Costrutti ed Applicazioni di Programmazione Generica in Linguaggi Object-Oriented

Generic programming is likely to become a new challenge for a critical mass of developers. Therefore, it is crucial to refine the support for generic programming in mainstream Object-Oriented languages — both at the design and at the implementation level — as well as to suggest novel ways to exploit the additional degree of expressiveness made available by genericity. This study is meant to provide a contribution towards bringing Java genericity to a more mature stage with respect to mainstream programming practice, by increasing the effectiveness of its implementation, and by revealing its full expressive power in real world scenario. With respect to the current research setting, the main contribution of the thesis is twofold. First, we propose a revised implementation for Java generics that greatly increases the expressiveness of the Java platform by adding reification support for generic types. Secondly, we show how Java genericity can be leveraged in a real world case-study in the context of the multi-paradigm language integration. Several approaches have been proposed in order to overcome the lack of reification of generic types in the Java programming language. Existing approaches tackle the problem of reification of generic types by defining new translation techniques which would allow for a runtime representation of generics and wildcards. Unfortunately most approaches suffer from several problems: heterogeneous translations are known to be problematic when considering reification of generic methods and wildcards. On the other hand, more sophisticated techniques requiring changes in the Java runtime, supports reified generics through a true language extension (where clauses) so that backward compatibility is compromised. In this thesis we develop a sophisticated type-passing technique for addressing the problem of reification of generic types in the Java programming language; this approach — first pioneered by the so called EGO translator — is here turned into a full-blown solution which reifies generic types inside the Java Virtual Machine (JVM) itself, thus overcoming both performance penalties and compatibility issues of the original EGO translator. Java-Prolog integration Integrating Object-Oriented and declarative programming has been the subject of several researches and corresponding technologies. Such proposals come in two flavours, either attempting at joining the two paradigms, or simply providing an interface library for accessing Prolog declarative features from a mainstream Object-Oriented languages such as Java. Both solutions have however drawbacks: in the case of hybrid languages featuring both Object-Oriented and logic traits, such resulting language is typically too complex, thus making mainstream application development an harder task; in the case of library-based integration approaches there is no true language integration, and some “boilerplate code” has to be implemented to fix the paradigm mismatch. In this thesis we develop a framework called PatJ which promotes seamless exploitation of Prolog programming in Java. A sophisticated usage of generics/wildcards allows to define a precise mapping between Object-Oriented and declarative features. PatJ defines a hierarchy of classes where the bidirectional semantics of Prolog terms is modelled directly at the level of the Java generic type-system.

Sonic Hedgehog pathway impairment in Neural Precursor Cells of the Ts65Dn mouse, an animal model of Down syndrome

Mental retardation in Down syndrome (DS) has been imputed to the decreased brain volume, which is evident starting from the early phases of development. Recent studies in a widely used mouse model of DS, the Ts65Dn mouse, have shown that neurogenesis is severely impaired during the early phases of brain development, suggesting that this defect may be a major determinant of brain hypotrophy and mental retardation in individuals with DS. Recently, it has been found that in the cerebellum of Ts65Dn mice there is a defective responsiveness to Sonic Hedgehog (Shh), a potent mitogen that controls cell division during brain development, suggesting that failure of Shh signaling may underlie the reduced proliferation potency in DS. Based on these premises, we sought to identify the molecular mechanisms underlying derangement of the Shh pathway in neural precursor cells (NPCs) from Ts65Dn mice. We found that the expression levels of the Shh receptor Patched1 (Ptch1) were increased compared to controls both at the RNA and protein level. Partial silencing of Ptch1 expression in trisomic NPCs restored cell proliferation, indicating that proliferation impairment was due to Ptch1 overexpression. We further found that the overexpression of Ptch1 in trisomic NPCs is related to increased levels of AICD, a transcription-promoting fragment of amyloid precursor protein (APP). Increased AICD binding to the Ptch1 promoter favored its acetylated status, thus enhancing Ptch1 expression. Taken together, these data provide novel evidence that Ptch1 over expression underlies derangement of the Shh pathway in trisomic NPCs, with consequent proliferation impairment. The demonstration that Ptch1 over expression in trisomic NPCs is due to an APP fragment provides a link between this trisomic gene and the defective neuronal production that characterizes the DS brain.