Critical materials for infrastructure: local vs global properties

Introducing new technologies into infrastructure (wind turbines, electric vehicles, low-carbon materials and so on) often demands materials that are ‘critical’; their supply is likely to be disrupted owing to limited reserves, geopolitical instability, environmental issues and/or increasing demand. Non-critical materials may become critical if introduced into infrastructure, owing to its gigatonne scale. This potentially poses significant risk to the development of low-carbon infrastructure. Analysis of this risk has previously overlooked the relationship between the ‘local properties’ that determine the selection of a technology and the overall vulnerability of the system, a global property. Treating materials or components as elements having fixed properties overlooks optima within the local–global variable space that could be exploited to minimise vulnerability while maximising performance. In this study, a framework for such analysis is presented along with a preliminary measure of relative materials criticality by way of a case study (a wind turbine generator). Although introduction of critical materials (in this case, rare earth metals) enhances technical performance by up to an order of magnitude, the associated increase in criticality may be two or three orders of magnitude. Analysis at the materials and component levels produces different results; design decisions should be based on analysis at several levels

Coordination of frontline defense mechanisms under severe oxidative stress

Inference of an environmental and gene regulatory influence network (EGRINOS) by integrating transcriptional responses to H2O2 and paraquat (PQ) has revealed a multi-tiered oxidative stress (OS)-management program to transcriptionally coordinate three peroxidase/catalase enzymes, two superoxide dismutases, production of rhodopsins, carotenoids and gas vesicles, metal trafficking, and various other aspects of metabolism.ChIP-chip, microarray, and survival assays have validated important architectural aspects of this network, identified novel defense mechanisms (including two evolutionarily distant peroxidase enxymes), and showed that general transcription factors of the transcription factor B family have an important function in coordinating the OS response (OSR) despite their inability to directly sense ROS.A comparison of transcriptional responses to sub-lethal doses of H2O2 and PQ with predictions of these responses made by an EGRIN model generated earlier from responses to other environmental factors has confirmed that a significant fraction of the OSR is made up of a generalized component that is also observed in response to other stressors.Analysis of active regulons within environment and gene regulatory influence network for OS (EGRINOS) across diverse environmental conditions has identified the specialized component of oxidative stress response (OSR) that is triggered by sub-lethal OS, but not by other stressors, including sub-inhibitory levels of redox-active metals, extreme changes in oxygen tension, and a sub-lethal dose of γ rays

Identification of Class I HLA T Cell Control Epitopes for West Nile Virus

The recent West Nile virus (WNV) outbreak in the United States underscores the importance of understanding human immune responses to this pathogen. Via the presentation of viral peptide ligands at the cell surface, class I HLA mediate the T cell recognition and killing of WNV infected cells. At this time, there are two key unknowns in regards to understanding protective T cell immunity: 1) the number of viral ligands presented by the HLA of infected cells, and 2) the distribution of T cell responses to these available HLA/viral complexes. Here, comparative mass spectroscopy was applied to determine the number of WNV peptides presented by the HLA-A*11:01 of infected cells after which T cell responses to these HLA/WNV complexes were assessed. Six viral peptides derived from capsid, NS3, NS4b, and NS5 were presented. When T cells from infected individuals were tested for reactivity to these six viral ligands, polyfunctional T cells were focused on the GTL9 WNV capsid peptide, ligands from NS3, NS4b, and NS5 were less immunogenic, and two ligands were largely inert, demonstrating that class I HLA reduce the WNV polyprotein to a handful of immune targets and that polyfunctional T cells recognize infections by zeroing in on particular HLA/WNV epitopes. Such dominant HLA/peptide epitopes are poised to drive the development of WNV vaccines that elicit protective T cells as well as providing key antigens for immunoassays that establish correlates of viral immunity. © 2013 Kaabinejadian et al

In the dedicated pursuit of dedicated capital: restoring an indigenous investment ethic to British capitalism

Tony Blair’s landslide electoral victory on May 1 (New Labour Day?) presents the party in power with a rare, perhaps even unprecedented, opportunity to revitalise and modernise Britain’s ailing and antiquated manufacturing economy.* If it is to do so, it must remain true to its long-standing (indeed, historic) commitment to restore an indigenous investment ethic to British capitalism. In this paper we argue that this in turn requires that the party reject the very neo-liberal orthodoxies which it offered to the electorate as evidence of its competence, moderation and ‘modernisation’, which is has internalised, and which it apparently now views as circumscribing the parameters of the politically and economically possible

Scaling up local energy infrastructure; An agent-based model of the emergence of district heating networks

The potential contribution of local energy infrastructure – such as heat networks – to the transition to a low carbon economy is increasingly recognised in international, national and municipal policy. Creating the policy environment to foster the scaling up of local energy infrastructure is, however, still challenging; despite national policy action and local authority interest the growth of heat networks in UK cities remains slow. Technoeconomic energy system models commonly used to inform policy are not designed to address institutional and governance barriers. We present an agent-based model of heat network development in UK cities in which policy interventions aimed at the institutional and governance barriers faced by diverse actors can be explored. Three types of project instigators are included – municipal, commercial and community – which have distinct decision heuristics and capabilities and follow a multi-stage development process. Scenarios of policy interventions developed in a companion modelling approach indicate that the effect of interventions differs between actors depending on their capabilities. Successful interventions account for the specific motivations and capabilities of different actors, provide a portfolio of support along the development process and recognise the important strategic role of local authorities in supporting low carbon energy infrastructure

