Sample records for axles

  1. An engineered Axl 'decoy receptor' effectively silences the Gas6-Axl signaling axis

    DOE PAGES

    Kariolis, Mihalis S.; Miao, Yu Rebecca; Jones, Douglas S.; ...

    2014-09-21

    Aberrant signaling through the Axl receptor tyrosine kinase has been associated with a myriad of human diseases, most notably metastatic cancer, identifying Axl and its ligand Gas6 as important therapeutic targets. Using rational and combinatorial approaches, we engineered an Axl ‘decoy receptor’ that binds Gas6 with high affinity and inhibits its function, offering an alternative approach from drug discovery efforts that directly target Axl. Four mutations within this high affinity Axl variant caused structural alterations in side chains across the Gas6/Axl binding interface, stabilizing a conformational change on Gas6. When reformatted as an Fc-fusion, the engineered decoy receptor bound tomore » Gas6 with femtomolar affinity, an 80-fold improvement compared to the wild-type Axl receptor, allowing effective sequestration of Gas6 and specific abrogation of Axl signaling. Additionally, increased Gas6 binding affinity was critical and correlative with the ability of decoy receptors to potently inhibit metastasis and disease progression in vivo.« less

  2. AXL mediates resistance to cetuximab therapy

    PubMed Central

    Brand, Toni M.; Iida, Mari; Stein, Andrew P.; Corrigan, Kelsey L.; Braverman, Cara; Luthar, Neha; Toulany, Mahmoud; Gill, Parkash S.; Salgia, Ravi; Kimple, Randall J.; Wheeler, Deric L.

    2014-01-01

    The EGFR antibody cetuximab is used to treat numerous cancers, but intrinsic and acquired resistance to this agent is a common clinical problem. In this study we show that overexpression of the oncogenic receptor kinase AXL is sufficient to mediate acquired resistance to cetuximab in models of non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC), where AXL was overexpressed, activated and tightly associated with EGFR expression in cells resistant to cetuximab (CtxR cells). Using RNAi methods and novel AXL targeting agents, we found that AXL activation stimulated cell proliferation, EGFR activation and MAPK signaling in CtxR cells. Notably, EGFR directly regulated the expression of AXL mRNA through MAPK signaling and the transcription factor c-Jun in CtxR cells, creating a positive feedback loop that maintained EGFR activation by AXL. Cetuximab-sensitive parental cells were rendered resistant to cetuximab by stable overexpression of AXL or stimulation with EGFR ligands, the latter of which increased AXL activity and association with the EGFR. In tumor xenograft assays, the development of resistance following prolonged treatment with cetuximab was associated with AXL hyperactivation and EGFR association. Furthermore, in an examination of patient-derived xenografts established from surgically resected HNSCCs, AXL was overexpressed and activated in tumors that displayed intrinsic resistance to cetuximab. Collectively, our results identify AXL as a key mediator of cetuximab resistance, providing a rationale for clinical evaluation of AXL targeting drugs to treat cetuximab-resistant cancers. PMID:25136066

  3. AXL mediates resistance to cetuximab therapy.

    PubMed

    Brand, Toni M; Iida, Mari; Stein, Andrew P; Corrigan, Kelsey L; Braverman, Cara M; Luthar, Neha; Toulany, Mahmoud; Gill, Parkash S; Salgia, Ravi; Kimple, Randall J; Wheeler, Deric L

    2014-09-15

    The EGFR antibody cetuximab is used to treat numerous cancers, but intrinsic and acquired resistance to this agent is a common clinical outcome. In this study, we show that overexpression of the oncogenic receptor tyrosine kinase AXL is sufficient to mediate acquired resistance to cetuximab in models of non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC), where AXL was overexpressed, activated, and tightly associated with EGFR expression in cells resistant to cetuximab (Ctx(R) cells). Using RNAi methods and novel AXL-targeting agents, we found that AXL activation stimulated cell proliferation, EGFR activation, and MAPK signaling in Ctx(R) cells. Notably, EGFR directly regulated the expression of AXL mRNA through MAPK signaling and the transcription factor c-Jun in Ctx(R) cells, creating a positive feedback loop that maintained EGFR activation by AXL. Cetuximab-sensitive parental cells were rendered resistant to cetuximab by stable overexpression of AXL or stimulation with EGFR ligands, the latter of which increased AXL activity and association with the EGFR. In tumor xenograft models, the development of resistance following prolonged treatment with cetuximab was associated with AXL hyperactivation and EGFR association. Furthermore, in an examination of patient-derived xenografts established from surgically resected HNSCCs, AXL was overexpressed and activated in tumors that displayed intrinsic resistance to cetuximab. Collectively, our results identify AXL as a key mediator of cetuximab resistance, providing a rationale for clinical evaluation of AXL-targeting drugs to treat cetuximab-resistant cancers. Cancer Res; 74(18); 5152-64. ©2014 AACR. ©2014 American Association for Cancer Research.

  4. Imaging Axl expression in pancreatic and prostate cancer xenografts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nimmagadda, Sridhar, E-mail: snimmag1@jhmi.edu; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287; Pullambhatla, Mrudula

