The co-evolution of technological promises, modelling, policies and climate change targets

The nature and framing of climate targets in international politics has changed substantially since their early expressions in the 1980s. Here, we describe their evolution in five phases-from 'climate stabilization' to specific 'temperature outcomes'-co-evolving with wider climate politics and policy, modelling methods and scenarios, and technological promises (from nuclear power to carbon removal). We argue that this co-evolution has enabled policy prevarication, leaving mitigation poorly delivered, yet the technological promises often remain buried in the models used to inform policy. We conclude with a call to recognise and break this pattern to unleash more effective and just climate policy. This Perspective maps the history of climate targets and shows how the international goal of avoiding dangerous climate change has been reinterpreted in the light of new modelling methods and technological promises, ultimately enabling policy prevarication and limiting mitigation

Nanobodies against the myelin enzyme CNPase as tools for structural and functional studies

2′,3′-Cyclic nucleotide 3′-phosphodiesterase (CNPase) is an abundant constituent of central nervous system non-compact myelin, and its loss in mice and humans causes neurodegeneration. Additionally, CNPase is frequently used as a marker antigen for myelinating cells. The catalytic activity of CNPase, the 3′-hydrolysis of 2′,3′-cyclic nucleotides, is well characterised in vitro, but the in vivo function of CNPase remains unclear. CNPase interacts with the actin cytoskeleton to counteract the developmental closure of cytoplasmic channels that travel through compact myelin; its enzymatic activity may be involved in adenosine metabolism and RNA degradation. We developed a set of high-affinity nanobodies recognising the phosphodiesterase domain of CNPase, and the crystal structures of each complex show that the five nanobodies have distinct epitopes. One of the nanobodies bound deep into the CNPase active site and acted as an inhibitor. Moreover, the nanobodies were characterised in imaging applications and as intrabodies, expressed in mammalian cells, such as primary oligodendrocytes. Fluorescently labelled nanobodies functioned in imaging of teased nerve fibres and whole brain tissue sections, as well as super-resolution microscopy. These anti-CNPase nanobodies provide new tools for structural and functional studies on myelin formation, dynamics, and disease, including high-resolution imaging of nerve tissue

Nanobodies against the myelin enzyme CNPase as tools for structural and functional studies

Abstract 2′,3′-Cyclic nucleotide 3′-phosphodiesterase (CNPase) is an abundant constituent of central nervous system non-compact myelin, and its loss in mice and humans causes neurodegeneration. Additionally, CNPase is frequently used as a marker antigen for myelinating cells. The catalytic activity of CNPase, the 3′-hydrolysis of 2′,3′-cyclic nucleotides, is well characterised in vitro, but the in vivo function of CNPase remains unclear. CNPase interacts with the actin cytoskeleton to counteract the developmental closure of cytoplasmic channels that travel through compact myelin; its enzymatic activity may be involved in adenosine metabolism and RNA degradation. We developed a set of high-affinity nanobodies recognising the phosphodiesterase domain of CNPase, and the crystal structures of each complex show that the five nanobodies have distinct epitopes. One of the nanobodies bound deep into the CNPase active site and acted as an inhibitor. Moreover, the nanobodies were characterised in imaging applications and as intrabodies, expressed in mammalian cells, such as primary oligodendrocytes. Fluorescently labelled nanobodies functioned in imaging of teased nerve fibres and whole brain tissue sections, as well as super-resolution microscopy. These anti-CNPase nanobodies provide new tools for structural and functional studies on myelin formation, dynamics, and disease, including high-resolution imaging of nerve tissue.Abstract 2′,3′-Cyclic nucleotide 3′-phosphodiesterase (CNPase) is an abundant constituent of central nervous system non-compact myelin, and its loss in mice and humans causes neurodegeneration. Additionally, CNPase is frequently used as a marker antigen for myelinating cells. The catalytic activity of CNPase, the 3′-hydrolysis of 2′,3′-cyclic nucleotides, is well characterised in vitro, but the in vivo function of CNPase remains unclear. CNPase interacts with the actin cytoskeleton to counteract the developmental closure of cytoplasmic channels that travel through compact myelin; its enzymatic activity may be involved in adenosine metabolism and RNA degradation. We developed a set of high-affinity nanobodies recognising the phosphodiesterase domain of CNPase, and the crystal structures of each complex show that the five nanobodies have distinct epitopes. One of the nanobodies bound deep into the CNPase active site and acted as an inhibitor. Moreover, the nanobodies were characterised in imaging applications and as intrabodies, expressed in mammalian cells, such as primary oligodendrocytes. Fluorescently labelled nanobodies functioned in imaging of teased nerve fibres and whole brain tissue sections, as well as super-resolution microscopy. These anti-CNPase nanobodies provide new tools for structural and functional studies on myelin formation, dynamics, and disease, including high-resolution imaging of nerve tissue

