PAX3/FOXO1 fusion gene status is the key prognostic molecular marker in rhabdomyosarcoma and significantly improves current risk stratification.

PURPOSE: To improve the risk stratification of patients with rhabdomyosarcoma (RMS) through the use of clinical and molecular biologic data. PATIENTS AND METHODS: Two independent data sets of gene-expression profiling for 124 and 101 patients with RMS were used to derive prognostic gene signatures by using a meta-analysis. These and a previously published metagene signature were evaluated by using cross validation analyses. A combined clinical and molecular risk-stratification scheme that incorporated the PAX3/FOXO1 fusion gene status was derived from 287 patients with RMS and evaluated. RESULTS: We showed that our prognostic gene-expression signature and the one previously published performed well with reproducible and significant effects. However, their effect was reduced when cross validated or tested in independent data and did not add new prognostic information over the fusion gene status, which is simpler to assay. Among nonmetastatic patients, patients who were PAX3/FOXO1 positive had a significantly poorer outcome compared with both alveolar-negative and PAX7/FOXO1-positive patients. Furthermore, a new clinicomolecular risk score that incorporated fusion gene status (negative and PAX3/FOXO1 and PAX7/FOXO1 positive), Intergroup Rhabdomyosarcoma Study TNM stage, and age showed a significant increase in performance over the current risk-stratification scheme. CONCLUSION: Gene signatures can improve current stratification of patients with RMS but will require complex assays to be developed and extensive validation before clinical application. A significant majority of their prognostic value was encapsulated by the fusion gene status. A continuous risk score derived from the combination of clinical parameters with the presence or absence of PAX3/FOXO1 represents a robust approach to improving current risk-adapted therapy for RMS.

Mobile Communications within the European Union: The Role of Location in the Evolution and Forecasting of the Diffusion Process

In the European Union, the importance of mobile communications was realized early on. The process of mobile communications becoming ubiquitous has taken time, as the innovation of mobile communications diffused into the society. The aim of this study is to find out how the evolution and spatial patterns of the diffusion of mobile communications within the European Union could be taken into account in forecasting the diffusion process. There is relatively lot of research of innovation diffusion on the individual (micro) andthe country (macro) level, if compared to the territorial level. Territorial orspatial diffusion refers either to the intra-country or inter-country diffusionof an innovation. In both settings, the dif- fusion of a technological innovation has gained scarce attention. This study adds knowledge of the diffusion between countries, focusing especially on the role of location in this process. The main findings of the study are the following: The penetration rates of the European Union member countries have become more even in the period of observation, from the year 1981 to 2000. The common digital GSM system seems to have hastened this process. As to the role of location in the diffusion process, neighboring countries have had similar diffusion processes. They can be grouped into three, the Nordic countries, the central and southern European countries, and the remote southern European countries. The neighborhood effect is also domi- nating in thegravity model which is used for modeling the adoption timing of the countries. The subsequent diffusion within a country, measured by the logistic model in Finland, is af- fected positively by its economic situation, and it seems to level off at some 92 %. Considering the launch of future mobile communications systemsusing a common standard should implicate an equal development between the countries. The launching time should be carefully selected as the diffusion is probably delayed in economic downturns. The location of a country, measured by distance, can be used in forecasting the adoption and diffusion. Fi- nally, the result of penetration rates becoming more even implies that in a relatively homoge- nous set of countries, such as the European Union member countries, the estimated final pene- tration of a single country can be used for approximating the penetration of the others. The estimated eventual penetration of Finland, some 92 %, should thus also be the eventual level for all the European Union countries and for the European Union as a whole.

