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Notch signaling is aberrantly activated in approximately 30% of hepatocellular carcinoma (HCC), significantly contributing to tumorigenesis and disease progression. Expression of the major Notch receptor, NOTCH1, is upregulated in HCC cells and correlates with advanced disease stages, although the molecular mechanisms underlying its overexpression remain unclear. Here, we report that expression of the intracellular domain of NOTCH1 (NICD1) is upregulated in HCC cells due to antagonism between the E3‐ubiquitin ligase F‐box/WD repeat‐containing protein 7 (FBXW7) and the large scaffold protein abnormal spindle‐like microcephaly‐associated protein (ASPM) isoform 1 (ASPM‐i1). Mechanistically, FBXW7‐mediated polyubiquitination and the subsequent proteasomal degradation of NICD1 are hampered by the interaction of NICD1 with ASPM‐i1, thereby stabilizing NICD1 and rendering HCC cells responsive to stimulation by Notch ligands. Consistently, downregulating ASPM‐i1 expression reduced the protein abundance of NICD1 but not its FBXW7‐binding‐deficient mutant. Reinforcing the oncogenic function of this regulatory module, the forced expression of NICD1 significantly restored the tumorigenic potential of ASPM‐i1‐deficient HCC cells. Echoing these findings, NICD1 was found to be strongly co‐expressed with ASPM‐i1 in cancer cells in human HCC tissues (P

Abstract ATP and its receptor P2RX7 exert a pivotal effect on antitumor immunity during chemotherapy-induced immunogenic cell death (ICD). Here, we demonstrated that TNFα-mediated PANX1 cleavage was essential for ATP release in response to chemotherapy in colorectal cancer (CRC). TNFα promoted PANX1 cleavage via a caspase 8/3-dependent pathway to enhance cancer cell immunogenicity, leading to dendritic cell maturation and T-cell activation. Blockade of the ATP receptor P2RX7 by the systemic administration of small molecules significantly attenuated the therapeutic efficacy of chemotherapy and decreased the infiltration of immune cells. In contrast, administration of an ATP mimic markedly increased the therapeutic efficacy of chemotherapy and enhanced the infiltration of immune cells in vivo. High PANX1 expression was positively correlated with the recruitment of DCs and T cells within the tumor microenvironment and was associated with favorable survival outcomes in CRC patients who received adjuvant chemotherapy. Furthermore, a loss-of-function P2RX7 mutation was associated with reduced infiltration of CD8+ immune cells and poor survival outcomes in patients. Taken together, these results reveal that TNFα-mediated PANX1 cleavage promotes ATP-P2RX7 signaling and is a key determinant of chemotherapy-induced antitumor immunity.

This study investigated the possible contributing factors to the digital gender divide and the spatial spillover effects of submarine communication cables on neighboring areas. Using spatial statistical models and global data, this study examined the Internet penetration rate and the digital gender divide in 186 countries. Data sources included open source data, social media, ITU and UNCTAD databases, and the World Bank. The study estimated the average male and female Internet users in 186 countries using Facebook API. The number of submarine communication cables between countries was used as the basis for constructing the spatial weights matrix. The countries with the highest Internet penetration rate were mostly in Europe. Those with the lowest Internet penetration rate were in Africa, Central Asia, and West Asia. Thirteen of the 15 countries with the worst Internet penetration rate were located in the African region. A significant digital gender divide arose in the developing and the least-developed countries. We argue that connectivity is key to the reduction of the digital gender divide and to ensuring that more women have access to the Internet. The study ascertains that the Internet penetration rate is related to the digital gender divide in individual countries and has a spatial spillover impact in surrounding nations connected by submarine communication cables. The study demonstrates that submarine cables serve as important infrastructure for closing the digital gender divide and deserve increased analytical attention.