    2014-01-10

    Highlights: •Axl is overexpressed in a variety of cancers. •Axl overexpression confers invasive phenotype. •Axl imaging would be useful for therapeutic guidance and monitoring. •Axl expression imaging is demonstrated in pancreatic and prostate cancer xenografts. •Graded levels of Axl expression imaging is feasible. -- Abstract: The receptor tyrosine kinase Axl is overexpressed in and leads to patient morbidity and mortality in a variety of cancers. Axl–Gas6 interactions are critical for tumor growth, angiogenesis and metastasis. The goal of this study was to investigate the feasibility of imaging graded levels of Axl expression in tumors using a radiolabeled antibody. We radiolabeledmore » anti-human Axl (Axl mAb) and control IgG1 antibodies with {sup 125}I with high specific radioactivity and radiochemical purity, resulting in an immunoreactive fraction suitable for in vivo studies. Radiolabeled antibodies were investigated in severe combined immunodeficient mice harboring subcutaneous CFPAC (Axl{sup high}) and Panc1 (Axl{sup low}) pancreatic cancer xenografts by ex vivo biodistribution and imaging. Based on these results, the specificity of [{sup 125}I]Axl mAb was also validated in mice harboring orthotopic Panc1 or CFPAC tumors and in mice harboring subcutaneous 22Rv1 (Axl{sup low}) or DU145 (Axl{sup high}) prostate tumors by ex vivo biodistribution and imaging studies at 72 h post-injection of the antibody. Both imaging and biodistribution studies demonstrated specific and persistent accumulation of [{sup 125}I]Axl mAb in Axl{sup high} (CFPAC and DU145) expression tumors compared to the Axl{sup low} (Panc1 and 22Rv1) expression tumors. Axl expression in these tumors was further confirmed by immunohistochemical studies. No difference in the uptake of radioactivity was observed between the control [{sup 125}I]IgG1 antibody in the Axl{sup high} and Axl{sup low} expression tumors. These data demonstrate the feasibility of imaging Axl expression in

  5. 49 CFR 215.105 - Defective axle.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Suspension System § 215.105 Defective axle. A railroad may not place or continue in service a car, if— (a) An axle on the car has a crack or is broken; (b) An axle on the car has a gouge in the surface that is— (1) Between...

  6. 49 CFR 215.105 - Defective axle.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Suspension System § 215.105 Defective axle. A railroad may not place or continue in service a car, if— (a) An axle on the car has a crack or is broken; (b) An axle on the car has a gouge in the surface that is— (1) Between...

  7. 49 CFR 215.105 - Defective axle.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Suspension System § 215.105 Defective axle. A railroad may not place or continue in service a car, if— (a) An axle on the car has a crack or is broken; (b) An axle on the car has a gouge in the surface that is— (1) Between...

  8. 49 CFR 215.105 - Defective axle.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Suspension System § 215.105 Defective axle. A railroad may not place or continue in service a car, if— (a) An axle on the car has a crack or is broken; (b) An axle on the car has a gouge in the surface that is— (1) Between...

  9. 49 CFR 215.105 - Defective axle.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Suspension System § 215.105 Defective axle. A railroad may not place or continue in service a car, if— (a) An axle on the car has a crack or is broken; (b) An axle on the car has a gouge in the surface that is— (1) Between...

  10. 49 CFR 230.99 - Tender truck axles.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Tenders Running Gear § 230.99 Tender truck axles. The minimum diameters of axles for various axle loads... wheel seat (in inches) Minimumdiameter of center (in inches) 50000 51/2 73/8 67/16 38000 5 63/4 57/8...

  11. Impact of Expression of Vimentin and Axl in Breast Cancer.

    PubMed

    Tanaka, Kimihiro; Tokunaga, Eriko; Inoue, Yuka; Yamashita, Nami; Saeki, Hiroshi; Okano, Shinji; Kitao, Hiroyuki; Oki, Eiji; Oda, Yoshinao; Maehara, Yoshihiko

    2016-12-01

    The association between Axl and vimentin protein expression has been observed in several cell lines. However, the clinical importance of Axl and vimentin expression in breast cancer have not been fully determined. The expressions of Axl and vimentin were evaluated by immunohistochemistry in a total of 343 patients with invasive ductal carcinoma. The relationships between expression of Axl and vimentin and clinicopathologic characteristics and prognosis were analyzed. Axl expression was classified into high (n = 170) and low (n = 173) expression groups. Axl expression alone was not associated with any clinicopathologic factor or prognosis. Coexistence of vimentin-positive and Axl-high expression was observed in 10.5% (n = 36). Vimentin-positive and Axl-high tumors were associated with triple-negative breast cancers (P = .0396) and with poor prognosis in terms of both recurrence-free survival (P = .0126) and overall survival (P = .0005) compared to the other groups, including vimentin-positive and Axl-low tumors, vimentin-negative and Axl-high tumors, and vimentin-negative and Axl-low tumors. Multivariate analysis showed that coexistence of vimentin-positive and Axl-high expression was an independent poor prognostic factor for recurrence-free survival (hazard ratio, 2.78; 95% confidence interval, 1.23-5.68; P = .0158) and overall survival (hazard ratio, 3.72; 95% confidence interval, 1.51-8.47; P = .0059). Coexistence of vimentin-positive and Axl-high expression is a poor prognostic factor for primary breast cancer. Vimentin and Axl expression might contribute to the aggressive phenotype in breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. AXL kinase as a novel target for cancer therapy

    PubMed Central

    Lee, Chang Youl; Zhang, Zhenfeng; Halmos, Balazs

    2014-01-01

    The AXL receptor tyrosine kinase and its major ligand, GAS6 have been demonstrated to be overexpressed and activated in many human cancers (such as lung, breast, and pancreatic cancer) and have been correlated with poor prognosis, promotion of increased invasiveness/metastasis, the EMT phenotype and drug resistance. Targeting AXL in different model systems with specific small molecule kinase inhibitors or antibodies alone or in combination with other drugs can lead to inactivation of AXL-mediated signaling pathways and can lead to regained drug sensitivity and improved therapeutic efficacy, defining AXL as a promising novel target for cancer therapeutics. This review highlights the data supporting AXL as a novel treatment candidate in a variety of cancers as well as the current status of drug development targeting the AXL/GAS6 axis and future perspectives in this emerging field. PMID:25337673

  13. Inhibition of Axl improves the targeted therapy against ALK-mutated neuroblastoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xu, Fei; Li, Hongling; Sun, Yong, E-mail: sunfanqi2010@163.com

