Changes of Vital Parameters after Administration of Butorphanol during Tiletamine-Zolazepam-Ketamine-Xylazine Anaesthesia for Joint Surgery in Miniature Pigs

The study compares the effects of butorphanol in pigs undergoing joint surgery in tiletamine-zolazepam-ketamine-xylazine (TKX) anaesthesia. A total of 12 pigs were divided into 2 groups by 6 animals - BUT (anaesthetized with TKX combination and butorphanol) and CON (control group - anaesthetized with TKX combination only). All pigs were sedated with a mix of tiletamin-zolazepam-ketamin-xylazin, put into total anaesthesia using propofol, and connected to an anaesthesiology unit (O2-Air). For 40 min we logged the heart rate (HR), respiratory rate (RR), mean arterial pressure (MAP), haemoglobin saturation by oxygen (SpO2) and end-tidal CO2 concentration (ETCO2) values. Ten minutes after connecting to the devices, the pigs in the BUT group were intravenously administered butorphanol (0.2 mg/kg) in the total volume of 2 ml, or physiological saline in the same volume. The pigs in the BUT group had a lower (p th, 10th and 25th min, and a lower RR in the 10th, 15th and 20th min. MAP, ETCO2 and SpO2 values did not differ substantially. Butorphanol can thus be identified as a suitable analgesic TKX supplement to anaesthesia of miniature pigs with minimum effect on vital functions

The first multi-model ensemble of regional climate simulations at kilometer-scale resolution, part I: evaluation of precipitation

Here we present the first multi-model ensemble of regional climate simulations at kilometer-scale horizontal grid spacing over a decade long period. A total of 23 simulations run with a horizontal grid spacing of ∼3 km, driven by ERA-Interim reanalysis, and performed by 22 European research groups are analysed. Six different regional climate models (RCMs) are represented in the ensemble. The simulations are compared against available high-resolution precipitation observations and coarse resolution (∼ 12 km) RCMs with parameterized convection. The model simulations and observations are compared with respect to mean precipitation, precipitation intensity and frequency, and heavy precipitation on daily and hourly timescales in different seasons. The results show that kilometer-scale models produce a more realistic representation of precipitation than the coarse resolution RCMs. The most significant improvements are found for heavy precipitation and precipitation frequency on both daily and hourly time scales in the summer season. In general, kilometer-scale models tend to produce more intense precipitation and reduced wet-hour frequency compared to coarse resolution models. On average, the multi-model mean shows a reduction of bias from ∼ −40% at 12 km to ∼ −3% at 3 km for heavy hourly precipitation in summer. Furthermore, the uncertainty ranges i.e. the variability between the models for wet hour frequency is reduced by half with the use of kilometer-scale models. Although differences between the model simulations at the kilometer-scale and observations still exist, it is evident that these simulations are superior to the coarse-resolution RCM simulations in the representing precipitation in the present-day climate, and thus offer a promising way forward for investigations of climate and climate change at local to regional scales

The first multi-model ensemble of regional climate simulations at kilometer-scale resolution. Part I: Evaluation of precipitation

Here we present the first multi-model ensemble of regional climate simulations at kilometer-scale horizontal grid spacing over a decade long period. A total of 23 simulations run with a horizontal grid spacing of ∼ 3 km, driven by ERA-Interim reanalysis, and performed by 22 European research groups are analysed. Six different regional climate models (RCMs) are represented in the ensemble. The simulations are compared against available high-resolution precipitation observations and coarse resolution (∼ 12 km) RCMs with parameterized convection. The model simulations and observations are compared with respect to mean precipitation, precipitation intensity and frequency, and heavy precipitation on daily and hourly timescales in different seasons. The results show that kilometer-scale models produce a more realistic representation of precipitation than the coarse resolution RCMs. The most significant improvements are found for heavy precipitation and precipitation frequency on both daily and hourly time scales in the summer season. In general, kilometer-scale models tend to produce more intense precipitation and reduced wet-hour frequency compared to coarse resolution models. On average, the multi-model mean shows a reduction of bias from ∼ −40 at 12 km to ∼ −3 at 3 km for heavy hourly precipitation in summer. Furthermore, the uncertainty ranges i.e. the variability between the models for wet hour frequency is reduced by half with the use of kilometer-scale models. Although differences between the model simulations at the kilometer-scale and observations still exist, it is evident that these simulations are superior to the coarse-resolution RCM simulations in the representing precipitation in the present-day climate, and thus offer a promising way forward for investigations of climate and climate change at local to regional scales. © 2021, The Author(s)

Reorganization Energy for Internal Electron Transfer in Multicopper Oxidases.

