621 research outputs found
Earthquake Accelerogram Selection and Scaling Procedures for Estimating the Distribution of Drift Response
The problem of selecting a suite of earthquake accelerograms for time-domain analyses is of particular practical and academic interest. Research in this field has led to numerous approaches for compiling suites of accelerograms that may be used to robustly estimate the median structural response. However, many applications in earthquake engineering require the estimation of the full distribution of a structural response parameter for a particular predefined scenario. This article presents an efficient procedure whereby the distributions of interstory or roof drifts may be well approximated. The procedure makes use of three-point approximations to continuous distributions and the strong correlation that exists between the spectral acceleration at the initial fundamental period of the structure and the drift response. The distributions obtained under the proposed approach are compared with a reference distribution assumed to represent the true underlying distribution of drift response. The reference distribution is defined through a regression analysis conducted on the results of time-domain analyses of a six-story reinforced-concrete frame building subjected to 1,666 unsealed natural accelerograms. The results indicate that robust estimates of the first and second moments of the distribution of logarithmic drift may be obtained by subjecting the structure to several accelerograms scaled to match three target spectra over a range of periods. The target spectra are defined by the numbers of standard deviations above or below the median 5%-damped spectral acceleration and correspond to the roots of a third-order Hermite polynomial. The results demonstrate that consideration of fifth-order Hermite polynomials does not lead to a significantly improved performance of the approac
Statistical modeling of ground motion relations for seismic hazard analysis
We introduce a new approach for ground motion relations (GMR) in the
probabilistic seismic hazard analysis (PSHA), being influenced by the extreme
value theory of mathematical statistics. Therein, we understand a GMR as a
random function. We derive mathematically the principle of area-equivalence;
wherein two alternative GMRs have an equivalent influence on the hazard if
these GMRs have equivalent area functions. This includes local biases. An
interpretation of the difference between these GMRs (an actual and a modeled
one) as a random component leads to a general overestimation of residual
variance and hazard. Beside this, we discuss important aspects of classical
approaches and discover discrepancies with the state of the art of stochastics
and statistics (model selection and significance, test of distribution
assumptions, extreme value statistics). We criticize especially the assumption
of logarithmic normally distributed residuals of maxima like the peak ground
acceleration (PGA). The natural distribution of its individual random component
(equivalent to exp(epsilon_0) of Joyner and Boore 1993) is the generalized
extreme value. We show by numerical researches that the actual distribution can
be hidden and a wrong distribution assumption can influence the PSHA negatively
as the negligence of area equivalence does. Finally, we suggest an estimation
concept for GMRs of PSHA with a regression-free variance estimation of the
individual random component. We demonstrate the advantages of event-specific
GMRs by analyzing data sets from the PEER strong motion database and estimate
event-specific GMRs. Therein, the majority of the best models base on an
anisotropic point source approach. The residual variance of logarithmized PGA
is significantly smaller than in previous models. We validate the estimations
for the event with the largest sample by empirical area functions. etc
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Synthesis of accelerograms compatible with the Chinese GB 50011-2001 design spectrum via harmonic wavelets: artificial and historic records
A versatile approach is employed to generate artificial accelerograms which satisfy the compatibility criteria prescribed by the Chinese aseismic code provisions GB 50011-2001. In particular, a frequency dependent peak factor derived by means of appropriate Monte Carlo analyses is introduced to relate the GB 50011-2001 design spectrum to a parametrically defined evolutionary power spectrum (EPS). Special attention is given to the definition of the frequency content of the EPS in order to accommodate the mathematical form of the aforementioned design spectrum. Further, a one-to-one relationship is established between the parameter controlling the time-varying intensity of the EPS and the effective strong ground motion duration. Subsequently, an efficient auto-regressive moving-average (ARMA) filtering technique is utilized to generate ensembles of non-stationary artificial accelerograms whose average response spectrum is in a close agreement with the considered design spectrum. Furthermore, a harmonic wavelet based iterative scheme is adopted to modify these artificial signals so that a close matching of the signals’ response spectra with the GB 50011-2001 design spectrum is achieved on an individual basis. This is also done for field recorded accelerograms pertaining to the May, 2008 Wenchuan seismic event. In the process, zero-phase high-pass filtering is performed to accomplish proper baseline correction of the acquired spectrum compatible artificial and field accelerograms. Numerical results are given in a tabulated format to expedite their use in practice
A randomized, crossover design study of sevelamer carbonate powder and sevelamer hydrochloride tablets in chronic kidney disease patients on haemodialysis
Background. Sevelamer carbonate is an improved, buffered form of sevelamer hydrochloride developed for the treatment of hyperphosphataemia in CKD patients. Sevelamer carbonate formulated as a powder for oral suspension presents a novel, patient-friendly alternative to tablet phosphate binders. This study compared the safety and efficacy of sevelamer carbonate powder with sevelamer hydrochloride tablets in CKD patients on haemodialysis
microRNA-155, induced by interleukin-1 f, represses the expression of microphthalmia-associated transcription factor (MITF-M) in melanoma cells.
