The muscle metabolome differs between healthy and frail older adults

Populations around the world are aging rapidly. Age-related loss of physiological functions negatively affects quality of life. A major contributor to the frailty syndrome of aging is loss of skeletal muscle. In this study we assessed the skeletal muscle biopsy metabolome of healthy young, healthy older and frail older subjects to determine the effect of age and frailty on the metabolic signature of skeletal muscle tissue. In addition, the effects of prolonged whole-body resistance-type exercise training on the muscle metabolome of older subjects were examined. The baseline metabolome was measured in muscle biopsies collected from 30 young, 66 healthy older subjects and 43 frail older subjects. Follow-up samples from frail older (24 samples) and healthy older subjects (38 samples) were collected after 6 months of prolonged resistance-type exercise training. Young subjects were included as a reference If thisgroup. Primary differences in skeletal muscle metabolite levels between young and healthy older subjects were related to mitochondrial function, muscle fiber type, and tissue turnover. Similar differences were observed when comparing frail older subjects with healthy older subjects at baseline. Prolonged resistance-type exercise training resulted in an adaptive response of amino acid metabolism, especially reflected in branched chain amino acids and genes related to tissue remodeling. The effect of exercise training on branched-chain amino acid-derived acylcarnitines in older subjects points to a downward shift in branched-chain amino acid catabolism upon training. We observed only modest correlations between muscle and plasma metabolite levels, which pleads against the use of plasma metabolites as a direct read-out of muscle metabolism and stresses the need for direct assessment of metabolites in muscle tissue biopsies

Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty

Global ageing poses a substantial economic burden on health and social care costs. Enabling a greater proportion of older people to stay healthy for longer is key to the future sustainability of health, social and economic policy. Frailty and associated decrease in resilience plays a central role in poor health in later life. In this study, we present a population level assessment of the metabolic phenotype associated with frailty. Analysis of serum from 1191 older individuals (aged between 56 and 84 years old) and subsequent longitudinal validation (on 786 subjects) was carried out using liquid and gas chromatography-mass spectrometry metabolomics and stratified across a frailty index designed to quantitatively summarize vulnerability. Through multivariate regression and network modelling and mROC modeling we identified 12 significant metabolites (including three tocotrienols and six carnitines) that differentiate frail and non-frail phenotypes. Our study provides evidence that the dysregulation of carnitine shuttle and vitamin E pathways play a role in the risk of frailty

Flutter of aircraft wings carrying a powered engine under roll maneuver

The flutter analysis of a swept aircraft wing-store configuration subjected to follower force and undergoing a roll maneuver is presented. Concentrated mass, follower force, and roll angular velocity terms are combined in the governing equations, which are obtained using the Hamilton's variational principle. The wing is modeled from a classical beam theory and incorporates bending-torsion flexibility. Heaviside and Dirac delta functions are used to consider the location and properties of the external mass and the follower force. Also, Peters's unsteady aerodynamic pressure loadings is considered and modified to take into account the effect of the wing sweep angle. The extended Galerkin's method is applied to convert the partial differential equations into a set of ordinary differential equations. Numerical simulations are validated with available published results. Simulation results are presented to show the effects on the wing flutter of the roll angular velocity, sweep angle, follower force, and store mass and its location. Results are indicative of the significant effect of the rigid-body roll angular velocity and the follower force on the wing-store dynamic stability. Furthermore, it is shown that the distances between the wing root and the aircraft center of gravity, acting location of the roll angular velocity, considerably affects the wing-engine flutter speed and frequenc

Chaotic and bifurcation dynamic behavior of functionally graded curved panels under aero-thermal loads

This paper presents the nonlinear analysis of functionally graded curved panels under high temperature supersonic gas flows. The aerothermoelastic governing equations are determined via Hamilton's variational principle. The von Karman nonlinear straindisplacement relations are used to account for large deflections. The material properties are assumed to be temperature-dependent and varying through the thickness direction according to a power law distribution in terms of the volume fractions of the constituent components. The panel is assumed to be infinitely long and simply supported. The Galerkin method is applied to convert the partial differential governing equation into a set of ordinary differential equations and the resulting system of nonlinear equations is solved through a numerical integration scheme. The effects of volume fraction index, curved panel height-rise, and aerodynamic pressure, in conjunction with the applied thermal loading, on the dynamical behavior of the panel are investigated. Regular and chaotic motions regime are determined through bifurcation analysis using Poincaré maps of maximum panel deflection, panel time history, phase-space and frequency spectra as qualitative tools, while Lyapunov's exponents and dimension are used as quantitative tools

Uncertainty propagation in vibrational characteristics of functionally graded carbon nanotube-reinforced composite shell panels

Understanding the effect of mechanical uncertainties can play a significant role in design of the nanocomposites. The uncertain natural frequencies of moderately thick doubly-curved functionally graded composite panels reinforced by carbon nanotube (CNT) are investigated. Specifically, doubly-curved shell panels, including spherical, cylindrical and hyperbolic paraboloid panels are examined. To evaluate uncertainty propagation, uncertainty resources including distribution of the CNT through the thickness as well as the mechanical properties of the CNT and polymer matrix are taken into consideration. To assess the propagated uncertainties in the vibrational characteristics of nanocomposite panels, the interval analysis method is employed while the mechanical properties of nanocomposite panels are predicted using the modified rule of mixture method. Based on the comparison between the results of the present study and those reported in the literature, the accuracy of the results is validated. The sensitivity analysis is performed to distinguish the most prominent uncertain variables. Furthermore, numerical results reveal the influences of various uncertainty resources on the upper and lower bounds of uncertain frequencies and uncertainty propagation percent

