Expression of RCAS1 Correlates with Urothelial Bladder Cancer Malignancy

RCAS1 is a protein that participates in regulation of the tumor microenvironment and its immune responses, all in order to evade the immune system. The aim of this study was to analyze RCAS1 expression in urothelial bladder cancer cells (and in fibroblasts and macrophages of the tumor stroma) and its relationship with the histological pattern of malignancy. Eighty-three postcystectomy patients were enrolled. We analyzed the histological maturity (grade), progress (pT stage), tissue invasion type (TIT), nonclassic differentiation number (NDN), and the ability to metastasize (pN). The expression of RCAS1 protein was analyzed by immunohistochemistry. Indicators of histological malignancy were observed solely in association with the RCAS1 expression in cells in the border parts (BPs) of the tumor. Histological malignancy of the tumor, indicated by the pT and pN, and metastasis-free survival time, correlated significantly with RCAS1 expression in tumor neoplastic cells, whereas malignancy determined by grade, TIT, and NDN correlated with RCAS1 expression in fibroblasts and macrophages in the tumor microenvironment. These findings suggest that the increased RCAS1 expression depends on its cellular source and that RCAS1 expression itself is a component of various signaling pathways. The immune escape occurs within the tumor BPs, where the increase in the RCAS1 expression occurs within tumor cells and stromal cells in its microenvironment. We conclude that the histological pattern of tumor malignancy, indicated by grade, TIT, NDN, pT, and pN is a morphological indicator of immune escape.     

On sorting triangles in a delaunay tessellation

In a two-dimensional Delaunay-triangulated domain, there exists a partial ordering of the triangles (with respect to a vertex) that is consistent with the two-dimensional visibility of the triangles from that vertex. An equivalent statement is that a polygon that is star-shaped with respect to a given vertex can be extended, one triangle at a time, until it includes the entire domain. Arbitrary planar triangulations do not possess this useful property which allows incremental processing of the triangles.This work was partially supported by the National Science Foundation's US-Italy Collaborative Research Program under Grant INT-8714578 and Information, Robotics, and Intelligent Research Grant IRI-8704781.     

The Computational Complexity of One-Dimensional Sandpiles

We prove that the one-dimensional sandpile prediction problem is in LOGDCFL, a subset of AC¹. The previously best known upper bound on the ACⁱ-scale was AC². Furthermore, we prove that the one-dimensional sandpile prediction problem is hard for TC⁰ and thus not in AC^1-ε for any constant ε > 0.     

Immobilization of an endopectinlyase on γ-alumina: Study of factors influencing the biocatalytic matrix stability

Endopectinlyase (EC 4.2.2.10) from Aspergillus japonicus was immobilized on to γ-alumina. Adsorption performed at pH 5·0 and a subsequent cross-linking phase using 0·1% glutaraldehyde were the chosen immobilization conditions. The comparison between the main biochemical parameters of the immobilized and free form of the enzyme showed that the immobilization procedure used did not affect the enzyme biochemical properties. The interactions between the carrier and the enzyme are essentially secondary bonding. In fact they depend on the pH and on the presence of phosphate ions in the medium. A tentative chemical model of the biocatalytic matrix thus obtained is proposed.     

Reward only is not enough: Evaluating and improving the fairness policy of the P2P file sharing network eMule/eDonkey

Limiting the threat of free-riding behavior is an important design issue for peer-to-peer (P2P) file sharing networks. However, the fairness policy that rewards contributors with credit in one of the most popular P2P file sharing networks, eMule/eDonkey, hasn’t been thoroughly studied. In this paper, motivated by our experiments with the eMule/eDonkey network, we firstly theoretically analyze the content exchange process with credit in eMule/eDonkey and then verify the mathematical model by an agent-based simulation. Both the numerical and simulation-based results confirm our discovery in the experiments that eMule/eDonkey’s local credit strategy can not provide enough fairness as it doesn’t explicitly punish free-riders. To overcome this drawback, we propose a new free-riding control scheme, which can simply maintain the current credit local structure and take advantage of the credit policy. Extensive numerical evaluation and simulation indicate that this scheme significantly improves system fairness.     

