Learning Agility and Adaptive Legged Locomotion via Curricular Hindsight Reinforcement Learning

Agile and adaptive maneuvers such as fall recovery, high-speed turning, and sprinting in the wild are challenging for legged systems. We propose a Curricular Hindsight Reinforcement Learning (CHRL) that learns an end-to-end tracking controller that achieves powerful agility and adaptation for the legged robot. The two key components are (I) a novel automatic curriculum strategy on task difficulty and (ii) a Hindsight Experience Replay strategy adapted to legged locomotion tasks. We demonstrated successful agile and adaptive locomotion on a real quadruped robot that performed fall recovery autonomously, coherent trotting, sustained outdoor speeds up to 3.45 m/s, and tuning speeds up to 3.2 rad/s. This system produces adaptive behaviours responding to changing situations and unexpected disturbances on natural terrains like grass and dirt

The Analysis of Key Factors Related to ADCs Structural Design

Antibody–drug conjugates (ADCs) have developed rapidly in recent decades. However, it is complicated to map out a perfect ADC that requires optimization of multiple parameters including antigens, antibodies, linkers, payloads, and the payload-linker linkage. The therapeutic targets of the ADCs are expected to express only on the surface of the corresponding target tumor cells. On the contrary, many antigens usually express on normal tissues to some extent, which could disturb the specificity of ADCs and limit their clinical application, not to mention the antibody is also difficult to choose. It requires to not only target and have affinity with the corresponding antigen, but it also needs to have a linkage site with the linker to load the payloads. In addition, the linker and payload are indispensable in the efficacy of ADCs. The linker is required to stabilize the ADC in the circulatory system and is brittle to release free payload while the antibody combines with antigen. Also, it is a premise that the dose of ADCs will not kill normal tissues and the released payloads are able to fulfill the killing potency in tumor cells at the same time. In this review, we mainly focus on the latest development of key factors affecting ADCs progress, including the selection of antibodies and antigens, the optimization of payload, the modification of linker, payload-linker linkage, and some other relevant parameters of ADCs

Baveno-VII criteria to predict decompensation and initiate non-selective beta-blocker in compensated advanced chronic liver disease patients

Background/Aims The utility of Baveno-VII criteria of clinically significant portal hypertension (CSPH) to predict decompensation in compensated advanced chronic liver disease (cACLD) patient needs validation. We aim to validate the performance of CSPH criteria to predict the risk of decompensation in an international real-world cohort of cACLD patients. Methods cACLD patients were stratified into three categories (CSPH excluded, grey zone, and CSPH). The risks of decompensation across different CSPH categories were estimated using competing risk regression for clustered data, with death and hepatocellular carcinoma as competing events. The performance of “treating definite CSPH” strategy to prevent decompensation using non-selective beta-blocker (NSBB) was compared against other strategies in decision curve analysis. Results One thousand one hundred fifty-nine cACLD patients (36.8% had CSPH) were included; 7.2% experienced decompensation over a median follow-up of 40 months. Non-invasive assessment of CSPH predicts a 5-fold higher risk of liver decompensation in cACLD patients (subdistribution hazard ratio, 5.5; 95% confidence interval, 4.0–7.4). “Probable CSPH” is suboptimal to predict decompensation risk in cACLD patients. CSPH exclusion criteria reliably exclude cACLD patients at risk of decompensation, regardless of etiology. Among the grey zone, the decompensation risk was negligible among viral-related cACLD, but was substantially higher among the non-viral cACLD group. Decision curve analysis showed that “treating definite CSPH” strategy is superior to “treating all varices” or “treating probable CSPH” strategy to prevent decompensation using NSBB. Conclusions Non-invasive assessment of CSPH may stratify decompensation risk and the need for NSBB in cACLD patients

Plasma-neutral gas interactions in various space environments: Assessment beyond simplified approximations as a Voyage 2050 theme

In the White Paper, submitted in response to the European Space Agency (ESA) Voyage 2050 Call, we present the importance of advancing our knowledge of plasma-neutral gas interactions, and of deepening our understanding of the partially ionized environments that are ubiquitous in the upper atmospheres of planets and moons, and elsewhere in space. In future space missions, the above task requires addressing the following fundamental questions: (A) How and by how much do plasma-neutral gas interactions influence the re-distribution of externally provided energy to the composing species? (B) How and by how much do plasma-neutral gas interactions contribute toward the growth of heavy complex molecules and biomolecules? Answering these questions is an absolute prerequisite for addressing the long-standing questions of atmospheric escape, the origin of biomolecules, and their role in the evolution of planets, moons, or comets, under the influence of energy sources in the form of electromagnetic and corpuscular radiation, because low-energy ion-neutral cross-sections in space cannot be reproduced quantitatively in laboratories for conditions of satisfying, particularly, (1) low-temperatures, (2) tenuous or strong gradients or layered media, and (3) in low-gravity plasma. Measurements with a minimum core instrument package (< 15 kg) can be used to perform such investigations in many different conditions and should be included in all deep-space missions. These investigations, if specific ranges of background parameters are considered, can also be pursued for Earth, Mars, and Venus

