Nonregular Abnormal Extremals of 2-Distribution: Existence, Second Variation, and Rigidity

We study existence and rigidity (W ¹ -isolatedness) of nonregular abnormal extremals of completely nonholonomic 2-distribution (nonregularity means that such extremals do not satisfy the strong generalized Legendre–Clebsch condition). Introducing the notion of diagonal form of the second variation, we generalize some results of A. Agrachev and A. Sarychev about rigidity of regular abnormal extremals to the nonregular case. In order to reduce the second variation to the diagonal form, we construct a special curve of Lagrangian subspaces, a Jacobi curve. We show that certain geometric properties of this curve (like simplicity) imply the rigidity of the corresponding abnormal extremal.     

Nitrate Esters of Heteroaromatic Compounds as Candida albicans CYP51 Enzyme Inhibitors

Four heteroaromatic compounds bearing nitrate esters were selected using a virtual‐screening procedure as putative sterol 14α‐demethylase (CYP51) Candida albicans inhibitors. Compounds were examined for their inhibition on C. albicans growth and biofilm formation as well as for their toxicity. NMR spectroscopy studies, in silico docking, and molecular dynamics simulations were used to investigate further the selectivity of these compounds to fungal CYP51. All compounds exhibited good antimicrobial properties, indicated with low minimal inhibitory concentrations and ability to inhibit formation of fungal biofilm. Moreover, all of the compounds had the ability to inhibit growth of C. albicans cells. N‐(2‐Nitrooxyethyl)‐1Η‐indole‐2‐carboxamide was the only compound with selectivity on C. albicans CYP51 that did not exhibit cytotoxic effect on cells isolated from liver and should be further investigated for selective application in new leads for the treatment of candidiasis.     

Protease activity of 1,10-phenanthroline-copper(I). Targeted scission of the catalytic site of carbonic anhydrase

To investigate the mechanism of scission of proteins by the chemical cleaving agent 1,10-phenanthroline-copper, the active sites of human carbonic anydrase I and bovine carbonic anhydrase II have been targeted for cleavage by a tight binding sulfonamide inhibitor tethered to the metal complex. The inhibitor-phenanthroline-copper conjugate binds to the carbonic anhydrases with sub-micromolar Kd's and, upon addition of a reducing agent, causes scission specifically within the active site of the enzymes to yield a discrete set of cleavage fragments. N- and C-terminal sequencing and mass spectrometric analysis of several fragments indicate that the C-terminal cleavage fragments have free amino groups at their N termini, thereby allowing facile location of the cut sites through standard Edman degradation. The N-terminal cleavage fragments do not have a free carboxyl group at their C termini. It is proposed that scission occurs by abstraction of H at Calpha, followed by oxidation at Calpha by the neighboring cupric ion and cleavage of the Calpha-C(O) bond to give an N-terminal fragment containing a C-terminal acyl amide, and an unstable C-terminal fragment containing an N-terminal isocyanate group which undergoes hydrolysis to a free amino terminus. Modeling of the inhibitor-phenanthroline-copper conjugate within the active site of human carbonic anhydrase I shows that the sites of cleavage that have been identified are fully consistent with the available structural data.     

Bore wear caused by firing steel monoblock bullets

The peculiar character of bore wear by steel monoblock bullets is presented. An effect of the turbulence of propellant gas with erosion particles on the wear of the near-surface bore layers in the process of firing is discovered.