The advantages and disadvantages of using scalar and vector ground motion intensity measures (IMs) are discussed for the local, story-level seismic response assessment of three-dimensional (3-D) buildings. Candidate IMs are spectral accelerations, at a single period ( Sa) or averaged over a period range ( Sa avg ). Consistent scalar and vector probabilistic seismic hazard analysis results were derived for each IM, as described in the companion paper in this issue ( Kohrangi et al. 2016 ). The response hazard curves were computed for three buildings with reinforced concrete infilled frames using the different IMs as predictors. Among the scalar IMs, Sa avg tends to be the best predictor of both floor accelerations and inter story drift ratios at practically any floor. However, there is an improvement in response estimation efficiency when employing vector IMs, specifically for 3-D buildings subjected to both horizontal components of ground motion. This improvement is shown to be most significant for a tall plan-asymmetric building.
No abstract is provided for this article.
Context and Objective Circulating cortisol fluctuates diurnally under the control of the “master” circadian CLOCK, while the peripheral “slave” counterpart of the latter regulates the transcriptional activity of the glucocorticoid receptor (GR) at local glucocorticoid target tissues through acetylation. In this manuscript, we studied the effect of CLOCK-mediated GR acetylation on the sensitivity of peripheral tissues to glucocorticoids in humans. Design and Participants We examined GR acetylation and mRNA expression of GR, CLOCK-related and glucocorticoid-responsive genes in peripheral blood mononuclear cells (PBMCs) obtained at 8 am and 8 pm from 10 healthy subjects, as well as in PBMCs obtained in the morning and cultured for 24 hours with exposure to 3-hour hydrocortisone pulses every 6 hours. We used EBV-transformed lymphocytes (EBVLs) as non-synchronized controls. Results GR acetylation was higher in the morning than in the evening in PBMCs, mirroring the fluctuations of circulating cortisol in reverse phase. All known glucocorticoid-responsive genes tested responded as expected to hydrocortisone in non-synchronized EBVLs, however, some of these genes did not show the expected diurnal mRNA fluctuations in PBMCs in vivo. Instead, their mRNA oscillated in a Clock- and a GR acetylation-dependent fashion in naturally synchronized PBMCs cultured ex vivo in the absence of the endogenous glucocorticoid, suggesting that circulating cortisol might prevent circadian GR acetylation-dependent effects in some glucocorticoid-responsive genes in vivo. Conclusions Peripheral CLOCK-mediated circadian acetylation of the human GR may function as a target-tissue, gene-specific counter regulatory mechanism to the actions of diurnally fluctuating cortisol, effectively decreasing tissue sensitivity to glucocorticoids in the morning and increasing it at night.
A bstract : Recent evidence indicates that glucocorticoids and catecholamines, the major stress hormones, inhibit the production of proinflammatory cytokines, such as interleukin (IL)‐12, tumor necrosis factor (TNF)‐α, and interferon (IFN)‐γ, whereas they stimulate the production of antiinflammatory cytokines, such as IL‐10, IL‐4, and transforming growth factor (TGF)‐β. Thus, systemically, an excessive immune response, through activation of the stress system, stimulates an important negative feedback mechanism, which protects the organism from an “overshoot” of proinflammatory cytokines and other products of activated macrophages with tissue‐damaging potential. Conversely, in certain local responses and under certain conditions, stress hormones actually may boost regional immune responses, through induction of TNF‐α, IL‐1, and IL‐8, and by inhibiting TGF‐β production. Therefore, conditions that are associated with significant changes in stress system activity, such as acute or chronic stress, cessation of chronic stress, severe exercise, and pregnancy and the postpartum period, through modulation of the systemic or local pro/antiinflammatory cytokine balance, may suppress or potentiate autoimmune diseases activity and/or progression.
Present building-specific loss assessment state-of-art involves the convolution of seismic hazard and building seismic demands. The latter is conditioned on spectral acceleration, Sa( T 1 ), at the building's first mode as the ground motion intensity measure (IM) and is typically estimated by carrying out nonlinear dynamic analyses on a two-dimensional (2-D) model. By new proposals on the use of improved IMs that can introduce higher fidelity, the accuracy in loss estimation becomes an open question. In reply, we offer a uniform basis for comparing the loss estimates for a set of eight different scalar and vector IMs whose hazard can be predicted with existing GMPEs. Despite all eight being legitimate IMs, and despite the consistent use of conditional spectrum record selection, we find large differences in the estimated loss hazard. This points to the large uncertainty still lingering when connecting hazard to loss. Among the IMs considered here, the vector IMs and at least a scalar average of spectral accelerations showed a remarkable stability in their predictions for the three-dimensional (3-D) buildings, pointing to a potential for reliable applications.
