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A matrix metalloproteinase 1 (MMP-1) inhibitor activity cliff was predicted using the SAR Matrix method. Compound 4 was predicted as a highly potent activity cliff partner and found to possess 60 times higher inhibitory activity against MMP-1 than the structurally related compound 3. Furthermore, pharmacophore fitting of synthesized compounds indicated that the correctly predicted activity cliff was caused by interactions between the trifluoromethyl group at para position in compound 4 and residue ARG214 of MMP-1.To evaluate clinical features and determine rehabilitation strategies of dysphagia, it is crucial to measure the exact response time of the pharyngeal swallowing reflex in a videofluoroscopic swallowing study (VFSS). However, measuring the response time of the pharyngeal swallowing reflex is labor-intensive and particularly for inexperienced clinicians, it can be difficult to measure the brief instance of the pharyngeal swallowing reflex by VFSS. To accurately measure the response time of the swallowing reflex, we present a novel framework, able to detect quick events. In this study, we evaluated the usefulness of machine learning analysis of a VFSS video for automatic measurement of the response time of a swallowing reflex in a pharyngeal phase. In total, 207 pharyngeal swallowing event clips, extracted from raw VFSS videos, were annotated at the starting point and end point of the pharyngeal swallowing reflex by expert clinicians as ground-truth. To evaluate the performance and generalization ability of our model, fivefold cross-validation was performed. The average success rates of detection of the class "during the swallowing reflex" for the training and validation datasets were 98.2% and 97.5%, respectively. The average difference between the predicted detection and the ground-truth at the starting point and end point of the swallowing reflex was 0.210 and 0.056 s, respectively. Therefore, the response times during pharyngeal swallowing reflex are automatically detected by our novel framework. This framework can be a clinically useful tool for estimating the absence or delayed response time of the swallowing reflex in patients with dysphagia and improving poor inter-rater reliability of evaluation of response time of pharyngeal swallowing reflex between expert and unskilled clinicians.A carbonate sample extracted from the depth of about 10 kft was subjected to uniaxial loading while the confining stress remained constant. Post-experiment inspection of the sample showed an inclined crack at an angle less than 20° to the horizontal. This subhorizontal crack orientation was contrary to the expected 45° inclination, the plane of the maximum shear stress. Coincidentally, as shown by CT-scan prior to loading, there was a boundary between two layers of different density inside the sample located almost exactly where the crack appeared. This density difference has arguably translated into the contrast in the elastic properties at the boundary. The hypothesis is that because of this elastic heterogeneity, an incipient crack developed at the boundary due to the unavoidable tensile stressing of the sample as it was brought to the benchtop from its original state of high confining stress at depth. Controlled uniaxial compression made the sample slip along this crack, which then developed into a prominent feature. This assumption was corroborated by a numerical experiment showing a strong von Mises stress concentration at the elastic contrast boundary during hydrostatic tensile loading. Another sample, from the same formation, but without strong density heterogeneity, exhibited a classic 45° crack after uniaxial loading. These results provide a novel and important insight into the mechanics, breakage, and strength of natural rock.The preparation of quantum systems and the execution of quantum information tasks between distant users are always affected by gravitational and relativistic effects. In this work, we quantitatively analyze how the curved space-time background of the Earth affects the classical and quantum correlations between photon pairs that are initially prepared in a two-mode squeezed state. click here More specifically, considering the rotation of the Earth, the space-time around the Earth is described by the Kerr metric. Our results show that these state correlations, which initially increase for a specific range of satellite's orbital altitude, will gradually approach a finite value with increasing height of satellite's orbit (when the special relativistic effects become relevant). More importantly, our analysis demonstrates that the changes of correlations generated by the total gravitational frequency shift could reach the level of [Formula see text] within the satellite's height at geostationary Earth orbits.To evaluate the clinical efficacy of single- and double- bundle individualized anatomic anterior cruciate ligament (ACL) reconstruction, we retrospectively analyzed the data and charts of 920 patients with ACL rupture who received individualized anatomic ACL reconstruction surgery at our center. All of the patients underwent arthroscopic ACL reconstruction with autologous hamstring tendons. The patients were divided into two groups the single-bundle individualized anatomic reconstruction group (N = 539), and the double-bundle individualized anatomic reconstruction group (N = 381). The IKDC, Lysholm and Tegner scores were used to subjectively evaluate the function of the knee joint during the postoperative follow-up. The Lachman test, pivot shift test and KT-3000 were used to objectively evaluate the stability of the knee. All 920 patients participated in clinical follow-up (average duration 27.91 ± 3.61 months) achieved satisfied outcomes with few complications. The postoperative IKDC, Lysholm and Tegner scores, and the objective evaluation of knee joint stability were significantly improved compared to the preoperative status in both groups (P  0.05). Therefore, no difference in terms of the IKDC, Lysholm and Tegner score, or KT-3000 was observed between the individualized anatomic single- and double-bundle ACL reconstruction techniques. Both techniques can be used to restore the stability and functionality of the knee joint with satisfactory short-term efficacy.