Damage tolerant composite wing panels for transport aircraft

Commercial aircraft advanced composite wing surface panels were tested for durability and damage tolerance. The wing of a fuel-efficient, 200-passenger airplane for 1990 delivery was sized using grahite-epoxy materials. The damage tolerance program was structured to allow a systematic progression from material evaluations to the optimized large panel verification tests. The program included coupon testing to evaluate toughened material systems, static and fatigue tests of compression coupons with varying amounts of impact damage, element tests of three-stiffener panels to evaluate upper wing panel design concepts, and the wing structure damage environment was studied. A series of technology demonstration tests of large compression panels is performed. A repair investigation is included in the final large panel test

Using primary care-based paper and telephone interventions to increase uptake of bowel scope screening in Yorkshire: A protocol of a randomised controlled trial

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Introduction Evidence suggests bowel scope screening (BSS) can significantly reduce an individual's risk of developing colorectal cancer (CRC). BSS for 55 year olds was therefore introduced to the English Bowel Cancer Screening Programme (BCSP) in 2013. However, the benefits are only gained from test completion and uptake is low (43%). Primary care involvement has consistently shown benefits to cancer screening uptake and so this study aims to build on this knowledge and evaluate general practitioner (GP) practice led interventions designed to increase BSS attendance. Methods and analysis A three-arm randomised controlled trial will be conducted to evaluate three interventions: one intervention for prospective BSS invitees (primer letter with locally tailored leaflet sent by an individual's GP practice) and two interventions for those who do not attend their BSS appointment (a self-referral letter sent by an individual's GP practice and a patient navigation call made on behalf of an individual's GP practice). The trial will be set in Yorkshire. Individuals soon to receive their invitation to attend BSS at one of the Hull and East Yorkshire Bowel Cancer Screening centre sites, will be randomly assigned to one of three groups: control (usual care; no input from GP practice), Intervention group A (primer letter/leaflet and a self-referral letter), Intervention group B (primer letter/leaflet and a patient navigation call). Attendance data will be obtained from the BCSP database (via National Health Service (NHS) Digital) 3 months after the last intervention. Regression analysis will compare uptake, and additional clinical outcomes, across the three groups. The analysis will be multivariate and adjust for several covariates including gender and area-level deprivation. Ethics and dissemination NHS ethical approval has been obtained from London-Harrow Research Ethics Committee. The results will be submitted for publication in a peer-reviewed journal and presented at conferences. Trial registration number ISRCTN16252122; Pre-results

A novel method for the nitration of deactivated aromatic compounds

Novel nitration systems comprising nitric acid, trifluoroacetic anhydride and zeolite Hβ, with or without acetic anhydride, are described. The system having no acetic anhydride is more active and readily nitrates deactivated substrates such as nitrobenzene, benzonitrile, benzoic acid or 4-nitrotoluene to give predominantly the product substituted meta to the deactivating group. The system incorporating acetic anhydride is more moderate in activity, and nitrates moderately deactivated systems such as halogenobenzenes quantitatively within two hours at ice–salt bath temperature, and provides very high selectivity for the para-nitrated product. This system also nitrates 2-nitrotoluene to give high selectivity for 2,4-dinitrotoluene production. Furthermore, the system can be used for direct double nitration of toluene and gives a 92% yield of 2,4-dinitrotoluene with a 2,4-∶2,6-dinitrotoluene ratio of 25∶1. Even greater selectivity (96% yield and 70∶1 selectivity) can be achieved in the latter reaction by conducting the reaction in one flask but in two stages, with trifluoroacetic anhydride added only in the second stage

Symmetric rearrangement of groundwater-fed streams

Yi, Robert, et al. “Symmetric Rearrangement of Groundwater-Fed Streams.” Proceedings of the Royal Society A: Mathematical, Physical and Engineering Science, vol. 473, no. 2207, Nov. 2017, p. 20170539

Purification and functional characterisation of rhiminopeptidase A, a novel aminopeptidase from the venom of Bitis gabonica rhinoceros

This study describes the discovery and characterisation of a novel aminopeptidase A from the venom of B. g. rhinoceros and highlights its potential biological importance. Similar to mammalian aminopeptidases, rhiminopeptidase A might be capable of playing roles in altering the blood pressure and brain function of victims. Furthermore, it could have additional effects on the biological functions of other host proteins by cleaving their N-terminal amino acids. This study points towards the importance of complete analysis of individual components of snake venom in order to develop effective therapies for snake bites

Phosphorothioate backbone modifications of nucleotide-based drugs are potent platelet activators

Nucleotide-based drug candidates such as antisense oligonucleotides, aptamers, immunoreceptor-activating nucleotides, or (anti)microRNAs hold great therapeutic promise for many human diseases. Phosphorothioate (PS) backbone modification of nucleotide-based drugs is common practice to protect these promising drug candidates from rapid degradation by plasma and intracellular nucleases. Effects of the changes in physicochemical properties associated with PS modification on platelets have not been elucidated so far. Here we report the unexpected binding of PS-modified oligonucleotides to platelets eliciting strong platelet activation, signaling, reactive oxygen species generation, adhesion, spreading, aggregation, and thrombus formation in vitro and in vivo. Mechanistically, the platelet-specific receptor glycoprotein VI (GPVI) mediates these platelet-activating effects. Notably, platelets from GPVI function-deficient patients do not exhibit binding of PS-modified oligonucleotides, and platelet activation is fully abolished. Our data demonstrate a novel, unexpected, PS backbone-dependent, platelet-activating effect of nucleotide-based drug candidates mediated by GPVI. This unforeseen effect should be considered in the ongoing development programs for the broad range of upcoming and promising DNA/RNA therapeutics