In this article, an innovative offline deep imitation learning algorithm for optimal trajectory planning is proposed. While many state‐of‐the‐art works achieved optimal trajectory planning, their systems were stable or quasistable, and their approaches rarely optimized the system's initial conditions (ICs). Here, a new unstable dynamic system task called “internal sliding object stabilization control” is proposed, modeled, and solved by deep imitation learning. Given the system's ICs, the neural networks (NNs) can imitate the iterative linear quadratic regulator (iLQR), generate optimal trajectories, and compute faster. A proportional–integral–derivative (PID) controller is used to track the unstable trajectories. Leveraging on the gradients of NNs, it can optimize the system's ICs, avoid obstacles stepwise, and ensure the worst bounds of NNs for safety. Subsequently, thorough simulations are conducted, including comparing the iLQR and PID controllers in the task, optimizing the system's different ICs by gradient descent, and finding the worst bound of the performance by gradient ascent. Results show that the proposed algorithm achieves considerably improved performance. Finally, experiments are conducted with a real manipulator to compare the proposed structure with the original iLQR. Results indicate that the proposed algorithm resembles the iLQR well. Program code and experiment results are in https://github.com/DanielYamChen/ISOSC.git.

Abstract Background yqiC is required for colonizing the Salmonella enterica serovar Typhimurium (S. Typhimurium) in human cells; however, how yqiC regulates nontyphoidal Salmonella (NTS) genes to influence bacteria–host interactions remains unclear. Methods The global transcriptomes of S. Typhimurium yqiC-deleted mutant (ΔyqiC) and its wild-type strain SL1344 after 2 h of in vitro infection with Caco-2 cells were obtained through RNA sequencing to conduct comparisons and identify major yqiC-regulated genes, particularly those involved in Salmonella pathogenicity islands (SPIs), ubiquinone and menaquinone biosynthesis, electron transportation chains (ETCs), and carbohydrate/energy metabolism. A Seahorse XFp Analyzer and assays of NADH/NAD+ and H2O2 were used to compare oxygen consumption and extracellular acidification, glycolysis parameters, adenosine triphosphate (ATP) generation, NADH/NAD+ ratios, and H2O2 production between ΔyqiC and SL1344. Results After S. Typhimurium interacts with Caco-2 cells, yqiC represses gene upregulation in aspartate carbamoyl transferase, type 1 fimbriae, and iron–sulfur assembly, and it is required for expressing ilvB operon, flagellin, tdcABCD, and dmsAB. Furthermore, yqiC is required for expressing mainly SPI-1 genes and specific SPI-4, SPI-5, and SPI-6 genes; however, it diversely regulates SPI-2 and SPI-3 gene expression. yqiC significantly contributes to menD expression in menaquinone biosynthesis. A Kyoto Encyclopedia of Genes and Genomes analysis revealed the extensive association of yqiC with carbohydrate and energy metabolism. yqiC contributes to ATP generation, and the analyzer results demonstrate that yqiC is required for maintaining cellular respiration and metabolic potential under energy stress and for achieving glycolysis, glycolytic capacity, and glycolytic reserve. yqiC is also required for expressing ndh, cydA, nuoE, and sdhB but suppresses cyoC upregulation in the ETC of aerobically and anaerobically grown S. Typhimurium; priming with Caco-2 cells caused a reversed regulation of yiqC toward upregulation in these ETC complex genes. Furthermore, yqiC is required for maintaining NADH/NAD+ redox status and H2O2 production. Conclusions Specific unreported genes that were considerably regulated by the colonization-associated gene yqiC in NTS were identified, and the key role and tentative mechanisms of yqiC in the extensive modulation of virulence factors, SPIs, ubiquinone and menaquinone biosynthesis, ETCs, glycolysis, and oxidative stress were discovered.

In this work, we examine a mixed oligopoly model within the framework of consistent conjectural variations, in which one of the producers is a labor-managed company competing with other private firms, and consumer demand is given by a discontinuous function. Private firms attempt to maximize their net profit while the labor-managed company attempts to maximize the convex combination of its net profit with an income-per-worker function, which describes the mixed nature of the model. Each producer conjectures the dependence of the market-clearing price on its own production volume and then selects its most suitable conjecture based on a verification procedure. We introduce the notions of exterior and interior equilibrium and prove the existence and uniqueness of the conjectural variation equilibrium, as well as the existence of the particular equilibrium states known as consistent. Finally, we analyze the behavior of the market’s consistent equilibrium state in response to changes in consumer demand.

