Multi-Polluntant Emission Control of Electric Power Plants

In contrast to past regulations for power plant air pollutants, there is a growing interest in a multi-pollutant perspective that would simultaneously address criteria pollutants, air toxics, and greenhouse gases

The active conformation of plasminogen activator inhibitor 1, a target for drugs to control fibrinolysis and cell adhesion

AbstractBackground: Plasminogen activator inhibitor 1 (PAI-1) is a serpin that has a key role in the control of fibrinolysis through proteinase inhibition. PAI-1 also has a role in regulating cell adhesion processes relevant to tissue remodeling and metastasis; this role is mediated by its binding to the adhesive glycoprotein vitronectin rather than by proteinase inhibition. Active PAI-1 is metastable and spontaneously transforms to an inactive latent conformation. Previous attempts to crystallize the active conformation of PAI-1 have failed.Results: The crystal structure of a stable quadruple mutant of PAI-1(Asn150→His, Lys154→Thr, Gln319→Leu, Met354→Ile) in its active conformation has been solved at a nominal 3 Å resolution. In two of four independent molecules within the crystal, the flexible reactive center loop is unconstrained by crystal-packing contacts and is disordered. In the other two molecules, the reactive center loop forms intimate loop–sheet interactions with neighboring molecules, generating an infinite chain within the crystal. The overall conformation resembles that seen for other active inhibitory serpins.Conclusions: The structure clarifies the molecular basis of the stabilizing mutations and the reduced affinity of PAI-1, on cleavage or in the latent form, for vitronectin. The infinite chain of linked molecules also suggests a new mechanism for the serpin polymerization associated with certain diseases. The results support the concept that the reactive center loop of an active serpin is flexible and has no defined conformation in the absence of intermolecular contacts. The determination of the structure of the active form constitutes an essential step for the rational design of PAI-1 inhibitors

A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization

Several lines of evidence suggest a link between the alpha7 neuronal nicotinic acetylcholine receptor (nAChR) and brain disorders including schizophrenia, Alzheimer's disease, and traumatic brain injury. The present work describes a novel molecule, 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596), which acts as a powerful positive allosteric modulator of the alpha7 nAChR. Discovered in a high-throughput screen, PNU-120596 increased agonist-evoked calcium flux mediated by an engineered variant of the human alpha7 nAChR. Electrophysiology studies confirmed that PNU-120596 increased peak agonist-evoked currents mediated by wild-type receptors and also demonstrated a pronounced prolongation of the evoked response in the continued presence of agonist. In contrast, PNU-120596 produced no detectable change in currents mediated by alpha4beta2, alpha3beta4, and alpha9alpha10 nAChRs. PNU-120596 increased the channel mean open time of alpha7 nAChRs but had no effect on ion selectivity and relatively little, if any, effect on unitary conductance. When applied to acute hippocampal slices, PNU-120596 increased the frequency of ACh-evoked GABAergic postsynaptic currents measured in pyramidal neurons; this effect was suppressed by TTX, suggesting that PNU-120596 modulated the function of alpha7 nAChRs located on the somatodendritic membrane of hippocampal interneurons. Accordingly, PNU-120596 greatly enhanced the ACh-evoked inward currents in these interneurons. Systemic administration of PNU-120596 to rats improved the auditory gating deficit caused by amphetamine, a model proposed to reflect a circuit level disturbance associated with schizophrenia. Together, these results suggest that PNU-120596 represents a new class of molecule that enhances alpha7 nAChR function and thus has the potential to treat psychiatric and neurological disorders

Conventionally trapped natural gas accumulations in the Jurassic tight sandstone reservoirs: A case study from the Center of the Western Sichuan Basin, SW China

Tight gas accumulations, commonly characterized by low permeability, low porosity, and complicated pore structure, are widely distributed in the Sichuan Basin. Recent exploration in the Chengdu Sag, Western Sichuan Basin has proven that Jurassic tight-sandstone reservoirs attach significant gas potential. However, long distance migration between source and reservoir intervals entangles understanding of the tight-gas accumulation mechanism. It is unclear whether producible gas in Jurassic intervals is either from “simple sweet-spots in a continuous accumulation” or “conventionally trapped accumulations in low-permeability reservoir rocks”. To identify the regionally active gas system and characterize the charging pattern, a geochemical study was performed by interpreting the gas molecular and carbon isotope compositions in Jurassic and conducting gas–source correlations as well as gas migration distance calculation with the relationship among δ 13 C 1 vs. R o vs. H (burial depth). Research results indicate that the Jurassic tight gases in Majing-Shifang areas are coal-derived dry gases generated by the primary cracking of kerogen. Gas/source correlation and gas migration distance calculation reveal that gases are mainly sourced from the Upper Triassic humic source rocks (T 3 x 5 , the fifth member of the Xujiahe Formation). Gas accumulations in the Jurassic Penglaizhen Formation were formed with an original vertical migration of about 2–3 km and then a long-distance lateral migration within tight sand layers, which is verified by the decreasing δ 13 C 1 and the general increasing i C 4 / n C 4 in the Penglaizhen Formation. The Jurassic tight-sandstone reservoirs in Majing-Shifang areas occur in low-porosity and low-permeability reservoir rocks in conventional lithological traps, which are not continuous-type gas accumulations or basin-centered gas systems. The faults in Majing area serve as dominant vertical conducting pathway and the relatively permeable intervals within Jurassic and microfractures play an important role in the development of the conventionally trapped natural gas accumulations