A UML profile for the OBO relation ontology

Background: Ontologies have increasingly been used in the biomedical domain, which has prompted the emergence of different initiatives to facilitate their development and integration. The Open Biological and Biomedical Ontologies (OBO) Foundry consortium provides a repository of life-science ontologies, which are developed according to a set of shared principles. This consortium has developed an ontology called OBO Relation Ontology aiming at standardizing the different types of biological entity classes and associated relationships. Since ontologies are primarily intended to be used by humans, the use of graphical notations for ontology development facilitates the capture, comprehension and communication of knowledge between its users. However, OBO Foundry ontologies are captured and represented basically using text-based notations. The Unified Modeling Language (UML) provides a standard and widely-used graphical notation for modeling computer systems. UML provides a well-defined set of modeling elements, which can be extended using a built-in extension mechanism named Profile. Thus, this work aims at developing a UML profile for the OBO Relation Ontology to provide a domain-specific set of modeling elements that can be used to create standard UML-based ontologies in the biomedical domain. Results: We have studied the OBO Relation Ontology, the UML metamodel and the UML profiling mechanism. Based on these studies, we have proposed an extension to the UML metamodel in conformance with the OBO Relation Ontology and we have defined a profile that implements the extended metamodel. Finally, we have applied the proposed UML profile in the development of a number of fragments from different ontologies. Particularly, we have considered the Gene Ontology (GO), the PRotein Ontology (PRO) and the Xenopus Anatomy and Development Ontology (XAO). Conclusions: The use of an established and well-known graphical language in the development of biomedical ontologies provides a more intuitive form of capturing and representing knowledge than using only text-based notations. The use of the profile requires the domain expert to reason about the underlying semantics of the concepts and relationships being modeled, which helps preventing the introduction of inconsistencies in an ontology under development and facilitates the identification and correction of errors in an already defined ontology.

Systematic Management of Variability in UML-based Software Product Lines

This paper presents SMarty, a variability management approach for UML-based software product lines (PL). SMarty is supported by a UML profile, the SMartyProfile, and a process for managing variabilities, the SMartyProcess. SMartyProfile aims at representing variabilities, variation points, and variants in UML models by applying a set of stereotypes. SMartyProcess consists of a set of activities that is systematically executed to trace, identify, and control variabilities in a PL based on SMarty. It also identifies variability implementation mechanisms and analyzes specific product configurations. In addition, a more comprehensive application of SMarty is presented using SEI's Arcade Game Maker PL. An evaluation of SMarty and related work are discussed.

QoS-aware model driven architecture through the UML and CIM

The specification of Quality of Service (QoS) constraints over software design requires measures that ensure such requirements are met by the delivered product. Achieving this goal is non-trivial, as it involves, at least, identifying how QoS constraint specifications should be checked at the runtime. In this paper we present an implementation of a Model Driven Architecture (MDA) based framework for the runtime monitoring of QoS properties. We incorporate the UML2 superstructure and the UML profile for Quality of Service to provide abstract descriptions of component-and-connector systems. We then define transformations that refine the UML2 models to conform with the Distributed Management Taskforce (DMTF) Common Information Model (CIM) (Distributed Management Task Force Inc. 2006), a schema standard for management and instrumentation of hardware and software. Finally, we provide a mapping the CIM metamodel to a .NET-based metamodel for implementation of the monitoring infrastructure utilising various .NET features including the Windows Management Instrumentation (WMI) interface.

Visual IMML: um perfil UML para a modelagem de interfaces de usuário

The software development processes proposed by the most recent approaches in Software Engineering make use old models. UML was proposed as the standard language for modeling. The user interface is an important part of the software and has a fundamental importance to improve its usability. Unfortunately the standard UML does not offer appropriate resources to model user interfaces. Some proposals have already been proposed to solve this problem: some authors have been using models in the development of interfaces (Model Based Development) and some proposals to extend UML have been elaborated. But none of them considers the theoretical perspective presented by the semiotic engineering, that considers that, through the system, the designer should be able to communicate to the user what he can do, and how to use the system itself. This work presents Visual IMML, an UML Profile that emphasizes the aspects of the semiotic engineering. This Profile is based on IMML, that is a declarative textual language. The Visual IMML is a proposal that aims to improve the specification process by using a visual modeling (using diagrams) language. It proposes a new set of modeling elements (stereotypes) specifically designed to the specification and documentation of user interfaces, considering the aspects of communication, interaction and functionality in an integrated manner

A Model-Based Development and Verification Framework for Distributed System-on-Chip Architecture

