Increased sensitivity of the ryanodine receptor to halothane-induced oligomerization in malignant hyperthermia-susceptible human skeletal muscle

Mutations in the skeletal muscle RyR1 isoform of the ryanodine receptor (RyR) Ca2+-release channel confer susceptibility to malignant hyperthermia, which may be triggered by inhalational anesthetics such as halothane. Using immunoblotting, we show here that the ryanodine receptor, calmodulin, junctin, calsequestrin, sarcalumenin, calreticulin, annexin-VI, sarco(endo)plasmic reticulum Ca2+-ATPase, and the dihydropyridine receptor exhibit no major changes in their expression level between normal human skeletal muscle and biopsies from individuals susceptible to malignant hyperthermia. In contrast, protein gel-shift studies with halothane-treated sarcoplasmic reticulum vesicles from normal and susceptible specimens showed a clear difference. Although the alpha2-dihydropyridine receptor and calsequestrin were not affected, clustering of the Ca2+-ATPase was induced at comparable halothane concentrations. In the concentration range of 0.014-0.35 mM halothane, anesthetic-induced oligomerization of the RyR1 complex was observed at a lower threshold concentration in the sarcoplasmic reticulum from patients with malignant hyperthermia. Thus the previously described decreased Ca2+-loading ability of the sarcoplasmic reticulum from susceptible muscle fibers is probably not due to a modified expression of Ca2+-handling elements, but more likely a feature of altered quaternary receptor structure or modified functional dynamics within the Ca2+-regulatory apparatus. Possibly increased RyR1 complex formation, in conjunction with decreased Ca2+ uptake, is of central importance to the development of a metabolic crisis in malignant hyperthermia

Search for the hero: an investigation into the sports heroes of British sports fans

This is an initial study into British sports fans’ heroes. A questionnaire was sent to 95 students (average age ¼ 19.75) to identify their sporting hero, the hero’s sport and nationality and the reasons for this choice. Football was the most common source of sports heroes, identified by 49% of participants with a sporting hero. The majority (60%, N ¼ 48) of heroes chosen by participants were British, with David Beckham the most popular choice. Differences were observed between the gender of participants, gender of hero chosen and the reasons for choosing the hero. The most common reason for selecting a hero was a personal trait rather than skill, while in the questionnaire a category of Local Affiliation was added to those suggested by previous work. It was concluded that to become a hero athletes should combine skill with devotion to family, charity work and a place in popular culture

Quantum Logic Gates and Nuclear Magnetic Resonance Pulse Sequences

We demonstrate how NMR can in principle be used to implement all the elements required to build quantum computers, and briefly discuss the potential applications of insights from quantum logic to the development of novel pulse sequences with applications in more conventional NMR experiments.Comment: Sixteen pages, no figures. Submitted to Journal of Magnetic Resonance. Primarily pedagogical rather than a description of novel research result

The Dirichlet Casimir effect for ϕ4\phi^4 theory in (3+1) dimensions: A new renormalization approach

We calculate the next to the leading order Casimir effect for a real scalar field, within $\phi^4$ theory, confined between two parallel plates in three spatial dimensions with the Dirichlet boundary condition. In this paper we introduce a systematic perturbation expansion in which the counterterms automatically turn out to be consistent with the boundary conditions. This will inevitably lead to nontrivial position dependence for physical quantities, as a manifestation of the breaking of the translational invariance. This is in contrast to the usual usage of the counterterms in problems with nontrivial boundary conditions, which are either completely derived from the free cases or at most supplemented with the addition of counterterms only at the boundaries. Our results for the massive and massless cases are different from those reported elsewhere. Secondly, and probably less importantly, we use a supplementary renormalization procedure, which makes the usage of any analytic continuation techniques unnecessary.Comment: JHEP3 format,20 pages, 2 figures, to appear in JHE

The detection of Gravitational Waves

This chapter is concerned with the question: how do gravitational waves (GWs) interact with their detectors? It is intended to be a theory review of the fundamental concepts involved in interferometric and acoustic (Weber bar) GW antennas. In particular, the type of signal the GW deposits in the detector in each case will be assessed, as well as its intensity and deconvolution. Brief reference will also be made to detector sensitivity characterisation, including very summary data on current state of the art GW detectors.Comment: 33 pages, 12 figures, LaTeX2e, Springer style files --included. For Proceedings of the ERE-2001 Conference (Madrid, September 2001

Adherence to the Dutch Breast Cancer Guidelines for Surveillance in Breast Cancer Survivors:Real-World Data from a Pooled Multicenter Analysis

