Residual stress of as-deposited and rolled Wire + Arc Additive Manufacturing Ti–6Al–4V components

Wire + arc additive manufacturing components contain significant residual stresses, which manifest in distortion. High-pressure rolling was applied to each layer of a linear Ti–6Al–4V wire + arc additive manufacturing component in between deposition passes. In rolled specimens, out-of-plane distortion was more than halved; a change in the deposits' geometry due to plastic deformation was observed and process repeatability was increased. The Contour method of residual stresses measurements showed that although the specimens still exhibited tensile stresses (up to 500 MPa), their magnitude was reduced by 60%, particularly at the interface between deposit and substrate. The results were validated with neutron diffraction measurements, which were in good agreement away from the baseplate

Achieving Sustainable Phosphorus Use in Food Systems through Circularisation

Publication history: Accepted - 28 May 2018; Published - 30 May 2018.The notion of a phosphorus (P) circular economy provides the philosophy, framework, and opportunity to enable food production systems to become more efficient, sustainable, and resilient to a future P scarcity or sudden price shock. Whilst P recovery and recycling are central strategies for closing the P cycle, additional gains in environmental performance of food systems can be obtained by further minimising the amounts of P (a) introduced into the food system by lowering system P demand and (b) lost from the system by utilising legacy P stores in the landscape. This minimisation is an important cascading component of circularisation because it reduces the amounts of P circulating in the system, the amounts of P required to be recycled/recovered and the storage of unused P in the landscape, whilst maintaining agricultural output. The potential for circularisation and minimisation depends on regional differences in these P flow dynamics. We consider incremental and transformative management interventions towards P minimisation within circular economies, and how these might be tempered by the need to deliver a range of ecosystem services. These interventions move away from current production philosophies based on risk-averse, insurance-based farming, and current consumption patterns which have little regard for their environmental impact. We argue that a greater focus on P minimisation and circularisation should catalyse different actors and sectors in the food chain to embrace P sustainability and should empower future research needs to provide the confidence for them to do so without sacrificing future regional food security.This paper was produced as part of the RePhoKUs project (The role of phosphorus in the sustainability and resilience of the UK food system) funded by BBSRC, ESRC, NERC, and the Scottish Government under the UK Global Food Security research programme (Grant No. BB/R005842/1)

Nutrient stripping: the global disparity between food security and soil nutrient stocks

1. The Green Revolution successfully increased food production but in doing so created a legacy of inherently leaky and unsustainable agricultural systems. Central to this are the problems of excessive nutrient mining. If agriculture is to balance the needs of food security with the delivery of other ecosystem services, then current rates of soil nutrient stripping must be reduced and the use of synthetic fertilisers made more efficient. 2. We explore the global extent of the problem, with specific emphasis on the failure of macronutrient management (e.g. nitrogen, phosphorus) to deliver continued improvements in yield and the failure of agriculture to recognise the seriousness of micronutrient depletion (e.g. copper, zinc, selenium). 3. Nutrient removals associated with the relatively immature, nutrient-rich soils of the UK are contrasted with the mature, nutrient-poor soils of India gaining insight into the emerging issue of nutrient stripping and the long-term implications for human health and soil quality. Whilst nutrient deficiencies are rare in developed countries, micronutrient deficiencies are commonly increasing in less-developed countries. Increasing rates of micronutrient depletion are being inadvertently accomplished through increasing crop yield potential and nitrogen fertiliser applications. 4. Amongst other factors, the spatial disconnects caused by the segregation and industrialisation of livestock systems, between rural areas (where food is produced) and urban areas (where food is consumed and human waste treated) are identified as a major constraint to sustainable nutrient recycling. 5. Synthesis and applications. This study advocates that agricultural sustainability can only be accomplished using a whole-systems approach that thoroughly considers nutrient stocks, removals, exports and recycling. Society needs to socially and environmentally re-engineer agricultural systems at all scales. It is suggested that this will be best realised by national-scale initiatives. Failure to do so will lead to an inevitable and rapid decline in the delivery of provisioning services within agricultural systems

OGA Inhibition By GlcNAc-Selenazoline

The title compound, which differs from the powerful O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline only at the chalcogen atom (Se for S), is a much weaker inhibitor in a direct OGA assay. In human cells, however, the selenazoline shows comparable ability to induce hyper-O-GlcNAc-ylation, and the two show similar reduction of insulin-stimulated translocation of glucose transporter 4 in differentiated 3T3 adipocytes. (C) 2010 Elsevier Ltd. All rights reserved

Molecules incorporating a benzothiazole core scaffold inhibit the N-myristoyltransferase of Plasmodium falciparum.

