Liveness-Driven Random Program Generation

Randomly generated programs are popular for testing compilers and program analysis tools, with hundreds of bugs in real-world C compilers found by random testing. However, existing random program generators may generate large amounts of dead code (computations whose result is never used). This leaves relatively little code to exercise a target compiler's more complex optimizations. To address this shortcoming, we introduce liveness-driven random program generation. In this approach the random program is constructed bottom-up, guided by a simultaneous structural data-flow analysis to ensure that the generator never generates dead code. The algorithm is implemented as a plugin for the Frama-C framework. We evaluate it in comparison to Csmith, the standard random C program generator. Our tool generates programs that compile to more machine code with a more complex instruction mix.Comment: Pre-proceedings paper presented at the 27th International Symposium on Logic-Based Program Synthesis and Transformation (LOPSTR 2017), Namur, Belgium, 10-12 October 2017 (arXiv:1708.07854

An Experimental Evaluation of Deliberate Unsoundness in a Static Program Analyzer

Abstract. Many practical static analyzers are not completely sound by design. Their designers trade soundness in order to increase automa-tion, improve performance, and reduce the number of false positives or the annotation overhead. However, the impact of such design decisions on the effectiveness of an analyzer is not well understood. In this pa-per, we report on the first systematic effort to document and evaluate the sources of unsoundness in a static analyzer. We present a code in-strumentation that reflects the sources of deliberate unsoundness in the.NET static analyzer Clousot. We have instrumented code from several open source projects to evaluate how often concrete executions violate Clousot’s unsound assumptions. In our experiments, this was the case in 8–29 % of all analyzed methods. Our approach and findings can guide users of static analyzers in using them fruitfully, and designers in finding good trade-offs.

Differentially Testing Soundness and Precision of Program Analyzers

In the last decades, numerous program analyzers have been developed both by academia and industry. Despite their abundance however, there is currently no systematic way of comparing the effectiveness of different analyzers on arbitrary code. In this paper, we present the first automated technique for differentially testing soundness and precision of program analyzers. We used our technique to compare six mature, state-of-the art analyzers on tens of thousands of automatically generated benchmarks. Our technique detected soundness and precision issues in most analyzers, and we evaluated the implications of these issues to both designers and users of program analyzers

Crystal structure of the TLDc domain of oxidation resistance protein 2 from zebrafish

The oxidation resistance proteins (OXR) help to protect eukaryotes from reactive oxygen species. The sole C-terminal domain of the OXR, named TLDc is sufficient to perform this function. However, the mechanism by which oxidation resistance occurs is poorly understood. We present here the crystal structure of the TLDc domain of the oxidation resistance protein 2 from zebrafish. The structure was determined by X-ray crystallography to atomic resolution (0.97Å) and adopts an overall globular shape. Two antiparallel β-sheets form a central β-sandwich, surrounded by two helices and two one-turn helices. The fold shares low structural similarity to known structures.Animal science

A high-affinity, bivalent PDZ domain inhibitor complexes PICK1 to alleviate neuropathic pain

Maladaptive plasticity involving increased expression of AMPA‐type glutamate receptors is involved in several pathologies, including neuropathic pain, but direct inhibition of AMPARs is associated with side effects. As an alternative, we developed a cell‐permeable, high‐affinity (~2 nM) peptide inhibitor, Tat‐P$_4$‐(C5)$_2$, of the PDZ domain protein PICK1 to interfere with increased AMPAR expression. The affinity is obtained partly from the Tat peptide and partly from the bivalency of the PDZ motif, engaging PDZ domains from two separate PICK1 dimers to form a tetrameric complex. Bivalent Tat‐P$_4$‐(C5)$_2$ disrupts PICK1 interaction with membrane proteins on supported cell membrane sheets and reduce the interaction of AMPARs with PICK1 and AMPA‐receptor surface expression in vivo. Moreover, Tat‐P$_4$‐(C5)$_2$ administration reduces spinal cord transmission and alleviates mechanical hyperalgesia in the spared nerve injury model of neuropathic pain. Taken together, our data reveal Tat‐P$_4$‐(C5)$_2$ as a novel promising lead for neuropathic pain treatment and expand the therapeutic potential of bivalent inhibitors to non‐tandem protein–protein interaction domains

Cerebellar Globular Cells Receive Monoaminergic Excitation and Monosynaptic Inhibition from Purkinje Cells

Inhibitory interneurons in the cerebellar granular layer are more heterogeneous than traditionally depicted. In contrast to Golgi cells, which are ubiquitously distributed in the granular layer, small fusiform Lugaro cells and globular cells are located underneath the Purkinje cell layer and small in number. Globular cells have not been characterized physiologically. Here, using cerebellar slices obtained from a strain of gene-manipulated mice expressing GFP specifically in GABAergic neurons, we morphologically identified globular cells, and compared their synaptic activity and monoaminergic influence of their electrical activity with those of small Golgi cells and small fusiform Lugaro cells. Globular cells were characterized by prominent IPSCs together with monosynaptic inputs from the axon collaterals of Purkinje cells, whereas small Golgi cells or small fusiform Lugaro cells displayed fewer and smaller spontaneous IPSCs. Globular cells were silent at rest and fired spike discharges in response to application of either serotonin (5-HT) or noradrenaline. The two monoamines also facilitated small Golgi cell firing, but only 5-HT elicited firing in small fusiform Lugaro cells. Furthermore, globular cells likely received excitatory monosynaptic inputs through mossy fibers. Because globular cells project their axons long in the transversal direction, the neuronal circuit that includes interplay between Purkinje cells and globular cells could regulate Purkinje cell activity in different microzones under the influence of monoamines and mossy fiber inputs, suggesting that globular cells likely play a unique modulatory role in cerebellar motor control