E-QED: Electrical Bug Localization During Post-Silicon Validation Enabled by Quick Error Detection and Formal Methods

During post-silicon validation, manufactured integrated circuits are extensively tested in actual system environments to detect design bugs. Bug localization involves identification of a bug trace (a sequence of inputs that activates and detects the bug) and a hardware design block where the bug is located. Existing bug localization practices during post-silicon validation are mostly manual and ad hoc, and, hence, extremely expensive and time consuming. This is particularly true for subtle electrical bugs caused by unexpected interactions between a design and its electrical state. We present E-QED, a new approach that automatically localizes electrical bugs during post-silicon validation. Our results on the OpenSPARC T2, an open-source 500-million-transistor multicore chip design, demonstrate the effectiveness and practicality of E-QED: starting with a failed post-silicon test, in a few hours (9 hours on average) we can automatically narrow the location of the bug to (the fan-in logic cone of) a handful of candidate flip-flops (18 flip-flops on average for a design with ~ 1 Million flip-flops) and also obtain the corresponding bug trace. The area impact of E-QED is ~2.5%. In contrast, deter-mining this same information might take weeks (or even months) of mostly manual work using traditional approaches

Lack of an Effect of Oral Iron Administration on Mycophenolic Acid Pharmacokinetics in Stable Renal Transplant Recipients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90055/1/phco.27.9.1272.pd

Double primary malignancies associated with colon cancer in patients with situs inversus totalis: two case reports

Situs inversus totalis (SIT) is not itself a premalignant condition, however, rare synchronous or metachronous multiple primary malignancies have been reported. Herein we present a case of synchronous transverse and sigmoid colon cancers and a case of metachronous rectosigmoid colon and gastric cancers in patients with SIT

Strategies in Case-Based Argumentation-Based Negotiation: An Application for the Tourism Domain

[EN] Negotiation is a key solution to find an agreement between conflicting parties especially during the purchase journey. This paper treats the negotiations between a travel agency and its customers in the domain of tourism. Both automated negotiation and argumentation are gathered to create a framework for automated agents, presenting a travel agency and its customers, to negotiate a trip and exchange arguments. Agents take advantage of their past experiences and use Case-Based Reasoning to select the best strategy to follow. We represent agents using two types of profiles, Argumentative profile that represents agents¿ ways of reasoning and Preference profile that embodies customers¿ preferences in the domain of tourism.Bouslama, R.; Jordán, J.; Heras, S.; Amor, NB. (2020). Strategies in Case-Based Argumentation-Based Negotiation: An Application for the Tourism Domain. Springer. 205-217. https://doi.org/10.1007/978-3-030-51999-5_17S205217Aamodt, A., Plaza, E.: Case-based reasoning: foundational issues, methodological variations, and system approaches. AI Commun. 7(1), 39–59 (1994)Adnan, M.H.M., Hassan, M.F., Aziz, I., Paputungan, I.V.: Protocols for agent-based autonomous negotiations: a review. In: ICCOINS, pp. 622–626. IEEE (2016)Amgoud, L., Parsons, S.: Agent dialogues with conflicting preferences. In: Meyer, J.-J.C., Tambe, M. (eds.) ATAL 2001. LNCS (LNAI), vol. 2333, pp. 190–205. Springer, Heidelberg (2002). https://doi.org/10.1007/3-540-45448-9_14Amgoud, L., Prade, H.: Generation and evaluation of different types of arguments in negotiation. In: NMR, pp. 10–15 (2004)Bouslama, R., Ayachi, R., Ben Amor, N.: A new generic framework for argumentation-based negotiation using case-based reasoning. In: Medina, J., et al. (eds.) IPMU 2018. CCIS, vol. 854, pp. 633–644. Springer, Cham (2018). https://doi.org/10.1007/978-3-319-91476-3_52Bouslama, R., Ayachi, R., Ben Amor, N.: A new generic framework for mediated multilateral argumentation-based negotiation using case-based reasoning. In: Kern-Isberner, G., Ognjanović, Z. (eds.) ECSQARU 2019. LNCS (LNAI), vol. 11726, pp. 14–26. Springer, Cham (2019). https://doi.org/10.1007/978-3-030-29765-7_2Dimopoulos, Y., Moraitis, P.: Advances in argumentation based negotiation. In: Negotiation and Argumentation in Multi-agent Systems: Fundamentals, Theories, Systems and Applications, pp. 82–125 (2014)Hadidi, N., Dimopoulos, Y., Moraitis, P.: Tactics and concessions for argumentation-based negotiation. In: Computational Models of Argument: Proceedings of COMMA 2012, vol. 245, pp. 285–296 (2012)Hadoux, E., Hunter, A.: Strategic sequences of arguments for persuasion using decision trees. In: AAAI (2017)Heras, S., Jordán, J., Botti, V., Julián, V.: Argue to agree: a case-based argumentation approach. IJAR 54(1), 82–108 (2013)Heras, S., Jordán, J., Botti, V., Julián, V.: Case-based strategies for argumentation dialogues in agent societies. Inf. Sci. 223, 1–30 (2013)Jennings, N.R., Faratin, P., Lomuscio, A.R., Parsons, S., Sierra, C., Wooldridge, M.: Automated negotiation: prospects, methods and challenges. Int. J. Group Decis. Negot. 10(2), 199–215 (2001)Lazar, C.M.: Internet-an aid for e-tourism. Ecoforum J. 8(1), 1–4 (2019)Lopes, F., Novais, A.Q., Coelho, H.: Bilateral negotiation in a multi-agent energy market. In: Huang, D.-S., Jo, K.-H., Lee, H.-H., Kang, H.-J., Bevilacqua, V. (eds.) ICIC 2009. LNCS, vol. 5754, pp. 655–664. Springer, Heidelberg (2009). https://doi.org/10.1007/978-3-642-04070-2_71Park, S., Tussyadiah, I., Mazanec, J., Fesenmaier, D.: Travel personae of american pleasure travelers: a network analysis. J. Travel Tour. Mark. 27, 797–811 (2010)Rahwan, I., Ramchurn, S.D., Jennings, N.R., Mcburney, P., Parsons, S., Sonenberg, L.: Argumentation-based negotiation. KER 18(4), 343–375 (2003)Rahwan, I., Sonenberg, L., McBurney, P.: Bargaining and argument-based negotiation: some preliminary comparisons. In: Rahwan, I., Moraïtis, P., Reed, C. (eds.) ArgMAS 2004. LNCS (LNAI), vol. 3366, pp. 176–191. Springer, Heidelberg (2005). https://doi.org/10.1007/978-3-540-32261-0_12Sierra, C., Jennings, N.R., Noriega, P., Parsons, S.: A framework for argumentation-based negotiation. In: Singh, M.P., Rao, A., Wooldridge, M.J. (eds.) ATAL 1997. LNCS, vol. 1365, pp. 177–192. Springer, Heidelberg (1998). https://doi.org/10.1007/BFb0026758Soh, L.K., Tsatsoulis, C.: Agent-based argumentative negotiations with case-based reasoning. In: AAAI Fall Symposium Series on Negotiation Methods for Autonomous Cooperative Systems, pp. 16–25 (2001)Sycara, K.P.: Persuasive argumentation in negotiation. Theory Decis. 28(3), 203–242 (1990). https://doi.org/10.1007/BF00162699Walton, D.: Argumentation Schemes for Presumptive Reasoning. Routledge, Abingdon (2013