Rising water temperature in rivers: Ecological impacts and future resilience

Rising water temperatures in rivers due to climate change are already having observable impacts on river ecosystems. Warming water has both direct and indirect impacts on aquatic life, and further aggravates pervasive issues such as eutrophication, pollution, and the spread of disease. Animals can survive higher temperatures through physiological and/or genetic acclimation, behavioral and phenological change, and range shifts to more suitable locations. As such, those animals that are adapted to cool-water regions typically found in high altitudes and latitudes where there are fewer dispersal opportunities are most at risk of future extinction. However, sub-lethal impacts on animal physiology and phenology, body-size, and trophic interactions could have significant population-level effects elsewhere. Rivers are vulnerable to warming because historic management has typically left them exposed to solar radiation through the removal of riparian shade, and hydrologically disconnected longitudinally, laterally, and vertically. The resilience of riverine ecosystems is also limited by anthropogenic simplification of habitats, with implications for the dispersal and resource use of resident organisms. Due to the complex indirect impacts of warming on ecosystems, and the species-specific physiological and behavioral response of organisms to warming, predicting how river ecosystems will change in the future is challenging. Restoring rivers to provide connectivity and heterogeneity of conditions would provide resilience to a range of expected co-occurring pressures, including warming, and should be considered a priority as part of global strategies for climate adaptation and mitigation. This article is categorized under: Science of Water > Water and Environmental Change Water and Life > Nature of Freshwater Ecosystems Water and Life > Stresses and Pressures on Ecosystems

Functional redundancy between RAP1 isoforms in murine platelet production and function

RAP GTPases, important regulators of cellular adhesion, are abundant signaling molecules in the platelet/megakaryocytic lineage. However, mice lacking the predominant isoform, RAP1B, display a partial platelet integrin activation defect and have a normal platelet count, suggesting the existence of a RAP1-independent pathway to integrin activation in platelets and a negligible role for RAP GTPases in megakaryocyte biology. To determine the importance of individual RAP isoforms on platelet production and on platelet activation at sites of mechanical injury or vascular leakage, we conditionally deleted Rap1a and/or Rap1b in the megakaryocytic lineage (mKO). Interestingly, Rap1a/b-mKO mice displayed a marked macrothrombocytopenia due to impaired pro- platelet formation by megakaryocytes. In platelets, RAP isoforms had both redundant and isoform-ˇspecific functions. Deletion of RAP1B, but not RAP1A, significantly reduced α- granule secretion and activation of the cytoskeleton regulator RAC1. Both isoforms significantly contributed to thromboxane A2 generation and the inside-out activation of platelet integrins. Combined deficiency of RAP1A and RAP1B markedly impaired platelet aggregation, spreading and clot retraction. Consistently, thrombus formation in physiological flow conditions was abolished in Rap1a/b-mKO, but not Rap1a-mKO or Rap1b-mKO platelets. Rap1a/b-mKO mice were strongly protected from experimental thrombosis and exhibited a severe defect in hemostasis after mechanical injury. Surprisingly, Rap1a/b-mKO platelets were indistinguishable from controls in their ability to prevent blood-lymphatic mixing during development and hemorrhage at sites of inflammation. In summary, our studies demonstrate an essential role for RAP1 signaling in platelet integrin activation and a critical role in platelet production. While important for hemostatic/thrombotic plug formation, platelet RAP1 signaling is dispensable for vascular integrity during development and inflammation

On the climate impacts of blue hydrogen production

Natural gas based hydrogen production with carbon capture and storage is referred to as blue hydrogen. If substantial amounts of CO2 from natural gas reforming are captured and permanently stored, such hydrogen could be a low-carbon energy carrier. However, recent research raises questions about the effective climate impacts of blue hydrogen from a life cycle perspective. Our analysis sheds light on the relevant issues and provides a balanced perspective on the impacts on climate change associated with blue hydrogen. We show that such impacts may indeed vary over large ranges and depend on only a few key parameters: the methane emission rate of the natural gas supply chain, the CO2 removal rate at the hydrogen production plant, and the global warming metric applied. State-of-the-art reforming with high CO2 capture rates combined with natural gas supply featuring low methane emissions does indeed allow for substantial reduction of greenhouse gas emissions compared to both conventional natural gas reforming and direct combustion of natural gas. Under such conditions, blue hydrogen is compatible with low-carbon economies and exhibits climate change impacts at the upper end of the range of those caused by hydrogen production from renewable-based electricity. However, neither current blue nor green hydrogen production pathways render fully “net-zero” hydrogen without additional CO2 removal