Damage in Polymer Bonded Energetic Composites: Effect of Loading Rate

Particulate composites are widely used in the materials world. An understanding of their damage behaviour under a variety of loading conditions is necessary to inform models of their response to external stimuli. In the present experimental study, fine and coarse grained RDX-HTPB composites have been used to investigate the effect of loading rate on the degree of damage produced in polymer bonded explosives subjected to varying degrees of uniaxial compression. High strain rate loading (4×10⁺³ s⁻¹) was achieved using a direct impact Hopkinson pressure bar and low strain rate loading (1×10⁻² s⁻¹) using an Instron mechanical testing machine. The causal metrics are the degree to which the samples were strained and the mechanical energy expended in straining them. The damage metric is the residual low rate compressive modulus of the samples. The quantitative, physically based, results discussed in terms of the Porter-Gould activated debonding damage model clearly demonstrate that for both fine and coarse fills there is a marked reduction in residual moduli as a function of imposed strain, and substantially less specific energy is required to cause the same level of damage at the lower strain-rate. In the case of the coarse grained composite there is some evidence for a change in damage mechanism at the higher strain-rate. We obtain a value for the measured work of adhesion and a measure of the effective modulus local to the damage site, as damage is actually occurring. The observed underlying behaviour should be broadly applicable to particulate composites, whenever stiff filler particles are held in a viscoelastic matrix.The authors wish to acknowledge financial support in the form of an Industrial CASE PhD Studentship for RLB funded by the UK Engineering and Physical Sciences Research Council (EPSRC) and by QinetiQ [EP/I501290/1]; UK MOD via a WSTC contract; DMW and APJ acknowledge the financial support of AWE.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s40870-016-0050-x The data underlying this article can be found at the following persistent URL: https://www.repository.cam.ac.uk/handle/1810/25319

The theory of international business: the role of economic models

This paper reviews the scope for economic modelling in international business studies. It argues for multi-level theory based on classic internalisation theory. It present a systems approach that encompasses both firm-level and industry-level analysis

CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity

Cancer cells exploit the expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) to subvert T-cell-mediated immunosurveillance. The success of therapies that disrupt PD-L1-mediated tumour tolerance has highlighted the need to understand the molecular regulation of PD-L1 expression1. Here we identify the uncharacterized protein CMTM6 as a critical regulator of PD-L1 in a broad range of cancer cells, by using a genome-wide CRISPR–Cas9 screen. CMTM6 is a ubiquitously expressed protein that binds PD-L1 and maintains its cell surface expression. CMTM6 is not required for PD-L1 maturation but co-localizes with PD-L1 at the plasma membrane and in recycling endosomes, where it prevents PD-L1 from being targeted for lysosome-mediated degradation. Using a quantitative approach to profile the entire plasma membrane proteome, we find that CMTM6 displays specificity for PD-L1. Notably, CMTM6 depletion decreases PD-L1 without compromising cell surface expression of MHC class I. CMTM6 depletion, via the reduction of PD-L1, significantly alleviates the suppression of tumour-specific T cell activity in vitro and in vivo. These findings provide insights into the biology of PD-L1 regulation, identify a previously unrecognized master regulator of this critical immune checkpoint and highlight a potential therapeutic target to overcome immune evasion by tumour cells.M.L.B. is supported by a Cancer Research UK Clinician Scientist Fellowship (C53779/A20097), Addenbrooke’s Charitable Trust award and NIHR fellowship. P.J.L. is supported by a Wellcome Trust PRF (101835/Z/13/Z) and work in the Lehner laboratory is supported by NHSBT, NIHR Cambridge BRC, a Wellcome Trust Strategic Award to CIMR, and the Addenbrooke’s Charitable Trust M.A.D. is supported by a Senior Leukaemia Foundation Australia Fellowship and work in the Dawson laboratory is supported by the NHMRC (Grants 1085015, 1106444 and 1106447) Cancer Council Victoria and Leukaemia Foundation Australia. Cancer Research UK (C53779/A20097

International diversification, legitimacy, and corporate social performance of extractive industry multinationals

This article examines how different international diversification strategies impact the legitimacy challenges multinationals face and the way they manage their corporate and social responsibilities. Analyzing these questions in a sample of companies in extractive industries, we find that those who pursue resource-seeking investments that involve locating extraction operations overseas respond with the largest improvement in their corporate-level social performance (CSP). Those pursuing efficiency-seeking by establishing processing subsidiaries abroad increase their CSP less, with the smallest increase for those pursuing market-seeking through marketing and sales operations overseas. For each type of activity established overseas, the increase in CSP becomes greater the more developed the company's home country and the larger its international footprint, but is not dependent on the host country's level of development. These findings suggest that, in today's globalized world, the legitimacy challenges that result from subsidiaries' activities increasingly need to be managed at a global, corporate level

