Pushover analysis for the seismic response prediction of cable-stayed bridges under multi-directional excitation

Cable-stayed bridges represent nowadays key points in transport networks and their seismic behavior needs to be fully understood, even beyond the elastic range of materials. Both nonlinear dynamic (NL-RHA) and static (pushover) procedures are currently available to face this challenge, each with intrinsic advantages and disadvantages, and their applicability in the study of the nonlinear seismic behavior of cable-stayed bridges is discussed here. The seismic response of a large number of finite element models with different span lengths, tower shapes and class of foundation soil is obtained with different procedures and compared. Several features of the original Modal Pushover Analysis (MPA) are modified in light of cable-stayed bridge characteristics, furthermore, an extension of MPA and a new coupled pushover analysis (CNSP) are suggested to estimate the complex inelastic response of such outstanding structures subjected to multi-axial strong ground motions

Estimating Probability of Failure of a Complex System Based on Inexact Information about Subsystems and Components, with Potential Applications to Aircraft Maintenance

In many real-life applications (e.g., in aircraft maintenance), we need to estimate the probability of failure of a complex system (such as an aircraft as a whole or one of its subsystems). Complex systems are usually built with redundancy allowing them to withstand the failure of a small number of components. In this paper, we assume that we know the structure of the system, and, as a result, for each possible set of failed components, we can tell whether this set will lead to a system failure. For each component A, we know the probability P(A) of its failure with some uncertainty: e.g., we know the lower and upper bounds P(A) and P(A) for this probability. Usually, it is assumed that failures of different components are independent events. Our objective is to use all this information to estimate the probability of failure of the entire the complex system. In this paper, we describe several methods for solving this problem, including a new efficient method for such estimation based on Cauchy deviates

Abacavir inhibits but does not cause self-reactivity to HLA-B*57:01-restricted EBV specific T cell receptors

Pre-existing pathogen-specific memory T cell responses can contribute to multiple adverse outcomes including autoimmunity and drug hypersensitivity. How the specificity of the T cell receptor (TCR) is subverted or seconded in many of these diseases remains unclear. Here, we apply abacavir hypersensitivity (AHS) as a model to address this question because the disease is linked to memory T cell responses and the HLA risk allele, HLA-B*57:01, and the initiating insult, abacavir, are known. To investigate the role of pathogen-specific TCR specificity in mediating AHS we performed a genome-wide screen for HLA-B*57:01 restricted T cell responses to Epstein-Barr virus (EBV), one of the most prevalent human pathogens. T cell epitope mapping revealed HLA-B*57:01 restricted responses to 17 EBV open reading frames and identified an epitope encoded by EBNA3C. Using these data, we cloned the dominant TCR for EBNA3C and a previously defined epitope within EBNA3B. TCR specificity to each epitope was confirmed, however, cloned TCRs did not cross-react with abacavir plus self-peptide. Nevertheless, abacavir inhibited TCR interactions with their cognate ligands, demonstrating that TCR specificity may be subverted by a drug molecule. These results provide an experimental road map for future studies addressing the heterologous immune responses of TCRs including T cell mediated adverse drug reactions

HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms

Background Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS) which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy which impacts future treatment choices. Variations in human leukocyte antigen (HLA) class I in particular have been associated with serious T-cell mediated adverse drug reactions which has led to preventive screening strategies for some drugs. Objective To determine if variation in the HLA region is associated with vancomycin-induced DRESS. Methods Probable vancomycin DRESS cases were matched 1:2 with tolerant controls based on sex, race, and age using BioVU, Vanderbilt’s deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by conditional logistic regression. An extended sample set from BioVU was utilized to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele. Results Twenty-three individuals met inclusion criteria for vancomycin-associated DRESS. 19/23 (82.6%) cases carried HLA-A*32:01 compared to 0/46 (0%) of the matched vancomycin tolerant controls (p=1x10-8) and 6.3% of the BioVU population (n=54,249) (p=2x10-16). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01 positive group indicated that 19.2% developed DRESS and did so within four weeks. Conclusions HLA-A*32:01 is strongly associated with vancomycin DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug and preserve future treatment options with co-administered antibiotics

Single-cell analysis shows that adipose tissue of persons with both HIV and diabetes is enriched for clonal, cytotoxic, and CMV-specific CD4+ T cells

Persons with HIV are at increased risk for diabetes mellitus compared with individuals without HIV. Adipose tissue is an important regulator of glucose and lipid metabolism, and adipose tissue T cells modulate local inflammatory responses and, by extension, adipocyte function. Persons with HIV and diabetes have a high proportion of CX3CR1+ GPR56+ CD57+ (C-G-C+) CD4+ T cells in adipose tissue, a subset of which are cytomegalovirus specific, whereas individuals with diabetes but without HIV have predominantly CD69+ CD4+ T cells. Adipose tissue CD69+ and C-G-C+ CD4+ T cell subsets demonstrate higher receptor clonality compared with the same cells in blood, potentially reflecting antigen-driven expansion, but C-G-C+ CD4+ T cells have a more inflammatory and cytotoxic RNA transcriptome. Future studies will explore whether viral antigens have a role in recruitment and proliferation of pro-inflammatory C-G-C+ CD4+ T cells in adipose tissue of persons with HIV

Effect of Magnetic-Field on the Microstructure and Macrosegregation in Directionally Solidified Pb-Sn Alloys

An investigation into the influence of a transverse magnetic field (0.45 T) on the mushy zone morphology and macrosegregation in directionally solidified hypoeutectic Pb-Sn alloy shows that the field has no influence on the morphology of dendritic arrays. The field does, however, cause severe distortion in the cellular array morphology. Cellular arrayed growth with the magnetic field results in an extensive channel formation in the mushy zone, as opposed to the well-aligned and uniformly distributed cells formed in the absence of the field. The channels are produced due to the anisotropy in the thermosolutal convection caused by the magnetic field. Macrosegregation, however, along the length of the directionally solidified samples is not influenced by this magnetic field for either the cellular or dendritic arrays

Primary Dendrite Distribution and Disorder During Directional Solidification of Pb-Sb Alloys

Pb-2.2 wt pct Sb and Pb-5.8 wt pet Sb alloys have been directionally solidified from a single-crystal seed with its [100] orientation parallel to the growth direction, to examine the primary dendrite distribution and disorder of the dendrite arrays. The dendrite distribution and ordering have been investigated using analysis techniques such as the Gauss-amplitude fit to the frequency distribution of nearest and higher-order spacings, minimum spanning tree (MST), Voronoi polygon, and Fourier transform (FT) of the dendrite centers. Since the arrangement of dendrites is driven by the requirement to accommodate side-branch growth along the (100) directions, the FT images of the fully developed dendrite centers contain spots which indicate this preferred alignment. A directional solidification distance of about three mushy-zone lengths is sufficient to ensure a steady-state dendritic array, in terms of reaching a constant mean primary spacing. However, local dendrite ordering continues throughout the directional solidification process. The interdendritic convection not only decreases the mean primary spacing, it also makes the dendrite array more disordered and reduces the ratio of the upper and lower spacing limits, as defined by the largest 5 pct and the smallest 5 pct of the population

Using Virtual Agents to Guide Attention in Multi-task Scenarios

Kulms P, Kopp S. Using Virtual Agents to Guide Attention in Multi-task Scenarios. In: Aylett R, Krenn B, Pelachaud C, Shimodaira H, eds. Intelligent Virtual Agents. Lecture Notes in Computer Science. Vol 8108. Berlin, Heidelberg: Springer Berlin Heidelberg; 2013: 295-302