Clinicopathological Significance and Prognostic Value of DNA Methyltransferase 1, 3a, and 3b Expressions in Sporadic Epithelial Ovarian Cancer

Altered DNA methylation of tumor suppressor gene promoters plays a role in human carcinogenesis and DNA methyltransferases (DNMTs) are responsible for it. This study aimed to determine aberrant expression of DNMT1, DNMT3a, and DNMT3b in benign and malignant ovarian tumor tissues for their association with clinicopathological significance and prognostic value. A total of 142 ovarian cancers and 44 benign ovarian tumors were recruited for immunohistochemical analysis of their expression. The data showed that expression of DNMT1, DNMT3a, and DNMT3b was observed in 76 (53.5%), 92 (64.8%) and 79 (55.6%) of 142 cases of ovarian cancer tissues, respectively. Of the serious tumors, DNMT3a protein expression was significantly higher than that in benign tumor samples (P = 0.001); DNMT3b was marginally significant down regulated in ovarian cancers compared to that of the benign tumors (P = 0.054); DNMT1 expression has no statistical difference between ovarian cancers and benign tumor tissues (P = 0.837). Of the mucious tumors, the expression of DNMT3a, DNMT3b, and DNMT1 was not different between malignant and benign tumors. Moreover, DNMT1 expression was associated with DNMT3b expression (P = 0.020, r = 0.195). DNMT1 expression was associated with age of the patients, menopause status, and tumor localization, while DNMT3a expression was associated with histological types and serum CA125 levels and DNMT3b expression was associated with lymph node metastasis. In addition, patients with DNMT1 or DNMT3b expression had a trend of better survival than those with negative expression. Co-expression of DNMT1 and DNMT3b was significantly associated with better overall survival (P = 0.014). The data from this study provided the first evidence for differential expression of DNMTs proteins in ovarian cancer tissues and their associations with clinicopathological and survival data in sporadic ovarian cancer patients

A Study of the Identification, Fragmentation Mode and Metabolic Pathways of Imatinib in Rats Using UHPLC-Q-TOF-MS/MS

In this study, The metabolites, metabolic pathways, and metabolic fragmentation mode of a tyrosine kinase inhibitor- (TKI-) imatinib in rats were investigated. The samples for analysis were pretreated via solid-phase extraction, and the metabolism of imatinib in rats was studied using ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). Eighteen imatinib metabolites were identified in rat plasma, 21 in bile, 18 in urine, and 12 in feces. Twenty-seven of the above compounds were confirmed as metabolites of imatinib and 9 of them were newly discovered for the first time. Oxidation, hydroxylation, dealkylation, and catalytic dehydrogenation are the main metabolic pathways in phase I. For phase II, the main metabolic pathways were N-acetylation, methylation, cysteine, and glucuronidation binding. The fragment ions of imatinib and its metabolites were confirmed to be produced by the cleavage of the C-N bond at the amide bond. The newly discovered metabolite of imatinib was identified by UHPLC-Q-TOF-MS/MS. The metabolic pathway of imatinib and its fragmentation pattern were summarized. These results could be helpful to study the safety of imatinib for clinical use

Characterization of fiber distribution in steel fiber reinforced cementitious composites with low water-binder ratio

449-457Image analysis technique is introduced to characterize fiber distribution in steel fiber reinforced cementitious composites. Through cutting and polishing of specimen, image acquisition of specimen surface, extraction of fiber feature, and measurement of related fiber parameters, i.e., dispersion coefficient and orientation factor, are given to quantitatively analyze fiber distribution. Effects of specimen size, fiber volume fraction and aggregate characteristics on fiber distribution are discussed. Results show that the dispersion coefficient increases with the increase of specimen size and with the decrease of fiber volume fraction and aggregate size, but the changes are small. The orientation factor of fiber is affected by boundary effect, while the influence will get smaller and smaller with the increase of specimen size, especially for the specimen size larger than 50 mm. With the increase of fiber volume fraction, the orientation factor in each direction deviates from 0.5, and the orientation factor in y-direction decreases. Aggregate characteristics have a significant effect on fiber distribution, with the increase of aggregate size, the orientation factors in x- and y- directions increases, while that in z-direction decreases. With the increase of aggregate content, the orientation factors in y- and z-directions increase, while that in x-direction decreases

Sensorless control of permanent magnet synchronous motor based on sliding mode adaptive system

The traditional mechanical encoder has been used to detect the position and speed of rotors in permanent magnet synchronous motor control system, which has the problems of high cost, low system reliability, being susceptible to interference and difficult to apply in a complex environment. A novel speed estimation method based on sliding mode adaptive system is proposed in this paper, which improves the speed estimation accuracy and system robustness to achieve motor speed sensorless control. The simulation results indicate that the control strategy could avoid the limitations of traditional mechanical encoders, and estimate the rotor speed and position angle accurately when suddenly applied load