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Advances in coarse-grained molecular dynamics (CGMD) simulations have extended the use of computational studies on biological macromolecules and their complexes, as well as the interactions of membrane protein and lipid complexes at a reduced level of representation, allowing longer and larger molecular dynamics simulations. Here, we present a computational platform dedicated to the preparation, running, and analysis of CGMD simulations. The platform is built on a completely revisited version of our Martini coarsE gRained MembrAne proteIn Dynamics (MERMAID) web server, and it integrates this with other three dedicated services. In its current version, the platform expands the existing implementation of the Martini force field for membrane proteins to also allow the simulation of soluble proteins using the Martini and the SIRAH force fields. Moreover, it offers an automated protocol for carrying out the backmapping of the coarse-grained description of the system into an atomistic one.

The translocator protein (TSPO) is a transmembrane protein present across the three domains of life. Its functional quaternary structure consists of one or more subunits. In mice, the dimer-to-monomer equilibrium is shifted in vitro towards the monomer by adding cholesterol, a natural component of mammalian membranes. Here, we present a coarse-grained molecular dynamics study on the mouse protein in the presence of a physiological content and of an excess of cholesterol. The latter turns out to weaken the interfaces of the dimer by clusterizing mostly at the inter-monomeric space and pushing the contact residues apart. It also increases the compactness and the rigidity of the monomer. These two factors might play a role for the experimentally observed incremented stability of the monomeric form with increased content of cholesterol. Comparison with simulations on bacterial proteins suggests that the effect of cholesterol is much less pronounced for the latter than for the mouse protein.

Software implementations of communication protocols connect systems and services by allowing them to exchange data and information. The increasing request of secure connectivity and communication highlights the relevance of automated security testing techniques, such as fuzzing, to be applied during the software development. This paper provides the results of a retrospective analysis conducted on a rapid review about fuzz security testing for software implementations of communication protocols. By extending and generalizing the analysis documented in an existing work, this paper aims at collecting and presenting emerged evidences that: (a) characterize the target software implementations to be tested; (b) investigate what are the existing fuzzing testing techniques; and (c) explore which of them are supported by available tools. Our analysis, based on the examination of 80 scientific sources, conducted us to identify several evidences: (i) the existing fuzz techniques are mainly black-box, require execution samples (e.g., traces) to be applied, use mutation-based data generation strategies, and analyze the responses of the target software implementation under test to detect potential vulnerabilities; (ii) recent trends show that deep-learning techniques are applied in generative fuzz techniques and that protocol state-coverage is used to collect feedback while exercising the system under test; (iii) the detected vulnerabilities are mainly related to memory management and input data validation; and (iv) most of the existing fuzz techniques are not supported by available tools, thus hampering their adoption.

Coarse-grained (CG) modelling with the Martini force field has come of age. By combining a variety of bead types and sizes with a new mapping approach, the newest version of the model is able to accurately simulate large biomolecular complexes at millisecond timescales. In this perspective, we discuss possible applications of the Martini 3 model in drug discovery and development pipelines and highlight areas for future development. Owing to its high simulation efficiency and extended chemical space, Martini 3 has great potential in the area of drug design and delivery. However, several aspects of the model should be improved before Martini 3 CG simulations can be routinely employed in academic and industrial settings. These include the development of automatic parameterisation protocols for a variety of molecule types, the improvement of backmapping procedures, the description of protein flexibility and the development of methodologies enabling efficient sampling. We illustrate our view with examples on key areas where Martini could give important contributions such as drugs targeting membrane proteins, cryptic pockets and protein–protein interactions and the development of soft drug delivery systems.

The increasing demand for complex and distributed software calls for novel software engineering methods and techniques, to create systems able to autonomously adapt to dynamically changing situations. In this paper, we present a framework for engineering requirements for adaptive software systems. The approach, called Tropos4AS, combines goal-oriented concepts and high-variability design methods. The Tropos4AS requirements model can be directly mapped to software prototypes with an agent-oriented architecture which can be executed for requirements validation and refinement. We give a comprehensive description of the framework, with conceptual models, modelling guidelines, and supporting tools. The applicability of the framework to requirements validation and refinement is illustrated through a case study. Two controlled experiments with subjects provide an empirical evaluation of the proposed modelling language, with statistical evidence of the effectiveness of the modelling approach for gathering requirements of adaptive systems.

