Evolution and Adaptability of Complex Applications Abstract In these days the applications become more complex that causes maintenance problems while evolving these applications. A change in one part of the applica- tion can significantly affect other parts of the application. The next aspect can be related systems which communicate with this application. They must be up- dated to satisfy their correct functionality. These problems can concern multiple domains, e.g., UML diagrams, XML schema diagrams, relational schemas, APIs, etc. We focus on this problem from the perspective of the MDA, which uses the platform independent model (PIM) for a general view of the problem and the platform specific model (PSM) for particular domains. Moreover, these models can be interconnected and related to each other. We propose novel PSM models from various widely used domains, operations over these models and algorithms for model transformations. Thanks to the MDA principle, it is possible to combine presented models and model a complex application. All models and related algorithms we present were experimentally implemented and tested in the DaemonX framework on real-world data for their verification. 1

In der Reihe .NET Business wird mit Agile MDA ein Lösungsansatz für die Umsetzung großer Softwareprojekte vorgestellt. Auch wenn die beschriebene Lösung nicht mit dem .NET Framework, sonderm mit Java umgesetzt wurde, lassen sich die aus dem Projekt gewonnenen Erkenntnisse grundsätzlich auch auf .NET-Projekte übertragen

Breast cancer is the most commonly occurring cancer worldwide, more than 2.26 million new cases occurred in women in 2020. Treatment for breast cancer is normally individualized to the patient based on the presence of different receptors, these receptors include HER2, progesterone, and estrogen. The presence of these receptors generally comes with an amenable prognosis, and a wide array of available treatments. There are types of breast cancers that do not have any of these receptors and tend to be much more aggressive. This type of cancer is called triple negative and represents about 10 percent of all breast cancer occurrences in the United States. The lack of receptors makes this type of cancer extremely difficult to treat and generally comes with a poor prognosis. In the present study, we used triple negative breast cancer cell line MDA-MB231, which is known to use actin remodeling to evade immunologic response. These cells were treated with two novel, structurally similar flavonoids, CT1 and CT3 derived from an ethnobotanically recognized species of Chromolaena. CT1 and CT3 are extracted from the leaves of Chromolaena tacotana and then isolated and purified by chromatography. These compounds are used to treat cancer cells, at different concentrations that include 5, 10, 20, 40 and 80mM. MTT assays are used to determine their effect on cell viability, and the mechanism of action was analyzed by immunoblotting and TUNEL.. CT1 has a significantly stronger inhibitory effect on MDA-MB231 cell viability as compared to CT3. Preliminary analysis of the mechanism of action of CT1 has revealed that it neither follows the canonical intrinsic apoptotic pathway nor the extrinsic pathway that involves the activated form of c-JUN. By up-regulating actin, triple negative breast cancer is able to evade immunologic response and cancer treatment. CT1, a novel flavonoid extracted from the leaves of Chromoleana tacotana has shown cytotoxic effects against triple negative breast cancer cells effectively bypassing the actin response. The mechanism of action is currently under study.

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Le circuit du médicament est un élément primordial dans l’organisation des établissements de santé. Sa sécurisation et sa modernisation permettent de baisser sensiblement le nombre de personnes victimes d’erreurs médicamenteuses et de réduire les coûts (augmentation du rendement, libération de poste préparateur et gain de temps infirmière. . .). L’utilisation de la DJIN (Dispensation Journalière Individuelle Nominative), de systèmes de préparation et de transport sécurisés (robots, circuit pneumatique, chariots de dispensation. . .), de systèmes de contrôle de l’administration au lit du patient sont les solutions permettant d’éviter les erreurs humaines. Nous proposons dans cette étude d’utiliser des concepts du milieu industriel pour améliorer la sécurité et la traçabilité du circuit du médicament. Nous utilisons le paradigme de Système Contrôlé par le Produit (SCP) qui propose de mettre le produit au coeur du système en utilisant des nouvelles technologies tel que la RFID. Nous comparons le circuit du médicament avec un système d’assemblage : l’opération d’assemblage est vue comme un ajout de médicaments et le produit comme la préparation de la prescription pour un patient. Le but de cette thèse est de proposer une méthodologie de réingénierie, basée surl e MDA et ASCI, pour le contrôle par le produit en synchronisant les flux physiques et informationnels, puis de l’appliquer au circuit du médicament. Enfin, nous l’instancions au CHU de Clermont-Ferrand en testant différents scénarios à travers un logiciel de simulation afin de proposer une aide à la décision pour les pharmaciens et les responsables du CHU. / The reengineering of the medication-use process is an important challenge in order to reduce medication errors and costs for the pharmacy (increase of the efficience ; reduce the amount of work time spent by nurses in the medication administration process. . .). The use of the nominative dispensing, automatic systems (robots, pneumatic circuit, cart dispensing. . .),control system of administration to the patient are solutions which can avoid the human errors. We propose in this study to use the concept used in industrial systems in order to improve the safety and the traceability on the medication-use process. We use the paradigm of Product Driven System which proposes to place the product in the centre of the system using identification technology as RFID. We made an analogy between the medication-use process and an assembly system : the product is considered as a preparation of the prescription for a patient and an operation of assembly is considered as an addition of medication. The goal of this thesis is to propose a reengineering methodology based on MDA (Model Driven Architecture) and ASDI (Analysis-Specification-Design-Implementation) in order to implement a system based on product driven synchronizing the physical and informational flow. In particular,this methodology is applied to the medicament-use process. Finally, we present an example of application of this modelling to the hospital of Clermont-Ferrand through simulation software which allows testing different scenarios to help the pharmacists and managers of the hospital to make up their decisions.