    2014-11-28

    Highlights: • First reported Axl is co-expressed with ALK in neuroblastoma tissues and cell lines. • Axl activation promotes cell growth and impairs the efficiency of ALK inhibitor. • Further found silence of Axl leads to increased sensitivity to ALK inhibitors. • Axl inhibitor promotes the efficiency of targeted therapy in vitro and in vivo. • Axl activation should be considered in the clinical application of ALK inhibitors. - Abstract: Neuroblastoma (NB) patients harboring mutated ALK can be expected to potentially benefit from targeted therapy based on ALK tyrosine kinase inhibitor (TKI), such as crizotinib and ceritinib. However, the effectmore » of the treatment varies with different individuals, although with the same genic changes. Axl receptor tyrosine kinase is expressed in a variety of human cancers, but little data are reported in NB, particularly in which carrying mutated ALK. In this study, we focus on the roles of Axl in ALK-mutated NB for investigating rational therapeutic strategy. We found that Axl is expressed in ALK-positive NB tissues and cell lines, and could be effectively activated by its ligand GAS6. Ligand-dependent Axl activation obviously rescued crizotinib-mediated suppression of cell proliferation in ALK-mutated NB cells. Genetic inhibition of Axl with specific small interfering RNA markedly increased the sensitivity of cells to ALK-TKIs. Furthermore, a small-molecule inhibitor of Axl significantly enhanced ALK-targeted therapy, as an increased frequency of apoptosis was observed in NB cells co-expressing ALK and Axl. Taken together, our results demonstrated that activation of Axl could lead to insensitivity to ALK inhibitors, and dual inhibition of ALK and Axl might be a potential therapeutic strategy against ALK-mutated NB.« less

  14. Better load-weight distribution is needed for tandem-axle logging trucks

    Treesearch

    John E. Baumgras

    1976-01-01

    To determine the GVW and axle weights of tandem-axle logging trucks hauling into two West Virginia sawmills, 543 truckloads of hardwood sawlogs were weighed. The results showed that less than 2 percent of the truckloads exceeded the 48,000 pound GVW limit. While 58 percent of the truckloads exceeded the 32,000 pound tandem-axle weight limit, the front-axle weights...

  15. Axl is not an indispensable factor for Zika virus infection in mice.

    PubMed

    Wang, Zhao-Yang; Wang, Zai; Zhen, Zi-Da; Feng, Kai-Hao; Guo, Jing; Gao, Na; Fan, Dong-Ying; Han, Dai-Shu; Wang, Pei-Gang; An, Jing

    2017-08-01

    Recently, Zika virus (ZIKV) outbreak has been associated with a sharp increase in cases of Guillain-Barré syndrome and severe fetal abnormalities. However, the mechanism underlying the interaction of ZIKV with host cells is not yet clear. Axl, a receptor tyrosine kinase, is postulated as a receptor for ZIKV entry; however, its in vivo role during ZIKV infection and its impact on the outcome of the disease have not been fully characterized and evaluated. Moreover, there are contradictory results on its involvement in ZIKV infection. Here we utilized Axl-deficient mice (Axl-/-) and their littermates (Axl+/-) to study the in vivo role of Axl in ZIKV infection. Our results showed that both Axl+/- and Axl-/- suckling mice supported the replication of ZIKV and presented clinical manifestations. No significant difference has been found between Axl-deficient mice and their littermates in terms of the survival rate, clinical manifestations, viral load, ZIKV distribution and histopathological changes in major organs. These results therefore indicate that Axl is not an indispensable factor for ZIKV infection in mice.

  16. Accurate Determination of Soluble Axl by Enzyme-Linked Immunosorbent Assay.

    PubMed

    Dengler, Mirko; Huber, Heidemarie; Müller, Christian J; Zellmer, Angela; Rauch, Peter; Mikulits, Wolfgang

    2016-11-01

    Levels of soluble Axl (sAxl) are routinely assessed in human sera by sandwich enzyme-linked immunosorbent assay (ELISA). Although sAxl values are suggested to diagnose different types of disorders, no uniform ELISA method is available, allowing the reliable interassay comparison between results. Furthermore, little is known about the stability of sAxl under storage conditions, which is a relevant parameter for biomedical trials. The evaluation of sAxl stability under various stress conditions and the determination of proper conditions to use the sAxl ELISA for routine clinical applications are of great interest. In this study, serum samples were subjected to freeze-thaw cycles and incubation at different temperatures to analyze the stability of sAxl by ELISA. Dilution and spike-in experiments were carried out to examine the impact of serum and diluent components on the ELISA performance. Various diluents and media were employed to resolve masking effects of the serum. The assay components were further optimized for long-term usability by treatment with stabilizers and validation under temperature stress. Indeed, sAxl showed long-term stability in serum during freeze-thaw cycles and incubation under temperature stress conditions. The dilution experiments revealed that unknown components in the serum caused masking effects that can be reduced by proper dilutions. The assay performance was further increased by using a standardized buffer system to dilute serum samples. Stabilization of coated plates and of streptavidin-horseradish peroxidase allowed long-term storage for up to 6 months. In sum, our data demonstrate proper ELISA conditions, allowing the accurate analysis of sAxl levels in human serum.

  17. 49 CFR 230.98 - Driving, trailing, and engine truck axles.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Driving, trailing, and engine truck axles. 230.98... Locomotives and Tenders Running Gear § 230.98 Driving, trailing, and engine truck axles. (a) Condemning defects. Driving, trailing, and engine truck axles with any of the following defects shall be removed from...

  18. 49 CFR 230.98 - Driving, trailing, and engine truck axles.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Locomotives and Tenders Running Gear § 230.98 Driving, trailing, and engine truck axles. (a) Condemning defects. Driving, trailing, and engine truck axles with any of the following defects shall be removed from... 49 Transportation 4 2011-10-01 2011-10-01 false Driving, trailing, and engine truck axles. 230.98...

