Reactive Turing Machines

We propose reactive Turing machines (RTMs), extending classical Turing machines with a process-theoretical notion of interaction, and use it to define a notion of executable transition system. We show that every computable transition system with a bounded branching degree is simulated modulo divergence-preserving branching bisimilarity by an RTM, and that every effective transition system is simulated modulo the variant of branching bisimilarity that does not require divergence preservation. We conclude from these results that the parallel composition of (communicating) RTMs can be simulated by a single RTM. We prove that there exist universal RTMs modulo branching bisimilarity, but these essentially employ divergence to be able to simulate an RTM of arbitrary branching degree. We also prove that modulo divergence-preserving branching bisimilarity there are RTMs that are universal up to their own branching degree. Finally, we establish a correspondence between executability and finite definability in a simple process calculus

MARL-iDR: Multi-Agent Reinforcement Learning for Incentive-based Residential Demand Response

This paper presents a decentralized Multi-Agent Reinforcement Learning (MARL) approach to an incentive-based Demand Response (DR) program, which aims to maintain the capacity limits of the electricity grid and prevent grid congestion by financially incentivizing residential consumers to reduce their energy consumption. The proposed approach addresses the key challenge of coordinating heterogeneous preferences and requirements from multiple participants while preserving their privacy and minimizing financial costs for the aggregator. The participant agents use a novel Disjunctively Constrained Knapsack Problem optimization to curtail or shift the requested household appliances based on the selected demand reduction. Through case studies with electricity data from $25$ households, the proposed approach effectively reduced energy consumption's Peak-to-Average ratio (PAR) by $14.48$% compared to the original PAR while fully preserving participant privacy. This approach has the potential to significantly improve the efficiency and reliability of the electricity grid, making it an important contribution to the management of renewable energy resources and the growing electricity demand.Comment: 8 pages, IEEE Belgrade PowerTech, 202

Experimental Tests of Free-Volume Tracer Diffusion in Water and Other Solvents

Using forced Rayleigh scattering, the tracer diffusion of methyl red through water and eight other solvents at different temperatures is investigated and the results are compared to the Cohen-Turnbull theory of free-volume diffusion. In seven solvents the effective non-Arrhenius activation energy measured experimentally agrees with the Cohen-Turnbull energy. In water, however, the diffusion can be described mathematically by the free volume model but there is a disagreement of more than an order of magnitude between these energies. We propose that the unique zero point free volume forced onto water by the strong hydrogen bonding requires a different mechanism for tracer motion

Transport and retention of the mitten crab (Eriocheir sinensis) in a Mid-Atlantic estuary: Predictions from a larval transport model

Invasive species cause extensive ecological damage in freshwater and marine habitats and are a threat to biodiversity in aquatic ecosystems world-wide. One such species, the Chinese mitten crab, Eriocheir sinensis, has invasive populations in northern Europe and San Francisco Bay, and there are confirmed reports of breeding female crabs in both the Chesapeake and Delaware Bays. Despite their threat to these ecosystems, there are still large gaps in the current understanding of this species\u27 larval biology that are critical to predicting the potential for large populations to establish in East Coast bays and estuaries. We addressed these issues by using a physical circulation model of Delaware Bay and the adjacent coastal ocean coupled to a modified particle advection scheme. We used this model to examine the effects of different physical mechanisms and larval behavior on transport, retention, and settlement of larvae in the bay. The circulation model produced flow fields using observed winds and river discharge for 2006 as well as systematic variations of river discharge and wind direction. Since little is known regarding mitten crab larval behavior, the larval component was purposefully general and incorporated a suite of behaviors such as tidal, diel, and ontogenetic vertical migration; however, results of this study showed that vertical migration affects the magnitude, but not locations of larval settlement. Simulations revealed that changes in the time and location of spawning can result in large variations in retention and settlement of larvae in Delaware Bay and the coastal ocean, due to seasonal variations of the physical flow field. Overall results of our study showed that the estuarine and coastal circulation typically found along the Middle Atlantic coast of the United States can result in significant retention of new and established E. sinensis populations in large estuaries as well as transport of larvae to new coastal locations

Depressive symptoms and risk of Alzheimer's disease in more highly educated older people

In an earlier study we observed that a depressive syndrome was highly predictive of developing Alzheimer's disease (AD) in older persons with normal baseline cognition and higher levels of education. We interpreted these findings as the depression being an early noncognitive manifestation of AD in persons with more cognitive reserve. The present study examines whether specific symptoms of depression can be identified that predict AD among older subjects with higher levels of education. In the community-based Amsterdam Study of the Elderly (AMSTEL), a sample of 3,147 nondemented persons with normal cognition, 65 to 84 years old, was selected and divided into subjects with >8 years and 8 years and 31 with 8 years of education depressed mood and subjective bradyphrenia were strongly associated with incident AD. No association between depressive symptoms and AD was observed among subjects with <or =8 years of education. Both depressed mood and subjective bradyphrenia seem to indicate subclinical AD in older people with higher levels of education. Clinicians should be alert that in these persons, AD may become apparent within a relatively short period of tim

