Learning Moore Machines from Input-Output Traces

The problem of learning automata from example traces (but no equivalence or membership queries) is fundamental in automata learning theory and practice. In this paper we study this problem for finite state machines with inputs and outputs, and in particular for Moore machines. We develop three algorithms for solving this problem: (1) the PTAP algorithm, which transforms a set of input-output traces into an incomplete Moore machine and then completes the machine with self-loops; (2) the PRPNI algorithm, which uses the well-known RPNI algorithm for automata learning to learn a product of automata encoding a Moore machine; and (3) the MooreMI algorithm, which directly learns a Moore machine using PTAP extended with state merging. We prove that MooreMI has the fundamental identification in the limit property. We also compare the algorithms experimentally in terms of the size of the learned machine and several notions of accuracy, introduced in this paper. Finally, we compare with OSTIA, an algorithm that learns a more general class of transducers, and find that OSTIA generally does not learn a Moore machine, even when fed with a characteristic sample

Warped Riemannian metrics for location-scale models

The present paper shows that warped Riemannian metrics, a class of Riemannian metrics which play a prominent role in Riemannian geometry, are also of fundamental importance in information geometry. Precisely, the paper features a new theorem, which states that the Rao-Fisher information metric of any location-scale model, defined on a Riemannian manifold, is a warped Riemannian metric, whenever this model is invariant under the action of some Lie group. This theorem is a valuable tool in finding the expression of the Rao-Fisher information metric of location-scale models defined on high-dimensional Riemannian manifolds. Indeed, a warped Riemannian metric is fully determined by only two functions of a single variable, irrespective of the dimension of the underlying Riemannian manifold. Starting from this theorem, several original contributions are made. The expression of the Rao-Fisher information metric of the Riemannian Gaussian model is provided, for the first time in the literature. A generalised definition of the Mahalanobis distance is introduced, which is applicable to any location-scale model defined on a Riemannian manifold. The solution of the geodesic equation is obtained, for any Rao-Fisher information metric defined in terms of warped Riemannian metrics. Finally, using a mixture of analytical and numerical computations, it is shown that the parameter space of the von Mises-Fisher model of $n$-dimensional directional data, when equipped with its Rao-Fisher information metric, becomes a Hadamard manifold, a simply-connected complete Riemannian manifold of negative sectional curvature, for $n = 2,\ldots,8$. Hopefully, in upcoming work, this will be proved for any value of $n$.Comment: first version, before submissio

Counting and effective rigidity in algebra and geometry

The purpose of this article is to produce effective versions of some rigidity results in algebra and geometry. On the geometric side, we focus on the spectrum of primitive geodesic lengths (resp., complex lengths) for arithmetic hyperbolic 2-manifolds (resp., 3-manifolds). By work of Reid, this spectrum determines the commensurability class of the 2-manifold (resp., 3-manifold). We establish effective versions of these rigidity results by ensuring that, for two incommensurable arithmetic manifolds of bounded volume, the length sets (resp., the complex length sets) must disagree for a length that can be explicitly bounded as a function of volume. We also prove an effective version of a similar rigidity result established by the second author with Reid on a surface analog of the length spectrum for hyperbolic 3-manifolds. These effective results have corresponding algebraic analogs involving maximal subfields and quaternion subalgebras of quaternion algebras. To prove these effective rigidity results, we establish results on the asymptotic behavior of certain algebraic and geometric counting functions which are of independent interest.Comment: v.2, 39 pages. To appear in Invent. Mat

Single and two-particle energy gaps across the disorder-driven superconductor-insulator transition

The competition between superconductivity and localization raises profound questions in condensed matter physics. In spite of decades of research, the mechanism of the superconductor-insulator transition (SIT) and the nature of the insulator are not understood. We use quantum Monte Carlo simulations that treat, on an equal footing, inhomogeneous amplitude variations and phase fluctuations, a major advance over previous theories. We gain new microscopic insights and make testable predictions for local spectroscopic probes. The energy gap in the density of states survives across the transition, but coherence peaks exist only in the superconductor. A characteristic pseudogap persists above the critical disorder and critical temperature, in contrast to conventional theories. Surprisingly, the insulator has a two-particle gap scale that vanishes at the SIT, despite a robust single-particle gap.Comment: 7 pages, 5 figures (plus supplement with 4 pages, 5 figures

Designed Azolopyridinium Salts Block Protective Antigen Pores In Vitro and Protect Cells from Anthrax Toxin

Background:Several intracellular acting bacterial protein toxins of the AB-type, which are known to enter cells by endocytosis, are shown to produce channels. This holds true for protective antigen (PA), the binding component of the tripartite anthrax-toxin of Bacillus anthracis. Evidence has been presented that translocation of the enzymatic components of anthrax-toxin across the endosomal membrane of target cells and channel formation by the heptameric/octameric PA63 binding/translocation component are related phenomena. Chloroquine and some 4-aminoquinolones, known as potent drugs against Plasmodium falciparium infection of humans, block efficiently the PA63-channel in a dose dependent way.Methodology/Principal Findings:Here we demonstrate that related positively charged heterocyclic azolopyridinium salts block the PA63-channel in the μM range, when both, inhibitor and PA63 are added to the same side of the membrane, the cis-side, which corresponds to the lumen of acidified endosomal vesicles of target cells. Noise-analysis allowed the study of the kinetics of the plug formation by the heterocycles. In vivo experiments using J774A.1 macrophages demonstrated that the inhibitors of PA63-channel function also efficiently block intoxication of the cells by the combination lethal factor and PA63 in the same concentration range as they block the channels in vitro.Conclusions/Significance:These results strongly argue in favor of a transport of lethal factor through the PA63-channel and suggest that the heterocycles used in this study could represent attractive candidates for development of novel therapeutic strategies against anthrax. © 2013 Beitzinger et al

Opportunities for organoids as new models of aging.

