The transient response of global-mean precipitation to increasing carbon dioxide levels

The transient response of global-mean precipitation to an increase in atmospheric carbon dioxide levels of 1% yr(-1) is investigated in 13 fully coupled atmosphere-ocean general circulation models (AOGCMs) and compared to a period of stabilization. During the period of stabilization, when carbon dioxide levels are held constant at twice their unperturbed level and the climate left to warm, precipitation increases at a rate of similar to 2.4% per unit of global-mean surface-air-temperature change in the AOGCMs. However, when carbon dioxide levels are increasing, precipitation increases at a smaller rate of similar to 1.5% per unit of global-mean surface-air-temperature change. This difference can be understood by decomposing the precipitation response into an increase from the response to the global surface-temperature increase (and the climate feedbacks it induces), and a fast atmospheric response to the carbon dioxide radiative forcing that acts to decrease precipitation. According to the multi-model mean, stabilizing atmospheric levels of carbon dioxide would lead to a greater rate of precipitation change per unit of global surface-temperature change

The relationship between web enjoyment and student perceptions and learning using a web-based tutorial

Web enjoyment has been regarded as a component of system experience. However, there has been little targeted research considering the role of web enjoyment alone in student learning using web-based systems. To address this gap, this study aims to examine the influence of web enjoyment on learning performance and perceptions by controlling system experience as a variable in the study. 74 students participated in the study, using a web-based tutorial covering subject matter in the area of 'Computation and algorithms'. Their learning performance was assessed with a pre-test and a post-test and their learning perceptions were evaluated with a questionnaire. The results indicated that there are positive relationships between the levels of web enjoyment and perceived usefulness and non-linear navigation for users with similar, significant levels of system experience. The implications of these findings in relation to web-based learning are explored and ways in which the needs of students who report different levels of web enjoyment might be met are discussed

Energy transitions and uncertainty: creating low carbon investment opportunities in the UK electricity sector

This paper examines how actors in the UK electricity sector are attempting to deliver investment in low carbon generation. Low carbon technologies, because of their relative immaturity, capital intensity and low operational costs, do not readily fit with existing electricity markets and investment templates which were designed for fossil fuel based energy. We analyse key electricity market and infrastructure policies in the UK and highlight how these are aimed at making low carbon technologies ‘investable’ by reducing uncertainty, managing investment risks and repositioning actors within the electricity socio-technical ‘regime’. We argue that our study can inform contemporary debates on the politics and governance of sustainability transitions by empirically investigating the agency of incumbent regime actors in the face of uncertainty and by offering critical insights on the role of markets and finance in shaping socio-technical change

Stakeholder Theory and Marketing: Moving from a Firm-Centric to a Societal Perspective

This essay is inspired by the ideas and research examined in the special section on “Stakeholder Marketing” of the Journal of Public Policy & Marketing in 2010. The authors argue that stakeholder marketing is slowly coalescing with the broader thinking that has occurred in the stakeholder management and ethics literature streams during the past quarter century. However, the predominant view of stakeholders that many marketers advocate is still primarily pragmatic and company centric. The position advanced herein is that stronger forms of stakeholder marketing that reflect more normative, macro/societal, and network-focused orientations are necessary. The authors briefly explain and justify these characteristics in the context of the growing “prosociety” and “proenvironment” perspectives—orientations that are also in keeping with the public policy focus of this journal. Under the “hard form” of stakeholder theory, which the authors endorse, marketing managers must realize that serving stakeholders sometimes requires sacrificing maximum profits to mitigate outcomes that would inflict major damage on other stakeholders, especially society

A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci

The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function

Differences in genotype and virulence among four multidrug-resistant <i>Streptococcus pneumoniae</i> isolates belonging to the PMEN1 clone

We report on the comparative genomics and characterization of the virulence phenotypes of four &lt;i&gt;S. pneumoniae&lt;/i&gt; strains that belong to the multidrug resistant clone PMEN1 (Spain&lt;sup&gt;23F&lt;/sup&gt; ST81). Strains SV35-T23 and SV36-T3 were recovered in 1996 from the nasopharynx of patients at an AIDS hospice in New York. Strain SV36-T3 expressed capsule type 3 which is unusual for this clone and represents the product of an in vivo capsular switch event. A third PMEN1 isolate - PN4595-T23 - was recovered in 1996 from the nasopharynx of a child attending day care in Portugal, and a fourth strain - ATCC700669 - was originally isolated from a patient with pneumococcal disease in Spain in 1984. We compared the genomes among four PMEN1 strains and 47 previously sequenced pneumococcal isolates for gene possession differences and allelic variations within core genes. In contrast to the 47 strains - representing a variety of clonal types - the four PMEN1 strains grouped closely together, demonstrating high genomic conservation within this lineage relative to the rest of the species. In the four PMEN1 strains allelic and gene possession differences were clustered into 18 genomic regions including the capsule, the blp bacteriocins, erythromycin resistance, the MM1-2008 prophage and multiple cell wall anchored proteins. In spite of their genomic similarity, the high resolution chinchilla model was able to detect variations in virulence properties of the PMEN1 strains highlighting how small genic or allelic variation can lead to significant changes in pathogenicity and making this set of strains ideal for the identification of novel virulence determinant

Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost

Background: Endovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection. Methods: Large vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$reference year 2014). Results: There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12-19). The median (IQR) disability-weighted utility score at 90 days was 0.65 (0.00-0.91) in the alteplase-only versus 0.91 (0.65-1.00) in the endovascular group (p = 0.005). Modeled life expectancy was greater in the endovascular versus alteplaseonly group (median 15.6 versus 11.2 years, p = 0.02). The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR) 5.5 (3.2-8.7) versus 8.9 (4.7-13.8), p = 0.02] and more QALY gained [median (IQR) 9.3 (4.2-13.1) versus 4.9 (0.3-8.5), p = 0.03]. Endovascular patients spent less time in hospital [median (IQR) 5 (3-11) days versus 8 (5-14) days, p = 0.04] and rehabilitation [median (IQR) 0 (0-28) versus 27 (0-65) days, p = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p = 0.008) offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515). The average saving per patient treated with thrombectomy was US$4,365. c Conclusion: Thrombectomy patients with large vessel occlusion and salvageable tissue on CT-perfusion had reduced length of stay and overall costs to 90 days. There was evidence of clinically relevant improvement in long-term survival and quality of life.Peer reviewe

Parameterization Effects in the analysis of AMI Sunyaev-Zel'dovich Observations

Most Sunyaev--Zel'dovich (SZ) and X-ray analyses of galaxy clusters try to constrain the cluster total mass and/or gas mass using parameterised models and assumptions of spherical symmetry and hydrostatic equilibrium. By numerically exploring the probability distributions of the cluster parameters given the simulated interferometric SZ data in the context of Bayesian methods, and assuming a beta-model for the electron number density we investigate the capability of this model and analysis to return the simulated cluster input quantities via three rameterisations. In parameterisation I we assume that the T is an input parameter. We find that parameterisation I can hardly constrain the cluster parameters. We then investigate parameterisations II and III in which fg(r200) replaces temperature as a main variable. In parameterisation II we relate M_T(r200) and T assuming hydrostatic equilibrium. We find that parameterisation II can constrain the cluster physical parameters but the temperature estimate is biased low. In parameterisation III, the virial theorem replaces the hydrostatic equilibrium assumption. We find that parameterisation III results in unbiased estimates of the cluster properties. We generate a second simulated cluster using a generalised NFW (GNFW) pressure profile and analyse it with an entropy based model to take into account the temperature gradient in our analysis and improve the cluster gas density distribution. This model also constrains the cluster physical parameters and the results show a radial decline in the gas temperature as expected. The mean cluster total mass estimates are also within 1 sigma from the simulated cluster true values. However, we find that for at least interferometric SZ analysis in practice at the present time, there is no differences in the AMI visibilities between the two models. This may of course change as the instruments improve.Comment: 19 pages, 13 tables, 24 figure

Hypergraph models of biological networks to identify genes critical to pathogenic viral response

Background: Representing biological networks as graphs is a powerful approach to reveal underlying patterns, signatures, and critical components from high-throughput biomolecular data. However, graphs do not natively capture the multi-way relationships present among genes and proteins in biological systems. Hypergraphs are generalizations of graphs that naturally model multi-way relationships and have shown promise in modeling systems such as protein complexes and metabolic reactions. In this paper we seek to understand how hypergraphs can more faithfully identify, and potentially predict, important genes based on complex relationships inferred from genomic expression data sets. Results: We compiled a novel data set of transcriptional host response to pathogenic viral infections and formulated relationships between genes as a hypergraph where hyperedges represent significantly perturbed genes, and vertices represent individual biological samples with specific experimental conditions. We find that hypergraph betweenness centrality is a superior method for identification of genes important to viral response when compared with graph centrality. Conclusions: Our results demonstrate the utility of using hypergraphs to represent complex biological systems and highlight central important responses in common to a variety of highly pathogenic viruses