456 research outputs found

    Limit Synchronization in Markov Decision Processes

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    Markov decision processes (MDP) are finite-state systems with both strategic and probabilistic choices. After fixing a strategy, an MDP produces a sequence of probability distributions over states. The sequence is eventually synchronizing if the probability mass accumulates in a single state, possibly in the limit. Precisely, for 0 <= p <= 1 the sequence is p-synchronizing if a probability distribution in the sequence assigns probability at least p to some state, and we distinguish three synchronization modes: (i) sure winning if there exists a strategy that produces a 1-synchronizing sequence; (ii) almost-sure winning if there exists a strategy that produces a sequence that is, for all epsilon > 0, a (1-epsilon)-synchronizing sequence; (iii) limit-sure winning if for all epsilon > 0, there exists a strategy that produces a (1-epsilon)-synchronizing sequence. We consider the problem of deciding whether an MDP is sure, almost-sure, limit-sure winning, and we establish the decidability and optimal complexity for all modes, as well as the memory requirements for winning strategies. Our main contributions are as follows: (a) for each winning modes we present characterizations that give a PSPACE complexity for the decision problems, and we establish matching PSPACE lower bounds; (b) we show that for sure winning strategies, exponential memory is sufficient and may be necessary, and that in general infinite memory is necessary for almost-sure winning, and unbounded memory is necessary for limit-sure winning; (c) along with our results, we establish new complexity results for alternating finite automata over a one-letter alphabet

    A Testis-Specific Chaperone and the Chromatin Remodeler ISWI Mediate Repackaging of the Paternal Genome

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    During spermatogenesis, the paternal genome is repackaged into a non-nucleosomal, highly compacted chromatin structure. Bioinformatic analysis revealed that Drosophila sperm chromatin proteins are characterized by a motif related to the high-mobility group (HMG) box, which we termed male-specific transcript (MST)-HMG box. MST77F is a MST-HMG-box protein that forms an essential component of sperm chromatin. The deposition of MST77F onto the paternal genome requires the chaperone function of tNAP, a testis-specific NAP protein. MST77F, in turn, enables the stable incorporation of MST35Ba and MST35Bb into sperm chromatin. Following MST-HMG-box protein deposition, the ATP-dependent chromatin remodeler ISWI mediates the appropriate organization of sperm chromatin. Conversely, at fertilization, maternal ISWI targets the paternal genome and drives its repackaging into de-condensed nucleosomal chromatin. Failure of this transition in ISWI mutant embryos is followed by mitotic defects, aneuploidy, and haploid embryonic divisions. Thus, ISWI enables bi-directional transitions between two fundamentally different forms of chromatin

    An Axiomatic Approach to Liveness for Differential Equations

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    This paper presents an approach for deductive liveness verification for ordinary differential equations (ODEs) with differential dynamic logic. Numerous subtleties complicate the generalization of well-known discrete liveness verification techniques, such as loop variants, to the continuous setting. For example, ODE solutions may blow up in finite time or their progress towards the goal may converge to zero. Our approach handles these subtleties by successively refining ODE liveness properties using ODE invariance properties which have a well-understood deductive proof theory. This approach is widely applicable: we survey several liveness arguments in the literature and derive them all as special instances of our axiomatic refinement approach. We also correct several soundness errors in the surveyed arguments, which further highlights the subtlety of ODE liveness reasoning and the utility of our deductive approach. The library of common refinement steps identified through our approach enables both the sound development and justification of new ODE liveness proof rules from our axioms.Comment: FM 2019: 23rd International Symposium on Formal Methods, Porto, Portugal, October 9-11, 201

    Emergence of four dimensional quantum mechanics from a deterministic theory in 11 dimensions

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    We develop a deterministic theory which accounts for the coupling of a high dimensional continuum of environmental excitations (called gravonons) to massive particle in a very localized and very weak fashion. For the model presented Schrodinger's equation can be solved practically exactly in 11 spacetime dimensions and the result demonstrates that as a function of time an incoming matter wave incident on a screen extinguishes, except at a single interaction center on the detection screen. This transition is reminiscent of the wave - particle duality arising from the "collapse" (also called "process one") postulated in the Copenhagen-von Neumann interpretation. In our theory it is replaced by a sticking process of the particle from the vacuum to the surface of the detection screen. This situation was verified in experiments by using massive molecules. In our theory this "wave-particle transition" is connected to the different dimensionalities of the space for particle motion and the gravonon dynamics, the latter propagating in the hidden dimensions of 11 dimensional spacetime. The fact that the particle is detected at apparently statistically determined points on the screen is traced back to the weakness and locality of the interaction with the gravonons which allows coupling on the energy shell alone. Although the theory exhibits a completely deterministic "chooser" mechanism for single site sticking, an apparent statistical character results, as it is found in the experiments, due to small heterogeneities in the atomic and gravonon structures

    Subunits of the Histone Chaperone CAF1 Also Mediate Assembly of Protamine-Based Chromatin

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    One of the most dramatic forms of chromatin reorganization occurs during spermatogenesis, when the paternal genome is repackaged from a nucleosomal to a protamine-based structure. We assessed the role of the canonical histone chaperone CAF1 in Drosophila spermatogenesis. In this process, CAF1 does not behave as a complex, but its subunits display distinct chromatin dynamics. During histone-to-protamine replacement, CAF1-p180 dissociates from the DNA while CAF1-p75 binds and stays on as a component of sperm chromatin. Association of CAF1-p75 with the paternal genome depends on CAF1-p180 and protamines. Conversely, CAF1-p75 binds protamines and is required for their incorporation into sperm chromatin. Histone removal, however, occurs independently of CAF1 or protamines. Thus, CAF1-p180 and CAF1-p75 function in a temporal hierarchy during sperm chromatin assembly, with CAF1-p75 acting as a protamine-loading factor. These results show that CAF1 subunits mediate the assembly of two fundamentally different forms of chromatin

