Thou Shalt is not You Will

In this paper we discuss some reasons why temporal logic might not be suitable to model real life norms. To show this, we present a novel deontic logic contrary-to-duty/derived permission paradox based on the interaction of obligations, permissions and contrary-to-duty obligations. The paradox is inspired by real life norms

Exploring Spirituality in Teaching Within a Christian School Context Through Collaborative Action Research

This article reports on a collaborative action research project conducted in New Zealand, during 2012, exploring spirituality in teaching within a Christian school context. The experienced primary school teacher participant chose to take action around the issue of personal fear and insecurity which were believed to be hindering professional growth and relationships. Through self-directed inquiry, critical reflective journaling, Bible study, fellowship and prayer with trusted friends, the teacher experienced a renewed sense of peace and freedom in Christ. This personal transformation was believed to be influential on subsequent professional practice, assisting the teacher to become more relational, responsive and compassionate. The findings provide a rich description of the participant’s spirituality, the lived reality of a person’s spiritual life. This report will be of interest to teachers, teacher-leaders and teacher-educators who desire to explore Christian spirituality through practitioner-led inquiry

Independent-Trajectories Thermodynamic-Integration Free-Energy Changes for Biomolecular Systems: Determinants of H5N1 Avian Influenza Virus Neuraminidase Inhibition by Peramivir

Free-energy changes are essential physicochemical quantities for understanding most biochemical processes. Yet, the application of accurate thermodynamic-integration (TI) computation to biological and macromolecular systems is limited by finite-sampling artifacts. In this paper, we employ independent-trajectories thermodynamic-integration (IT-TI) computation to estimate improved free-energy changes and their uncertainties for (bio)molecular systems. IT-TI aids sampling statistics of the thermodynamic macrostates for flexible associating partners by ensemble averaging of multiple, independent simulation trajectories. We study peramivir (PVR) inhibition of the H5N1 avian influenza virus neuraminidase flexible receptor (N1). Binding site loops 150 and 119 are highly mobile, as revealed by N1-PVR 20-ns molecular dynamics. Due to such heterogeneous sampling, standard TI binding free-energy estimates span a rather large free-energy range, from a 19% underestimation to a 29% overestimation of the experimental reference value (−62.2 ± 1.8 kJ mol−1). Remarkably, our IT-TI binding free-energy estimate (−61.1 ± 5.4 kJ mol−1) agrees with a 2% relative difference. In addition, IT-TI runs provide a statistics-based free-energy uncertainty for the process of interest. Using ∼800 ns of overall sampling, we investigate N1-PVR binding determinants by IT-TI alchemical modifications of PVR moieties. These results emphasize the dominant electrostatic contribution, particularly through the N1 E277−PVR guanidinium interaction. Future drug development may be also guided by properly tuning ligand flexibility and hydrophobicity. IT-TI will allow estimation of relative free energies for systems of increasing size, with improved reliability by employing large-scale distributed computing

Catalytic Cycle of Multicopper Oxidases Studied by Combined Quantum- and Molecular-Mechanical Free-Energy Perturbation Methods

We have used combined quantum mechanical and molecular mechanical free-energy perturbation methods in combination with explicit solvent simulations to study the reaction mechanism of the multicopper oxidases, in particular the regeneration of the reduced state from the native intermediate. For 52 putative states of the trinuclear copper cluster, differing in the oxidation states of the copper ions and the protonation states of water- and O2-derived ligands, we have studied redox potentials, acidity constants, isomerisation reactions, as well as water- and O2 binding reactions. Thereby, we can propose a full reaction mechanism of the multicopper oxidases with atomic detail. We also show that the two copper sites in the protein communicate so that redox potentials and acidity constants of one site are affected by up to 0.2 V or 3 pKa units by a change in the oxidation state of the other site

A Deontic Logic Reasoning Infrastructure

A flexible infrastructure for the automation of deontic and normative reasoning is presented. Our motivation is the development, study and provision of legal and moral reasoning competencies in future intelligent machines. Since there is no consensus on the “best” deontic logic formalisms and since the answer may be application specific, a flexible infrastructure is proposed in which candidate logic formalisms can be varied, assessed and compared in experimental ethics application studies. Our work thus links the historically rich research areas of classical higher-order logic, deontic logics, normative reasoning and formal ethics