Using digital technology to protect health in prolonged poor air quality episodes: a case study of the AirRater App during the Australian 2019–20 fires

In the southern hemisphere summer of 2019–20, Australia experienced its most severe bushfire season on record. Smoke from fires affected 80% of the population, with large and prolonged exceedances of the Australian National Air Quality Standard for fine particulate matter (PM2.5) recorded in all major population centers. We examined if AirRater, a free smartphone app that reports air quality and tracks user symptoms in near real‐time, assisted those populations to reduce their smoke exposure and protect their health. We distributed an online survey to over 13,000 AirRater users to assess how they used this information during the 2019-20 bushfire season, and why it was helpful to aid decision‐making in reducing personal smoke exposure. We received responses from 1732 users (13.3%). Respondents reported the app was highly useful, supporting informed decision‐making regarding daily activities during the smoke‐affected period. Commonly reported activities supported by information provided through the app were staying inside (76%), rescheduling or planning outdoor activities (64%), changing locations to less affected areas (29%) and informing decisions on medication use (15%). Innovative and easy‐to‐use smartphone apps such as AirRater, that provide individual‐level and location‐specific data, can enable users to reduce their exposure to environmental hazards and therefore protect their health

Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants

Viruses manipulate host factors to enhance their replication and evade cellular restriction. We used multiplex tandem mass tag (TMT)-based whole cell proteomics to perform a comprehensive time course analysis of >6500 viral and cellular proteins during HIV infection. To enable specific functional predictions, we categorized cellular proteins regulated by HIV according to their patterns of temporal expression. We focussed on proteins depleted with similar kinetics to APOBEC3C, and found the viral accessory protein Vif to be necessary and sufficient for CUL5-dependent proteasomal degradation of all members of the B56 family of regulatory subunits of the key cellular phosphatase PP2A (PPP2R5A-E). Quantitative phosphoproteomic analysis of HIV-infected cells confirmed Vif-dependent hyperphosphorylation of >200 cellular proteins, particularly substrates of the aurora kinases. The ability of Vif to target PPP2R5 subunits is found in primate and non-primate lentiviral lineages, and remodeling of the cellular phosphoproteome is therefore a second ancient and conserved Vif function.This work was supported by a Wellcome Trust PRF (101835/Z/13/Z) to PJL and RTF to NJM (093964/Z/10/Z), NHSBT and the NIHR Cambridge BRC, a Wellcome Trust Strategic Award to CIMR, and the Addenbrooke’s Charitable Trust

The impact of product attributes and emerging technologies on firms’ international configuration

International business literature has largely explained the international dispersion of firms’ activities as a choice based on trade-offs between cost minimisation, knowledge seeking, managing transaction costs and maintaining control. By incorporating insights from operations management, we propose a framework that explicitly takes into account products’ physical and knowledge attributes that constrain the viable international configuration options available to firms. Linking the characteristics of a product to the scope for horizontal and vertical decoupling in a value network allows us to re-frame recent discussions in the literature about fragmentation of activities vs tasks and to develop an overall picture of the way industry-specific peculiarities characterise (and also constrain) viable international configurations. We show how our framework can be used to interpret data on the scope for decoupling and dispersion collected from industry experts and elucidate the relationships between configuration options and measures of product characteristics. We then utilise this framework to predict how emerging technologies will reshape the international configuration options available to firms.EPSR

Manufacturing Development of the NCSX Modular Coil Windings

The modular coils on the National Compact Stellarator Experiment (NCSX) present a number of significant engineering challenges due to their complex shapes, requirements for high dimensional accuracy and the high current density required in the modular coils due to space constraints. In order to address these challenges, an R&D program was established to develop the conductor, insulation scheme, manufacturing techniques, and procedures. A prototype winding named Twisted Racetrack Coil (TRC) was of particular importance in dealing with these challenges. The TRC included a complex shaped winding form, conductor, insulation scheme, leads and termination, cooling system and coil clamps typical of the modular coil design. Even though the TRC is smaller in size than a modular coil, its similar complex geometry provided invaluable information in developing the final design, metrology techniques and development of manufacturing procedures. In addition a discussion of the development of the copper rope conductor including "Keystoning" concerns; the epoxy impregnation system (VPI) plus the tooling and equipment required to manufacture the modular coils will be presented