Prostate-specific membrane antigen (PSMA) is an excellent biomarker for the early diagnosis of prostate cancer progression and metastasis. The most promising PSMA-targeted agents in the clinical phase are based on the Lys−urea−Glu motif, in which Lys and Glu are α-(L)-amino acids. In this study, we aimed to determine the effect of βand γ-amino acids in the S1 pocket on the binding affinity for PSMA. We synthesized and evaluated the βand γ-amino acid analogues with (S)-or (R)-configuration with keeping α-(L)-Glu as the S1′-binding pharmacophore. The structure−activity relationship studies identified that compound 13c, a β-amino acid analogue with (R)-configuration, exhibited the most potent PSMA inhibitory activity with an IC 50 value of 3.97 nM. The X-ray crystal structure of PSMA in complex with 13c provided a mechanistic basis for the stereochemical preference of PSMA, which can guide the development of future PSMA inhibitors.
An inexpensive and effective technique based on machine learning (ML) algorithms with impedance characterization to sense and classify mixed gases is presented. Specifically, this method demonstrates that ML algorithms can distinguish hidden and valuable feature information such as different gas molecules from surface‐charged activated carbon fibers. The feature information used for ML is obtained by measuring the impedance and fitting the measured values to an equivalent circuit model. The mixed gases are classified using such feature information to train various automatic classifiers. The collected data consist of the resistances and capacitances extracted from best fitting results in Cole–Cole plots, and they are 5D vectors. The data processed with unsupervised learning are clustered, evaluated with Silhouette scores, and then the unique hidden patterns of individual gases in the mixed gases are obtained. When the supervised ML algorithm, k‐nearest neighbor classifier, is used for the analytical features, all combinations of gases have 94% classification accuracy, demonstrating the superiority of the proposed technique.
The formation of titanium carbonitride has been used as a conventional method to protect the refractory wear in the hearth. Because titanium carbonitride is formed only in the molten iron, the area that can form a protective layer in the hearth is limited. There is another possibility to protect the refractory wear by introducing the compounds with high melting point in the slags. If the compounds with high melting point are simultaneously formed in the molten iron and slag by adding TiO2, it might be more effective to form the protective layer and to prevent the refractory wear of hearth. However, the change of slag compositions and the formation of slag compounds can affect the slag viscosity and critical temperature, which might cause serious problems with blast furnace operation.In this study, to find the slag compositions for the effective compounds formation with maintaining the slag fluidity, the viscosity measurements, in-situ observation of compound formation by a confocal laser scanning microscopy and thermodynamical evaluation by FactSage has been carried out. Based on these results, the suitable slag compositions were suggested to form a protective layer in the hearth.
BackgroundSuspension ligamentoplasty using abductor pollicis longus (APL) tendon without bone tunneling, was introduced as one of the techniques for treatment of advanced first carpometacarpal (CMC) arthritis. The purpose of this study was to evaluate the radiologic and clinical results of APL suspension ligamentoplasty.MethodsThe medical records of 19 patients who underwent APL suspension ligamentoplasty for advanced first CMC arthritis between January 2008 and May 2012 were reviewed retrospectively. The study included 13 female and 6 male patients, whose mean age was 62 years (range, 43 to 82 years). For clinical evaluation, we assessed the grip and pinch power, radial and volar abduction angle, thumb adduction (modified Kapandji index), including visual analogue scale (VAS) and Disabilities of the Arm, Shoulder and Hand (DASH) scores. Radiologic evaluation was performed using simple radiographs.ResultsThe mean follow-up was 36 months (range, 19 to 73.7 months). Mean power improved from 18.3 to 27 kg for grip power, from 2.8 to 3.5 kg for tip pinch, and from 4.3 to 5.4 kg for power pinch. All patients showed decreased VAS from 7.2 to 1.7. Radial abduction improved from 71° preoperatively to 82° postoperatively. The modified Kapandji index showed improvement from 6 to 7.3, and mean DASH was improved from 41 to 17.8. The height of the space decreased from 10.8 to 7.1 mm. Only one case had a complication involving temporary sensory loss of the first dorsal web space, which resolved spontaneously.ConclusionsThe APL suspension ligamentoplasty for treatment of advanced first CMC arthritis yielded satisfactory functional results.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.