EXPERIMENTAL STUDY OF TWO LARGE-SCALE MODELS’ SEAKEEPING PERFORMANCE IN COASTAL WAVES

Actual sea waves and vessel motion are an unsteady nonlinear random process. The currently adopted test to simulate wave impact of vessel models in tank can\u27t fully reveal the impact of real sea waves on vessel swing motion. In this paper the buoy wave height meter is adopted to carry out measurements and analyses of the coastal wave environment. The correlation between the coastal wave spectra and the ocean wave spectra is analyzed. The test system is established for remote control and telemetry self-propelled vessel models suitable for the experiment conducted in the coastal areas. The seakeeping performance test is conducted for the same tonnage of round bilge vessel model and the deep-V hybrid monohull of large-scale vessel model under the coastal wave conditions. The experimental results are compared with the test results of small-scale vessel model in the towing tank. The experimental results show that the seakeeping performance of the deep-V hybrid monohull is improved by a wide margin in contrast to that of the round bilge model, and there is a marked difference between the motion characteristics of large-scale vessel models in the coastal wave environment and that of small-scale vessel models in tank

The chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) controls cellular quiescence by hyperpolarizing the cell membrane during diapause in the crustacean Artemia

Cellular quiescence, a reversible state in which growth, proliferation, and other cellular activities are arrested, is important for self-renewal, differentiation, development, regeneration, and stress resistance. However, the physiological mechanisms underlying cellular quiescence remain largely unknown. In the present study, we used embryos of the crustacean Artemia in the diapause stage, in which these embryos remain quiescent for prolonged periods, as a model to explore the relationship between cell-membrane potential (V-mem) and quiescence. We found that V-mem is hyperpolarized and that the intracellular chloride concentration is high in diapause embryos, whereas V-mem is depolarized and intracellular chloride concentration is reduced in postdiapause embryos and during further embryonic development. We identified and characterized the chloride ion channel protein cystic fibrosis transmembrane conductance regulator (CFTR) of Artemia (Ar-CFTR) and found that its expression is silenced in quiescent cells of Artemia diapause embryos but remains constant in all other embryonic stages. Ar-CFTR knockdown and GlyH-101-mediated chemical inhibition of Ar-CFTR produced diapause embryos having a high V-mem and intracellular chloride concentration, whereas control Artemia embryos released free-swimming nauplius larvae. Transcriptome analysis of embryos at different developmental stages revealed that proliferation, differentiation, and metabolism are suppressed in diapause embryos and restored in postdiapause embryos. Combined with RNA sequencing (RNA-Seq) of GlyH-101-treated MCF-7 breast cancer cells, these analyses revealed that CFTR inhibition down-regulates the Wnt and Aurora Kinase A (AURKA) signaling pathways and up-regulates the p53 signaling pathway. Our findings provide insight into CFTR-mediated regulation of cellular quiescence and V-mem in the Artemia model

Phase Control on Surface for the Stabilization of High Energy Cathode Materials of Lithium Ion Batteries.

The development of high energy electrode materials for lithium ion batteries is challenged by their inherent instabilities, which become more aggravated as the energy densities continue to climb, accordingly causing increasing concerns on battery safety and reliability. Here, taking the high voltage cathode of LiNi0.5Mn1.5O4 as an example, we demonstrate a protocol to stabilize this cathode through a systematic phase modulating on its particle surface. We are able to transfer the spinel surface into a 30 nm shell composed of two functional phases including a rock-salt one and a layered one. The former is electrochemically inert for surface stabilization while the latter is designated to provide necessary electrochemical activity. The precise synthesis control enables us to tune the ratio of these two phases, and achieve an optimized balance between improved stability against structural degradation without sacrificing its capacity. This study highlights the critical importance of well-tailored surface phase property for the cathode stabilization of high energy lithium ion batteries

Doxorubicin in Combination with a Small TGFβ Inhibitor: A Potential Novel Therapy for Metastatic Breast Cancer in Mouse Models

Recent studies suggested that induction of epithelial-mesenchymal transition (EMT) might confer both metastatic and self-renewal properties to breast tumor cells resulting in drug resistance and tumor recurrence. TGFbeta is a potent inducer of EMT and has been shown to promote tumor progression in various breast cancer cell and animal models.We report that chemotherapeutic drug doxorubicin activates TGFbeta signaling in human and murine breast cancer cells. Doxorubicin induced EMT, promoted invasion and enhanced generation of cells with stem cell phenotype in murine 4T1 breast cancer cells in vitro, which were significantly inhibited by a TGFbeta type I receptor kinase inhibitor (TbetaRI-KI). We investigated the potential synergistic anti-tumor activity of TbetaR1-KI in combination with doxorubicin in animal models of metastatic breast cancer. Combination of Doxorubicin and TbetaRI-KI enhanced the efficacy of doxorubicin in reducing tumor growth and lung metastasis in the 4T1 orthotopic xenograft model in comparison to single treatments. Doxorubicin treatment alone enhanced metastasis to lung in the human breast cancer MDA-MB-231 orthotopic xenograft model and metastasis to bone in the 4T1 orthotopic xenograft model, which was significantly blocked when TbetaR1-KI was administered in combination with doxorubicin.These observations suggest that the adverse activation of TGFbeta pathway by chemotherapeutics in the cancer cells together with elevated TGFbeta levels in tumor microenvironment may lead to EMT and generation of cancer stem cells resulting in the resistance to the chemotherapy. Our results indicate that the combination treatment of doxorubicin with a TGFbeta inhibitor has the potential to reduce the dose and consequently the toxic side-effects of doxorubicin, and improve its efficacy in the inhibition of breast cancer growth and metastasis