Loss of expression of surface antigens represents a significant problem for cancer immunotherapy. Microphthalmia-associated transcription factor (MITF-M) regulates melanocyte fate by driving expression of many differentiation genes, whose protein products can be recognized by cytolytic T lymphocytes. We previously reported that interleukin-1
f (IL-1
f) can downregulate MITF-M levels. Here we show that downregulation of MITF-M expression by IL-1
f was paralleled by an upregulation of miR-155 expression in four melanoma lines. We confirmed that miR-155 was able to target endogenous MITF-M in melanoma cells and demonstrated a role for miR-155 in the IL-1
f-induced repression of MITF-M by using an antagomiR. Notably, we also observed a strong negative correlation between MITF-M and miR-155 levels in a mouse model of melanoma. Taken together, our results indicate that MITF-M downregulation by inflammatory stimuli might be partly due to miR-155 upregulation. This could represent a novel mechanism of melanoma immune escape in an inflammatory microenvironment
Comparisons among the five ground-motion models developed using RESORCE for the prediction of response spectral accelerations due to earthquakes in Europe and the Middle East
This article presents comparisons among the five ground-motion models described in other articles within this special issue, in terms of data selection criteria, characteristics of the models and predicted peak ground and response spectral accelerations. Comparisons are also made with predictions from the Next Generation Attenuation (NGA) models to which the models presented here have similarities (e.g. a common master database has been used) but also differences (e.g. some models in this issue are nonparametric). As a result of the differing data selection criteria and derivation techniques the predicted median ground motions show considerable differences (up to a factor of two for certain scenarios), particularly for magnitudes and distances close to or beyond the range of the available observations. The predicted influence of style-of-faulting shows much variation among models whereas site amplification factors are more similar, with peak amplification at around 1s. These differences are greater than those among predictions from the NGA models. The models for aleatory variability (sigma), however, are similar and suggest that ground-motion variability from this region is slightly higher than that predicted by the NGA models, based primarily on data from California and Taiwan
Assessing the Effect of Piperacillin/Tazobactam on Hematological Parameters in Patients Admitted with Moderate or Severe Foot Infections
Introduction: Piperacillin/tazobactam is a commonly used antibiotic for the empirical treatment of severe diabetic foot infections. One of the most feared complications of this drug is the development of pancytopenia. The aim of this study was to determine whether the use of piperacillin/tazobactam caused any hematological changes in patients admitted with severe diabetes-related foot infections from a specialist multidisciplinary foot clinic. Specifically, looking at whether it caused anemia, leukopenia, neutropenia, or thrombocytopenia. Methods: A 1-year retrospective analysis of patients admitted to a tertiary care center for treatment of diabetes-related foot infection using piperacillin/tazobactam. Hematological indices, urea and electrolytes, and C-reactive protein (CRP) were recorded pretreatment, during treatment, and posttreatment. HbA1c, vitamin B12, folate, thyroid-stimulating hormone, and free thyroxin were also analyzed to exclude any potential confounders as a cause of pancytopenia. Results: A total of 154 patients were admitted between 1 January 2016 and 31 December 2016 who received piperacillin/tazobactam for severe diabetes-related foot infection. On admission, white cell count and CRP were raised and fell significantly within the first 48 h. Other hematological factors did not change. Five patients developed a mild pancytopenia, of which three were unexplained. Conclusion: In this relatively small cohort, pancytopenia did not occur. As such, piperacillin/tazobactam appeared to have a low risk of adverse hematological outcomes and remains the treatment of choice for severe diabetes-related foot infections