  19. AXL is a logical molecular target in head and neck squamous cell carcinoma

    PubMed Central

    Brand, Toni M.; Iida, Mari; Stein, Andrew P.; Corrigan, Kelsey L.; Braverman, Cara M.; Coan, John; Pearson, Hannah E.; Bahrar, Harsh; Fowler, Tyler L.; Bednarz, Bryan P.; Saha, Sandeep; Yang, David; Gill, Parkash S.; Lingen, Mark W.; Saloura, Vassiliki; Villaflor, Victoria M.; Salgia, Ravi; Kimple, Randall J.; Wheeler, Deric L.

    2016-01-01

    Purpose Head and neck squamous cell carcinoma (HNSCC) represents the eighth most common malignancy worldwide. Standard of care treatments for HNSCC patients include surgery, radiation and chemotherapy. Additionally, the anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab is often used in combination with these treatment modalities. Despite clinical success with these therapeutics, HNSCC remains a difficult to treat malignancy. Thus, identification of new molecular targets is critical. Experimental Design In the current study, the receptor tyrosine kinase AXL was investigated as a molecular target in HNSCC using established cell lines, HNSCC patient derived xenografts (PDXs), and human tumors. HNSCC dependency on AXL was evaluated with both anti-AXL siRNAs and the small molecule AXL inhibitor R428. Furthermore, AXL inhibition was evaluated with standard of care treatment regimes used in HNSCC. Results AXL was found to be highly overexpressed in several models of HNSCC, where AXL was significantly associated with higher pathologic grade, presence of distant metastases and shorter relapse free survival in patients with HNSCC. Further investigations indicated that HNSCC cells were reliant on AXL for cellular proliferation, migration, and invasion. Additionally, targeting AXL increased HNSCC cell line sensitivity to chemotherapy, cetuximab, and radiation. Moreover, radiation resistant HNSCC cell line xenografts and PDXs expressed elevated levels of both total and activated AXL, indicating a role for AXL in radiation resistance. Conclusion Collectively, this study provides evidence for the role of AXL in HNSCC pathogenesis and supports further pre-clinical and clinical evaluation of anti-AXL therapeutics for the treatment of patients with HNSCC. PMID:25767293

  20. Gas6 - Axl receptor signaling is regulated by glucose in vascular smooth muscle cells

    PubMed Central

    Cavet, Megan E.; Smolock, Elaine M.; Ozturk, Oktay H.; World, Cameron; Pang, Jinjiang; Konishi, Atsushi; Berk, Bradford C.

    2009-01-01

    Objective The receptor tyrosine kinase Axl and its ligand Gas6 are involved in the development of renal diabetic disease. In vascular smooth muscle cells (VSMC) Axl is activated by reactive oxygen species and stimulates migration and cell survival, suggesting a role for Axl in the vascular complications of diabetes. Methods and Results We investigated the effect of varying glucose concentration on Axl signaling in VSMC. Glucose exerted powerful effects on Gas6-Axl signaling with greater activation of Akt and mTOR in low glucose, and greater activation of ERK1/2 in high glucose. Plasma membrane distribution and tyrosine phosphorylation of Axl were not affected by glucose. However, co-immunoprecipitation studies demonstrated that glucose changed the interaction of Axl with its binding partners. Specifically, binding of Axl to the p85 subunit of PI3-kinase was increased in low glucose, whereas binding to SHP-2 was increased in high glucose. Furthermore, Gas6-Axl induced migration was increased in high glucose, while Gas6-Axl mediated inhibition of apoptosis was greater in low glucose. Conclusion This study demonstrates a role for glucose in altering Axl signaling through coupling to binding partners, and suggests a mechanism by which Axl contributes to VSMC dysfunction in diabetes. PMID:18292389

  1. Influence of Initial Inclined Surface Crack on Estimated Residual Fatigue Lifetime of Railway Axle

    NASA Astrophysics Data System (ADS)

    Náhlík, Luboš; Pokorný, Pavel; Ševčík, Martin; Hutař, Pavel

    2016-11-01

    Railway axles are subjected to cyclic loading which can lead to fatigue failure. For safe operation of railway axles a damage tolerance approach taking into account a possible defect on railway axle surface is often required. The contribution deals with an estimation of residual fatigue lifetime of railway axle with initial inclined surface crack. 3D numerical model of inclined semi-elliptical surface crack in railway axle was developed and its curved propagation through the axle was simulated by finite element method. Presence of press-fitted wheel in the vicinity of initial crack was taken into account. A typical loading spectrum of railway axle was considered and residual fatigue lifetime was estimated by NASGRO approach. Material properties of typical axle steel EA4T were considered in numerical calculations and lifetime estimation.

  2. Downregulation of Axl in non-MYCN amplified neuroblastoma cell lines reduces migration.

    PubMed

    Duijkers, Floor A M; Meijerink, Jules P P; Pieters, Rob; van Noesel, Max M

    2013-05-25

    Neuroblastomas (NBL) are common pediatric solid tumors with a variable clinical course. At diagnosis half of all neuroblastoma patients presents with metastatic disease. The mechanisms of metastasis are largely unknown. Gene expression profiles (HU133plus2.0 arrays, Affymetrix) of 17 NBL and 5 peripheral neuro-ectodermal cell lines were used to identify a subgroup of non-MYCN amplified (non-NMA) NBL cell lines with a distinct gene expression profile and characterized by high expression of AXL. Axl is a tyrosine kinase receptor which plays a role in the metastatic process of several types of cancer. We hypothesized that Axl contributes to the metastasizing potential of non-NMA NBL and tested if AXL silencing diminishes malignant properties of high Axl expressing cell lines. AXL was silenced in two non-NMA NBL cell lines by using a lentiviral shRNA construct that was able to transduce these cell lines with more than 90% infection efficiency. Axl mRNA and protein level were efficiently knocked-down resulting in a decrease of migration of Axl positive cell lines GI-M-EN and SH-EP-2, and decreased invasion of GI-M-EN. Morphologically, Axl knockdown induced more rounded cells with a loss of contact. Intracellularly, we observed induction of stress fibers (immunofluorescence F-actin). These changes in cytoskeleton were associated with decreased migration, but were not accompanied by changes in genes involved in epithelial to mesenchymal transition such as CDH2, VIM or MMP9. No effects were observed for cell proliferation, apoptosis or downstream pathways. In conclusion, AXL is identified as a possible mediator of NBL metastasis. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Compilation of load spectrum of loader drive axle

