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Cardiovascular diseases are the leading cause of death worldwide. Early detection of abnormal vascular morphologies like aneurysms in the abdominal (abdominal aortic aneurysm, AAA) or thoracic aorta (thoracic aortic aneurysm, TAA) are essential to prevent fatal events. The aim of this study is the development of a patient-specific simulation model to obtain statistical information about ab- /normal pressure-flow conditions to improve the basic understanding and methods for the early detection of diseases. For this purpose, the numerical cardiovascular modeling tool SISCA was used, to generate a series of simulations by Monte- Carlo parameter variation. The considered variational scenario was built upon a control group of normal patients, deriving two pathological conditions for AAA and TAA with different severity and location. Therefore, the nominal diameters were enlarged between 200 % and 500 %, while the length of the aneurysms were modified within a range of 30 and 90 mm. Within each statistical set the convergence was tested by the bootstrap method ensuring that within a set of 3500 runs a 2 % deviation error of the mean value of the blood pressure was obtained compared to a set of 10000 runs.The parameter variation method allows the generation of disease specific data in the context of physiological/clinical findings and consequently the disease specific quantification of signal uncertainties and variances.

Hypothesis: This article presents a free-radical polymerization method in a mesostructured system - free of any surfactants, protective colloids, or other auxiliary agents. It is applicable for a large variety of industrially relevant vinylic monomers. The aim of this work is to study the impact of surfactant-free mesostructuring on the polymerization kinetics and the polymer derived., Experiments: So-called surfactant-free microemulsions (SFME) were investigated as reaction media with a simple composition comprising water, a hydrotrope (ethanol, n-propanol, isopropanol, tert-butyl alcohol), and the monomer as the reactive oil phase (methyl methacrylate). Polymerization reactions were performed using oil-soluble, thermal- and UV-active initiators (surfactant-free microsuspension polymerization) and water-soluble, redox-active initiators (surfactant-free microemulsion polymerization). Structural analysis of the SFMEs used and the polymerization kinetics were followed by dynamic light scattering (DLS). Dried polymers were analyzed with regard to their conversion yield by mass balance, the corresponding molar masses were determined using gel permeation chromatography (GPC), and the morphology was investigated by light microscopy., Findings: All alcohols are suitable hydrotropes to form SFMEs, except for ethanol, which forms a molecularly disperse system. We observe significant differences in the polymerization kinetics and the molar masses of the polymers obtained. Ethanol leads to significantly higher molar masses. Within a system, higher concentrations of the other alcohols investigated give rise to less pronounced mesostructuring, lower conversions, and lower average molar masses. It could be demonstrated that the effective concentration of alcohol in the oil-rich pseudophases as well as the repulsive effect of the surfactant-free, alcohol-rich interphases constitute the relevant factors influencing polymerization. Concerning the morphology, the polymers derived range from powder-like polymers in the so-called "pre-Ouzo region" over porous-solid polymers in the bicontinuous region to dense, almost compacted, transparent polymers in unstructured regions, comparable to the findings for surfactant-based systems reported in the literature. Polymerizations in SFME comprise a new intermediate between well-known solution (i.e., molecularly dispersed) and microemulsion respectively microsuspension polymerization processes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this paper, we consider the influence of H-bond donor and acceptor functionalities on the formation of mesoscale inhomogeneities in ternary systems. It was found that hydrogen-bonding re-enforces such structures, but is not necessarily a prerequisite for the occurrence of mesoscale, microemulsion-like structuring in ternary surfactant-free microemulsions (SFME) and consequently, hydrogen-bonding-free microemulsions (HBFME) exist. The evaluated ternary systems were investigated by means of dynamic light scattering (DLS) and computer-based calculation methods. Theoretical COSMO-RS based calculations were applied to provide an explanation for different hydrotropic efficiencies, and COSMOplex calculations were used to predict and evaluate the propensity of the molecules to form mesoscale structures in SFME and HBFME. Microemulsion-like fluctuations could be observed in the COSMOplex simulations and correlate fairly well with the appearance of mesoscopic structures observed in SFME and HBFME, although the free energy differences in the formation of aggregate structures in the investigated systems are very small, in the range of 0.05 kcal mol -1 .

