Substrate-based protein engineering of a flavoprotein oxidase for improved alcohol over-oxidation

The oxidation of alcohols to the corresponding carbonyl compounds represents a convenient strategy for the selective introduction of carbon-acceptor units into carbohydrate-based starting materials from renewable resources. A simple system to accomplish this transformation is by using flavin-containing alcohol oxidases. However, with prim-alcohols, the oxidation does not necessarily stop at the aldehyde stage, but may furnish the carboxylic acid via \u27over\u27-oxidation of the aldehyde hydrate.[1] In order to develop an alcohol oxidase for the efficient transformation of alcohols into carboxylic acids, we chose the recently discovered (5-hydroxymethyl)furfural oxidase (HMFO), which converts not only the eponymous (5-hydroxymethyl)furfural, but also a range of aromatic and allylic alcohols (Figure 1).[2]In order to improve the performance of HMFO for over-oxidation, we anticipated an improved stabilisation of the aldehyde hydrate in the active site to be a crucial factor. After inspection of the HMFO crystal structure, two positions were identified, where hydrogen bond donating and accepting amino acids were introduced, in order to stabilize the gem-diol moiety.[3] Indeed, one of the new HMFO variants exhibited a significantly increased activity for the formation of carboxylic acids from benzylic alcohols. Please click Additional Files below to see the full abstract

EuLerian Identification of ascending AirStreams (ELIAS 2.0) in numerical weather prediction and climate models - Part 2: Model application to different datasets

Warm conveyor belts (WCBs) affect the atmospheric dynamics in midlatitudes and are highly relevant for total and extreme precipitation in many parts of the extratropics. Thus, these airstreams and their effect on midlatitude weather should be well represented in numerical weather prediction (NWP) and climate models. This study applies newly developed convolutional neural network (CNN) models which allow the identification of footprints of WCB inflow, ascent, and outflow from a limited number of predictor fields at comparably low spatiotemporal resolution. The goal of the study is to demonstrate the versatile applicability of the CNN models to different datasets and that their application yields qualitatively and quantitatively similar results as their trajectory-based counterpart, which is most frequently used to objectively identify WCBs. The trajectory-based approach requires data at higher spatiotemporal resolution, which are often not available, and is computationally more expensive. First, an application to reanalyses reveals that the well-known relationship between WCB ascent and extratropical cyclones as well as between WCB outflow and blocking anticyclones is also found for WCB footprints identified with the CNN models. Second, the application to Japanese 55-year reanalyses shows how the CNN models may be used to identify erroneous predictor fields that deteriorate the models\u27 reliability. Third, a verification of WCBs in operational European Centre for Medium-Range Weather Forecasts (ECMWF) ensemble forecasts for three Northern Hemisphere winters reveals systematic biases over the North Atlantic with both the trajectory-based approach and the CNN models. The ensemble forecasts\u27 skill tends to be lower when being evaluated with the trajectory approach due to the fine-scale structure of WCB footprints in comparison to the rather smooth CNN-based WCB footprints. A final example demonstrates the applicability of the CNN models to a convection-permitting simulation with the ICOsahedral Nonhydrostatic (ICON) NWP model. Our study illustrates that deep learning methods can be used efficiently to support process-oriented understanding of forecast error and model biases and opens numerous directions for future research

Linear programming approach for solving stochastic control problem on networks with discounted transition costs

Секция 10. Теоретическая информатикаThe infinite horizon stochastic control problem on network with expected total discounted cost optimization criterion is studied. A linear programming approach for solving this problem on networks is developed. Moreover, a polynomial tim

Mean-Field Dynamics: Singular Potentials and Rate of Convergence

We consider the time evolution of a system of $N$ identical bosons whose interaction potential is rescaled by $N^{-1}$. We choose the initial wave function to describe a condensate in which all particles are in the same one-particle state. It is well known that in the mean-field limit $N \to \infty$ the quantum $N$-body dynamics is governed by the nonlinear Hartree equation. Using a nonperturbative method, we extend previous results on the mean-field limit in two directions. First, we allow a large class of singular interaction potentials as well as strong, possibly time-dependent external potentials. Second, we derive bounds on the rate of convergence of the quantum $N$-body dynamics to the Hartree dynamics.Comment: Typos correcte

In vitro cell compatibility and antibacterial activity of microencapsulated doxycycline designed for improved localized therapy of septic arthritis

OBJECTIVES: For the treatment of septic arthritis in large animals, the local application of antibiotics as a slow release system may be an appropriate means to reach high local bioactivity and low systemic side effects and drug residues. In this study, doxycycline microspheres were developed and tested in vitro for their drug-release properties, suitability for intra-articular application and antimicrobial activity. METHODS: The development of a slow release system was achieved by microencapsulation of the drug into poly(lactide-co-glycolide) microspheres by a novel ultrasonic atomization method. Drug elution was evaluated from microspheres dispersed in elution medium at pre-defined time points by HPLC. Joint-tissue compatibility was tested on cultured bovine synoviocytes by evaluating the expression of pro-inflammatory cytokine mRNA and the production of nitric oxide (NO). Finally, the antimicrobial activity of the released antibiotic was assessed with gram-negative and gram-positive bacteria exposed to release medium sampled at days 1, 7 and 12 after microsphere suspension. RESULTS: An adequate size of the microspheres, sufficient stabilization of doxycycline in aqueous environment and drug release (25 mg microspheres in 4 mL medium) above MIC for bacteria usually isolated in bovine and equine joints were obtained over 15 days. Although the cytokine mRNA expression reflected the excellent tissue compatibility, the results with NO yielded contradictory results. Antimicrobial tests of the release medium proved to match perfectly the activity of non-encapsulated, free doxycycline as reported in the literature. CONCLUSIONS: The newly developed doxycycline delivery system achieved the target specifications and is ready for in vivo testin

Adiabatic Pair Creation

We give here the proof that pair creation in a time dependent potentials is possible. It happens with probability one if the potential changes adiabatically in time and becomes overcritical, that is when an eigenvalue enters the upper spectral continuum. The potential may be assumed to be zero at large negative and positive times. The rigorous treatment of this effect has been lacking since the pioneering work of Beck, Steinwedel and Suessmann in 1963 and Gershtein and Zeldovich in 1970.Comment: 53 pages, 1 figure. Editorial changes on page 22 f

Everything Hits at Once: How Remote Rainfall Matters for the Prediction of the 2021 North American Heat Wave

In June 2021, Western North America experienced an intense heat wave with unprecedented temperatures and far-reaching socio-economic consequences. Anomalous rainfall in the West Pacific triggers a cascade of weather events across the Pacific, which build up a high-amplitude ridge over Canada and ultimately lead to the heat wave. We show that the response of the jet stream to diabatically enhanced ascending motion in extratropical cyclones represents a predictability barrier with regard to the heat wave magnitude. Therefore, probabilistic weather forecasts are only able to predict the extremity of the heat wave once the complex cascade of weather events is captured. Our results highlight the key role of the sequence of individual weather events in limiting the predictability of this extreme event. We therefore conclude that it is not sufficient to consider such rare events in isolation but it is essential to account for the whole cascade over different spatiotemporal scales