    NASA Astrophysics Data System (ADS)

    Wei, Yongxiang; Zhu, Haoyue; Tang, Heng; Yuan, Qunwei

    2018-03-01

    In order to study the preparation method of gear fatigue load spectrum for loaders, the load signal of four typical working conditions of loader is collected. The signal that reflects the law of load change is obtained by preprocessing the original signal. The torque of the drive axle is calculated by using the rain flow counting method. According to the operating time ratio of each working condition, the two dimensional load spectrum based on the real working conditions of the drive axle of loader is established by the cycle extrapolation and synthesis method. The two-dimensional load spectrum is converted into one-dimensional load spectrum by means of the mean of torque equal damage method. Torque amplification includes the maximum load torque of the main reduction gear. Based on the theory of equal damage, the accelerated cycles are calculated. In this way, the load spectrum of the loading condition of the drive axle is prepared to reflect loading condition of the loader. The load spectrum can provide reference for fatigue life test and life prediction of loader drive axle.

  4. The tumour suppressor OPCML promotes AXL inactivation by the phosphatase PTPRG in ovarian cancer.

    PubMed

    Antony, Jane; Zanini, Elisa; Kelly, Zoe; Tan, Tuan Zea; Karali, Evdoxia; Alomary, Mohammad; Jung, Youngrock; Nixon, Katherine; Cunnea, Paula; Fotopoulou, Christina; Paterson, Andrew; Roy-Nawathe, Sushmita; Mills, Gordon B; Huang, Ruby Yun-Ju; Thiery, Jean Paul; Gabra, Hani; Recchi, Chiara

    2018-06-15

    In ovarian cancer, the prometastatic RTK AXL promotes motility, invasion and poor prognosis. Here, we show that reduced survival caused by AXL overexpression can be mitigated by the expression of the GPI-anchored tumour suppressor OPCML Further, we demonstrate that AXL directly interacts with OPCML, preferentially so when AXL is activated by its ligand Gas6. As a consequence, AXL accumulates in cholesterol-rich lipid domains, where OPCML resides. Here, phospho-AXL is brought in proximity to the lipid domain-restricted phosphatase PTPRG, which de-phosphorylates the RTK/ligand complex. This prevents AXL-mediated transactivation of other RTKs (cMET and EGFR), thereby inhibiting sustained phospho-ERK signalling, induction of the EMT transcription factor Slug, cell migration and invasion. From a translational perspective, we show that OPCML enhances the effect of the phase II AXL inhibitor R428 in vitro and in vivo We therefore identify a novel mechanism by which two spatially restricted tumour suppressors, OPCML and PTPRG, coordinate to repress AXL-dependent oncogenic signalling. © 2018 The Authors.

  5. Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies

    DOE PAGES

    Kariolis, Mihalis S.; Miao, Yu Rebecca; Diep, Anh; ...

    2016-11-28

    The AXL receptor and its activating ligand, growth arrest–specific 6 (GAS6), are important drivers of metastasis and therapeutic resistance in human cancers. Given the critical roles that GAS6 and AXL play in refractory disease, this signaling axis represents an attractive target for therapeutic intervention. But, the strong picomolar binding affinity between GAS6 and AXL and the promiscuity of small molecule inhibitors represent important challenges faced by current anti-AXL therapeutics. We have addressed these obstacles by engineering a second-generation, high-affinity AXL decoy receptor with an apparent affinity of 93 femtomolar to GAS6. Our decoy receptor, MYD1-72, profoundly inhibited disease progression inmore » aggressive preclinical models of human cancers and induced cell killing in leukemia cells. When directly compared with the most advanced anti-AXL small molecules in the clinic, MYD1-72 achieved superior antitumor efficacy while displaying no toxicity. Furthermore, we uncovered a relationship between AXL and the cellular response to DNA damage whereby abrogation of AXL signaling leads to accumulation of the DNA-damage markers γH2AX, 53BP1, and RAD51. MYD1-72 exploited this relationship, leading to improvements upon the therapeutic index of current standard-of-care chemotherapies in preclinical models of advanced pancreatic and ovarian cancer.« less

  6. Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kariolis, Mihalis S.; Miao, Yu Rebecca; Diep, Anh

    The AXL receptor and its activating ligand, growth arrest–specific 6 (GAS6), are important drivers of metastasis and therapeutic resistance in human cancers. Given the critical roles that GAS6 and AXL play in refractory disease, this signaling axis represents an attractive target for therapeutic intervention. But, the strong picomolar binding affinity between GAS6 and AXL and the promiscuity of small molecule inhibitors represent important challenges faced by current anti-AXL therapeutics. We have addressed these obstacles by engineering a second-generation, high-affinity AXL decoy receptor with an apparent affinity of 93 femtomolar to GAS6. Our decoy receptor, MYD1-72, profoundly inhibited disease progression inmore » aggressive preclinical models of human cancers and induced cell killing in leukemia cells. When directly compared with the most advanced anti-AXL small molecules in the clinic, MYD1-72 achieved superior antitumor efficacy while displaying no toxicity. Furthermore, we uncovered a relationship between AXL and the cellular response to DNA damage whereby abrogation of AXL signaling leads to accumulation of the DNA-damage markers γH2AX, 53BP1, and RAD51. MYD1-72 exploited this relationship, leading to improvements upon the therapeutic index of current standard-of-care chemotherapies in preclinical models of advanced pancreatic and ovarian cancer.« less