In the present contribution, we investigated the influence of the structuring of surfactant-free microemulsions (SFME) (water/1-propanol/limonene and water/tert-butanol/limonene) on the enzyme activity of horseradish peroxidase (HRP). To this purpose, the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) with hydrogen peroxide was chosen as a model reaction. Enzymatic activities in SFMEs of varying compositions were investigated by UV-Vis spectroscopy and compared to the enzyme activity in pure buffer solution. Dynamic light, small-angle-X-ray scattering and conductivity measurements were performed in order to obtain structural information on the used SFMEs. Findings presented in this study revealed that the ability of short-chain alcohols to form mesostructures (aqueous aggregates in oil) has a crucial effect on the enzyme activity in SFMEs. Mesoscale structuring with 1-propanol (NPA) was found to be more pronounced than for the more hydrophobic tert-butanol (TBA). It was concluded that the most pronounced mesoscale-structured SFMEs lead to the highest enzymatic activities., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aqueous solutions of five lanthanide salts: LaCl3, La(NO3)3, La2(SO4)3, Eu(NO3)3 and Eu2(SO4)3 have been studied at 25 °C by dielectric relaxation spectroscopy over the frequency range 0.05 ≤ ν/GHz ≤ 89. Detailed analysis of the solvent-related modes located at higher frequencies showed that both La3+ and Eu3+ are strongly hydrated, even including partial formation of a third hydration shell similar to that of Al3+(aq). Up to two solute-related modes could be detected at lower frequencies, due to the formation of various types of 1 : 1 ion pairs (IPs). All five salts showed modest levels of association in the order Cl- < NO3- ≪ SO42-, mostly in the form of double-solvent-separated IPs with small amounts of solvent-shared IPs. Overall association constants, , calculated from the stepwise IP formation constants were consistent with literature values.

In this contribution, we (i) link the mesoscopic structuring of the binary structured solvent mixture H 2 O/tert-butanol (TBA) to the kinetics and the efficacy of the oxidation of benzyl alcohol (BA) to the corresponding aldehyde catalyzed by H 5 PMo 10 V 2 O 40 . We also compare the catalytic efficacy of this reaction in the mesoscopically structured solvent H 2 O/TBA to an unstructured (or very weakly structured) solvent H 2 O/ethanol (EtOH). In this context, we (ii) also give a methodological outline on how to study systematically the catalytic efficacy of chemical reactions as a function of the mesoscale structuring of a binary solvent. We demonstrate that the obtained yields of benzyl aldehyde depend on the type of mesoscopic structuring of the binary solvent H 2 O/TBA. An elevated catalytic performance of at least 100% is found for unstructured binary mixtures H 2 O/TBA compared to compartmented binary mixtures H 2 O/TBA. We conclude that compartmentation of both the organic substrate and the catalyst in TBA and water-rich micro phases seems to be unfavorable for the catalytic efficacy.

In the present contribution, the pre-structuring of binary mixtures of hydrotropes and H 2 O is linked to the solubilisation of poorly water miscible compounds. We have chosen a series of short-chain alcohols as hydrotropes and benzyl alcohol, limonene and a hydrophobic azo-dye (Disperse Red 13) as organic compounds to be dissolved. A very weak pre-structuring is found for ethanol/H 2 O and 2-propanol/H 2 O mixtures. Pre-structuring is most developed for binary 1-propanol/H 2 O and tert-butanol/H 2 O mixtures and supports the bicontinuity model of alcohol-rich and water-rich domains as already postulated by Anisimov et al. Such a pre-structuring leads to a high solubilisation power for poorly water miscible components (limonene and Disperse Red, characterized by high octanol/water partition coefficients, log(P) values of 4.5 and 4.85), whereas a very weak pre-structuring leads to a high solubilisation power for slightly water miscible components (benzyl alcohol). This difference in solubilisation power can be linked to (i) the formation of mesoscale structures in the cases of ethanol and 2-propanol and (ii) the extension of pre-structures in the cases of 1-propanol and tert-butanol. Three different solubilisation mechanisms could be identified: bulk solubilisation, interface solubilisation and a combination of both. These supramolecular structures in binary and ternary systems were investigated by small-and-wide-angle X-ray and neutron scattering, dynamic light scattering and conductivity measurements (in the presence of small amounts of salt).

