Hardness of deriving invertible sequences from finite state machines

© Springer International Publishing AG 2017.Many test generation algorithms use unique input/output sequences (UIOs) that identify states of the finite state machine specification M. However, it is known that UIO checking the existence of UIO sequences is PSPACE-complete. As a result, some UIO generation algorithms utilise what are called invertible sequences; these allow one to construct additional UIOs once a UIO has been found. We consider three optimisation problems associated with invertible sequences: deciding whether there is a (proper) invertible sequence of length at least K; deciding whether there is a set of invertible sequences for state set S′ that contains at most K input sequences; and deciding whether there is a single input sequence that defines invertible sequences that take state set S″ to state set S′. We prove that the first two problems are NP-complete and the third is PSPACE-complete. These results imply that we should investigate heuristics for these problems

Toward an Energy Efficient Language and Compiler for (Partially) Reversible Algorithms

We introduce a new programming language for expressing reversibility, Energy-Efficient Language (Eel), geared toward algorithm design and implementation. Eel is the first language to take advantage of a partially reversible computation model, where programs can be composed of both reversible and irreversible operations. In this model, irreversible operations cost energy for every bit of information created or destroyed. To handle programs of varying degrees of reversibility, Eel supports a log stack to automatically trade energy costs for space costs, and introduces many powerful control logic operators including protected conditional, general conditional, protected loops, and general loops. In this paper, we present the design and compiler for the three language levels of Eel along with an interpreter to simulate and annotate incurred energy costs of a program.Comment: 17 pages, 0 additional figures, pre-print to be published in The 8th Conference on Reversible Computing (RC2016

Magnetic signatures of plasma-depleted flux tubes in the Saturnian inner magnetosphere

Initial Cassini observations have revealed evidence for interchanging magnetic flux tubes in the inner Saturnian magnetosphere. Some of the reported flux tubes differ remarkably by their magnetic signatures, having a depressed or enhanced magnetic pressure relative to their surroundings. The ones with stronger fields have been interpreted previously as either outward moving mass-loaded or inward moving plasma-depleted flux tubes based on magnetometer observations only. We use detailed multi-instrumental observations of small and large density depletions in the inner Saturnian magnetosphere from Cassini Rev. A orbit that enable us to discriminate amongst the two previous and opposite interpretations. Our analysis undoubtedly confirms the similar nature of both types of reported interchanging magnetic flux tubes, which are plasma-depleted, whatever their magnetic signatures are. Their different magnetic signature is clearly an effect associated with latitude. These Saturnian plasma-depleted flux tubes ultimately may play a similar role as the Jovian ones

Cassini in situ observations of long duration magnetic reconnection in Saturn’s magnetotail

Magnetic reconnection is a fundamental process in solar system and astrophysical plasmas, through which stored magnetic energy associated with current sheets is converted into thermal, kinetic and wave energy1, 2, 3, 4. Magnetic reconnection is also thought to be a key process involved in shedding internally produced plasma from the giant magnetospheres at Jupiter and Saturn through topological reconfiguration of the magnetic field5, 6. The region where magnetic fields reconnect is known as the diffusion region and in this letter we report on the first encounter of the Cassini spacecraft with a diffusion region in Saturn’s magnetotail. The data also show evidence of magnetic reconnection over a period of 19?h revealing that reconnection can, in fact, act for prolonged intervals in a rapidly rotating magnetosphere. We show that reconnection can be a significant pathway for internal plasma loss at Saturn6. This counters the view of reconnection as a transient method of internal plasma loss at Saturn5, 7. These results, although directly relating to the magnetosphere of Saturn, have applications in the understanding of other rapidly rotating magnetospheres, including that of Jupiter and other astrophysical bodies

Internally driven large-scale changes in the size of Saturn's magnetosphere

Saturn’s magnetic field acts as an obstacle to solar wind flow, deflecting plasma around the planet and forming a cavity known as the magnetosphere. The magnetopause defines the boundary between the planetary and solar dominated regimes, and so is strongly influenced by the variable nature of pressure sources both outside and within. Following from Pilkington et al. (2014), crossings of the magnetopause are identified using 7 years of magnetic field and particle data from the Cassini spacecraft and providing unprecedented spatial coverage of the magnetopause boundary. These observations reveal a dynamical interaction where, in addition to the external influence of the solar wind dynamic pressure, internal drivers, and hot plasma dynamics in particular can take almost complete control of the system’s dayside shape and size, essentially defying the solar wind conditions. The magnetopause can move by up to 10–15 planetary radii at constant solar wind dynamic pressure, corresponding to relatively “plasma-loaded” or “plasma-depleted” states, defined in terms of the internal suprathermal plasma pressure

