Effect of misaligned bearing support performance on natural frequencies of marine propulsion shafting

The influences of bearing support performance which would be affected by the quality of shafting alignment apparently on the lateral vibration natural frequencies of marine propulsion shafting are analyzed in this paper. A three dimensional finite element model representing the entire propulsion shafting, including the bearings, shaft and propeller, has been developed using finite element software for lateral vibration analyses. The effects of the number of bearings, the stiffness and effective contact length of the bearings on the natural frequencies of the shaft are studied respectively. The simulation analysis show that the bearing of a certain position often only has a significant impact on the frequencies of a certain order or a few orders, and the natural frequencies of the shaft can be transferred to avoid the resonance speeds through the reasonable arrangement and performance design of the shaft bearings. In addition, the curve alignment technology is also presented to improve the current shafting alignment quality and misalignment angle error, so as to ensure the design performance of radial bearings. Experimental results show that the curve alignment technology is an effective method to reduce the uneven load and eccentric wear of the bearings, which are beneficial to avoid the resonance vibration and improve the life and stability of shaft system

Analysis of dynamic characteristic for misalignment-spline gear shaft based on whole transfer matrix method

Spline-gear-shaft (SGF), which is mainly composed of gear and spline shaft, is an important transmission system of RAT (driving the generator to output power with ram air). And its dynamic characteristics affect performance of RAT greatly. In this situation, gear coupling and spline coupling, must be taken into account when analyzing dynamics characteristics of SGF. The misalignment of axis for internal and external spline is inevitable owing to mass eccentricity and unconstrained in axial direction in a high-speed operation. Consequently, the dynamic model of SGF is established considering gear coupling and spline coupling based on whole transfer matrix method (WTMM) in this paper. In addition, numerical calculation method of meshing force for spline teeth under the condition of misalignment is presented considering the distribution force on contact surface of spline teeth in this paper, based on this, the coupled transfer matrix of misaligned spline coupling is established and the dynamic characteristics of SGF is analyzed using whole transfer matrix method with Riccati (WTMMR). The test experiments of dynamic characteristics for SGF are carried out by using portable vibration monitoring analyzer in this paper, furthermore, the time-frequency characteristics of SGF are analyzed through the analysis and processing of acceleration signal. The orders of magnitude for the first four natural frequencies with WTMMR are respectively consistent with experiment results, and the relative error is in the accepted range. Therefore, the correctness of solving meshing force and WTMMR for SGF are all verified. Moreover, it also shows that WTMMR is suitable for the analysis of complex coupled systems SGF and provides a new thought for dynamic analysis of complex shafting and promotes dynamic analysis to efficient and streamlined development

Giant palaeo-landslide dammed the Yangtze river

Field evidence is presented to demonstrate that a very large landslide blocked the Jinsha River (the main stem of the Yangtze) near the present day town of Qiaojia, Yunnan Province. The discovery is significant because no persistent river-blocking landslide has been reported so far downstream in a major catchment. At the location of the landslide dam the upstream catchment area is 445 × 103 km^2. Sediments deposited behind the dam indicate that the minimum crest height was approximately 200 m with a lake volume of 11.4 +/− 1.3 km^3. The landslide occurred on the western (Sichuan) side of the river and displaced an estimated volume of at least 3.75 km^3, with material riding up to 550 m above the river on the eastern (Yunnan) side of the valley. The location is at the intersection of the Xiaojiang and Zemuhe fault zones which form part of the eastern boundary fault of the Sichuan-Yunnan Fault Block, an area where many earthquakes exceeding magnitude 7.0 have been documented in the historical record

Targeting translation initiation by synthetic rocaglates for treating MYC-driven lymphomas.

