Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer

Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.     

Lithium disilicate glass produced at high pressure: Characterization of structural,thermal and mechanical properties

In this work, high-density lithium disilicate (LS₂) vitreous systems were produced by melting and quenching under high pressure (7.7 GPa) following two distinct experimental routes. In the first case, LS₂ glass was remelted at 7.7 GPa and 1600°C and, then, quenched. In the second case, a stoichiometric mixture of precursor oxides (Li₂O and SiO₂) was melted at 1600°C and 7.7 GPa before quenching. A reference LS₂ glass sample was produced at atmospheric pressure using conventional melting and quenching procedure. The samples were characterized by X-ray diffraction, differential thermal analysis, and instrumented ultramicro hardness measurements. X-ray diffraction confirmed that all samples were amorphous and thermal analysis suggests that different glassy structures were produced depending on the route of synthesis. Hardness and elastic modulus of the glasses produced under high pressure were higher than those of the reference glass, reflecting the irreversible densification effect induced by the high-pressure processing.     

Software reuse: The Brazilian industry scenario

This paper aims at identifying some of the key factors in adopting an organization-wide software reuse program. The factors are derived from practical experience reported by industry professionals, through a survey involving 57 Brazilian small, medium and large software organizations. Some of them produce software with commonality between applications, and have mature processes, while others successfully achieved reuse through isolated, ad hoc efforts. The paper compiles the answers from the survey participants, showing which factors were more associated with reuse success. Based on this relationship, a guide is presented, pointing out which factors should be more strongly considered by small, medium and large organizations attempting to establish a reuse program.     

Estimating vulnerability to risks: an application in a biofuel supply chain

In the present work, we propose a theoretical model to identify and prioritize risks involved in a biofuel supply chain. We adopt a set of indicators associated with determinant factors of the supply chain to identify risks that are characterized through a risk matrix. We consider the five largest world biodiesel producers and included China due to its global market importance and potential impacts of its growth on the environment and society. To determine the impacts and the probability of occurrence of risks, we use the Canberra distance, as metrics. To facilitate the analysis and interpretation, a convenient manner is to express the results in terms of matrices. To exemplify the potentiality of the scheme and for the sake of simplicity, a more comprehensive discussion is focused on the Brazilian case, restricted to the Technology and Innovation, and Integration, Logistics and Infrastructure determining factors (dimensions) of the biodiesel supply chain. Concerning these determining factors, the Brazilian biodiesel chain shows strong vulnerability when compared with developed and developing countries, despite that the evolution of the data over recent years indicates small improvements in Integration, Logistics and Infrastructure dimension. Although in this work the calculations are restricted to the Canberra distance, the present approach may be applied to other distances to compare or validate the results. This work presents a contribution to model vulnerability to risks, providing to policy makers and stakeholders a tool to design, analyze and improve sustainability system by measuring its risks. The study of the contribution of each indicator suggests corrections to be taken and which indicators should be prioritized.     

A declarative two-level framework to specify and verify workflow and authorization policies in service-oriented architectures

The specification of distributed service-oriented applications spans several levels of abstraction, e.g., the protocol for exchanging messages, the set of interface functionalities, the types of the manipulated data, the workflow, the access policy, etc. Many (even executable) specification languages are available to describe each level in separation. However, these levels may interact in subtle ways (for example, the control flow may depend on the values of some data variables) so that a precise abstraction of the application amounts to more than the sum of its per level components. This problem is even more acute in the design phase when automated analysis techniques may greatly help the difficult task of building “correct” applications faced by designers. To alleviate this kind of problems, this paper introduces a framework for the formal specification and automated analysis of distributed service-oriented applications in two levels: one for the workflow and one for the authorization policies. The former allows one to precisely describe the control and data parts of an application with their mutual dependencies. The latter focuses on the specification of the criteria for granting or denying third-party applications the possibility to access shared resources or to execute certain interface functionalities. These levels can be seen as abstractions of one or of several levels of specification mentioned above. The novelty of our proposal is the possibility to unambiguously specify the—often subtle—interplay between the workflow and policy levels uniformly in the same framework. Additionally, our framework allows us to define and investigate verification problems for service-oriented applications (such as executability and invariant checking) and give sufficient conditions for their decidability. These results are non-trivial because their scope of applicability goes well beyond the case of finite state spaces allowing for applications manipulating variables ranging over infinite domains. As proof of concept, we show the suitability and flexibility of our approach on two quite different examples inspired by industrial case studies.     

Combination of convex theories: Modularity,deduction completeness,and explanation

Decision procedures are key components of theorem provers and constraint satisfaction systems. Their modular combination is of prime interest for building efficient systems, but their effective use is often limited by poor interface capabilities, when such procedures only provide a simple “sat/unsat” answer. In this paper, we develop a framework to design cooperation schemas between such procedures while maintaining modularity of their interfaces. First, we use the framework to specify and prove the correctness of classic combination schemas by Nelson–Oppen and Shostak. Second, we introduce the concept of deduction complete satisfiability procedures, we show how to build them for large classes of theories, then we provide a schema to modularly combine them. Third, we consider the problem of modularly constructing explanations for combinations by re-using available proof-producing procedures for the component theories.     

A systematic mapping study of software product lines testing

Context

In software development, Testing is an important mechanism both to identify defects and assure that completed products work as specified. This is a common practice in single-system development, and continues to hold in Software Product Lines (SPL). Even though extensive research has been done in the SPL Testing field, it is necessary to assess the current state of research and practice, in order to provide practitioners with evidence that enable fostering its further development.

Objective

This paper focuses on Testing in SPL and has the following goals: investigate state-of-the-art testing practices, synthesize available evidence, and identify gaps between required techniques and existing approaches, available in the literature.

Method

A systematic mapping study was conducted with a set of nine research questions, in which 120 studies, dated from 1993 to 2009, were evaluated.

Results

Although several aspects regarding testing have been covered by single-system development approaches, many cannot be directly applied in the SPL context due to specific issues. In addition, particular aspects regarding SPL are not covered by the existing SPL approaches, and when the aspects are covered, the literature just gives brief overviews. This scenario indicates that additional investigation, empirical and practical, should be performed.

Conclusion

The results can help to understand the needs in SPL Testing, by identifying points that still require additional investigation, since important aspects regarding particular points of software product lines have not been addressed yet.