The capabilities and thus, design complexity of VLSI-based embedded systems have increased tremendously in recent years, riding the wave of Moore’s law. The time-to-market requirements are also shrinking, imposing challenges to the designers, which in turn, seek to adopt new design methods to increase their productivity. As an answer to these new pressures, modern day systems have moved towards on-chip multiprocessing technologies. New architectures have emerged in on-chip multiprocessing in order to utilize the tremendous advances of fabrication technology. Platform-based design is a possible solution in addressing these challenges. The principle behind the approach is to separate the functionality of an application from the organization and communication architecture of hardware platform at several levels of abstraction. The existing design methodologies pertaining to platform-based design approach don’t provide full automation at every level of the design processes, and sometimes, the co-design of platform-based systems lead to sub-optimal systems. In addition, the design productivity gap in multiprocessor systems remain a key challenge due to existing design methodologies. This thesis addresses the aforementioned challenges and discusses the creation of a development framework for a platform-based system design, in the context of the SegBus platform - a distributed communication architecture. This research aims to provide automated procedures for platform design and application mapping. Structural verification support is also featured thus ensuring correct-by-design platforms. The solution is based on a model-based process. Both the platform and the application are modeled using the Unified Modeling Language. This thesis develops a Domain Specific Language to support platform modeling based on a corresponding UML profile. Object Constraint Language constraints are used to support structurally correct platform construction. An emulator is thus introduced to allow as much as possible accurate performance estimation of the solution, at high abstraction levels. VHDL code is automatically generated, in the form of “snippets” to be employed in the arbiter modules of the platform, as required by the application. The resulting framework is applied in building an actual design solution for an MP3 stereo audio decoder application.

Framework orientado a objetos para projeto de hardware e software embarcados para sistemas tempo-real

A crescente complexidade dos sistemas tempo-real embarcados demanda novas metodologias e ferramentas para gerenciar os problemas de projeto, análise, integração e validação de sistemas complexos. Este trabalho aborda o tema co-projeto de sistemas tempo-real embarcados, propondo estratégias para a integração das fases iniciais de modelagem de um sistema tempo-real embarcado com as fases subseqüentes do projeto, como a implementação do software e do hardware. É proposto um framework orientado a objetos que permite a criação de modelos orientados a objetos de sistemas tempo-real embarcados, utilizando conceitos temporais similares aos propostos em UML-RT (ou mais especificamente no UML Profile for Schedulability, Performance and Time). É proposta uma estratégia de mapeamento dos requisitos temporais dos diagramas UMLRT para uma interface de programação (API) baseada na “Especificação Tempo-Real para Java” (Real-Time Specification for Java ou RTSJ), a qual pode ser executada tanto em software – em programas RTSJ executando em máquinas virtuais Java (JVM) tempo-real – ou em hardware – em processadores Java Tempo-Real. Para permitir o mapeamento para hardware são propostas extensões tempo-real ao processador Java FemtoJava, desenvolvido no âmbito de dissertações de mestrado e projetos de pesquisa no PPGC, criando-se um novo processador tempo-real denominado de RT-FemtoJava. Dentre as extensões propostas ao processador FemtoJava destaca-se a inclusão de um relógio de tempo-real e o suporte a instruções para alocação e manipulação de objetos. Os conceitos propostos foram validados no âmbito de estudos de caso, sendo os resultados obtidos descritos na presente dissertação.

AutoWebS: um Ambiente para Modelagem e Geração Automática de ServiçosWeb Semânticos

Typically Web services contain only syntactic information that describes their interfaces. Due to the lack of semantic descriptions of the Web services, service composition becomes a difficult task. To solve this problem, Web services can exploit the use of ontologies for the semantic definition of service s interface, thus facilitating the automation of discovering, publication, mediation, invocation, and composition of services. However, ontology languages, such as OWL-S, have constructs that are not easy to understand, even for Web developers, and the existing tools that support their use contains many details that make them difficult to manipulate. This paper presents a MDD tool called AutoWebS (Automatic Generation of Semantic Web Services) to develop OWL-S semantic Web services. AutoWebS uses an approach based on UML profiles and model transformations for automatic generation of Web services and their semantic description. AutoWebS offers an environment that provides many features required to model, implement, compile, and deploy semantic Web services

An Approach to Representing the Process of Information Business Modeling

The compact and visualized documenting of information business modeling is a major prerequisite for comprehending its basic concepts, as well as for its effective application and improvement. The documenting of this process is related to its modeling. Thus, the process of information business modeling can be represented by its own tools. Being based on this thesis, the authors suggest an approach to representing the process of information business modeling. A profile for its documenting has been developed for the purpose.

Profile Of The Use Of Disease Modifying Drugs In The Brazilian Registry Of Spondyloarthritides.

