A comparison of track model formulations for simulation of dynamic vehicle–track interaction in switches and crossings

This paper compares different track model formulations for the simulation of dynamic vehicle–track interaction in switches and crossings (S&C, turnouts) in a multi-body simulation (MBS) environment. The investigations are an extension of the S&C simulation Benchmark with the addition of a finite element model of a 60E1-760-1:15 turnout. This model constitutes a common reference from which four different track formulations are derived: co-running, modal superposition, finite element incorporated into the MBS model and finite element coupled to MBS using a co-simulation approach. For the different track models, the difference in modelling technique, results, simulation time, and suitability for different simulation tasks is compared. A good agreement is found between the different track model formulations for wheel–rail contact forces and rail displacements. This study found a better agreement between co-running and structural track models compared to previous studies in the prediction of wheel–rail contact forces. This appears to be due to the increased complexity of co-running track model used in this study together with a tuning of the co-running track model to the reference model in a wider frequency range. For the reader interested to reproduce the results in this paper, the reference track model is available for download

Amelioration of Ductular Reaction by Stem Cell Derived Extracellular Vesicles in MDR2 Knockout Mice via Lethal-7 microRNA

Cholangiopathies are diseases that affect cholangiocytes, the cells lining the biliary tract. Liver stem cells (LSCs) are able to differentiate into all cells of the liver and possibly influence the surrounding liver tissue by secretion of signaling molecules. One way in which cells can interact is through secretion of extracellular vesicles (EVs), which are small membrane-bound vesicles that contain proteins, microRNAs (miRNAs), and cytokines. We evaluated the contents of liver stem cell–derived EVs (LSCEVs), compared their miRNA contents to those of EVs isolated from hepatocytes, and evaluated the downstream targets of these miRNAs. We finally evaluated the crosstalk among LSCs, cholangiocytes, and human hepatic stellate cells (HSCs). We showed that LSCEVs were able to reduce ductular reaction and biliary fibrosis in multidrug resistance protein 2 (MDR2)−/− mice. Additionally, we showed that cholangiocyte growth was reduced and HSCs were deactivated in LSCEV-treated mice. Evaluation of LSCEV contents compared with EVs derived from hepatocytes showed a large increase in the miRNA, lethal-7 (let-7). Further evaluation of let-7 in MDR2−/− mice and human primary sclerosing cholangitis samples showed reduced levels of let-7 compared with controls. In liver tissues and isolated cholangiocytes, downstream targets of let-7 (identified by ingenuity pathway analysis), Lin28a (Lin28 homolog A), Lin28b (Lin28 homolog B), IL-13 (interleukin 13), NR1H4 (nuclear receptor subfamily 1 group H member 4) and NF-κB (nuclear factor kappa B), are elevated in MDR2−/− mice, but treatment with LSCEVs reduced levels of these mediators of ductular reaction and biliary fibrosis through the inhibition of NF-κB and IL-13 signaling pathways. Evaluation of crosstalk using cholangiocyte supernatants from LSCEV-treated cells on cultured HSCs showed that HSCs had reduced levels of fibrosis and increased senescence. Conclusion: Our studies indicate that LSCEVs could be a possible treatment for cholangiopathies or could be used for target validation for future therapies

Stem cell-based approach in diabetes and pancreatic cancer management

Stem cell-mediated therapy is a promising strategy for treating pancreatic diseases such as Type-1 diabetes (T1D) and pancreatic cancers. Although islet transplantation has been reported to be an effective diabetes therapy, its worldwide application is extremely limited due to the shortage of donor islets and immune rejection problems. Stem cell-based approach for islet neogenesis in vivo could provide a promising alternative source of islets for treating diabetes. On the other hand, targeting the cancer stem cells could be very effective for the treatment of pancreatic cancers. In this review, we focused on the present progress in the field of adult pancreatic stem cells, stem cell-mediated strategies for treating T1D, and pancreatic cancer stem cells, while discussing of the possible challenges involved in them

Histone H2A and H2B Deubiquitinase in Developmental Disease and Cancer

Histone H2A and H2B ubiquitination represents a widely used mechanism for a variety of regulatory transcriptional programs. In this review, structural and functional studies of histone H2A and histone H2B deubiquitinase (DUB), DUB including 2A-DUB, BRCA1-associated protein-1, USP3, UBP8, and USP16, and their role in developmental disease and carcinogenesis were recapitulated. Also the progress in developing small molecular inhibitors targeting DUBs and their application in colon cancer, B-cell lymphoma, and multiple myeloma were summarized. Overall, the study seek to strengthen the understanding on how these DUBs contribute to normal and malignant tissue development thus aiding in improving the design of therapeutic strategies used for diagnosis and prognosis of the disease

Melanoma Antigen Gene Family in the Cancer Immunotherapy

Recent progression in cancer immunotherapy made checkpoint blockade and T-cell engineering excitingly successful in clinical trials. The melanoma antigen gene (MAGE) protein family has been noticed for their restricted expression in reproductive tissues and a wide variety of cancer types for decades. Tumor-specific expression pattern and antigenic properties made MAGE family members a promising cancer immunotherapy target. This review introduces the background of cancer immunotherapy and MAGE family members while highlighting the recent developments in the implication of MAGE family in different contexts of cancer immunotherapy and enlisting the outstanding questions in the field