Final approach and flare control of a flexible aircraft in crosswind landings

In this paper, the flight simulation and control of a flexible aircraft in landing is presented. The discrete form of hybrid-state equations of motion in terms of quasi coordinates takes into account the coupling between elastic and rigid-body degrees of freedom and provides the framework for the controller design and simulation. The wings of the aircraft are modeled as cantilever beams undergoing bending and torsion about their elastic axis. Distributed variables are discretized in space using the Galerkin method, and unsteady aerodynamic forces are computed using strip theory and finite state induced-flow theory. A landing condition in which the elastic aircraft encounters a crosswind all the way before touchdown is considered. To design the control system, nonlinear coupled equations of motion are linearized about the trim condition and separated into two sets of decoupled equations, in which the elastic variables affect lateral-directional equations. The landing phase is divided into the final approach and flare phases and, for each phase, separate controllers are designed for longitudinal- and lateral-directional channels. An optimal-integral feedforward control scheme is implemented to accomplish the autolanding, while suppressing the wind effects on the flight path. The performance of the control system is examined through nonlinear simulatio

Thermoelastic vibration of doubly-curved nano-composite shells reinforced by graphene nanoplatelets

The thermo-mechanical vibration characteristics of doubly-curved nano-composite shells reinforced by graphene nanoplatelets are investigated by considering a uniform distribution of graphene and a first-order shear deformation theory. The mechanical properties of the nano-composite shells are estimated by using the modified HalpinTsai model. The governing equations are first derived by a variational formulation using Hamiltons principle and are solved using the Galerkin technique. Numerical results are presented for various shell curvatures and compared with those available in the archival literature. Furthermore, parametric studies are offered to highlight the significant influence of graphene nanoplatelets weight fraction, dimensions of graphene nanoplatelets, and temperature variation, on the free vibration of the nano-composite shells

Transcriptome as marker for nutrition-related health: added value of time course analyses during challenge tests before and after energy restriction

Phenotypic flexibility is used as a measure for health and can be studied during nutritional challenge tests. Changes in gene expression are early markers and give insight into mechanisms. Energy restriction (ER) has a variety of beneficial health effects and can be used to investigate different health states to study postprandial changes during challenge tests. Objective: We aimed to determine the postprandial effects of a 20% ER diet on whole genome expression profiles of peripheral blood mononuclear cells (PBMCs). Materials and methods: 72 healthy, overweight men and women, aged 50-65, were subjected to an oral glucose tolerance test (OGTT) and a mixed meal test (MMT), before and after a 12 week intervention with either a 20% ER diet or a control diet. Total RNA from PBMCs was isolated at fasting, and at postprandially during the OGTT at 30, 60, and 120 min and during the MMT at 60, 120, 240, and 360 min. RNA of all time points was used to evaluate whole genome gene expression response using Affymetrix microarrays, resulting in a number of 1231 arrays. Results and conclusions: Upon 20% ER, gene sets involved in OXPHOS, cell adhesion, energy metabolism, immune system, cell cycle, and DNA replication were increased. Upon an OGTT, OXPHOS, cell adhesion, and DNA replication gene sets were decreased after ER. Also, some postprandial effects seem to happen in the control group, but at a later stage. We concluded that ER increased phenotypic flexibility by means on increased use of OXPHOS pathways, and that the response to an OGTT seemed faster upon ER than upon a control die

Transcriptome as marker for nutrition-related health: added value of time course analyses during challenge tests before and after energy restriction

Phenotypic flexibility is used as a measure for health and can be studied during nutritional challenge tests. Changes in gene expression are early markers and give insight into mechanisms. Energy restriction (ER) has a variety of beneficial health effects and can be used to investigate different health states to study postprandial changes during challenge tests. Objective: We aimed to determine the postprandial effects of a 20% ER diet on whole genome expression profiles of peripheral blood mononuclear cells (PBMCs). Materials and methods: 72 healthy, overweight men and women, aged 50-65, were subjected to an oral glucose tolerance test (OGTT) and a mixed meal test (MMT), before and after a 12 week intervention with either a 20% ER diet or a control diet. Total RNA from PBMCs was isolated at fasting, and at postprandially during the OGTT at 30, 60, and 120 min and during the MMT at 60, 120, 240, and 360 min. RNA of all time points was used to evaluate whole genome gene expression response using Affymetrix microarrays, resulting in a number of 1231 arrays. Results and conclusions: Upon 20% ER, gene sets involved in OXPHOS, cell adhesion, energy metabolism, immune system, cell cycle, and DNA replication were increased. Upon an OGTT, OXPHOS, cell adhesion, and DNA replication gene sets were decreased after ER. Also, some postprandial effects seem to happen in the control group, but at a later stage. We concluded that ER increased phenotypic flexibility by means on increased use of OXPHOS pathways, and that the response to an OGTT seemed faster upon ER than upon a control die