MYC-driven lymphomas, especially those with concurrent MYC and BCL2 dysregulation, are currently a challenge in clinical practice due to rapid disease progression, resistance to standard chemotherapy, and high risk of refractory disease. MYC plays a central role by coordinating hyperactive protein synthesis with upregulated transcription in order to support rapid proliferation of tumor cells. Translation initiation inhibitor rocaglates have been identified as the most potent drugs in MYC-driven lymphomas as they efficiently inhibit MYC expression and tumor cell viability. We found that this class of compounds can overcome eIF4A abundance by stabilizing target mRNA-eIF4A interaction that directly prevents translation. Proteome-wide quantification demonstrated selective repression of multiple critical oncoproteins in addition to MYC in B-cell lymphoma including NEK2, MCL1, AURKA, PLK1, and several transcription factors that are generally considered undruggable. Finally, (-)-SDS-1-021, the most promising synthetic rocaglate, was confirmed to be highly potent as a single agent, and displayed significant synergy with the BCL2 inhibitor ABT199 in inhibiting tumor growth and survival in primary lymphoma cells in vitro and in patient-derived xenograft mouse models. Overall, our findings support the strategy of using rocaglates to target oncoprotein synthesis in MYC-driven lymphomas.P30 CA036727 - NCI NIH HHS; R24 GM111625 - NIGMS NIH HHS; R35 GM118173 - NIGMS NIH HHS; LB506 - Nebraska Department of Health and Human Services (Nebraska DHHS)Accepted manuscriptSupporting documentatio

Repurposing Niclosamide as a Novel Anti-SARS-CoV-2 Drug by Restricting Entry Protein CD147

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic, and the search for effective treatments has been limited. Furthermore, the rapid mutations of SARS-CoV-2 have posed challenges to existing vaccines and neutralizing antibodies, as they struggle to keep up with the increased viral transmissibility and immune evasion. However, there is hope in targeting the CD147-spike protein, which serves as an alternative point for the entry of SARS-CoV-2 into host cells. This protein has emerged as a promising therapeutic target for the development of drugs against COVID-19. Here, we demonstrate that the RNA-binding protein Human-antigen R (HuR) plays a crucial role in the post-transcriptional regulation of CD147 by directly binding to its 3′-untranslated region (UTR). We observed a decrease in CD147 levels across multiple cell lines upon HuR depletion. Furthermore, we identified that niclosamide can reduce CD147 by lowering the cytoplasmic translocation of HuR and reducing CD147 glycosylation. Moreover, our investigation revealed that SARS-CoV-2 infection induces an upregulation of CD147 in ACE2-expressing A549 cells, which can be effectively neutralized by niclosamide in a dose-dependent manner. Overall, our study unveils a novel regulatory mechanism of regulating CD147 through HuR and suggests niclosamide as a promising therapeutic option against COVID-19

Recent Changes of Suspended Sediment Yields in the Upper Yangtze River and Its Headwater Tributaries

Abstract: Suspended sediment yields in the Upper Yangtze River and its four headwater tributaries (i.e., Jinsha, Min, Jialing and Wu) have declined significantly during the recent decades. Compared with 1956Compared with -1970, mean annual suspended sediment yield during 2001-2011wasreduced by 84% in the Upper Yangtze River at Yichang, by 34% in the Jinsha at Pingshan, by 84% in the Jialing at Beibei, by 75% in the Wu at Wulong, and by 48% in the Min at Gaochang. Linking the observed decadal changes of runoff discharge and suspended sediment load to dam construction and multiple environmental rehabilitation projects (e.g., soil-water conservation, reforestation) during the past decades, it can be concluded that the construction of large dams on the main stem and major tributaries of the Upper Yangtze River has played a principal role in the reduction of fluvial suspended sediment yields, while the environment rehabilitation projects may make limited contributions to the changes in suspended sediment yields except for the Jialing River

Double-blind comparison of ziprasidone and risperidone in the treatment of Chinese patients with acute exacerbation of schizophrenia

