Direct estimation of seismic response in reduced-degree-of-freedom isolation and energy dissipation systems

A methodology for the development of design tools for direct estimation of peak inelastic response in reduced-degree-of-freedom (RDOF) isolation and energy dissipation systems is presented. The suggested procedure is an extension of an earlier method addressing purely hysteretic isolation systems. Herein, the dynamic equation of motion is first normalised to reduce the number of design parameters that significantly affect the response. The sensitivity of normalised response quantities to the amplitude of the ground motion is then investigated through extensive parametric nonlinear dynamic analyses of isolated single-degree-of-freedom (SDOF) systems with linear viscous damping using code-based target spectra. Regression analysis is subsequently employed to develop generalised design equations (GDEs) suitable for design. Further investigations are made to address nonlinear viscous damping and the effect of the transverse component of seismic action in two-degree-of freedom (2DOF) systems under bidirectional excitation, making the procedure applicable to common bridge isolation schemes. GDEs constitute an alternative to equivalent linearisation approaches commonly adopted by codes, informing the selection among alternative isolation and energy dissipations schemes without requiring iterative analysis. The approach is incorporated in the Deformation-Based Design methodology for seismically isolated bridges in a forthcoming paper

2'-O-(2-methoxyethyl) nucleosides are not phosphorylated or incorporated into the genome of Human Lymphoblastoid TK6 Cells

Nucleoside analogues with 2'-modified sugar moieties are often used to improve the RNA target affinity and nuclease resistance of therapeutic oligonucleotides in preclinical and clinical development. Despite their enhanced nuclease resistance, oligonucleotides could slowly degrade releasing nucleoside analogues that have the potential to become phosphorylated and incorporated into cellular DNA and RNA. For the first time, the phosphorylation and DNA and RNA incorporation of 2'-O-(2-methoxyethyl) (2'-O-MOE) nucleoside analogues have been investigated. Using LC/MS/MS, we showed that enzymes in the nucleotide salvage pathway including deoxycytidine kinase (dCK) and thymidine kinase (TK1) displayed poor reactivity toward 2'-O-MOE nucleoside analogues. On the other hand, 2'-fluoro (F) nucleosides, regardless of the nucleobase, were efficiently phosphorylated to their monophosphate forms by dCK and TK1. Consistent with their efficient phosphorylation by dCK and TK1, 2'-F nucleosides analogues were incorporated into cellular DNA and RNA while no incorporation was detected with 2'-O-MOE nucleoside analogues. In conclusion, these data suggest that the inability of dCK and TK1 to create the monophosphates of 2'-O-MOE nucleoside analogues reduces the risk of their incorporation into cellular DNA and RNA

On chains in HH-closed topological pospaces

We study chains in an $H$-closed topological partially ordered space. We give sufficient conditions for a maximal chain $L$ in an $H$-closed topological partially ordered space such that $L$ contains a maximal (minimal) element. Also we give sufficient conditions for a linearly ordered topological partially ordered space to be $H$-closed. We prove that any $H$-closed topological semilattice contains a zero. We show that a linearly ordered $H$-closed topological semilattice is an $H$-closed topological pospace and show that in the general case this is not true. We construct an example an $H$-closed topological pospace with a non-$H$-closed maximal chain and give sufficient conditions that a maximal chain of an $H$-closed topological pospace is an $H$-closed topological pospace.Comment: We have rewritten and substantially expanded the manuscrip

Field pathogenomics reveals the emergence of a diverse wheat yellow rust population

