Search

Jiachen Yu,1,* Yingchun Zhang,1,* Rong Ran,2,* Zixiao Kong,3 Duoyi Zhao,1 Wei Zhao,1 Yingxin Yang,4 Lianbo Gao,5 Zhiyu Zhang1 1Department of Orthopedics, the Fourth Affiliated Hospital of China Medical University, China Medical University, Shen Yang, 110032, People’s Republic of China; 2Department of Anesthesia, the Fourth Affiliated Hospital of China Medical University, China Medical University, Shen Yang, 110032, People’s Republic of China; 3China Medical University, Shen Yang, 110032, People’s Republic of China; 4General Hospital of Northern Theater Command, China Medical University, Shen Yang, 110032, People’s Republic of China; 5Department of Neurology, the Fourth Affiliated Hospital of China Medical University, China Medical University, Shen Yang, 110032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiyu Zhang; Lianbo Gao, The Fourth Affiliated Hospital of China Medical University, No. 4 Chongshan Road, Huanggu District, Shenyang, Liaoning, People’s Republic of China, Email zyzhang@cmu.edu.cn; lbgao@cmu.edu.cnAbstract: The development of therapeutic drugs and methods has been greatly facilitated by the emergence of tumor models. However, due to their inherent complexity, establishing a model that can fully replicate the tumor tissue situation remains extremely challenging. With the development of tissue engineering, the advancement of bioprinting technology has facilitated the upgrading of tumor models. This article focuses on the latest advancements in bioprinting, specifically highlighting the construction of 3D tumor models, and underscores the integration of these two technologies. Furthermore, it discusses the challenges and future directions of related techniques, while also emphasizing the effective recreation of the tumor microenvironment through the emergence of 3D tumor models that resemble in vitro organs, thereby accelerating the development of new anticancer therapies.Keywords: bioprinting, bioink, organoids, tumor spheroids, tumor chips

Timed Failure Propagation Graphs (TFPGs) have been widely used for the failure modeling and diagnosis of safety-critical systems. Currently most TFPGs are manually constructed by system experts, a process that can be time-consuming, error-prone, and even impossible for systems with highly nonlinear and machine-learning-based components. This letter proposes a new type of TFPGs, called Real-Valued Timed Failure Propagation Graphs (rTFPGs), designed for continuous-state systems. More importantly, it presents a systematic way of constructing rTFPGs by combining the powers of human experts and data-driven methods: first, an expert constructs a partial rTFPG based on his/her expertise; then a data-driven algorithm refines the rTFPG by adding nodes and edges based on a given set of labeled signals. The proposed approach has been successfully implemented and evaluated on three case studies.

Multiple-player games involving cooperative and adversarial agents are a type of problems of great practical significance. In this letter, we consider an attack-defense game with a single attacker and multiple defenders. The attacker attempts to enter a protected region, while the defenders attempt to defend the same region and capture the attacker outside the region. We propose a distributed pursuit-defense strategy for the defenders' cooperative defense against the attacker. Inside a bounded, convex, two-dimensional space, the defenders choose among an area-decreasing, a distance-decreasing, or a pursuing strategy. We prove that our strategy guarantees the attacker to be captured before entering the protected region in a finite time. We also demonstrate with simulations that a human-controlled attacker is unable to enter a protected region when multiple defenders are using our pursuit-defense strategy.

Mitigating ground effect becomes a big challenge for autonomous aerial vehicles when they are flying in close proximity to the ground. This paper aims to develop a precise model of ground effect on mini quadcopters, provide an advanced control algorithm to counter the model uncertainty and, as a result, improves the command tracking performance when the vehicle is in the ground effect region. The mathematical model of ground effect has been established through a series of experiments and validated by a flight test. The experiments show that the total thrust generated by rotors increases linearly as the vehicle gets closer to the ground, which is different from the commonly-used ground effect model for a single rotor vehicle. In addition, the model switches from a piecewise linear to a quadratic function when the rotor to rotor distance is increased. A control architecture that utilizes the model reference adaptive controller (MRAC) has also been designed, where MRAC is added to the altitude loop. The performance of the proposed control algorithm has been evaluated through a set of flight tests on a mini quadcopter platform and compared with a traditional proportional–integral–derivative (PID) controller. The results demonstrate that MRAC dramatically improves the tracking performance of altitude command and can reduce the rise time by 80 % under the ground effect.