Microemulsion electrokinetic chromatography (MEEKC) is a powerful tool to separate neutral species based on differences in their hydrophobic and hydrophilic properties. However, as a major drawback the conventionally used SDS based microemulsions are not compatible with electrospray ionization mass spectrometry (ESI-MS). In this work, a surfactant-free microemulsion (SFME) consisting of water, ethanol, and 1-octanol is used for surfactant-free microemulsion electrokinetic chromatography (SF-MEEKC). Ammonium acetate was added to the SFME enabling electrophoretic separations. The stability of SFMEs containing ammonium acetate was investigated using small-angle X-ray scattering and dynamic light scattering. A method for the separation of a model system of hydrophobic and hydrophilic neutral vitamins, namely the vitamins B 2 and D 3 , and the cationic vitamin B 1 was developed using UV/VIS detection. The influence of the ammonium acetate concentration on the separation performance was studied in detail. The method was characterized concerning reproducibility of migration times and peak areas and concerning the linearity of the calibration data. Furthermore, SF-MEEKC was coupled to ESI-MS investigating the compatibility between SFMEs and the ESI process. The signal intensities of ESI-MS measurements of the model analytes were comparable for SFMEs and aqueous systems. Finally, the vitamin D 3 content of a drug treating vitamin D 3 deficiency was determined by SF-MEEKC coupled to ESI-MS using 25-hydroxycholecalciferol as an internal standard. Graphical abstract The concept of surfactant-free microemulsion electrokinetic chromatography coupled to electrospray ionization mass spectrometry.

Thymidine kinase (TK), which is induced by Herpes Simplex Virus 1 (HSV1), plays a key role in the antiviral activity of guanine derivatives such as aciclovir (ACV). In contrast, ACV shows only low affinity to the corresponding host cell enzyme. In order to define the differences in substrate binding of the two enzymes on molecular level, models for the three-dimensional (3-D) structures of the active sites of HSV1-TK and human TK were developed. The reconstruction of the active sites of HSV1-TK and human TK were developed. The reconstruction of the active sites started from primary and secondary structure analysis of various kinases. The results were validated to homologous enzymes with known 3-D structures. The models predict that both enzymes consist of a central core beta-sheet structure, connected by loops and alpha-helices very similar to the overall structure of other nucleotide binding enzymes. The phosphate binding site is made up of a highly conserved glycine-rich loop at the N-terminus of the proteins and a conserved region at the C-terminus. The thymidine recognition site was found about 100 amino acids downstream from the phosphate binding loop. The differing substrate specificity of human and HSV1-TK can be explained by amino-acid substitutions in the homologous regions. To achieve a better understanding of the structure of the active site and how the thymidine kinase proteins interact with their substrates, the corresponding complexes of thymidine and dihydroxypropoxyguanine (DHPG) with HSV1 and human TK were built. For the docking of the guanine derivative, the X-ray structure of Elongation Factor Tu (EF-Tu), co-crystallized with guanosine diphosphate, was taken as reference. Fitting of thymidine into the active sites was done with respect to similar interactions found in thymidylate kinase. To complement the analysis of the 3-D structures of the two kinases and the substrate enzyme interactions, site-directed mutagenesis of the thymidine recognition site of HSV1-TK has been undertaken, changing Asp162 in the thymidine recognition site into Asn. First investigations reveal that the enzymatic activity of the mutant protein is destroyed.

Adjacent peptide segments covering the complete sequence of herpes-simplex-virus type-1 thymidine kinase (HSV1-TK) of 376 amino acids were synthesized in order to experimentally verify the three-dimensional structure of the HSV1-TK active site, which was previously determined by molecular modeling. 26 peptides have been prepared by multiple solid-phase synthesis using the 9-fluorenylmethoxycarbonyl strategy. The purified peptides were linked covalently to bovine serum albumin. The peptide/ELISA of the synthesized bovine-serum-albumin conjugates using polyclonal rabbit anti(HSV1-TK)serum resulted in ten epitopes, which correlate excellently with the computer-proposed active site of HSV1-TK. CD spectra of the HSV1-TK peptides were recorded in trifluoroethanol/water (9:1 by vol.) An eigenvalue method based on CD spectra of 15 well known protein structures was used to calculate the relative percentage of secondary structures from the CD data. The computer model of the HSV1-TK showed full conformity with the folding pattern determined by CD of the synthetic peptide segments. Therefore, conformational peptide mapping with CD-based secondary structures combined with epitope mapping from the peptide/ELISA is an efficient and reliable method to support computer-aided protein design.

The amino acid sequence of 14 thymidine kinases and three other nucleotide binding enzymes have been compared by alignment of their primary and secondary structure. The overall alignment revealed five homologous regions, which are supposed to be part of the active site with a common three dimensional structure. Analysis of mutant enzymes brings further evidence for the importance of those regions. Single point mutations are responsible for an amino acid exchange within the homologous sequences thereby affecting the normal function of the enzymes. The substituted amino acids are essential for the binding function and, therefore, building part of an active site. After identification of the homologous regions we tried to fit the HSV 1 thymidine kinase on the known 3D-structure of adenylate kinase to reconstruct the essential binding regions of thymidine kinase as far as possible.