17 research outputs found

    Hidden regularity in singular optimal control of port-Hamiltonian systems

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    We study the problem of state transition on a finite time interval with minimal energy supply for linear port-Hamiltonian systems. While the cost functional of minimal energy supply is intrinsic to the port-Hamiltonian structure, the necessary conditions of optimality resulting from Pontryagin's maximum principle may yield singular arcs. The underlying reason is the linear dependence on the control, which makes the problem of determining the optimal control as a function of the state and the adjoint more complicated or even impossible. To resolve this issue, we fully characterize regularity of the (differential-algebraic) optimality system by using the interplay of the cost functional and the dynamics. In case of the optimality DAE being characterized by a regular matrix pencil, we fully determine the control on the singular arc. In case of singular matrix pencils of the optimality system, we propose an approach to compute rank-minimal quadratic perturbations of the objective such that the optimal control problem becomes regular. We illustrate the applicability of our results by a general second-order mechanical system and a discretized boundary-controlled heat equation.Comment: 21 page

    Complications and clinical outcome of hepatic artery embolisation in patients with hereditary haemorrhagic telangiectasia

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    BACKGROUND: Hepatic artery embolisation (HAE) in patients with hereditary haemorrhagic telangiectasia (HHT) is controversial because of the associated complications and unproven long-term benefit. We present our results in 20 such patients over a time span of 17 years. METHODS: Staged HAE was performed using polyvinyl alcohol (PVA) particles and coils. Complications, clinical symptoms and cardiac output were assessed before and after therapy as well as at the end of follow-up (median 92 months, range 26–208 months). RESULTS: Two patients died within 30 days following HAE (10 %). Four further deaths resulted from causes unrelated to HAE. Ischaemic cholangitis, cholecystitis and focal hepatic necrosis with biliary sepsis necessitated re-intervention in four patients. In all but one patient, clinical symptoms resolved with mean cardiac output falling from 11.84 ± 3.22 l/min pre-treatment to 8.13 ± 2.67 l/min at the end of follow-up (P < 0.001). One patient required liver transplantation for de novo symptoms of portal hypertension 4 years after primary symptoms had been cured by HAE. CONCLUSION: The 30-day mortality of HAE in patients with HHT is 10 %. The rate of complications requiring re-intervention is 20 %. Clinical response at long-term follow-up is satisfactory. KEY POINTS: • Hepatic artery embolisation (HAE) in hereditary haemorrhagic telangiectasia (HHT) provides long-term benefit. • Mortalities of HAE and liver transplantation in HHT patients are comparable. • In HHT, complications of HAE are lower than those of liver transplantation. • Complications of HAE can be further reduced by refinement of technique. • Complications include ischaemic cholangitis, hepatic necrosis, biliary sepsis and death

    A Spider Toxin Exemplifies the Promises and Pitfalls of Cell-Free Protein Production for Venom Biodiscovery

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    Arthropod venoms offer a promising resource for the discovery of novel bioactive peptides and proteins, but the limited size of most species translates into minuscule venom yields. Bioactivity studies based on traditional fractionation are therefore challenging, so alternative strategies are needed. Cell-free synthesis based on synthetic gene fragments is one of the most promising emerging technologies, theoretically allowing the rapid, laboratory-scale production of specific venom components, but this approach has yet to be applied in venom biodiscovery. Here, we tested the ability of three commercially available cell-free protein expression systems to produce venom components from small arthropods, using U2-sicaritoxin-Sdo1a from the six-eyed sand spider Hexophtalma dolichocephala as a case study. We found that only one of the systems was able to produce an active product in low amounts, as demonstrated by SDS-PAGE, mass spectrometry, and bioactivity screening on murine neuroblasts. We discuss our findings in relation to the promises and limitations of cell-free synthesis for venom biodiscovery programs in smaller invertebrates

    A research agenda for the science of actionable knowledge: Drawing from a review of the most misguided to the most enlightened claims in the science-policy interface literature

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    Linking science with action affords a prime opportunity to leverage greater societal impact from research and increase the use of evidence in decision-making. Success in these areas depends critically upon processes of producing and mobilizing knowledge, as well as supporting and making decisions. For decades, scholars have idealized and described these social processes in different ways, resulting in numerous assumptions that now variously guide engagements at the interface of science and society. We systematically catalog these assumptions based on prior research on the science-policy interface, and further distill them into a set of 26 claims. We then elicit expert perspectives (n = 16) about these claims to assess the extent to which they are accurate or merit further examination. Out of this process, we construct a research agenda to motivate future scientific research on actionable knowledge, prioritizing areas that experts identified as critical gaps in understanding of the science-society interface. The resulting agenda focuses on how to define success, support intermediaries, build trust, and evaluate the importance of consensus and its alternatives – all in the diverse contexts of science-society-decision-making interactions. We further raise questions about the centrality of knowledge in these interactions, discussing how a governance lens might be generative of efforts to support more equitable processes and outcomes. We offer these suggestions with hopes of furthering the science of actionable knowledge as a transdisciplinary area of inquiry
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