Featherweight VeriFast

VeriFast is a leading research prototype tool for the sound modular verification of safety and correctness properties of single-threaded and multithreaded C and Java programs. It has been used as a vehicle for exploration and validation of novel program verification techniques and for industrial case studies; it has served well at a number of program verification competitions; and it has been used for teaching by multiple teachers independent of the authors. However, until now, while VeriFast's operation has been described informally in a number of publications, and specific verification techniques have been formalized, a clear and precise exposition of how VeriFast works has not yet appeared. In this article we present for the first time a formal definition and soundness proof of a core subset of the VeriFast program verification approach. The exposition aims to be both accessible and rigorous: the text is based on lecture notes for a graduate course on program verification, and it is backed by an executable machine-readable definition and machine-checked soundness proof in Coq

Whey proteins interact with lipids during autoxidation primarly via the production of reactive carbonyl species

Nowadays, it is well recognized that polyunsaturated fatty acids (PUFAs) can provide extensive nutritional and health benefits. Thus, ω-3 PUFAs have been considered to contribute to the prevention of several diseases. Recognition of the potential benefits of ω-3 fatty acids has stimulated increased interest towards the fortification of foods with oils rich in these particular fatty acids. However, enrichment of food products with such unsaturated fatty acids should be carefully evaluated since they are highly susceptible to oxidation. Moreover, exposure of proteins to peroxidizing lipids or their secondary breakdown products may induce severe changes in proteins, including polymerization, insolubilization and formation of lipid – protein complexes. Several amino acids, but mainly mainly cysteine, methionine, histidine, tyrosine and lysine are affected by the secondary lipid oxidation products, therefore leading to reductions of their availability. The objective of this study was to characterize changes induced in whey protein isolate (a mixture of α-lactalbumin and β-lactoglobulin) through oxidation with oils with different unsaturation degrees and different initial oxidation status. The incubation of whey proteins with oils caused an increase in protein bound carbonyl content through the interaction of lipid oxidation products with the amino acids. Changes in the amino acid composition were therefore also observed mostly upon incubation with fish and highly oxidized soybean oil. Interaction of proteins with lipid oxidation products was taking place via interaction of the reactive carbonyl species formed thus leading to protein aggregates formation. Protein aggregation was therefore one of the most prominent consequence of the interaction of whey proteins with oxidizing lipids

On Q-polynomial regular near 2d-gons

We discuss thick regular near 2d-gons with a Q-polynomial collinearity graph. For da parts per thousand yen4, we show that apart from Hamming near polygons and dual polar spaces there are no thick Q-polynomial regular near polygons. We also show that no regular near hexagons exist with parameters (s, t (2), t) equal to (3, 1, 34), (8, 4, 740), (92, 64, 1314560), (95, 19, 1027064) or (105, 147, 2763012). Such regular near hexagons are necessarily Q-polynomial. All these nonexistence results imply the nonexistence of distance-regular graphs with certain classical parameters. We also discuss some implications for the classification of dense near polygons with four points per line

The Belgian Electronic Identity Card: a Verification Case Study

In the field of annotation-based source code level program verification for Java-like languages, separation-logic based verifiers offer a promising alternative to classic JML based verifiers such as ESC/Java2, the Mobius tool or Spec#. Researchers have demonstrated the advantages of separation logic based verification by showing that it is feasible to verify very challenging (though very small) sample code, such as design patterns, or highly concurrent code. However, there is little experience in using this new breed of verifiers on real code. In this paper we report on our experience of verifying several thousands of lines of Java Card code using VeriFast, one of the state-of-the-art separation logic based verifiers. We quantify annotation overhead, verification performance, and impact on code quality (number of bugs found). Finally, our experiments suggest a number of potential improvements to the VeriFast tool

The N‐terminal p.(Ser38Cys) TIMP3 mutation underlying Sorsby fundus dystrophy is a founder mutation disrupting an intramolecular disulfide bond

Sorsby fundus dystrophy (SFD) is a macular degeneration caused by mutations in TIMP3, the majority of which introduce a novel cysteine. However, the exact molecular mechanisms underlying SFD remain unknown. We aimed to provide novel insights into the functional consequences of a distinct N-terminal mutation. Haplotype reconstruction in three SFD families revealed that the identified c.113C>G, p.(Ser38Cys) mutation is a founder in Belgian and northern French families with a late-onset SFD phenotype. Functional consequences of the p.(Ser38Cys) mutation were investigated by high-resolution Western blot analysis of wild type and mutant TIMP3 using patient fibroblasts and in vitro generated proteins, and by molecular modeling of TIMP3 and its interaction partners. We could not confirm a previous hypothesis on dimerization of mutant TIMP3 proteins. However, we identified aberrant intramolecular disulfide bonding. Our data provide evidence for disruption of the established Cys36-Cys143 disulfide bond and formation of a novel Cys36-Cys38 bond, possibly associated with increased glycosylation of the protein. In conclusion, we propose a novel pathogenetic mechanism underlying the p.(Ser38Cys) TIMP3 founder mutation involving intramolecular disulfide bonding. These results provide new insights into the pathogenesis of SFD and other retinopathies linked to mutations in TIMP3, such as age-related macular degeneration

High-grade endometrial stromal sarcoma presenting in a 28-year-old woman during pregnancy: a case report

<p>Abstract</p> <p>Introduction</p> <p>To the best of our knowledge, soft tissue sarcomas have not prevously been reported as a complication during pregnancy.</p> <p>Case presentation</p> <p>A 28-year-old Caucasian woman was diagnosed with a transperitoneal sarcoma during pregnancy. Morphological, immunohistochemical, chromosomal and mutational analyses pointed towards a high-grade endometrial stromal sarcoma. Although surgery and chemotherapy are possible during pregnancy, we were unable to perform these in this case.</p> <p>Conclusion</p> <p>The potential to treat gynecological cancer during pregnancy should always be assessed individually.</p

Processing by proprotein convertases is required for glypican-3 modulation of cell survival, Wnt signaling, and gastrulation movements

Glypican (GPC)-3 inhibits cell proliferation and regulates cell survival during development. This action is demonstrated by GPC3 loss-of-function mutations in humans and mice. Here, we show that the GPC3 core protein is processed by a furinlike convertase. This processing is essential for GPC3 modulating Wnt signaling and cell survival in vitro and for supporting embryonic cell movements in zebrafish. The processed GPC3 core protein is necessary and sufficient for the cell-specific induction of apoptosis, but in vitro effects on canonical and noncanonical Wnt signaling additionally require substitution of the core protein with heparan sulfate. Wnt 5A physically associates only with processed GPC3, and only a form of GPC3 that can be processed by a convertase is able to rescue epiboly and convergence/extension movements in GPC3 morphant embryos. Our data imply that the Simpson–Golabi–Behmel syndrome may in part result from a loss of GPC3 controls on Wnt signaling, and suggest that this function requires the cooperation of both the protein and the heparan sulfate moieties of the proteoglycan