Effect of Mechanical and Geometric Mismatching on Fatigue and Damage of Welded Joints

The future of high technology welded constructions will be characterised by higher strength materials and improved weld quality with respect to fatigue resistance. The expected implementation of high quality high strength steel welds will require that more attention be given to the issues of crack initiation and mechanical mismatching. Experiments and finite element analyses were performed within the framework of continuum damage mechanics to investigate the effect of mismatching of welded joints on void nucleation and coalescence during monotonic loading. It was found that the damage of undermatched joints mainly occurred in the sandwich layer and the damageresistance of the joints decreases with the decrease of the sandwich layer width. The damage of over-matched joints mainly occurred in the base metal adjacent to the sandwich layer and the damage resistance of the joints increases with thedecrease of the sandwich layer width. The mechanisms of the initiation of the micro voids/cracks were found to be cracking of the inclusions or the embrittled second phase, and the debonding of the inclusions from the matrix. Experimental fatigue crack growth rate testing showed that the fatigue life of under-matched central crack panel specimens is longer than that of over-matched and even-matched specimens. Further investigation by the elastic-plastic finite element analysis indicated that fatigue crack closure, which originated from the inhomogeneousyielding adjacent to the crack tip, played an important role in the fatigue crack propagation. The applicability of the J integral concept to the mismatched specimens with crack extension under cyclic loading was assessed. The concept of fatigue class used by the International Institute of Welding was introduced in the parametric numerical analysis of several welded joints. The effect of weld geometry and load condition on fatigue strength of ferrite-pearlite steel joints was systematically evaluated based on linear elastic fracture mechanics. Joint types included lap joints, angle joints and butt joints. Various combinations of the tensile and bending loads were considered during the evaluation with the emphasis focused on the existence of both root and toe cracks. For a lap joint with asmall lack-of-penetration, a reasonably large weld leg and smaller flank angle were recommended for engineering practice in order to achieve higher fatigue strength. It was found that the fatigue strength of the angle joint depended strongly on the location and orientation of the preexisting crack-like welding defects, even if the joint was welded with full penetration. It is commonly believed that the double sided butt welds can have significantly higher fatigue strength than that of a single sided welds, but fatigue crack initiation and propagation can originate from the weld root if the welding procedure results in a partial penetration. It is clearly shown that the fatigue strength of the butt joint could be improved remarkably by ensuring full penetration. Nevertheless, increasing the fatigue strength of a butt joint by increasing the size of the weld is an uneconomical alternative.

Implementación de una herramienta de gestión de cambios dentro del ERP eSengoⓇ, e introducción al ERP eSengoⓇ y al framework SherpaBeansⓇ

Esta memoria trata sobre la implementación de un gestor de peticiones de cambio, basado en los estándares definidos por ITIL. Este gestor se implementa dentro del ERP eSengo, desarrollado por Isencia S.L. También se hace una breve explicación sobre los submódulos que han sido necesarios y los estados de flujo de ejecución del gestor. Además se explican características sobre el ERP eSengo y sobre la plataforma basada en Java Beans, SherpaBeans, también desarrollada por Isencia, a parte de enumerar las tecnologías que esta plataforma utiliza.

Evaluating the Trabecular Micro-Bypass Stent Combined with Phacoemulsification Compared to Phacoemulsification Alone.

Aim: The aim of this study was to assess the effect of iStent (trabecular micro-bypass stent) implantation in combination with phacoemulsification on IOP and glaucoma medications and to compare this to the outcome of phacoemulsification alone. Patients and Methods: A retrospective consecutive comparative review was undertaken. 131 eyes with ocular hypertension and medically controlled glaucoma underwent phacoemulsification alone (n = 78 group I) or combined with gonioscopic-guided implantation of one iStent (n = 31, group II) or two iStents (n = 22, group III). Patients were assessed at postoperative weeks 1, 3 and 6, and months 3 and 6. Pre- and post-operative measures included visual acuity, IOP and glaucoma medications. Results: Post-operatively at 6 months, mean IOP decreased from 16.3 mmHg to 14.2 mmHg in group I (p < 0.01), from 16.7 mmHg to 15.1 mmHg in group II (p < 0.16) and from 17.0 to 13.8 in group III (p = 0.05). Mean glaucoma medication decreased from 1.9 to 1.6 in group I (8 %, p = 0.12), from 2.5 to 0.8 in group II (27 %, p = 0.04), and from 2.1 to 1.0 in group III (45 %, p < 0.01). Conclusions: iStent implantation resulted in similar IOP reduction to phacoemulsification alone but achieved a significantly greater reduction in glaucoma medications. This may improve compliance and quality of life, and reduce health care costs in patients with early to moderate glaucoma.

