CrimsonHex: a service oriented repository of specialised learning objects

The corner stone of the interoperability of eLearning systems is the standard definition of learning objects. Nevertheless, for some domains this standard is insufficient to fully describe all the assets, especially when they are used as input for other eLearning services. On the other hand, a standard definition of learning objects in not enough to ensure interoperability among eLearning systems; they must also use a standard API to exchange learning objects. This paper presents the design and implementation of a service oriented repository of learning objects called crimsonHex. This repository is fully compliant with the existing interoperability standards and supports new definitions of learning objects for specialized domains. We illustrate this feature with the definition of programming problems as learning objects and its validation by the repository. This repository is also prepared to store usage data on learning objects to tailor the presentation order and adapt it to learner profiles.

Disposable immunosensor using a simple method for oriented antibody immobilization for label-free real-time detection of an oxidative stress biomarker implicated in cancer diseases

This work proposes a novel approach for a suitable orientation of antibodies (Ab) on an immunosensing platform, applied here to the determination of 8-hydroxy-2′-deoxyguanosine (8OHdG), a biomarker of oxidative stress that has been associated to chronic diseases, such as cancer. The anti-8OHdG was bound to an amine modified gold support through its Fc region after activation of its carboxylic functions. Non-oriented approaches of Ab binding to the platform were tested in parallel, in order to show that the presented methodology favored Ab/Ag affinity and immunodetection of the antigen. The immunosensor design was evaluated by quartz-crystal microbalance with dissipation, atomic force microscopy, electrochemical impedance spectroscopy (EIS) and square-wave voltammetry. EIS was also a suitable technique to follow the analytical behavior of the device against 8OHdG. The affinity binding between 8OHdG and the antibody immobilized in the gold modified platform increased the charge transfer resistance across the electrochemical set-up. The observed behavior was linear from 0.02 to 7.0 ng/mL of 8OHdG concentrations. The interference from glucose, urea and creatinine was found negligible. An attempt of application to synthetic samples was also successfully conducted. Overall, the presented approach enabled the production of suitably oriented Abs over a gold platform by means of a much simpler process than other oriented-Ab binding approaches described in the literature, as far as we know, and was successful in terms of analytical features and sample application.

Oriented Tailoring of Plastic Antibodies for Prostate Specific Antigen and Application of the Imprinted Material as Ionophore in Potentiometric Detection

Prostate Specific Antigen (PSA) is the biomarker of choice for screening prostate cancer throughout the population, with PSA values above 10 ng/mL pointing out a high probability of associated cancer1. According to the most recent World Health Organization (WHO) data, prostate cancer is the commonest form of cancer in men in Europe2. Early detection of prostate cancer is thus very important and is currently made by screening PSA in men over 45 years old, combined with other alterations in serum and urine parameters. PSA is a glycoprotein with a molecular mass of approximately 32 kDa consisting of one polypeptide chain, which is produced by the secretory epithelium of human prostate. Currently, the standard methods available for PSA screening are immunoassays like Enzyme-Linked Immunoabsorbent Assay (ELISA). These methods are highly sensitive and specific for the detection of PSA, but they require expensive laboratory facilities and high qualify personal resources. Other highly sensitive and specific methods for the detection of PSA have also become available and are in its majority immunobiosensors1,3-5, relying on antibodies. Less expensive methods producing quicker responses are thus needed, which may be achieved by synthesizing artificial antibodies by means of molecular imprinting techniques. These should also be coupled to simple and low cost devices, such as those of the potentiometric kind, one approach that has been proven successful6. Potentiometric sensors offer the advantage of selectivity and portability for use in point-of-care and have been widely recognized as potential analytical tools in this field. The inherent method is simple, precise, accurate and inexpensive regarding reagent consumption and equipment involved. Thus, this work proposes a new plastic antibody for PSA, designed over the surface of graphene layers extracted from graphite. Charged monomers were used to enable an oriented tailoring of the PSA rebinding sites. Uncharged monomers were used as control. These materials were used as ionophores in conventional solid-contact graphite electrodes. The obtained results showed that the imprinted materials displayed a selective response to PSA. The electrodes with charged monomers showed a more stable and sensitive response, with an average slope of -44.2 mV/decade and a detection limit of 5.8X10-11 mol/L (2 ng/mL). The corresponding non-imprinted sensors showed smaller sensitivity, with average slopes of -24.8 mV/decade. The best sensors were successfully applied to the analysis of serum samples, with percentage recoveries of 106.5% and relatives errors of 6.5%.