Heat shock protein (HSP) 40 has emerged as a key factor in both innate and adaptive immunity, whereas the role of HLJ1, a molecular chaperone in HSP40 family, in modulating endotoxin-induced sepsis severity is still unclear. During lipopolysaccharide (LPS)-induced endotoxic shock, HLJ1 knockout mice shows reduced organ injury and IFN-γ (interferon-γ)-dependent mortality. Using single-cell RNA sequencing, we characterize mouse liver nonparenchymal cell populations under LPS stimulation, and show that HLJ1 deletion affected IFN-γ-related gene signatures in distinct immune cell clusters. In CLP models, HLJ1 deletion reduces IFN-γ expression and sepsis mortality rate when mice are treated with antibiotics. HLJ1 deficiency also leads to reduced serum levels of IL-12 in LPS-treated mice, contributing to dampened production of IFN-γ in natural killer cells but not CD4+ or CD8+ T cells, and subsequently to improved survival rate. Adoptive transfer of HLJ1-deleted macrophages into LPS-treated mice results in reduced IL-12 and IFN-γ levels and protects the mice from IFN-γ-dependent mortality. In the context of molecular mechanisms, HLJ1 is an LPS-inducible protein in macrophages and converts misfolded IL-12p35 homodimers to monomers, which maintains bioactive IL-12p70 heterodimerization and secretion. This study suggests HLJ1 causes IFN-γ-dependent septic lethality by promoting IL-12 heterodimerization, and targeting HLJ1 has therapeutic potential in inflammatory diseases involving activated IL-12/IFN-γ axis.

Human noroviruses (HuNoV) are major causes of acute gastroenteritis around the world. The high mutation rate and recombination potential of noroviruses are significant challenges in studying the genetic diversity and evolution pattern of novel strains. In this review, we describe recent advances in the development of technologies for not only the detection but also the analysis of complete genome sequences of noroviruses and the future prospects of detection methods for tracing the evolution and genetic diversity of human noroviruses. The mechanisms of HuNoV infection and the development of antiviral drugs have been hampered by failure to develop the infectious virus in a cell model. However, recent studies have demonstrated the potential of reverse genetics for the recovery and generation of infectious viral particles, suggesting the utility of this genetics-based system as an alternative for studying the mechanisms of viral infection, such as cell entry and replication.

This article reports the construction of an articulated manipulator’s hybrid dynamic model and trajectory planning and optimization of the manipulator using deep reinforcement learning (RL) on the dynamic model. The hybrid model was composed of a physical-based reduced-order dynamic model, linear friction and damping terms, and a deep neural network model to compensate for the nonlinear characteristics of the manipulator. The hybrid model then served as the digital twin of the manipulator for trajectory planning to optimize energy efficiency and operation speed by using RL while taking obstacle avoidance into consideration. The proposed strategy was simulated and experimentally validated. The energy consumption along paths was reduced and the speed was increased so the manipulator could achieve more efficient motion.

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with the colorectum as its major target organ. Involvement of the upper gastrointestinal tract in UC is rare and presents with nonspecific endoscopic and microscopic characteristics. Recent studies have demonstrated proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) to be a serological marker for differentiating UC from Crohn's disease in children and for detecting disease activity and nonresponse to steroid therapy and antitumor necrotizing factor-α agents. Herein, we report a 13-year-old female patient mainly presenting with recurrent bilious vomiting who was initially diagnosed with acute gastroenteritis. Intestinal pseudo-obstruction was confirmed through observation of a patent but segmentally dilated jejunum in the barium follow-through examination and other imaging; such obstruction can be attributed to backwash ileitis, superior mesenteric artery syndrome, ileus due to hypokalemia, or PR3-associated enteritis. Laboratory data revealed leukocytosis with neutrophil predominance and serum antinuclear antibody and PR3-ANCA positivity. Overlapping syndrome with autoimmune diseases was suspected. Pathology revealed a crypt abscess with aggregates of neutrophils consistent with UC but did not indicate vasculitis. The in situ immunohistochemical staining revealed PR3 density mainly in the colon and focally in the duodenum. To our knowledge, this is the first case report with in situ pathological evidence of PR3 in inflamed intestinal tissues in a patient with UC and with rare initial presentation of intestinal pseudo-obstruction–induced recurrent bilious vomiting. Whether the clinical features of the present case constitute overlap syndrome with other autoimmune disease or a disease variation of UC warrants further investigation. Notably, the patient's serum PR3-ANCA titers remained high in coincidence with increased disease activity and nonresponse to steroid therapy, but became lower after infliximab treatment. PR3-ANCA as a potential serum biomarker to aid in making differential diagnoses of UC in children, correlating disease activity, and predicting therapeutic responses was also reviewed.

