Mutational analysis of a heterogeneous nuclear ribonucleoprotein A2 response element for RNA trafficking

Cytoplasmic transport and localization of mRNA has been reported for a range of oocytes and somatic cells. The heterogeneous nuclear ribonucleoprotein (hnRNP) A2 response element (A2RE) is a 21-nucleotide segment of the myelin basic protein mRNA that is necessary and sufficient for cytoplasmic transport of this message in oligodendrocytes. The predominant A2RE-binding protein in rat brain has previously been identified as hnRNP A2. Here we report that an 11-nucleotide subsegment of the A2RE (A2RE11) was as effective as the full-length A2RE in binding hnRNP A2 and mediating transport of heterologous RNA in oligodendrocytes. Point mutations of the A2RE11 that eliminated binding to hnRNP A2 also markedly reduced the ability of these oligoribonucleotides to support RNA transport. Oligodendrocytes treated with antisense oligonucleotides directed against the translation start site of hnRNP A2 had reduced levels of this protein and disrupted transport of microinjected myelin basic protein RNA. Several A2RE-like sequences from localized neuronal RNAs also bound hnRNP A2 and promoted RNA transport in oligodendrocytes. These data demonstrate the specificity of A2RE recognition by hnRNP A2, provide direct evidence for the involvement of hnRNP A2 in cytoplasmic RNA transport, and suggest that this protein may interact with a wide variety of localized messages that possess A2RE-like sequences

A Denotational Account of Untyped Normalization by Evaluation

We show that the standard normalization-by-evaluation construction for the simply-typed ### -calculus has a natural counterpart for the untyped ## -calculus, with the central type-indexed logical relation replaced by a "recursively defined" invariant relation, in the style of Pitts. In fact, the construction can be seen as generalizing a computational-adequacy argument for an untyped, call-by-name language to normalization instead of evaluation. In th

Completeness of global evaluation logic

Monads serve the abstract encapsulation of side effects in semantics and functional programming. Various monad-based specification languages have been introduced in order to express requirements on generic side-effecting programs. A basic role is played here by global evaluation logic, concerned with formulae which may be thought of as being universally quantified over the state space; this formalism is the fundament of more advanced logics such as monad-based Hoare logic or dynamic logic. We prove completeness of global evaluation logic for models in cartesian categories with a distinguished Heyting algebra object

Nominal Lawvere Theories

Abstract. Lawvere theories provide a category theoretic view of equa-tional logic, identifying equational theories with small categories equipped with finite products. This formulation allows equational theories to be investigated as first class mathematical entities. However, many formal systems, particularly in computer science, are described by equations modulated by side conditions asserting the “freshness of names”; these may be expressed as theories of Nominal Equational Logic (NEL). This paper develops a correspondence between NEL-theories and certain cat-egories that we call nominal Lawvere theories

A Fresh Calculus for Name Management

We define a basic calculus for name management, which combines three ingredients: extensible records (in a simplified form), names (as in FreshML), computational types (to allow computational effects, including generation of fresh names). The calculus supports the use of symbolic names for programming in-the-large, eg it subsumes Ancona and Zucca\u2019s calculus for module systems, and for meta-programming (but not the intensional analysis of object level terms supported by FreshML), eg it subsumes (and improves) Nanevski and Pfenning\u2019s calculus for meta-programming with names and necessity. Moreover, it models some aspects of Java\u2019s class loaders

Beluga: Programming with dependent types, contextual data, and contexts

Abstract. The logical framework LF provides an elegant foundation for specifying formal systems and proofs and it is used successfully in a wide range of applications such as certifying code and mechanizing metatheory of programming languages. However, incorporating LF technology into functional programming to allow programmers to specify and reason about formal guarantees of their programs from within the programming language itself has been a major challenge. In this paper, we present an overview of Beluga, a framework for programming and reasoning with formal systems. It supports specifying formal systems in LF and it also provides a dependently typed functional language that supports analyzing and manipulating LF data via pattern matching. A distinct feature of Beluga is its direct support for reasoning with contexts and contextual objects. Taken together these features lead to a powerful language which supports writing compact and elegant proofs.

Program Generation and Components

The first part of the paper gives a brief overview of meta-programming, in particular program generation, and its use in software development. The second part introduces a basic calculus, related to FreshML, that supports program generation (as described through examples and a translation of MetaML into it) and programming in-the-large (this is demonstrated by a translation of CMS into it)