Thermostabile Bindung von Aromastoffen an Stärke Teil 1: Bindung durch Gefriertrocknen

Thermostable Binding of Aroma Compounds to Starch. Part 1: Binding by Freeze-Drying. By freeze-drying of aqueous emulsions or suspensions of menthol, pyrazine, thymol, vanillin or peppermint oil and solutions of native or modified starches, amylose, amylopectin Or β-cyclodextrin sorbates were prepared. After heating to 180°C the aroma compounds were bound thermostable and in most cases also stable during extrusion. In general the adsorbed amounts decreased in the order cyclodextrin, amylose, potato starch, waxy maize starch, maize or tapioca starch, wheat starch, amylopectin. Some modified maize starches adsorbed greater amounts than native maize starch. Menthol and thymol were better bound to high-amylose starches, vanillin and pyrazine better to high-amylopectin starches, but vanillin best to cyclodextrin and pyrazine to maltodextrin (DE 4–5). The desorption of the aroma compounds during chewing in the mouth was limited after formation of channel inclusion compounds with amylose.     

Site-Directed Immobilization of an Engineered Bone Morphogenetic Protein 2 (BMP2) Variant to Collagen-Based Microspheres Induces Bone Formation In Vivo

For the treatment of large bone defects, the commonly used technique of autologous bone grafting presents several drawbacks and limitations. With the discovery of the bone-inducing capabilities of bone morphogenetic protein 2 (BMP2), several delivery techniques were developed and translated to clinical applications. Implantation of scaffolds containing adsorbed BMP2 showed promising results. However, off-label use of this protein-scaffold combination caused severe complications due to an uncontrolled release of the growth factor, which has to be applied in supraphysiological doses in order to induce bone formation. Here, we propose an alternative strategy that focuses on the covalent immobilization of an engineered BMP2 variant to biocompatible scaffolds. The new BMP2 variant harbors an artificial amino acid with a specific functional group, allowing a site-directed covalent scaffold functionalization. The introduced artificial amino acid does not alter BMP2′s bioactivity in vitro. When applied in vivo, the covalently coupled BMP2 variant induces the formation of bone tissue characterized by a structurally different morphology compared to that induced by the same scaffold containing ab-/adsorbed wild-type BMP2. Our results clearly show that this innovative technique comprises translational potential for the development of novel osteoinductive materials, improving safety for patients and reducing costs.     

Covalently Immobilized Regenerable Immunoaffinity Layer with Orientation-Controlled Antibodies Based on Z-Domain Autodisplay

A regenerable immunoaffinity layer comprising covalently immobilized orientation-controlled antibodies was developed for use in a surface plasmon resonance (SPR) biosensor. For antibody orientation control, antibody-binding Z-domain-autodisplaying Escherichia coli (E. coli) cells and their outer membrane (OM) were utilized, and a disuccinimidyl crosslinker was employed for covalent antibody binding. To fabricate the regenerable immunoaffinity layer, capture antibodies were bound to autodisplayed Z-domains, and then treated with the crosslinker for chemical fixation to the Z-domains. Various crosslinkers, namely disuccinimidyl glutarate (DSG), disuccinimidyl suberate (DSS) and poly (ethylene glycol)-ylated bis (sulfosuccinimidyl)suberate (BS(PEG)₅), were evaluated, and DSS at a concentration of 500 μM was confirmed to be optimal. The E. coli-cell-based regenerable HRP immunoassay was evaluated employing three sequential HRP treatment and regeneration steps. Then, the Oms of E. coli cells were isolated and layered on a microplate and regenerable OM-based HRP immunoassaying was evaluated. Five HRP immunoassays with four regeneration steps were found to be feasible. This regenerable, covalently immobilized, orientation-controlled OM-based immunoaffinity layer was applied to an SPR biosensor, which was capable of quantifying C-reactive protein (CRP). Five regeneration cycles were repeated using the demonstrated immunoaffinity layer with a signal difference of <10%.     