Due to its high versatility and scalability, manual grinding is an important and widely used technology in production for rework, repair, deburring, and finishing of large or unique parts. To make the process more interactive and reliable, manual grinding needs to incorporate "skill-based design," which models a person-based system and can go significantly beyond the considerations of traditional human factors and ergonomics to encompass both processing parameters (e.g., feed rate, tool path, applied forces, material removal rate (MRR)), and machined surface quality (e.g., surface roughness). This study quantitatively analyzes the characteristics of complex techniques involved in manual operations. A series of experiments have been conducted using subjects of different levels of skill, while analyzing their visual gaze, cutting force, tool path, and workpiece quality. Analysis of variance (ANOVA) and multivariate regression analysis were performed and showed that the unique behavior of the operator affects the process performance measures of specific energy consumption and MRR. In the future, these findings can be used to predict product quality and instruct new practitioners.

The inherent and increasing complexity of many cyber-physical systems (CPSs) makes it challenging for human users or designers to comprehend and interpret their performance. This issue, without proper attention paid, may lead to unwanted and even catastrophic consequences, particularly with safety-critical CPSs. This paper presents a new methodology of enabling (i) a human to interrogate a CPS by inquiring with questions written in formal logic and (ii) the CPS to interpret its performance precisely in the context of the inquiry. This formal interpretation problem is first formulated as temporal logic inference problem, which, aided by the concept of robustness degree, can be converted into an optimisation problem with probably approximately correct solutions. A new Gaussian-process-based active learning algorithm is then proposed to address the potential computational budget issue arising from solving the optimisation problem. Both theoretical and empirical analyses are carried out to demonstrate the performance of the proposed algorithm. Finally, a detailed case study on automotive mechatronic design is provided to showcase the proposed formal interpretation methodology.

This paper studies artistic expression in human movement by exploring the performance art form salsa. The motions of a salsa performance are constructed as concatenations of motion primitives, each of which specifies the movement of the dance pair over the course of eight musical beats. To analyze the syntax of artistic expression, the choreography of dance performances is represented by a transition model that is based on humanoid robot representations of the dancers. In order to assess the quality of a performance, two distinct metrics are explored. By integrating the performance metrics into the proposed transition system, it is possible to create an algorithm that is capable of autonomously recognizing the dance moves and evaluating the quality of the performance with a score. To validate the model, a dance pair performed four distinct salsa dance sequences observed by an artificially intelligent (AI) judge. The video recordings of the performances are also shown to a dance audience for evaluation. By looking at the correlation between the dance audience and the AI judge's scores, we conclude that the proposed model performs well in evaluating the artistic merit of the dance.

This paper presents new techniques to analyze and understand the sensorimotor characteristics of manual operations such as grinding, and links their influence on process performance. A grinding task, though simple, requires the practitioner to combine elements from the large repertoire of his or her skillset. Based on the joint gaze, force, and velocity data collected from a series of manual grinding experiments, we have compared operators with different levels of experience and quantitatively described characteristics of human manual skill and their effects on manufacturing process parameters such as cutting energy, surface finish, and material removal rate (MRR). For instance, we find that an experienced subject performs the task in a precise manner by moving the tool in complex paths, with lower applied forces and velocities, and short fixations compared to a novice. A detailed understanding of gaze-motor behavior broadens our knowledge of how a manual task is executed. Our results help to provide this extra insight, and impact future efforts in workforce training as well as the digitalization of manual expertise, thereby facilitating the transformation of raw data into product-specific knowledge.

The increased complexity of modern systems necessitates automated anomaly detection methods to detect possible anomalous behavior determined by malfunctions or external attacks. We present formal methods for inferring (via supervised learning) and detecting (via unsupervised learning) anomalous behavior. Our procedures use data to construct a signal temporal logic (STL) formula that describes normal system behavior. This logic can be used to formulate properties such as 'If the train brakes within 500 m of the platform at a speed of 50 km/hr, then it will stop in at least 30 s and at most 50 s.' Our procedure infers not only the physical parameters involved in the formula (e.g., 500 m in the example above) but also its logical structure. STL gives a more human-readable representation of behavior than classifiers represented as surfaces in high-dimensional feature spaces. The learned formula enables us to perform early detection by using monitoring techniques and anomaly mitigation by using formal synthesis techniques. We demonstrate the power of our methods with examples of naval surveillance and a train braking system.

