Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease and P. falciparum Malaria

Significantly more potent second generation 4-amino-7-chloroquinoline (4,7-ACQ) based inhibitors of the botulinum neurotoxin serotype A (BoNT/A) light chain were synthesized. Introducing an amino group at the C(3) position of the cholate component markedly increased potency (IC50 values for such derivatives ranged from 0.81 to 2.27 mu M). Two additional subclasses were prepared: bis(steroidal)-4,7-ACQ derivatives and bis(4,7-ACQ)cholate derivatives; both classes provided inhibitors with nanomolar-range potencies (e.g., the K-i of compound 67 is 0.10 mu M). During BoNT/A challenge using primary neurons, select derivatives protected SNAP-25 by up to 89%. Docking simulations were performed to rationalize the compounds' in vitro potencies. In addition to specific residue contacts, coordination of the enzyme's catalytic zinc and expulsion of the enzyme's catalytic water were a consistent theme. With respect to antimalarial activity, the compounds provided better IC90 activities against chloroquine resistant (CQR) malaria than CQ, and seven compounds were more active than mefloquine against CQR strain W2

Školní atlas 'Dnešní svět'

9

Výškové a souřadnicové systémy v Česku

8

Analýza charakteristiky zkreslení Q na podkladě Eckertových zobrazení

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Temperature-Dependent Recombination Processes in Small-Sized PbSe/PbS Core/Shell Colloidal Quantum Dots

The work focuses on the optical investigation of temperature-dependent recombination processes in small-sized PbSe/PbS core/shell colloidal quantum dots (CQDs) with core diameter of (2 – 2.5) nm and the shell thickness of (0.5 – 1.0) nm under air-free conditions and after air exposure. These CQDs have a tunable absorption edge around 1 μm and a rather narrow photoluminescence linewidth, their emission recombination process is characterized by the μs time-scale and by longer radiative lifetimes in the entire temperature range and especially at low temperatures (a 2.6-fold increase) as compared to the corresponding PbSe samples. The PbSe/PbS core/shell CQDs are oxidation-stable towards time-limited air exposure. <p>DOI: <a href="http://dx.doi.org/10.5755/j01.ms.20.2.6321">http://dx.doi.org/10.5755/j01.ms.20.2.6321</a></p

Transformation of data and information into knowledge in the production enterprise and their use in the sales department

Modern age is associated with massive deployment of information technology in businesses that are forced to work with a wealth of data and information. Businesses are trying to make the most effective use of knowledge not only from real data, but they often have to rely on their employees' knowledge. Increasing fluctuation of employees and the resulting outflow of knowledge will force businesses to increasingly make use of knowledge management. The article describes the process of looking for the context and the implications of selecting contracts to transform them into information and knowledge on the example of a real business. The verified process is transformed into a design of knowledge system, which results in the recommended generated rule for selecting sales department orders to ensure profitability for the business