PrIC3: Property Directed Reachability for MDPs

IC3 has been a leap forward in symbolic model checking. This paper proposes PrIC3 (pronounced pricy-three), a conservative extension of IC3 to symbolic model checking of MDPs. Our main focus is to develop the theory underlying PrIC3. Alongside, we present a first implementation of PrIC3 including the key ingredients from IC3 such as generalization, repushing, and propagation

Commentary: Selecting synaptic partners: GRASPing the role of UNC- 6/netrin

Forming synaptic connections of the appropriate strength between specific neurons is crucial for constructing neural circuits to control behavior. A recent paper in Neural Development describes the use of a synapse-specific label in Caenorhabditis elegans to implicate local UNC-6/netrin signaling in this developmental process. Thus, as well as their well known roles in cell migration and axon guidance, UNC-6/netrin signals distinguish an appropriate synaptic partner from other potential targets

Viunalikeviruses are environmentally common agents of horizontal gene transfer in pathogens and biocontrol bacteria.

Bacteriophages have been used as natural biocontrol and therapeutic agents, but also as biotechnological tools for bacterial engineering. We showed recently that the transducing bacteriophage ϕMAM1 is a ViI-like phage and a member of the new genus, 'Viunalikevirus'. Here, we show that four additional ViI-like phages and three new environmentally isolated viunalikeviruses, all infecting plant and human pathogens, are very efficient generalised transducers capable of transducing chromosomal markers at frequencies of up to 10(-4) transductants per plaque-forming unit. We also demonstrate the interstrain transduction of plasmids and chromosomal markers, including genes involved in anabolism, genes for virulence and genes encoding secondary metabolites involved in biocontrol. We propose that all viunalikeviruses are likely to perform efficient horizontal gene transfer. Viunalikeviruses therefore represent useful agents for functional genomics and bacterial engineering, and for chemical and synthetic biology studies, but could be viewed as inappropriate choices for phage therapy.This research was supported by the EU Marie-Curie Intra-European Fellowship for Career Development (FP7- PEOPLE-2011-IEF) grant number 298003.This is the version of record of the article "Viunalikeviruses are environmentally common agents of horizontal gene transfer in pathogens and biocontrol bacteria" published in ISME Journal on August 2104 under the NPG Open Access option. The published version of record is available on the journal website at http://dx.doi.org/10.1038/ismej.2014.15

Pseudogap temperature as a Widom line in doped Mott insulators

The pseudogap refers to an enigmatic state of matter with unusual physical properties found below a characteristic temperature $T^*$ in hole-doped high-temperature superconductors. Determining $T^*$ is critical for understanding this state. Here we study the simplest model of correlated electron systems, the Hubbard model, with cluster dynamical mean-field theory to find out whether the pseudogap can occur solely because of strong coupling physics and short nonlocal correlations. We find that the pseudogap characteristic temperature $T^*$ is a sharp crossover between different dynamical regimes along a line of thermodynamic anomalies that appears above a first-order phase transition, the Widom line. The Widom line emanating from the critical endpoint of a first-order transition is thus the organizing principle for the pseudogap phase diagram of the cuprates. No additional broken symmetry is necessary to explain the phenomenon. Broken symmetry states appear in the pseudogap and not the other way around.Comment: 6 pages, 4 figures and supplementary information; published versio

Spin correlations in the electron-doped high-transition-temperature superconductor Nd{2-x}Ce{x}CuO{4+/-delta}

High-transition-temperature (high-Tc) superconductivity develops near antiferromagnetic phases, and it is possible that magnetic excitations contribute to the superconducting pairing mechanism. To assess the role of antiferromagnetism, it is essential to understand the doping and temperature dependence of the two-dimensional antiferromagnetic spin correlations. The phase diagram is asymmetric with respect to electron and hole doping, and for the comparatively less-studied electron-doped materials, the antiferromagnetic phase extends much further with doping [1, 2] and appears to overlap with the superconducting phase. The archetypical electron-doped compound Nd{2-x}Ce{x}CuO{4\pm\delta} (NCCO) shows bulk superconductivity above x \approx 0.13 [3, 4], while evidence for antiferromagnetic order has been found up to x \approx 0.17 [2, 5, 6]. Here we report inelastic magnetic neutron-scattering measurements that point to the distinct possibility that genuine long-range antiferromagnetism and superconductivity do not coexist. The data reveal a magnetic quantum critical point where superconductivity first appears, consistent with an exotic quantum phase transition between the two phases [7]. We also demonstrate that the pseudogap phenomenon in the electron-doped materials, which is associated with pronounced charge anomalies [8-11], arises from a build-up of spin correlations, in agreement with recent theoretical proposals [12, 13].Comment: 5 pages, 4 figure