Semantic Web applications: a framework for industry and business exploitation – What is needed for the adoption of the Semantic Web from the market and industry

In recent years, Semantic Web (SW) research has resulted in significant outcomes. Various industries have adopted SW technologies, while the ‘deep web’ is still pursuing the critical transformation point, in which the majority of data found on the deep web will be exploited through SW value layers. In this article we analyse the SW applications from a ‘market’ perspective. We are setting the key requirements for real-world information systems that are SW-enabled and we discuss the major difficulties for the SW uptake that has been delayed. This article contributes to the literature of SW and knowledge management providing a context for discourse towards best practices on SW-based information systems.

A web ontologies framework for digital rights management

In order to improve the management of copyright in the Internet, known as Digital Rights Management, there is the need for a shared language for copyright representation. Current approaches are based on purely syntactic solutions, i.e. a grammar that defines a rights expression language. These languages are difficult to put into practise due to the lack of explicit semantics that facilitate its implementation. Moreover, they are simple from the legal point of view because they are intended just to model the usage licenses granted by content providers to end-users. Thus, they ignore the copyright framework that lies behind and the whole value chain from creators to end-users. Our proposal is to use a semantic approach based on semantic web ontologies. We detail the development of a copyright ontology in order to put this approach into practice. It models the copyright core concepts for creation, rights and the basic kinds of actions that operate on content. Altogether, it allows building a copyright framework for the complete value chain. The set of actions operating on content are our smaller building blocks in order to cope with the complexity of copyright value chains and statements and, at the same time, guarantee a high level of interoperability and evolvability. The resulting copyright modelling framework is flexible and complete enough to model many copyright scenarios, not just those related to the economic exploitation of content. The ontology also includes moral rights, so it is possible to model this kind of situations as it is shown in the included example model for a withdrawal scenario. Finally, the ontology design and the selection of tools result in a straightforward implementation. Description Logic reasoners are used for license checking and retrieval. Rights are modelled as classes of actions, action patterns are modelled also as classes and the same is done for concrete actions. Then, to check if some right or license grants an action is reduced to check for class subsumption, which is a direct functionality of these reasoners.

Collaborative explicit plasticity framework: a conceptual scheme for the generation of plastic and group-aware user interfaces

The advent of new advances in mobile computing has changed the manner we do our daily work, even enabling us to perform collaborative activities. However, current groupware approaches do not offer an integrating and efficient solution that jointly tackles the flexibility and heterogeneity inherent to mobility as well as the awareness aspects intrinsic to collaborative environments. Issues related to the diversity of contexts of use are collected under the term plasticity. A great amount of tools have emerged offering a solution to some of these issues, although always focused on individual scenarios. We are working on reusing and specializing some already existing plasticity tools to the groupware design. The aim is to offer the benefits from plasticity and awareness jointly, trying to reach a real collaboration and a deeper understanding of multi-environment groupware scenarios. In particular, this paper presents a conceptual framework aimed at being a reference for the generation of plastic User Interfaces for collaborative environments in a systematic and comprehensive way. Starting from a previous conceptual framework for individual environments, inspired on the model-based approach, we introduce specific components and considerations related to groupware.

First systematic chemical profiling of cocaine police seizures in Finland in the framework of an intelligence-led approach

For the first time in Finland, the chemical profiling of cocaine specimens was performed at the National Bureau of Investigation (NBI). The main goals were to determine the chemical composition of cocaine specimens sold in the Finnish market and to study the distribution networks of cocaine in order to provide intelligence related to its trafficking. An analytical methodology enabling through one single GC-MS injection the determination of the added cutting agents (adulterants and diluents), the cocaine purity and the chemical profile (based on the major and minor alkaloids) for each specimen was thus implemented and validated. The methodology was found to be efficient for the discrimination between specimens coming from the same source and specimens coming from different sources. The results highlighted the practical utility of the chemical profiling, especially for supporting the investigation through operational intelligence and improving the knowledge related to the cocaine trafficking through strategic intelligence.

