Pay Attention to How You Drive: Safe and Adaptive Model-Based Reinforcement Learning for Off-Road Driving

Autonomous off-road driving is challenging as risky actions taken by the robot may lead to catastrophic damage. As such, developing controllers in simulation is often desirable as it provides a safer and more economical alternative. However, accurately modeling robot dynamics is difficult due to the complex robot dynamics and terrain interactions in unstructured environments. Domain randomization addresses this problem by randomizing simulation dynamics parameters, however this approach sacrifices performance for robustness leading to policies that are sub-optimal for any target dynamics. We introduce a novel model-based reinforcement learning approach that aims to balance robustness with adaptability. Our approach trains a System Identification Transformer (SIT) and an Adaptive Dynamics Model (ADM) under a variety of simulated dynamics. The SIT uses attention mechanisms to distill state-transition observations from the target system into a context vector, which provides an abstraction for its target dynamics. Conditioned on this, the ADM probabilistically models the system's dynamics. Online, we use a Risk-Aware Model Predictive Path Integral controller (MPPI) to safely control the robot under its current understanding of the dynamics. We demonstrate in simulation as well as in multiple real-world environments that this approach enables safer behaviors upon initialization and becomes less conservative (i.e. faster) as its understanding of the target system dynamics improves with more observations. In particular, our approach results in an approximately 41% improvement in lap-time over the non-adaptive baseline while remaining safe across different environments

Business Process Text Sketch Automation Generation Using Large Language Model

Business Process Management (BPM) is gaining increasing attention as it has the potential to cut costs while boosting output and quality. Business process document generation is a crucial stage in BPM. However, due to a shortage of datasets, data-driven deep learning techniques struggle to deliver the expected results. We propose an approach to transform Conditional Process Trees (CPTs) into Business Process Text Sketches (BPTSs) using Large Language Models (LLMs). The traditional prompting approach (Few-shot In-Context Learning) tries to get the correct answer in one go, and it can find the pattern of transforming simple CPTs into BPTSs, but for close-domain and CPTs with complex hierarchy, the traditional prompts perform weakly and with low correctness. We suggest using this technique to break down a difficult CPT into a number of basic CPTs and then solve each one in turn, drawing inspiration from the divide-and-conquer strategy. We chose 100 process trees with depths ranging from 2 to 5 at random, as well as CPTs with many nodes, many degrees of selection, and cyclic nesting. Experiments show that our method can achieve a correct rate of 93.42%, which is 45.17% better than traditional prompting methods. Our proposed method provides a solution for business process document generation in the absence of datasets, and secondly, it becomes potentially possible to provide a large number of datasets for the process model extraction (PME) domain.Comment: 10 pages, 7 figure

Discovery of Novel 4-Arylisochromenes as Anticancer Agents Inhibiting Tubulin Polymerization

XJP-L (8), a derivative of the natural product (±)-7,8-dihydroxy-3-methylisochroman-4-one isolated from the peel of Musa sapien tum L., was found to exhibit weak inhibitory activity of tubulin polymerization (IC50 = 10.6 μM) in our previous studies. Thus, a series of 4-arylisochromene derivatives were prepared by incorporating the trimethoxyphenyl moiety into 8, among which compound (±)-19b was identified as the most potent compound with IC50 values ranging from 10 to 25 nM against a panel of cancer cell lines. Further mechanism studies demonstrated that (±)-19b disrupted the intracellular microtubule network, caused G2/M phase arrest, induced cell apoptosis, and depolarized mitochondria of K562 cells. Moreover, (±)-19b exhibited potent in vitro antivascular and in vivo antitumor activities. Notably, the R-configured enantiomer of (±)-19b, which was prepared by chiral separation, was slightly more potent than (±)-19b and was much more potent than the S-configured enantiomer in both antiproliferative and antitubulin assays. Our findings suggest that (±)-19b deserves further research as a potential antitubulin agent for the treatment of cancers

Design, synthesis and biological evaluation of quinoline-indole derivatives as anti-tubulin agents targeting the colchicine binding site

A series of novel isocombretastatin A-4 (isoCA-4) analogs were designed and synthesized by replacing 3,4,5-trimethoylphenyl and isovanillin of isoCA-4 with quinoline and indole moieties, respectively. The structure activity relationships (SARs) of these synthesized quinoline-indole derivatives have been intensively investigated. Two compounds 27c and 34b exhibited the most potent activities against five cancer cell lines with IC50 values ranging from 2 to 11 nM, which were comparable to those of Combretastatin A-4 (CA-4, 1). Further mechanism investigations revealed that 34b effectively inhibited the microtubule polymerization by binding to the colchicine site of tubulin. Further cellular mechanism studies elucidated that 34b disrupted cell microtubule networks, arrested the cell cycle at G2/M phase, induced apoptosis and depolarized mitochondria of K562 cells. Moreover, 34b displayed potent anti-vascular activity in both wound healing and tube formation assays. Importantly, 27c and 34b significantly inhibited tumor growth in H22 xenograft models without apparent toxicity, suggesting that 27c and 34b deserve further research as potent antitumor agents for cancer therapy

Case report: Minimally invasive removal of a dislodged thoracoamniotic shunt with an integral cystoscope in a preterm infant

