Refinement Type Inference via Horn Constraint Optimization

We propose a novel method for inferring refinement types of higher-order functional programs. The main advantage of the proposed method is that it can infer maximally preferred (i.e., Pareto optimal) refinement types with respect to a user-specified preference order. The flexible optimization of refinement types enabled by the proposed method paves the way for interesting applications, such as inferring most-general characterization of inputs for which a given program satisfies (or violates) a given safety (or termination) property. Our method reduces such a type optimization problem to a Horn constraint optimization problem by using a new refinement type system that can flexibly reason about non-determinism in programs. Our method then solves the constraint optimization problem by repeatedly improving a current solution until convergence via template-based invariant generation. We have implemented a prototype inference system based on our method, and obtained promising results in preliminary experiments.Comment: 19 page

Speeding up the constraint-based method in difference logic

"The final publication is available at http://link.springer.com/chapter/10.1007%2F978-3-319-40970-2_18"Over the years the constraint-based method has been successfully applied to a wide range of problems in program analysis, from invariant generation to termination and non-termination proving. Quite often the semantics of the program under study as well as the properties to be generated belong to difference logic, i.e., the fragment of linear arithmetic where atoms are inequalities of the form u v = k. However, so far constraint-based techniques have not exploited this fact: in general, Farkas’ Lemma is used to produce the constraints over template unknowns, which leads to non-linear SMT problems. Based on classical results of graph theory, in this paper we propose new encodings for generating these constraints when program semantics and templates belong to difference logic. Thanks to this approach, instead of a heavyweight non-linear arithmetic solver, a much cheaper SMT solver for difference logic or linear integer arithmetic can be employed for solving the resulting constraints. We present encouraging experimental results that show the high impact of the proposed techniques on the performance of the VeryMax verification systemPeer ReviewedPostprint (author's final draft

ERP evidence suggests executive dysfunction in ecstasy polydrug users

Background: Deficits in executive functions such as access to semantic/long-term memory have been shown in ecstasy users in previous research. Equally, there have been many reports of equivocal findings in this area. The current study sought to further investigate behavioural and electro-physiological measures of this executive function in ecstasy users. Method: Twenty ecstasy–polydrug users, 20 non-ecstasy–polydrug users and 20 drug-naïve controls were recruited. Participants completed background questionnaires about their drug use, sleep quality, fluid intelligence and mood state. Each individual also completed a semantic retrieval task whilst 64 channel Electroencephalography (EEG) measures were recorded. Results: Analysis of Variance (ANOVA) revealed no between-group differences in behavioural performance on the task. Mixed ANOVA on event-related potential (ERP) components P2, N2 and P3 revealed significant between-group differences in the N2 component. Subsequent exploratory univariate ANOVAs on the N2 component revealed marginally significant between-group differences, generally showing greater negativity at occipito-parietal electrodes in ecstasy users compared to drug-naïve controls. Despite absence of behavioural differences, differences in N2 magnitude are evidence of abnormal executive functioning in ecstasy–polydrug users

Altered Error Processing following Vascular Thalamic Damage: Evidence from an Antisaccade Task

Event-related potentials (ERP) research has identified a negative deflection within about 100 to 150 ms after an erroneous response – the error-related negativity (ERN) - as a correlate of awareness-independent error processing. The short latency suggests an internal error monitoring system acting rapidly based on central information such as an efference copy signal. Studies on monkeys and humans have identified the thalamus as an important relay station for efference copy signals of ongoing saccades. The present study investigated error processing on an antisaccade task with ERPs in six patients with focal vascular damage to the thalamus and 28 control subjects. ERN amplitudes were significantly reduced in the patients, with the strongest ERN attenuation being observed in two patients with right mediodorsal and ventrolateral and bilateral ventrolateral damage, respectively. Although the number of errors was significantly higher in the thalamic lesion patients, the degree of ERN attenuation did not correlate with the error rate in the patients. The present data underline the role of the thalamus for the online monitoring of saccadic eye movements, albeit not providing unequivocal evidence in favour of an exclusive role of a particular thalamic site being involved in performance monitoring. By relaying saccade-related efference copy signals, the thalamus appears to enable fast error processing. Furthermore early error processing based on internal information may contribute to error awareness which was reduced in the patients

Long-term culture of genome-stable bipotent stem cells from adult human liver.

Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. The cells can readily be converted into functional hepatocytes in vitro and upon transplantation in vivo. Organoids from α1-antitrypsin deficiency and Alagille syndrome patients mirror the in vivo pathology. Clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy.This work was supported by grants to MH (EU/236954) and to HC (The United European Gastroenterology Federation (UEGF) Research Prize 2010, EU/232814-StemCellMark and NWO/116002008). MH is supported by The Wellcome Trust Sir Henry Dale fellowship. The Rspo cell line was kindly provided by Dr. Calvin Kuo.This is the final published version. It first appeared at http://www.cell.com/abstract/S0092-8674%2814%2901566-9

Time Course of the Neural Activity Related to Behavioral Decision-Making as Revealed by Event-Related Potentials

