Suppression of beta1,3galactosyltransferase beta3Gal-T5 in cancer cells reduces sialyl-Lewis a and enhances poly-N-acetyllactosamines and sialyl-Lewis x on O-glycans

We investigated the role of beta 3 Gal-T5, a member of the beta 1,3galactosyltransferase (beta 1,3Gal-T) family, in cancer-associated glycosylation, focusing on the expression of sialyl-Lewis a (sLea, the epitope of CA19.9 antigen), poly N-acetyllactosamines, and sialyl-Lewis x (sLex) antigen. A clone permanently expressing an antisense fragment of beta 3Gal-T5 was obtained from the human pancreas adenocarcinoma cell line BxPC3 and characterized. Both beta 1,3Gal-T activity and sLea expression are dramatically impaired in the clone. Analysis of the oligosaccharides synthesized in cells metabolically labelled with tritiated galactose shows that a relevant amount of radioactivity is associated to large O-glycans. Endo-beta-galactosidase mostly releases NeuAc alpha 2-3Gal beta 1-3[Fuc alpha 1-4]GlcNAc beta 1-3Gal and NeuAc alpha 2-3Gal beta 1-3GlcNAc beta 1-3Gal from such O-glycans of BxPC3 membranes, but GlcNAc beta 1-3Gal and type 2 chain oligosaccharides, including NeuAc alpha 2-3Gal beta 1-4[Fuc alpha 1-3]GlcNAc beta 1-3Gal, from those of the antisense clone. Furthermore, BxPC3 cells secrete sLea in the culture media but not sLex, while antisense clone secretes mostly sLex, and accumulation of both antigens is prevented by benzyl-alpha-GalNAc. These data indicate that beta 3Gal-T5 suppression turns synthesis of type 1 chain O-glycans to poly N-acetyllactosamine elongation and termination by sLex. In other cell lines and clones, beta 3Gal-T5 transcript, beta 1,3Gal-T activity, and sLea antigen are also correlated, but quantitatively the relative expression ratios are very different from cell type to cell type. We suggest that beta 3Gal-T5 plays a relevant role in gastrointestinal and pancreatic tissues counteracting the glycosylation pattern associated to malignancy, and is necessary for the synthesis and secretion of CA19.9 antigen, whose expression still depends on multiple interacting factors

Opinion formation models based on game theory

A way to simulate the basic interactions between two individuals with different opinions, in the context of strategic game theory, is proposed. Various games are considered, which produce different kinds of opinion formation dynamics. First, by assuming that all individuals (players) are equals, we obtain the bounded confidence model of continuous opinion dynamics proposed by Deffuant et al. In such a model a tolerance threshold is defined, such that individuals with difference in opinion larger than the threshold can not interact. Then, we consider that the individuals have different inclinations to change opinion and different abilities in convincing the others. In this way, we obtain the so-called ``Stubborn individuals and Orators'' (SO) model, a generalization of the Deffuant et al. model, in which the threshold tolerance is different for every couple of individuals. We explore, by numerical simulations, the dynamics of the SO model, and we propose further generalizations that can be implemented.Comment: 18 pages, 4 figure

Analysis of the commutation error of filtering operators for the double-averaged equations of flows in porous media in a LES formalism