In this work, we give an elementary proof of the transformation formula for the Dedekind eta function under the action of the modular group PSL (2;Z). We start by giving a proof of the transformation formula η(τ) under the transformation τ →-1/τ, using the Jacobi triple product identity and the Poisson summation formula. After we establish some identities for the Dedekind sum, the transformation formula for η(τ) under the transformation induced by a general element of the modular group PSL (2;Z) is derived by induction. [ABSTRACT FROM AUTHOR]

Ziyan Kong,1,2,* Xuemei Liu,3,* Chenxi Li,1,* Siyun Cheng,1 Fei Xu,3 Bing Gu1,4 1Medical Technology School, Xuzhou Medical University, Xuzhou, Jiangsu Province, People’s Republic of China; 2Department of Laboratory Medicine, The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu Province, People’s Republic of China; 3Department of Laboratory Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 4Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei XuDepartment of Laboratory Medicine, Children’s Hospital of Nanjing Medical University, Nanjing 210009, People’s Republic of ChinaEmail 350826448@qq.comBing GuDepartment of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, People’s Republic of ChinaEmail gb20031129@163.comPurpose: The continuous emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a serious public health problem globally, especially for children, but data on CRKP infection in pediatric patients are limited. This study aimed to identify epidemiological and molecular patterns of CRKP among pediatric patients in Jiangsu province, China.Patients and Methods: CRKP were consecutively collected from the Children’s Hospital of Nanjing Medical University in China from July 2018 to May 2019. Then, CRKP strains were performed for further study: antimicrobial susceptibility testing, drug-resistance determinants screening and homology analysis.Results: We collected 94 CRKP from 94 children. Overall, blaKPC-2 (79.8%) was the predominant carbapenemase gene, followed by blaNDM-1(14.9%), blaIMP-4 (5.3%) and blaNDM-5(4.3%). Notably, two isolates coharbored blaKPC-2 and blaIMP-4, and two isolates coharbored blaKPC-2 and blaNDM-5. MLST analysis revealed that 14 distinct sequence types (STs) were identified, of which ST11 was the most common sequence type identified. Moreover, two novel STs, ST4854 and ST4855, were detected in this study. PFGE revealed that a predominant cluster consisting of KPC-2-producing CRKP ST11 clone isolates was identified and was distributed mainly in the pediatric intensive care unit (PICU) and cardiac intensive care unit (CCU). Moreover, this is the first report to identify the dissemination of ST716 CRKP coproducing KPC-2 and IMP-4 clones.Conclusion: Clonal dissemination of KPC-2-producing CRKP ST11 was observed in multiple departments. Moreover, two novel STs (ST4854 and ST4855) were identified, which indicates an increased diversity of CRKP strains. To our knowledge, this is the first report that identified the dissemination of Klebsiella pneumoniae coproducing KPC-2 and IMP-4 clones among children, which represents a significant health risk to pediatric patients. Active surveillance and effective control measures are urgently needed to prevent further transmission of these strains among children.Keywords: Klebsiella pneumoniae, carbapenemase, KPC-2, ST11, clonal dissemination, children

This paper reports our progress in developing techniques for “parsing” raw gaze and force data from manual grinding tasks into a principled model. A grinding task, though simple, requires the practitioner to combine elements from the large repertoire of her skillset. Based on the joint, gaze, and force data collected from a series of experiments, and by extending existing scanpath methods, we develop a visualization method called Gaze-Motor Space-Time Cube (GMSTC), which can help us gain insight into the joint gaze-motor routine existing in complex manual tasks. For instance, there exists a strong correlation between the spectra of a subject's fixation and force distributions. Such insight might be hard to extract through an examination of either the gaze or the force data separately. Furthermore, by comparing data obtained from operators with different levels of skill, we are able to quantitatively describe characteristics of human manual skill. For instance, we find that an experienced subject exhibits longer fixation durations and smaller fixation variations than an intermediate one. A detailed understanding of gaze-motor behavior broadens our knowledge of how a manual task is executed. Our results help to provide this extra insight, and have implications in the way in which knowledge and manual expertise is transferred from one generation of practitioners to the next.

