Cell surface IL-1α trafficking is specifically inhibited by interferon-γ, and associates with the membrane via IL-1R2 and GPI anchors.

IL-1 is a powerful cytokine that drives inflammation and modulates adaptive immunity. Both IL-1α and IL-1β are translated as proforms that require cleavage for full cytokine activity and release, while IL-1α is reported to occur as an alternative plasma membrane-associated form on many cell types. However, the existence of cell surface IL-1α (csIL-1α) is contested, how IL-1α tethers to the membrane is unknown, and signaling pathways controlling trafficking are not specified. Using a robust and fully validated system, we show that macrophages present bona fide csIL-1α after ligation of TLRs. Pro-IL-1α tethers to the plasma membrane in part through IL-1R2 or via association with a glycosylphosphatidylinositol-anchored protein, and can be cleaved, activated, and released by proteases. csIL-1α requires de novo protein synthesis and its trafficking to the plasma membrane is exquisitely sensitive to inhibition by IFN-γ, independent of expression level. We also reveal how prior csIL-1α detection could occur through inadvertent cell permeabilisation, and that senescent cells do not drive the senescent-associated secretory phenotype via csIL-1α, but rather via soluble IL-1α. We believe these data are important for determining the local or systemic context in which IL-1α can contribute to disease and/or physiological processes.Work was funded by British Heart Foundation Grants FS/13/3/30038, FS/18/19/33371 and RG/16/8/32388 to MCHC, the BHF Cambridge CRE RE/13/6/30180, and the Cambridge NIHR Biomedical Research Centr

Risk-Targeted Selection of Agricultural Holdings for Post-Epidemic Surveillance: Estimation of Efficiency Gains

Current post-epidemic sero-surveillance uses random selection of animal holdings. A better strategy may be to estimate the benefits gained by sampling each farm and use this to target selection. In this study we estimate the probability of undiscovered infection for sheep farms in Devon after the 2001 foot-and-mouth disease outbreak using the combination of a previously published model of daily infection risk and a simple model of probability of discovery of infection during the outbreak. This allows comparison of the system sensitivity (ability to detect infection in the area) of arbitrary, random sampling compared to risk-targeted selection across a full range of sampling budgets. We show that it is possible to achieve 95% system sensitivity by sampling, on average, 945 farms with random sampling and 184 farms with risk-targeted sampling. We also examine the effect of ordering samples by risk to expedite return to a disease-free status. Risk ordering the sampling process results in detection of positive farms, if present, 15.6 days sooner than with randomly ordered sampling, assuming 50 farms are tested per day

Quantitative phase contrast optimised cancerous cell differentiation via ptychography

This paper shows that visible-light ptychography can be used to distinguish quantitatively between healthy and tumorous unstained cells. Advantages of ptychography in comparison to conventional phase-sensitive imaging techniques are highlighted. A novel procedure to automatically refocus ptychographic reconstructions is also presented, which improves quantitative analysis

Isothermal differential scanning calorimetry analysis of the anionic polymerisation of polyamide-6: separation by dual asymmetric Gaussians

The use of a reactive processing approach for the manufacture of thermoplastic composites is of increasing interest owing to the potential for lower melt viscosities, processing temperatures, and cycle times. These reactive systems, such as the anionic polymerisation of polyamide-6 (APA6), lack the depth of characterisation and modelling required for mould flow simulation for the purposes of part quality assurance and process optimisation as desirable for industrial application. This is particularly important in reactive systems, owing to the potential of part failure through inadequate polymer conversion, and the nature of thermoplastic polymer crystallisation which will occur simultaneously with polymerisation in these systems. A typical experimental technique for the kinetic analysis of polymerisation is through use of Differential Scanning Calorimetry (DSC) to measure the reaction exotherms. Unfortunately, as polymerisation and crystallisation occur simultaneously, the resulting exotherms obscure each other in thermal analysis techniques, inhibiting independent model fitting. An algorithmic approach to the interpretation of kinetic information obtained by isothermal DSC is implemented and discussed, with gaussian curve parameters for a variety of isothermal temperatures and initiator/activator concentrations presented

