The intrinsic load-resisting capacity of kinesin

Conventional kinesin is a homodimeric motor protein that is capable of walking unidirectionally along a cytoskeletal filament. While previous experiments indicated unyielding unidirectionality against an opposing load up to the so-called stall force, recent experiments also observed limited processive backwalking under superstall loads. This theoretical study seeks to elucidate the molecular mechanical basis for kinesin's steps over the full range of external loads that can possibly be applied to the dimer. We found that kinesin's load-resisting capacity is largely determined by a synergic ratchet-and-pawl mechanism inherent in the dimer. Load susceptibility of this inner molecular mechanical mechanism underlies kinesin's response to various levels of external loads. Computational implementation of the mechanism enabled us to rationalize major trends observed experimentally in kinesin's stalemate and consecutive back steps. The study also predicts several distinct features of kinesin's load-affected motility, which are seemingly counterintuitive but readily verifiable by future experiment.Comment: 44 pages, 6 figure

Fundamental limits on key rates in device-independent quantum key distribution

In this paper, we introduce intrinsic non-locality as a quantifier for Bell non-locality, and we prove that it satisfies certain desirable properties such as faithfulness, convexity, and monotonicity under local operations and shared randomness. We then prove that intrinsic non-locality is an upper bound on the secret-key-agreement capacity of any device-independent protocol conducted using a device characterized by a correlation $p$. We also prove that intrinsic steerability is an upper bound on the secret-key-agreement capacity of any semi-device-independent protocol conducted using a device characterized by an assemblage $\hat{\rho}$. We also establish the faithfulness of intrinsic steerability and intrinsic non-locality. Finally, we prove that intrinsic non-locality is bounded from above by intrinsic steerability.Comment: 44 pages, 4 figures, final version accepted for publication in New Journal of Physic

Intrinsic aerobic capacity sets a divide for aging and longevity

<p><b>Rationale:</b> Low aerobic exercise capacity is a powerful predictor of premature morbidity and mortality for healthy adults as well as those with cardiovascular disease. For aged populations, poor performance on treadmill or extended walking tests indicates closer proximity to future health declines. Together, these findings suggest a fundamental connection between aerobic capacity and longevity.</p> <p><b>Objectives:</b> Through artificial selective breeding, we developed an animal model system to prospectively test the association between aerobic exercise capacity and survivability (aerobic hypothesis).</p> <p><b>Methods and Results:</b> Laboratory rats of widely diverse genetic backgrounds (N:NIH stock) were selectively bred for low or high intrinsic (inborn) treadmill running capacity. Cohorts of male and female rats from generations 14, 15, and 17 of selection were followed for survivability and assessed for age-related declines in cardiovascular fitness including maximal oxygen uptake (VO<sub>2max</sub>), myocardial function, endurance performance, and change in body mass. Median lifespan for low exercise capacity rats was 28% to 45% shorter than high capacity rats (hazard ratio, 0.06; P<0.001). VO<sub>2max</sub>, measured across adulthood was a reliable predictor of lifespan (P<0.001). During progression from adult to old age, left ventricular myocardial and cardiomyocyte morphology, contractility, and intracellular Ca<sup>2+</sup> handling in both systole and diastole, as well as mean blood pressure, were more compromised in rats bred for low aerobic capacity. Physical activity levels, energy expenditure (Vo<sub>2</sub>), and lean body mass were all better sustained with age in rats bred for high aerobic capacity.</p> <p><b>Conclusions:</b> These data obtained from a contrasting heterogeneous model system provide strong evidence that genetic segregation for aerobic exercise capacity can be linked with longevity and are useful for deeper mechanistic exploration of aging.</p&gt

Extrinsic and intrinsic curvatures in thermodynamic geometry

We investigate the intrinsic and extrinsic curvatures of certain hypersurfaces in the thermodynamic geometry of a physical system and show that they contain useful thermodynamic information. For an anti-Reissner-Nordstr\"{o}m-(A)de Sitter black hole (Phantom), the extrinsic curvature of a constant $Q$ hypersurface has the same sign as the heat capacity around the phase transition points. For a Kerr-Newmann-AdS (KN-AdS) black hole, the extrinsic curvature of $Q \to 0$ hypersurface (Kerr black hole) or $J \to 0$ hypersurface (RN black black hole) has the same sign as the heat capacity around the phase transition points. The extrinsic curvature also diverges at the phase transition points. The intrinsic curvature of the hypersurfaces diverges at the critical points but has no information about the sign of the heat capacity. Our study explains the consistent relationship holding between the thermodynamic geometry of the KN-AdS black holes and those of the RN and Kerr ones \cite{ref1}. This approach can be easily generalized to an arbitrary thermodynamic system.Comment: 10 pages, 4 figure

Life-course inequalities in intrinsic capacity and healthy ageing, China

Objective To investigate the contribution of early-life factors on intrinsic capacity of Chinese adults older than 45 years. Methods We used data on 21 783 participants from waves 1 (2011) and 2 (2013) of the China Health and Retirement Longitudinal Study (CHARLS), who also participated in the 2014 CHARLS Life History Survey to calculate a previously validated measure of intrinsic capacity. We considered 11 early-life factors and investigated their direct association with participants’ intrinsic capacity later in life, as well as their indirect association through four current socioeconomic factors. We used multivariable linear regression and the decomposition of the concentration index to investigate the contribution of each determinant to intrinsic capacity inequalities. Findings Participants with a favourable environment in early life (that is, parental education, childhood health and neighbourhood environment) had a significantly higher intrinsic capacity score in later life. For example, participants with a literate father recorded a 0.040 (95% confidence interval, CI: 0.020 to 0.051) higher intrinsic capacity score than those with an illiterate father. This inequality was greater for cognitive, sensory and psychological capacities than locomotion and vitality. Overall, early-life factors directly explained 13.92% (95% CI: 12.07 to 15.77) of intrinsic capacity inequalities, and a further 28.57% (95% CI: 28.19 to 28.95) of these inequalities through their influence on current socioeconomic inequalities. Conclusion Unfavourable early-life factors appear to decrease late-life health status in China, particularly cognitive, sensory and psychological capacities, and these effects are exacerbated by cumulative socioeconomic inequalities over a person’s life course