Design and development of machinery to plant daffodil bulbs in upland pasture and harvest the above ground biomass

The number of people suffering from dementia is considerable and growing at a significant rate. Alzheimer’s disease accounts for between 50 and 75% of these cases. Galantamine is a pharmaceutical compound that has been an approved treatment for Alzheimer’s disease since 1998. Galantamine can be synthesised chemically but it is a difficult and expensive process. Producing galantamine from the alkeloid galanthamine extracted from daffodils is more cost effective, but supplies are limited. Research has suggested that the environmental challenges associated with upland areas trigger a higher concentration of galanthamine in daffodils compared to daffodils grown under lowland conditions. A 4.5 year UK Agri-Tech Catalyst Industrial Research project is investigating daffodil-derived galanthamine production by integrating daffodil growing into permanent upland sheep pasture. The aim is to increase the economic sustainability of hill farming by providing farmers with a high value supplementary daffodil crop while maintaining a traditional farming system. Machinery is readily available for lowland daffodil production for the cut flower market and for the production of bulbs. Soils are typically deep, fertile and free draining. However, the UK uplands are characterised by low temperatures; exposure to wind; high rainfall; winter snow and frosts; thin impoverished stony soils; a shortage of major nutrients and steep slopes. As part of the research project Harper Adams University agricultural engineers have developed machines for planting daffodil bulbs and harvesting the above ground daffodil biomass in these arduous upland grassland pastures. The planter uses belts to meter and deliver bulbs from the storage hopper to two drop chutes positioned above the purpose built ground opening winged tines. The harvester removes and collects the above ground biomass which is then transferred to sealed containers before being processed

A Spaetzle-like role for Nerve Growth Factor β in vertebrate immunity to Staphylococcus aureus

Many key components of innate immunity to infection are shared between Drosophila and humans. However, the fly Toll ligand Spaetzle is not thought to have a vertebrate equivalent. We have found that the structurally related cystine-knot protein, nerve growth factor β (NGFβ), plays an unexpected Spaetzle-like role in immunity to Staphylococcus aureus infection in chordates. Deleterious mutations of either human NGFβ or its high-affinity receptor tropomyosin-related kinase receptor A (TRKA) were associated with severe S. aureus infections. NGFβ was released by macrophages in response to S. aureus exoproteins through activation of the NOD-like receptors NLRP3 and NLRC4 and enhanced phagocytosis and superoxide-dependent killing, stimulated proinflammatory cytokine production, and promoted calcium-dependent neutrophil recruitment. TrkA knockdown in zebrafish increased susceptibility to S. aureus infection, confirming an evolutionarily conserved role for NGFβ-TRKA signaling in pathogen-specific host immunity

PGE₂ production at sites of tissue injury promotes an anti-inflammatory neutrophil phenotype and determines the outcome of inflammation resolution in vivo

Neutrophils are the first immune cells recruited to a site of injury or infection, where they perform many functions. Having completed their role, neutrophils must be removed from the inflammatory site—either by apoptosis and efferocytosis or by reverse migration away from the wound—for restoration of normal tissue homeostasis. Disruption of these tightly controlled physiological processes of neutrophil removal can lead to a range of inflammatory diseases. We used an in vivo zebrafish model to understand the role of lipid mediator production in neutrophil removal. Following tailfin amputation in the absence of macrophages, neutrophillic inflammation does not resolve, due to loss of macrophage-dependent handling of eicosanoid prostaglandin E2 (PGE2) that drives neutrophil removal via promotion of reverse migration. Knockdown of endogenous PGE synthase gene reveals PGE2 as essential for neutrophil inflammation resolution. Furthermore, PGE2 is able to signal through EP4 receptors during injury, causing an increase in Alox12 production and switching toward anti-inflammatory eicosanoid signaling. Our data confirm regulation of neutrophil migration by PGE2 and LXA4 (lipoxin A4) in an in vivo model of inflammation resolution. This pathway may contain therapeutic targets for driving inflammation resolution in chronic inflammatory disease

15-keto-prostaglandin E2 activates host peroxisome proliferator-activated receptor gamma (PPAR-γ) to promote Cryptococcus neoformans growth during infection

