Regularized numerical integration of multibody dynamics with the generalized method

This paper discusses the consistent regularization property of the generalized α method when applied as an integrator to an initial value high index and singular differential-algebraic equation model of a multibody system. The regularization comes from within the discretization itself and the discretization remains consistent over the range of values the regularization parameter may take. The regularization involves increase of the smallest singular values of the ill-conditioned Jacobian of the discretization and is different from Baumgarte and similar techniques which tend to be inconsistent for poor choice of regularization parameter. This regularization also helps where pre-conditioning the Jacobian by scaling is of limited effect, for example, when the scleronomic constraints contain multiple closed loops or singular configuration or when high index path constraints are present. The feed-forward control in Kane’s equation models is additionally considered in the numerical examples to illustrate the effect of regularization. The discretization presented in this work is adopted to the first order DAE system (unlike the original method which is intended for second order systems) for its A-stability and same order of accuracy for positions and velocities.     

Confinement and phase transitions

Using a density dependent quark mass to express non-perturbative interaction effects, we calculate the critical density for a phase transition between nuclear and quark matter atT=0.     

An example of a regular space that is not completely regular

A simpler example of regular space that is not completely regular is attempted.     

Chromatographic and spectral investigations on the in vivo metabolites of 6-nitrobenzo[a]pyrene

6-Nitrobenzo[a]pyrene (6-NBaP) occurs in the environment, is mutagenic in the Ames assay in the presence of added S9 and is carcinogenic to male but not female mouse liver when injected intraperitoneally (i.p.) into mice. In order to understand what kinds of active metabolites could have been produced in vivo, both male and female mice were injected i.p. with 6-NBaP in dimethyl sulfoxide. Twenty-four hours after injection, urine, feces, blood, liver and spleen (non-target tissue) were examined for metabolites by chromatographic and high-resolution mass spectral means. On the basis of the mass spectral fragmentation patterns of synthetic and metabolic standards, it was observed that both male and female animals excreted ring-hydroxylated metabolites of 6-NBaP in the urine to differing extents. Male animals additionally excreted 6-aminobenzo[a]pyrene and the significance of this observation is discussed.     

Processing multimode binding situations in simulation-based prediction of ligand-macromolecule affinities

The linear response (LR) approximation and similar approaches belong to practical methods for estimation of ligand-receptor binding affinities. The approaches correlate experimental binding affinities with the changes upon binding of the ligand electrostatic and van der Waals energies and of solvation characteristics. These attributes are expressed as ensemble averages that are obtained by conformational sampling of the protein-ligand complex and of the free ligand by molecular dynamics or Monte Carlo simulations. We observed that outliers in the LR correlations occasionally exhibit major conformational changes of the complex during sampling. We treated the situation as a multimode binding case, for which the observed association constant is the sum of the partial association constants of individual states/modes. The resulting nonlinear expression for the binding affinities contains all the LR variables for individual modes that are scaled by the same two to four adjustable parameters as in the one-mode LR equation. The multimode method was applied to inhibitors of a matrix metalloproteinase, where this treatment improved the explained variance in experimental activity from 75% for the unimode case to about 85%. The predictive ability scaled accordingly, as verified by extensive cross-validations.     

Ruthenium and osmium carbonyl clusters incorporating stannylene and stannyl ligands

