What role for the bioeconomy in an electrified transportation sector?

The growth of the bioeconomy has recently been slowed by over production of petroleum and natural gas from unconventional domestic reserves, which has reduced demand for biofuels. In the longer term, liquid transportation fuels, both petroleum- and bio-based, are threatened by electrification of the transportation sector, which will benefit from the use of low-cost natural gas to generate electricity for battery electric vehicles. Low-cost natural gas in the USA is attractive for other applications as well, including the production of certain petrochemicals. On the other hand, natural gas is not suitable for producing many high molecular weight petrochemicals. Cost-competitive biorenewable versions of these products will need to be commercialized if petroleum is to be displaced without causing substantial economic distortions. This article reviews the available bio-based pathways and the current state of research on their technical and, where available, economic feasibility

Crowdsourcing Linked Data on listening experiences through reuse and enhancement of library data

Research has approached the practice of musical reception in a multitude of ways, such as the analysis of professional critique, sales figures and psychological processes activated by the act of listening. Studies in the Humanities, on the other hand, have been hindered by the lack of structured evidence of actual experiences of listening as reported by the listeners themselves, a concern that was voiced since the early Web era. It was however assumed that such evidence existed, albeit in pure textual form, but could not be leveraged until it was digitised and aggregated. The Listening Experience Database (LED) responds to this research need by providing a centralised hub for evidence of listening in the literature. Not only does LED support search and reuse across nearly 10,000 records, but it also provides machine-readable structured data of the knowledge around the contexts of listening. To take advantage of the mass of formal knowledge that already exists on the Web concerning these contexts, the entire framework adopts Linked Data principles and technologies. This also allows LED to directly reuse open data from the British Library for the source documentation that is already published. Reused data are re-published as open data with enhancements obtained by expanding over the model of the original data, such as the partitioning of published books and collections into individual stand-alone documents. The database was populated through crowdsourcing and seamlessly incorporates data reuse from the very early data entry phases. As the sources of the evidence often contain vague, fragmentary of uncertain information, facilities were put in place to generate structured data out of such fuzziness. Alongside elaborating on these functionalities, this article provides insights into the most recent features of the latest instalment of the dataset and portal, such as the interlinking with the MusicBrainz database, the relaxation of geographical input constraints through text mining, and the plotting of key locations in an interactive geographical browser

Regulation of neutrophilic inflammation by proteinase-activated receptor 1 during bacterial pulmonary infection

Neutrophils are key effector cells of the innate immune response to pathogenic bacteria, but excessive neutrophilic inflammation can be associated with bystander tissue damage. The mechanisms responsible for neutrophil recruitment to the lungs during bacterial pneumonia are poorly defined. In this study, we focus on the potential role of the major high-affinity thrombin receptor, proteinase-activated receptor 1 (PAR-1), during the development of pneumonia to the common lung pathogen Streptococcus pneumoniae. Our studies demonstrate that neutrophils were indispensable for controlling S. pneumoniae outgrowth but contributed to alveolar barrier disruption. We further report that intra-alveolar coagulation (bronchoalveolar lavage fluid thrombin-antithrombin complex levels) and PAR-1 immunostaining were increased in this model of bacterial lung infection. Functional studies using the most clinically advanced PAR-1 antagonist, SCH530348, revealed a key contribution for PAR-1 signaling in influencing neutrophil recruitment to lung airspaces in response to both an invasive and noninvasive strain of S. pneumoniae (D39 and EF3030) but that PAR-1 antagonism did not impair the ability of the host to control bacterial outgrowth. PAR-1 antagonist treatment significantly decreased pulmonary levels of IL-1β, CXCL1, CCL2, and CCL7 and attenuated alveolar leak. Ab neutralization studies further demonstrated a nonredundant role for IL-1β, CXCL1, and CCL7 in mediating neutrophil recruitment in response to S. pneumoniae infection. Taken together, these data demonstrate a key role for PAR-1 during S. pneumoniae lung infection that is mediated, at least in part, by influencing multiple downstream inflammatory mediators

Selective Inhibitors of Kv11.1 Regulate IL-6 Expression by Macrophages in Response to TLR/IL-1R Ligands

