UTxO- vs Account-Based Smart Contract Blockchain Programming Paradigms

We implement two versions of a simple but illustrative smart contract: one in Solidity on the Ethereum blockchain platform, and one in Plutus on the Cardano platform, with annotated code excerpts and with source code attached. We get a clearer view of the Cardano programming model in particular by introducing a novel mathematical abstraction which we call Idealised EUTxO. For each version of the contract, we trace how the architectures of the underlying platforms and their mathematics affects the natural programming styles and natural classes of errors. We prove some simple but novel results about alpha-conversion and observational equivalence for Cardano, and explain why Ethereum does not have them. We conclude with a wide-ranging and detailed discussion in the light of the examples, mathematical model, and mathematical results so far

Game semantic analysis of equivalence in IMJ

Using game semantics, we investigate the problem of verifying contextual equivalences in Interface Middleweight Java (IMJ), an imperative object calculus in which program phrases are typed using interfaces. Working in the setting where data types are non-recursive and restricted to finite domains, we identify the frontier between decidability and undecidability by reference to the structure of interfaces present in typing judgments. In particular, we show how to determine the decidability status of problem instances (over a fixed type signature) by examining the position of methods inside the term type and the types of its free identifiers. Our results build upon the recent fully abstract game semantics of IMJ. Decidability is proved by translation into visibly pushdown register automata over infinite alphabets with fresh-input recognition

A Class of Automata for the Verification of Infinite, Resource-Allocating Behaviours

Process calculi for service-oriented computing often feature generation of fresh resources. So-called nominal automata have been studied both as semantic models for such calculi, and as acceptors of languages of finite words over infinite alphabets. In this paper we investi-gate nominal automata that accept infinite words. These automata are a generalisation of deterministic Muller automata to the setting of nominal sets. We prove decidability of complement, union, intersection, emptiness and equivalence, and determinacy by ultimately periodic words. The key to obtain such results is to use finite representations of the (otherwise infinite-state) defined class of automata. The definition of such operations enables model checking of process calculi featuring infinite behaviours, and resource allocation, to be implemented using classical automata-theoretic methods

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

A formalized general theory of syntax with bindings

We present the formalization of a theory of syntax with bindings that has been developed and refined over the last decade to support several large formalization efforts. Terms are defined for an arbitrary number of constructors of varying numbers of inputs, quotiented to alpha-equivalence and sorted according to a binding signature. The theory includes a rich collection of properties of the standard operators on terms, such as substitution and freshness. It also includes induction and recursion principles and support for semantic interpretation, all tailored for smooth interaction with the bindings and the standard operators

Identifying the Rules of Engagement Enabling Leukocyte Rolling, Activation, and Adhesion

The LFA-1 integrin plays a pivotal role in sustained leukocyte adhesion to the endothelial surface, which is a precondition for leukocyte recruitment into inflammation sites. Strong correlative evidence implicates LFA-1 clustering as being essential for sustained adhesion, and it may also facilitate rebinding events with its ligand ICAM-1. We cannot challenge those hypotheses directly because it is infeasible to measure either process during leukocyte adhesion following rolling. The alternative approach undertaken was to challenge the hypothesized mechanisms by experimenting on validated, working counterparts: simulations in which diffusible, LFA1 objects on the surfaces of quasi-autonomous leukocytes interact with simulated, diffusible, ICAM1 objects on endothelial surfaces during simulated adhesion following rolling. We used object-oriented, agent-based methods to build and execute multi-level, multi-attribute analogues of leukocytes and endothelial surfaces. Validation was achieved across different experimental conditions, in vitro, ex vivo, and in vivo, at both the individual cell and population levels. Because those mechanisms exhibit all of the characteristics of biological mechanisms, they can stand as a concrete, working theory about detailed events occurring at the leukocyte–surface interface during leukocyte rolling and adhesion experiments. We challenged mechanistic hypotheses by conducting experiments in which the consequences of multiple mechanistic events were tracked. We quantified rebinding events between individual components under different conditions, and the role of LFA1 clustering in sustaining leukocyte–surface adhesion and in improving adhesion efficiency. Early during simulations ICAM1 rebinding (to LFA1) but not LFA1 rebinding (to ICAM1) was enhanced by clustering. Later, clustering caused both types of rebinding events to increase. We discovered that clustering was not necessary to achieve adhesion as long as LFA1 and ICAM1 object densities were above a critical level. Importantly, at low densities LFA1 clustering enabled improved efficiency: adhesion exhibited measurable, cell level positive cooperativity