A formin-nucleated actin aster concentrates cell wall hydrolases for cell fusion in fission yeast.

Cell-cell fusion is essential for fertilization. For fusion of walled cells, the cell wall must be degraded at a precise location but maintained in surrounding regions to protect against lysis. In fission yeast cells, the formin Fus1, which nucleates linear actin filaments, is essential for this process. In this paper, we show that this formin organizes a specific actin structure-the actin fusion focus. Structured illumination microscopy and live-cell imaging of Fus1, actin, and type V myosins revealed an aster of actin filaments whose barbed ends are focalized near the plasma membrane. Focalization requires Fus1 and type V myosins and happens asynchronously always in the M cell first. Type V myosins are essential for fusion and concentrate cell wall hydrolases, but not cell wall synthases, at the fusion focus. Thus, the fusion focus focalizes cell wall dissolution within a broader cell wall synthesis zone to shift from cell growth to cell fusion.

A logic programming framework for possibilistic argumentation: formalization and logical properties

In the last decade defeasible argumentation frameworks have evolved to become a sound setting to formalize commonsense, qualitative reasoning. The logic programming paradigm has shown to be particularly useful for developing different argument-based frameworks on the basis of different variants of logic programming which incorporate defeasible rules. Most of such frameworks, however, are unable to deal with explicit uncertainty, nor with vague knowledge, as defeasibility is directly encoded in the object language. This paper presents Possibilistic Logic Programming (P-DeLP), a new logic programming language which combines features from argumentation theory and logic programming, incorporating as well the treatment of possibilistic uncertainty. Such features are formalized on the basis of PGL, a possibilistic logic based on G¨odel fuzzy logic. One of the applications of P-DeLP is providing an intelligent agent with non-monotonic, argumentative inference capabilities. In this paper we also provide a better understanding of such capabilities by defining two non-monotonic operators which model the expansion of a given program P by adding new weighed facts associated with argument conclusions and warranted literals, respectively. Different logical properties for the proposed operators are studied

Insertion of a malE B-Galactosidase fusion protein into the envelope of Escherichia coli disrupts biogenesis of outer membrane proteins and processing of inner membrane proteins

The synthesis of a membrane-bound MalE ,B-galactosidase hybrid protein, when induced by growth of Escherichia coli on maltose, leads to inhibition of cell division and eventually a reduced rate of mass increase. In addition, the relative rate of synthesis of outer membrane proteins, but not that of inner membrane proteins, was reduced by about 50%o. Kinetic experiments demonstrated that this reduction coincided with the period of maximum synthesis of the hybrid protein (and another maltose-inducible protein, LamB). The accumulation of this abnormal protein in the envelope therefore appeared specifically to inhibit the synthesis, the assembly of outer membrane proteins, or both, indicating that the hybrid protein blocks some export site or causes the sequestration of some limiting factor(s) involved in the export process. Since the MalE protein is normally located in the periplasm, the results also suggest that the synthesis of periplasmic and outer membrane proteins may involve some steps in common. The reduced rate of synthesis of outer membrane proteins was also accompanied by the accumulation in the envelope of at least one outer membrane protein and at least two inner membrane proteins as higher-molecular-weight forms, indicating that processing (removal of the N-terminal signal sequence) was also disrupted by the presence of the hybrid protein. These results may indicate that the assembly of these membrane proteins is blocked at a relatively late step rather than at the level of primary recognition of some site by the signal sequence. In addition, the results suggest that some step common to the biogenesis of quite different kinds of envelope protein is blocked by the presence of the hybrid protein.