The mechanism by which the platelet-endothelial cell adhesion molecule PECAM-1 regulates leukodiapedesis, vascular endothelial integrity, and proinflammatory cytokine expression in vivo is not known. We recently identified PECAM-1 as a negative regulator of Kv11.1, a specific voltage-gated potassium channel that functioned in human macrophages to reset a resting membrane potential following depolarization. We demonstrate here that dofetilide (DOF), a selective inhibitor of the Kv11.1 current, had a profound inhibitory effect on neutrophil recruitment in mice following TLR/IL-1R–elicited peritonitis or intrascrotal injection of IL-1β, but had no effect on responses seen with TNFα. Furthermore, inhibitors of Kv11.1 (DOF, E4031, and astemizole), but not Kv1.3 (margatoxin), suppressed the expression of IL-6 and MCP-1 cytokines by murine resident peritoneal macrophages, while again having no effect on TNFα. In contrast, IL-6 expression by peritoneal mesothelial cells was unaffected. Using murine P388 cells, which lack endogenous C/EBPβexpression and are unresponsive to LPS for the expression of both IL-6 and MCP-1, we observed that DOF inhibited LPS-induced expression of IL-6 mRNA following ectopic expression of wild-type C/EBPβ, but not a serine-64 point mutant. Finally, DOF inhibited the constitutive activation of cdk2 in murine peritoneal macrophages; cdk2 is known to phosphorylate C/EBPβ at serine-64. Taken together, our results implicate a potential role for Kv11.1 in regulating cdk2 and C/EBPβ activity, where robust transactivation of both IL-6 and MCP-1 transcription is known to be dependent on serine-64 of C/EBPβ. Our data might also explain the altered phenotypes displayed by PECAM-1 knockout mice in several disease models

Liver transplantation for type I and type IV glycogen storage disease

Progressive liver failure or hepatic complications of the primary disease led to orthotopic liver transplantation in eight children with glycogen storage disease over a 9-year period. One patient had glycogen storage disease (GSD) type I (von Gierke disease) and seven patients had type IV GSD (Andersen disease). As previously reported [19], a 16.5-year-old-girl with GSD type I was successfully treated in 1982 by orthotopic liver transplantation under cyclosporine and steroid immunosuppression. The metabolic consequences of the disease have been eliminated, the renal function and size have remained normal, and the patient has lived a normal young adult life. A late portal venous thrombosis was treated successfully with a distal splenorenal shunt. Orthotopic liver transplantation was performed in seven children with type N GSD who had progressive hepatic failure. Two patients died early from technical complications. The other five have no evidence of recurrent hepatic amylopectinosis after 1.1–5.8 postoperative years. They have had good physical and intellectual maturation. Amylopectin was found in many extrahepatic tissues prior to surgery, but cardiopathy and skeletal myopathy have not developed after transplantation. Postoperative heart biopsies from patients showed either minimal amylopectin deposits as long as 4.5 years following transplantation or a dramatic reduction in sequential biopsies from one patient who initially had dense myocardial deposits. Serious hepatic derangement is seen most commonly in types T and IV GSD. Liver transplantation cures the hepatic manifestations of both types. The extrahepatic deposition of abnormal glycogen appears not to be problematic in type I disease, and while potentially more threatening in type IV disease, may actually exhibit signs of regression after hepatic allografting

Derivation of the blackfold effective theory

We study fluctuations and deformations of black branes over length scales larger than the horizon radius. We prove that the Einstein equations for the perturbed p-brane yield, as constraints, the equations of the effective blackfold theory. We solve the Einstein equations for the perturbed geometry and show that it remains regular on and outside the black brane horizon. This study provides an ab initio derivation of the blackfold effective theory and gives explicit expressions for the metrics near the new black holes and black branes that result from it, to leading order in a derivative expansion.Comment: 20 pages. v4: Typo corrected in eq. (6.11) -- erratum in the published versio

Near Horizon of 5D Rotating Black Holes from 2D Perspective

We study the CFT dual to five dimensional extremal rotating black holes, by investigating the two dimensional perspective of their near horizon geometry. From two dimensional point of view, we show that both gauge fields, related to the two rotations, appear in the same manner in the asymptotic symmetry and in the associated central charge. We find that, our results are in perfect agreement with the generalization of Kerr/CFT approach to five dimensional extremal rotating black holes.Comment: The last version to appear in the European Physical Journal

Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas