Title page Glucuronide production by whole-cell biotransformation using genetically engineered fission yeast S. pombe

Abstract Drug metabolites generated by UDP glycosyltransferases (UGTs) are needed for drug development and toxicity studies, especially in the context of safety testing of metabolites during drug development. Since chemical metabolite synthesis can be arduous, various biological approaches have been developed; however, no whole-cell biotransformation with recombinant microbes that express human UGTs was yet achieved. In this study we expressed human UDP glucose-6-dehydrogenase (UGDH) together with several human or rat UGT isoforms in the fission yeast Schizosaccharomyces pombe and generated strains that catalyze the whole-cell glucuronidation of standard substrates. Moreover, we established two methods to obtain stable isotope-labeled glucuronide metabolites: The first uses a labeled aglycon, while the second employs 13 C 6 -glucose as a metabolic precursor of isotope-labeled UDPglucuronic acid (UDP-GA) and yields a sixfold labeled glucuronide. The system described here should lead to a significant facilitation in the production of both labeled and unlabeled drug glucuronides for industry and academia. DMD 30965

A new aircraft architecture based on the ACHEON Coanda effect nozzle: flight model and energy evaluation

Purpose Aeronautic transport has an effective necessity of reducing fuel consumption and emissions to deliver efficiency and competitiveness driven by today commercial and legislative requirements. Actual aircraft configurations scenario allows envisaging the signs of a diffused technological maturity and they seem very near their limits. This scenario clearly shows the necessity of radical innovations with particular reference to propulsion systems and to aircraft architecture consequently. Methods This paper presents analyses and discusses a promising propulsive architecture based on an innovative nozzle, which allows realizing the selective adhesion of two impinging streams to two facing jets to two facing Coanda surfaces. This propulsion system is known with the acronym ACHEON (Aerial Coanda High Efficiency Orienting Nozzle). This paper investigates how the application of an all-electric ACHEONs propulsion system to a very traditional commuter aircraft can improve its relevant performances. This paper considers the constraints imposed by current state-of-the-art electric motors, drives, storage and conversion systems in terms of both power/energy density and performance and considers two different aircraft configurations: one using battery only and one adopting a more sophisticated hybrid cogeneration. The necessity of producing a very solid analysis has forced to limit the deflection of the jet in a very conservative range (±15°) with respect to the horizontal. This range can be surely produced also by not optimal configurations and allow minimizing the use of DBD. From the study of general flight dynamics equations of the aircraft in two-dimensional form it has been possible to determine with a high level of accuracy the advantages that ACHEON brings in terms of reduced stall speed and of reduced take-off and landing distances. Additionally, it includes an effective energy analysis focusing on the efficiency and environmental advantages of the electric ACHEON based propulsion by assuming the today industrial grade high capacity batteries with a power density of 207 Wh/kg. Results It has been clearly demonstrated that a short flight could be possible adopting battery energy storage, and longer duration could be possible by adopting a more sophisticated cogeneration system, which is based on cogeneration from a well-known turboprop, which is mostly used in helicopter propulsion. This electric generation system can be empowered by recovering the heat and using it to increase the temperature of the jet. It is possible to transfer this considerable amount of heat to the jet by convection and direct fluid mixing. In this way, it is possible to increase the energy of the jets of an amount that allows more than recover the pressure losses in the straitening section. In this case, it is then possible to demonstrate an adequate autonomy of flight and operative range of the aircraft. The proposed architecture, which is within the limits of the most conservative results obtained, demonstrates significant additional benefits for aircraft manoeuvrability. In conclusion, this paper has presented the implantation of ACHEON on well-known traditional aircraft, verifying the suitability and effectiveness of the proposed system both in terms of endurance with a cogeneration architecture and in terms of manoeuvrability. It has demonstrated the potential of the system in terms of both takeoff and landing space requirements. Conclusions This innovation opens interesting perspectives for the future implementation of this new vector and thrust propulsion system, especially in the area of greening the aeronautic sector. It has also demonstrated that ACHEON has the potential of renovating completely a classic old aircraft configuration such as the one of Cessna 402

Choosing the Best Gene Predictions with GeneValidator.

GeneValidator is a tool for determining whether the characteristics of newly predicted protein-coding genes are consistent with those of similar sequences in public databases. For this, it runs up to seven comparisons per gene. Results are shown in an HTML report containing summary statistics and graphical visualizations that aim to be useful for curators. Results are also presented in CSV and JSON formats for automated follow-up analysis.Here, we describe common usage scenarios of GeneValidator that use the JSON output results together with standard UNIX tools. We demonstrate how GeneValidator's textual output can be used to filter and subset large gene sets effectively. First, we explain how low-scoring gene models can be identified and extracted for manual curation-for example, as input for genome browsers or gene annotation tools. Second, we show how GeneValidator's HTML report can be regenerated from a filtered subset of GeneValidator's JSON output. Subsequently, we demonstrate how GeneValidator's GUI can be used to complement manual curation efforts. Additionally, we explain how GeneValidator can be used to merge information from multiple annotations by automatically selecting the higher-scoring gene model at each common gene locus. Finally, we show how GeneValidator analyses can be optimized when using large BLAST databases

Integration of smart nanomaterials for highly selective disposable sensors and their forensic applications in amphetamine determination

Screening drugs on the street and biological samples pose a challenge to law enforcement agencies due to existing detection methods and instrument limitations. Herein we present a graphene-assisted molecularly imprinted polymer nanoparticle-based sensor for amphetamine. These nanoparticles are electroactive by incorporating ferrocene in their structure. These particles act as specific actuators in electrochemical sensors, and the presence of a ferrocene redox probe embedded in the structure allows the detection of non-electroactive amphetamine. In a control approach, nanoparticles were covalently immobilised onto electrochemical sensors by drop-casting using silanes. Alternatively, nanoparticles were immobilised employing 3D printing and a graphene ink composite. The electrochemical performance of both approaches was evaluated. As a result, 3D printed nanoMIPs/graphene sensors displayed the highest selectivity in spiked human plasma, with sensitivity at 73 nA nM−1, LOD of 68 nM (RSD 2.4%) when compared to the silane drop cast electrodes. The main advantage of the optimised 3D printing technology is that it allows quantitative determination of amphetamine, a non-electroactive drug, challenging to detect with conventional electrochemical sensors. In addition, the cost-efficient 3D printing method makes these sensors easy to manufacture, leading to robust, highly selective and sensitive sensors. As proof of concept, sensors were evaluated on the street specimens and clinically relevant samples and successfully validated using UPLC-MS