An energy preserving upscaling technique for enhanced volume rendering of medical data

Proc. 3D Anatomical Human Summer School 2010, 23-24 May, Chania, Greece: EU Marie Curie Research Training Network. 2010.In this paper we describe an edge-directed optimization-based method for volumetric data supersampling. Our method faces the problem of partial volume effect by upscaling the volumetric data, subdividing voxels in smaller parts and performing an optimization step keeping constant the energy of each original subdivided voxel while enhancing edge continuity. Experimental tests show the good quality of the results obtained with our approach. Furthermore, we show how offline 3D upscaling of volumes can be coupled with recent techniques to perform high quality volume rendering of large datsets, obtaining a better inspection of medical volumetric data.In corso di stamp

Un sistema multiprocessore per la simulazione della chirurgia sull'osso temporale

Nel presente articolo si presenta un simulatore per l’addestramento alla chirurgia dell’osso temporale. Il sistema si basa su modelli volumetrici direttamente derivati da dati 3D di TAC e MR. Il ritorno di sensazioni in tempo reale viene fornito all’utente per mezzo di tecniche di rendering volumetrico e di modellazione di sensazioni aptiche. I vincoli nelle prestazioni imposti dal sistema percettivo umano sono soddisfatti sfruttando il parallelismo attraverso il disaccoppiamento della simulazione su una piattaforma di PC multi-processore. In quest’articolo, vengono descritti in dettaglio i componenti del sistema e lo stato attuale dell’integrazione dei medesimi

A Grid-enabled web portal for NMR structure refinement with AMBER

Abstract Motivation: The typical workflow for NMR structure determination involves collecting thousands of conformational restraints, calculating a bundle of 20–40 conformers in agreement with them and refining the energetics of these conformers. The structure calculation step employs simulated annealing based on molecular dynamics (MD) simulations with very simplified force fields. The value of refining the calculated conformers using restrained MD (rMD) simulations with state-of-art force fields is documented. This refinement however presents various subtleties, from the proper formatting of conformational restraints to the definition of suitable protocols. Results: We describe a web interface to set up and run calculations with the AMBER package, which we called AMPS-NMR (AMBER-based Portal Server for NMR structures). The interface allows the refinement of NMR structures through rMD. Some predefined protocols are provided for this purpose, which can be personalized; it is also possible to create an entirely new protocol. AMPS-NMR can handle various restraint types. Standard rMD refinement in explicit water of the structures of three different proteins are shown as examples. AMPS-NMR additionally includes a workspace for the user to store different calculations. As an ancillary service, a web interface to AnteChamber is available, enabling the calculation of force field parameters for organic molecules such as ligands in protein–ligand adducts. Availability and Implementation: AMPS-NMR is embedded within the NMR services of the WeNMR project and is available at http://py-enmr.cerm.unifi.it/access/index/amps-nmr; its use requires registration with a digital certificate. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online

Involvement of bradykinin B2 receptor in pathological vascularization in oxygen-induced retinopathy in mice and rabbit cornea

The identification of components of the kallikrein-kinin system in the vitreous from patients with microvascular retinal diseases suggests that bradykinin (BK) signaling may contribute to pathogenesis of retinal vascular complications. BK receptor 2 (B2R) signaling has been implicated in both pro-inflammatory and pro-angiogenic effects promoted by BK. Here, we investigated the role of BK/B2R signaling in the retinal neovascularization in the oxygen-induced retinopathy (OIR) model. Blockade of B2R signaling by the antagonist fasitibant delayed retinal vascularization in mouse pups, indicating that the retinal endothelium is a target of the BK/B2R system. In the rabbit cornea assay, a model of pathological neoangiogenesis, the B2 agonist kallidin induced vessel sprouting and promoted cornea opacity, a sign of edema and tissue inflammation. In agreement with these results, in the OIR model, a blockade of B2R signaling significantly reduced retinal neovascularization, as determined by the area of retinal tufts, and, in the retinal vessel, it also reduced vascular endothelial growth factor and fibroblast growth factor-2 expression. All together, these findings show that B2R blockade reduces retinal neovascularization and inhibits the expression of proangiogenic and pro-inflammatory cytokines, suggesting that targeting B2R signaling may be an effective strategy for treating ischemic retinopathy

Inhibition of cell cycle progression by the hydroxytyrosol-cetuximab combination yields enhanced chemotherapeutic efficacy in colon cancer cells

Hydroxytyrosol (HT), a polyphenol of olive oil, downregulates epidermal growth factor (EGFR) expression and inhibits cell proliferation in colon cancer (CC) cells, with mechanisms similar to that activated by the EGFR inhibitor, cetuximab. Here, we studied whether HT treatment would enhance the cetuximab inhibitory effects on cell growth in CC cells. HT-cetuximab combination showed greater efficacy in reducing cell growth in HT- 29 and WiDr cells at concentrations 10 times lower than when used as single agents. This reduction was clearly linked to cell cycle blockade, occurring at G2/M phase. The cell cycle arrest in response to combination treatment is related to cyclins B, D1, and E, and cyclin-dependent kinase (CDK) 2, CDK4, and CDK6 down-regulation, and to the concomitant over-expression of CDK inhibitors p21 and p27. HT and cetuximab stimulated a caspase-independent cell death cascade, promotedtranslocation of apoptosis-inducing factor (AIF) from mitochondria to nucleus and activated the autophagy process. Notably, normal colon cells and keratinocytes were less susceptible to comboinduced cell death and EGFR downregulation. These results suggest a potential role of diet, containing olive oil, during cetuximab chemotherapy of colon tumor. HT may be a competent therapeutic agent in CC enhancing the effects of EGFR inhibitors

Molecular dynamics simulations of metalloproteins: A folding study of rubredoxin from <em>Pyrococcus furiosus</em>