Process modelling in Anionically Polymerised Polyamide-6 (APA6) for the in situ polymerisation of composite matrices

The in situ reactive formation of thermoplastics provides a new and powerful avenue for the generation of tougher, recyclable composite materials. A molten low viscosity monomer is combined with an activator and initiator mixture before being injected into a mould where a rapid, by-product free polymerisation process occurs. The by-product free, anionic ring opening polymerisation of polyamide-6 from -caprolactam is one such example of a well-developed and commercially available system. Whilst this system is commercially used for the casting of polymer structures, its potential for composite applications is yet to be exploited. Table 1 compares the system to that of an epoxy resin, comparing infusion viscosities, times, and temperatures, showcasing its suitability as a composite matrix

Combining nanoscale manipulation with macroscale relocation of single quantum dots

We have controllably positioned, with nanometre precision, single CdSe quantum dots referenced to a registration template such that the location of a given nanoparticle on a macroscopic (≈1 cm2) sample surface can be repeatedly revisited. The atomically flat sapphire substrate we use is particularly suited to optical measurements of the isolated quantum dots, enabling combined manipulation–spectroscopy experiments on a single particle. Automated nanoparticle manipulation and imaging routines have been developed so as to facilitate the rapid assembly of specific nanoparticle arrangements

Process modelling of anionically polymerised polyamide-6 for application in thermoplastic reactive resin transfer moulding (R-RTM)

The reactive processing of thermoplastics holds great promise for the rapid manufacture of tough composites for semi-structural applications, especially in the automotive sector. Anionically Polymerised Polyamide-6 (APA6) is a leading candidate for reactive processing among thermoplastics which forms the focus of this work. However, the reactive pathway for the in situ formation of thermoplastic composites is yet to be exploited commercially. A significant roadblock to their use is a lack of system understanding and poor reproducibility in terms of properties and degree of conversion. In this, in situ processing of thermoplastics is a particular complication from the traditional manufacture of thermosets or melt processing of thermoplastics due to interplay of the variables: conversion, crystallinity, and viscosity. As processing is ideally conducted below the final melting temperature of the matrix (to both significantly reduce the time to solidification and the thermal degradation of the matrix), the ring opening polymerisation of the monomer, and the crystallisation of these newly formed polymer chains occurs simultaneously. The degree and effect of this interplay defines the final monomer conversion and polymer crystallinity and ultimately the mechanical properties of the composite. This work presents modelling activities undertaken through the following of the thermal process of the reaction by Differential Scanning Calorimetry (DSC), fitting kinetic and crystallisation models, and developing a so-called Time-Temperature Transformation (TTT) diagram to aid in process design and parameter selection. An example TTT diagram is shown in Fig. 1. These models are then compared to thermal profile and properties of a composite part manufactured through Reactive-Resin Transfer Moulding (R-RTM) of the APA6 system. This work presents a methodology for the generation of these TTT diagrams as well as highlights further complications in regards to the modelling of the system, most significantly its sensitivity to oxygen, moisture, and catalyst aging

Mechanical properties of polyamide 11 reinforced with cellulose nanofibres from Triodia pungens

There is a growing demand for the development of new renewable materials and the replacement of fossil fuel based polymers with bio-based polymers and composites. Cellulose nanofibres (CNF) is an emerging nano-reinforcement agent for polymers to improve mechanical properties. The preparation and properties of bionanocomposites consisting of spinifex cellulose nanofibres and bio-based polyamide 11 are reported. The freeze-dried nanofibres derived from a native Australian grass, Triodia pungens (spinifex), and wood were first premixed with the polymer at low concentration (0.1–0.5 wt%) using a jet mill, prior to melt-compounding via extrusion and injection-moulding of test specimens. The thermal and decomposition behaviours, as characterised by TGA and DSC, remained mostly unchanged. DSC and XRD show that crystallinity is largely unaffected by the presence of CNF, and thus all property changes may be attributed solely to the reinforcement effect of the fibres. Product specimens reinforced with CNF produced from spinifex (SCNF), showed an increase in tensile strength (+\ua023%), toughness (+\ua061%) and impact strength (+\ua067%)