Label-free human chorionic gonadotropin detection at picogram levels using oriented antibodies bound to graphene screen-printed electrodes

Human chorionic gonadotropin (hCG) is a key diagnostic marker of pregnancy and an important biomarker for cancers in the prostate, ovaries and bladder and therefore of great importance in diagnosis. For this purpose, a new immunosensor of screen-printed electrodes (SPEs) is presented here. The device was fabricated by introducing a polyaniline (PANI) conductive layer, via in situ electropolymerization of aniline, onto a screen-printed graphene support. The PANI-coated graphene acts as the working electrode of a three terminal electrochemical sensor. The working electrode is functionalised with anti-hCG, by means of a simple process that enabled oriented antibody binding to the PANI layer. The antibody was attached to PANI following activation of the –COOH group at the Fc terminal. Functionalisation of the electrode was analysed and optimized using Electrochemical Impedance Spectroscopy (EIS). Chemical modification of the surface was characterised using Fourier transform infrared, and Raman spectroscopy with confocal microscopy. The graphene–SPE–PANI devices displayed linear responses to hCG in EIS assays from 0.001 to 50 ng mL−1 in real urine, with a detection limit of 0.286 pg mL−1. High selectivity was observed with respect to the presence of the constituent components of urine (urea, creatinine, magnesium chloride, calcium chloride, sodium dihydrogen phosphate, ammonium chloride, potassium sulphate and sodium chloride) at their normal levels, with a negligible sensor response to these chemicals. Successful detection of hCG was also achieved in spiked samples of real urine from a pregnant woman. The immunosensor developed is a promising tool for point-of-care detection of hCG, due to its excellent detection capability, simplicity of fabrication, low-cost, high sensitivity and selectivity.

Orthogonal persistence in Java supported by aspect- oriented programming and reflection

The persistence concern implemented as an aspect has been studied since the appearance of the Aspect-Oriented paradigm. Frequently, persistence is given as an example that can be aspectized, but until today no real world solution has applied that paradigm. Such solution should be able to enhance the programmer productivity and make the application less prone to errors. To test the viability of that concept, in a previous study we developed a prototype that implements Orthogonal Persistence as an aspect. This first version of the prototype was already fully functional with all Java types including arrays. In this work the results of our new research to overcome some limitations that we have identified on the data type abstraction and transparency in the prototype are presented. One of our goals was to avoid the Java standard idiom for genericity, based on casts, type tests and subtyping. Moreover, we also find the need to introduce some dynamic data type abilities. We consider that the Reflection is the solution to those issues. To achieve that, we have extended our prototype with a new static weaver that preprocesses the application source code in order to introduce changes to the normal behavior of the Java compiler with a new generated reflective code.

An aspect-oriented framework for orthogonal persistence

The life cycle of software applications in general is very short and with extreme volatile requirements. Within these conditions programmers need development tools and techniques with an extreme level of productivity. We consider the code reuse as the most prominent approach to solve that problem. Our proposal uses the advantages provided by the Aspect-Oriented Programming in order to build a reusable framework capable to turn both programmer and application oblivious as far as data persistence is concerned, thus avoiding the need to write any line of code about that concern. Besides the benefits to productivity, the software quality increases. This paper describes the actual state of the art, identifying the main challenge to build a complete and reusable framework for Orthogonal Persistence in concurrent environments with support for transactions. The present work also includes a successfully developed prototype of that framework, capable of freeing the programmer of implementing any read or write data operations. This prototype is supported by an object oriented database and, in the future, will also use a relational database and have support for transactions.