Background Norovirus (NoV) infection is common in pediatric patients with immunodeficiency and is more likely to cause severe disease. Objective Our study aims to figure out the clinical differences and distribution of intestinal microbiota in immunocompromised children with NoV gastroenteritis. Methods Pediatric patients admitted to Shang-Ho Hospital with diagnosis of acute gastroenteritis including different immune status were enrolled and their medical records were reviewed. NoV gastroenteritis was validated using RT-PCR molecular methods. Viral shedding period was determined by real-time RT-PCR assays. Intestinal microbiota enrichment analysis was carried out by next generation sequencing after fecal DNA extraction and subsequent Linear Discriminant Analysis (LDA) Effect Size (LEfSe) method. Results Significantly higher frequency of diarrhea [mean, (IQR), 3.8 (3–5) /day] and longer viral shedding time [mean, IQR, 8.5 (5–13) days] was found in immunocompromised NoV infections than in immunocompetent patients without NoV infections (p = 0.013*) and immunocompetent patients with NoV infections (p = 0.030**). The fever prevalence was significantly lower in immunocompromised NoV infections than in different immune or infection status. Intestinal microbiota metagenomics analysis showed no significant community richness difference while the LEfSe analysis showed a significant difference in commensal richness at the phylum level, the family level, and the genus level in patients under different immune status. Conclusion We evaluated the clinical significances and microbiota composition in immunocompromised children with norovirus gastroenteritis. This will further facilitate studies of the interaction between the intestinal microbiota in such patients with precise determination of their bacterial infection control and probiotic supplements strategy.

Resveratrol (RSV) has been demonstrated to ameliorate nonalcoholic fatty liver disease (NAFLD) in animal studies. However, RSV was given with the dosage that ranged from 7 to 300 mg/kg body weight (BW). Hence, the study aimed to investigate the efficacy of RSV at a lower dosage on high cholesterol-fructose diet (HCFD)-induced rat model of NAFLD. In the study, male Sprague-Dawley rats were fed with HCFD for 15 weeks. RSV was also given at a daily dose of 1 mg/kg BW for 15 days or 15 weeks by oral delivery. At sacrifice, plasma and liver specimens were acquired for detections of alanine and aspartate aminotransferases, proinflammatory cytokines, and lipid contents. Histological examinations and Western blotting analysis were performed using liver tissues. The results showed that RSV administration reduced plasma levels of aminotransferases and proinflammatory cytokines including interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) in HCFD-induced NAFLD. RSV also mitigated hepatic lipid accumulation and expression of IL-1β, IL-6, and TNF-α. Besides, phosphorylation of signal transducer and activator of transcription 3 (STAT3) was reduced with RSV supplementation in the liver of HCFD-fed rats. We concluded that low-dose RSV supplementation attenuated hepatic inflammation and lipid accumulation in HCFD-induced NAFLD. The ameliorative effect of RSV on NAFLD could be associated with downregulation of phosphorylated STAT3.

