Rendezvous Planning for Multiple Autonomous Underwater Vehicles using a Markov Decision Process

Multiple Autonomous Underwater Vehicles (AUVs) are a potential alternative to conventional large manned vessels for mine countermeasure (MCM) operations. Online mission planning for cooperative multi-AUV network often relies or predefined contingency on reactive methods and do not deliver an optimal end-goal performance. Markov Decision Process (MDP) is a decision-making framework that allows an optimal solution, taking into account future decision estimates, rather than having a myopic view. However, most real-world problems are too complex to be represented by this framework. We deal with the complexity problem by abstracting the MCM scenario with a reduced state and action space, yet retaining the information that defines the goal and constraints coming from the application. Another critical part of the model is the ability of the vehicles to communicate and enable a cooperative mission. We use the Rendezvous Point (RP) method. The RP schedules meeting points for the vehicles throughput the mission. Our model provides an optimal action selection solution for the multi-AUV MCM problem. The computation of the mission plan is performed in the order of minutes. This quick execution demonstrates the model is feasible for real-time applications

Preparation and Characterization of Biobased Poly(Ethylene- 2,5-Furan Dicarboxylate)/Clay Nanocomposites

Poly(ethylene 2,5-furan dicarboxylate)/Clay nanocomposites was prepared via esterification and polycondensation reaction. Biobased monomer was first intercalated into the interlayer regions of clay minerals by ion exchange reaction. Then, the clay was dispersed in the monomer at different loading degrees to conduct the polymerization process. Polymerization through the interlayer of the clay led to the exfoliated poly(ethylene-2,5-furan dicarboxylate)/montmorillonite nanocomposite formation. X-ray diffraction (XRD) analysis revealed that the resultant nanocomposites exhibited exfoliated polymer/clay nanocompositesKeywords: Poly(ethylene-2,5- furan dicarboxylate); renewable polymers; nanocomposites, montmorinollit

ω-Transaminases for the amination of functionalised cyclic ketones

The potential of a number of enantiocomplementary ω-transaminases (ω-TAms) in the amination of cyclic ketones has been investigated. After a preliminary screening of several compounds with increasing complexity, different approaches to shift the equilibrium of the reaction to the amine products were studied, and reaction conditions (temperature and pH) optimised. Interestingly, 2-propylamine as an amine donor was tolerated by all five selected ω-TAms, and therefore used in further experiments. Due to the higher conversions observed and interest in chiral amines studies then focused on the amination of α-tetralone and 2-methylcyclohexanone. Both ketones were aminated to give the corresponding amine with at least one of the employed enzymes. Moreover, the amination of 2-methylcyclohexanone was investigated in more detail due to the different stereoselectivities observed with TAms used. The highest yields and stereoselectivities were obtained using the ω-TAm from Chromobacterium violaceum (CV-TAm), producing 2-methylcyclohexylamine with complete stereoselectivity at the (1S)-amine position and up to 24 : 1 selectivity for the cis : trans [(1S,2R) : (1S,2S)] isomer

TOWARDS AN AUTOMATED FEEDBACK COACHING SUPPORT SYSTEM FOR SPRINT PERFORMANCE MONITORING

The purpose of this study was to investigate the feasibility of developing a cost-effective, automated performance feedback system to support sprint coaching. The proposed system is designed to deliver step length, step frequency, contact time and 10 m split time information of multiple athletes training on an indoor track. An integrated systems approach was chosen combining the novel Pisa Light-Gate (PLG) and Step Information Monitoring Systems (SIMS). Current results indicate data accuracy of RMS 1.662 cm for step length, RMS 0.977 ms for foot contact time and a split time detection accuracy of 8.45 ± 6.85 ms. These results suggest that the proposed integrated system, using off-the-shelf equipment, would go beyond currently available coaching tools by providing automated and highly accurate sprint performance information for multiple athletes

'Dopamine-first' mechanism enables the rational engineering of the norcoclaurine synthase aldehyde activity profile

Norcoclaurine synthase (NCS) (EC 4.2.1.78) catalyzes the Pictet–Spengler condensation of dopamine and an aldehyde, forming a substituted (S)-tetrahydroisoquinoline, a pharmaceutically important moiety. This unique activity has led to NCS being used for both in vitro biocatalysis and in vivo recombinant metabolism. Future engineering of NCS activity to enable the synthesis of diverse tetrahydroisoquinolines is dependent on an understanding of the NCS mechanism and kinetics. We assess two proposed mechanisms for NCS activity: (a) one based on the holo X-ray crystal structure and (b) the ‘dopamine-first’ mechanism based on computational docking. Thalictrum flavum NCS variant activities support the dopamine-first mechanism. Suppression of the non-enzymatic background reaction reveals novel kinetic parameters for NCS, showing it to act with low catalytic efficiency. This kinetic behaviour can account for the ineffectiveness of recombinant NCS in in vivo systems, and also suggests NCS may have an in planta role as a metabolic gatekeeper. The amino acid substitution L76A, situated in the proposed aldehyde binding site, results in the alteration of the enzyme's aldehyde activity profile. This both verifies the dopamine-first mechanism and demonstrates the potential for the rational engineering of NCS activity

Pictet-Spenglerases in Alkaloid Biosynthesis: future applications in Biocatalysis

Pictet-Spenglerases provide a key role in the biosynthesis of many biologically-active alkaloids. There is increasing use of these biocatalysts as an alternative to traditional organic synthetic methods as they provide stereoselective and regioselective control under mild conditions. Products from these enzymes also contain privileged drug scaffolds (such as tetrahydroisoquinoline or b-carboline moieties), so there is interest in the characterisation and use of these enzymes as versatile biocatalysts to synthesize analogues of the corresponding natural products for drug discovery. This review discusses all known Pictet- Spenglerase enzymes and their applications as biocatalysts. Rebecca , John M. , Nicholas H. and Helen C.

