Petri nets for systems and synthetic biology

We give a description of a Petri net-based framework for modelling and analysing biochemical pathways, which uni¯es the qualita- tive, stochastic and continuous paradigms. Each perspective adds its con- tribution to the understanding of the system, thus the three approaches do not compete, but complement each other. We illustrate our approach by applying it to an extended model of the three stage cascade, which forms the core of the ERK signal transduction pathway. Consequently our focus is on transient behaviour analysis. We demonstrate how quali- tative descriptions are abstractions over stochastic or continuous descrip- tions, and show that the stochastic and continuous models approximate each other. Although our framework is based on Petri nets, it can be applied more widely to other formalisms which are used to model and analyse biochemical networks

Biobehavioral effects of Tai Chi Qigong in men with prostate cancer: Study design of a three-arm randomized clinical trial.

Fatigue is often one of the most commonly reported symptoms in prostate cancer survivors, but it is also one of the least understood cancer-related symptoms. Fatigue is associated with psychological distress, disruptions in sleep quality, and impairments in health-related quality of life. Moreover, inflammatory processes and changes related to the hypothalamic-pituitary-adrenal (HPA) axis and/or autonomic nervous system may also play a role in cancer-related fatigue. Thus, effective treatments for fatigue in prostate cancer survivors represent a current unmet need. Prior research has shown that Tai Chi Qigong, a mind-body exercise intervention, can improve physical and emotional health. Herein, we describe the protocol of the ongoing 3-arm randomized controlled Health Empowerment & Recovery Outcomes (HERO) clincal trial. One hundred sixty-six prostate cancer survivors with fatigue are randomized to a modified Tai Chi Qigong intervention (TCQ), intensity-matched body training intervention (BT), or usual care (UC) condition. Guided by biopsychosocial and psychoneuroimmunology models, we propose that TCQ, as compared to BT or UC will: i) reduce fatigue (primary outcome) in prostate cancer survivors; ii) reduce inflammation; and iii) regulate the expression of genes from two major functional clusters: a) inflammation, vasodilation and metabolite sensing and b) energy and adrenergic activation. Assessments are conducted at baseline, the 6-week midpoint of the intervention, and 1 week, 3 months, and 12 months post-intervention. If our findings show that TCQ promotes recovery from prostate cancer and its treatment, this type of intervention can be integrated into survivorship care plans as the standard of care. The study's findings will also provide novel information about underlying biobehavioral mechanisms of cancer-related fatigue. Trial registration number:NCT03326713; clinicaltrials.gov

Formal Modeling of Connectionism using Concurrency Theory, an Approach Based on Automata and Model Checking

This paper illustrates a framework for applying formal methods techniques, which are symbolic in nature, to specifying and verifying neural networks, which are sub-symbolic in nature. The paper describes a communicating automata [Bowman & Gomez, 2006] model of neural networks. We also implement the model using timed automata [Alur & Dill, 1994] and then undertake a verification of these models using the model checker Uppaal [Pettersson, 2000] in order to evaluate the performance of learning algorithms. This paper also presents discussion of a number of broad issues concerning cognitive neuroscience and the debate as to whether symbolic processing or connectionism is a suitable representation of cognitive systems. Additionally, the issue of integrating symbolic techniques, such as formal methods, with complex neural networks is discussed. We then argue that symbolic verifications may give theoretically well-founded ways to evaluate and justify neural learning systems in the field of both theoretical research and real world applications

Exploration and Design of High Performance Variation Tolerant On-Chip Interconnects

Siirretty Doriast

The evolutionary biology of dance without frills

Recently psychologists have taken up the question of whether dance is reliant on unique human adaptations, or whether it is rooted in neural and cognitive mechanisms shared with other species 1, 2. In its full cultural complexity, human dance clearly has no direct analog in animal behavior. Most definitions of dance include the consistent production of movement sequences timed to an external rhythm. While not sufficient for dance, modes of auditory-motor timing, such as synchronization and entrainment, are experimentally tractable constructs that may be analyzed and compared between species. In an effort to assess the evolutionary precursors to entrainment and social features of human dance, Laland and colleagues [2] have suggested that dance may be an incidental byproduct of adaptations supporting vocal or motor imitation — referred to here as the ‘imitation and sequencing’ hypothesis. In support of this hypothesis, Laland and colleagues rely on four convergent lines of evidence drawn from behavioral and neurobiological research on dance behavior in humans and rhythmic behavior in other animals. Here, we propose a less cognitive, more parsimonious account for the evolution of dance. Our ‘timing and interaction’ hypothesis suggests that dance is scaffolded off of broadly conserved timing mechanisms allowing both cooperative and antagonistic social coordination

From Parallel Sequence Representations to Calligraphic Control: A Conspiracy of Neural Circuits

