Loading protocols for European regions of low to moderate seismicity

Existing loading protocols for quasi-static cyclic testing of structures are based on recordings from regions of high seismicity. For regions of low to moderate seismicity they overestimate imposed cumulative damage demands. Since structural capacities are a function of demand, existing loading protocols applied to specimens representative of structures in low to moderate seismicity regions might underestimate structural strength and deformation capacity. To overcome this problem, this paper deals with the development of cyclic loading protocols for European regions of low to moderate seismicity. Cumulative damage demands imposed by a set of 60 ground motion records are evaluated for a wide variety of SDOF systems that reflect the fundamental properties of a large portion of the existing building stock. The ground motions are representative of the seismic hazard level corresponding to a 2% probability of exceedance in 50 years in a European moderate seismicity region. To meet the calculated cumulative damage demands, loading protocols for different structural types and vibration periods are developed. For comparison, cumulative seismic demands are also calculated for existing protocols and a set of records that was used in a previous study on loading protocols for regions of high seismicity. The median cumulative demands for regions of low to moderate seismicity are significantly less than those of existing protocols and records of high seismicity regions. For regions of low to moderate seismicity the new protocols might therefore result in larger strength and deformation capacities and hence in more cost-effective structural configurations or less expensive retrofit measures

A vector-valued ground motion intensity measure incorporating normalized spectral area

A vector-valued intensity measure is presented, which incorporates a relative measure represented by the normalized spectral area. The proposed intensity measure is intended to have high correlation with specific relative engineering demand parameters, which collectively can provide information regarding the damage state and collapse potential of the structure. Extensive dynamic analyses are carried out on a single-degree-of-freedom system with a modified Clough–Johnston hysteresis model, using a dataset of 40 ground motions, in order to investigate the proposed intensity measure characteristics. Response is expressed using the displacement ductility, and the normalized hysteretic energy, both of which are relative engineering demand parameters. Through regression analysis the correlation between the proposed intensity measure and the engineering demand parameters is evaluated. Its domain of applicability is investigated through parametric analysis, by varying the period and the strain-hardening stiffness. Desirable characteristics such as efficiency, sufficiency, and statistical independence are examined. The proposed intensity measure is contrasted to another one, with respect to its correlation to the engineering demand parameters. An approximate procedure for estimating the optimum normalized spectral area is also presented. It is demonstrated that the proposed intensity measure can be used in intensity-based assessments, and, with proper selection of ground motions, in scenario-based assessments

Do MZ twins have discordant experiences of friendship? : A qualitative hypothesis-generating MZ twin differences study

[This corrects the article DOI: 10.1371/journal.pone.0180521.]

A Novel Classification of Lung Cancer into Molecular Subtypes

The remarkably heterogeneous nature of lung cancer has become more apparent over the last decade. In general, advanced lung cancer is an aggressive malignancy with a poor prognosis. The discovery of multiple molecular mechanisms underlying the development, progression, and prognosis of lung cancer, however, has created new opportunities for targeted therapy and improved outcome. In this paper, we define “molecular subtypes” of lung cancer based on specific actionable genetic aberrations. Each subtype is associated with molecular tests that define the subtype and drugs that may potentially treat it. We hope this paper will be a useful guide to clinicians and researchers alike by assisting in therapy decision making and acting as a platform for further study. In this new era of cancer treatment, the ‘one-size-fits-all’ paradigm is being forcibly pushed aside—allowing for more effective, personalized oncologic care to emerge

Genetic and Environmental Influences on Female Sexual Orientation, Childhood Gender Typicality and Adult Gender Identity

Background: Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates – childhood gender typicality (CGT) and adult gender identity (AGI). However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women. Methodology/Principal Findings: Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426) who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%), AGI (11%) and CGT (31%). For the multivariate analyses, a common pathway model best fitted the data. Conclusions/Significance: This indicated that a single latent variable influenced by a genetic component and common nonshared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation

ReSETting PP2A tumour suppressor activity in blast crisis and imatinib-resistant chronic myelogenous leukaemia

The deregulated kinase activity of p210-BCR/ABL oncoproteins, hallmark of chronic myelogenous leukaemia (CML), induces and sustains the leukaemic phenotype, and contributes to disease progression. Imatinib mesylate, a BCR/ABL kinase inhibitor, is effective in most of chronic phase CML patients. However, a significant percentage of CML patients develop resistance to imatinib and/or still progresses to blast crisis, a disease stage that is often refractory to imatinib therapy. Furthermore, there is compelling evidence indicating that the CML leukaemia stem cell is also resistant to imatinib. Thus, there is still a need for new drugs that, if combined with imatinib, will decrease the rate of relapse, fully overcome imatinib resistance and prevent blastic transformation of CML. We recently reported that the activity of the tumour suppressor protein phosphatase 2A (PP2A) is markedly inhibited in blast crisis CML patient cells and that molecular or pharmacologic re-activation of PP2A phosphatase led to growth suppression, enhanced apoptosis, impaired clonogenic potential and decreased in vivo leukaemogenesis of imatinib-sensitive and -resistant (T315I included) CML-BC patient cells and/or BCR/ABL+ myeloid progenitor cell lines. Thus, the combination of PP2A phosphatase-activating and BCR/ABL kinase-inhibiting drugs may represent a powerful therapeutic strategy for blast crisis CML patients

A Seismic Performance Classification Framework to Provide Increased Seismic Resilience

Several performance measures are being used in modern seismic engineering applications, suggesting that seismic performance could be classified a number of ways. This paper reviews a range of performance measures currently being adopted and then proposes a new seismic performance classification framework based on expected annual losses (EAL). The motivation for an EAL-based performance framework stems from the observation that, in addition to limiting lives lost during earthquakes, changes are needed to improve the resilience of our societies, and it is proposed that increased resilience in developed countries could be achieved by limiting monetary losses. In order to set suitable preliminary values of EAL for performance classification, values of EAL reported in the literature are reviewed. Uncertainties in current EAL estimates are discussed and then an EAL-based seismic performance classification framework is proposed. The proposal is made that the EAL should be computed on a storey-by-storey basis in recognition that EAL for different storeys of a building could vary significantly and also recognizing that a single building may have multiple owners

Extensive Gene-Specific Translational Reprogramming in a Model of B Cell Differentiation and Abl-Dependent Transformation

To what extent might the regulation of translation contribute to differentiation programs, or to the molecular pathogenesis of cancer? Pre-B cells transformed with the viral oncogene v-Abl are suspended in an immortalized, cycling state that mimics leukemias with a BCR-ABL1 translocation, such as Chronic Myelogenous Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL). Inhibition of the oncogenic Abl kinase with imatinib reverses transformation, allowing progression to the next stage of B cell development. We employed a genome-wide polysome profiling assay called Gradient Encoding to investigate the extent and potential contribution of translational regulation to transformation and differentiation in v-Abl-transformed pre-B cells. Over half of the significantly translationally regulated genes did not change significantly at the level of mRNA abundance, revealing biology that might have been missed by measuring changes in transcript abundance alone. We found extensive, gene-specific changes in translation affecting genes with known roles in B cell signaling and differentiation, cancerous transformation, and cytoskeletal reorganization potentially affecting adhesion. These results highlight a major role for gene-specific translational regulation in remodeling the gene expression program in differentiation and malignant transformation