Use of communities of practice in business and health care sectors: A systematic review

<p>Abstract</p> <p>Background</p> <p>Since being identified as a concept for understanding knowledge sharing, management, and creation, communities of practice (CoPs) have become increasingly popular within the health sector. The CoP concept has been used in the business sector for over 20 years, but the use of CoPs in the health sector has been limited in comparison.</p> <p>Objectives</p> <p>First, we examined how CoPs were defined and used in these two sectors. Second, we evaluated the evidence of effectiveness on the health sector CoPs for improving the uptake of best practices and mentoring new practitioners.</p> <p>Methods</p> <p>We conducted a search of electronic databases in the business, health, and education sectors, and a hand search of key journals for primary studies on CoP groups. Our research synthesis for the first objective focused on three areas: the authors' interpretations of the CoP concept, the key characteristics of CoP groups, and the common elements of CoP groups. To examine the evidence on the effectiveness of CoPs in the health sector, we identified articles that evaluated CoPs for improving health professional performance, health care organizational performance, professional mentoring, and/or patient outcome; and used experimental, quasi-experimental, or observational designs.</p> <p>Results</p> <p>The structure of CoP groups varied greatly, ranging from voluntary informal networks to work-supported formal education sessions, and from apprentice training to multidisciplinary, multi-site project teams. Four characteristics were identified from CoP groups: social interaction among members, knowledge sharing, knowledge creation, and identity building; however, these were not consistently present in all CoPs. There was also a lack of clarity in the responsibilities of CoP facilitators and how power dynamics should be handled within a CoP group. We did not find any paper in the health sector that met the eligibility criteria for the quantitative analysis, and so the effectiveness of CoP in this sector remained unclear.</p> <p>Conclusion</p> <p>There is no dominant trend in how the CoP concept is operationalized in the business and health sectors; hence, it is challenging to define the parameters of CoP groups. This may be one of the reasons for the lack of studies on the effectiveness of CoPs in the health sector. In order to improve the usefulness of the CoP concept in the development of groups and teams, further research will be needed to clarify the extent to which the four characteristics of CoPs are present in the mature and emergent groups, the expectations of facilitators and other participants, and the power relationship within CoPs.</p

A formally verified abstract account of Gödel's incompleteness theorems

We present an abstract development of Gödel’s incompleteness theorems, performed with the help of the Isabelle/HOL theorem prover. We analyze sufficient conditions for the theorems’ applicability to a partially specified logic. In addition to the usual benefits of generality, our abstract perspective enables a comparison between alternative approaches from the literature. These include Rosser’s variation of the first theorem, Jeroslow’s variation of the second theorem, and the S ́wierczkowski–Paulson semantics-based approach. As part of our framework’s validation, we upgrade Paulson’s Isabelle proof to produce a mech- anization of the second theorem that does not assume soundness in the standard model, and in fact does not rely on any notion of model or semantic interpretation

Chromatin and epigenetics: current biophysical views

Recent advances in high-throughput sequencing experiments and their theoretical descriptions have determined fast dynamics of the "chromatin and epigenetics" field, with new concepts appearing at high rate. This field includes but is not limited to the study of DNA-protein-RNA interactions, chromatin packing properties at different scales, regulation of gene expression and protein trafficking in the cell nucleus, binding site search in the crowded chromatin environment and modulation of physical interactions by covalent chemical modifications of the binding partners. The current special issue does not pretend for the full coverage of the field, but it rather aims to capture its development and provide a snapshot of the most recent concepts and approaches. Eighteen open-access articles comprising this issue provide a delicate balance between current theoretical and experimental biophysical approaches to uncover chromatin structure and understand epigenetic regulation, allowing free flow of new ideas and preliminary results