Children in reviews: Methodological issues in child-relevant evidence syntheses

BACKGROUND: The delivery of optimal medical care to children is dependent on the availability of child relevant research. Our objectives were to: i) systematically review and describe how children are handled in reviews of drug interventions published in the Cochrane Database of Systematic Reviews (CDSR); and ii) determine when effect sizes for the same drug interventions differ between children and adults. METHODS: We systematically identified all of the reviews relevant to child health in the CDSR 2002, Issue 4. Reviews were included if they investigated the efficacy or effectiveness of a drug intervention for a condition that occurs in both children and adults. Information was extracted on review characteristics including study methods, results, and conclusions. RESULTS: From 1496 systematic reviews, 408 (27%) were identified as relevant to both adult and child health; 52% (213) of these included data from children. No significant differences were found in effect sizes between adults and children for any of the drug interventions or conditions investigated. However, all of the comparisons lacked the power to detect a clinically significant difference and wide confidence intervals suggest important differences cannot be excluded. A large amount of data was unavailable due to inadequate reporting at the trial and systematic review level. CONCLUSION: Overall, the findings of this study indicate there is a paucity of child-relevant and specific evidence generated from evidence syntheses of drug interventions. The results indicate a need for a higher standard of reporting for participant populations in studies of drug interventions

Crystal structures of the NO sensor NsrR reveal how its iron-sulfur cluster modulates DNA binding

NsrR from Streptomyces coelicolor (Sc) regulates the expression of three genes through the progressive degradation of its [4Fe–4S] cluster on nitric oxide (NO) exposure. We report the 1.95 Å resolution crystal structure of dimeric holo-ScNsrR and show that the cluster is coordinated by the three invariant Cys residues from one monomer and, unexpectedly, Asp8 from the other. A cavity map suggests that NO displaces Asp8 as a cluster ligand and, while D8A and D8C variants remain NO sensitive, DNA binding is affected. A structural comparison of holo-ScNsrR with an apo-IscR-DNA complex shows that the [4Fe–4S] cluster stabilizes a turn between ScNsrR Cys93 and Cys99 properly oriented to interact with the DNA backbone. In addition, an apo ScNsrR structure suggests that Asn97 from this turn, along with Arg12, which forms a salt-bridge with Asp8, are instrumental in modulating the position of the DNA recognition helix region relative to its major groove

ADAM12 is a circulating marker for stromal activation in pancreatic cancer and predicts response to chemotherapy

This work was supported by KWF Dutch Cancer Society (UVA 2012–5607 and UVA 2013–5932

Group differences in physician responses to handheld presentation of clinical evidence: a verbal protocol analysis

<p>Abstract</p> <p>Background</p> <p>To identify individual differences in physicians' needs for the presentation of evidence resources and preferences for mobile devices.</p> <p>Methods</p> <p>Within-groups analysis of responses to semi-structured interviews. Interviews consisted of using prototypes in response to task-based scenarios. The prototypes were implemented on two different form factors: a tablet style PC and a pocketPC. Participants were from three user groups: general internists, family physicians and medicine residents, and from two different settings: urban and semi-urban. Verbal protocol analysis, which consists of coding utterances, was conducted on the transcripts of the testing sessions. Statistical relationships were investigated between staff physicians' and residents' background variables, self-reported experiences with the interfaces, and verbal code frequencies.</p> <p>Results</p> <p>47 physicians were recruited from general internal medicine, family practice clinics and a residency training program. The mean age of participants was 42.6 years. Physician specialty had a greater effect on device and information-presentation preferences than gender, age, setting or previous technical experience. Family physicians preferred the screen size of the tablet computer and were less concerned about its portability. Residents liked the screen size of the tablet, but preferred the portability of the pocketPC. Internists liked the portability of the pocketPC, but saw less advantage to the large screen of the tablet computer (F[2,44] = 4.94, p = .012).</p> <p>Conclusion</p> <p>Different types of physicians have different needs and preferences for evidence-based resources and handheld devices. This study shows how user testing can be incorporated into the process of design to inform group-based customization.</p

Temporary Closure of the Open Abdomen: A Systematic Review on Delayed Primary Fascial Closure in Patients with an Open Abdomen

Background This study was designed to systematically review the literature to assess which temporary abdominal closure (TAC) technique is associated with the highest delayed primary fascial closure (FC) rate. In some cases of abdominal trauma or infection, edema or packing precludes fascial closure after laparotomy. This "open abdomen'' must then be temporarily closed. However, the FC rate varies between techniques. Methods The Cochrane Register of Controlled Trials, MEDLINE, and EMBASE databases were searched until December 2007. References were checked for additional studies. Search criteria included (synonyms of) "open abdomen,'' "fascial closure,'' "vacuum,'' "reapproximation,'' and "ventral hernia.'' Open abdomen was defined as "the inability to close the abdominal fascia after laparotomy.'' Two reviewers independently extracted data from original articles by using a predefined checklist. Results The search identified 154 abstracts of which 96 were considered relevant. No comparative studies were identified. After reading them, 51 articles, including 57 case series were included. The techniques described were vacuum-assisted closure (VAC; 8 series), vacuum pack (15 series), artificial burr (4 series), Mesh/sheet (16 series), zipper (7 series), silo (3 series), skin closure (2 series), dynamic retention sutures (DRS), and loose packing (1 series each). The highest FC rates were seen in the artificial burr (90%), DRS (85%), and VAC (60%). The lowest mortality rates were seen in the artificial burr (17%), VAC (18%), and DRS (23%). Conclusions These results suggest that the artificial burr and the VAC are associated with the highest FC rates and the lowest mortality rate