The ether functionality represents a very common motif in organic chemistry and especially the methyl ether is commonly found in natural products. Its formation and cleavage can be achieved via countless chemical procedures. Nevertheless, since in particular the cleavage often involves harsh reaction conditions, milder alternatives are highly demanded. Very recently, we have reported on a biocatalytic shuttle catalysis concept for reversible cleavage and formation of phenolic O‐methyl ethers employing a corrinoid‐dependent methyl transferase system from the anaerobic organism Desulfitobacterium hafniense. Here we report the technical study of this system, focusing on the demethylation of guaiacol as model reaction. The optimal buffer‐, pH‐, temperature‐ and cofactor‐preferences were determined as well as the influence of organic co‐solvents. Beside methyl cobalamin also hydroxocobalamin turned out to be a suitable cofactor species, although the latter required activation. Various O‐methyl phenyl ethers were successfully demethylated with conversions up to 82% at 10 mM substrate concentration.
The prediction of monoclonal antibody (mAb) disposition within solid tumors for individual patients is difficult due to inter-patient variability in tumor physiology. Improved a priori prediction of mAb pharmacokinetics in tumors may facilitate the development of patient-specific dosing protocols and facilitate improved selection of patients for treatment with anti-cancer mAb. Here, we report the use of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), with tumor penetration of the contrast agent gadobutrol used as a surrogate, to improve physiologically based pharmacokinetic model (PBPK) predictions of cetuximab pharmacokinetics in epidermal growth factor receptor (EGFR) positive xenografts. In the initial investigations, mice bearing Panc-1, NCI-N87, and LS174T xenografts underwent DCE-MRI imaging with the contrast agent gadobutrol, followed by intravenous dosing of an 125Iodine-labeled, non-binding mAb (8C2). Tumor concentrations of 8C2 were determined following the euthanasia of mice (3 h–6 days after 8C2 dosing). Potential predictor relationships between DCE-MRI kinetic parameters and 8C2 PBPK parameters were evaluated through covariate modeling. The addition of the DCE-MRI parameter Ktrans alone or Ktrans in combination with the DCE-MRI parameter Vp on the PBPK parameters for tumor blood flow (QTU) and tumor vasculature permeability (σTUV) led to the most significant improvement in the characterization of 8C2 pharmacokinetics in individual tumors. To test the utility of the DCE-MRI covariates on a priori prediction of the disposition of mAb with high-affinity tumor binding, a second group of tumor-bearing mice underwent DCE-MRI imaging with gadobutrol, followed by the administration of 125Iodine-labeled cetuximab (a high-affinity anti-EGFR mAb). The MRI-PBPK covariate relationships, which were established with the untargeted antibody 8C2, were implemented into the PBPK model with considerations for EGFR expression and cetuximab-EGFR interaction to predict the disposition of cetuximab in individual tumors (a priori). The incorporation of the Ktrans MRI parameter as a covariate on the PBPK parameters QTU and σTUV decreased the PBPK model prediction error for cetuximab tumor pharmacokinetics from 223.71 to 65.02%. DCE-MRI may be a useful clinical tool in improving the prediction of antibody pharmacokinetics in solid tumors. Further studies are warranted to evaluate the utility of the DCE-MRI approach to additional mAbs and additional drug modalities. 相似文献
The production of liquid hydrocarbons based on CO2 and renewable H2 is a multi‐step process consisting of water electrolysis, reverse water‐gas shift, and Fischer‐Tropsch synthesis (FTS). The syngas will then also contain CO2 and probably sometimes H2O, too. Therefore, the kinetics of FTS on a commercial cobalt catalyst was studied with syngas containing CO, CO2, H2, and H2O. The intrinsic kinetic parameters as well as the influence of pore diffusion (technical particles) were determined. CO2 and H2O showed only negligible or minor influence on the reaction rate. The intrinsic kinetic parameters of the rate of CO consumption were evaluated using a Langmuir‐Hinshelwood (LH) approach. The effectiveness factor describing diffusion limitations was calculated by two different Thiele moduli. The first one was derived by a simplified pseudo first‐order approach, the second one by the LH approach. Only the latter, more complex model is in good agreement with the experimental results. 相似文献