We have calculated the reorganization energy for the intramolecular electron transfer between the reduced type 1 copper site and the peroxy intermediate of the trinuclear cluster in the multicopper oxidase CueO. The calculations are performed at the combined quantum mechanics and molecular mechanics (QM/MM) level, based on molecular dynamics simulations with tailored potentials for the two copper sites. We obtain a reorganization energy of 91-133 kJ/mol, depending on the theoretical treatment. The two Cu sites contribute by 12 and 22 kJ/mol to this energy, whereas the solvent contribution is 34 kJ/mol. The rest comes from the protein, involving small contributions from many residues. We have also estimated the energy difference between the two electron-transfer states and show that the reduction of the peroxy intermediate is exergonic by 43-87 kJ/mol, depending on the theoretical method. Both the solvent and the protein contribute to this energy difference, especially charged residues close to the two Cu sites. We compare these estimates with energies obtained from QM/MM optimizations and QM calculations in a vacuum and discuss differences between the results obtained at various levels of theory

Catalytic Cycle of Multicopper Oxidases Studied by Combined Quantum- and Molecular-Mechanical Free-Energy Perturbation Methods

We have used combined quantum mechanical and molecular mechanical free-energy perturbation methods in combination with explicit solvent simulations to study the reaction mechanism of the multicopper oxidases, in particular the regeneration of the reduced state from the native intermediate. For 52 putative states of the trinuclear copper cluster, differing in the oxidation states of the copper ions and the protonation states of water- and O2-derived ligands, we have studied redox potentials, acidity constants, isomerisation reactions, as well as water- and O2 binding reactions. Thereby, we can propose a full reaction mechanism of the multicopper oxidases with atomic detail. We also show that the two copper sites in the protein communicate so that redox potentials and acidity constants of one site are affected by up to 0.2 V or 3 pKa units by a change in the oxidation state of the other site

On the damage mechanism of a cold rolling roll: Finite element analysis and material characterization

A detailed failure analysis of a cold rolling roll after service is proposed; the numerical simulation was performed following a semi-analytical approach. A finite element analysis of the roll was performed by using the pressure distribution obtained with the Bland and Ford solution of the Von Karman's equation. According to previous studies available in literature on rolling fatigue, the Crossland multiaxial fatigue criterion was applied to perform a durability analysis. Fatigue limit under fully reversed bending of the cemented carbide material of the roll was obtained with Murakami Endo equation, applied close to a pore. Material characterization was performed with SEM and EDXS in proximity of the fracture surface. The failure analysis showed that the rolls failed primarily because of rolling fatigue, starting from an internal pore that acted as local stress raiser. The pore was positioned at 600\ub5m from the surface , where the Crossland criteria gives high criticality

π-Frontier molecular orbitals in S = 2 ferryl species and elucidation of their contributions to reactivity

S = 2 FeIV═O species are key intermediates in the catalysis of most nonheme iron enzymes. This article presents detailed spectroscopic and high-level computational studies on a structurally-defined S = 2 FeIV═O species that define its frontier molecular orbitals, which allow its high reactivity. Importantly, there are both π- and σ-channels for reaction, and both are highly reactive because they develop dominant oxyl character at the transition state. These π- and σ-channels have different orientation dependences defining how the same substrate can undergo different reactions (H-atom abstraction vs. electrophilic aromatic attack) with FeIV═O sites in different enzymes, and how different substrates can undergo different reactions (hydroxylation vs. halogenation) with an FeIV═O species in the same enzyme