Few studies have evaluated the profile of use of disease modifying drugs (DMD) in Brazilian patients with spondyloarthritis (SpA). A common research protocol was applied prospectively in 1505 patients classified as SpA by criteria of the European Spondyloarthropathies Study Group (ESSG), followed at 29 referral centers in Rheumatology in Brazil. Demographic and clinical variables were obtained and evaluated, by analyzing their correlation with the use of DMDs methotrexate (MTX) and sulfasalazine (SSZ). At least one DMD was used by 73.6% of patients: MTX by 29.2% and SSZ by 21.7%, while 22.7% used both drugs. The use of MTX was significantly associated with peripheral involvement, and SSZ was associated with axial involvement, and the two drugs were more administered, separately or in combination, in the mixed involvement (p < 0.001). The use of a DMD was significantly associated with Caucasian ethnicity (MTX , p = 0.014), inflammatory back pain (SSZ, p = 0.002) , buttock pain (SSZ, p = 0.030), neck pain (MTX, p = 0.042), arthritis of the lower limbs (MTX, p < 0.001), arthritis of the upper limbs (MTX, p < 0.001), enthesitis (p = 0.007), dactylitis (MTX, p < 0.001), inflammatory bowel disease (SSZ, p < 0.001) and nail involvement (MTX, p < 0.001). The use of at least one DMD was reported by more than 70% of patients in a large cohort of Brazilian patients with SpA, with MTX use more associated with peripheral involvement and the use of SSZ more associated with axial involvement.

Identification Of Target Genes Using Gene Expression Profile Of Granulocytes From Patients With Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors.

Differential gene expression analysis by suppression subtractive hybridization with correlation to the metabolic pathways involved in chronic myeloid leukemia (CML) may provide a new insight into the pathogenesis of CML. Among the overexpressed genes found in CML at diagnosis are SEPT5, RUNX1, MIER1, KPNA6 and FLT3, while PAN3, TOB1 and ITCH were decreased when compared to healthy volunteers. Some genes were identified and involved in CML for the first time, including TOB1, which showed a low expression in patients with CML during tyrosine kinase inhibitor treatment with no complete cytogenetic response. In agreement, reduced expression of TOB1 was also observed in resistant patients with CML compared to responsive patients. This might be related to the deregulation of apoptosis and the signaling pathway leading to resistance. Most of the identified genes were related to the regulation of nuclear factor κB (NF-κB), AKT, interferon and interleukin-4 (IL-4) in healthy cells. The results of this study combined with literature data show specific gene pathways that might be explored as markers to assess the evolution and prognosis of CML as well as identify new therapeutic targets.

Magnesium-deficient High-fat Diet: Effects On Adiposity, Lipid Profile And Insulin Sensitivity In Growing Rats.

To determine if magnesium deficiency aggravates the effects of a high-fat diet in growing rats in terms of obesity, lipid profile and insulin resistance. The study population comprised 48 newly weaned male Wistar Hannover rats distributed into four groups according to diet, namely, control group (CT; n = 8), control diet provided ad libitum; pair-feeding control group (PF; n = 16), control diet but in the same controlled amount as animals that received high-fat diets; high-fat diet group (HF; n = 12), and magnesium-deficient high-fat diet group (HFMg(-); n = 12). The parameters investigated were adiposity index, lipid profile, magnesium status, insulin sensitivity and the phosphorylation of proteins involved in the insulin-signaling pathway, i.e. insulin receptor β-subunit, insulin receptor substrate 1 and protein kinase B. The HF and HFMg(-) groups were similar regarding gain in body mass, adiposity index and lipid profile, but were significantly different from the PF group. The HFMg(-) group exhibited alterations in magnesium homeostasis as revealed by the reduction in urinary and bone concentrations of the mineral. No inter-group differences were observed regarding glucose homeostasis. Protein phosphorylation in the insulin-signaling pathway was significantly reduced in the high-fat groups compared with the control groups, demonstrating that the intake of fat-rich diets increased insulin resistance, a syndrome that was aggravated by magnesium deficiency. Under the experimental conditions tested, the intake of a magnesium-deficient high-fat diet led to alterations in the insulin-signaling pathway and, consequently, increased insulin resistance.

Evolution Of The Deaths Registry System In Brazil: Associations With Changes In The Mortality Profile, Under-registration Of Death Counts, And Ill-defined Causes Of Death.

This paper examines the spatial pattern of ill-defined causes of death across Brazilian regions, and its relationship with the evolution of completeness of the deaths registry and changes in the mortality age profile. We make use of the Brazilian Health Informatics Department mortality database and population censuses from 1980 to 2010. We applied demographic methods to evaluate the quality of mortality data for 137 small areas and correct for under-registration of death counts when necessary. The second part of the analysis uses linear regression models to investigate the relationship between, on the one hand, changes in death counts coverage and age profile of mortality, and on the other, changes in the reporting of ill-defined causes of death. The completeness of death counts coverage increases from about 80% in 1980-1991 to over 95% in 2000-2010 at the same time the percentage of ill-defined causes of deaths reduced about 53% in the country. The analysis suggests that the government's efforts to improve data quality are proving successful, and they will allow for a better understanding of the dynamics of health and the mortality transition.