Chemoenzymatic microfluidic cascade reaction: Coupling of a diels-alder reaction with a transketolase-catalyzed reaction

A chemoenzymatic microfluidic cascade reaction is demonstrated for the first time, where a Diels-Alder reaction is followed by a transketolase reaction, for the synthesis of 3,4-dimethylcyclohex-3-ene-2’-keto-1’,3’- propanediols, which are used as scaffolds for a number of interesting pharmaceutical compounds. For an efficient organic synthesis, an enzymatic reaction would be advantageous, as it would minimize the number of process steps by eliminating the need for protective chemistry [1]. However, most catalysts and reactions conditions used with DA reactions are not compatible with a subsequent enzymatic reaction (issues revolve e.g. around solvent compatibility, differing reaction rates, and mis-match of pH). We used the spatial confinement of reactions afforded by cascaded microreactors, which has been well established for enzyme-enzyme reactions [2], to overcome these challenges and to achieve a chemoenzymatic reaction in continuous flow. Each reaction was optimized individually or in a step-wise synthesis, considering solvents and catalyst combinations, before being coupled in continuous flow

Engineering transketolase to accept both unnatural donor and acceptor substrates and produce α‐hydroxyketones

A narrow substrate range is a major limitation in exploiting enzymes more widely as catalysts in synthetic organic chemistry. For enzymes using two substrates, the simultaneous optimisation of both substrate specificities is also required for the rapid expansion of accepted substrates. Transketolase (TK) catalyses the reversible transfer of a C2‐ketol unit from a donor substrate to an aldehyde acceptor and suffers the limitation of narrow substrate scope for industrial applications. Herein, TK from Escherichia coli was engineered to accept both pyruvate, as a novel donor substrate, and unnatural acceptor aldehydes, including propanal, pentanal, hexanal and 3‐formylbenzoic acid (FBA). Twenty single‐mutant variants were first designed and characterised experimentally. Beneficial mutations were then recombined to construct a small library. Screening of this library identified the best variant with a 9.2‐fold improvement in the yield towards pyruvate and propionaldehyde, relative to wild‐type (WT). Pentanal and hexanal were used as acceptors to determine stereoselectivities of the reactions, which were found to be higher than 98% enantiomeric excess (ee) for the S configuration. Three variants were identified to be active for the reaction between pyruvate and 3‐FBA. The best variant was able to convert 47% of substrate into product within 24 h, whereas no conversion was observed for WT. Docking experiments suggested a cooperation between the mutations responsible for donor and acceptor recognition, which would promote the activity towards both the acceptor and donor. The variants obtained have the potential to be used for developing catalytic pathways to a diverse range of high‐value products

Library of norcoclaurine synthases and their immobilization for biocatalytic transformations

Norcoclaurine synthases (NCS), catalyzing a Pictet-Spengler reaction in plants as one of the first enzymes in the biosynthetic benzylisoquinoline pathway, were investigated for biocatalytic transformations. The library of norcoclaurine synthases available was extended by two novel NCSs from Argemone mexicana (AmNCS1, AmNCS2) and one new NCS from Corydalis saxicola (CsNCS); furthermore, it was shown that the NCS from Papaver bracteatum (PbNCS) is a highly productive catalyst leading to the isoquinoline product with up to >99% e.e. Under certain conditions lyophilized whole E. coli cells containing the various overexpressed NCS turned out to be suitable catalysts. The reaction using dopamine as substrate bears several challenges such as the spontaneous non-stereoselective background reaction and side reactions. The PbNCS enzyme was successfully immobilized on various carriers whereby EziG3 proved to be the best suited for biotransformations. Dopamine showed limited stability in solution resulting in the coating of the catalyst over time, which could be solved by the addition of ascorbic acid (e.g. 1 mg/ml) as antioxidant

Drug delivery, biodistribution and anti-EGFR activity: theragnostic nanoparticles for simultaneous in vivo delivery of tyrosine kinase inhibitors and kinase activity biosensors

In vivo delivery of small molecule therapeutics to cancer cells, assessment of the selectivity of administration, and measuring the efficacity of the drug in question at the molecule level, are important ongoing challenges in developing new classes of cancer chemotherapeutics. One approach that has the potential to provide targeted delivery, tracking of biodistribution and readout of efficacy, is to use multimodal theragnostic nanoparticles to deliver the small molecule therapeutic. In this paper, we report the development of targeted theragnostic lipid/peptide/DNA lipopolyplexes. These simultaneously deliver an inhibitor of the EGFR tyrosine kinase, and plasmid DNA coding for a Crk-based biosensor, Picchu-X, which when expressed in the target cells can be used to quantify the inhibition of EGFR in vivo in a mouse colorectal cancer xenograft model. Reversible bioconjugation of a known analogue of the tyrosine kinase inhibitor Mo-IPQA to a cationic peptide, and co-formulation with peptides containing both EGFR-binding and cationic sequences, allowed for good levels of inhibitor encapsulation with targeted delivery to LIM1215 colon cancer cells. Furthermore, high levels of expression of the Picchu-X biosensor in the LIM1215 cells in vivo allowed us to demonstrate, using fluorescence lifetime microscopy (FLIM)-based biosensing, that EGFR activity can be successfully suppressed by the tyrosine kinase inhibitor, released from the lipopolyplexes. Finally, we measured the biodistribution of lipopolyplexes containing 125I-labelled inhibitors and were able to demonstrate that the lipopolyplexes gave significantly higher drug delivery to the tumors compared with free drug