Virtual Reality Games for Motor Rehabilitation

This paper presents a fuzzy logic based method to track user satisfaction without the need for devices to monitor users physiological conditions. User satisfaction is the key to any product’s acceptance; computer applications and video games provide a unique opportunity to provide a tailored environment for each user to better suit their needs. We have implemented a non-adaptive fuzzy logic model of emotion, based on the emotional component of the Fuzzy Logic Adaptive Model of Emotion (FLAME) proposed by El-Nasr, to estimate player emotion in UnrealTournament 2004. In this paper we describe the implementation of this system and present the results of one of several play tests. Our research contradicts the current literature that suggests physiological measurements are needed. We show that it is possible to use a software only method to estimate user emotion

Eliminating grammatical function assignment from hierarchical models of speech production: Evidence from the conceptual accessibility of referents

ABSTRACTThe assignment of grammatical functions has been a key feature of hierarchical (serial) models of speech production since their inception in the 1970s. This article argues that grammatical function assignment is neither sufficient nor necessary in such models. It reports a study of the effects of the conceptual accessibility of referents on the selection of English dative syntactic frames in production and shows that the effects relate to linear precedence rather than grammatical function assignment. A secondary topic addressed in the same study is whether second language speakers of English have difficulty integrating syntactic knowledge where it interfaces with conceptual accessibility in speech production. Findings suggest that advanced proficiency speakers do not and are qualitatively similar to native speakers. The implications of this for the interface hypothesis about second language acquisition are discussed.</jats:p

Teleology and Realism in Leibniz's Philosophy of Science

This paper argues for an interpretation of Leibniz’s claim that physics requires both mechanical and teleological principles as a view regarding the interpretation of physical theories. Granting that Leibniz’s fundamental ontology remains non-physical, or mentalistic, it argues that teleological principles nevertheless ground a realist commitment about mechanical descriptions of phenomena. The empirical results of the new sciences, according to Leibniz, have genuine truth conditions: there is a fact of the matter about the regularities observed in experience. Taking this stance, however, requires bringing non-empirical reasons to bear upon mechanical causal claims. This paper first evaluates extant interpretations of Leibniz’s thesis that there are two realms in physics as describing parallel, self-sufficient sets of laws. It then examines Leibniz’s use of teleological principles to interpret scientific results in the context of his interventions in debates in seventeenth-century kinematic theory, and in the teaching of Copernicanism. Leibniz’s use of the principle of continuity and the principle of simplicity, for instance, reveal an underlying commitment to the truth-aptness, or approximate truth-aptness, of the new natural sciences. The paper concludes with a brief remark on the relation between metaphysics, theology, and physics in Leibniz

Grüneisen parameter of hcp‐Fe to 171 GPa

We measured the phonon density of states (DOS) of hexagonal close-packed iron (ɛ-Fe) with high statistical quality using nuclear resonant inelastic X-ray scattering and in situ X-ray diffraction experiments between pressures of 30 GPa and 171 GPa and at 300 K, with a neon pressure medium up to 69 GPa. The shape of the phonon DOS remained similar at all compression points, while the maximum (cutoff) energy increased regularly with decreasing volume. As a result, we present a generalized scaling law to describe the volume dependence of ɛ-Fe's total phonon DOS which, in turn, is directly related to the ambient temperature vibrational Grüneisen parameter (γ_(vib)). Fitting our individual γ_(vib) data points with γ_(vib) = γ_(vib),0(V/V0)^q, a common parameterization, we found an ambient pressure γ_(vib,0) = 2.0 ± 0.1 for the range q = 0.8 to 1.2. We also determined the Debye sound velocity (v_D) from the low-energy region of the phonon DOS and our in situ measured volumes, and used the volume dependence of v_D to determine the commonly discussed Debye Grüneisen parameter (γ_D). Comparing our γ_(vib)(V) and γ_D(V), we found γ_(vib) to be ∼10% larger than γ_D at any given volume. Finally, applying our γ_(vib)(V) to a Mie-Grüneisen type relationship and an approximate form of the empirical Lindemann melting criterion, we predict the vibrational thermal pressure and estimate the high-pressure melting behavior of ɛ-Fe at Earth's core pressures

Field‐testing polyethylene passive samplers for the detection of neutral polyfluorinated alkyl substances in air and water