The kinetics of isothermal, solution copolymerization of vinyl chloroacetate (VCLAC) with vinyl acetate (VAC) in methyl isobutyl ketone (MIBK) has been investigated using a continuous flow stirred-tank reactor (CSTR). The initiator used was 2,2′-azobis 2,4-dimethyl valeronitrile (ADVN). Polymerizations were carried out to moderately high conversions, necessitating the use of a modified parameter estimation method to determine the reactivity ratios. The copolymer composition conforms to terminal model kinetics. The values obtained for r1 and r2 are 1.18 and 0.80, respectively, with VCLAC as M1 and VAC as M2. Both values are close to unity indicating random copolymerization. The cross termination factor ? strongly depends on the composition of the comonomer feed ratio, implying that the chain-termination step is possibly diffusion controlled. The variation of ? could also be caused by chain transfer to the solvent retarding the reaction rate. Such a possibility is consistent with the observed reduction in the molecular weight of the copolymer in the presence of the solvent. The approach to steady-state in the reactor was characterized. It was not possible to obtain good agreement between experiment and simulation with a single value of the ? factor. 相似文献
Small punch testing of Fe3Al-based intermetallic alloy with Cr, Mn and Ce additions was performed in temperature range 773–873 K. It is shown that the testing procedure enables to study the creep properties of the alloy. The time dependence of the central deflection resembles creep curves observed in conventional uniaxial creep testing and the minimum deflection rate can be determined. Similarly as in conventional creep tests, the deflection process is then analyzed in terms of the activation energy and force exponent. In accordance with the phase structure of the alloy, two distinct areas can be observed. In the B2 range, the activation energy equals 181 kJ/mol; the force exponent is about 4.6. In the DO3 range, the activation energy equals 82 kJ/mol and the stress exponent is about 44. The transformation temperature DO3B2 is close to 812 K. The technique can be used for an estimation of creep resistance. 相似文献
The kinetics of isothermal, photoinitiated, solution polymerization of 1-vinyl-2-methylimidazole (MVI) was studied using the standard dilatometric technique. The photoinitiators used were aromatic carbonyl compounds. Most of the experiments were carried out using methanol as solvent, but other solvents were also used. The reaction follows the classical kinetic scheme for free radical polymerization. The activation energy for the polymerization is 3.9 kcal/mol. The polymerization is greatly accelerated by the presence of water in reaction medium. Among the three photoinitiators tried, 2,2′-diethoxyacetophenone (DEAP) has the highest quantum efficiency for the polymerization of MVI. 相似文献
Business Process Management (BPM) has gained a lot of popularity in the last two decades, since it allows organizations to manage and optimize their business processes. However, purchasing a BPM system can be an expensive investment for a company, since not only the software itself needs to be purchased, but also hardware is required on which the process engine should run, and personnel need to be hired or allocated for setting up and maintaining the hardware and the software. Cloud computing gives its users the opportunity of using computing resources in a pay-per-use manner, and perceiving these resources as unlimited. Therefore, the application of cloud computing technologies to BPM can be extremely beneficial specially for small and middle-size companies. Nevertheless, the fear of losing or exposing sensitive data by placing these data in the cloud is one of the biggest obstacles to the deployment of cloud-based solutions in organizations nowadays. In this paper we introduce a transformation-based approach that allows companies to control the parts of their business processes that should be allocated to their own premises and to the cloud, to avoid unwanted exposure of confidential data and to profit from the high performance of cloud environments. In our approach, the user annotates activities and data that should be placed in the cloud or on-premise, and an automated transformation generates the process fragments for cloud and on-premise deployment. The paper discusses the challenges of developing the transformation and presents a case study that demonstrates the applicability of the approach. 相似文献
In this paper a new approach to a conditional probability is studied in more general structure called a D-poset. The authors go into the inner structure of a conditional system which is a crucial notion for the existence of a conditional state. An independence of elements in a D-poset with respect to a state is defined. 相似文献
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