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The ionomer state in the catalyst ink of a proton exchange membrane fuel cell (PEMFC) plays a critical role in the formation of the catalyst/ionomer interface on the catalyst layer (CL). In this study, the effect of ionomer dispersion state on catalyst ink dispersion and the construction of a reasonable CL was investigated. The study of catalyst inks revealed that the dispersion of n-propanol (NPA) -ionomer dispersion or sonication could effectively reduce the catalyst particle size in inks. For shear-dispersion and homogenizer-dispersion inks, the catalyst particle size was reduced from 6.17 nm to 5.12 nm and from 5.12 nm to 4.67 nm, respectively. The ionomer dispersion was capable of significantly reducing the size of agglomerates in the ink, which resulted in a reduction in the particle size of agglomerates on the surface of the cathode CL and an improvement in its flatness. The pore size distributions of the MEA cathode catalyst layers showed that water bath ultrasonic treatment of the ionomer could result in a more reasonable pore structure for the catalyst layer. The single-cell test revealed that changing the ionomer's dispersion state could significantly increase the fuel cell's output voltage to 0.707 V at 1000 mA cm−2, and the cell's power density to 1028 mW cm−2 at 2000 mA cm−2.

SAR in the previously described spirocyclic ROMK inhibitor series was further evolved from lead 4 by modification of the spirocyclic core and identification of novel right-side pharmacophores. In this process, it was discovered that the spiropyrrolidinone core with the carbonyl group α to the spirocenter was preferred for potent ROMK activity. Efforts aimed at decreasing hERG affinity within the series led to the discovery of multiple novel right-hand pharmacophores including 3-methoxythiadiazole, 2-methoxypyrimidine, and pyridazinone. The most promising candidate is pyridazinone analog 32 that showed an improved functional hERG/ROMK potency ratio and preclinical PK profile. In vivo evaluation of 32 demonstrated blood pressure lowering effects in the spontaneously hypertensive rat model.

A spirocyclic class of ROMK inhibitors was developed containing a structurally diverse heterocyclic sulfone moiety and spirocyclic core starting from lead 1. These compounds not only displayed exquisite ROMK potency but significantly improved selectivity over hERG. The lead compounds were found to have favorable pharmacokinetic properties and displayed robust diuretic, natriuretic and blood pressure lowering effects in spontaneously hypertensive rats.

Following the discovery of small molecule acyl piperazine ROMK inhibitors, the acyl octahydropyrazino[2,1-c][1,4]oxazine series was identified. This series displays improved ROMK/hERG selectivity, and as a consequence, the resulting ROMK inhibitors do not evoke QTc prolongation in an in vivo cardiovascular dog model. Further efforts in this series led to the discovery of analogs with improved pharmacokinetic profiles. This new series also retained comparable ROMK potency compared to earlier leads.

In this study, we provide a photocurable chitosan bioink (CHI-MA), which can be used for the digital light processing (DLP) technology. The CHI-MA precursors were facilely synthesized by grafting chitosan molecular chains with methacryloyl groups. We investigated the effect of parameters, including the concentration and substitution degree (DS) of CHI-MA, on the rheology and the photocuring of bioinks and the mechanical property of photo-crosslinked gels. Using the CHI-MA with a high DS (33.6 %), the curing time to print a 150 μm thick hydrogel layer can be controlled within a reasonable short time period. Additionally, the cytotoxicity test shows that both the photocuring process and the photo-crosslinked hydrogels exhibit an excellent biocompatibility. Through the DLP printing, the CHI-MA bioink can be processed into complex 3D hydrogel structures with high-resolution, high-fidelity and good biocompatibility. It indicates that the photocurable CHI-MA would be a good bioink suitable for the DLP printing.

Weak machinery fault detection is a difficult task because of two main reasons (1) At the early stage of fault development, signature of fault related component performs incompletely and is quite different from that at the apparent failure stage. In most instances, it seems almost identical with the normal operating state. (2) The fault feature is always submerged and distorted by relatively strong background noise and macro-structural vibrations even if the fault component already performs completely, especially when the structure of fault components and interference are close. To solve these problems, we should penetrate into the underlying structure of the signal. Sparse representation provides a class of algorithms for finding succinct representations of signal that capture higher-level features in the data. With the purpose of extracting incomplete or seriously overwhelmed fault components, a sparse representation based latent components decomposition method is proposed in this paper. As a special case of sparse representation, shift-invariant sparse coding algorithm provides an effective basis functions learning scheme for capturing the underlying structure of machinery fault signal by iteratively solving two convex optimization problems: an L1-regularized least squares problem and an L2-constrained least squares problem. Among these basis functions, fault feature can be probably contained and extracted if optimal latent component is filtered. The proposed scheme is applied to analyze vibration signals of both rolling bearings and gears. Experiment of accelerated lifetime test of bearings validates the proposed method׳s ability of detecting early fault. Besides, experiments of fault bearings and gears with heavy noise and interference show the approach can effectively distinguish subtle differences between defect and interference. All the experimental data are analyzed by wavelet shrinkage and basis pursuit de-noising (BPDN) method for comparison.

A sub-class of distinct small molecule ROMK inhibitors were developed from the original lead 1. Medicinal chemistry endeavors led to novel ROMK inhibitors with good ROMK functional potency and improved hERG selectivity. Two of the described ROMK inhibitors were characterized for the first in vivo proof-of-concept biology studies, and results from an acute rat diuresis model confirmed the hypothesis that ROMK inhibitors represent new mechanism diuretic and natriuretic agents.