Modern Web applications offer a rich and unique user experience by taking advantages of the so called Web 2.0 technologies, among which Ajax. Ajax supports the intensive use of asynchronous communication between client-pages and the Web server and it allows on-the-fly manipulations of client-pages content and structure to realize a rich, dynamic and interactive user interface. Correspondingly, new types of faults that cannot be easily revealed by existing Web testing techniques are associated with modern Ajax-based applications. In our previous investigations, we used state-based testing for event sequence generation and it proved to be quite effective in exposing Ajax specific faults. However, the search space of the semantically interacting event sequences is huge, as it can grow exponentially with the event sequence length. In this paper, we apply search-based algorithms, namely hill climbing and simulated annealing, to the problem of generating maximally diverse event sequences of various lengths. In this way, we control the size of the generated test suites, while keeping the included test cases as diverse as possible. We evaluate the performance of the algorithms on two open source Ajax applications.

Aceruloplasminemia is a rare autosomal recessive genetic disease characterized by mild microcytic anemia, diabetes, retinopathy, liver disease, and progressive neurological symptoms due to iron accumulation in pancreas, retina, liver, and brain. The disease is caused by mutations in the Ceruloplasmin (CP) gene that produce a strong reduction or absence of ceruloplasmin ferroxidase activity, leading to an impairment of iron metabolism. Most patients described so far are from Japan. Prompt diagnosis and therapy are crucial to prevent neurological complications since, once established, they are usually irreversible. Here, we describe the largest series of non-Japanese patients with aceruloplasminemia published so far, including 13 individuals from 11 families carrying 13 mutations in the CP gene (7 missense, 3 frameshifts, and 3 splicing mutations), 10 of which are novel. All missense mutations were studied by computational modeling. Clinical manifestations were heterogeneous, but anemia, often but not necessarily microcytic, was frequently the earliest one. This study confirms the clinical and genetic heterogeneity of aceruloplasminemia, a disease expected to be increasingly diagnosed in the Next-Generation Sequencing (NGS) era. Unexplained anemia with low transferrin saturation and high ferritin levels without inflammation should prompt the suspicion of aceruloplasminemia, which can be easily confirmed by low serum ceruloplasmin levels. Collaborative joint efforts are needed to better understand the pathophysiology of this potentially disabling disease.

Migrating legacy applications toward service-oriented systems is a hard task complicated by the lack of appropriate approaches and tools. In this paper, a stepwise approach is proposed to migrate a Java application into an equivalent application composed of a set of Web services invoked by an orchestrator. In each migration step, a portion of the target application is identified and migrated into a Web service. In this approach, the role of testing is central since after each migration step the new service-oriented application is tested with the aim of checking “its equivalence” with the original version. An experiment based on four Java applications has been conducted to tune the approach and evaluate applicability and effort involved in the migration process. The obtained results confirm the viability of the proposed approach and highlight some encountered SOA migration difficulties.

This special section is devoted to a selection of papers that have been originally published in the Proceedings of the International Workshop on Web Quality, Verification and Validation (WQVV) held in Como, Italy, in July 2007. The workshop was part of the Seventh International Conference on Web Engineering (ICWE 2007). These papers investigate different issues of two fundamental “aspects” of quality and dependability of modern Web systems: testing and security. The main contribution of this special section consists in trying to bring the gap between research and “industrial” practice in Web systems. The use of new technologies, tools and methodologies is increasing in the Web and it makes the systems more and more interactive and responsive than in the past. Therefore, limits and problems related to specific aspects of systems quality and dependability are investigated, and new approaches and ideas are proposed to overcome such limitations.

Asynchronous Javascript And XML (AJAX) is a recent technology used to develop rich and dynamic Web applications. Different from traditional Web applications, AJAX applications consist of a single page whose elements are updated dynamically in response to callbacks activated asynchronously by the user or by a server message. On the one hand, AJAX improves the responsiveness and usability of a Web application, but on the other hand, it makes the testing phase more difficult. In this paper, our state-based testing technique, developed to test AJAX-based applications, is compared to existing Web testing techniques, such as white-box and black-box ones. To this aim, an experiment based on two case studies has been conducted to evaluate effectiveness and test effort involved in the compared Web testing techniques. In particular, the capability of each technique to reveal injected faults of different fault categories is analyzed in detail. The associated effort was also measured. The results show that state-based testing is complementary to the existing Web testing techniques and can reveal faults otherwise unnoticed or hard to reveal with the other techniques.