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The cyclic GMP-AMP synthase (cGAS) catalyzes the synthesis of the multifunctional second messenger, cGAMP, in metazoans. Although numerous cGAS homologues are predicted in protein databases, the catalytic activity towards cGAMP synthesis has been proven for only four of them. Therefore, we selected five novel and yet uncharacterized cGAS homologues, which cover a broad range in the field of vertebrates. Cell-free protein synthesis (CFPS) was used for a pre-screening to investigate if the cGAS...
Background:The raised demand of cannabis as a medicinal plant in recent years led to an increased interest in understanding the biosynthetic routes of cannabis metabolites. Since there is no established protocol to generate stable gene knockouts in cannabis, the use of a virus-induced gene silencing (VIGS) method, resulting in a gene knockdown, to study gene functions is desirable.Results:For this, a computational approach was employed to analyze the Cannabis sativa L. transcriptomic and geno...
The long-term stability of pharmaceutical formulations of poorly-soluble drugs in polymers determines their bioavailability and therapeutic applicability. However, these formulations do not only often tend to crystallize during storage, but also tend to undergo unwanted amorphous-amorphous phase separations (APS). Whereas the crystallization behavior of APIs in polymers has been measured and modeled during the last years, the APS phenomenon is still poorly understood. In this study, the cryst...
In recent years gas-liquid flow in microchannels has drawn much attention in the research fields of analytics and applications, such as in oxidations or hydrogenations. Since surface forces are increasingly important on the small scale, bubble coalescence is detrimental and leads to Taylor bubble flow in microchannels with low surface-to-volume ratio. To overcome this limitation, we have investigated the gas–liquid flow through micronozzles and, specifically, the bubble breakup behind the noz...
Modifier adaptation with quadratic approximation (in short MAWQA) can adapt the operating condition of a process to its economic optimum by combining the use of a theoretical process model and of the collected data during process operation. The efficiency of the MAWQA algorithm can be attributed to a well-designed mechanism which ensures the improvement of the economic performance by taking necessary explorative moves. This paper gives a detailed study of the mechanism of performing explorati...
In this paper, we deal with the model-based time-optimal operation of a batch diafiltration process in the presence of membrane fouling. Membrane fouling poses one of the major problems in the field of membrane processes. We model the fouling behavior and estimate its parameters using various methods. Least-squares, least-squares with a moving horizon, recursive least-squares methods and the extended Kalman filter are applied and discussed for the estimation of the fouling behavior on-line du...
Extensive phytochemical analysis of different root fractions of Jatropha pelargoniifolia Courb. (Euphorbiaceae) has resulted in the isolation and identification of 22 secondary metabolites. 6-hydroxy-8-methoxycoumarin-7-O-β-d-glycopyranoside (15) and 2-hydroxymethyl N-methyltryptamine (18) were isolated and identified as new compounds along with the known diterpenoid (1, 3, 4, and 7), triterpenoid (2 and 6), flavonoid (5, 11, 13, 14, and 16), coumarinolignan (8–10), coumarin (15), pyrimidine ...
Fusicocca-2,10(14)-diene (FCdiene) is a tricyclic diterpene which has many pharmaceutical applications, for example, it is a precursor for different anticancer drugs, including fusicoccin A. Chemical synthesis of this diterpene is not economical as it requires 14 steps with several stereospecific reactions. FCdiene is naturally produced at low titers in phytopathogenic filamentous fungi. However, production of FCdiene can be achieved via expression of fusicoccadiene synthase in yeast. The obj...
In the framework of Quality-by-Design (QbD), the inline determination of process parameters or quality attributes of a product using sufficient process analytical technology (PAT) is a center piece for the establishment of continuous processes as a standard pharmaceutical technology. In this context, Twin-Screw-Extrusion (TSE) processes, such as Hot-Melt-Extrusion (HME), are one key aspect of current research. The main benefit of this process technology is the combination of different unit op...