A functional assay for microRNA target identification and validation
MicroRNAs (miRNA) are a class of small RNA molecules that regulate numerous critical cellular processes and bind to partially complementary sequences resulting in down-regulation of their target genes. Due to the incomplete homology of the miRNA to its target site identification of miRNA target genes is difficult and currently based on computational algorithms predicting large numbers of potential targets for a given miRNA. To enable the identification of biologically relevant miRNA targets, we describe a novel functional assay based on a 3′-UTR-enriched library and a positive/negative selection strategy. As proof of principle we have used mir-130a and its validated target MAFB to test this strategy. Identification of MAFB and five additional targets and their subsequent confirmation as mir-130a targets by western blot analysis and knockdown experiments validates this strategy for the functional identification of miRNA targets
Proton Pump Inhibitors Exert Anti-Allergic Effects by Reducing TCTP Secretion
BACKGROUND:Extracellular translationally controlled tumor protein (TCTP) is known to play a role in human allergic responses. TCTP has been identified outside of macrophages, in activated mononuclear cells, and in biological fluids from allergic patients. Even TCTP devoid of signal sequences, is secreted to extracellular environment by an yet undefined mechanism. This study is aimed at understanding the mechanism of TCTP release and its regulation. A secondary goal is to see if inhibitors of TCTP release can serve as potential anti-allergic asthmatic drugs. METHODOLOGY/PRINCIPAL FINDINGS:Using Western blotting assay in HEK293 and U937 cells, we found that TCTP secretion is reduced by omeprazole and pantoprazole, both of which are proton pump inhibitors. We then transfected HEK293 cells with proton pump expression vectors to search for the effects of exogeneously overexpressed H(+)/K(+)-ATPase on the TCTP secretion. Based on these in vitro data we checked the in vivo effects of pantoprazole in a murine model of ovalbumin-induced allergy. Omeprazole and pantoprazole reduced TCTP secretion from HEK293 and U937 cells in a concentration-dependent fashion and the secretion of TCTP from HEK293 cells increased when they over-expressed H(+)/K(+)-ATPase. In a murine model of ovalbumin-induced allergy, pretreatment with pantoprazole reduced infiltration of inflammatory cells, increased goblet cells, and increased TCTP secretion induced by OVA challenge. CONCLUSION:Since Omeprazole and pantoprazole decrease the secretion of TCTP which is associated with the development of allergic reaction, they may have the potential to serve as anti-allergic (asthmatic) drugs
Seismic risk assessment for developing countries : Pakistan as a case study
Modern Earthquake Risk Assessment (ERA) methods usually require seismo-tectonic information for Probabilistic Seismic Hazard Assessment (PSHA) that may not be readily available in developing countries. To bypass this drawback, this paper presents a practical event-based PSHA method that uses instrumental seismicity, available historical seismicity, as well as limited information on geology and tectonic setting. Historical seismicity is integrated with instrumental seismicity to determine the long-term hazard. The tectonic setting is included by assigning seismic source zones associated with known major faults. Monte Carlo simulations are used to generate earthquake catalogues with randomized key hazard parameters. A case study region in Pakistan is selected to demonstrate the effectiveness of the method. The results indicate that the proposed method produces seismic hazard maps consistent with previous studies, thus being suitable for generating such maps in regions where limited data are available. The PSHA procedure is developed as an integral part of an ERA framework named EQRAM. The framework is also used to determine seismic risk in terms of annual losses for the study region
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