The Human Fungal Pathogen Cryptococcus neoformans Escapes Macrophages by a Phagosome Emptying Mechanism That Is Inhibited by Arp2/3 Complex-Mediated Actin Polymerisation

The lysis of infected cells by disease-causing microorganisms is an efficient but risky strategy for disseminated infection, as it exposes the pathogen to the full repertoire of the host's immune system. Cryptococcus neoformans is a widespread fungal pathogen that causes a fatal meningitis in HIV and other immunocompromised patients. Following intracellular growth, cryptococci are able to escape their host cells by a non-lytic expulsive mechanism that may contribute to the invasion of the central nervous system. Non-lytic escape is also exhibited by some bacterial pathogens and is likely to facilitate long-term avoidance of the host immune system during latency. Here we show that phagosomes containing intracellular cryptococci undergo repeated cycles of actin polymerisation. These actin ‘flashes’ occur in both murine and human macrophages and are dependent on classical WASP-Arp2/3 complex mediated actin filament nucleation. Three dimensional confocal imaging time lapse revealed that such flashes are highly dynamic actin cages that form around the phagosome. Using fluorescent dextran as a phagosome membrane integrity probe, we find that the non-lytic expulsion of Cryptococcus occurs through fusion of the phagosome and plasma membranes and that, prior to expulsion, 95% of phagosomes become permeabilised, an event that is immediately followed by an actin flash. By using pharmacological agents to modulate both actin dynamics and upstream signalling events, we show that flash occurrence is inversely related to cryptococcal expulsion, suggesting that flashes may act to temporarily inhibit expulsion from infected phagocytes. In conclusion, our data reveal the existence of a novel actin-dependent process on phagosomes containing cryptococci that acts as a potential block to expulsion of Cryptococcus and may have significant implications for the dissemination of, and CNS invasion by, this organism.\ud \u

The Nrf2 inhibitor brusatol is a potent antitumour agent in an orthotopic mouse model of colorectal cancer

