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The low permeability of coal seams is a constraint in the efficient production of coalbed methane. However, the presence of natural fractures in coal enhances the permeability, and prior knowledge of sub‐surface fractures in coal seams is vital to identify the prospective seam. This paper investigates the anisotropy and identifies fractures by processing the advanced sonic and resistivity image logs to mitigate challenges in the reservoir. Anisotropy is estimated from the difference in the travel time between fast and slow shear waves. The application of Alford's rotation technique determines the fast shear wave polarization angle which is consistent with the fracture orientation along the NE–SW or NW–SE direction in coal seams. Moreover, the crossover of fast and slow shear waves in the slowness versus frequency plot indicates stress‐induced anisotropy that originates from fractures. Besides, drilling‐induced fractures observed along NE–SW in the resistivity image log indicate the maximum horizontal stress direction. Results from this study compare coal seams based on fractures in adopting better operational activities for optimized production and future geomechanical studies in the Bokaro coalfield situated in India. [ABSTRACT FROM AUTHOR]

The production of coalbed methane gas depends upon various factors such as permeability, gas content, gas saturation and seam thickness. The low permeability in coal is a constraint in the gas extraction process. However, the presence of natural fractures and cleats in coal increases the permeability; therefore, its identification is necessary to establish the prospectivity. Hence, a methodology is used to process the Stoneley waveform in the Bokaro coalfield located in India to obtain slowness magnitude from the semblance analysis. The separation of directly transmitted and reflected Stoneley waves determines the reflection coefficient and attenuation, and its analysis emphasizes the presence of fractures. In coal seams, the average reflection coefficient ranges from 0.42 to 2.44 and attenuation ranges from 0.2 dB to 12.68 dB. The Stoneley slowness versus frequency plot shows a constant slowness with increasing frequency in the non‐fractured seams, whereas a dispersive trend is observed in the fractured seams. Fractures are also distinguished from the cross‐plot of compressional/shear versus Stoneley velocity. The observation of higher reflection coefficient, attenuation and slowness‐frequency dispersion in coal seams indicates extensive fractures/cleats that corroborate with the resistivity image log correlation. Thus, the study helps to distinguish between fractured and non‐fractured coal seams from the integrated approach of reflection coefficient, attenuation and dispersion analysis of Stoneley waves supported by the identification of fractures from resistivity image log for optimization in coalbed methane production in the development phase. [ABSTRACT FROM AUTHOR]

The structural and functional consequences of positively charged, negatively charged, and neutral groups incorporated at the para position of benzenesulfonamide carbonic anhydrase (CA) inhibitors are reported. The results have indicated that positively charged moieties should be avoided in the design of linker segments and such charges are more poorly tolerated by CA I when compared to CA II.

The recombinant form of human carbonic anhydrase-II is utilized as the enzyme source and benzenesulfonamide and its derivatives as inhibitors. The steady-state kinetics revealed that the attachment of iminodiacetate (IDA)-Cu(super 2+) to benzenesulfonamide enhanced its binding affinity for hCA-II by about 40-fold.

The atomic-resolution crystal structures of human carbonic anhydrases I and II complexed with 'two-prong' inhibitors are described, where each inhibitor has a benzenesulfonamide prong and a cupric iminodiacetate prong separated by linkers of different lengths and compositions. The results provide the first evidence verifying the structural basis of nanometer affinity measured for two-prong inhibitors targeting the carbonic anhydrases.

Arguments on detailed structural-functional investigations of enzymes-ligand interactions are presented that might provide insights into designing the isozyme-specific inhibitors of carbonic anhydrases (CAs). The experimental data provides a detailed account of the microscopic pathways for the binding of dansylamide to the active sites of human carbonic anhydrrase I (hCA I) and II (hCA II).

Two 'two-prong' ligands, L1 and L2, were synthesized by attaching iminodiacetate (IDA)-bound Cu2(super +2) to benzenesulfonamide via different chain length spacers and their binding affinities were compared with their parent compounds for recombinant human carbonic anhydrase I (hCA-I). The results indicate that differential binding of L1 versus L2 to hCA-I is encoded in the chain length of the spacer moiety.

A general strategy of inhibitor design, which overcomes the limitation of the active-site based design alone, is described. The studies state that in the two-prong approach the binding energy of the inhibitors are derived not only from the interaction at the active site region but also from the interactions of IDA-Cu (super 2+) to the surface exposed histidire residues.

