A mathematical understanding of how cytoplasmic dynein walks on microtubules

Cytoplasmic dynein 1 (hereafter referred to simply as dynein) is a dimeric motor protein that walks and transports intracellular cargos towards the minus end of microtubules. In this article, we formulate, based on physical principles, a mechanical model to describe the stepping behaviour of cytoplasmic dynein walking on microtubules from the cell membrane towards the nucleus. Unlike previous studies on physical models of this nature, we base our formulation on the whole structure of dynein to include the temporal dynamics of the individual subunits such as the cargo ( for example, an endosome, vesicle or bead), two rings of six ATPase domains associated with diverse cellular activities (AAAþ rings) and the microtubule-binding domains which allow dynein to bind to microtubules. This mathematical framework allows us to examine experimental observations on dynein across a wide range of different species, as well as being able to make predictions on the temporal behaviour of the individual components of dynein not currently experimentally measured. Furthermore, we extend the model framework to include backward stepping, variable step size and dwelling. The power of our model is in its predictive nature; first it reflects recent experimental observations that dynein walks on microtubules using a weakly coordinated stepping pattern with predominantly not passing steps. Second, the model predicts that interhead coordination in the ATP cycle of cytoplasmic dynein is important in order to obtain the alternating stepping patterns and long run lengths seen in experiments

Exercise Addiction Prevalence and Correlates in the Absence of Eating Disorder Symptomology: A Systematic Review and Meta-analysis

BACKGROUND: Exercise addiction (EA) can be debilitating and can be a symptom of an eating disorder. To date, the prevalence rates of EA without indicated eating disorders in the general population and associated correlates remain unreported. METHODS: Two authors searched major databases from inception to 31/12/2018 to identify studies investigating the prevalence of EA in any population without indicated eating disorders. We conducted a random effects meta-analysis to report (i) prevalence rates of EA using the exercise addiction inventory and exercise dependence scale and compare sub-populations, (ii) compare methods of EA measurement and explore heterogeneity, and (iii) report on correlates. RESULTS: A total of 13 studies including 3635 people were included. The prevalence of EA among general exercisers was 8.1% (95% CI 1.5%-34.2%), amateur competitive athletes was 5.0% (95% CI 1.3%-17.3%), and university students was 5.5% (95% CI 1.4-19.1%%). Overall prevalence rates varied depending on the EA measurement tool. EA subjects were more likely to have lower levels of overall wellbeing (only in amateur competitive athletes), higher anxiety levels, and have greater frontal brain activity. CONCLUSIONS: EA is prevalent in the absence of indicated eating disorders across populations but varies depending on measurement tool. Further research is needed to explore EA without indicated eating disorders in different populations using homogenous measurement tools, further determine psychological correlates, and examine which measures of EA without indicated eating disorders predict poor health outcomes

The Initial Mass Function in disc galaxies and in galaxy clusters: the chemo-photometric picture

The observed brightness of the Tully-Fisher relation suggests a low stellar M/L ratio and a "bottom-light" IMF in disc galaxies, but the corresponding efficiency of chemical enrichment tends to exceed the observational estimates. Either suitable tuning of the IMF slope and mass limits or metal outflows from disc galaxies must then be invoked. A standard Solar Neighbourhood IMF cannot explain the high metallicity of the hot intra-cluster medium: a different IMF must be at work in clusters of galaxies. Alternatively, if the IMF is universal and chemical enrichment is everywhere as efficient as observed in clusters, substantial loss of metals must occur from the Solar Neighbourhood and from disc galaxies in general; a "non-standard" scenario challenging our understanding of disc galaxy formation.Comment: 6 pages, 4 figures; in Proceedings of IMF@50: the Initial Mass Function 50 years later; Corbelli, Palla and Zinnecker (eds.

On the numerical evaluation of algebro-geometric solutions to integrable equations

Physically meaningful periodic solutions to certain integrable partial differential equations are given in terms of multi-dimensional theta functions associated to real Riemann surfaces. Typical analytical problems in the numerical evaluation of these solutions are studied. In the case of hyperelliptic surfaces efficient algorithms exist even for almost degenerate surfaces. This allows the numerical study of solitonic limits. For general real Riemann surfaces, the choice of a homology basis adapted to the anti-holomorphic involution is important for a convenient formulation of the solutions and smoothness conditions. Since existing algorithms for algebraic curves produce a homology basis not related to automorphisms of the curve, we study symplectic transformations to an adapted basis and give explicit formulae for M-curves. As examples we discuss solutions of the Davey-Stewartson and the multi-component nonlinear Schr\"odinger equations.Comment: 29 pages, 20 figure