  7. Axl acts as a tumor suppressor by regulating LIGHT expression in T lymphoma

    PubMed Central

    Young, Kon-Ji; Park, A-Reum; Choi, Ha-Rim; Lee, Hwa-Youn; Kim, Su-Man; Chung, Byung Yeoup; Park, Chul-Hong; Choi, Hyo Jin; Ko, Young-Hyeh; Bai, Hyoung-Woo; Kang, Hyung-Sik

    2017-01-01

    Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers. LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is a ligand that induces robust anti-tumor immunity by enhancing the recruitment and activation of effector immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T lymphoma cells that stably overexpressed Axl also showed high expression of LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT expression was upregulated through activation of the PI3K/AKT signaling pathway and transcriptional induction by Sp1. The lytic activity of cytotoxic T lymphocytes and natural killer cells was enhanced by EL4-Axl cells. In addition, tumor volume and growth were markedly reduced due to enhanced apoptotic cell death in EL4-Axl tumor-bearing mice as compared to control mice. We also observed upregulated expression of CCL5 and its receptor, CCR5, and enhanced intratumoral infiltration of cytotoxic T lymphocytes and natural killer cells in EL4-Axl-bearing mice as compared to mock controls. These data strongly suggested that Axl exerts novel tumor suppressor effects by inducing upregulation of LIGHT in the tumor microenvironment of T lymphoma. PMID:28423548

  8. Axl acts as a tumor suppressor by regulating LIGHT expression in T lymphoma.

    PubMed

    Lee, Eun-Hee; Kim, Eun-Mi; Ji, Kon-Young; Park, A-Reum; Choi, Ha-Rim; Lee, Hwa-Youn; Kim, Su-Man; Chung, Byung Yeoup; Park, Chul-Hong; Choi, Hyo Jin; Ko, Young-Hyeh; Bai, Hyoung-Woo; Kang, Hyung-Sik

    2017-03-28

    Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers. LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is a ligand that induces robust anti-tumor immunity by enhancing the recruitment and activation of effector immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T lymphoma cells that stably overexpressed Axl also showed high expression of LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT expression was upregulated through activation of the PI3K/AKT signaling pathway and transcriptional induction by Sp1. The lytic activity of cytotoxic T lymphocytes and natural killer cells was enhanced by EL4-Axl cells. In addition, tumor volume and growth were markedly reduced due to enhanced apoptotic cell death in EL4-Axl tumor-bearing mice as compared to control mice. We also observed upregulated expression of CCL5 and its receptor, CCR5, and enhanced intratumoral infiltration of cytotoxic T lymphocytes and natural killer cells in EL4-Axl-bearing mice as compared to mock controls. These data strongly suggested that Axl exerts novel tumor suppressor effects by inducing upregulation of LIGHT in the tumor microenvironment of T lymphoma.

  9. Experimental investigation by laser ultrasonics for high speed train axle diagnostics.

    PubMed

    Cavuto, A; Martarelli, M; Pandarese, G; Revel, G M; Tomasini, E P

    2015-01-01

    The present paper demonstrates the applicability of a laser-ultrasonic procedure to improve the performances of train axle ultrasonic inspection. The method exploits an air-coupled ultrasonic probe that detects the ultrasonic waves generated by a high-power pulsed laser. As a result, the measurement chain is completely non-contact, from generation to detection, this making it possible to considerably speed up inspection time and make the set-up more flexible. The main advantage of the technique developed is that it works in thermo-elastic regime and it therefore can be considered as a non-destructive method. The laser-ultrasonic procedure investigated has been applied for the inspection of a real high speed train axle provided by the Italian railway company (Trenitalia), on which typical fatigue defects have been expressly created according to standard specifications. A dedicated test bench has been developed so as to rotate the axle with the angle control and to speed up the inspection of the axle surface. The laser-ultrasonic procedure proposed can be automated and is potentially suitable for regular inspection of train axles. The main achievements of the activity described in this paper are: – the study of the effective applicability of laser-ultrasonics for the diagnostic of train hollow axles with variable sections by means of a numerical FE model, – the carrying out of an automated experiment on a real train axle, – the analysis of the sensitivity to experimental parameters, like laser source – receiving probe distance and receiving probe angular position, – the demonstration that the technique is suitable for the detection of surface defects purposely created on the train axle. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. 2. DETAIL VIEW OF JOURNAL LATHE, AXLE FINISHING AREA. Grinding ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. DETAIL VIEW OF JOURNAL LATHE, AXLE FINISHING AREA. Grinding bearing diameters on locomotive axle. Norton grinder, 1942 (dated). Melvin Grassmeyer, operator. - Juniata Shops, Machine Shop No. 1, East of Fourth Avenue at Third Street, Altoona, Blair County, PA

  11. 3. DETAIL VIEW OF JOURNAL LATHE, AXLE FINISHING AREA. Grinding ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. DETAIL VIEW OF JOURNAL LATHE, AXLE FINISHING AREA. Grinding bearing diameters on locomotive axle. Norton grinder, 1942 (dated). Melvin Grassmeyer, operator. - Juniata Shops, Machine Shop No. 1, East of Fourth Avenue at Third Street, Altoona, Blair County, PA

  12. Inhibition of the Receptor Tyrosine Kinase AXL Restores Paclitaxel Chemosensitivity in Uterine Serous Cancer.

    PubMed

    Palisoul, Marguerite L; Quinn, Jeanne M; Schepers, Emily; Hagemann, Ian S; Guo, Lei; Reger, Kelsey; Hagemann, Andrea R; McCourt, Carolyn K; Thaker, Premal H; Powell, Matthew A; Mutch, David G; Fuh, Katherine C