Calligraphic writing presents a rich set of challenges to the human movement control system. These challenges include: initial learning, and recall from memory, of prescribed stroke sequences; critical timing of stroke onsets and durations; fine control of grip and contact forces; and letter-form invariance under voluntary size scaling, which entails fine control of stroke direction and amplitude during recruitment and derecruitment of musculoskeletal degrees of freedom. Experimental and computational studies in behavioral neuroscience have made rapid progress toward explaining the learning, planning and contTOl exercised in tasks that share features with calligraphic writing and drawing. This article summarizes computational neuroscience models and related neurobiological data that reveal critical operations spanning from parallel sequence representations to fine force control. Part one addresses stroke sequencing. It treats competitive queuing (CQ) models of sequence representation, performance, learning, and recall. Part two addresses letter size scaling and motor equivalence. It treats cursive handwriting models together with models in which sensory-motor tmnsformations are performed by circuits that learn inverse differential kinematic mappings. Part three addresses fine-grained control of timing and transient forces, by treating circuit models that learn to solve inverse dynamics problems.National Institutes of Health (R01 DC02852

Circadian rest-activity rhythms predict cognitive function in early Parkinson's disease independently of sleep

BACKGROUND: Cognitive impairment is a common and debilitating symptom of Parkinson's disease (PD), and its etiology is likely multifactorial. One candidate mechanism is circadian disruption. Although there is evidence of circadian abnormalities in PD, no studies have directly assessed their association with cognitive impairment. OBJECTIVES: Investigate whether circadian rest-activity rhythm is associated with cognitive function in PD independently of sleep. METHODS: Thirty-five participants with PD wore wrist actigraph monitors and completed sleep diaries for 7 to 10 days, then underwent neuropsychological testing. Rest-activity rhythm was characterized using nonparametric circadian rhythm analysis of actigraphy data. Objective sleep parameters were also estimated using actigraphy data. Hierarchical regression models assessed the independent contributions of sleep and rest-activity rhythm to cognitive performance. RESULTS: Less stable day-to-day rest-activity rhythm was associated with poorer executive, visuospatial, and psychomotor functioning, but not with memory. Hierarchical regressions showed that interdaily stability's contribution to cognitive performance was independent of sleep's contributions. Whereas sleep contributed to executive function, but not psychomotor or visuospatial performance, rest-activity rhythm stability significantly contributed to variance in all three of these domains, uniquely accounting for 14.4% to 17.6% of their performance variance. CONCLUSIONS: Our findings indicate that circadian rest-activity rhythm is associated with cognitive impairment independently of sleep. This suggests the possible utility of rest-activity rhythm as a biomarker for circadian function in PD. Future research should explore interventions to stabilize behavioral rhythms in order to strengthen circadian function, which, in turn, may reduce cognitive impairment in PD.R00 HL102241 - NHLBI NIH HHS; R01 AG048108 - NIA NIH HHSAccepted manuscrip

Computational Modeling of Complex Protein Activity Networks

Because of the numerous entities interacting, the complexity of the networks that regulate cell fate makes it impossible to analyze and understand them using the human brain alone. Computational modeling is a powerful method to unravel complex systems. We recently described the development of a user-friendly computational tool, Analysis of Networks with Interactive MOdeling (ANIMO). ANIMO is a powerful tool to formalize knowledge on molecular interactions. This formalization entails giving a precise mathematical (formal) description of molecular states and of interactions between molecules. Such a model can be simulated, thereby in silico mimicking the processes that take place in the cell. In sharp contrast to classical graphical representations of molecular interaction networks, formal models allow in silico experiments and functional analysis of the dynamic behavior of the network. In addition, ANIMO was developed specifically for use by biologists who have little or no prior modeling experience. In this chapter, we guide the reader through the ANIMO workflow using osteoarthritis (OA) as a case study. WNT, IL-1β, and BMP signaling and cross talk are used as a concrete and illustrative model

Proceedings of the First NASA Formal Methods Symposium

Topics covered include: Model Checking - My 27-Year Quest to Overcome the State Explosion Problem; Applying Formal Methods to NASA Projects: Transition from Research to Practice; TLA+: Whence, Wherefore, and Whither; Formal Methods Applications in Air Transportation; Theorem Proving in Intel Hardware Design; Building a Formal Model of a Human-Interactive System: Insights into the Integration of Formal Methods and Human Factors Engineering; Model Checking for Autonomic Systems Specified with ASSL; A Game-Theoretic Approach to Branching Time Abstract-Check-Refine Process; Software Model Checking Without Source Code; Generalized Abstract Symbolic Summaries; A Comparative Study of Randomized Constraint Solvers for Random-Symbolic Testing; Component-Oriented Behavior Extraction for Autonomic System Design; Automated Verification of Design Patterns with LePUS3; A Module Language for Typing by Contracts; From Goal-Oriented Requirements to Event-B Specifications; Introduction of Virtualization Technology to Multi-Process Model Checking; Comparing Techniques for Certified Static Analysis; Towards a Framework for Generating Tests to Satisfy Complex Code Coverage in Java Pathfinder; jFuzz: A Concolic Whitebox Fuzzer for Java; Machine-Checkable Timed CSP; Stochastic Formal Correctness of Numerical Algorithms; Deductive Verification of Cryptographic Software; Coloured Petri Net Refinement Specification and Correctness Proof with Coq; Modeling Guidelines for Code Generation in the Railway Signaling Context; Tactical Synthesis Of Efficient Global Search Algorithms; Towards Co-Engineering Communicating Autonomous Cyber-Physical Systems; and Formal Methods for Automated Diagnosis of Autosub 6000