5-Hydroxydecanoate (5-HD) blocks pharmacological and ischaemic preconditioning, and has been postulated to be a specific inhibitor of mitochondrial ATP-sensitive K+ (KATP) channels. However, recent work has shown that 5-HD is activated to 5-hydroxydecanoyl-CoA (5-HD-CoA), which is a substrate for the first step ofβ-oxidation. We have now analysed the completeβ-oxidation of 5-HD-CoA using specially synthesised (and purified) substrates and enzymes, as well as isolated rat liver and heart mitochondria, and compared it with the metabolism of the physiological substrate decanoyl-CoA. At the second step ofβ-oxidation, catalysed by enoyl-CoA hydratase, enzyme kinetics were similar using either decenoyl-CoA or 5-hydroxydecenoyl-CoA as substrate. The last two steps were investigated using l-3-hydroxyacyl-CoA dehydrogenase (HAD) coupled to 3-ketoacyl-CoA thiolase.Vmax for the metabolite of 5-HD (3,5-dihydroxydecanoyl-CoA) was fivefold slower than for the corresponding metabolite of decanoate (l-3-hydroxydecanoyl-CoA). The slower kinetics were not due to accumulation ofd-3-hydroxyoctanoyl-CoA since this enantiomer did not inhibit HAD. Molecular modelling of HAD complexed with 3,5-dihydroxydecanoyl-CoA suggested that the 5-hydroxyl group could decrease HAD turnover rate by interacting with critical side chains. Consistent with the kinetic data, 5-hydroxydecanoyl-CoA alone acted as a weak substrate in isolated mitochondria, whereas addition of 100μm5-HD-CoA inhibited the metabolism of decanoyl-CoA or lauryl-carnitine. In conclusion, 5-HD is activated, transported into mitochondria and metabolised viaβ-oxidation, albeit with rate-limiting kinetics at the penultimate step. This creates a bottleneck forβ-oxidation of fatty acids. The complex metabolic effects of 5-HD invalidate the use of 5-HD as a blocker of mitochondrial KATP channels in studies of preconditioning. [ABSTRACT FROM AUTHOR]

We offer a novel methodology for formulating liposomes by incorporating sequence-specific collagen-mimetic peptides such that they are specifically "uncorked" by a matrix metalloproteinase, MMP-9. By encapsulating carboxyfluorescein (as a self-quenching fluorescent dye), we demonstrate that the time-dependent release of the dye from liposomes is due to the specific enzymatic cleavage of the surface-exposed collagen-mimetic peptides. The specificity of such cleavage is attested by the fact that the liposomal "uncorking" and their content release occur only by MMP-9 and not by a general proteolytic enzyme, trypsin, despite the fact that the collagen mimetic peptides contain the trypsin cleavage site. The mechanistic details underlying the formulations of liposomes and their enzyme-selective "uncorking" and content release are discussed. Arguments are presented that such liposomes can be fine-tuned to serve as the drug delivery vehicles for the detection and treatment of various human diseases, which occur due to the overexpression of a variety of pathogenic matrix metalloproteinases.

5-Hydroxydecanoate (5-HD) blocks pharmacological and ischaemic preconditioning, and has been postulated to be a specific inhibitor of mitochondrial ATP-sensitive K(+) (K(ATP)) channels. However, recent work has shown that 5-HD is activated to 5-hydroxydecanoyl-CoA (5-HD-CoA), which is a substrate for the first step of beta-oxidation. We have now analysed the complete beta-oxidation of 5-HD-CoA using specially synthesised (and purified) substrates and enzymes, as well as isolated rat liver and heart mitochondria, and compared it with the metabolism of the physiological substrate decanoyl-CoA. At the second step of beta-oxidation, catalysed by enoyl-CoA hydratase, enzyme kinetics were similar using either decenoyl-CoA or 5-hydroxydecenoyl-CoA as substrate. The last two steps were investigated using l-3-hydroxyacyl-CoA dehydrogenase (HAD) coupled to 3-ketoacyl-CoA thiolase. V(max) for the metabolite of 5-HD (3,5-dihydroxydecanoyl-CoA) was fivefold slower than for the corresponding metabolite of decanoate (l-3-hydroxydecanoyl-CoA). The slower kinetics were not due to accumulation of d-3-hydroxyoctanoyl-CoA since this enantiomer did not inhibit HAD. Molecular modelling of HAD complexed with 3,5-dihydroxydecanoyl-CoA suggested that the 5-hydroxyl group could decrease HAD turnover rate by interacting with critical side chains. Consistent with the kinetic data, 5-hydroxydecanoyl-CoA alone acted as a weak substrate in isolated mitochondria, whereas addition of 100 mum 5-HD-CoA inhibited the metabolism of decanoyl-CoA or lauryl-carnitine. In conclusion, 5-HD is activated, transported into mitochondria and metabolised via beta-oxidation, albeit with rate-limiting kinetics at the penultimate step. This creates a bottleneck for beta-oxidation of fatty acids. The complex metabolic effects of 5-HD invalidate the use of 5-HD as a blocker of mitochondrial K(ATP) channels in studies of preconditioning.