Nowadays, the grinding process is mostly automatic, yet post-grinding quality inspection is mostly carried out manually. Although the conventional inspection technique may have cumbersome setup and tuning processes, the data-driven model, with its vision-based dataset, provides an opportunity to automate the inspection process. In this study, a convolutional neural network technique with transfer learning is proposed for three kinds of inspections based on 750–1000 surface raw images of the ground workpieces in each task: classifying the grit number of the abrasive belt that grinds the workpiece, estimating the surface roughness of the ground workpiece, and classifying the degree of wear of the abrasive belts. The results show that a deep convolutional neural network can recognize the texture on the abrasive surface images and that the classification model can achieve an accuracy of 0.9 or higher. In addition, the external coaxial white light was the most suitable light source among the three tested light sources: the external coaxial white light, the high-angle ring light, and the external coaxial red light. Finally, the model that classifies the degree of wear of the abrasive belts can also be utilized as the abrasive belt life estimator.

For businesses that provide delivery services, the efficiency of the delivery process in terms of punctuality is very important. In addition to increasing customer trust, efficient route management, and selection are required to reduce vehicle fuel costs and expedite delivery. Some small and medium businesses still use conventional methods to manage delivery routes. Decisions to manage delivery schedules and routes do not use any specific methods to expedite the delivery settlement process. This process is inefficient, takes a long time, increases costs and is prone to errors. Therefore, the Dijkstra algorithm has been used to improve the delivery management process. A delivery management system was developed to help managers and drivers schedule efficient ways to deliver product orders to recipients. Based on testing, the Dijkstra algorithm that has been included in the nearest route search function for the delivery process has worked well. This system is expected to improve the efficient management and delivery of orders.

Nowadays, it is convenient for us to use a search engine to get our needed information. But sometimes it will misunderstand the information because of the different media reports. The Recommender System (RS) is popular to use for every business since it can provide information for users that will attract more revenues for companies. But also, sometimes the system will recommend unneeded information for users. Because of this, this paper provided an architecture of a recommender system that could base on user-oriented preference. This system is called UOP-RS. To make the UOP-RS significantly, this paper focused on movie theatre information and collect the movie database from the IMDb website that provides information related to movies, television programs, home videos, video games, and streaming content that also collects many ratings and reviews from users. This paper also analyzed individual user data to extract the user’s features. Based on user characteristics, movie ratings/scores, and movie results, a UOP-RS model was built. In our experiment, 5000 IMDb movie datasets were used and 5 recommended movies for users. The results show that the system could return results on 3.86 s and has a 14% error on recommended goods when training data as . At the end of this paper concluded that the system could quickly recommend users of the goods which they needed. The proposed system will extend to connect with the Chatbot system that users can make queries faster and easier from their phones in the future.

Background: As growing evidence links gut microbiota with the therapeutic efficacy and side effects of anti-hyperglycemic drugs, this article aims to provide a systematic review of the reciprocal interactions between anti-hyperglycemic drugs and gut microbiota taxa, which underlie the effect of the gut microbiome on diabetic control via bug-host interactions.Method: We followed the PRISMA requirements to perform a systematic review on human vs. animal gut microbiota data in PubMed, SCOPUS, and EMBASE databases, and used Cochrane, ROBIN-I, and SYRCLE tools to assess potential bias risks. The outcomes of assessment were trends on gut microbiota taxa, diversity, and associations with metabolic control (e.g., glucose, lipid) following anti-hyperglycemic treatment.Results: Of 2,804 citations, 64 studies (17/humans; 47/mice) were included. In human studies, seven were randomized trials using metformin or acarbose in obese, pre-diabetes, and type 2 diabetes (T2D) patients. Treatment of pre-diabetes and newly diagnosed T2D patients with metformin or acarbose was associated with decreases in genus of Bacteroides, accompanied by increases in both Bifidobacterium and Lactobacillus. Additionally, T2D patients receiving metformin showed increases in various taxa of the order Enterobacteriales and the species Akkermansia muciniphila. Of seven studies with significant differences in beta-diversity, the incremental specific taxa were associated with the improvement of glucose and lipid profiles. In mice, the effects of metformin on A. muciniphila were similar, but an inverse association with Bacteroides was reported. Animal studies on other anti-hyperglycemic drugs, however, showed substantial variations in results.Conclusions: The changes in specific taxa and β-diversity of gut microbiota were associated with metformin and acarbose in humans while pertinent information for other anti-hyperglycemic drugs could only be obtained in rodent studies. Further human studies on anti-hyperglycemic drugs other than metformin and acarbose are needed to explore gut microbiota's role in their therapeutic efficacies and side effects.

