Endoplasmic Reticulum Stress is Transmissible among Cells of the Central Nervous System

Improper protein folding and trafficking are common pathological events observed in various cell types in neurodegenerative diseases. If the protein quality control mechanisms of the endoplasmic reticulum (ER) fail to re-establish proteostasis, misfolded proteins accumulate within the lumen of the ER and perturb normal cellular processes. While low-level stimulation of the unfolded protein response (UPR) is considered a beneficial physiological response to transient protein misfolding stress, or ER stress, sustained UPR activation resulting from prolonged ER stress can promote neurotoxicity. The cell-autonomous mechanisms of the UPR have been extensively characterized in the context of neuropathology. Nevertheless, there still remain unanswered questions regarding the cell-extrinsic role of the UPR under normal physiology, and how this mechanism is compromised in diseased states. To address this, we evaluated whether transferring conditioned media from ER stressed astrocytes to different cell types could modulate their functional characteristics. Our results indicate that ER stressed astrocytes secrete a mediator(s) which regulates both inflammatory and ER stress responses in other astrocytes and neurons in vitro. Initial exposure to this stress factor(s) confers resistance against subsequent ER stress to neurons by engaging the adaptive signals of the neuronal UPR. However, persistent exposure to this unidentified mediator(s) suppresses the initial protective effect and becomes cytotoxic. Overall, these findings provide insight into the cell-nonautonomous influence of ER stress on cells of the central nervous system. Further understanding the molecular mechanisms underlying this mode of intercellular communication would present novel therapeutic opportunities to treat neurodegenerative diseases

Vibration analysis and intelligent control of flexible rotor systems using smart materials

Flexible rotor-bearing system stability is a very important subject impacting the design, control, maintenance and operating safety. As the rotor bearing-system dynamic nonlinearities are significantly more prominent at higher rotating speeds, the demand for better performance through higher speeds has rendered the use of linear approaches for analysis both inadequate and ineffective. To address this need, it becomes important that nonlinear rotor-dynamic responses indicative of the causes of nonlinearity, along with the bifurcated dynamic states of instabilities, be fully studied. The objectives of this research are to study rotor-dynamic instabilities induced by mass unbalance and to use smart materials to stabilise the performance of the flexible rotor-system. A comprehensive mathematical model incorporating translational and rotational inertia, bending stiffness and gyroscopic moment is developed. The dynamic end conditions of the rotor comprising of the active bearing-induced axial force is modelled, the equations of motion are derived using Lagrange equations and the Rayleigh-Ritz method is used to study the basic phenomena on simple systems. In this thesis the axial force terms included in the equations of motion provide a means for axially directed harmonic force to be introduced into the system. The Method of Multiple Scales is applied to study the nonlinear equations obtained and their stabilities. The Dynamics 2 software is used to numerically explore the inception and progression of bifurcations suggestive of the changing rotor-dynamic state and impending instability. In the context of active control of flexible rotors, smart materials particularly SMAs and piezoelectric stack actuators are introduced. The application of shape memory alloy (SMA) elements integrated within glass epoxy composite plates and shells has resulted in the design of a novel smart bearing based on the principle of antagonistic action in this thesis. Previous work has shown that a single SMA/composite active bearing can be very effective in both altering the natural frequency of the fundamental whirl mode as well as the modal amplitude. The drawback with that design has been the disparity in the time constant between the relatively fast heating phase and the much slower cooling phase which is reliant on forced air, or some other form of cooling. This thesis presents a modified design which removes the aforementioned existing shortcomings. This form of design means that the cooling phase of one half, still using forced air, is significantly assisted by switching the other half into its heating phase, and vice versa, thereby equalising the time constants, and giving a faster push-pull load on the centrally located bearing; a loading which is termed ‘antagonistic’ in this present dissertation. The piezoelectric stack actuator provides an account of an investigation into possible dynamic interactions between two nonlinear systems, each possessing nonlinear characteristics in the frequency domain. Parametric excitations are deliberately introduced into a second flexible rotor system by means of a piezoelectric exciter to moderate the response of the pre-existing mass-unbalance vibration inherent to the rotor. The intended application area for this SMA/composite and piezoelectric technologies are in industrial rotor systems, in particular very high-speed plant, such as small light pumps, motor generators, and engines for aerospace and automotive application

Static DC to DC Power Conditioning-Active Ripple Filter, 1 MHZ DC to DC Conversion, and Nonlinear Analysis

Dc to dc static power conditioning systems on unmanned spacecraft have as their inputs highly fluctuating dc voltages which they condition to regulated dc voltages. These input voltages may be less than or greater than the desired regulated voltages. The design of two circuits which address specific problems in the design of these power conditioning systems and a nonlinear analysis of one of the circuits are discussed. The first circuit design is for a nondissipative active ripple filter which uses an operational amplifier to amplify and cancel the sensed ripple voltage. A dc to dc converter operating at a switching frequency of 1 MHz is the second circuit discussed. A nonlinear analysis of the type of dc to dc converter utilized in designing the 1 MHz converter is included

Power System Simulation, Control and Optimization

This Special Issue “Power System Simulation, Control and Optimization” offers valuable insights into the most recent research developments in these topics. The analysis, operation, and control of power systems are increasingly complex tasks that require advanced simulation models to analyze and control the effects of transformations concerning electricity grids today: Massive integration of renewable energies, progressive implementation of electric vehicles, development of intelligent networks, and progressive evolution of the applications of artificial intelligence

International Conference on Mathematical Analysis and Applications in Science and Engineering – Book of Extended Abstracts

The present volume on Mathematical Analysis and Applications in Science and Engineering - Book of Extended Abstracts of the ICMASC’2022 collects the extended abstracts of the talks presented at the International Conference on Mathematical Analysis and Applications in Science and Engineering – ICMA2SC'22 that took place at the beautiful city of Porto, Portugal, in June 27th-June 29th 2022 (3 days). Its aim was to bring together researchers in every discipline of applied mathematics, science, engineering, industry, and technology, to discuss the development of new mathematical models, theories, and applications that contribute to the advancement of scientific knowledge and practice. Authors proposed research in topics including partial and ordinary differential equations, integer and fractional order equations, linear algebra, numerical analysis, operations research, discrete mathematics, optimization, control, probability, computational mathematics, amongst others. The conference was designed to maximize the involvement of all participants and will present the state-of- the-art research and the latest achievements.info:eu-repo/semantics/publishedVersio

Advanced methods for the solution of differential equations

This book is based on a course presented at the Lewis Research Center for engineers and scientists who were interested in increasing their knowledge of differential equations. Those results which can actually be used to solve equations are therefore emphasized; and detailed proofs of theorems are, for the most part, omitted. However, the conclusions of the theorems are stated in a precise manner, and enough references are given so that the interested reader can find the steps of the proofs

Evolutionary genomics : statistical and computational methods

This open access book addresses the challenge of analyzing and understanding the evolutionary dynamics of complex biological systems at the genomic level, and elaborates on some promising strategies that would bring us closer to uncovering of the vital relationships between genotype and phenotype. After a few educational primers, the book continues with sections on sequence homology and alignment, phylogenetic methods to study genome evolution, methodologies for evaluating selective pressures on genomic sequences as well as genomic evolution in light of protein domain architecture and transposable elements, population genomics and other omics, and discussions of current bottlenecks in handling and analyzing genomic data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and expert implementation advice that lead to the best results. Authoritative and comprehensive, Evolutionary Genomics: Statistical and Computational Methods, Second Edition aims to serve both novices in biology with strong statistics and computational skills, and molecular biologists with a good grasp of standard mathematical concepts, in moving this important field of study forward