The constant increase of computational power has made feasible to investigate the folding mechanism of small proteins using molecular dynamics (MD). Metal-binding proteins (metalloproteins) are usually complicated to model, largely due to the presence of the metal cofactor. Thus, the study of metal-coupled folding is still challenging. In this work, we addressed the folding process of Pyrococcus furiosus rubredoxin (PfRd), a 53-residue protein binding a single iron ion, using different MD methods. Starting from an extended conformation of the polypeptide chain where we preserved the coordination of the metal ion, a classical MD simulation and an extensive accelerated MD run were performed to reconstruct the folding process of the metal-bound protein. For comparison, we simulated also the dynamics of folded PfRd devoid of the metal cofactor (apo-form), starting from the folded structure. For these MD trajectories, we computed various structural and biochemical properties. In addition, we took advantage of available experimental data to quantify the degree to which our simulations sampled conformations close to the native folded state. We observed that the compaction of the hydrophobic core is the main feature driving the folding of the structure. However, we could not reach a fully folded conformation within our trajectories, because of the incomplete removal of the solvent from the core. Altogether, the various MD simulations, including that of the folded apo-form of the protein, suggest that an improvement in the accuracy of the protein force-field is still needed

Prostaglandin E2 Regulates Angiogenesis via Activation of Fibroblast Growth Factor Receptor-1

Prostaglandin E(2) (PGE(2)) behaves as a mitogen in epithelial tumor cells as well as in many other cell types. We investigated the actions of PGE(2) on microvascular endothelial cells (capillary venular endothelial cells) with the purpose of delineating the signaling pathway leading to the acquisition of the angiogenic phenotype and to new vessel formation. PGE(2) (100 nM) produced activation of the fibroblast growth factor receptor 1 (FGFR-1), as measured by its phosphorylation, but not of vascular endothelial growth factor receptor 2. PGE(2) stimulated the EP3 subtype receptor, as deduced by abrogation of EP3 Galpha(i) subunit activity through pertussis toxin. Consistent with this result, in human umbilical venular endothelial cells missing the EP3 receptor, PGE(2) did not phosphorylate FGFR-1. Upon binding to its receptor, PGE(2) initiated an autocrine/paracrine signaling cascade involving the intracellular activation of c-Src, activation of matrix metalloproteinase (predominantly MMP2), which in turn caused the mobilization of membrane-anchored fibroblast growth factor-2 (FGF-2). In fact, in cells unable to release FGF-2 the transfection with both FGFR-1 and EP3 did not result in FGFR-1 phosphorylation in response to PGE(2). Relevance for the FGF2-FGFR-1 system was highlighted by confocal analysis, showing receptor internalization after cell exposure to the prostanoid. ERK1/2 appeared to be the distal signal involved, its phosphorylation being sensitive to either cSrc inhibitor or FGFR-1 blocker. Finally, PGE(2) stimulated cell migration and capillary formation in aortic rings, which were severely reduced by inhibitors of signaling molecules or by receptor antagonist. In conclusion, this study provides evidence for the involvement of FGFR-1 through FGF2 in eliciting PGE(2) angiogenic responses. This signaling pattern is similar to the autocrine-paracrine mechanism which operates in endothelial cells to support neovascular growth

Automated Determination of Nuclear Magnetic Resonance Chemical Shift Perturbations in Ligand Screening Experiments:The PICASSO Web Server

[Image: see text] Nuclear magnetic resonance (NMR) is an effective, commonly used experimental approach to screen small organic molecules against a protein target. A very popular method consists of monitoring the changes of the NMR chemical shifts of the protein nuclei upon addition of the small molecule to the free protein. Multidimensional NMR experiments allow the interacting residues to be mapped along the protein sequence. A significant amount of human effort goes into manually tracking the chemical shift variations, especially when many signals exhibit chemical shift changes and when many ligands are tested. Some computational approaches to automate the procedure are available, but none of them as a web server. Furthermore, some methods require the adoption of a fairly specific experimental setup, such as recording a series of spectra at increasing small molecule:protein ratios. In this work, we developed a tool requesting a minimal amount of experimental data from the user, implemented it as an open-source program, and made it available as a web application. Our tool compares two spectra, one of the free protein and one of the small molecule:protein mixture, based on the corresponding peak lists. The performance of the tool in terms of correct identification of the protein-binding regions has been evaluated on different protein targets, using experimental data from interaction studies already available in the literature. For a total of 16 systems, our tool achieved between 79% and 100% correct assignments, properly identifying the protein regions involved in the interaction

Practical line rasterization for multi-resolution textures

Draping 2D vectorial information over a 3D terrain elevation model is usually performed by real-time rendering to texture. In the case of linear feature representation, there are several specific problems using the texturing approach, specially when using multi-resolution textures. These problems are related to visual quality, aliasing artifacts and rendering performance. In this paper, we address the problems of 2D line rasterization on a multi-resolution texturing engine from a pragmatical point of view; some alternative solutions are presented, compared and evaluated. For each solution we have analyzed the visual quality, the impact on the rendering performance and the memory consumption. The study performed in this work is based on an OpenGL implementation of a clipmap-based multi-resolution texturing system, and is oriented towards the use of inexpensive consumer graphics hardware. 1

Mastoidectomy simulation with combined visual and haptic feedback

Mastoidectomy is one of the most common surgical procedures relating to the petrous bone. In this paper we describe our preliminary results in the realization of a virtual reality mastoidectomy simulator. Our system is designed to work on patient-specific volumetric object models directly derived from 3D CT and MRI images. The paper summarizes the detailed task analysis performed in order to define the system requirements, introduces the architecture of the prototype simulator, and discusses the initial feedback received from selected end users.17-2