Background: The aim of the study was to evaluate the efficacy and safety of ziprasidone versus risperidone in Chinese subjects with acute exacerbation of schizophrenia. Methods: In patients meeting the Chinese Classification of Mental Disorders criteria for schizophrenia and with a Positive and Negative Syndrome Scale (PANSS) total score >= 60 were randomly assigned to six weeks of double-blind treatment with ziprasidone 40-80 mg twice daily or risperidone 1-3 mg bid, flexibly dosed. Noninferiority was demonstrated if the upper limit of the two-sided 95% confidence interval (CI) for the difference in PANSS total score improvement from baseline in the evaluable population was smaller than the prespecified noninferiority margin of 10 units. Results: The intent-to-treat population comprised 118 ziprasidone-treated and 121 risperidone-treated subjects. Improvement (reduction) from baseline to week 6 in PANSS total score was (-35.6 [95% CI: -38.6, -32.6]) for ziprasidone and (-37.1 [95% CI: -39.9, -34.4]) for risperidone. Noninferiority was demonstrated in the evaluable population with a difference score of 1.5 [95% CI: -2.5, 5.5]. Mean prolactin levels decreased at week 6 compared with baseline for ziprasidone (-3.5 ng/mL), but significantly increased for risperidone (61.1 ng/mL; P < 0.001). More risperidone-treated subjects (14.9%) than ziprasidone-treated subjects (4.2%) reported weight gain >= 7%. Akathisia and somnolence in the ziprasidone group and akathisia and insomnia in the risperidone group were the most common side effects. Treatment-related/treatment-emergent adverse events were reported by 79.7% and 71.1% of ziprasidone-treated and risperidone-treated subjects, respectively. Conclusion: In Chinese subjects, ziprasidone was as effective as risperidone, with less weight gain and less prolactin elevation.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000294955100009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Clinical NeurologyPsychiatrySCI(E)PubMed3ARTICLE77-85

MicroRNA miR-34 Inhibits Human Pancreatic Cancer Tumor-Initiating Cells

This is the published version, also available here: http://dx.doi.org/10.1371/journal.pone.0006816.Background MicroRNAs (miRNAs) have been implicated in cancer initiation and progression via their ability to affect expression of genes and proteins that regulate cell proliferation and/or cell death. Transcription of the three miRNA miR-34 family members was recently found to be directly regulated by p53. Among the target proteins regulated by miR-34 are Notch pathway proteins and Bcl-2, suggesting the possibility of a role for miR-34 in the maintenance and survival of cancer stem cells. Methodology/Principal Findings We examined the roles of miR-34 in p53-mutant human pancreatic cancer cell lines MiaPaCa2 and BxPC3, and the potential link to pancreatic cancer stem cells. Restoration of miR-34 expression in the pancreatic cancer cells by either transfection of miR-34 mimics or infection with lentiviral miR-34-MIF downregulated Bcl-2 and Notch1/2. miR-34 restoration significantly inhibited clonogenic cell growth and invasion, induced apoptosis and G1 and G2/M arrest in cell cycle, and sensitized the cells to chemotherapy and radiation. We identified that CD44+/CD133+ MiaPaCa2 cells are enriched with tumorsphere-forming and tumor-initiating cells or cancer stem/progenitor cells with high levels of Notch/Bcl-2 and loss of miR-34. More significantly, miR-34 restoration led to an 87% reduction of the tumor-initiating cell population, accompanied by significant inhibition of tumorsphere growth in vitro and tumor formation in vivo. Conclusions/Significance Our results demonstrate that miR-34 may restore, at least in part, the tumor suppressing function of the p53 in p53-deficient human pancreatic cancer cells. Our data support the view that miR-34 may be involved in pancreatic cancer stem cell self-renewal, potentially via the direct modulation of downstream targets Bcl-2 and Notch, implying that miR-34 may play an important role in pancreatic cancer stem cell self-renewal and/or cell fate determination. Restoration of miR-34 may hold significant promise as a novel molecular therapy for human pancreatic cancer with loss of p53–miR34, potentially via inhibiting pancreatic cancer stem cells