© Evans et al. Nrf2 is a transcription factor that regulates cellular stress response and irinotecan-metabolising pathways. Its aberrant activity has been reported in a number of cancers, although relatively few studies have explored a role for Nrf2 in colorectal cancer (CRC). This study assessed the expression of Nrf2 in patient CRC tissues and explored the effect of Nrf2 modulation alone, or in combination with irinotecan, in human (HCT116) and murine (CT26) cell lines in vitro and in an orthotopic syngeneic mouse model utilising bioluminescent imaging. Using a tissue microarray, Nrf2 was found to be overexpressed (p < 0.01) in primary CRC and metastatic tissue relative to normal colon, with a positive correlation between Nrf2 expression in matched primary and metastatic samples. In vitro experiments in CRC cell lines revealed that Nrf2 siRNA and brusatol, which is known to inhibit Nrf2, decreased viability and sensitised cells to irinotecan toxicity. Furthermore, brusatol effectively abrogated CRC tumour growth in subcutaneously and orthotopicallyallografted mice, resulting in an average 8-fold reduction in luminescence at the study end-point (p=0.02). Our results highlight Nrf2 as a promising drug target in the treatment of CRC

Load-sharing policies in parallel simulation of agent-based demographic models

Execution parallelism in agent-Based Simulation (ABS) allows to deal with complex/large-scale models. This raises the need for runtime environments able to fully exploit hardware parallelism, while jointly offering ABS-suited programming abstractions. In this paper, we target last-generation Parallel Discrete Event Simulation (PDES) platforms for multicore systems. We discuss a programming model to support both implicit (in-place access) and explicit (message passing) interactions across concurrent Logical Processes (LPs). We discuss different load-sharing policies combining event rate and implicit/explicit LPs’ interactions. We present a performance study conducted on a synthetic test case, representative of a class of agent-based models.Peer ReviewedPostprint (author's final draft

Unique and conserved MicroRNAs in wheat chromosome 5D revealed by next-generation sequencing

MicroRNAs are a class of short, non-coding, single-stranded RNAs that act as post-transcriptional regulators in gene expression. miRNA analysis of Triticum aestivum chromosome 5D was performed on 454 GS FLX Titanium sequences of flow sorted chromosome 5D with a total of 3,208,630 good quality reads representing 1.34x and 1.61x coverage of the short (5DS) and long (5DL) arms of the chromosome respectively. In silico and structural analyses revealed a total of 55 miRNAs; 48 and 42 miRNAs were found to be present on 5DL and 5DS respectively, of which 35 were common to both chromosome arms, while 13 miRNAs were specific to 5DL and 7 miRNAs were specific to 5DS. In total, 14 of the predicted miRNAs were identified in wheat for the first time. Representation (the copy number of each miRNA) was also found to be higher in 5DL (1,949) compared to 5DS (1,191). Targets were predicted for each miRNA, while expression analysis gave evidence of expression for 6 out of 55 miRNAs. Occurrences of the same miRNAs were also found in Brachypodium distachyon and Oryza sativa genome sequences to identify syntenic miRNA coding sequences. Based on this analysis, two other miRNAs: miR1133 and miR167 were detected in B. distachyon syntenic region of wheat 5DS. Five of the predicted miRNA coding regions (miR6220, miR5070, miR169, miR5085, miR2118) were experimentally verified to be located to the 5D chromosome and three of them : miR2118, miR169 and miR5085, were shown to be 5D specific. Furthermore miR2118 was shown to be expressed in Chinese Spring adult leaves. miRNA genes identified in this study will expand our understanding of gene regulation in bread wheat

MaxMin Linear Initialization for Fuzzy C-Means

International audienceClustering is an extensive research area in data science. The aim of clustering is to discover groups and to identify interesting patterns in datasets. Crisp (hard) clustering considers that each data point belongs to one and only one cluster. However, it is inadequate as some data points may belong to several clusters, as is the case in text categorization. Thus, we need more flexible clustering. Fuzzy clustering methods, where each data point can belong to several clusters, are an interesting alternative. Yet, seeding iterative fuzzy algorithms to achieve high quality clustering is an issue. In this paper, we propose a new linear and efficient initialization algorithm MaxMin Linear to deal with this problem. Then, we validate our theoretical results through extensive experiments on a variety of numerical real-world and artificial datasets. We also test several validity indices, including a new validity index that we propose, Transformed Standardized Fuzzy Difference (TSFD)

Rabies screen reveals GPe control of cocaine-triggered plasticity.

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the increase in GPe labelling. Inhibition of GPe activity revealed that it contributes to two forms of cocaine-triggered behavioural plasticity, at least in part by disinhibiting dopamine neurons in the ventral tegmental area. These results suggest that rabies-based unbiased screening of changes in input populations can identify previously unappreciated circuit elements that critically support behavioural adaptations