Recombinant N-myristoyltransferase of Plasmodium falciparum (termed PfNMT) has been used in the development of a SPA (scintillation proximity assay) suitable for automation and high-throughput screening of inhibitors against this enzyme. The ability to use the SPA has been facilitated by development of an expression and purification system which yields considerably improved quantities of soluble active recombinant PfNMT compared with previous studies. Specifically, yields of pure protein have been increased from 12 microg x l(-1) to >400 microg x l(-1) by use of a synthetic gene with codon usage optimized for expression in an Escherichia coli host. Preliminary small-scale 'piggyback' inhibitor studies using the SPA have identified a family of related molecules containing a core benzothiazole scaffold with IC50 values 80% at a concentration of 10 microM

Molecular determinants of binding to the Plasmodium subtilisin-like protease 1.

PfSUB1, a subtilisin-like protease of the human malaria parasite Plasmodium falciparum, is known to play important roles during the life cycle of the parasite and has emerged as a promising antimalarial drug target. In order to provide a detailed understanding of the origin of binding determinants of PfSUB1 substrates, we performed molecular dynamics simulations in combination with MM-GBSA free energy calculations using a homology model of PfSUB1 in complex with different substrate peptides. Key interactions, as well as residues that potentially make a major contribution to the binding free energy, are identified at the prime and nonprime side of the scissile bond and comprise peptide residues P4 to P2'. This finding stresses the requirement for peptide substrates to interact with both prime and nonprime side residues of the PfSUB1 binding site. Analyzing the energetic contributions of individual amino acids within the peptide-PfSUB1 complexes indicated that van der Waals interactions and the nonpolar part of solvation energy dictate the binding strength of the peptides and that the most favorable interactions are formed by peptide residues P4 and P1. Hot spot residues identified in PfSUB1 are dispersed over the entire binding site, but clustered areas of hot spots also exist and suggest that either the S4-S2 or the S1-S2' binding site should be exploited in efforts to design small molecule inhibitors. The results are discussed with respect to which binding determinants are specific to PfSUB1 and, therefore, might allow binding selectivity to be obtained

Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans

Are stakeholders ready to transform phosphorus use in food systems A transdisciplinary study in a livestock intensive system.

Publication history: Accepted - 18 January 2022; Published online - 12 February 2022.Food systems worldwide are vulnerable to Phosphorus (P) supply disruptions and price fluctuations. Current P use is also highly inefficient, generating large surpluses and pollution. Global food security and aquatic ecosystems are in jeopardy if transformative action is not taken. This paper pivots from earlier (predominantly conceptual) work to develop and analyse a P transdisciplinary scenario process, assessing stakeholders potential for transformative thinking in P use in the food system. Northern Ireland, a highly livestock-intensive system, was used as case study for illustrating such process. The stakeholder engagement takes a normative stance in that it sets the explicit premise that the food system needs to be transformed and asks stakeholders to engage in a dialogue on how that transformation can be achieved. A Substance Flow Analysis of P flows and stocks was employed to construct visions for alternative futures and stimulate stakeholder discussions on system responses. These were analysed for their transformative potential using a triple-loop social learning framework. For the most part, stakeholder responses remained transitional or incremental, rather than being fundamentally transformative. The process did unveil some deeper levers that could be acted upon to move the system further along the spectrum of transformational change (e.g. changes in food markets, creation of new P markets, destocking, new types of land production and radical land use changes), providing clues of what an aspirational system could look like. Replicated and adapted elsewhere, this process can serve as diagnostics of current stakeholders thinking and potential, as well as for the identification of those deeper levers, opening up avenues to work upon for global scale transformation.This research forms part of the RephoKUs project (The role of Phosphorus in the Resilience and Sustainability of the UK food system), funded by the Global Food Security’s ‘Resilience of the UK Food System' Programme with funding from the UK’s Biotechnology and Biological Science Research Council (BBSRC), the Economic and Social Research Council (ESRC), the Natural Environment Research Council (NERC) and the Scottish Government (Grant No. BB/R005842/1