A Game-Theoretic Foundation for the Maximum Software Resilience against Dense Errors

Safety-critical systems need to maintain their functionality in the presence of multiple errors caused by component failures or disastrous environment events. We propose a game-theoretic foundation for synthesizing control strategies that maximize the resilience of a software system in defense against a realistic error model. The new control objective of such a game is called $k$ -resilience. In order to be $k$ -resilient, a system needs to rapidly recover from infinitely many waves of a small number of up to $k$ close errors provided that the blocks of up to $k$ errors are separated by short time intervals, which can be used by the system to recover. We first argue why we believe this to be the right level of abstraction for safety critical systems when local faults are few and far between. We then show how the analysis of $k$ -resilience problems can be formulated as a model-checking problem of a mild extension to the alternating-time $\mu$ -calculus (AMC). The witness for $k$ resilience, which can be provided by the model checker, can be used for providing control strategies that are optimal with respect to resilience. We show that the computational complexity of constructing such optimal control strategies is low and demonstrate the feasibility of our approach through an implementation and experimental results

Persistent clinical efficacy and safety of anti-tumour necrosis factor \textgreeka therapy with infliximab in patients with ankylosing spondylitis over 5 years: evidence for different types of response

Background: There is insufficient evidence for the long-term efficacy and safety of anti-tumour necrosis factor therapy in patients with ankylosing spondylitis (AS). This is the first report on the treatment with infliximab over 5 years.Methods: As part of a multicentre randomised trial, 69 patients with active AS at baseline (BL) have been continuously treated with infliximab (5 mg/kg i.v. every 6 weeks)---except for a short discontinuation after 3 years (FU1). The primary outcome of this extension was remission according to the ASsessment in Ankylosing Spondylitis (ASAS) criteria at the end of year 5 of the study (FU2).Results: Of the 43 patients who completed year 3, 42 agreed to continue, 38 of which (90.5%) finished year 5 (55% of 69 initially). Partial clinical remission was achieved in 13 of 38 patients (34.2%) at FU1 and FU2. At FU2, the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was 2.5±1.9 (BL:6.4, FU1:2.5). BASDAI values <4 were seen in 79% of patients at both, FU1 and FU2. ASAS 20% and 40% responses were seen in 32 (84%) and 24 (63%) patients at FU2, respectively. Most patients classified as non-responders at FU2 were part-time responders, as all but one patient achieved an ASAS 20% response at least once within the last 2 years. Three types of responders were identified. No major side effects occurred during years 4 and 5 of infliximab therapy.Conclusions: Infliximab is safe and efficacious in AS patients over 5 years. The majority of the patients remained on treatment and had rather persistent levels of low disease activity. Different response types could be identified

Rotational Cooling of Polar Molecules by Stark-tuned Cavity Resonance

A general scheme for rotational cooling of diatomic heteronuclear molecules is proposed. It uses a superconducting microwave cavity to enhance the spontaneous decay via Purcell effect. Rotational cooling can be induced by sequentially tuning each rotational transition to cavity resonance, starting from the highest transition level to the lowest using an electric field. Electrostatic multipoles can be used to provide large confinement volume with essentially homogeneous background electric field.Comment: 10 pages, 6 figure

Multi-Player and Multi-Choice Quantum Game

We investigate a multi-player and multi-choice quantum game. We start from two-player and two-choice game and the result is better than its classical version. Then we extend it to N-player and N-choice cases. In the quantum domain, we provide a strategy with which players can always avoid the worst outcome. Also, by changing the value of the parameter of the initial state, the probabilities for players to obtain the best payoff will be much higher that in its classical version.Comment: 4 pages, 1 figur

Local Strategy Improvement for Parity Game Solving

The problem of solving a parity game is at the core of many problems in model checking, satisfiability checking and program synthesis. Some of the best algorithms for solving parity game are strategy improvement algorithms. These are global in nature since they require the entire parity game to be present at the beginning. This is a distinct disadvantage because in many applications one only needs to know which winning region a particular node belongs to, and a witnessing winning strategy may cover only a fractional part of the entire game graph. We present a local strategy improvement algorithm which explores the game graph on-the-fly whilst performing the improvement steps. We also compare it empirically with existing global strategy improvement algorithms and the currently only other local algorithm for solving parity games. It turns out that local strategy improvement can outperform these others by several orders of magnitude

New Deterministic Algorithms for Solving Parity Games

We study parity games in which one of the two players controls only a small number $k$ of nodes and the other player controls the $n-k$ other nodes of the game. Our main result is a fixed-parameter algorithm that solves bipartite parity games in time $k^{O(\sqrt{k})}\cdot O(n^3)$, and general parity games in time $(p+k)^{O(\sqrt{k})} \cdot O(pnm)$, where $p$ is the number of distinct priorities and $m$ is the number of edges. For all games with $k = o(n)$ this improves the previously fastest algorithm by Jurdzi{\'n}ski, Paterson, and Zwick (SICOMP 2008). We also obtain novel kernelization results and an improved deterministic algorithm for graphs with small average degree