BACKGROUND: Emerging and re-emerging pathogens imperil public health and global food security. Responding to these threats requires improved surveillance and diagnostic systems. Despite their potential, genomic tools have not been readily applied to emerging or re-emerging plant pathogens such as the wheat yellow (stripe) rust pathogen Puccinia striiformis f. sp. tritici (PST). This is due largely to the obligate parasitic nature of PST, as culturing PST isolates for DNA extraction remains slow and tedious. RESULTS: To counteract the limitations associated with culturing PST, we developed and applied a field pathogenomics approach by transcriptome sequencing infected wheat leaves collected from the field in 2013. This enabled us to rapidly gain insights into this emerging pathogen population. We found that the PST population across the United Kingdom (UK) underwent a major shift in recent years. Population genetic structure analyses revealed four distinct lineages that correlated to the phenotypic groups determined through traditional pathology-based virulence assays. Furthermore, the genetic diversity between members of a single population cluster for all 2013 PST field samples was much higher than that displayed by historical UK isolates, revealing a more diverse population of PST. CONCLUSIONS: Our field pathogenomics approach uncovered a dramatic shift in the PST population in the UK, likely due to a recent introduction of a diverse set of exotic PST lineages. The methodology described herein accelerates genetic analysis of pathogen populations and circumvents the difficulties associated with obligate plant pathogens. In principle, this strategy can be widely applied to a variety of plant pathogens

Comparing Models for Early Warning Systems of Neglected Tropical Diseases

Early Warning Systems (EWS) are management tools to predict the occurrence of epidemics. They are based on the dependence of a given infectious disease on environmental variables. Although several neglected tropical diseases are sensitive to the effect of climate, our ability to predict their dynamics has been barely studied. In this paper, we use several models to determine if the relationship between cases and climatic variability is robust—that is, not simply an artifact of model choice. We propose that EWS should be based on results from several models that are to be compared in terms of their ability to predict future number of cases. We use a specific metric for this comparison known as the predictive R2, which measures the accuracy of the predictions. For example, an R2 of 1 indicates perfect accuracy for predictions that perfectly match observed cases. For cutaneous leishmaniasis, R2 values range from 72% to77%, well above predictions using mean seasonal values (64%). We emphasize that predictability should be evaluated with observations that have not been used to fit the model. Finally, we argue that EWS should incorporate climatic variables that are known to have a consistent relationship with the number of observed cases

Addressing the needs of children with disabilities experiencing disaster or terrorism

Purpose of review: This paper reviews the empirical literature on psychosocial factors relating to children with disabilities in the context of disaster or terrorism. Recent findings: Research indicates individuals with disabilities experience increased exposure to hazards due to existing social disparities and barriers associated with disability status. However, studies on the psychological effects of disaster/terrorism on children with preexisting disabilities are exceedingly few and empirical evidence of the effectiveness of trauma-focused therapies for this population is limited. Secondary adversities, including social stigma and health concerns, also compromise the recovery of these children post-disaster/terrorism. Schools and teachers appear to be particularly important in the recovery of children with disabilities to disaster. Disasters, terrorism, and war all contribute to the incidence of disability, as well as disproportionately affect children with preexisting disabilities. Summary: Disaster preparedness interventions and societal changes are needed to decrease the disproportionate environmental and social vulnerability of children with disabilities to disaster and terrorism

NMDA and Dopamine Converge on the NMDA-Receptor to Induce ERK Activation and Synaptic Depression in Mature Hippocampus

The formation of enduring internal representation of sensory information demands, in many cases, convergence in time and space of two different stimuli. The first conveys the sensory input, mediated via fast neurotransmission. The second conveys the meaning of the input, hypothesized to be mediated via slow neurotransmission. We tested the biochemical conditions and feasibility for fast (NMDA) and slow (dopamine) neurotransmission to converge on the Mitogen Activated Protein Kinase signaling pathways, crucial in several forms of synaptic plasticity, and recorded its effects upon synaptic transmission. We detected differing kinetics of ERK2 activation and synaptic strength changes in the CA1 for low and high doses of neurotransmitters in hippocampal slices. Moreover, when weak fast and slow inputs are given together, they converge on ERK2, but not on p38 or JNK, and induce strong short-term synaptic depression. Surprisingly, pharmacological analysis revealed that a probable site of such convergence is the NMDA receptor itself, suggesting it serves as a detector and integrator of fast and slow neurotransmission in the mature mammalian brain, as revealed by ERK2 activation and synaptic function