Modelling and peeling extended sources with shapelets: a Fornax A case study

To make a power spectrum (PS) detection of the 21 cm signal from the Epoch of Reionisation (EoR), one must avoid/subtract bright foreground sources. Sources such as Fornax A present a modelling challenge due to spatial structures spanning from arc seconds up to a degree. We compare modelling with multi-scale (MS) CLEAN components to 'shapelets', an alternative set of basis functions. We introduce a new image-based shapelet modelling package, SHAMFI. We also introduce a new CUDA simulation code (WODEN) to generate point source, Gaussian, and shapelet components into visibilities. We test performance by modelling a simulation of Fornax A, peeling the model from simulated visibilities, and producing a residual PS. We find the shapelet method consistently subtracts large-angular-scale emission well, even when the angular-resolution of the data is changed. We find that when increasing the angular-resolution of the data, the MS CLEAN model worsens at large angular-scales. When testing on real MWA data, the expected improvement is not seen in real data because of the other dominating systematics still present. Through further simulation we find the expected differences to be lower than obtainable through current processing pipelines. We conclude shapelets are worthwhile for subtracting extended galaxies, and may prove essential for an EoR detection in the future, once other systematics have been addressed.Comment: 17 pages, 11 Figures, accepted for publication in Publications of the Astronomical Society of Australia (18/05/2020). "For the SHAMFI code, see: https://github.com/JLBLine/SHAMFI" . "For the SHAMFI documentation, see: https://shamfi.readthedocs.io/" . "For the WODEN code and documentation see: https://github.com/JLBLine/WODEN

Examination of phase transformations and decomposition chemistry in thermally aged thin-film explosives

To develop predictive models for the response of weapon systems to abnormal thermal environments, such as cookoff, an improved understanding of temperature-dependent thermophysical phenomena (such as phase transformations) and decomposition chemistry in totally confined explosive samples is needed. It is particularly important to examine the effects of maintaining-intimate contact between the decomposition products and the remaining condensed-phase explosive during slow reaction at elevated temperatures since confinement of the decomposition products may significantly affect thermophysical phenomena and decomposition reaction rates. The purpose of this work has been to examine experimentally the effects on condensed-phase chemistry which result when decomposition products remain in intimate contact with the reacting explosive during isothermal aging experiments at temperatures below those of the DTA exotherm for the explosive. To provide confinement, minimize vapor space, and permit condensed-phase chemical analysis, experiments were done using thin-film samples of the explosive, which were pressed and sealed between two infrared-transmitting windows, so that condensed-phase chemistry could be monitored using infrared spectroscopy. Experiments were done with NC, HMX, HMX-NC composite, and RDX samples. Results from the experiments with NC showed that for some decomposition mechanisms, the reaction rates for confined samples compared favorably with published reaction rates from unconfined samples. However, the results also demonstrated that for other mechanisms, the reaction rates were significantly affected by confinement of the decomposition products. The experiments with HMX and RDX indicated that some decomposition occurred at temperatures well below the temperatures of the respective DTA exotherms, and the experiments with HMX-NC composite samples showed some interaction between NC and HMX at temperatures as low as 150{degrees}C

Galactic Collapse of Scalar Field Dark Matter

We present a scenario for galaxy formation based on the hypothesis of scalar field dark matter. We interpret galaxy formation through the collapse of a scalar field fluctuation. We find that a cosh potential for the self-interaction of the scalar field provides a reasonable scenario for galactic formation, which is in agreement with cosmological observations and phenomenological studies in galaxies.Comment: 4 pages, 3 figue

Evolutionary Multi-Objective Design of SARS-CoV-2 Protease Inhibitor Candidates

Computational drug design based on artificial intelligence is an emerging research area. At the time of writing this paper, the world suffers from an outbreak of the coronavirus SARS-CoV-2. A promising way to stop the virus replication is via protease inhibition. We propose an evolutionary multi-objective algorithm (EMOA) to design potential protease inhibitors for SARS-CoV-2's main protease. Based on the SELFIES representation the EMOA maximizes the binding of candidate ligands to the protein using the docking tool QuickVina 2, while at the same time taking into account further objectives like drug-likeliness or the fulfillment of filter constraints. The experimental part analyzes the evolutionary process and discusses the inhibitor candidates.Comment: 15 pages, 7 figures, submitted to PPSN 202

EWPD Constraints on Flavor Symmetric Vector Fields

Electroweak precision data constraints on flavor symmetric vector fields are determined. The flavor multiplets of spin one that we examine are the complete set of fields that couple to quark bi-linears at tree level while not initially breaking the quark global flavor symmetry group. Flavor safe vector masses proximate to, and in some cases below, the electroweak symmetry breaking scale are found to be allowed. Many of these fields provide a flavor safe mechanism to explain the t tbar forward backward anomaly, and can simultaneously significantly raise the allowed values of the Standard Model Higgs mass consistent with electroweak precision data.Comment: Matches version published in JHE

Arte convenzionale – ovvero – perché non possono esistere artisti realmente anticonformisti

The representation of the artist is generally that of a nonconformist, a lonely Bohemian eager to revolutionise the world from his studio. From this perspective, the traditional interpretation of art history is one of linear progress, spurred on by moments of innovation aiming at new states of conventionalism. This article shows how such a perspective has much to do with the philosophy of modern times, even though it doesn’t provide a satisfactory explanation of the meaning and development of art throughout the centuries, bound as they are instead to the necessity of convention with the values of society (or of its élite) rather than on wild individualism