Structural Synthesis for GXW Specifications

We define the GXW fragment of linear temporal logic (LTL) as the basis for synthesizing embedded control software for safety-critical applications. Since GXW includes the use of a weak-until operator we are able to specify a number of diverse programmable logic control (PLC) problems, which we have compiled from industrial training sets. For GXW controller specifications, we develop a novel approach for synthesizing a set of synchronously communicating actor-based controllers. This synthesis algorithm proceeds by means of recursing over the structure of GXW specifications, and generates a set of dedicated and synchronously communicating sub-controllers according to the formula structure. In a subsequent step, 2QBF constraint solving identifies and tries to resolve potential conflicts between individual GXW specifications. This structural approach to GXW synthesis supports traceability between requirements and the generated control code as mandated by certification regimes for safety-critical software. Synthesis for GXW specifications is in PSPACE compared to 2EXPTIME-completeness of full-fledged LTL synthesis. Indeed our experimental results suggest that GXW synthesis scales well to industrial-sized control synthesis problems with 20 input and output ports and beyond.Comment: The long (including appendix) version being reviewed by CAV'16 program committee. Compared to the submitted version, one author (out of her wish) is moved to the Acknowledgement. (v2) Corrected typos. (v3) Add an additional remark over environment assumption and easy corner case

RSPO3 expands intestinal stem cell and niche compartments and drives tumorigenesis

Objective The gross majority of colorectal cancer cases results from aberrant Wnt/ß-catenin signalling through adenomatous polyposis coli (APC) or CTNNB1 mutations. However, a subset of human colon tumours harbour, mutually exclusive with APC and CTNNB1 mutations, gene fusions in RSPO2 or RSPO3, leading to enhanced expression of these R-spondin genes. This suggested that RSPO activation can substitute for the most common mutations as an alternative driver for intestinal cancer. Involvement of RSPO3 in tumour growth was recently shown in RSPO3-fusion-positive xenograft models. The current study determines the extent into which solely a gain in RSPO3 actually functions as a driver of intestinal cancer in a direct, causal fashion, and addresses the in vivo activities of RSPO3 in parallel. Design We generated a conditional Rspo3 transgenic mouse model in which the Rspo3 transgene is expressed upon Cre activity. Cre is provided by cross-breeding with Lgr5-GFP-CreERT2 mice. Results Upon in vivo Rspo3 expression, mice rapidly developed extensive hyperplastic, adenomatous and adenocarcinomatous lesions throughout the intestine. RSPO3 induced the expansion of Lgr5+ stem cells, Paneth cells, non-Paneth cell label-retaining cells and Lgr4+ cells, thus promoting both intestinal stem cell and niche compartments. Wnt/ß-catenin signalling was modestly increased upon Rspo3 expression and mutant Kras synergised with Rspo3 in hyperplastic growth. Conclusions We provide in vivo evidence that RSPO3 stimulates the crypt stem cell and niche compartments and drives rapid intestinal tumorigenesis. This establishes RSPO3 as a potent driver of intestinal cancer and proposes RSPO3 as a candidate target for therapy in patients with colorectal cancer harbouring RSPO3 fusions

Transcriptional regulation of the urokinase receptor (u-PAR) - A central molecule of invasion and metastasis

The phenomenon of tumor-associated proteolysis has been acknowledged as a decisive step in the progression of cancer. This short review focuses on the urokinase receptor (u-PAR), a central molecule involved in tumor-associated invasion and metastasis, and summarizes the transcriptional regulation of u-PAR. The urokinase receptor (u-PAR) is a heavily glycosylated cell surface protein and binds the serine protease urokinase specifically and with high affinity. It consists of three similar cysteine-rich repeats and is anchored to the cell membrane via a GPI-anchor. The u-PAR gene comprises 7 exons and is located on chromosome 19q13. Transcriptional activation of the u-PAR promoter region can be induced by binding of transcription factors (Sp1, AP-1, AP-2, NF-kappaB). One current study gives an example for transcriptional downregulation of u-PAR through a PEA3/ets transcriptional silencing element. Knowledge of the molecular regulation of this molecule in tumor cells could be very important for diagnosis and therapy in the near future

LES-based Study of the Roughness Effects on the Wake of a Circular Cylinder from Subcritical to Transcritical Reynolds Numbers

This paper investigates the effects of surface roughness on the flow past a circular cylinder at subcritical to transcritical Reynolds numbers. Large eddy simulations of the flow for sand grain roughness of size k/D = 0.02 are performed (D is the cylinder diameter). Results show that surface roughness triggers the transition to turbulence in the boundary layer at all Reynolds numbers, thus leading to an early separation caused by the increased momentum deficit, especially at transcritical Reynolds numbers. Even at subcritical Reynolds numbers, boundary layer instabilities are triggered in the roughness sublayer and eventually lead to the transition to turbulence. The early separation at transcritical Reynolds numbers leads to a wake topology similar to that of the subcritical regime, resulting in an increased drag coefficient and lower Strouhal number. Turbulent statistics in the wake are also affected by roughness; the Reynolds stresses are larger due to the increased turbulent kinetic energy production in the boundary layer and separated shear layers close to the cylinder shoulders.We acknowledge “Red Española de Surpercomputación” (RES) for awarding us access to the MareNostrum III machine based in Barcelona, Spain (Ref. FI-2015-2-0026 and FI-2015-3-0011). We also acknowledge PRACE for awarding us access to Fermi and Marconi Supercomputers at Cineca, Italy (Ref. 2015133120). Oriol Lehmkuhl acknowledges a PDJ 2014 Grant by AGAUR (Generalitat de Catalunya). Ugo Piomelli acknowledges the support of the Natural Sciences and Engineering Research Council (NSERC) of Canada under the Discovery Grant Programme (Grant No. RGPIN-2016-04391). Ricard Borrell acknowledges a Juan de la Cierva postdoctoral grant (IJCI-2014-21034). Ivette Rodriguez, Oriol Lehmkuhl, Ricard Borrell and Assensi Oliva acknowledge Ministerio de Economía y Competitividad, Secretaría de Estado de Investigación, Desarrollo e Innovación, Spain (ref. ENE2014-60577-R).Peer ReviewedPostprint (author's final draft