This paper develops a decoupled multi-loop control for a two-wheeled inverted pendulum (TWIP) robot that can assist user’s with walking. The TWIP robot is equipped with two wheels driven by electrical motors. We derive the system’s transfer function and design a robust loop-shaping controller to balance the system. The simulation and experimental results show that the TWIP system can be balanced but might experience velocity drifts because its balancing point is affected by model variations and disturbances. Therefore, we propose a multi-loop control layout consisting of a velocity loop and a position loop for the TWIP robot. The velocity loop can adjust the balancing point in real-time and regulate the forward velocity, while the position loop can achieve position tracking. For walking assistance, we design a decoupled control structure that transfers the linear and rotational motions of the robot to the commands of two parallel motors. We implement the designed controllers for simulation and experiments and show that the TWIP system employing the proposed decoupled multi-loop control can provide satisfactory responses when assisting with walking.

Background: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy. Methods: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange. Results: KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis. Conclusion: Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG-135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.

Overexpression of anti-apoptotic proteins MCL1 and Bcl-xL are frequently observed in many cancers. Inhibitors targeting MCL1 are in clinical development, however numerous cancer models are intrinsically resistant to this approach. To discover mechanisms underlying resistance to MCL1 inhibition, we performed multiple flow-cytometry based genome-wide CRISPR screens interrogating two drugs that directly (MCL1i) or indirectly (CDK9i) target MCL1. Remarkably, both screens identified three components (CUL5, RNF7 and UBE2F) of a cullin-RING ubiquitin ligase complex (CRL5) that resensitized cells to MCL1 inhibition. We find that levels of the BH3-only pro-apoptotic proteins Bim and Noxa are proteasomally regulated by the CRL5 complex. Accumulation of Noxa caused by depletion of CRL5 components was responsible for re-sensitization to CDK9 inhibitor, but not MCL1 inhibitor. Discovery of a novel role of CRL5 in apoptosis and resistance to multiple types of anticancer agents suggests the potential to improve combination treatments.

The ABC classification problem is approached as a ranking problem by the most current classification models; that is, a group of inventory items is expressed according to its overall weighted score of criteria in descending order. In this paper, we present an extended version of the Hadi-Vencheh model for multiple-criteria ABC inventory classification. The proposed model is one based on the nonlinear weighted product method (WPM), which determines a common set of weights for all items. Our proposed nonlinear WPM incorporates multiple criteria with different measured units without converting the performance of each inventory item, in terms of converting each criterion into a normalized attribute value, thereby providing an improvement over the model proposed by Hadi-Vencheh. Our study mainly includes various criteria for ABC classification and demonstrates an efficient algorithm for solving nonlinear programming problems, in which the feasible solution set does not have to be convex. The algorithm presented in this study substantially improves the solution efficiency of the canonical coordinates method (CCM) algorithm when applied to large-scale, nonlinear programming problems. The modified algorithm was tested to compare our proposed model results to the results derived using the Hadi-Vencheh model and demonstrate the algorithm’s efficacy. The practical objectives of the study were to develop an efficient nonlinear optimization solver by optimizing the quality of existing solutions, thus improving time and space efficiency.

We report on a sensor data fusion algorithm via an extended Kalman filter for estimating the spatial motion of a bipedal robot. Through fusing the sensory information from joint encoders, a 6-axis inertial measurement unit and a 2-axis inclinometer, the robot’s body state at a specific fixed position can be yielded. This position is also equal to the CoM when the robot is in the standing posture suggested by the detailed CAD model of the robot. In addition, this body state is further utilized to provide sensory information for feedback control on a bipedal robot with walking gait. The overall control strategy includes the proposed body state estimator as well as the damping controller, which regulates the body position state of the robot in real-time based on instant and historical position tracking errors. Moreover, a posture corrector for reducing unwanted torque during motion is addressed. The body state estimator and the feedback control structure are implemented in a child-size bipedal robot and the performance is experimentally evaluated.