Thermodynamic analysis of the refining of technical boron nitride

The efficiency of the process of refining technical boron nitride was assessed based on calculations of the chemical equilibrium in the B-N-O-C-Cl-H system. Three refining mixtures, CCl₄ + H₂, CCl₄ + NH₃ and CHCl₃ + NH₃, were considered. The analysis indicates that the use of ammonia-containing mixtures is more convenient, a lower residual oxygen content, lower contamination of the product by carbon and a better overall boron balance emerging. The calculations of the equilibrium composition of the solid phase enabled suitable technological conditions of the refining process (temperature and starting composition of the gaseous phase) to be established. The calculated results are compared with experimental data, and some observed differences are discussed.     

The Landscape of microRNAs in βCell: Between Phenotype Maintenance and Protection

Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia mainly due to pancreatic β cell death and/or dysfunction, caused by several types of stress such as glucotoxicity, lipotoxicity and inflammation. Different patho-physiological mechanisms driving β cell response to these stresses are tightly regulated by microRNAs (miRNAs), a class of negative regulators of gene expression, involved in pathogenic mechanisms occurring in diabetes and in its complications. In this review, we aim to shed light on the most important miRNAs regulating the maintenance and the robustness of β cell identity, as well as on those miRNAs involved in the pathogenesis of the two main forms of diabetes mellitus, i.e., type 1 and type 2 diabetes. Additionally, we acknowledge that the understanding of miRNAs-regulated molecular mechanisms is fundamental in order to develop specific and effective strategies based on miRNAs as therapeutic targets, employing innovative molecules.     

Connexin 43 and Connexin 26 Involvement in the Ponatinib-Induced Cardiomyopathy: Sex-Related Differences in a Murine Model

Cardiac connexins (Cxs) are proteins responsible for proper heart function. They form gap junctions that mediate electrical and chemical signalling throughout the cardiac system, and thus enable a synchronized contraction. Connexins can also individually participate in many signal transduction pathways, interacting with intracellular proteins at various cellular compartments. Altered connexin expression and localization have been described in diseased myocardium and the aim of this study is to assess the involvement of Cx43, Cx26, and some related molecules in ponatinib-induced cardiac toxicity. Ponatinib is a new multi-tyrosine kinase inhibitor that has been successfully used against human malignancies, but its cardiotoxicity remains worrisome. Therefore, understanding its signaling mechanism is important to adopt potential anti cardiac damage strategies. Our experiments were performed on hearts from male and female mice treated with ponatinib and with ponatinib plus siRNA-Notch1 by using immunofluorescence, Western blotting, and proteomic analyses. The altered cardiac function and the change in Cxs expression observed in mice after ponatinib treatment, were results dependent on the Notch1 pathway and sex. Females showed a lower susceptibility to ponatinib than males. The downmodulation of cardiac Cx43, Cx26 and miR-122, high pS368-Cx43 phosphorylation, cell viability and survival activation could represent some of the female adaptative/compensatory reactions to ponatinib cardiotoxicity.     

Structural optimization strategies to design green products

This paper addresses the need for a structured approach to environmental assessment and improvement. We propose a computer-aided methodology, named Eco-OptiCAD, based on the integration of Structural Optimization and Life Cycle Assessment (LCA) tools. Eco-OptiCAD supports the designer during product development, highlighting when and where the core of the environmental impact lies. Furthermore, it provides effective tools to address such impacts, improving the original product, while ensuring structural and functional requirements. It foresees the synergic use of (1) virtual prototyping tools, such as 3D CAD, Finite Element Analysis (FEA) and Structural optimization, (2) function modeling methodology and (3) Life Cycle Assessment (LCA) tools. The kernel of the methodology is constituted by a set of optimization strategies and a module, named Life Cycle Mapping (LCM). In particular, we have conceived ten optimization strategies converting environmental objectives and constraints into structural and geometrical parameters. They enable the designer to generate alternative green scenarios according to the triad shape–material–production. The LCM tool has been specifically developed to easily trace the growth of environmental impacts throughout the product's life cycle and allow the user to focus his effort on the most relevant aspects. Thanks to the integration of the structural optimizer with an LCA map, the designer becomes aware of the consequences that each change in the geometry, the material or the manufacturing process will produce on the environmental impact of the product throughout its life cycle. With a complete view of the product life cycle, the designer can improve a single phase, while retaining a global perspective; thus avoiding the possibility of gaining a local green improvement at the cost of a global increase in environmental impacts.     

Time-domain Analysis of Laboratory Experiments on the Transient Pressure Damping in a Leaky Polymeric Pipe

Water Resources Management - The pressure damping occurring in pressurized pipes with a leak during transients has been examined as a diagnostic tool – the so-called transient damping method...