Refinement-based verification of sequential implementations of Stateflow charts

Simulink/Stateflow charts are widely used in industry for the specification of control systems, which are often safety-critical. This suggests a need for a formal treatment of such models. In previous work, we have proposed a technique for automatic generation of formal models of Stateflow blocks to support refinement-based reasoning. In this article, we present a refinement strategy that supports the verification of automatically generated sequential C implementations of Stateflow charts. In particular, we discuss how this strategy can be specialised to take advantage of architectural features in order to allow a higher level of automation.Comment: In Proceedings Refine 2011, arXiv:1106.348

New features of quantum discord uncovered by q-entropies

The notion of quantum discord introduced by Ollivier and Zurek [Phys. Rev. Lett 88, 017901 (2001)] (see also Henderson and Vedral [J. Phys. A 34, 6899 (2001)]) has attracted increasing attention, in recent years, as an entropic quantifier of non-classical features pertaining to the correlations exhibited by bipartite quantum systems. Here we generalize the notion so as to encompass power-law q-entropies (that reduce to the standard Shannon entropy in the limit $q \to 1$) and study the concomitant consequences. The ensuing, new discord-like measures we advance describe aspects of non-classicality that are different from those associated with the standard quantum discord. A particular manifestation of this difference concerns a feature related to order. Let $D_1$ stand for the standard, Shannon-based discord measure and $D_q$ for the $q \ne 1$ one. If two quantum states $A$, $B$ are such that $D_1(A) > D_1(B)$, this order-relation does not remain invariant under a change from $D_1$ to $D_q$.Comment: 11 pages, 8 figure

An adaptive delayed acknowledgment strategy to improve TCP performance in multi-hop wireless networks.

In multi-hop wireless networks, transmission control protocol (TCP) suffers from performance deterioration due to poor wireless channel characteristics. Earlier studies have shown that the small TCP acknowledgments consume as much wireless resources as the long TCP data packets. Moreover, generating an acknowledgment (ACK) for each incoming data packet reduces the performance of TCP. The main factor affecting TCP performance in multi-hop wireless networks is the contention and collision between ACK and data packets that share the same path. Thus, lowering the number of ACKs using the delayed acknowledgment option defined in IETF RFC 1122 will improve TCP performance. However, large cumulative ACKs will induce packet loss due to retransmission time-out at the sender side of TCP. Motivated by this understanding, we propose a new TCP receiver with an adaptive delayed ACK strategy to improve TCP performance in multi-hop wireless networks. Extensive simulations have been done to prove and evaluate our strategy over different topologies. The simulation results demonstrate that our strategy can improve TCP performance significantly

Large Interruptions of GAA Repeat Expansion Mutations in Friedreich Ataxia Are Very Rare

Friedreich ataxia is a multi-system autosomal recessive inherited disorder primarily caused by homozygous GAA repeat expansion mutations within intron 1 of the frataxin gene. The resulting deficiency of frataxin protein leads to progressive mitochondrial dysfunction, oxidative stress, and cell death, with the main affected sites being the large sensory neurons of the dorsal root ganglia and the dentate nucleus of the cerebellum. The GAA repeat expansions may be pure (GAA)n in sequence or may be interrupted with regions of non-GAA sequence. To our knowledge, there has been no large-scale study of FRDA patient DNA samples to determine the frequency of large interruptions in GAA repeat expansions. Therefore, we have investigated a panel of 245 Friedreich ataxia patient and carrier DNA samples using GAA repeat PCR amplification and MboII restriction enzyme digestion. We demonstrate that the vast majority (97.8%) of Friedreich ataxia GAA repeat expansion samples do not contain significant sequence changes that would result in abnormal MboII digestion profiles, indicating that they are primarily pure GAA repeats. These results show for the first time that large interruptions in the GAA repeats are very rare

Large interruptions of GAA repeat expansiopns mutations in Friedreich ataxia are very rare

