Cofactor regeneration by a soluble pyridine nucleotide transhydrogenase for biological production of hydromorphone

We have applied the soluble pyridine nucleotide transhydrogenase of Pseudomonas fluorescens to a cell-free system for the regeneration of the nicotinamide cofactors NAD and NADP in the biological production of the important semisynthetic opiate drug hydromorphone. The original recombinant whole-cell system suffered from cofactor depletion resulting from the action of an NADP(+)-dependent morphine dehydrogenase and an NADH-dependent morphinone reductase. By applying a soluble pyridine nucleotide transhydrogenase, which can transfer reducing equivalents between NAD and NADP, we demonstrate with a cell-free system that efficient cofactor cycling in the presence of catalytic amounts of cofactors occurs, resulting in high yields of hydromorphone. The ratio of morphine dehydrogenase, morphinone reductase, and soluble pyridine nucleotide transhydrogenase is critical for diminishing the production of the unwanted by-product dihydromorphine and for optimum hydromorphone yields. Application of the soluble pyridine nucleotide transhydrogenase to the whole-cell system resulted in an improved biocatalyst with an extended lifetime. These results demonstrate the usefulness of the soluble pyridine nucleotide transhydrogenase and its wider application as a tool in metabolic engineering and biocatalysis

The Dilemma of Foraging Herbivores: Dealing with Food and Fear

For foraging herbivores, both food quality and predation risk vary across the landscape. Animals should avoid low-quality food patches in favour of high-quality ones, and seek safe patches while avoiding risky ones. Herbivores often face the foraging dilemma, however, of choosing between high-quality food in risky places or low-quality food in safe places. Here, we explore how and why the interaction between food quality and predation risk affects foraging decisions of mammalian herbivores, focusing on browsers confronting plant toxins in a landscape of fear. We draw together themes of plant–herbivore and predator–prey interactions, and the roles of animal ecophysiology, behaviour and personality. The response of herbivores to the dual costs of food and fear depends on the interplay of physiology and behaviour. We discuss detoxification physiology in dealing with plant toxins, and stress physiology associated with perceived predation risk. We argue that behaviour is the interface enabling herbivores to stay or quit food patches in response to their physiological tolerance to these risks. We hypothesise that generalist and specialist herbivores perceive the relative costs of plant defence and predation risk differently and intra-specifically, individuals with different personalities and physiologies should do so too, creating individualised landscapes of food and fear. We explore the ecological significance and emergent impacts of these individual-based foraging outcomes on populations and communities, and offer predictions that can be clearly tested. In doing so, we provide an integrated platform advancing herbivore foraging theory with food quality and predation risk at its core

Self-Organization in Urban Regeneration: A Two-Case Comparative Research

Urban regeneration processes in which local stakeholders take the lead are interesting for realizing tailor made and sustainable urban regeneration, but are also faced with serious difficulties. We use the concept of self-organization from complexity theory to examine the relationship between local stakeholders’ initiatives and vital urban regeneration processes. We conducted a two-case comparative research, Caterham Barracks and Broad Street Business Improvement Districts Birmingham (UK), in which local stakeholders take the lead. We analyse the evolution of these regeneration processes by using two different manifestations of self-organization: autopoietic and dissipative self-organization. We found that a balanced interplay between autopoietic and dissipative self-organization of local stakeholders is important for vital urban regeneration processes to establish. We elaborate four explanatory conditions for this interplay. These conditions provide at the one hand stability and identity development, but also the needed connections with established actors and institutions around urban regeneration and flexibility to adjust to evolving demands during the process of regeneration. However, consolidation of such initiatives does mean a challenge for existing structures for the government, market and society that will need to adapt and change their roles to new governance realities. In this way self-organizing processes become meaningful in the regeneration of urban areas

Medical Specialists' Perspectives on the Influence of Electronic Medical Record Use on the Quality of Hospital Care:Semistructured Interview Study

Objective: The aim of this study was to examine how, and by which aspects, the relationship between EMR use and the quality of care in hospitals is influenced according to medical specialists. Methods: To answer this question, a qualitative study was conducted in the period of August-October 2018. Semistructured interviews of around 90 min were conducted with 11 medical specialists from 11 different Dutch hospitals. For analysis of the answers, we used a previously published taxonomy of factors that can influence the use of EMRs. Results: The professional experience of the participating medical specialists varied between 5 and 27 years. Using the previously published taxonomy, these medical specialists considered technical barriers the most significant for EMR use. The suboptimal change processes surrounding implementation were also perceived as a major barrier. A final major problem is related to the categories “social” (their relationships with the patients and fellow care providers), “psychological” (based on their personal issues, knowledge, and perceptions), and “time” (the time required to select, implement, and learn how to use EMR systems and subsequently enter data into the system). However, the medical specialists also identified potential technical facilitators, particularly in the assured availability of information to all health care professionals involved in the care of a patient. They see promise in using EMRs for medical decision support to improve the quality of care but consider these possibilities currently lacking. Conclusions: The 11 medical specialists shared positive experiences with EMR use when comparing it to formerly used paper records. The fact that involved health care professionals can access patient data at any time they need is considered important. However, in practice, potential quality improvement lags as long as decision support cannot be applied because of the lack of a fully coded patient record

Understanding IFNλ in rheumatoid arthritis

Unraveling the mechanisms underlying the inflammatory response in rheumatoid arthritis is crucial in order to better understand the disease and to develop novel therapeutic approaches. Although the effect of type I interferons on fibroblasts and in the context of rheumatoid arthritis has been described for some time, little is known on the effects of the type III interferons, also known as IFNλ. In a previous issue, Xu and colleagues demonstrate that one of the members of the IFNλ family, IFNλ1, enhances Toll-like receptor expression and consequently promotes the production of proinflammatory cytokines known to be involved in initiating and maintaining the inflammatory responses in rheumatoid arthritis

Rapid manufacturing of color-based hemispherical soft tactile fingertips

Tactile sensing can provide access to information about the contact (i.e. slippage, surface feature, friction), which is out of reach of vision but crucial for manipulation. To access this information, a dense measurement of the deformation of soft fingertips is necessary. Recently, tactile sensors that rely on a camera looking at a deformable membrane have demonstrated that a dense measurement of the contact is possible. However, their manufacturing can be time-consuming and labor-intensive. Here, we show a new design method that uses multi-color additive manufacturing and silicone casting to efficiently manufacture soft marker-based tactile sensors that are able to capture with high-resolution the three-dimensional deformation field at the interface. Each marker is composed of two superimposed color filters. The subtractive color mixing encodes the normal deformation of the membrane, and the lateral deformation is found by centroid detection. With this manufacturing method, we can reach a density of 400 markers on a 21 mm radius hemisphere, allowing for regular and dense measurement of the deformation. We calibrated and validated the approach by finding the curvature of objects with a threefold increase in accuracy as compared to previous implementations. The results demonstrate a simple yet effective approach to manufacturing artificial fingertips for capturing a rich image of the tactile interaction at the location of contact

The Gaugings of Maximal D=6 Supergravity

We construct the most general gaugings of the maximal D=6 supergravity. The theory is (2,2) supersymmetric, and possesses an on-shell SO(5,5) duality symmetry which plays a key role in determining its couplings. The field content includes 16 vector fields that carry a chiral spinor representation of the duality group. We utilize the embedding tensor method which determines the appropriate combinations of these vectors that participate in gauging of a suitable subgroup of SO(5,5). The construction also introduces the magnetic duals of the 5 two-form potentials and 16 vector fields.Comment: 34 pages, latex, reference added, typo's corrected and minor improvements mad