Keeping calm in the face of change: towards optimisation of FRP by reasoning about change

Functional Reactive Programming (FRP) is an approach to reactive programming where systems are structured as networks of functions operating on signals (time-varying values). FRP is based on the synchronous data-flow paradigm and supports both (an approximation to) continuous-time and discrete-time signals (hybrid systems).What sets FRP apart from most other languages for similar applications is its support for systems with dynamic structure and for higher-order reactive constructs. This paper contributes towards advancing the state of the art of FRP implementation by studying the notion of signal change and change propagation in a setting of structurally dynamic networks of n-ary signal functions operating on mixed continuous-time and discrete-time signals. We first define an ideal denotational semantics (time is truly continuous) for this kind of FRP, along with temporal properties, expressed in temporal logic, of signals and signal functions pertaining to change and change propagation. Using this framework, we then show how to reason about change; specifically, we identify and justify a number of possible optimisations, such as avoiding recomputation of unchanging values. Note that due to structural dynamism, and the fact that the output of a signal function may change because time is passing even if the input is unchanging, the problem is significantly more complex than standard change propagation in networks with static structure

Lucy-n: a n-Synchronous Extension of Lustre

International audienceSynchronous functional languages such as Lustre or Lucid Synchrone define a restricted class of Kahn Process Networks which can be executed with no buffer. Every expression is associated to a clock indicating the instants when a value is present. A dedicated type system, the clock calculus, checks that the actual clock of a stream equals its expected clock and thus does not need to be buffered. The n-synchrony relaxes synchrony by allowing the communication through bounded buffers whose size is computed at compile-time. It is obtained by extending the clock calculus with a subtyping rule which defines buffering points. This paper presents the first implementation of the n-synchronous model inside a Lustre-like language called Lucy-n. The language extends Lustre with an explicit buffer construct whose size is automatically computed during the clock calculus. This clock calculus is defined as an inference type system and is parametrized by the clock language and the algorithm used to solve subtyping constraints. We detail here one algorithm based on the abstraction of clocks, an idea originally introduced in [APLAS08]. The paper presents a simpler, yet more precise, clock abstraction for which the main algebraic properties have been proved in Coq. Finally, we illustrate the language on various examples including a video application

Sustained PGC-1α2 or PGC-1α3 expression induces astrocyte dysfunction and degeneration

Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) transcriptional coactivators are key regulators of energy metabolism-related genes and are expressed in energy-demanding tissues. There are several PGC-1α variants with different biological functions in different tissues. The brain is one of the tissues where the role of PGC-1α isoforms remains less explored. Here, we used a toxin-based mouse model of Parkinson's disease (PD) and observed that the expression levels of variants PGC-1α2 and PGC-1α3 in the nigrostriatal pathway increases at the onset of dopaminergic cell degeneration. This increase occurs concomitant with an increase in glial fibrillary acidic protein levels. Since PGC-1α coactivators regulate cellular adaptive responses, we hypothesized that they could be involved in the modulation of astrogliosis induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Therefore, we analysed the transcriptome of astrocytes transduced with expression vectors encoding PGC-1α1 to 1α4 by massively parallel sequencing (RNA-seq) and identified the main cellular pathways controlled by these isoforms. Interestingly, in reactive astrocytes the inflammatory and antioxidant responses, adhesion, migration, and viability were altered by PGC-1α2 and PGC-1α3, showing that sustained expression of these isoforms induces astrocyte dysfunction and degeneration. This work highlights PGC-1α isoforms as modulators of astrocyte reactivity and as potential therapeutic targets for the treatment of PD and other neurodegenerative disorders

Tumores malignos do intestino delgado

Os tumores do intestino delgado são raros e a maioria das lesões neoplásicas sintomáticas é maligna.Os neoplasmas benignos são um pouco mais freqüentes e ambos estão relacionados a um diagnóstico difícil, pois determinam queixas abdominais inespecíficas, comuns a uma grande variedade de afecções digestivas. Exames de imagem e endoscópicos podem ser úteis para o diagnóstico, mas freqüentemente não são conclusivos. Para os blastomas primários, a ressecção cirúrgica é a opção de escolha, porém, para os metastáticos, a terapêutica operatória deve ser reservada para os casos complicados por obstrução, hemorragia ou perfuração. O presente estudo tem por finalidade analisar retrospectivamente 13 casos de lesões malignas do intestino delgado, num período de 28 anos. Verificou-se maior incidência de tumores primários (69,2%) e de linfomas (30,7%). Entre os secundários, as mestástases por adenocarcinoma foram as mais freqüentes (15,4%). Enterectomia segmentar foi o procedimento cirúrgico mais realizado (84,6%) e a mortalidade hospitalar foi de 15,4%. A sobrevida de cinco anos foi nula para os pacientes portadores de metástases, enquanto que para os primários foi de 44,4%, sugerindo um melhor prognóstico para as neoplasias primitivas, independentemente do tipo histológico da neoplasia