Unter dem Terminus der MDA (Model Driven Architecture)versteht man eine Methode, Anwendungen im Rahmen der UML zu spezifizieren und ablauffähigen Programm-Code durch automatische Generierung zu erzeugen. Am Lehrstuhl für Datenbanken existiert in diesem Zusammenhang das GignoMDA-Projekt, daß sich mit der modellgetriebenen Entwicklung von Datenbankenanwendungen beschäftigt. Als wesentlicher Bestandteil der jeweiligen Anwendung sind Datenmodelle jedoch, genau wie die Anwendungsarchitektur selbst, Anpassungen an sich veränderte Zielstellungen und Umgebungsbedingungen unterworfen. Es stellt sich also die Notwendigkeit der Überführung von Datenbeständen in neu generierte Zielsysteme, als Bestandteil eines vollständig modellgetriebenen Ansatzes dar. Diese Arbeit stellt ein Konzept zur Schema- und Datenmigration bei der Weiterentwicklung der Anwendungs-Datenbankmodelle vor. Dabei werden Datenmigrationen, gemäß dem MDA-Ansatz, als Modell in UML ausgedrückt und anschließend zur automatischen Erzeugung von plattformabhängigen Migrationsmodellen genutzt. Aus diesen Migrationsmodellen können so, Datenbanktechnik basierte Programme (ETL, Stored Procedures) zur effizienten Ausführung von Migrationen generiert werden.

Diese Diplomarbeit behandelt das Themengebiet der automatischen Erzeugung von grafischen Benutzeroberflächen (GUIs) im Kontext von Webservices. Es geht dabei konkret um einen Editor, mit dem Hinweise zur Generierung von Dialogen erstellt werden können. Diese Hinweise sollen dann von den dialogerzeugenden Anwendungen einbezogen werden, um eine dynamische Interaktion mit Webservices durch beliebige Nutzer ohne dienstspezifische Software zu ermöglichen. Die Arbeit führt in die aktuellen Techniken zur GUI-Generierung ein und stellt Transformationsprinzipien vor, die eine Generierung ausgehend von einem formalen Datenmodell ermöglichen. Dabei müssen mangelnde Modellparameter in Beschreibungen von Webservices manuell ausgeglichen werden (WSGUI-Konzepte). Diese Zielstellung führt zum Entwurf des WSGUI-Editors. Die anschließende Implementierung berücksichtigt darüber hinaus Integrationsaspekte wie die Publizierung von WSGUI-Hinweisen, Einbindung von GUI-Übersetzungen und eine Vorschau auf die zu generierenden Dialoge. Abgeschlossen wird die Arbeit mit einer Bewertung des Editors, aber auch einer Reihe von Vorschlägen zur Vereinfachung ähnlich gelagerter zukünftiger Projekte im Umfeld von Webservices.

Based on the increasing complexity of modern avionics, the associated system design processes moved towards Model Driven Architecture (MDA) based processes. Additionally, the demand for higher system autonomy features requires means to further modularise mission systems and to define and establish interactions among the systems’ individual components. Therefore, the ideas of service-oriented computing are currently adapted to established, model driven design processes. With respect to modelling interactions for service components, current approaches are limited to only a fixed set of communication primitives, restricting a service designer’s expressiveness to specify service interaction. In consequence, interaction patterns not included in this basic set have to be reflected in application code, mangling application and communication logic. Furthermore, when service functionality relies on communication semantics which are not provided by the underlying set of primitives, additional emulation behaviour has to be added to the service which makes this mangling even worse. Platform independence is reduced as services can not easily be ported to platforms not natively supporting the selected primitives which contradicts the ideas of model-driven development. Addressing these limitations, this thesis proposes a new model-driven service development process based on Interaction Templates (ITs), promoting interactions among service participants to first class modelling entities. The process focuses on modelling the interactions among service participants. Interaction semantics are explicitly specified in models, beyond pure stereotyping, and gain increased platform independence for services with respect to communication. The process exploits automated Model-to-Model (M2M) and Model-to-Text (M2T) transformations to assist service implementation and to automatically derive interaction realisations on concrete target platforms. This allows for easy replacement and inter-mixing of communication middleware to realise a service’s interactions. This way, services become independent of the underlying communication primitives by only relying on ITs and not platform primitives which are hidden behind ITs. In turn, realising ITs on concrete platforms is not affected by their utilisation for service interaction. Beside the novel modelling process itself, the presented work defines a Unified Modeling Language (UML) profile, referred to as UML Profile for Interaction-centric Services (UP4IS), which directly supports the adaptation of standard UML language constructs and tools for the proposed modelling approach. The whole development process is demonstrated via the specification of a simple video recording systems consisting of two services. The services themselves are based on a representative IT library which forms an essential part of the presented case study. Using these service and IT models, the thesis emphasises the necessary model transformation and code generation steps to derive service implementations based on the abstract models.

