic paths can gain benefits from our algorithm. The computational saving is even more important for 3D medical images with tubular structures and for higher dimensional data.ou

Tidal amplification and along-strike process variability in a mixed-energy paralic system prograding onto a low accommodation shelf, Edgeøya, Svalbard

The study describes the depositional development and sediment partitioning in a prograding paralic Triassic succession. The deposits are associated with the advance of large prism-scale clinoforms across a shallower platform area. Approaching the platform, the limited accommodation and associated relative higher rates of deposition generated straighter clinoforms with lower foreset angles. The vertical restriction across the platform is interpreted to have amplified the tidal signature. Sediment was redistributed from the coast into increasingly sandy delta-front deposits, compared to offshore equivalents. The deposits comprise extensive compound dune fields of amalgamated and increasingly clean sandbodies up-section. Rapid deposition of significant amounts of sand led to differential subsidence and growth-faulting in the delta front, with downthrown fault blocks further amplifying the tidal energy through funnelling. A mixed-energy environment created along-strike variability along the delta front with sedimentation governing process-regime. Areas of lower sedimentation were reworked by wave and storm-action, whereas high sedimentation rates preserved fluvially dominated mouth bars. A major transgression, however, favoured tidally dominated deposits also in these areas, attributed to increasing rugosity of the coastline. Formation of an extensive subaqueous platform between the coast and delta front dampened incoming wave energy, and tidally dominated deposits dominate the near-shore successions. Meanwhile formation of wave-built sand-bars atop the platform attest to continued wave influence. The strong tidal regime led to the development of a heterolithic near-shore tidally dominated channel system, and sandier fluvial channels up-river. The highly meandering tidal channels incising the subaqueous platform form kilometre wide successions of inclined heterolithic stratification. The fluvially dominated channels which govern deposition on the delta plain are narrower and slightly less deep, straighter, generally symmetric and filled with cleaner sands. This study provides important insight into tidal amplification and sand redistribution during shallowing on a wide shelf, along with along-strike process-regime variability resulting from variations in sediment influx

Implementations and Experimental Studies of Dynamic Graph Algorithms

Dynamic graph algorithms have been extensively studied in the last two decades due to their wide applicability in many contexts. Recently, several implementations and experimental studies have been conducted investigating the practical merits of fundamental techniques and algorithms. In most cases, these algorithms required sophisticated engineering and fine-tuning to be turned into efficient implementations. In this paper, we survey several implementations along with their experimental studies for dynamic problems on undirected and directed graphs. The former case includes dynamic connectivity, dynamic minimum spanning trees, and the sparsification technique. The latter case includes dynamic transitive closure and dynamic shortest paths. We also discuss the design and implementation of a software library for dynamic graph algorithms