Clash of Geofutures and the Remaking of Planetary Order: Faultlines underlying Conflicts over Geoengineering Governance

Climate engineering (geoengineering) is rising up the global policy agenda, partly because international divisions pose deep challenges to collective climate mitigation. However, geoengineering is similarly subject to clashing interests, knowledge‐traditions and geopolitics. Modelling and technical assessments of geoengineering are facilitated by assumptions of a single global planner (or some as yet unspecified rational governance), but the practicality of international governance remains mostly speculative. Using evidence gathered from state delegates, climate activists and modellers, we reveal three underlying and clashing ‘geofutures’: an idealised understanding of governable geoengineering that abstracts from technical and political realities; a situated understanding of geoengineering emphasising power hierarchies in world order; and a pragmatist precautionary understanding emerging in spaces of negotiation such as UN Environment Assembly (UNEA). Set in the wider historical context of climate politics, the failure to agree even to a study of geoengineering at UNEA indicates underlying obstacles to global rules and institutions for geoengineering posed by divergent interests and underlying epistemic and political differences. Technology assessments should recognise that geoengineering will not be exempt from international fractures; that deployment of geoengineering through imposition is a serious risk; and that contestations over geofutures pertain, not only to climate policy, but also the future of planetary order

Coal and Climate Change

This overview adopts a critical social science perspective to examine the state of play and potential futures for coal in the context of climate change. It introduces key trends in coal consumption, production and trade, before appraising the relevant literature. Finding surprisingly little literature directly focussed on coal and climate change compared with related fields, it appraises existing work and highlights key areas for future work. In addition to established bodies of work on the situated politics of coal and the political economy of coal, new work calling for demand side policies to be supplemented with supply side policies highlights the increasing importance of how normative contestations drive debates over coal, suggesting that future work needs to engage not only much more directly with climate change as an issue, but particularly with the place of coal in a just transition. Because of coal’s mammoth contribution to climate change and the complex political economy which drives its production and consumption, it is likely that coal will remain at the centre of difficult questions about the relationship between climate action and development for some time

Higher order cumulant based parameter estimation in nonlinear time series models

Parameter estimation in nonlinear time-series models based on higher order cumulant matching is proposed in this paper. The cumulant estimates are computed from measured and simulated data and a cost function computed from second and fourth order cumulants is used. To simplify the calculations a reduced cost function is suggested using low-dimensional slices of the cumulant functions. The estimation method is illustrated on a numerical example.</p

Control relevant identification of nonlinear systems using linear models

In this contribution we consider control of nonlinear systems by means of linear time-invariant model based control design. It is shown that a desired closed loop response of the nonlinear system for a given reference signal can be achieved using a controller based on a linear model. This is possible if the linear model used in the control design is able to capture the input/output behaviour of the nonlinear system for the desired response. An identification method, designed for this purpose, is presented and illustrated on an numerical example.</p

Evoked Potential Enhancement Using a Neurophysiologically-based Model

Summary Objective: Single trial evoked potentials (EP) are generally obscured by the much larger spontaneous or background electroencephalogram (EEG). A novel method was developed to enhance single trial EPs. The potential of this approach was explored using actual flash evoked visual EPs. Method: The basic procedure is a variant of the adaptive filtering approach. At the core of our method is a mathematical, but neurophysiologically-realistic, nonlinear model of the cortical structures involved in generating EEG and EP activity. The model parameters are adjusted by a genetic algorithm in such a way that the model output resembles the actually observed pre-stimulus EEG activity. When post-stimulus EEG is passed through the inverse model, enhancement of the single trial EP should, theoretically, occur. Results: Evidence was found that, in case of visual evoked potentials obtained by flashing light through closed eyelids, alpha activity continues to around 150 ms post-stimulus, at which point a low frequency potential arises, cresting 100 ms later and disappearing after another 100 ms or so. Also, it was found that an individual’s response varies considerably from trial to trial. Conclusion: The inverse modeling approach presented here is effective at enhancing single trial EP activity. One potential application is to distinguish trials that contain a response from those that do not, which could result in improved ensemble averages.</jats:p