    2017-12-01

    Uterine serous cancer (USC) is aggressive, and the majority of recurrent cases are chemoresistant. Because the receptor tyrosine kinase AXL promotes invasion and metastasis of USC and is implicated in chemoresistance in other cancers, we assessed the role of AXL in paclitaxel resistance in USC, determined the mechanism of action, and sought to restore chemosensitivity by inhibiting AXL in vitro and in vivo We used short hairpin RNAs and BGB324 to knock down and inhibit AXL. We assessed sensitivity of USC cell lines to paclitaxel and measured paclitaxel intracellular accumulation in vitro in the presence or absence of AXL. We also examined the role of the epithelial-mesenchymal transition (EMT) in AXL-mediated paclitaxel resistance. Finally, we treated USC xenografts with paclitaxel, BGB324, or paclitaxel plus BGB324 and monitored tumor burden. AXL expression was higher in chemoresistant USC patient tumors and cell lines than in chemosensitive tumors and cell lines. Knockdown or inhibition of AXL increased sensitivity of USC cell lines to paclitaxel in vitro and increased cellular accumulation of paclitaxel. AXL promoted chemoresistance even in cells that underwent the EMT in vitro Finally, in vivo studies of combination treatment with BGB324 and paclitaxel showed a greater than 51% decrease in tumor volume after 2 weeks of treatment when compared with no treatment or single-agent treatments ( P < 0.001). Our results show that AXL expression mediates chemoresistance independent of EMT and prevents accumulation of paclitaxel. This study supports the continued investigation of AXL as a clinical target, particularly in chemoresistant USC. Mol Cancer Ther; 16(12); 2881-91. ©2017 AACR . ©2017 American Association for Cancer Research.

  13. Soluble Axl Is Generated by ADAM10-Dependent Cleavage and Associates with Gas6 in Mouse Serum†

    PubMed Central

    Budagian, Vadim; Bulanova, Elena; Orinska, Zane; Duitman, Erwin; Brandt, Katja; Ludwig, Andreas; Hartmann, Dieter; Lemke, Greg; Saftig, Paul; Bulfone-Paus, Silvia

    2005-01-01

    Axl receptor tyrosine kinase exists as a transmembrane protein and as a soluble molecule. We show that constitutive and phorbol 12-myristate 13-acetate-induced generation of soluble Axl (sAxl) involves the activity of disintegrin-like metalloproteinase 10 (ADAM10). Spontaneous and inducible Axl cleavage was inhibited by the broad-spectrum metalloproteinase inhibitor GM6001 and by hydroxamate GW280264X, which is capable of blocking ADAM10 and ADAM17. Furthermore, murine fibroblasts deficient in ADAM10 expression exhibited a significant reduction in constitutive and inducible Axl shedding, whereas reconstitution of ADAM10 restored sAxl production, suggesting that ADAM10-mediated proteolysis constitutes a major mechanism for sAxl generation in mice. Partially overlapping 14-amino-acid stretch deletions in the membrane-proximal region of Axl dramatically affected sAxl generation, indicating that these regions are involved in regulating the access of the protease to the cleavage site. Importantly, relatively high circulating levels of sAxl are present in mouse sera in a heterocomplex with Axl ligand Gas6. Conversely, two other family members, Tyro3 and Mer, were not detected in mouse sera and conditioned medium. sAxl is constitutively released by murine primary cells such as dendritic and transformed cell lines. Upon immobilization, sAxl promoted cell migration and induced the phosphorylation of Axl and phosphatidylinositol 3-kinase. Thus, ADAM10-mediated generation of sAxl might play an important role in diverse biological processes. PMID:16227584

  14. Novel wavelet threshold denoising method in axle press-fit zone ultrasonic detection

    NASA Astrophysics Data System (ADS)

    Peng, Chaoyong; Gao, Xiaorong; Peng, Jianping; Wang, Ai

    2017-02-01

    Axles are important part of railway locomotives and vehicles. Periodic ultrasonic inspection of axles can effectively detect and monitor axle fatigue cracks. However, in the axle press-fit zone, the complex interface contact condition reduces the signal-noise ratio (SNR). Therefore, the probability of false positives and false negatives increases. In this work, a novel wavelet threshold function is created to remove noise and suppress press-fit interface echoes in axle ultrasonic defect detection. The novel wavelet threshold function with two variables is designed to ensure the precision of optimum searching process. Based on the positive correlation between the correlation coefficient and SNR and with the experiment phenomenon that the defect and the press-fit interface echo have different axle-circumferential correlation characteristics, a discrete optimum searching process for two undetermined variables in novel wavelet threshold function is conducted. The performance of the proposed method is assessed by comparing it with traditional threshold methods using real data. The statistic results of the amplitude and the peak SNR of defect echoes show that the proposed wavelet threshold denoising method not only maintains the amplitude of defect echoes but also has a higher peak SNR.

  15. AXL promotes Zika virus infection in astrocytes by antagonizing type I interferon signalling.

    PubMed

    Chen, Jian; Yang, Yi-Feng; Yang, Yu; Zou, Peng; Chen, Jun; He, Yongquan; Shui, Sai-Lan; Cui, Yan-Ru; Bai, Ru; Liang, Ya-Jun; Hu, Yunwen; Jiang, Biao; Lu, Lu; Zhang, Xiaoyan; Liu, Jia; Xu, Jianqing

    2018-03-01

    Zika virus (ZIKV) is associated with neonatal microcephaly and Guillain-Barré syndrome 1,2 . While progress has been made in understanding the causal link between ZIKV infection and microcephaly 3-9 , the life cycle and pathogenesis of ZIKV are less well understood. In particular, there are conflicting reports on the role of AXL, a TAM family kinase receptor that was initially described as the entry receptor for ZIKV 10-22 . Here, we show that while genetic ablation of AXL protected primary human astrocytes and astrocytoma cell lines from ZIKV infection, AXL knockout did not block the entry of ZIKV. We found, instead, that the presence of AXL attenuated the ZIKV-induced activation of type I interferon (IFN) signalling genes, including several type I IFNs and IFN-stimulating genes. Knocking out type I IFN receptor α chain (IFNAR1) restored the vulnerability of AXL knockout astrocytes to ZIKV infection. Further experiments suggested that AXL regulates the expression of SOCS1, a known type I IFN signalling suppressor, in a STAT1/STAT2-dependent manner. Collectively, our results demonstrate that AXL is unlikely to function as an entry receptor for ZIKV and may instead promote ZIKV infection in human astrocytes by antagonizing type I IFN signalling.