IntroductionFetal pleural effusion is a rare condition that is associated with significant mortality. Although the insertion of fetal thoracoamniotic shunts can improve perinatal outcomes, there are several associated complications, such as intrathoracic dislodgement of the shunts. The optimal neonatal treatment for retained shunts remains uncertain.Case DescriptionA male infant was born at 32 weeks of gestation. He had antenatal hydrothorax that was detected at 27 weeks of gestation and was managed by intrauterine thoracoamniotic shunting. However, the shunt catheter dislodged into the fetal chest, which caused reaccumulated pleural effusion and respiratory distress requiring ventilatory support after birth. After the patient’s condition stabilized, minimally invasive removal of the retained catheter was performed on day 17 of life using an integral pediatric cystoscope via a 3-mm thoracic incision. The procedure took approximately 5 min. The postoperative course was uneventful, and the patient, who was discharged 39 days postnatally, is thriving at the 6-month follow-up.ConclusionsWe present a novel and effective approach to the management of an intrathoracic shunt using an integral cystoscope. This approach may offer a valuable alternative to traditional thoracoscopy in the neonatal period

Facile One-Pot Synthesis of Self-Assembled Folate-Biotin-Pullulan Nanoparticles for Targeted Intracellular Anticancer Drug Delivery

The self-assembled folate-biotin-pullulan (FBP) nanoparticles (NPs) were prepared by facile one-pot synthesis and their physicochemical properties were characterized. The self-assembled FBP NPs were used as an anticancer drug nanocarrier entrapping doxorubicin (DOX) for targeting folate-receptors-overexpressing cancer cells. The identification of prepared NPs to folate-receptor-expressing cancer cells (KB cells) was affirmed by cell viability measurement, folate competition test, and flow cytometric analysis. Compared with the naked DOX and DOX/BP NPs, the DOX/FBP NPs had lower IC50 value compared to KB cells as a result of the folate-receptor-mediated endocytosis process. The cytotoxicity of DOX/FBP NPs to KB cells could be inhibited competitively by free folate. The cellular intake pattern of naked DOX and drug-loaded NPs was identified by confocal laser scanning microscopy (CLSM) observation and the higher cellular uptake of drug for DOX/FBP NPs over naked DOX was observed. The prepared FBP NPs had the potential to be used as a powerful carrier to target anticancer drugs to folate-receptor-expressing tumor cells and reduce cytotoxicity to normal tissues

A Novel Facile and Green Synthesis Protocol to Prepare High Strength Regenerated Silk Fibroin/SiO 2 Composite Fiber

Abstract(#br)In this work, regenerated silk fibroin (RSF) and silicon dioxide (SiO 2 ) composite fiber was successfully extruded by wet spinning method. The effect of SiO 2 addition on structure of the composite fiber at microscopic level is studied, which subsequently correlated to the mechanical performance. The best concentration ratio for composite fiber is identified by screening SiO 2 concentration from 0.025 w/w% to 0.5 w/w%. The experimental results revealed that the SiO 2 at a low concentration of 0.1 w/w% was well distributed. The breaking stress, breaking strain and Young’s modulus at 0.1 w/w% SiO 2 addition of the RSF fibers increased considerably compared to the neat RSF fibers from 243±3 to 458±21 MPa, 51±4 % to 54±7 % and 6.34±0.55 to 11.69±1.12 GPa, respectively. To the..

Loss of BMP signaling through BMPR1A in osteoblasts leads to greater collagen cross-link maturation and material-level mechanical properties in mouse femoral trabecular compartments

Bone morphogenetic protein (BMP) signaling pathways play critical roles in skeletal development and new bone formation. Our previous study, however, showed a negative impact of BMP signaling on bone mass because of the osteoblast-specific loss of a BMP receptor (i.e. BMPR1A) showing increased trabecular bone volume and mineral density in mice. Here, we investigated the bone quality and biomechanical properties of the higher bone mass associated with BMPR1A deficiency using the osteoblast-specific Bmpr1a conditional knockout (cKO) mouse model. Collagen biochemical analysis revealed greater levels of the mature cross-link pyridinoline in the cKO bones, in parallel with upregulation of collagen modifying enzymes. Raman spectroscopy distinguished increases in the mature to immature cross-link ratio and mineral to matrix ratio in the trabecular compartments of cKO femora, but not in the cortical compartments. The mineral crystallinity was unchanged in the cKO in either the trabecular or cortical compartments. Further, we tested the intrinsic material properties by nanoindentation and found significantly higher hardness and elastic modulus in the cKO trabecular compartments, but not in the cortical compartments. Four point bending tests of cortical compartments showed lower structural biomechanical properties (i.e. strength and stiffness) in the cKO bones due to the smaller cortical areas. However, there were no significant differences in biomechanical performance at the material level, which was consistent with the nanoindentation test results on the cortical compartment. These studies emphasize the pivotal role of BMPR1A in the determination of bone quality and mechanical integrity under physiological conditions, with different impact on femoral cortical and trabecular compartments

Tubulin inhibitors targeting the colchicine binding site: a perspective of privileged structures

The vital roles of microtubule in mitosis and cell division make it an attractive target for antitumor therapy. Colchicine binding site of tubulin is one of the most important pockets that have been focused on to design tubulin-destabilizing agents. Over the past few years, a large number of colchicine binding site inhibitors (CBSIs) have been developed inspired by natural products or synthetic origins, and many moieties frequently used in these CBSIs are structurally in common. In this review, we will classify the CBSIs into classical CBSIs and nonclassical CBSIs according to their spatial conformations and binding modes with tubulin, and highlight the privileged structures from these CBSIs in the development of tubulin inhibitors targeting the colchicine binding site