The biology of aging is challenging to study, particularly in humans. As a result, model organisms are used to approximate the physiological context of aging in humans. However, the best model organisms remain expensive and time-consuming to use. More importantly, they may not reflect directly on the process of aging in people. Human cell culture provides an alternative, but many functional signs of aging occur at the level of tissues rather than cells and are therefore not readily apparent in traditional cell culture models. Organoids have the potential to effectively balance between the strengths and weaknesses of traditional models of aging. They have sufficient complexity to capture relevant signs of aging at the molecular, cellular, and tissue levels, while presenting an experimentally tractable alternative to animal studies. Organoid systems have been developed to model many human tissues and diseases. Here we provide a perspective on the potential for organoids to serve as models for aging and describe how current organoid techniques could be applied to aging research

Prevalence of Symptomatic Heart Failure with Reduced and with Normal Ejection Fraction in an Elderly General Population-The CARLA Study

Background/Objectives: Chronic heart failure (CHF) is one of the most important public health concerns in the industrialized world having increasing incidence and prevalence. Although there are several studies describing the prevalence of heart failure with reduced ejection fraction (HFREF) and heart failure with normal ejection fraction (HFNEF) in selected populations, there are few data regarding the prevalence and the determinants of symptomatic heart failure in the general population. Methods: Cross-sectional data of a population-based German sample (1,779 subjects aged 45-83 years) were analyzed to determine the prevalence and determinants of chronic SHF and HFNEF defined according to the European Society of Cardiology using symptoms, echocardiography and serum NT-proBNP. Prevalence was age-standardized to the German population as of December 31st, 2005. Results: The overall age-standardized prevalence of symptomatic CHF was 7.7% (95%CI 6.0-9.8) for men and 9.0% (95%CI 7.0-11.5) for women. The prevalence of CHF strongly increased with age from 3.0% among 45-54- year-old subjects to 22.0% among 75-83- year-old subjects. Symptomatic HFREF could be shown in 48% (n = 78), symptomatic HFNEF in 52% (n = 85) of subjects with CHF. The age-standardized prevalence of HFREF was 3.8 % (95%CI 2.4-5.8) for women and 4.6 % (95%CI 3.6-6.3) for men. The age-standardized prevalence of HFNEF for women and men was 5.1 % (95%CI 3.8-7.0) and 3.0 % (95%CI 2.1-4.5), respectively. Persons with CHF were more likely to have hypertension (PR = 3.4; 95%CI 1.6-7.3) or to have had a previous myocardial infarction (PR = 2.5, 95%CI 1.8-3.5). Conclusion: The prevalence of symptomatic CHF appears high in this population compared with other studies. While more women were affected by HFNEF than men, more male subjects suffered from HFREF. The high prevalence of symptomatic CHF seems likely to be mainly due to the high prevalence of cardiovascular risk factors in this population

Systemic hematogenous maintenance of memory inflation by MCMV infection.

Several low-grade persistent viral infections induce and sustain very large numbers of virus-specific effector T cells. This was first described as a response to cytomegalovirus (CMV), a herpesvirus that establishes a life-long persistent/latent infection, and sustains the largest known effector T cell populations in healthy people. These T cells remain functional and traffic systemically, which has led to the recent exploration of CMV as a persistent vaccine vector. However, the maintenance of this remarkable response is not understood. Current models propose that reservoirs of viral antigen and/or latently infected cells in lymph nodes stimulate T cell proliferation and effector differentiation, followed by migration of progeny to non-lymphoid tissues where they control CMV reactivation. We tested this model using murine CMV (MCMV), a natural mouse pathogen and homologue of human CMV (HCMV). While T cells within draining lymph nodes divided at a higher rate than cells elsewhere, antigen-dependent proliferation of MCMV-specific effector T cells was observed systemically. Strikingly, inhibition of T cell egress from lymph nodes failed to eliminate systemic T cell division, and did not prevent the maintenance of the inflationary populations. In fact, we found that the vast majority of inflationary cells, including most cells undergoing antigen-driven division, had not migrated into the parenchyma of non-lymphoid tissues but were instead exposed to the blood supply. Indeed, the immunodominance and effector phenotype of inflationary cells, both of which are primary hallmarks of memory inflation, were largely confined to blood-localized T cells. Together these results support a new model of MCMV-driven memory inflation in which most immune surveillance occurs in circulation, and in which most inflationary effector T cells are produced in response to viral antigen presented by cells that are accessible to the blood supply