Mobilių technologijų populiarėjimas tarp vartotojų ir jų platformų įvairovė skatina mobilių programėlių kūrėjus užimti vis didesnę rinkos dalį. Kiekviena mobili platforma turi savo specifiką, todėl kūrėjams reikia vis daugiau žinių arba specialistų kuriant mobilias aplikacijas, tam reikalinga papildomų resursų, apmokymų,kaštų ir laiko. Vienas iš galimų problemos sprendimų, sukurti tam tikrus įrankius, kurie mobilių programėlių projektavimo ir kūrimo bei testavimo etape, leistų automatiškai suprojektuoti, suprogramuoti mobilias aplikacijas, nepriklausomai kokiai platformai išlaikant tos programėlės logiką. Tam pakaktų mobilių programų kūrėjams turėti vienai mobiliai platformai aprašytą modelį arba programėlę, ir iš jų remiantis MDA (Model Dirven Architecture) metodologijomis arba aprašytais karkasais atliktų transformacijas į reikiamą platformą. Šiame darbe pateikimas MDA principais paremtos sukurtos priemonės , kurios, atlieka programų transformacijas iš Android į Windows Phone. Įrodant transformacijų svarbą, atliktas transformavimo priemonių tyrimas, įvedant tam tikras metrikas ir jų palyginimą tarp atskirai realizuotų programų, šių priemonių transformuotų programų ir naudojant universalias priemones kaip JavaScript arba žiniatinklio principu veikiančių programų. / There is growth of mobile technologies and platforms providing for users so and developers of mobile applications need to take a larger market. There is some specificity of platforms, therefore developer needs a more knowledge or experts of mobile application developing where require a more resources, training, costs and it takes a time. One of the possible solutions to the problem, to make the tools which allow design and create mobile applications independent by platform keep the logic in design and development or testing phase. This is sufficient for developers to design or creates one mobile applications and using methods of Mobile Driven Architecture (MDA) and frameworks create transformations more applications many platforms. In this research paper representing the tools developed based MDA to carry out transformations from Android to Windows Phone. To prove the importance of transformations performed research of transformation tools with certain comparison of metrics between the programs of separated implementation, these tools transformed programs and used universal tools like JavaScript or web-based software implementation.