BACKGROUND: Regular follow-up after treatment for breast cancer is crucial to detect potential recurrences and second contralateral breast cancer in an early stage. However, information about follow-up patterns in the Netherlands is scarce. PATIENTS AND METHODS: Details concerning diagnostic procedures and policlinic visits in the first 5 years following a breast cancer diagnosis were gathered between 2009 and 2019 for 9916 patients from 4 large Dutch hospitals. This information was used to analyze the adherence of breast cancer surveillance to guidelines in the Netherlands. Multivariable logistic regression was used to relate the average number of a patient’s imaging procedures to their demographics, tumor–treatment characteristics, and individual locoregional recurrence risk (LRR), estimated by a risk-prediction tool, called INFLUENCE. RESULTS: The average number of policlinic contacts per patient decreased from 4.4 in the first to 2.0 in the fifth follow-up year. In each of the 5 follow-up years, the share of patients without imaging procedures was relatively high, ranging between 31.4% and 33.6%. Observed guidelines deviations were highly significant (P < .001). A higher age, lower UICC stage, and having undergone radio- or chemotherapy were significantly associated with a higher chance of receiving an imaging procedure. The estimated average LRR-risk was 3.5% in patients without any follow-up imaging compared with 2.3% in patients with the recommended number of 5 imagings. CONCLUSION: Compared to guidelines, more policlinic visits were made, although at inadequate intervals, and fewer imaging procedures were performed. The frequency of imaging procedures did not correlate with the patients’ individual risk profiles for LRR

Finite element simulation of three-dimensional free-surface flow problems

An adaptive finite element algorithm is described for the stable solution of three-dimensional free-surface-flow problems based primarily on the use of node movement. The algorithm also includes a discrete remeshing procedure which enhances its accuracy and robustness. The spatial discretisation allows an isoparametric piecewise-quadratic approximation of the domain geometry for accurate resolution of the curved free surface. The technique is illustrated through an implementation for surface-tension-dominated viscous flows modelled in terms of the Stokes equations with suitable boundary conditions on the deforming free surface. Two three-dimensional test problems are used to demonstrate the performance of the method: a liquid bridge problem and the formation of a fluid droplet

Test of Sum Rules in Nucleon Transfer Reactions

The quantitative consistency of nucleon transfer reactions as a probe of the occupancy of valence orbits in nuclei is tested. Neutron-adding, neutron-removal, and proton-adding transfer reactions were measured on the four stable even Ni isotopes, with particular attention to the cross section determinations. The data were analyzed consistently in terms of the distorted wave Born approximation to yield spectroscopic factors. Valence-orbit occupancies were extracted, utilizing the Macfarlane-French sum rules. The deduced occupancies are consistent with the changing number of valence neutrons, as are the vacancies for protons, both at the level of <5%. While there has been some debate regarding the true “observability” of spectroscopic factors, the present results indicate that empirically they yield self-consistent results

S(C)ENTINEL - monitoring automated vehicles with olfactory reliability displays

Overreliance in technology is safety-critical and it is assumed that this could have been a main cause of severe accidents with automated vehicles. To ease the complex task of per- manently monitoring vehicle behavior in the driving en- vironment, researchers have proposed to implement relia- bility/uncertainty displays. Such displays allow to estimate whether or not an upcoming intervention is likely. However, presenting uncertainty just adds more visual workload on drivers, who might also be engaged in secondary tasks. We suggest to use olfactory displays as a potential solution to communicate system uncertainty and conducted a user study (N=25) in a high-fidelity driving simulator. Results of the ex- periment (conditions: no reliability display, purely visual reliability display, and visual-olfactory reliability display) comping both objective (task performance) and subjective (technology acceptance model, trust scales, semi-structured interviews) measures suggest that olfactory notifications could become a valuable extension for calibrating trust in automated vehicles

Valence nucleon populations in the Ni isotopes

Measurements of neutron-adding, neutron-removing, and proton-adding reactions were carried out for the four stable even Ni isotopes. Particular attention was paid to obtaining precise values of the cross sections at the peaks of the angular distributions. Tests with sum rules for the neutron data indicate that the results are self-consistent at the level of a few tenths of a nucleon. Data on proton-adding reactions were also obtained and analyzed with a slightly different method—while these data are also consistent, the ambiguities are larger. The occupancies of the neutron orbits derived from the data, the proton vacancies, and the energy centroids of the neutron, neutron-hole, and proton single-particle excitations are obtained. The data also provide some estimate about the closure of the 0f7/2 shell. The results are compared to shell-model calculations and may serve as a reference point for future exploration