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101.
Claudia Siverino Shorouk Fahmy-Garcia Didem Mumcuoglu Heike Oberwinkler Markus Muehlemann Thomas Mueller Eric Farrell Gerjo J. V. M. van Osch Joachim Nickel 《International journal of molecular sciences》2022,23(7)
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. 相似文献
102.
Jong-Min Park Mi Yeon Kim Joachim Jose Min Park 《International journal of molecular sciences》2022,23(1)
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%. 相似文献
103.
Mario Fleischer Lukas Schumann Anne Hartmann Reuben Scott Walker Liliana Ifrim Dorothea von Zadow Jonas Lüske Joachim Seybold Martin Kriegel Dirk Mürbe 《Journal of the Royal Society Interface》2022,19(187)
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. 相似文献
104.
Dr. Lukas Kröger Dr. Constantin G. Daniliuc Deeba Ensan Sebastian Borgert Dr. Christian Nienberg Miriam Lauwers Dr. Michaela Steinkrüger Prof. Joachim Jose Dr. Markus Pietsch Prof. Bernhard Wünsch 《ChemMedChem》2020,15(10):871-881
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 (Ki=4.9 μM) of the lead compound (+)- 3 a (Ki=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 (Ki=3.6 μM) and the N-methylimide (+)- 10 a (Ki=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 (Ki=1.8 μM) of this series of compounds. 相似文献
105.
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, 相似文献
106.
CeO2 samples doped with 10, 1.0, and 0.1 mol% Y2 O3 and undoped CeO2 samples of high purity were studied by impedance spectroscopy at temperatures <800°C and under various oxygen partial pressures. According to microstructural investigations by SEM and analytical STEM (equipped with EDXS), the grain boundaries were free of any second phase, providing direct grain-to-grain contacts. An amorphous siliceous phase was detected at only a few triple junctions, if at all; as a result, its contribution to the grain-boundary resistance was negligible. Nevertheless, the specific grain-boundary conductivities were still 2–7 orders of magnitude lower than the bulk conductivities, depending on dopant concentration, temperature, and oxygen partial pressure. The charge carrier transport across the grain boundaries occurred only through the grain-to-grain contacts, whose properties were then determined by the space-charge layer. The space-charge potential in acceptor-doped CeO2 was positive, causing the simultaneous depletion of oxygen vacancies and accumulation of electrons in the space-charge layer. The very low grain-boundary conductivities can be accounted for by the oxygen-vacancy depletion; the accumulation of electrons became evident in weakly doped and undoped CeO2 at high temperatures and under low oxygen partial pressures. 相似文献
107.
Thomas Diemant Zhong Zhao Hubert Rauscher Joachim Bansmann R. Jürgen Behm 《Topics in Catalysis》2007,44(1-2):83-93
The interaction of CO with structurally well-defined, planar Au/TiO2 model catalysts at elevated pressures (up to 50 mbar) was studied in-situ by polarization-modulated infrared reflection absorption spectroscopy and ex-situ by X-ray photoelectron spectroscopy performed before and after CO exposure. The results indicate a CO-induced partial reduction
of the oxide surface, which is evidenced by a low frequency C–O vibration at 2060 cm−1, combined with a spreading of the Au nanoparticles due to a modification of the Au-oxide interface energy. In a 2:1 CO:O2 atmosphere, TiO2 support reduction was not observed, and a pre-reduced surface was re-oxidized. The consequences of these results for the
understanding of the CO oxidation mechanism on Au/TiO2 (model) catalysts are discussed. 相似文献
108.
Development of Diaminoquinazoline Histone Lysine Methyltransferase Inhibitors as Potent Blood‐Stage Antimalarial Compounds
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Dr. Sandeep Sundriyal Dr. Nicholas A. Malmquist Dr. Joachim Caron Scott Blundell Dr. Feng Liu Xin Chen Nitipol Srimongkolpithak Prof. Jian Jin Prof. Susan A. Charman Prof. Artur Scherf Dr. Matthew J. Fuchter 《ChemMedChem》2014,9(10):2360-2373
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. 相似文献
109.
Chandolia RK Luetjens CM Wistuba J Yeung CH Nieschlag E Simoni M 《Reproduction (Cambridge, England)》2006,132(2):355-363
Data on pubertal maturation in male marmoset, a model for human reproduction, are scant and conflicting. We collected data on novel parameters to characterize puberty. Twenty-five marmoset monkeys were assigned to five age groups by weeks (wk): 21 (pre-pubertal), 43 (onset of puberty), 52 (fully pubertal), 70 (mature), and 116 (fully adult). Serum and intratesticular testosterone and pituitary bioactive chorionic gonadotropin (bioCG) were measured. Testicular development was assessed by ultrasonography, histology, and flow cytometry. Three consecutive blood samples revealed extreme fluctuations in testosterone concentrations, suggesting an erratic secretion. Age-related changes in serum testosterone and pituitary bioCG concentrations were observed. Intratesticular androgens (ITAs) showed high fluctuations within groups at all ages and were high in some animals by 21 wk. Unexpectedly, no correlation between pituitary bioCG and serum testosterone or ITAs was found, but these parameters significantly correlated with testicular weight and volume. These observations were consistent a dependence on the testis growth on bioCG. Unfortunately, the low serum levels of bioCG were not measurable in this study. At 43 wk, the animals reached puberty. At 52 wk of age, animals attained maximum body and epididymal weights and qualitatively normal spermatogenesis, but testes continued growing, reaching a maximum of all parameters at 70 wk of age, without further major changes at the age of 116 wk. It is concluded that (1) gonadal activation is evident at wk 21, (2) the male marmoset reaches the pubertal threshold around 43 wk of age, attains qualitative parameters at 52 wk, matures further to sexual maturity at 70 wk, and (3) serum testosterone and ITAs are highly variable without any identifiable correlation with pituitary bioCG. 相似文献
110.
Siegfried Hring Dieter Kleine Joachim Ulbricht 《Advanced Synthesis \u0026amp; Catalysis》1978,320(3):473-481
On the Free Radical Copolymerization of Unsaturated Isocyanates with Vinylchloride The free radical copolymerization of vinyl-, isopropenyl- and p-vinyl-phenylisocyanate with vinylchloride in mass and tetrahydrofurane solution at 50°C is investigated. The incorporation of the isocyanate monomers in the copolymers is favoured. These monomers effect a great decrease of the rate of copolymerization and a crosslinking of the formed homo- and copolymers, whose extent depends on the kind and the quantity of the incorporated monomers. The crosslinking is caused by the forming of isocyanurate units. 相似文献