Untargeted NMR Metabolomics Reveals Alternative Biomarkers and Pathways in Alkaptonuria

Alkaptonuria (AKU) is an ultra-rare metabolic disease caused by the accumulation of homogentisic acid (HGA), an intermediate product of phenylalanine and tyrosine degradation. AKU patients carry variants within the gene coding for homogentisate-1,2-dioxygenase (HGD), which are responsible for reducing the enzyme catalytic activity and the consequent accumulation of HGA and formation of a dark pigment called the ochronotic pigment. In individuals with alkaptonuria, ochronotic pigmentation of connective tissues occurs, leading to inflammation, degeneration, and eventually osteoarthritis. The molecular mechanisms underlying the multisystemic development of the disease severity are still not fully understood and are mostly limited to the metabolic pathway segment involving HGA. In this view, untargeted metabolomics of biofluids in metabolic diseases allows the direct investigation of molecular species involved in pathways alterations and their interplay. Here, we present the untargeted metabolomics study of AKU through the nuclear magnetic resonance of urine from a cohort of Italian patients; the study aims to unravel molecular species and mechanisms underlying the AKU metabolic disorder. Dysregulation of metabolic pathways other than the HGD route and new potential biomarkers beyond homogentisate are suggested, contributing to a more comprehensive molecular signature definition for AKU and the development of future adjuvant treatment. © 2022 by the authors

Is Quantum Chaos Weaker Than Classical Chaos?

We investigate chaotic behavior in a 2-D Hamiltonian system - oscillators with anharmonic coupling. We compare the classical system with quantum system. Via the quantum action, we construct Poincar\'{e} sections and compute Lyapunov exponents for the quantum system. We find that the quantum system is globally less chaotic than the classical system. We also observe with increasing energy the distribution of Lyapunov exponts approaching a Gaussian with a strong correlation between its mean value and energy.Comment: text (LaTeX) + 7 figs.(ps

Chaos in effective classical and quantum dynamics

We investigate the dynamics of classical and quantum N-component phi^4 oscillators in the presence of an external field. In the large N limit the effective dynamics is described by two-degree-of-freedom classical Hamiltonian systems. In the classical model we observe chaotic orbits for any value of the external field, while in the quantum case chaos is strongly suppressed. A simple explanation of this behaviour is found in the change in the structure of the orbits induced by quantum corrections. Consistently with Heisenberg's principle, quantum fluctuations are forced away from zero, removing in the effective quantum dynamics a hyperbolic fixed point that is a major source of chaos in the classical model.Comment: 6 pages, RevTeX, 5 figures, uses psfig, changed indroduction and conclusions, added reference

Quantum Chaos at Finite Temperature

We use the quantum action to study quantum chaos at finite temperature. We present a numerical study of a classically chaotic 2-D Hamiltonian system - harmonic oscillators with anharmonic coupling. We construct the quantum action non-perturbatively and find temperature dependent quantum corrections in the action parameters. We compare Poincar\'{e} sections of the quantum action at finite temperature with those of the classical action.Comment: Text (LaTeX), Figs. (ps

Quantum Chaos Versus Classical Chaos: Why is Quantum Chaos Weaker?

We discuss the questions: How to compare quantitatively classical chaos with quantum chaos? Which one is stronger? What are the underlying physical reasons

Riemannian theory of Hamiltonian chaos and Lyapunov exponents

This paper deals with the problem of analytically computing the largest Lyapunov exponent for many degrees of freedom Hamiltonian systems. This aim is succesfully reached within a theoretical framework that makes use of a geometrization of newtonian dynamics in the language of Riemannian geometry. A new point of view about the origin of chaos in these systems is obtained independently of homoclinic intersections. Chaos is here related to curvature fluctuations of the manifolds whose geodesics are natural motions and is described by means of Jacobi equation for geodesic spread. Under general conditions ane effective stability equation is derived; an analytic formula for the growth-rate of its solutions is worked out and applied to the Fermi-Pasta-Ulam beta model and to a chain of coupled rotators. An excellent agreement is found the theoretical prediction and the values of the Lyapunov exponent obtained by numerical simulations for both models.Comment: RevTex, 40 pages, 8 PostScript figures, to be published in Phys. Rev. E (scheduled for November 1996

Study of dynamic buckling in droppers of high-speed railway line catenary during pantograph passage|Studio del dynamic buckling nei pendini conduttori di una catenaria AV al passaggio del pantografo

The dynamical actions to which the catenary dropper is subjected during the pantograph passage can become very relevant for high speeds of railway vehicle. In some very rare and isolated cases, premature failure of the dropper positioned near the suspension and/or near the auto tensioning devices in catenaries for High Speed (HS) operation has been observed. In order to understand the phenomenon, an analysis developed in several activities was carried out, including numerical analyses and in line and in laboratory experimental activities. A final phase of the investigation was dedicated to the development of a prototype of a dropper specifically designed on the basis of the results obtained from this study with the aim of improving the dropper fatigue behaviour. The new dropper could be used in critical points of the overhead line, such as near the suspension and/or near the auto tensioning devices