Fluorotelomer alcohols (FTOHs), perfluorooctane‐sulfonamidoethanols (FOSEs), perfluorooctane‐sulfonamides (FOSAs), and other poly‐ and perfluorinated alkyl substances (PFASs) are common and ubiquitous byproducts of industrial telomerization processes. They can degrade into various perfluorinated carboxylic acids, which are persistent organic contaminants of concern. We assessed the use of polyethylene (PE) passive samplers as a sampling tool for neutral PFAS precursors during field‐deployments in air and water. A wide range of neutral PFASs was detected in polyethylene sheets exposed in wastewater treatment effluents in August 2017. Equilibration times for most neutral PFASs were on the order of 1 to 2 wk. Based on known sampling rates, the partitioning constants between polyethylene and water, KPEw, were derived. Log KPEw values were mostly in the range of 3 to 4.5, with the greatest values for 8:2 FTOH, 10:2 FTOH, and n‐ethyl‐FOSE. To test the utility of polyethylene for gas‐phase compounds, parallel active and passive sampling was performed in ambient air in Providence (RI, USA) in April 2016. Most PFASs equilibrated within 2 to 7 d. The greatest concentrations in polyethylene samplers were detected for MeFOSE and EtFOSE. Polyethylene/air partitioning constants, log KPEa, were approximately 7 to 8 for the FTOHs, and approached 9 for n‐methyl‐FOSA and n‐methyl‐FOSE. Polyethylene sheets showed promise as a passive sampling approach for neutral PFASs in air and water. Environ Toxicol Chem 2018;9999:1–9. © 2018 SETA

Altered channel gating mechanism for CFTR inhibition by a high-affinity thiazolidinone blocker

AbstractThe thiazolidinone CFTRinh-172 was identified recently as a potent and selective blocker of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel. Here, we characterized the CFTRinh-172 inhibition mechanism by patch-clamp and short-circuit analysis using cells stably expressing wild-type and mutant CFTRs. CFTRinh-172 did not alter CFTR unitary conductance (8 pS), but reduced open probability by >90% with Ki≈0.6 μM. This effect was due to increased mean channel closed time without changing mean channel open time. Short-circuit current experiments indicated similar CFTRinh-172 inhibitory potency (Ki≈0.5 μM) for inhibition of Cl− current in wild-type, G551D, and G1349D CFTR; however, Ki was significantly reduced to 0.2 μM for ΔF508 CFTR. Our studies provide evidence for CFTR inhibition by CFTRinh-172 by a mechanism involving altered CFTR gating

Cyclic Boronates Inhibit All Classes of β-Lactamase

β-Lactamase-mediated resistance is a growing threat to the continued use of β-lactam antibiotics. The use of the β-lactam-based serine-β-lactamase (SBL) inhibitors clavulanic acid, sulbactam, tazobactam, and, more recently, the non-β-lactam inhibitor avibactam has extended the utility of β-lactams against bacterial infections demonstrating resistance via these enzymes. These molecules are, however, ineffective against the metallo-β-lactamases (MBLs), which catalyse their hydrolysis. To date, there are no clinically available metallo-β-lactamase inhibitors. Co-production of MBLs and SBLs in resistant infections is, thus, of major clinical concern. The development of ‘dual-action' inhibitors, targeting both SBLs and MBLs, is of interest, but these are considered difficult to achieve due to the structural and mechanistic differences between the two enzyme classes. We recently reported evidence that cyclic boronates can inhibit both serine- and metallo-β-lactmases. Here we report that cyclic boronates are able to inhibit all four classes of β-lactamase, including the class A extended spectrum β-lactamase, CTX-M-15, the class C enzyme, AmpC from Pseudomonas aeruginosa, and class D OXA enzymes with carbapenem-hydrolysing capabilities. We demonstrate that cyclic boronates can potentiate the use of β-lactams against Gram-negative clinical isolates expressing a variety of β-lactamases. Comparison of a crystal structure of a CTX-M-15:cyclic boronate complex with structures of cyclic boronates complexed with other β-lactamases reveals remarkable conservation of the small molecule binding mode, supporting our proposal that these molecules work by mimicking the common tetrahedral anionic intermediate present in both serine- and metallo-β-lactamase catalysis

Ribosomal oxygenases are structurally conserved from prokaryotes to humans

2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation of gene expression via demethylation of N-methylated chromatin components1,2 and in the hydroxylation of transcription factors3 and splicing factor proteins4. Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transfer RNA5,6,7 and ribosomal proteins8 have been shown to be important in translation relating to cellular growth, TH17-cell differentiation and translational accuracy9,10,11,12. The finding that ribosomal oxygenases (ROXs) occur in organisms ranging from prokaryotes to humans8 raises questions as to their structural and evolutionary relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation in the ribosomal proteins RPL27A and RPL8, respectively. The functional assignments of ROXs open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in the residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with those of human MINA53 and NO66 reveals highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-dependent oxygenases. ROX structures with and without their substrates support their functional assignments as hydroxylases but not demethylases, and reveal how the subfamily has evolved to catalyse the hydroxylation of different residue side chains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-domain-containing hydroxylases, including the hypoxia-inducible factor asparaginyl hydroxylase FIH and histone Nε-methyl lysine demethylases, identifies branch points in 2OG-dependent oxygenase evolution and distinguishes between JmjC-containing hydroxylases and demethylases catalysing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate-oxidizing species reacts. This coordination flexibility has probably contributed to the evolution of the wide range of reactions catalysed by oxygenases