Copyright © 2018 Al-Mahdawi, Ging, Bayot, Cavalcanti, La Cognata, Cavallaro, Giunti and Pook. Friedreich ataxia is a multi-system autosomal recessive inherited disorder primarily caused by homozygous GAA repeat expansion mutations within intron 1 of the frataxin gene. The resulting deficiency of frataxin protein leads to progressive mitochondrial dysfunction, oxidative stress and cell death, with the main affected sites being the large sensory neurons of the dorsal root ganglia and the dentate nucleus of the cerebellum. The GAA repeat expansions may be pure (GAA)n in sequence or may be interrupted with regions of non-GAA sequence. To our knowledge there has been no large-scale study of FRDA patient DNA samples to determine the frequency of large interruptions in GAA repeat expansions. Therefore, we have investigated a panel of 245 Friedreich ataxia patient and carrier DNA samples using GAA repeat PCR amplification and MboII restriction enzyme digestion. We demonstrate that the vast majority (97.8%) of Friedreich ataxia GAA repeat expansion samples do not contain significant sequence changes that would result in abnormal MboII digestion profiles, indicating that they are primarily pure GAA repeats. These results show for the first time that large interruptions in the GAA repeats are very rare.European Union Seventh Framework Programm

Large Interruptions of GAA Repeat Expansion Mutations in Friedreich Ataxia Are Very Rare

Friedreich ataxia is a multi-system autosomal recessive inherited disorder primarily caused by homozygous GAA repeat expansion mutations within intron 1 of the frataxin gene. The resulting deficiency of frataxin protein leads to progressive mitochondrial dysfunction, oxidative stress, and cell death, with the main affected sites being the large sensory neurons of the dorsal root ganglia and the dentate nucleus of the cerebellum. The GAA repeat expansions may be pure (GAA)n in sequence or may be interrupted with regions of non-GAA sequence. To our knowledge, there has been no large-scale study of FRDA patient DNA samples to determine the frequency of large interruptions in GAA repeat expansions. Therefore, we have investigated a panel of 245 Friedreich ataxia patient and carrier DNA samples using GAA repeat PCR amplification and MboII restriction enzyme digestion. We demonstrate that the vast majority (97.8%) of Friedreich ataxia GAA repeat expansion samples do not contain significant sequence changes that would result in abnormal MboII digestion profiles, indicating that they are primarily pure GAA repeats. These results show for the first time that large interruptions in the GAA repeats are very rare

miR-22 and miR-205 Drive Tumor Aggressiveness of Mucoepidermoid Carcinomas of Salivary Glands

Publisher Copyright: Copyright © 2022 Naakka, Barros-Filho, Adnan-Awad, Al-Samadi, Marchi, Kuasne, Korelin, Suleymanova, Brown, Scapulatempo-Neto, Lourenço, Castilho, Kowalski, Mäkitie, Araújo, Leivo, Rogatto, Salo and Passador-Santos.Objectives: To integrate mRNA and miRNA expression profiles of mucoepidermoid carcinomas (MECs) and normal salivary gland (NSGs) tissue samples and identify potential drivers. Material and Methods: Gene and miRNA expression arrays were performed in 35 MECs and six NSGs. Results: We found 46 differentially expressed (DE) miRNAs and 3,162 DE mRNAs. Supervised hierarchical clustering analysis of the DE transcripts revealed two clusters in both miRNA and mRNA profiles, which distinguished MEC from NSG samples. The integrative miRNA-mRNA analysis revealed a network comprising 696 negatively correlated interactions (44 miRNAs and 444 mRNAs) involving cell signaling, cell cycle, and cancer-related pathways. Increased expression levels of miR-205-5p and miR-224-5p and decreased expression levels of miR-139-3p, miR-145-3p, miR-148a-3p, miR-186-5p, miR-338-3p, miR-363-3p, and miR-4324 were significantly related to worse overall survival in MEC patients. Two overexpressed miRNAs in MEC (miR-22 and miR-205) were selected for inhibition by the CRISPR-Cas9 method. Cell viability, migration, and invasion assays were performed using an intermediate grade MEC cell line. Knockout of miR-205 reduced cell viability and enhanced ZEB2 expression, while miR-22 knockout reduced cell migration and invasion and enhanced ESR1 expression. Our results indicate a distinct transcriptomic profile of MEC compared to NSG, and the integrative analysis highlighted miRNA-mRNA interactions involving cancer-related pathways, including PTEN and PI3K/AKT. Conclusion: The in vitro functional studies revealed that miR-22 and miR-205 deficiencies reduced the viability, migration, and invasion of the MEC cells suggesting they are potential oncogenic drivers in MEC.Peer reviewe