Internally driven large-scale changes in the size of Saturn's magnetosphere

Saturn’s magnetic field acts as an obstacle to solar wind flow, deflecting plasma around the planet and forming a cavity known as the magnetosphere. The magnetopause defines the boundary between the planetary and solar dominated regimes, and so is strongly influenced by the variable nature of pressure sources both outside and within. Following from Pilkington et al. (2014), crossings of the magnetopause are identified using 7 years of magnetic field and particle data from the Cassini spacecraft and providing unprecedented spatial coverage of the magnetopause boundary. These observations reveal a dynamical interaction where, in addition to the external influence of the solar wind dynamic pressure, internal drivers, and hot plasma dynamics in particular can take almost complete control of the system’s dayside shape and size, essentially defying the solar wind conditions. The magnetopause can move by up to 10–15 planetary radii at constant solar wind dynamic pressure, corresponding to relatively “plasma-loaded” or “plasma-depleted” states, defined in terms of the internal suprathermal plasma pressure

Brain immune cells undergo cGAS-STING-dependent apoptosis during herpes simplex virus type 1 infection

Protection of the brain from viral infections involves the type I interferon (IFN-I) system, defects in which renders humans susceptible to herpes simplex encephalitis (HSE). However, excessive cerebral IFN-I levels leads to pathologies, suggesting the need for tight regulation of responses. Based on data from mouse models, human HSE cases, and primary cell culture systems, we here show that microglia and other immune cells undergo apoptosis in the HSV-1-infected brain through a mechanism dependent on the cyclic GMP-AMP synthase (cGAS) - stimulator of interferon genes (STING) pathway, but independent of IFN-I. HSV-1 infection of microglia induced cGAS-dependent apoptosis at high viral doses, while lower viral doses led to IFN-I responses. Importantly, inhibition of caspase activity prevented microglial cell death and augmented IFN-I responses. Accordingly, HSV-1-infected organotypic brain slices, or mice treated with caspase inhibitor, exhibited lower viral load and improved outcome of infection. Collectively, we identify an activation-induced apoptosis program in brain immune cells which down-modulates local immune responses

Temporal trends of molecular markers associated with artemether- lumefantrine tolerance/resistance in Bagamoyo district, Tanzania

Background: Development and spread of Plasmodium falciparum resistance to artemisinin-based combination therapy (ACT) constitutes a major threat to recent global malaria control achievements. Surveillance of molecular markers could act as an early warning system of ACT-resistance before clinical treatment failures are apparent. The aim of this study was to analyse temporal trends of established genotypes associated with artemether-lumefantrine tolerance/resistance before and after its deployment as first-line treatment for uncomplicated malaria in Tanzania 2006. Methods: Single nucleotide polymorphisms in the P. falciparum multidrug resistance gene 1 (pfmdr1) N86Y, Y184F, D1246Y and P. falciparum chloroquine transporter gene (pfcrt) K76T were analysed from dried blood spots collected during six consecutive studies from children with uncomplicated P. falciparum malaria in Fukayosi village, Bagamoyo District, Tanzania, between 2004-2011. Results: There was a statistically significant yearly increase of pfmdr1 N86, 184F, D1246 and pfcrt K76 between 2006-2011 from 14% to 61% (yearly OR = 1.38 [95% CI 1.25-1.52] p \u3c 0.0001), 14% to 35% (OR = 1.17 [95% CI 1.07-1.30] p = 0.001), 54% to 85% (OR = 1.21 [95% CI 1.03-1.42] p = 0.016) and 49% to 85% (OR = 1.33 [95% CI 1.17-1.51] p \u3c 0.0001), respectively. Unlike for the pfmdr1 SNP, a significant increase of pfcrt K76 was observed already between 2004-2006, from 26% to 49% (OR = 1.68 [95% CI 1.17-2.40] p = 0.005). From 2006 to 2011 the pfmdr1 NFD haplotype increased from 10% to 37% (OR = 1.25 [95% CI 1.12-1.39] p \u3c 0.0001), whereas the YYY haplotype decreased from 31% to 6% (OR = 0.73 [95% CI 0.56-0.98] p = 0.018). All 390 successfully analysed samples had one copy of the pfmdr1 gene. Conclusion: The temporal selection of molecular markers associated with artemether-lumefantrine tolerance/resistance may represent an early warning sign of impaired future drug efficacy. This calls for stringent surveillance of artemether-lumefantrine efficacy in Tanzania and emphasizes the importance of molecular surveillance as a complement to standard in vivo trials. © 2013 Malmberg et al.; licensee BioMed Central Ltd