Transactions and schema evolution in a persistent object-oriented programming system

Applications are subject of a continuous evolution process with a profound impact on their underlining data model, hence requiring frequent updates in the applications' class structure and database structure as well. This twofold problem, schema evolution and instance adaptation, usually known as database evolution, is addressed in this thesis. Additionally, we address concurrency and error recovery problems with a novel meta-model and its aspect-oriented implementation. Modern object-oriented databases provide features that help programmers deal with object persistence, as well as all related problems such as database evolution, concurrency and error handling. In most systems there are transparent mechanisms to address these problems, nonetheless the database evolution problem still requires some human intervention, which consumes much of programmers' and database administrators' work effort. Earlier research works have demonstrated that aspect-oriented programming (AOP) techniques enable the development of flexible and pluggable systems. In these earlier works, the schema evolution and the instance adaptation problems were addressed as database management concerns. However, none of this research was focused on orthogonal persistent systems. We argue that AOP techniques are well suited to address these problems in orthogonal persistent systems. Regarding the concurrency and error recovery, earlier research showed that only syntactic obliviousness between the base program and aspects is possible. Our meta-model and framework follow an aspect-oriented approach focused on the object-oriented orthogonal persistent context. The proposed meta-model is characterized by its simplicity in order to achieve efficient and transparent database evolution mechanisms. Our meta-model supports multiple versions of a class structure by applying a class versioning strategy. Thus, enabling bidirectional application compatibility among versions of each class structure. That is to say, the database structure can be updated because earlier applications continue to work, as well as later applications that have only known the updated class structure. The specific characteristics of orthogonal persistent systems, as well as a metadata enrichment strategy within the application's source code, complete the inception of the meta-model and have motivated our research work. To test the feasibility of the approach, a prototype was developed. Our prototype is a framework that mediates the interaction between applications and the database, providing them with orthogonal persistence mechanisms. These mechanisms are introduced into applications as an {\it aspect} in the aspect-oriented sense. Objects do not require the extension of any super class, the implementation of an interface nor contain a particular annotation. Parametric type classes are also correctly handled by our framework. However, classes that belong to the programming environment must not be handled as versionable due to restrictions imposed by the Java Virtual Machine. Regarding concurrency support, the framework provides the applications with a multithreaded environment which supports database transactions and error recovery. The framework keeps applications oblivious to the database evolution problem, as well as persistence. Programmers can update the applications' class structure because the framework will produce a new version for it at the database metadata layer. Using our XML based pointcut/advice constructs, the framework's instance adaptation mechanism is extended, hence keeping the framework also oblivious to this problem. The potential developing gains provided by the prototype were benchmarked. In our case study, the results confirm that mechanisms' transparency has positive repercussions on the programmer's productivity, simplifying the entire evolution process at application and database levels. The meta-model itself also was benchmarked in terms of complexity and agility. Compared with other meta-models, it requires less meta-object modifications in each schema evolution step. Other types of tests were carried out in order to validate prototype and meta-model robustness. In order to perform these tests, we used an OO7 small size database due to its data model complexity. Since the developed prototype offers some features that were not observed in other known systems, performance benchmarks were not possible. However, the developed benchmark is now available to perform future performance comparisons with equivalent systems. In order to test our approach in a real world scenario, we developed a proof-of-concept application. This application was developed without any persistence mechanisms. Using our framework and minor changes applied to the application's source code, we added these mechanisms. Furthermore, we tested the application in a schema evolution scenario. This real world experience using our framework showed that applications remains oblivious to persistence and database evolution. In this case study, our framework proved to be a useful tool for programmers and database administrators. Performance issues and the single Java Virtual Machine concurrent model are the major limitations found in the framework.