Larotrectinib efficacy and safety in TRK fusion cancer: An expanded clinical dataset showing consistency in an age and tumor agnostic approach

Background: TRK fusion cancer results from gene fusions involving NTRK1, NTRK2 or NTRK3. Larotrectinib, the first selective TRK inhibitor, has demonstrated an overall response rate (ORR) of 75% with a favorable safety profile in the first 55 consecutively enrolled adult and pediatric patients with TRK fusion cancer (Drilon et al.,NEJM2018). Here, we report the clinical activity of larotrectinib in an additional 35 TRK fusion cancer patients and provide updated follow-up of the primary analysis set (PAS) of 55 patients as of 19thFeb 2018. Methods: Patients with TRK fusion cancer detected by molecular profiling from 3 larotrectinib clinical trials (NCT02122913, NCT02637687, and NCT02576431) were eligible.Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Disease status was assessed using RECIST version 1.1. Results: As of Feb 2018, by independent review, 6 PRs in the PAS deepened to CRs. The median duration of response (DoR) and progression-free survival in the PAS had still not been reached, with 12.9 months median follow-up. At 1 year, 69% of responses were ongoing, 58% of patients remained progression-free and 90% of patients were alive. An additional 19 children and 25 adults (age range, 0.1-78 years) with TRK fusion cancer were enrolled after the PAS, and included cancers of the salivary gland, thyroid, lung, colon, melanoma, sarcoma, GIST and congenital mesoblastic nephroma. In 35 evaluable patients, the ORR by investigator assessment was 74% (5 CR, 21 PR, 6 SD, 2 PD, 1 not determined). In these patients, with median follow-up of 5.5 months, median DoR had not yet been reached, and 88% of responses were ongoing at 6 months, consistent with the PAS. Adverse events (AEs) were predominantly grade 1, with dizziness, increased AST/ALT, fatigue, nausea and constipation the most common AEs reported in ≥ 10% of patients. No AE of grade 3 or 4 related to larotrectinib occurred in more than 5% of patients. Conclusions: TRK fusions are detected in a broad range of tumor types. Larotrectinib is an effective age- and tumor-agnostic treatment for TRK fusion cancer with a positive safety profile. Screening patients for NTRK gene fusions in solid- and brain tumors should be actively considered

Identification of TUB as a novel candidate gene influencing body weight in humans

Previously, we identified a locus on 11p influencing obesity in families with type 2 diabetes. Based on mouse studies, we selected TUB as a functional candidate gene and performed association studies to determine whether this controls obesity. We analyzed the genotypes of 13 single nucleotide polymorphisms (SNPs) around TUB in 492 unrelated type 2 diabetic patients with known BMI values. One SNP (rs1528133) was found to have a significant effect on BMI (1.54 kg/m(2), P = 0.006). This association was confirmed in a population enriched for type 2 diabetes, using 750 individuals who were not selected for type 2 diabetes. Two SNPs in linkage disequilibrium with rs1528133 and mapping to the 3' end of TUB, rs2272382, and rs2272383 also affected BMI by 1.3 kg/m2 (P = 0.016 and P = 0.010, respectively). Combined analysis confirmed this association (P = 0.005 and P = 0.002, respectively). Moreover, comparing 349 obese subjects (BMI >30 kg/m(2)) from the combined cohort with 289 normal subjects (BMI <25 kg/m(2)) revealed that the protective alleles have a lower frequency in obese subjects (odds ratio 1.32 [95% CI 1.04-1.67], P = 0.022). Altogether, data from the tubby mouse as well as these data suggest that TUB could be an important factor in controlling the central regulation of body weight in humans

Expressiveness modulo Bisimilarity of Regular Expressions with Parallel Composition (Extended Abstract)

The languages accepted by finite automata are precisely the languages denoted by regular expressions. In contrast, finite automata may exhibit behaviours that cannot be described by regular expressions up to bisimilarity. In this paper, we consider extensions of the theory of regular expressions with various forms of parallel composition and study the effect on expressiveness. First we prove that adding pure interleaving to the theory of regular expressions strictly increases its expressiveness up to bisimilarity. Then, we prove that replacing the operation for pure interleaving by ACP-style parallel composition gives a further increase in expressiveness. Finally, we prove that the theory of regular expressions with ACP-style parallel composition and encapsulation is expressive enough to express all finite automata up to bisimilarity. Our results extend the expressiveness results obtained by Bergstra, Bethke and Ponse for process algebras with (the binary variant of) Kleene's star operation.Comment: In Proceedings EXPRESS'10, arXiv:1011.601