EVALUATION OF WIND AND WAVE ENVIRONMENT ADAPTABILITY OF SHIPS

The environment adaptability especially integrated sailing performance in rough sea of ships is very important. In this paper the evaluation index system and method of wind and wave environment adaptability were proposed. Then the relative importance of the given indices was analyzed, and the weighting coefficients of the indices were given by estimation matrixes. Besides this the evaluation equation was built. And the AHP method and the method based on fuzzy theory were used for evaluating the environment adaptability of a hybrid monohull and a round bilge monohull. Furthermore, the effect of different models and weighting coefficients given by different matrixes for evaluation results were analyzed. The research indicated that the choice of evaluating parameters had great influence on the evaluation results, and the weighting coefficients were the difficult point but critical point for environment adaptability evaluation of ships

Aphid Endosymbiont Facilitates Virus Transmission by Modulating the Volatile Profile of Host Plants

BACKGROUND: Most plant viruses rely on vectors for their transmission and spread. One of the outstanding biological questions concerning the vector-pathogen-symbiont multi-trophic interactions is the potential involvement of vector symbionts in the virus transmission process. Here, we used a multi-factorial system containing a non-persistent plant virus, cucumber mosaic virus (CMV), its primary vector, green peach aphid, Myzus persicae, and the obligate endosymbiont, Buchnera aphidicola to explore this uncharted territory. RESULTS: Based on our preliminary research, we hypothesized that aphid endosymbiont B. aphidicola can facilitate CMV transmission by modulating plant volatile profiles. Gene expression analyses demonstrated that CMV infection reduced B. aphidicola abundance in M. persicae, in which lower abundance of B. aphidicola was associated with a preference shift in aphids from infected to healthy plants. Volatile profile analyses confirmed that feeding by aphids with lower B. aphidicola titers reduced the production of attractants, while increased the emission of deterrents. As a result, M. persicae changed their feeding preference from infected to healthy plants. CONCLUSIONS: We conclude that CMV infection reduces the B. aphidicola abundance in M. persicae. When viruliferous aphids feed on host plants, dynamic changes in obligate symbionts lead to a shift in plant volatiles from attraction to avoidance, thereby switching insect vector’s feeding preference from infected to healthy plants

Novel indolylarylsulfone derivatives as covalent HIV-1 reverse transcriptase inhibitors specifically targeting the drug-resistant mutant Y181C

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are widely used in combination therapies against HIV-1. However, emergent and transmitted drug resistance compromise their efficacy in the clinical setting. Y181C is selected in patients receiving nevirapine, etravirine and rilpivirine, and together with K103N is the most prevalent NNRTI-associated mutation in HIV-infected patients. Herein, we report on the design, synthesis and biological evaluation of a novel series of indolylarylsulfones bearing acrylamide or ethylene sulfonamide reactive groups as warheads to inactivate Cys181-containing HIV-1 RT via a Michael addition reaction. Compounds I-7 and I-9 demonstrated higher selectivity towards the Y181C mutant than against the wild-type RT, in nucleotide incorporation inhibition assays. The larger size of the NNRTI binding pocket in the mutant enzyme facilitates a better fit for the active compounds, while stacking interactions with Phe227 and Pro236 contribute to inhibitor binding. Mass spectrometry data were consistent with the covalent modification of the RT, although off-target reactivity constitutes a major limitation for further development of the described inhibitors.by grants PID2019-104176RB-I00/AEI/10.13039/501100011033) (Spanish Ministry of Science and Innovation) and 2019AEP001 (CSIC), as well as an institutional grant of Fundación Ramón Areces (awarded to the CBMSO)

MDAD: A Special Resource for Microbe-Drug Associations

The human-associated microbiota is diverse and complex. It takes an essential role in human health and behavior and is closely related to the occurrence and development of disease. Although the diversity and distribution of microbial communities have been widely studied, little is known about the function and dynamics of microbes in the human body or the complex mechanisms of interaction between them and drugs, which are important for drug discovery and design. A high-quality comprehensive microbe and drug association database will be extremely beneficial to explore the relationship between them. In this article, we developed the Microbe-Drug Association Database (MDAD), a collection of clinically or experimentally supported associations between microbes and drugs, collecting 5,055 entries that include 1,388 drugs and 180 microbes from multiple drug databases and related publications. Moreover, we provided detailed annotations for each record, including the molecular form of drugs or hyperlinks from DrugBank, microbe target information from Uniprot and the original reference links. We hope MDAD will be a useful resource for deeper understanding of microbe and drug interactions and will also be beneficial to drug design, disease therapy and human health