Alkylthio-substituierte Bis(benzol-1,2-dithiolato)zinkate,Benzol-1,2-dithiole und -1,2-dithiolate – Edukte für Dibenzo[c,g](1,2,5,6)tetrathiocine und Benzo[c](1,2,3)-trithiole; Untersuchungen zu Benzodithieten und ortho-Dithiobenzochinonen

Alkylthiosubstituted Bis(benzene-1,2-dithiolato)zincates, Benzene-1,2-dithioles, and -1,2-dithiolates – Educts for Dibenzo[c,g](1,2,5,6)tetrathiocins, and Benzo[c](1,2,3)trithioles; Investigations on Benzodithietes and ortho-Dithiobenzochinones Using benzenehexathiolate 1 it is possible to synthesize alkylthio-substituted benzo-1,3-dithiole-2-thiones 2 , or -ones 3 and benzo-di(1,3-dithiole-2-thiones) 4 , or -ones 5 , resp., which were cleaved under basic conditions. The generated benzene-1,2-dithiolates 7 were isolated as benzene-dithiolato zincates 8 , benzene-1,2-dithioles 11 , and benzene-1-thiole-2-thiolates 10 . Dibenzo[c,g](1,2,5,6)-tetrathiocins 9 were synthesized by oxidation of 7 or 8 in good yields. For the per(methylthio)-substituted tetrathiocin 9a the twist conformation was proved by x-ray structure analysis. The tetrathiocin 9a was probably formed via the orthodithiobenzoquinone 13a . Photolysis of 3a at room temperature in solution led to 9a and tetrakis(methylthio)benzo[c] (1,2,3)trithiole 12a as the main product, which was also formed by irradiation of 9a . The trithioles 12 were formed from 8 by reaction with sulfur dichloride. 12a was investigated by x-ray structure analysis. ortho-Dithiobenzoquinone 13c can be claimed as an intermediate upon irradiation of benzo-1,3-dithiol-2-one 3c in an argon matrix at 10 K. Depending on the wavelength the equilibrium lies either on the side of dithiobenzoquinone 13c or benzodithiete 14c . The same is true for system 15/16 , which can be reached by flash vacuum pyrolysis of 3c .     

Pre-adolescent children exhibit lower aerosol particle volume emissions than adults for breathing,speaking, singing and shouting

Speaking and singing are activities linked to increased aerosol particle emissions from the respiratory system, dependent on the utilized vocal intensity. As a result, these activities have experienced considerable restrictions in enclosed spaces since the onset of the COVID-19 pandemic due to the risk of infection from the SARS-CoV-2 virus, transmitted by virus-carrying aerosols. These constraints have affected public education and extracurricular activities for children as well, from in-person music instruction to children’s choirs. However, existing risk assessments for children have been based on emission measurements of adults. To address this, we measured the particle emission rates of 15 pre-adolescent children, all eight to ten years old, with a laser particle counter for the test conditions: breathing at rest, speaking, singing and shouting. Compared with values taken from 15 adults, emission rates for breathing, speaking and singing were significantly lower for children. Particle emission rates were reduced by a factor of 4.3 across all conditions, whereas emitted particle volume rates were reduced by a factor of 4.8. These data can supplement SARS-CoV-2 risk management scenarios for various school and extracurricular settings.     

Synthesis and SAR of Tetracyclic Inhibitors of Protein Kinase CK2 Derived from Furocarbazole W16