The continuum approach employing porous media models is an attractive solution method in the area of Computational Fluid Dynamics (CFD) simulation of fixed-bed reactors due to its robustness and efficiency. This paper applies the double-averaging methodology to refine the mathematical basis for the continuum approach, opening a way to alleviate its main limitations: space-invariant averaging volume and inaccurate treatment of the porous/non-porous interface. The averaging operator is recast as a general space-time filter and a detailed analysis of commutation errors is performed, using a classic Large Eddy Simulation (LES) formalism. An explicit filtering framework has been implemented in the open-source CFD library OpenFOAM to carry out an a-posteriori evaluation of the unclosed terms appearing in the Double-Averaged Navier-Stokes (DANS) equations also considering a space-varying filter width. Two resolved simulations have been performed. First, the flow around a single, stationary particle has been considered and used to validate derived equations and the filtering procedure. Second, an LES of the turbulent flow in a channel partly occupied with a porous medium has been conducted. The results have been filtered, and the commutation error at the porous-fluid interface has been evaluated and compared to the prediction of two models. The significance of the commutation error terms is also discussed and assessed. Finally, the solver for DANS equations has been developed and used to simulate both of the studied geometries. The magnitude of the error associated with neglecting the commutation errors has been investigated and an LES simulation combined with a porous drag model was performed. Very encouraging results have been obtained indicating that the inaccuracy of the drag closure overshadows the error related to the commutation of operators.Comment: This material has been submitted to Physics of Fluids. It contains 33 pages and 21 Figure

Generating high-efficiency swimming kinematics using hydrodynamic eigenmode decomposition

This paper explores the use of hydrodynamic eigenmode decomposition as a means of generating optimal swimming kinematics of slender three-dimensional bodies. The eigenvectors of the unsteady hydrodynamic system are used as basis functions for the response to external forcing, such as perturbations generated by the deformation of the body. Exploiting the orthogonality of the modes, we show that swimming according to a single appropriately selected hydrodynamic eigenmode results in high-efficiency swimming. To demonstrate this result, we use an inviscid three-dimensional vortex lattice model to investigate the hydrodynamic eigenmodes of a selection of geometries. We find that for all of the body geometries tested, hydrodynamic efficiency far exceeding that of pure heaving or pitching can be achieved. All eigenmodes tested produce high-efficiency motion, as long as the beat frequency is higher than the mode's “cut-in” frequency for thrust generation. The eigenmodes show qualitative similarity to swimming patterns observed in nature and also correspond well to the existing classifications of undulatory and oscillatory swimming. This study demonstrates that the hydrodynamic eigenmode analysis can generate high-efficiency swimming kinematics based only on information about the body and wake geometry, and as such, this method has significant potential for further development and application to autonomous underwater vehicle design

Fast calculation of real fluid properties for steam turbine CFD analysis with the new IAPWS standard on the spline-based table look-Up method (SBTL)

Workshop byl částečně podpořen projektem CZ.1.07/2.3.00/20.0139. Tento projekt je spolufinancován Evropským sociálním fondem a státním rozpočtem České republiky

Robotic-Assisted Surgery Improves the Quality of Total Mesorectal Excision for Rectal Cancer Compared to Laparoscopy: Results of a Case-Controlled Analysis.

BACKGROUND: The use of a robotic surgical system is claimed to allow precise traction and counter-traction, especially in a narrow pelvis. Whether this translates to improvement of the quality of the resected specimen is not yet clear. The aim of the study was to compare the quality of the TME and the short-term oncological outcome between robotic and laparoscopic rectal cancer resections. METHODS: 20 consecutive robotic TME performed in a single institution for rectal cancer (Rob group) were matched 1:2 to 40 laparoscopic resections (Lap group) for gender, body mass index (BMI), and distance from anal verge on rigid proctoscopy. The quality of TME was assessed by 2 blinded and independent pathologists and reported according to international standardized guidelines. RESULTS: Both samples were well matched for gender, BMI (median 25.9 vs. 24.2 kg/m(2), p = 0.24), and level of the tumor (4.1 vs. 4.8 cm, p = 0.20). The quality of the TME was better in the Robotic group (complete TME: 95 vs. 55 %; p = 0.0003, nearly complete TME 5 vs. 37 %; p = 0.04, incomplete TME 0 vs. 8 %, p = 0.09). A trend for lower positive circumferential margin was observed in the Robotic group (10 vs. 25 %, p = 0.1). CONCLUSIONS: These results suggest that robotic-assisted surgery improves the quality of TME for rectal cancer. Whether this translates to better oncological outcome needs to be further investigated