Maria Stuart

"Maria Stuart, described as Schiller’s most perfect play, is a finely balanced, inventive account of the last day of the captive Queen of Scotland, caught up in a great contest for the throne of England after the death of Henry VIII and over the question of England’s religious confession. Hope for and doubt about Mary’s deliverance grow in the first two acts, given to the Scottish and the English queen respectively, reach crisis at the center of the play, where the two queens meet in a famous scene in a castle park, and die away in acts four and five, as the action advances to its inevitable end. The play is at once classical tragedy of great fineness, costume drama of the highest order—a spectacle on the stage—and one of the great moments in the long tradition of classical rhetoric, as Elizabeth’s ministers argue for and against execution of a royal prisoner. Flora Kimmich’s new translation carefully preserves the spirit of the original: the pathos and passion of Mary in captivity, the high seriousness of Elizabeth’s ministers in council, and the robust comedy of that queen’s untidy private life. Notes to the text identify the many historical figures who appear in the text, describe the political setting of the action, and draw attention to the structure of the play. Roger Paulin’s introduction discusses the many threads of the conflict in Maria Stuart and enriches our understanding of this much-loved, much-produced play. Maria Stuart is the last of a series of five new translations of Schiller’s major plays, accompanied by notes to the text and an authoritative introduction.

Increasing reliability by means of efficient configurations for high redundancy actuators

A high redundancy actuator (HRA) is composed of a high number of actuation elements, increasing both the travel and the force above the capability of an individual element. This provides inherent fault tolerance: if one of the elements fails, the capabilities of the actuator may be reduced, but it does not become dysfunctional. This paper analyses the likelihood of reductions in capabilities. The actuator is considered as a multi-state system, and the approach for k-out-of-n:G systems can be extended to cover the case of the HRA. The result is a probability distribution that quantifies the capability of the HRA. By comparing the distribution for different configurations, it is possible to identify the optimal configuration of an HRA for a given situation

Analysing the reliability of actuation elements in series and parallel configurations for high-redundancy actuation

A high-redundancy actuator (HRA) is an actuation system composed of a high number of actuation elements, increasing both travel and force above the capability of an individual element. This approach provides inherent fault tolerance: if one of the elements fails, the capabilities of the whole actuator may be reduced, but it retains core functionality. Many different configurations are possible, with different implications for the actuator capability and reliability. This article analyses the reliability of the HRA based on the likelihood of an unacceptable reduction in capability. The analysis of the HRA is a highly structured problem, but it does not fit into known reliability categories (such as the k-out-of-n system), and a fault-tree analysis becomes prohibitively large. Instead, a multi-state systems approach is pursued here, which provides an easy, concise and efficient reliability analysis of the HRA. The resulting probability distribution can be used to find the optimal configuration of an HRA for a given set of requirements

Prazosin during threat discrimination boosts memory of the safe stimulus

The α-1 adrenoreceptor antagonist prazosin has shown promise in the treatment of post-traumatic stress disorder (PTSD) symptoms, but its mechanisms are not well understood. Here we administered prazosin or placebo prior to threat conditioning (day 1) and tested subsequent extinction (day 2) and reextinction (day 3) in healthy human participants. Prazosin did not affect threat conditioning but augmented stimulus discrimination during extinction and reextinction, via lower responding to the safe stimulus. These results suggest that prazosin during threat acquisition may have influenced encoding or consolidation of safety processing in particular, subsequently leading to enhanced discrimination between the safe and threatening stimuli

Ferrociphenol lipid nanocapsule delivery by mesenchymal stromal cells in brain tumor therapy

The prognosis of patients with malignant glioma remains extremely poor despite surgery and improvements in radio- and chemo-therapies. Thus, treatment strategies that specifically target these tumors have the potential to greatly improve therapeutic outcomes. "Marrow-isolated adult multilineage inducible" cells (MIAMI cells) are a subpopulation of mesenchymal stromal cells (MSCs) which possess the ability to migrate to brain tumors. We have previously shown that MIAMI cells were able to efficiently incorporate lipid nanocapsules (LNCs) without altering either their stem cell properties or their migration capacity. In this study, we assessed whether the cytotoxic effects of MIAMI cells loaded with LNCs containing an organometallic complex (ferrociphenol or Fc-diOH) could be used to treat brain tumors. The results showed that MIAMI cells internalized Fc-diOH-LNCs and that this internalization did not induce MIAMI cell death. Furthermore, Fc-diOH-LNC-loaded MIAMI cells produced a cytotoxic effect on U87MG glioma cells in vitro. This cytotoxic effect was validated in vivo after intratumoral injection of Fc-diOH-LNC-loaded MIAMI cells in a heterotopic U87MG glioma model in nude mice. These promising results open up a new field of treatment in which cellular vehicles and nanoparticles can be combined to treat brain tumors