Membrane Lipid Profile Monitored By Mass Spectrometry Detected Differences Between Fresh And Vitrified In Vitro-produced Bovine Embryos.

Summary This study aimed to evaluate the impact of vitrification on membrane lipid profile obtained by mass spectrometry (MS) of in vitro-produced bovine embryos. Matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS) has been used to obtain individual embryo membrane lipid profiles. Due to conditions of analysis, mainly membrane lipids, most favorably phosphatidylcholines (PCs) and sphingomyelins (SMs) have been detected. The following ions described by their mass-to-charge ratio (m/z) and respective attribution presented increased relative abundance (1.2-20×) in the vitrified group: 703.5 [SM (16:0) + H]+; 722.5 [PC (40:3) + Na]+; 758.5 [PC (34:2) + H]+; 762.5 [PC (34:0) + H]+; 790.5 [PC (36:0) + H]+ and 810.5 [PC (38:4) + H]+ and/or [PC (36:1) + Na]+. The ion with a m/z 744.5 [PCp (34:1) and/or PCe (34:2)] was 3.4-fold more abundant in the fresh group. Interestingly, ions with m/z 722.5 or 744.5 indicate the presence of lipid species, which are more resistant to enzymatic degradation as they contain fatty acyl residues linked through ether type bonds (alkyl ether or plasmalogens, indicated by the lowercase 'e' and 'p', respectively) to the glycerol structure. The results indicate that cryopreservation impacts the membrane lipid profile, and that these alterations can be properly monitored by MALDI-MS. Membrane lipids can therefore be evaluated by MALDI-MS to monitor the effect of cryopreservation on membrane lipids, and to investigate changes in lipid profile that may reflect the metabolic response to the cryopreservation stress or changes in the environmental conditions.

Long-term Prospects For The Environmental Profile Of Advanced Sugar Cane Ethanol.

This work assessed the environmental impacts of the production and use of 1 MJ of hydrous ethanol (E100) in Brazil in prospective scenarios (2020-2030), considering the deployment of technologies currently under development and better agricultural practices. The life cycle assessment technique was employed using the CML method for the life cycle impact assessment and the Monte Carlo method for the uncertainty analysis. Abiotic depletion, global warming, human toxicity, ecotoxicity, photochemical oxidation, acidification, and eutrophication were the environmental impacts categories analyzed. Results indicate that the proposed improvements (especially no-til farming-scenarios s2 and s4) would lead to environmental benefits in prospective scenarios compared to the current ethanol production (scenario s0). Combined first and second generation ethanol production (scenarios s3 and s4) would require less agricultural land but would not perform better than the projected first generation ethanol, although the uncertainties are relatively high. The best use of 1 ha of sugar cane was also assessed, considering the displacement of the conventional products by ethanol and electricity. No-til practices combined with the production of first generation ethanol and electricity (scenario s2) would lead to the largest mitigation effects for global warming and abiotic depletion. For the remaining categories, emissions would not be mitigated with the utilization of the sugar cane products. However, this conclusion is sensitive to the displaced electricity sources.

Kinase Inhibitor Profile For Human Nek1, Nek6, And Nek7 And Analysis Of The Structural Basis For Inhibitor Specificity.

Human Neks are a conserved protein kinase family related to cell cycle progression and cell division and are considered potential drug targets for the treatment of cancer and other pathologies. We screened the activation loop mutant kinases hNek1 and hNek2, wild-type hNek7, and five hNek6 variants in different activation/phosphorylation statesand compared them against 85 compounds using thermal shift denaturation. We identified three compounds with significant Tm shifts: JNK Inhibitor II for hNek1(Δ262-1258)-(T162A), Isogranulatimide for hNek6(S206A), andGSK-3 Inhibitor XIII for hNek7wt. Each one of these compounds was also validated by reducing the kinases activity by at least 25%. The binding sites for these compounds were identified by in silico docking at the ATP-binding site of the respective hNeks. Potential inhibitors were first screened by thermal shift assays, had their efficiency tested by a kinase assay, and were finally analyzed by molecular docking. Our findings corroborate the idea of ATP-competitive inhibition for hNek1 and hNek6 and suggest a novel non-competitive inhibition for hNek7 in regard to GSK-3 Inhibitor XIII. Our results demonstrate that our approach is useful for finding promising general and specific hNekscandidate inhibitors, which may also function as scaffolds to design more potent and selective inhibitors.