Nonlinear static procedures, which relate the seismic demand of a structure to that of an equivalent single-degree-of-freedom (SDOF) oscillator, are well-established tools in the performance based earthquake engineering framework and have gradually found their way into modern codes for seismic design and assessment.Initially, such procedures made recourse to inelastic spectra derived for simple elastic-plastic or bilinear oscillators, but the request for demand estimates, which delve deeper into the inelastic range, shifted the trend towards investigating the seismic demand of oscillators with more complex backbone curves.Meanwhile, the engineering relevance of near-source (NS) pulse-like ground motions has been receiving increased attention, since it has been recognized that such ground motions can induce a distinctive type of inelastic demand.Pulse-like NS ground motions are usually the result of rupture directivity, where seismic waves generated at different points along the rupture front arrive at a site at the same time, leading to a double-sided velocity pulse, which delivers most of the seismic energy.Recent research has led to a methodology being proposed for incorporating this NS effect in the implementation of nonlinear static procedures.Both of the aforementioned lines of earthquake engineering research motivate the present study, which investigates the ductility demands imposed by pulse-like NS ground motions on SDOF oscillators who feature pinching hysteretic behavior with trilinear backbone curves.This investigation uses incremental dynamic analysis (IDA) considering a suite of one hundred and thirty pulse-like-identified ground motions.Median, as well as 16% and 84% fractile, IDA curves are calculated, on which an analytical model is fitted.Least-squares estimates are obtained for the model parameters, which importantly include pulse period Tp.The resulting equations effectively constitute an R-μ-T/Tp relation for pulse-like NS motions.A potential application of this result is briefly demonstrated in an illustrative example of NS seismic demand estimation.
A risk-consistent approach is proposed for the evaluation of behaviour factors that are compatible with Eurocode 8 using nonlinear static and dynamic analysis. The proposed process comprises seven discrete steps, involving hazard assessment and record selection at multiple sites, designing and modelling multiple archetype buildings and assessing their performance vis-à-vis target safety objectives. In all cases, uncertainty is incorporated and propagated to the final results whereby a flexible verification procedure is offered to account for the confidence of the investigator on the data available. The value added goes beyond the current state of art, offering a consistent risk basis for the seismic design of different systems that is compatible with current uniform hazard design spectra and future risk-targeted hazard maps.
Critical illness leads to a coordinated reaction that is categorized as the stress response; activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system leads to metabolic and cardiovascular changes that are generally directed toward maintenance of homeostasis. The HPA axis and the sympathetic nervous system are linked via reciprocally activating brainstem pathways. The immune system acts via cytokines, which are hormones, to activate the HPA axis. Glucocorticoid secretion suppresses immune activity, thus completing an immune-HPA feedback loop. Restraint of immune activity may be a major function of glucocorticoids during stress, thus averting the potential for immune-mediated damage to healthy tissues. Cortisol also acts to produce adaptive metabolic, cardiovascular, and cognitive changes. Activation of the stress system is also associated with inhibition of thyroid, gonadal, and growth axes through neuroendocrine and peripheral mechanisms; such effects can be seen as directed toward conservation of energy. There is growing evidence that hyperfunction and hypofunction of the integrated stress system may lead to a variety of previously unexplained disorders. Recently, a more detailed understanding of the stress system combined with astute clinical observation of critically ill patients has led to promising new avenues for therapeutic investigation.
I. INTRODUCTION The nervous, endocrine, and immune systems secrete and respond to various regulatory molecules including steroids, neuropeptides, cytokines, prostanoids, and neurotransmitters, which provide the molecular basis for neuroendocrine-immune responses during disturbances of homeostasis. The central effectors of these responses include the locus ceruleusnoradrenaline (LC-NA)/autonomic (sympathetic) neurons of the hypothalamus and brain stem and the corticotropin-releasing hormone (CRH)/arginine-vasopressin (AVP) neurons of the paraventricular nucleus of the hypothalamus, which respectively regulate the peripheral activities of the systemic/adrenomedullary sympathetic nervous systems (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. Activation of the LC-NA/autonomic system and HPA axis results in systemic elevations of catecholamines (CAs) and glucocorticoids (GCs), respectively, that act in concert to maintain a steady state (Chrousos, 1995).
Aging is a complex biological process characterized by the progressive accumulation of cellular and molecular damage, leading to functional decline and increased susceptibility to age-related diseases. Central to this process is cellular senescence, a state of irreversible cell cycle arrest that acts as both a protective mechanism against tumorigenesis and a contributor to tissue degeneration. Herein, we explore the genetic and molecular mechanisms underlying aging, with a focus on telomere dynamics, the <i>Klotho</i> gene, angiotensin-converting enzyme (ACE), and the NF-κB pathway. Telomeres, which serve as protective caps at chromosome ends, shorten with each cell division, leading to replicative senescence, while the enzyme telomerase plays a pivotal role in maintaining telomere length and cellular longevity. The <i>Klotho</i> gene encoding for an aging suppressor influences insulin/IGF-1 signaling and has antioxidant properties that protect against oxidative stress. ACE, through its dual role in regulating blood pressure and degrading amyloid-beta, impacts longevity and age-related pathologies. The NF-κB pathway drives chronic inflammation or "inflammaging," contributing to the onset of age-related diseases. Understanding these pathways offers promising avenues for therapeutic interventions to extend health span and lifespan. Targeting mechanisms such as telomerase activation, <i>Klotho</i> supplementation, ACE inhibition, and NF-κB modulation hold potential for combating the detrimental effects of aging and promoting healthier aging in the population.