Equivalence of switching linear systems by bisimulation

A general notion of hybrid bisimulation is proposed for the class of switching linear systems. Connections between the notions of bisimulation-based equivalence, state-space equivalence, algebraic and input–output equivalence are investigated. An algebraic characterization of hybrid bisimulation and an algorithmic procedure converging in a finite number of steps to the maximal hybrid bisimulation are derived. Hybrid state space reduction is performed by hybrid bisimulation between the hybrid system and itself. By specializing the results obtained on bisimulation, also characterizations of simulation and abstraction are derived. Connections between observability, bisimulation-based reduction and simulation-based abstraction are studied.\ud \u

Dynamics of DNA replication loops reveal temporal control of lagging-strand synthesis

In all organisms, the protein machinery responsible for the replication of DNA, the replisome, is faced with a directionality problem. The antiparallel nature of duplex DNA permits the leading-strand polymerase to advance in a continuous fashion, but forces the lagging-strand polymerase to synthesize in the opposite direction. By extending RNA primers, the lagging-strand polymerase restarts at short intervals and produces Okazaki fragments. At least in prokaryotic systems, this directionality problem is solved by the formation of a loop in the lagging strand of the replication fork to reorient the lagging-strand DNA polymerase so that it advances in parallel with the leading-strand polymerase. The replication loop grows and shrinks during each cycle of Okazaki fragment synthesis. Here we use single-molecule techniques to visualize, in real time, the formation and release of replication loops by individual replisomes of bacteriophage T7 supporting coordinated DNA replication. Analysis of the distributions of loop sizes and lag times between loops reveals that initiation of primer synthesis and the completion of an Okazaki fragment each serve as a trigger for loop release. The presence of two triggers may represent a fail-safe mechanism ensuring the timely reset of the replisome after the synthesis of every Okazaki fragment.

Comparison of the efficacy and safety outcomes of edoxaban in 8040 women versus 13 065 men with atrial fibrillation in the ENGAGE AF-TIMI 48 trial.

BACKGROUND: Female sex is an independent risk factor for stroke and systemic embolic events in patients with atrial fibrillation. This study aimed to examine the efficacy and safety profile of edoxaban in women versus men. METHODS: The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) randomly assigned 21 105 patients (8040 women) with atrial fibrillation and CHADS2 score ≥2 either to a higher-dose edoxaban regimen, a lower-dose edoxaban regimen, or warfarin. The primary end points of the trial were the composite of stroke or systemic embolic events (efficacy), and International Society on Thrombosis and Haemostasis-defined major bleeding (safety). RESULTS: In comparison with men, women were older, had lower body weight, were more likely to have hypertension and renal dysfunction, but less likely to smoke, drink alcohol, or have diabetes or coronary artery disease. Pretreatment endogenous factor Xa activity was significantly higher in women than in men (92.5% versus 86.1%, P<0.001). Treatment with edoxaban in women resulted in greater peak edoxaban concentration and inhibition of endogenous factor Xa in comparison with men, resulting in similar endogenous factor Xa activity between the sexes 2 to 4 hours after dose. Treatment with higher-dose edoxaban regimen (versus warfarin) resulted in similar reduction in the risk of stroke/systemic embolic events (women: hazard ratio [HR], 0.87 [0.69-1.11], men: HR, 0.87 [0.71-1.06]; P-interaction=0.97) and major bleeding (women: HR, 0.74 [0.59-0.92], men: HR, 0.84 [0.72-0.99]; P-interaction=0.34) in women and men. However, women assigned to higher-dose edoxaban regimen experienced greater reductions in hemorrhagic stroke (HR, 0.30 [95% CI, 0.15-0.59] versus HR, 0.70 [95% CI, 0.46-1.06]), intracranial bleeding (HR, 0.20 [95% CI, 0.10-0.39] versus HR, 0.63 [95% CI, 0.44-0.89]), and life-threatening or fatal bleeding (HR, 0.25 [95% CI, 0.15-0.42] versus HR, 0.72 [95% CI, 0.54-0.96]) than men (each P-interaction<0.05). CONCLUSIONS: Despite many differences in baseline characteristics between women and men and higher baseline endogenous factor Xa levels in women, the intensity of anticoagulation achieved with edoxaban between the sexes was similar. Treatment with higher-dose edoxaban regimen resulted in an even greater reduction in hemorrhagic stroke and several serious bleeding outcomes in women than in men, whereas the efficacy profile was similar between sexes