91 research outputs found
Representing Terrain With Mathematical Operators
This work describes a mathematical representation of terrain data consisting of a novel operation, the “drill”. It facilitates the representation of legal terrains, capturing the richness of the physics of the terrain’s generation by digging channels in the surface. Given our current reliance on digital map data, hand-held devices, and GPS navigation systems, the accuracy and compactness of terrain data representations are becoming increasingly important. Representing a terrain as a series of operations that can procedurally regenerate the terrains allows for compact representation that retains more information than height fields, TINs, and other popular representations. Our model relies on the hydrography information extracted from the terrain, and so drainage information is retained during encoding. To determine the shape of the drill along each channel in the channel network, a cross section of the channel is extracted, and a quadratic polynomial is fit to it. We extract the drill representation from a mountainous dataset, using a series of parameters (including size and area of influence of the drill, as well as the density of the hydrography data), and present the accuracy calculated using a series of metrics. We demonstrate that the drill operator provides a viable and accurate terrain representation that captures both the terrain shape and the richness of its generation
PDE 7 Inhibitors: New Potential Drugs for the Therapy of Spinal Cord Injury
BACKGROUND: Primary traumatic mechanical injury to the spinal cord (SCI) causes the death of a number of neurons that to date can neither be recovered nor regenerated. During the last years our group has been involved in the design, synthesis and evaluation of PDE7 inhibitors as new innovative drugs for several neurological disorders. Our working hypothesis is based on two different facts. Firstly, neuroinflammation is modulated by cAMP levels, thus the key role for phosphodiesterases (PDEs), which hydrolyze cAMP, is undoubtedly demonstrated. On the other hand, PDE7 is expressed simultaneously on leukocytes and on the brain, highlighting the potential crucial role of PDE7 as drug target for neuroinflammation. METHODOLOGY/PRINCIPAL FINDINGS: Here we present two chemically diverse families of PDE7 inhibitors, designed using computational techniques such as virtual screening and neuronal networks. We report their biological profile and their efficacy in an experimental SCI model induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. We have selected two candidates, namely S14 and VP1.15, as PDE7 inhibitors. These compounds increase cAMP production both in macrophage and neuronal cell lines. Regarding drug-like properties, compounds were able to cross the blood brain barrier using parallel artificial membranes (PAMPA) methodology. SCI in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and production of a range of inflammatory mediators, tissue damage, and apoptosis. Treatment of the mice with S14 and VP1.15, two PDE7 inhibitors, significantly reduced the degree of spinal cord inflammation, tissue injury (histological score), and TNF-α, IL-6, COX-2 and iNOS expression. CONCLUSIONS/SIGNIFICANCE: All these data together led us to propose PDE7 inhibitors, and specifically S14 and VP1.15, as potential drug candidates to be further studied for the treatment of SCI
On complexity of lobbying in multiple referenda
Lobbying, Referendum, Parametrized complexity, D72,
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