Some Effects of Extreme Shortening on Frog Skeletal Muscle

We have established that the sarcolemma of frog skeletal muscle is so firmly tied in at each sarcomere level near the M line, as well as near the Z line, that it is thrown into folds or festoons when the fibers shorten. The attachment is not broken even when the fibers shorten to 25% of optimum tension length. Such extreme shortening affects both the morphology and physiology of the muscle; the morphological change seems to be limited to the myofilaments. The physiological effects in frog sartorius muscle include an increase in resting oxygen consumption and changes in the relation between fiber length and isometric tension similar to those found in isolated muscle fibers

The resource theory of quantum reference frames: manipulations and monotones

Every restriction on quantum operations defines a resource theory, determining how quantum states that cannot be prepared under the restriction may be manipulated and used to circumvent the restriction. A superselection rule is a restriction that arises through the lack of a classical reference frame and the states that circumvent it (the resource) are quantum reference frames. We consider the resource theories that arise from three types of superselection rule, associated respectively with lacking: (i) a phase reference, (ii) a frame for chirality, and (iii) a frame for spatial orientation. Focussing on pure unipartite quantum states (and in some cases restricting our attention even further to subsets of these), we explore single-copy and asymptotic manipulations. In particular, we identify the necessary and sufficient conditions for a deterministic transformation between two resource states to be possible and, when these conditions are not met, the maximum probability with which the transformation can be achieved. We also determine when a particular transformation can be achieved reversibly in the limit of arbitrarily many copies and find the maximum rate of conversion. A comparison of the three resource theories demonstrates that the extent to which resources can be interconverted decreases as the strength of the restriction increases. Along the way, we introduce several measures of frameness and prove that these are monotonically nonincreasing under various classes of operations that are permitted by the superselection rule.Comment: 37 pages, 4 figures, Published Versio

Translating the potential of the urine steroid metabolome to stage NAFLD (TrUSt-NAFLD): study protocol for a multicentre, prospective validation study.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) affects approximately one in four individuals and its prevalence continues to rise. The advanced stages of NAFLD with significant liver fibrosis are associated with adverse morbidity and mortality outcomes. Currently, liver biopsy remains the 'gold-standard' approach to stage NAFLD severity. Although generally well tolerated, liver biopsies are associated with significant complications, are resource intensive, costly, and sample only a very small area of the liver as well as requiring day case admission to a secondary care setting. As a result, there is a significant unmet need to develop non-invasive biomarkers that can accurately stage NAFLD and limit the need for liver biopsy. The aim of this study is to validate the use of the urine steroid metabolome as a strategy to stage NAFLD severity and to compare its performance against other non-invasive NAFLD biomarkers. METHODS AND ANALYSIS: The TrUSt-NAFLD study is a multicentre prospective test validation study aiming to recruit 310 patients with biopsy-proven and staged NAFLD across eight centres within the UK. 150 appropriately matched control patients without liver disease will be recruited through the Oxford Biobank. Blood and urine samples, alongside clinical data, will be collected from all participants. Urine samples will be analysed by liquid chromatography-tandem mass spectroscopy to quantify a panel of predefined steroid metabolites. A machine learning-based classifier, for example, Generalized Matrix Relevance Learning Vector Quantization that was trained on retrospective samples, will be applied to the prospective steroid metabolite data to determine its ability to identify those patients with advanced, as opposed to mild-moderate, liver fibrosis as a consequence of NAFLD. ETHICS AND DISSEMINATION: Research ethical approval was granted by West Midlands, Black Country Research Ethics Committee (REC reference: 21/WM/0177). A substantial amendment (TrUSt-NAFLD-SA1) was approved on 26 November 2021. TRIAL REGISTRATION NUMBER: ISRCTN19370855

Dual roles for LUBAC signaling in thymic epithelial cell development and survival

Thymic epithelial cells (TECs) form a unique microenvironment that orchestrates T cell differentiation and immunological tolerance. Despite the importance of TECs for adaptive immunity, there is an incomplete understanding of the signalling networks that support their differentiation and survival. We report that the linear ubiquitin chain assembly complex (LUBAC) is essential for medullary TEC (mTEC) differentiation, cortical TEC survival and prevention of premature thymic atrophy. TEC-specific loss of LUBAC proteins, HOIL-1 or HOIP, severely impaired expansion of the thymic medulla and AIRE-expressing cells. Furthermore, HOIL-1-deficiency caused early thymic atrophy due to Caspase-8/MLKL-dependent apoptosis/necroptosis of cortical TECs. By contrast, deficiency in the LUBAC component, SHARPIN, caused relatively mild defects only in mTECs. These distinct roles for LUBAC components in TECs correlate with their function in linear ubiquitination, NFκB activation and cell survival. Thus, our findings reveal dual roles for LUBAC signaling in TEC differentiation and survival