A Reversible Colorimetric and Fluorescence “Turn-Off” Chemosensor for Detection of Cu2+ and Its Application in Living Cell Imaging

Dual-function chemosensors that combine the capability of colorimetric and fluorimetric detection of Cu2+ are still relatively rare. Herein, we report that a 3-hydroxyflavone derivative (E)-2-(4-(dimethylamino)styryl)-3-hydroxy-4H-chromen-4-one (4), which is a red-emitting fluorophore, could serve as a reversible colorimetric and fluorescence “turn-off” chemosensor for the detection of Cu2+. Upon addition of Cu2+ to 4 in neutral aqueous solution, a dramatic color change from yellow to purple-red was clearly observed, and its fluorescence was markedly quenched, which was attributed to the complexation between the chemosensor and Cu2+. Conditions of the sensing process had been optimized, and the sensing studies were performed in a solution of ethanol/phosphate buffer saline (v/v = 3:7, pH = 7.0). The sensing system exhibited high selectivity towards Cu2+. The limit of naked eye detection of Cu2+ was determined at 8 × 10−6 mol/L, whereas the fluorescence titration experiment showed a detection limit at 5.7 × 10−7 mol/L. The complexation between 4 and Cu2+ was reversible, and the binding constant was found to be 3.2 × 104 M−1. Moreover, bioimaging experiments showed that 4 could penetrate the cell membrane and respond to the intracellular changes of Cu2+ within living cells, which indicated its potential for biological applications

Generation of a squamous cell carcinoma mouse model for lineage tracing of BMI1+ cancer stem cells

Summary: BMI1-expressing cancer stem cells (CSCs) play a key role in the development, progression, therapy resistance, recurrence, and metastasis of head and neck squamous cell carcinoma (HNSCC). Here, we present a chemically-induced HNSCC mouse model, genetically and pathologically similar to human HNSCC. This protocol describes how to use genetic lineage tracing based on the Cre-loxP recombination strategy, which allows us to study the regulation and targeting of BMI1+ CSCs in primary tumors and lymph node metastases.For complete details on the use and execution of this protocol, please refer to Chen et al. (2017) and Jia et al. (2020

A new hybrid model to predict the electrical load in five states of Australia

Short-term electrical load forecasting is an important part in the management of electrical power because electrical load is an extreme, complex non-linear system. To obtain parameter values that provide better performances with high precision, this paper proposes a new hybrid electrical load forecasting model, which combines ensemble empirical mode decomposition, extreme learning machine, and grasshopper optimization algorithm for short-term load forecasting. The most important difference that distinguishes this electrical load forecasting model from other models is that grasshopper optimization can search suitable parameters (weight values and threshold values) of extreme learning machine, while traditional parameters are selected randomly. It is applied in Australia electrical load prediction to show its superiority and applicability. The simulation studies are carried out using a data set collected from five main states (New South Wales, Queensland, Tasmania, South Australia and Victoria) in Australia from February 1 to February 27, 2018. Compared with all considered basic models, the proposed hybrid model has the best performance in predicting electrical load

Metal Content and Enrichment in Bivalves within the Drainage Area of Seawater Used for a Desulfurization Process in Zhanjiang Bay, China

As heavy metals are easy to accumulate and have strong biological toxicity, they pose a potential threat to human health by entering the human body through the cumulative effect of marine life. Land-based input is an important source of heavy metals in the ocean, which has a great influence on coastal water quality. In this study, the spatial distribution characteristics of heavy metals (Zn, Cu, Cd, Pb, Cr, As) in the coastal waters of the desulfurization process outlet of a power plant in Zhanjiang Bay were investigated, and the enrichment behavior of heavy metals by organisms (oysters and barnacles) were also studied. The results showed that, before the seawater desulfurization system was closed, there were high concentrations of heavy metals (Cu, Zn, Cd, Pb and Cr) in the surface seawater near the drainage outlet. The concentrations of these heavy metals in the surface seawater were higher than those in the bottom seawater within 100 m of the drainage outlet. After the seawater desulfurization system was closed, the average concentrations of Cu, Cr and As in seawater at each station decreased by 17.04%, 37.52% and 29.53%, respectively, while the average concentrations of Zn, Cd and Pb increased by 17.05%, 32.87% and 48.77%, respectively. Single factor pollution index (SFI) and bio-concentration factor (BCF) showed that there was a potential high accumulation risk of Zn in oysters and barnacles near the drainage outlet of desulfurization wastewater (0.5 < SFI < 1 and BCF > 1000). The SFI and BCF of each metal in oysters and barnacles decreased with the increase in distance from the drainage outlet. Generally, the coastal water quality of desulfurization process drainage area in Zhanjiang Bay were below the class Ⅱof the “Seawater quality standard” (GB 3097-1997) of China. However, the heavy metals content in seawater and organisms near the drainage outlet is slightly higher. This suggested that if the seawater desulfurization process runs for a long time, it will have a negative impact on the coastal water and organisms