The serine/threonine kinase CK2 modulates the activity of more than 300 proteins and thus plays a crucial role in various physiological and pathophysiological processes including neurodegenerative disorders of the central nervous system and cancer. The enzymatic activity of CK2 is controlled by the equilibrium between the heterotetrameric holoenzyme CK2α₂β₂ and its monomeric subunits CK2α and CK2β. A series of analogues of W16 ((3aR,4S,10S,10aS)-4-{[(S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}-10-(3,4,5-trimethoxyphenyl)-4,5,10,10a-tetrahydrofuro[3,4-b]carbazole-1,3(3aH)-dione ((+)- 3 a )) was prepared in an one-pot, three-component Levy reaction. The stereochemistry of the tetracyclic compounds was analyzed. Additionally, the chemically labile anhydride structure of the furocarbazoles 3 was replaced by a more stable imide ( 9 ) and N-methylimide ( 10 ) substructure. The enantiomer (−)- 3 a (K_i=4.9 μM) of the lead compound (+)- 3 a (K_i=31 μM) showed a more than sixfold increased inhibition of the CK2α/CK2β interaction (protein-protein interaction inhibition, PPII) in a microscale thermophoresis (MST) assay. However, (−)- 3 a did not show an increased enzyme inhibition of the CK2α₂β₂ holoenzyme, the CK2α subunit or the mutated CK2α′ ^C336S subunit in the capillary electrophoresis assay. In the pyrrolocarbazole series, the imide (−)- 9 a (K_i=3.6 μM) and the N-methylimide (+)- 10 a (K_i=2.8 μM) represent the most promising inhibitors of the CK2α/CK2β interaction. However, neither compound could inhibit enzymatic activity. Unexpectedly, the racemic tetracyclic pyrrolocarbazole (±)- 12 , with a carboxy moiety in the 4-position, displays the highest CK2α/CK2β interaction inhibition (K_i=1.8 μM) of this series of compounds.     

圆筒织物的连续脱水开布

详细描述了Suvac Cut脱水开幅机.与离心脱水开幅机相比,叙述了这一连续工艺的优点.利用真空脱水技术,阔幅圆筒织物可在连续工艺中脱水和开幅,     

Development of Diaminoquinazoline Histone Lysine Methyltransferase Inhibitors as Potent Blood‐Stage Antimalarial Compounds

Modulating epigenetic mechanisms in malarial parasites is an emerging avenue for the discovery of novel antimalarial drugs. Previously we demonstrated the potent in vitro and in vivo antimalarial activity of (1‐benzyl‐4‐piperidyl)[6,7‐dimethoxy‐2‐(4‐methyl‐1,4‐diazepin‐1‐yl)‐4‐quinazolinyl]amine (BIX01294; 1 ), a known human G9a inhibitor, together with its dose‐dependent effects on histone methylation in the malarial parasite. This work describes our initial medicinal chemistry efforts to optimise the diaminoquinazoline chemotype for antimalarial activity. A variety of analogues were designed by substituting the 2 and 4 positions of the quinazoline core, and these molecules were tested against Plasmodium falciparum (3D7 strain). Several analogues with IC₅₀ values as low as 18.5 nM and with low mammalian cell toxicity (HepG2) were identified. Certain pharmacophoric features required for antimalarial activity were found to be analogous to the previously published SAR of these analogues for G9a inhibition, thereby suggesting potential similarities between the malarial and human HKMT targets of this chemotype. Physiochemical, in vitro activity, and in vitro metabolism studies were also performed for a select set of potent analogues to evaluate their potential as antimalarial leads.     

Optimised plasma stabilisation at TEXTOR with an advanced, real-time digital control scheme

The tokamak TEXTOR at the Research Centre in Jülich is in operation since more than 25 years. The various control systems at the start, in 1982, were based on analogue techniques, a standard at the time, and were later partly replaced by specially developed digital systems. These systems proved their robustness over the years. As a replacement for the old system, off-the-shelf products were used to ensure continuity, reliability and to reduce the development cost. To provide advanced control scenarios, the new system allows the implementation of more sophisticated algorithms for magnetic and kinetic control. The LabVIEW Real-Time (RT) modules and real-time hardware from National Instruments satisfy these requirements to a large extent. The new system has already been successfully commissioned at TEXTOR and is used to calculate in real-time the plasma density profile (10 ms), the Shafranov shift (10 ms), the plasma vertical and horizontal position (20 $\mu$s) and to control the plasma shape (1 ms). TEXTOR has circular plasmas and has an iron core. Its central part is operated in saturation. During the saturation phase, stray fields change the plasma shape from nearly circular to slightly triangular. By using a shape-control coil set, we can control and adjust the plasma form. The new real-time system is presented as well as the implemented control applications.