Objective: To study the time course of the electrocortical activity evoked by gains and losses in the Iowa Gambling Task (IGT), the brain sources of this electrical activity, and its association with behavioral parameters of task performance in order to achieve a better knowledge of decision-making processes. Method: Event-related potentials (ERPs) were obtained from a 64-channel EEG in 25 participants when performing the IGT. Brain source localization analyses of the ERP components were also assessed. Results: ERP amplitudes were sensitive to gains and losses. An early fronto-central negativity was elicited when feedback was provided for both gains and losses, and correlated with the number of gains at FCz and with the number of both gains and losses at Cz. The P200 component had larger amplitudes to losses and correlated positively with the number of losses. Feedback related negativity (FRN) was higher at frontal, temporal and occipital electrodes in trials with monetary losses. In addition, trials with monetary losses elicited larger P300 magnitudes than trials with monetary gains at all electrode localizations. Conclusions: All ERP components (except P300) were related to participants’ performance in the IGT. Amplitudes of P200 and P300 were associated with the conscious recognition of the error during the decision-making. Performance data and source analysis underline the importance of the medial prefrontal cortex when processing feedback about monetary losses in the IGT.This research was supported by grants from the Spanish Ministry of Science and Innovation (Ministerio de Ciencia y Tecnología), European Regional Development Funds (ERDF) and Ministry of Economy, Industry and Competitiveness (Ministerio de Economía, Industria y Competitividad, Gobierno de España). References: PSI2008-04394, PSI2017-88388-C4-1-R and PSI2017-88388-C4-3-R

Brain Activity in Fairness Consideration during Asset Distribution: Does the Initial Ownership Play a Role?

Previous behavioral studies have shown that initial ownership influences individuals’ fairness consideration and other-regarding behavior. However, it is not entirely clear whether initial ownership influences the brain activity when a recipient evaluates the fairness of asset distribution. In this study, we randomly assigned the bargaining property (monetary reward) to either the allocator or the recipient in the ultimatum game and let participants of the study, acting as recipients, receive either disadvantageous unequal, equal, or advantageous unequal offers from allocators while the event-related potentials (ERPs) were recorded. Behavioral results showed that participants were more likely to reject disadvantageous unequal and equal offers when they initially owned the property as compared to when they did not. The two types of unequal offers evoked more negative going ERPs (the MFN) than the equal offers in an early time window and the differences were not modulated by the initial ownership. In a late time window, however, the P300 responses to division schemes were affected not only by the type of unequal offers but also by whom the property was initially assigned to. These findings suggest that while the MFN may function as a general mechanism that evaluates whether the offer is consistent or inconsistent with the equity rule, the P300 is sensitive to top-down controlled processes, into which factors related to the allocation of attentional resources, including initial ownership and personal interests, come to play

Fleeting Perceptual Experience and the Possibility of Recalling Without Seeing

We explore an intensely debated problem in neuroscience, psychology and philosophy: the degree to which the “phenomenological consciousness” of the experience of a stimulus is separable from the “access consciousness” of its reportability. Specifically, it has been proposed that these two measures are dissociated from one another in one, or both directions. However, even if it was agreed that reportability and experience were doubly dissociated, the limits of dissociation logic mean we would not be able to conclusively separate the cognitive processes underlying the two. We take advantage of computational modelling and recent advances in state-trace analysis to assess this dissociation in an attentional/experiential blink paradigm. These advances in state-trace analysis make use of Bayesian statistics to quantify the evidence for and against a dissociation. Further evidence is obtained by linking our finding to a prominent model of the attentional blink – the Simultaneous Type/Serial Token model. Our results show evidence for a dissociation between experience and reportability, whereby participants appear able to encode stimuli into working memory with little, if any, conscious experience of them. This raises the possibility of a phenomenon that might be called sight-blind recall, which we discuss in the context of the current experience/reportability debate

The rate of facultative sex governs the number of expected mating types in isogamous species

It is unclear why sexually reproducing isogamous species frequently contain just two self-incompatible mating types. Deterministic theory suggests that since rare novel mating types experience a selective advantage (by virtue of their many potential partners), the number of mating types should consistently grow. However, in nature, species with thousands of mating types are exceedingly rare. Several competing theories for the predominance of species with two mating types exist, yet they lack an explanation for how many are possible and in which species to expect high numbers. Here, we present a theoretical null model that explains the distribution of mating type numbers using just three biological parameters: mutation rate, population size and the rate of sex. If the number of mating types results from a mutation–extinction balance, the rate of sexual reproduction plays a crucial role. If sex is facultative and rare (a very common combination in isogamous species), mating type diversity will remain low. In this rare sex regime, small fitness differences between the mating types lead to more frequent extinctions, further lowering mating type diversity. We also show that the empirical literature supports the role of drift and facultativeness of sex as a determinant of mating type dynamics

The rate of facultative sex governs the number of expected mating types in isogamous species

It is unclear why sexually reproducing isogamous species frequently contain just two self-incompatible mating types. Deterministic theory suggests that since rare novel mating types experience a selective advantage (by virtue of their many potential partners), the number of mating types should consistently grow. However, in nature, species with thousands of mating types are exceedingly rare. Several competing theories for the predominance of species with two mating types exist, yet they lack an explanation for how many are possible and in which species to expect high numbers. Here, we present a theoretical null model that explains the distribution of mating type numbers using just three biological parameters: mutation rate, population size and the rate of sex. If the number of mating types results from a mutation–extinction balance, the rate of sexual reproduction plays a crucial role. If sex is facultative and rare (a very common combination in isogamous species), mating type diversity will remain low. In this rare sex regime, small fitness differences between the mating types lead to more frequent extinctions, further lowering mating type diversity. We also show that the empirical literature supports the role of drift and facultativeness of sex as a determinant of mating type dynamics