    Testing Reactive Probabilistic Processes

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    We define a testing equivalence in the spirit of De Nicola and Hennessy for reactive probabilistic processes, i.e. for processes where the internal nondeterminism is due to random behaviour. We characterize the testing equivalence in terms of ready-traces. From the characterization it follows that the equivalence is insensitive to the exact moment in time in which an internal probabilistic choice occurs, which is inherent from the original testing equivalence of De Nicola and Hennessy. We also show decidability of the testing equivalence for finite systems for which the complete model may not be known

    Effects of proton versus photon irradiation on (lymph) angiogenic, inflammatory, proliferative and anti-tumor immune responses in head and neck squamous cell carcinoma

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    International audienceThe proximity of organs at risk makes the treatment of head and neck squamous cell carcinoma (HNSCC) challenging by standard radiotherapy. The higher precision in tumor targeting of proton (P) therapy could promote it as the treatment of choice for HNSCC. Besides the physical advantage in dose deposition, few is known about the biological impact of P versus photons (X) in this setting. To investigate the comparative biological effects of P versus X radiation in HNSCC cells, we assessed the relative biological effectiveness (RBE), viability, proliferation and mRNA levels for genes involved in (lymph)angiogenesis, inflammation, proliferation and anti-tumor immunity. These parameters, particularly VEGF-C protein levels and regulations, were documented in freshly irradiated and/or long-term surviving cells receiving low/high-dose, single (SI)/multiple (MI) irradiations with P/X. The RBE was found to be 1.1 Key (lymph)angiogenesis and inflammation genes were downregulated (except for vegf-c) after P and upregulated after X irradiation in MI surviving cells, demonstrating a more favorable profile after P irradiation. Both irradiation types stimulated vegf-c promoter activity in a NF-κB-dependent transcriptional regulation manner, but at a lesser extent after P, as compared to X irradiation, which correlated with mRNA and protein levels. The cells surviving to MI by P or X generated tumors with higher volume, anarchic architecture and increased density of blood vessels. Increased lymphangiogenesis and a transcriptomic analysis in favor of a more aggressive phenotype were observed in tumors generated with X-irradiated cells. Increased detection of lymphatic vessels in relapsed tumors from patients receiving X radiotherapy was consistent with these findings. This study provides new data about the biological advantage of P, as compared to X irradiation. In addition to its physical advantage in dose deposition, P irradiation may help to improve treatment approaches for HNSCC

    Holocene land-use evolution and associated soil erosion in the French Prealps inferred from Lake Paladru sediments and archaeological evidences

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    International audienceA source-to-sink multi-proxy approach has been performed within Lake Paladru (492 m a.s.l., French Prealps) catchment and a six-meter long sediment sequence retrieved from the central lacustrine basin. The combination of minerogenic signal, specific organic markers of autochthonous and allochthonous supply and archaeological data allows the reconstruction of a continuous record of past human disturbances. Over the last 10000 years, the lacustrine sedimentation was dominated by autochthonous carbonates and the watershed was mostly forest-covered. However, seven phases of higher accumulation rate, soil erosion, algal productivity and landscape disturbances have been identified and dated from 8400-7900, 6000-4800, 4500-3200, 2700-2050 cal BP as well as AD 350-850, AD 1250-1850 and after AD 1970. Before 5200 cal BP, soil erosion is interpreted as resulting from climatic deterioration phases toward cooler and wetter conditions. During the Mid-Late Holocene period, erosion fluxes and landscape disturbances are always associated with prehistorical and historical human activities and amplified by climatic oscillations. Such changes in human land-used led to increasing minerogenic supply and nutrients loading that affected lacustrine trophic levels, especially during the last 1600 years. In addition, organic and molecular markers document previously unknown human settlements around Lake Paladru during the Bronze and the Iron Ages

    Till death (or an intruder) do us part: intrasexual-competition in a monogamous Primate

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    Polygynous animals are often highly dimorphic, and show large sex-differences in the degree of intra-sexual competition and aggression, which is associated with biased operational sex ratios (OSR). For socially monogamous, sexually monomorphic species, this relationship is less clear. Among mammals, pair-living has sometimes been assumed to imply equal OSR and low frequency, low intensity intra-sexual competition; even when high rates of intra-sexual competition and selection, in both sexes, have been theoretically predicted and described for various taxa. Owl monkeys are one of a few socially monogamous primates. Using long-term demographic and morphological data from 18 groups, we show that male and female owl monkeys experience intense intra-sexual competition and aggression from solitary floaters. Pair-mates are regularly replaced by intruding floaters (27 female and 23 male replacements in 149 group-years), with negative effects on the reproductive success of both partners. Individuals with only one partner during their life produced 25% more offspring per decade of tenure than those with two or more partners. The termination of the pair-bond is initiated by the floater, and sometimes has fatal consequences for the expelled adult. The existence of floaters and the sporadic, but intense aggression between them and residents suggest that it can be misleading to assume an equal OSR in socially monogamous species based solely on group composition. Instead, we suggest that sexual selection models must assume not equal, but flexible, context-specific, OSR in monogamous species.Wenner-Gren Foundation, L.S.B. Leakey Foundation, the National Geographic Society, National Science Foundation (BCS- 0621020), the University of Pennsylvania Research Foundation and the Zoological Society of San Diego, German Science Foundation (HU 1746-2/1
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