Jun Luo1 ,* Dan Wang2 ,* Xuechao Wan,2 Yangguang Xu,2 Yali Lu,2 Zhe Kong,2 Dujian Li,1 Wei Gu,1 Chenji Wang,2 Yao Li,2 Chaoneng Ji,2 Shaohua Gu,2 Yaoting Xu1 1Department of Urology, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaohua Gu; Yaoting Xu Email shaohuagu@fudan.edu.cn; ytxu64@vip.163.comIntroduction: Prostate cancer (PCa) is the most commonly diagnosed cancer and the third leading cause of cancer-related death in males in the United States. Despite the initial efficacy of androgen deprivation therapy in prostate cancer (PCa) patients, most patients progress to castration-resistant prostate cancer. However, the mechanisms underlying the androgen-independent progression of PCa remain largely unknown.Methods: In this study, we established a PCa cell line (LNCaP-AI) by maintaining LNCaP cells under androgen-depleted conditions. To explore the cellular and molecular mechanisms of androgen-independent growth of PCa, we analyzed the gene expression patterns in androgen-independent prostate cancer (AIPC) compared with that in androgen-dependent prostate cancer (ADPC). KEGG pathway analysis revealed that Wnt signaling pathways were activated after androgen deprivation therapy (ADT). In vitro experiments showed that the inhibition of Wnt pathway reduced AIPC cell growth by inhibiting cell cycle progression and promoting apoptosis. Furthermore, WNT5A, LEF1 were identified as direct targets of AR by chromatin immunoprecipitation (ChIP) assay and public ChIP-seq datasets analysis.Results: In the present study, we found a regulatory mechanism through which crosstalk between androgen receptor (AR) and Wnt signals promoted androgen-independent conversion of PCa. The Wnt pathway was inhibited by androgen in androgen-dependent prostate cancer cells, but this blocking effect was not elicited in androgen-independent prostate cancer (AIPC) cells. Moreover, Wnt pathway genes WNT5A and LEF1 were directly downregulated by AR. In vitro experiments showed that inhibition of the Wnt pathways repressed AIPC cell growth by inhibiting cell cycle progression and promoting apoptosis. We found that WNT5A and LEF1 were downregulated in low-grade PCa but upregulated in metastatic PCa.Conclusion: In summary, we revealed that crosstalk between AR and Wnt signaling pathways promotes androgen-independent growth of PCa, which may provide novel therapeutic opportunities for castration-resistant prostate cancer.Keywords: Wnt pathway, prostate cancer, androgen receptor, androgen deprivation therapy

Ziyan Kong,1,* Rui Cai,1,* Chen Cheng,1 Chuanling Zhang,2 Haiquan Kang,3 Ping Ma,3 Bing Gu1,3 1Medical Technology School, Xuzhou Medical University, Xuzhou, Jiangsu Province, People’s Republic of China; 2Department of Laboratory Medicine, XuZhou Children’s Hospital, Xuzhou, Jiangsu Province, People’s Republic of China; 3Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bing GuDepartment of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, People’s Republic of ChinaTel +8615862163560Email gb20031129@163.comPurpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) have emerged worldwide and also being a major threat to children and neonate. In this study, we describe a nosocomial outbreak of NDM-5-producing Klebsiella pneumoniae in neonatal unit of a teaching hospital in China from September 2015 to September 2016.Patients and methods: We collected 12 carbapenem-resistant K. pneumoniae outbreak strains from 12 newborns and characterized these isolates for their antimicrobial susceptibility, clone relationships, and multi-locus sequence types using vitek-2 compact system, pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Resistant genes were detected by using PCR and sequencing. Plasmid conjugation experiment was carried out to determine the transferability of carbapenem resistance. PCR-based replicon typing (PBRT), S1 nuclease-PFGE, and southern blotting were conducted for plasmid profiling.Results: All 12 K. pneumoniae isolates were resistant to carbapenems and carried blaNDM-5, blaTEM-1 and blaSHV-11. Furthermore, PFGE analysis showed that NDM-5-producing K. pneumoniae were clonally related and MLST assigned them to sequence type 337. Conjugative assays showed that plasmids harboring blaNDM-5 gene were self-transmissible. Plasmid analysis suggested that all blaNDM-5 gene located on a ∼45 kb IncX3 type plasmid.Conclusion: To the best of our knowledge, this is the first report of a clone outbreak of blaNDM-5-carrying K. pneumoniae isolates from neonates. There is an urgent need for effective infection control measures to prevent blaNDM-5 variants from becoming epidemic in the neonates in the future.Keywords: Klebsiella pneumoniae, carbapenemases, blaNDM-5, ST337, neonate, IncX3