The overproduction of reactive oxygen and nitrogen species or the reduction in the antioxidant capacity results in the oxidative stress. The lipid peroxidation involves the oxidative deterioration of polyunsaturated fatty acids and it process is involved in the pathogenesis of diseases such as cancer, diabetes, atherosclerosis and neuro-degenerative diseases. Since it is complex to carry out the free radical quantification directly in vivo, it is necessary to do the measure of their reaction products and the malondialdehyde (MDA) is one of the most known secondary products of the lipid peroxidation used as an indicator of cell membrane injury. The MDA has been measured by its reaction with the thiobarbituric acid (TBA), which produces the MDA-TBA2 complex that can be detected by spectrophotometry method known such thiobarbituric acid reactive substances (TBARS). However, the major problem in this method is the lack of specificity, once TBA reacts with a variety of compounds, overestimating the real levels of MDA. Thus, methods involving high performance liquid chromatography (HPLC) have been reported, which are specifics and sensitive. In this study, a rapid and reliable method was optimized and validated to quantify plasmatic MDA by HPLC, using visible detection. The analytical parameters evaluated were: linearity, precision, accuracy, recovery, sensibility, robustness, and stability. The optimized method was applied in subjects from a retirement home in Santa Maria. The plasma sample underwent alkaline hydrolysis with NaOH, to a complete release of protein bound to the MDA, followed to acid deproteinization with H3PO4 and derivatization with TBA. To removal of interferents, a sample extraction with n-butanol before the chromatographic injection was carried out. The MDA analysis was performed in a C18 column, integrated with a guard-column. The mobile phase was constituted by KH2PO4 2.5 mM and methanol (50:50), with isocratic elution and detection at 532 nm. The assay was linear from 0.28 to 6.6 μM. The precisions intra and inter-day were obtained with CV% < 4% and < 11%, respectively. The accuracy (bias%) ranged from -4.1 to 2% and the recovery ranged from 95.9 to 102.7%. The limit of detection was 0.05 μM and the limit of quantification was 0.17 μM. For the stability test, it was observed that the MDA standard solutions were stable for, at least, 18 months at -20ºC. The plasma sample was stable for 24h when it was stored at -20ºC, but it was not stable at 4ºC. After alkaline hydrolysis storage at -20ºC, plasmatic MDA was not stable; on the other hand, the sample remained stable for 30 days after TBA reaction storage at -20ºC. After n-butanol extraction storage, the MDA levels were stable for 3 days at -20ºC. The method was applied in plasma samples in healthy subjects from 60 to 80 years. The elderly subjects had MDA plasma levels of 4.45 ± 0.81 μM for women and 4.60 ± 0.95 μM for men, without a significant difference. These levels were considered such as reference values to this age in our laboratory. Thus, the results demonstrated that a simple, rapid and specific technique was optimized and validated. The method showed to be consistent in all analytical parameters and can be used in the routines in clinical laboratories. / A superprodução de espécies reativas de oxigênio e nitrogênio ou a redução na capacidade antioxidante resulta no estresse oxidativo. A peroxidação lipídica envolve a degradação oxidativa de ácidos graxos polinsaturados e este processo está envolvido na patogênese de doenças como câncer, diabetes, aterosclerose e doenças neurodegenerativas. Já que a quantificação direta de radicais livres in vivo é complexa, torna-se necessário realizar a medida de seus produtos de reação, e o malondialdeído (MDA) é um dos produtos secundários da peroxidação lipídica mais conhecidos utilizado como indicador de injúria da membrana celular. O MDA tem sido medido através de sua reação com o ácido tiobarbitúrico (TBA), o qual produz o complexo MDA-TBA2, detectado por espectrofotometria método conhecido como substâncias reativas ao ácido tiobarbitúrico (TBARS). Porém, o maior problema neste método é a falta de especificidade, uma vez que o TBA reage com uma variedade de compostos, superestimando os valores reais de MDA. Assim, métodos envolvendo cromatografia líquida de alta eficiência (CLAE) têm sido descritos, sendo mais específicos e sensíveis. Neste estudo, um método rápido e confiável para quantificar MDA plasmático por CLAE, com detecção visível, foi otimizado e validado. Os parâmetros analíticos avaliados foram: linearidade, precisão, exatidão, recuperação, sensibilidade, robustez e estabilidade. O método otimizado foi aplicado em pessoas de um asilo da cidade de Santa Maria. As amostras de plasma sofreram hidrólise alcalina com NaOH, para uma liberação completa das proteínas ligadas ao MDA, seguida por desproteinização ácida com H3PO4 e derivatização com TBA. Para remoção de interferentes, realizou-se extração da amostra com n-butanol antes da injeção no cromatógrafo. A análise de MDA foi feita em coluna C18, integrada a uma pré-coluna. A fase móvel constituía de KH2PO4 2,5 mM e metanol (50:50), com eluição isocrática e detecção a 532 nm. A análise foi linear de 0,28 a 6,6 μM. As precisões intra e inter-dia foram obtidas com CV% < 4% a < 11%, respectivamente. A exatidão (bias%) variou de -4,1 a 2% e a recuperação variou de 95,9 a 102,7%. O limite de detecção foi de 0,05 μM e o limite de quantificação foi de 0,17μM. Para os testes de estabilidade, observou-se que as soluções padrões de MDA foram estáveis por, no mínimo, 18 meses a -20ºC. O plasma foi estável por 24h quando estocado a -20ºC e instável 4ºC. Armazenado a -20ºC após hidrólise alcalina, o MDA plasmático não permaneceu estável; por outro lado, as amostras continuaram estáveis por 30 dias quando armazenadas após derivatização com TBA, a -20ºC. Depois da extração com n-butanol, os níveis de MDA foram estáveis por 3 dias armazenados a -20ºC. O método foi aplicado em amostras de plasma de indivíduos saudáveis entre 60 e 80 anos. Os idosos apresentaram níveis plasmáticos de MDA de 4,45 ± 0,81 μM para mulheres e 4,60 ± 0,95μM para homens, sem diferença significativa. Estes valores foram considerados como valores de referência para esta faixa etária em nosso laboratório. Assim sendo, os resultados demonstraram que uma técnica simples, rápida e específica foi otimizada e validada. O método mostrou ser confiável em todos os parâmetros analíticos, e pode ser usado em rotinas nos laboratórios clínicos.