Experimental GHZ Entanglement beyond Qubits

The Greenberger-Horne-Zeilinger (GHZ) argument provides an all-or-nothing contradiction between quantum mechanics and local-realistic theories. In its original formulation, GHZ investigated three and four particles entangled in two dimensions only. Very recently, higher dimensional contradictions especially in three dimensions and three particles have been discovered but it has remained unclear how to produce such states. In this article we experimentally show how to generate a three-dimensional GHZ state from two-photon orbital-angular-momentum entanglement. The first suggestion for a setup which generates three-dimensional GHZ entanglement from these entangled pairs came from using the computer algorithm Melvin. The procedure employs novel concepts significantly beyond the qubit case. Our experiment opens up the possibility of a truly high-dimensional test of the GHZ-contradiction which, interestingly, employs non-Hermitian operators.Comment: 6+6 pages, 8 figure

The acquisition of Sign Language: The impact of phonetic complexity on phonology

Research into the effect of phonetic complexity on phonological acquisition has a long history in spoken languages. This paper considers the effect of phonetics on phonological development in a signed language. We report on an experiment in which nonword-repetition methodology was adapted so as to examine in a systematic way how phonetic complexity in two phonological parameters of signed languages — handshape and movement — affects the perception and articulation of signs. Ninety-one Deaf children aged 3–11 acquiring British Sign Language (BSL) and 46 hearing nonsigners aged 6–11 repeated a set of 40 nonsense signs. For Deaf children, repetition accuracy improved with age, correlated with wider BSL abilities, and was lowest for signs that were phonetically complex. Repetition accuracy was correlated with fine motor skills for the youngest children. Despite their lower repetition accuracy, the hearing group were similarly affected by phonetic complexity, suggesting that common visual and motoric factors are at play when processing linguistic information in the visuo-gestural modality

Nucleation of a sodium droplet on C60

We investigate theoretically the progressive coating of C60 by several sodium atoms. Density functional calculations using a nonlocal functional are performed for NaC60 and Na2C60 in various configurations. These data are used to construct an empirical atomistic model in order to treat larger sizes in a statistical and dynamical context. Fluctuating charges are incorporated to account for charge transfer between sodium and carbon atoms. By performing systematic global optimization in the size range 1<=n<=30, we find that Na_nC60 is homogeneously coated at small sizes, and that a growing droplet is formed above n=>8. The separate effects of single ionization and thermalization are also considered, as well as the changes due to a strong external electric field. The present results are discussed in the light of various experimental data.Comment: 17 pages, 10 figure

The role of Comprehension in Requirements and Implications for Use Case Descriptions

Within requirements engineering it is generally accepted that in writing specifications (or indeed any requirements phase document), one attempts to produce an artefact which will be simple to comprehend for the user. That is, whether the document is intended for customers to validate requirements, or engineers to understand what the design must deliver, comprehension is an important goal for the author. Indeed, advice on producing ‘readable’ or ‘understandable’ documents is often included in courses on requirements engineering. However, few researchers, particularly within the software engineering domain, have attempted either to define or to understand the nature of comprehension and it’s implications for guidance on the production of quality requirements. Therefore, this paper examines thoroughly the nature of textual comprehension, drawing heavily from research in discourse process, and suggests some implications for requirements (and other) software documentation. In essence, we find that the guidance on writing requirements, often prevalent within software engineering, may be based upon assumptions which are an oversimplification of the nature of comprehension. Hence, the paper examines guidelines which have been proposed, in this case for use case descriptions, and the extent to which they agree with discourse process theory; before suggesting refinements to the guidelines which attempt to utilise lessons learned from our richer understanding of the underlying discourse process theory. For example, we suggest subtly different sets of writing guidelines for the different tasks of requirements, specification and design

Cymantrene–Triazole "Click" Products: Structural Characterization and Electrochemical Properties

We report the first known examples of triazole-derivatized cymantrene complexes (η5-[4-substituted triazol-1-yl]cyclopentadienyl)tricarbonylmanganese(I), obtained via a “click” chemical synthesis, bearing a phenyl, 3-aminophenyl, or 4-aminophenyl moiety at the 4-position of the triazole ring. Structural characterization data using multinuclear NMR, UV–vis, ATR-IR, and mass spectrometric methods are provided, as well as crystallographic data for (η5-[4-phenyltriazol-1-yl]cyclopentadienyl)tricarbonylmanganese(I) and (η5-[4-(3-aminophenyl)triazol-1-yl]cyclopentadienyl)tricarbonylmanganese(I). Cyclic voltammetric characterization of the redox behavior of each of the three cymantrene–triazole complexes is presented together with digital simulations, in situ infrared spectroelectrochemistry, and DFT calculations to extract the associated kinetic and thermodynamic parameters. The trypanocidal activity of each cymantrene–triazole complex is also examined, and these complexes are found to be more active than cymantrene alone