Cryptococcus neoformans is one of the leading causes of invasive fungal infection in humans worldwide. C. neoformans uses macrophages as a proliferative niche to increase infective burden and avoid immune surveillance. However, the specific mechanisms by which C. neoformans manipulates host immunity to promote its growth during infection remain ill-defined. Here we demonstrate that eicosanoid lipid mediators manipulated and/or produced by C. neoformans play a key role in regulating pathogenesis. C. neoformans is known to secrete several eicosanoids that are highly similar to those found in vertebrate hosts. Using eicosanoid deficient cryptococcal mutants Δplb1 and Δlac1, we demonstrate that prostaglandin E2 is required by C. neoformans for proliferation within macrophages and in vivo during infection. Genetic and pharmacological disruption of host PGE2 synthesis is not required for promotion of cryptococcal growth by eicosanoid production. We find that PGE2 must be dehydrogenated into 15-keto-PGE2 to promote fungal growth, a finding that implicated the host nuclear receptor PPAR-γ. C. neoformans infection of macrophages activates host PPAR-γ and its inhibition is sufficient to abrogate the effect of 15-keto-PGE2 in promoting fungal growth during infection. Thus, we describe the first mechanism of reliance on pathogen-derived eicosanoids in fungal pathogenesis and the specific role of 15-keto-PGE2 and host PPAR-γ in cryptococcosis

Distributed Stochastic Power Control in Ad-hoc Networks: A Nonconvex Case

Utility-based power allocation in wireless ad-hoc networks is inherently nonconvex because of the global coupling induced by the co-channel interference. To tackle this challenge, we first show that the globally optimal point lies on the boundary of the feasible region, which is utilized as a basis to transform the utility maximization problem into an equivalent max-min problem with more structure. By using extended duality theory, penalty multipliers are introduced for penalizing the constraint violations, and the minimum weighted utility maximization problem is then decomposed into subproblems for individual users to devise a distributed stochastic power control algorithm, where each user stochastically adjusts its target utility to improve the total utility by simulated annealing. The proposed distributed power control algorithm can guarantee global optimality at the cost of slow convergence due to simulated annealing involved in the global optimization. The geometric cooling scheme and suitable penalty parameters are used to improve the convergence rate. Next, by integrating the stochastic power control approach with the back-pressure algorithm, we develop a joint scheduling and power allocation policy to stabilize the queueing systems. Finally, we generalize the above distributed power control algorithms to multicast communications, and show their global optimality for multicast traffic.Comment: Contains 12 pages, 10 figures, and 2 tables; work submitted to IEEE Transactions on Mobile Computin

A Spaetzle-like role for nerve growth factor beta in vertebrate immunity to Staphylococcus aureus

Many key components of innate immunity to infection are shared between Drosophila and humans. However, the fly Toll ligand Spaetzle is not thought to have a vertebrate equivalent. We have found that the structurally related cystine-knot protein, nerve growth factor β (NGFβ), plays an unexpected Spaetzle-like role in immunity to Staphylococcus aureus infection in chordates. Deleterious mutations of either human NGFβ or its high-affinity receptor tropomyosin-related kinase receptor A (TRKA) were associated with severe S. aureus infections. NGFβ was released by macrophages in response to S. aureus exoproteins through activation of the NOD-like receptors NLRP3 and NLRC4 and enhanced phagocytosis and superoxide-dependent killing, stimulated proinflammatory cytokine production, and promoted calcium-dependent neutrophil recruitment. TrkA knockdown in zebrafish increased susceptibility to S. aureus infection, confirming an evolutionarily conserved role for NGFβ-TRKA signaling in pathogen-specific host immunity

Stationary cocycles and Busemann functions for the corner growth model

We study the directed last-passage percolation model on the planar square lattice with nearest-neighbor steps and general i.i.d. weights on the vertices, out- side of the class of exactly solvable models. Stationary cocycles are constructed for this percolation model from queueing fixed points. These cocycles serve as bound- ary conditions for stationary last-passage percolation, solve variational formulas that characterize limit shapes, and yield existence of Busemann functions in directions where the shape has some regularity. In a sequel to this paper the cocycles are used to prove results about semi-infinite geodesics and the competition interface