Over recent years Twin-Screw-Extrusion (TSE) has been established as a platform technology for pharmaceutical manufacturing. Compared to other continuous operation, one of the major benefits of this method is the combination of several unit operations within one apparatus. Several of these are linked to the Residence Time Distribution (RTD), which is typically expressed by the residence time density function. One relevant aspect for pharmaceutical processes is the mixing capacity, which is re...
This contribution deals with an experimental investigation of the optimization potential of Stirling engines and similar regenerative machines by an enhanced design of the cylinder liner and the seal. The latter is mounted at the bottom end of the gap surrounding pistons and displacers that separate cylinder volumes at different temperature levels. The thermal loss associated with this gap may amount to more than 10% of the heat input into these machines. Mostly, its design is reduced to an e...
In this work, the solubilities of pharmaceutical cocrystals in solvent/anti-solvent systems were predicted using PC-SAFT in order to increase the efficiency of cocrystal formation processes. Modeling results and experimental data were compared for the cocrystal system nicotinamide/succinic acid (2:1) in the solvent/anti-solvent mixtures ethanol/water, ethanol/acetonitrile and ethanol/ethyl acetate at 298.15 K and in the ethanol/ethyl acetate mixture also at 310.15 K. The solubility of the inv...
HMF synthesis typically requires high temperature and is carried out in aqueous solutions. In this work, the low-temperature dehydration of fructose to HMF in different deep eutectic solvents (DES) was investigated. We found a very active and selective reaction system consisting of the DES tetraethyl ammonium chloride as hydrogen bond acceptor (HBA) and levulinic acid as hydrogen bond donor (HBD) in a molar ratio of 1:2 leading to a maximum HMF yield of 68% after 120 h at 323 K. The DES still...
Studying biological phenomena of individual cells is enabled by matching the scales of microbes and cultivation devices. We present a versatile, chemically inert microfluidic lab-on-a-chip (LOC) device for biological and chemical analyses of isolated microorganisms. It is based on the Envirostat concept and guarantees constant environmental conditions. A new manufacturing process for direct fusion bonding chips with functional microelectrodes for selective and gentle cell manipulation via neg...
This dataset in brief is related to the research letter entitled "Nicotine-free, nontransgenic tobacco (Nicotiana tabacuml.) edited by CRISPR-Cas9" [1]. Cured tobacco products with a significantly reduced nicotine content helps people to overcome their nicotine addiction. Here we summarize additional data and method descriptions of the generation process of a nicotine-free, nontransgenic tobacco plant. This included the cloning, transformation and regeneration of transgenic tobacco plants, fo...
Recently, submicron particles have been discussed as a means to increase the bioavailability of poorly water-soluble drugs. Separation of these small particles is done with both fibre and membrane filters, as well as electrostatic precipitators. A major disadvantage of an electrostatic precipitator (ESP) is the agglomerate formation on the precipitation electrode. These agglomerates frequently show low bioavailability, due to the decreased specific surface area and poor wettability. In this w...
Understanding and quantification of cosolvent influences on enzyme-catalyzed reactions are driven by a twofold interest. On the one hand, cosolvents can simulate the cellular environment for deeper understanding of in cellulo reaction conditions. On the other hand, cosolvents are applied in biotechnology to tune yield and kinetics of reactions. Further, cosolvents are even present inherently, for example, for reactions with cofactor regeneration or for enzymes that need cosolvents in a functi...
Aqueous Two-Phase Extraction is known to be a gentle separation technique for biochemical molecules where product partitioning is fast. However, the reason for the high mass transfer rates has not been investigated, yet. Many researchers claim that the low interfacial tension facilitates the formation of very small droplets and with it a large interfacial area causing a fast partitioning. However, an experimental evidence for this hypothesis has not been published yet. In this study, the mass...
Biosurfactants offer environmental as well as health benefits over traditionally used chemical surfactants and heterologous production from engineered microorganisms has been demonstrated, offering containable as well as scalable production of these alternative chemicals. Low product titers and cost intensive downstream processing are the main hurdles for economical biosurfactant production at industrial scales. Increased biosurfactant concentrations are found in the liquid fraction of the fo...