The reaction of [Ru(3)(CO)(12)] with Ph(3)SnSPh in refluxing benzene furnished the bimetallic Ru-Sn compound [Ru(3)(CO)(8)(mu-SPh)(2)(mu(3)-SnPh(2))(SnPh(3))(2)] which consists of a SnPh(2) stannylene bonded to three Ru atoms to give a planar tetra-metal core, with two peripheral SnPh(3) ligands. The stannylene ligand forms a very short bond to one Ru atom [Sn-Ru 2.538(1) A] and very long bonds to the other two [Sn-Ru 3.074(1) A]. The germanium compound [Ru(3)(CO)(8)(mu-SPh)(2)(mu(3)-GePh(2))(GePh(3))(2)] was obtained from the reaction of [Ru(3)(CO)(12)] with Ph(3)GeSPh and has a similar structure to that of as evidenced by spectroscopic data. Treatment of [Os(3)(CO)(10)(MeCN)(2)] with Ph(3)SnSPh in refluxing benzene yielded the bimetallic Os-Sn compound [Os(3)(CO)(9)(mu-SPh)(mu(3)-SnPh(2))(MeCN)(eta(1)-C(6)H(5))] . Cluster has a superficially similar planar metal core, but with a different bonding mode with respect to that of . The Ph(2)Sn group is bonded most closely to Os(2) and Os(3) [2.786 and 2.748 A respectively] with a significantly longer bond to Os(1), 2.998 A indicating a weak back-donation to the Sn. The reaction of the bridging dppm compound [Ru(3)(CO)(10)(mu-dppm)] with Ph(3)SnSPh afforded [Ru(3)(CO)(6)(mu-dppm)(mu(3)-S)(mu(3)-SPh)(SnPh(3))] . Compound contains an open triangle of Ru atoms simultaneously capped by a sulfido and a PhS ligand on opposite sides of the cluster with a dppm ligand bridging one of the Ru-Ru edges and a Ph(3)Sn group occupying an axial position on the Ru atom not bridged by the dppm ligand.     

Epigenetic Modifiers Affect the Bioactive Compounds Secreted by an Endophyte of the Tropical Plant Piper longum

Seven endophytic fungi were isolated from the tropical medicinal plant Piper longum L. After preliminary screening, Phomopsis heveicola was selected for the epigenetic activation treatments. The antibacterial, antifungal, and antioxidant potentials of crude extracts obtained from the treatments (with and without epigenetic modifiers) were analyzed in vitro. The extracts inhibited growth of the human pathogens Pseudomonas aeruginosa, Shigella sonnei, Streptococcus pyogenes, and Salmonella typhi, as well as the phytopathogens Puccinia recondita, Rhizoctonia solani, Phytophthora infestans, and Botrytis cinerea. Furthermore, DPPH-scavenging activity was higher in valproic acid treated extracts. Volatile chemicals with known biological activities (measured with GC-MS/MS), were released in the valproic acid treatment. The antimicrobial potentials of the extracts were confirmed using MRM/MS analysis. The experiments revealed a new promising endophytic fungus, P. heveicola, to be utilized in biological plant protection and in biomedical applications.     

Antimicrobial Activity of Dihydroisocoumarin Isolated from Wadi Lajab Sediment-Derived Fungus Penicillium chrysogenum: In Vitro and In Silico Study

Antibiotic resistance is considered a major health concern globally. It is a fact that the clinical need for new antibiotics was not achieved until now. One of the most commonly prescribed classes of antibiotics is β-Lactam antibiotics. However, most bacteria have developed resistance against β-Lactams by producing enzymes β-Lactamase or penicillinase. The discovery of new β-Lactamase inhibitors as new antibiotics or antibiotic adjuvants is essential to avoid future catastrophic pandemics. In this study, five dihydroisocoumarin: 6-methoxy mellein (1); 5,6-dihydroxymellein (2); 6-hydroxymellein (3); 4-chloro-6-hydroxymellein (4) and 4-chloro-5,6-di-hydroxymellein (5) were isolated from Wadi Lajab sediment-derived fungus Penicillium chrysogenum, located 15 km northwest of Jazan, KSA. The elucidation of the chemical structures of the isolated compounds was performed by analysis of their NMR, MS. Compounds 1–5 were tested for antibacterial activities against Gram-positive and Gram-negative bacteria. All of the compounds exhibited selective antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Bacillus licheniformis except compound 3. The chloro-dihydroisocoumarin derivative, compound 4, showed potential antimicrobial activities against all of the tested strains with the MIC value between 0.8–5.3 μg/mL followed by compound 5, which exhibited a moderate inhibitory effect. Molecular docking data showed good affinity with the isolated compounds to β-Lactamase enzymes of bacteria; NDM-1, CTX-M, OXA-48. This work provides an effective strategy for compounds to inhibit bacterial growth or overcome bacterial resistance.