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In this paper I would like to offer a new framework for hypothetical reasoning, with the goal of predicting what scenarios we consider when we interpret a conditional or causal claim (such as a sentence containing the word because). The idea is that when we interpret a conditional or causal claim, we identify a part of the world to change and imagine changing that. Sentences are about parts of the world: when we interpret a conditional antecedent or because clause, we allow the part of the world it is about to vary. This expands our modal horizons, which we restrict to those scenarios where the sentence we are asked to imagine true is indeed true. To evaluate a whole conditional or causal claim we look to the possible futures after this change. My main evidence for this approach is that it gives just the right range of hypothetical scenarios to account for how we interpret both conditionals and causal claims. Some approaches (such as Stalnaker and Lewis's semantics of conditionals based on similarity, and Kratzer's premise semantics) consider too few scenarios, while others (such as Fine's 2012 truthmaker semantics of conditionals) consider too many. The present approach inhabits a Goldilocks zone between these extremes: not too restrictive, not too permissive, but just right.

© 2020 Institution of Engineering and Technology. All rights reserved. An eccentric position diagnosis method of static eccentricity (SE) fault of external rotor permanent magnet synchronous motor (ER-PMSM) is presented. Firstly, an analytical model of no-load radial magnetic field of ER-PMSM is established. Analytical models of no-load Back-EMF of both unit motors and the whole motor are carried out and are verified by finite element method (FEM) and experimental measurements. Then, the influences of SE ratio, SE circumferential angle, winding distribution mode and number of parallel branches on no-load radial magnetic field and no-load Back-EMF are analyzed based on these analytical models. The results show that SE does not affect the frequency characteristics of no-load radial magnetic field, but changes space order characteristics. On one hand, for ER-PMSM, of which the number of unit motors is equal to 1, SE causes no-load Back-EMF distortion. On the other hand, for ER-PMSM, of which the number of unit motors is greater than 1, SE does not affect no-load Back-EMF of the whole motor, but it still leads to no-load Back-EMF distortion of unit motors. Therefore, based on total harmonic distortion (THD) of no-load Back-EMF of unit motor, a projection method of intersection lines for SE fault diagnosis of ER-PMSM is proposed finally.

Summary To warrant the quality of the secretory proteome, stringent control systems operate at the endoplasmic reticulum (ER)-Golgi interface, preventing the release of nonnative products. Incompletely assembled oligomeric proteins that are deemed correctly folded must rely on additional quality control mechanisms dedicated to proper assembly. Here we unveil how ERp44 cycles between cisGolgi and ER in a pH-regulated manner, patrolling assembly of disulfide-linked oligomers such as IgM and adiponectin. At neutral, ER-equivalent pH, the ERp44 carboxy-terminal tail occludes the substrate-binding site. At the lower pH of the cisGolgi, conformational rearrangements of this peptide, likely involving protonation of ERp44’s active cysteine, simultaneously unmask the substrate binding site and −RDEL motif, allowing capture of orphan secretory protein subunits and ER retrieval via KDEL receptors. The ERp44 assembly control cycle couples secretion fidelity and efficiency downstream of the calnexin/calreticulin and BiP-dependent quality control cycles., Graphical Abstract, Highlights • ERp44 governs a pH-regulated assembly control cycle in the early secretory pathway • Accessibility of ERp44’s active site and –RDEL ER retrieval motif is pH dependent • Unmasking of ERp44’s active site likely involves protonation of cysteine 29 • ERp44 captures client proteins at cisGolgi-equivalent pH for retrieval to the ER

"Thermophilic enzymes face the challenge of maintaining optimal catalytic activity at temperatures nearing the boiling point of water, hence, they can be used as interesting model systems to understand the evolution of enzymes, as well as the molecular strategies developed as defence against thermal denaturation. Several comparisons between the structures of homologous isozymes from mesophilic and thermophilic organisms highlighted specific properties of folded proteins that may contribute to thermal stability. Moreover, the understanding of general strategies that may enhance the stability of enzymes at high temperatures could be beneficial for the engineering of biocatalysts in industrial processes. . Here we report a comparative structure-thermostability analysis of a panel of tetrameric nucleoside hydrolase (NH) enzymes from mesophiles and thermophiles by a combined structural and spectroscopic characterization that utilize principal component analysis (PCA) and differential scanning fluorimetry (DSF). . The availability of high-resolution structures of NH enzymes isolated from both mesophilic and hyperthermophilic organisms belonging to the same structural homology group, emphasizes the elements that lead to enhanced stability and underscores that resistance to thermal denaturation can be achieved using a combination of different structural solutions. Apparently, each organism can employ a different combination of stabilizing structural features to achieve the required level of NH stability. However, the multivariate analysis highlights how the NHs from mesophilic and thermophilic organisms here considered can be clustered according to the type and extent of specific features used for optimization. The results obtained indicate that the inclusion of salt bridges at the intersubunit contact surfaces is the only shared strategy in both mesophilic and thermophilic organisms to modulate the stability of NHs.. "