Although prostate cancer (PCa) is the second leading cause of cancer death among men worldwide, not all men diagnosed with PCa will die from the disease. A critical challenge, therefore, is to distinguish indolent PCa from more advanced forms to guide appropriate treatment decisions. We used Enhanced Reduced Representation Bisulfite Sequencing, a genome-wide high-coverage single-base resolution DNA methylation method to profile seven localized PCa samples, seven matched benign prostate tissues, and six aggressive castration-resistant prostate cancer (CRPC) samples. We integrated these data with RNA-seq and whole-genome DNA-seq data to comprehensively characterize the PCa methylome, detect changes associated with disease progression, and identify novel candidate prognostic biomarkers. Our analyses revealed the correlation of cytosine guanine dinucleotide island (CGI)-specific hypermethylation with disease severity and association of certain breakpoints (deletion, tandem duplications, and interchromosomal translocations) with DNA methylation. Furthermore, integrative analysis of methylation and single-nucleotide polymorphisms (SNPs) uncovered widespread allele-specific methylation (ASM) for the first time in PCa. We found that most DNA methylation changes occurred in the context of ASM, suggesting that variations in tumor epigenetic landscape of individuals are partly mediated by genetic differences, which may affect PCa disease progression. We further selected a panel of 13 CGIs demonstrating increased DNA methylation with disease progression and validated this panel in an independent cohort of 20 benign prostate tissues, 16 PCa, and 8 aggressive CRPCs. These results warrant clinical evaluation in larger cohorts to help distinguish indolent PCa from advanced disease.

This paper reports the algorithm of trajectory planning and the strategy of four-leg coordination for quasi-static stair climbing in a quadruped robot. This development is based on the geometrical interactions between robot legs and the stair, starting from single-leg analysis, followed by two-leg collaboration, and then four-leg coordination. In addition, a brief study on the robot’s locomotion stability is also included. Finally, simulation and experimental testing were executed to evaluate the performance of the algorithm.

The derivation of linear acceleration, angular acceleration, and angular velocity states from a 12-axis gyroscope-free inertial measurement unit that utilizes four 3-axis accelerometer measurements at four distinct locations is reported. Particularly, a new algorithm which derives the angular velocity from its quadratic form and derivative form based on the context-based interacting multiple model is demonstrated. The performance of the system was evaluated under arbitrary 3-dimensional motion.

We report on the methodology of developing compliant, half-circular, and composite robot legs with designable stiffness. First, force-displacement experiments on flat cantilever composites made by one or multifiberglass cloths are executed. By mapping the cantilever mechanics to the virtual spring model, the equivalent elastic moduli of the composites can be derived. Next, by using the model that links the curved beam mechanics back to the virtual spring, the resultant stiffness of the composite in a half-circular shape can be estimated without going through intensive experimental tryouts. The overall methodology has been experimentally validated, and the fabricated composites were used on a hexapod robot to perform walking and leaping behaviors.

We report on the model-based development of a monkey robot that is capable of performing continuous brachiation locomotion on swingable rod, as the intermediate step toward studying brachiation on the soft rope or on horizontal ropes with both ends fixed. The work is different from other previous works where the model or the robot swings on fixed bars. The model, which is composed of two rigid links, was inspired by the dynamic motion of primates. The model further served as the design guideline for a robot that has five degree of freedoms: two on each arm for rod changing and one on the waist to initiate a swing motion. The model was quantitatively formulated, and its dynamic behavior was analyzed in simulation. Further, a two-stage controller was developed within the simulation environment, where the first stage used the natural dynamics of a two-link pendulum-like model, and the second stage used the angular velocity feedback to regulate the waist motion. Finally, the robot was empirically built and evaluated. The experimental results confirm that the robot can perform model-like swing behavior and continuous brachiation locomotion on rods.