  16. Impact of Trunnion Axle Groups on the Performance of Highway Infrastructure

    DOT National Transportation Integrated Search

    2001-03-01

    The trunnion axle configuration has gained favor with many carriers of oversized and overweight loads. In addition, the frequency of interstate hauling of these specialized loads is increasing. The trunnion axle configuration allows for placement of ...

  17. Single-axle, double-axis solar tracker

    NASA Technical Reports Server (NTRS)

    Brantley, L. W.; Lawson, B. D.

    1979-01-01

    Solar concentrator tracking mechanism consisting of angular axle and two synchronized drive motors, follows seasonal as well as diurnal changes in earth's orientation with respect to incoming sunlight.

  18. Axl as a mediator of cellular growth and survival

    PubMed Central

    Axelrod, Haley; Pienta, Kenneth J.

    2014-01-01

    The control of cellular growth and proliferation is key to the maintenance of homeostasis. Survival, proliferation, and arrest are regulated, in part, by Growth Arrest Specific 6 (Gas6) through binding to members of the TAM receptor tyrosine kinase family. Activation of the TAM receptors leads to downstream signaling through common kinases, but the exact mechanism within each cellular context varies and remains to be completely elucidated. Deregulation of the TAM family, due to its central role in mediating cellular proliferation, has been implicated in multiple diseases. Axl was cloned as the first TAM receptor in a search for genes involved in the progression of chronic to acute-phase leukemia, and has since been established as playing a critical role in the progression of cancer. The oncogenic nature of Axl is demonstrated through its activation of signaling pathways involved in proliferation, migration, inhibition of apoptosis, and therapeutic resistance. Despite its recent discovery, significant progress has been made in the development of effective clinical therapeutics targeting Axl. In order to accurately define the role of Axl in normal and diseased processes, it must be analyzed in a cell type-specific context. PMID:25344858

  19. Axl as a mediator of cellular growth and survival.

    PubMed

    Axelrod, Haley; Pienta, Kenneth J

    2014-10-15

    The control of cellular growth and proliferation is key to the maintenance of homeostasis. Survival, proliferation, and arrest are regulated, in part, by Growth Arrest Specific 6 (Gas6) through binding to members of the TAM receptor tyrosine kinase family. Activation of the TAM receptors leads to downstream signaling through common kinases, but the exact mechanism within each cellular context varies and remains to be completely elucidated. Deregulation of the TAM family, due to its central role in mediating cellular proliferation, has been implicated in multiple diseases. Axl was cloned as the first TAM receptor in a search for genes involved in the progression of chronic to acute-phase leukemia, and has since been established as playing a critical role in the progression of cancer. The oncogenic nature of Axl is demonstrated through its activation of signaling pathways involved in proliferation, migration, inhibition of apoptosis, and therapeutic resistance. Despite its recent discovery, significant progress has been made in the development of effective clinical therapeutics targeting Axl. In order to accurately define the role of Axl in normal and diseased processes, it must be analyzed in a cell type-specific context.

  20. Therapeutic Activity of Anti-AXL Antibody against Triple-Negative Breast Cancer Patient-Derived Xenografts and Metastasis.

    PubMed

    Leconet, Wilhem; Chentouf, Myriam; du Manoir, Stanislas; Chevalier, Clément; Sirvent, Audrey; Aït-Arsa, Imade; Busson, Muriel; Jarlier, Marta; Radosevic-Robin, Nina; Theillet, Charles; Chalbos, Dany; Pasquet, Jean-Max; Pèlegrin, André; Larbouret, Christel; Robert, Bruno

    2017-06-01

    Purpose: AXL receptor tyrosine kinase has been described as a relevant molecular marker and a key player in invasiveness, especially in triple-negative breast cancer (TNBC). Experimental Design: We evaluate the antitumor efficacy of the anti-AXL monoclonal antibody 20G7-D9 in several TNBC cell xenografts or patient-derived xenograft (PDX) models and decipher the underlying mechanisms. In a dataset of 254 basal-like breast cancer samples, genes correlated with AXL expression are enriched in EMT, migration, and invasion signaling pathways. Results: Treatment with 20G7-D9 inhibited tumor growth and bone metastasis formation in AXL-positive TNBC cell xenografts or PDX, but not in AXL-negative PDX, highlighting AXL role in cancer growth and invasion. In vitro stimulation of AXL-positive cancer cells by its ligand GAS6 induced the expression of several EMT-associated genes ( SNAIL, SLUG , and VIM ) through an intracellular signaling implicating the transcription factor FRA-1, important in cell invasion and plasticity, and increased their migration/invasion capacity. 20G7-D9 induced AXL degradation and inhibited all AXL/GAS6-dependent cell signaling implicated in EMT and in cell migration/invasion. Conclusions: The anti-AXL antibody 20G7-D9 represents a promising therapeutic strategy in TNBC with mesenchymal features by inhibiting AXL-dependent EMT, tumor growth, and metastasis formation. Clin Cancer Res; 23(11); 2806-16. ©2016 AACR . ©2016 American Association for Cancer Research.

  1. Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma.

    PubMed

    Müller, Judith; Krijgsman, Oscar; Tsoi, Jennifer; Robert, Lidia; Hugo, Willy; Song, Chunying; Kong, Xiangju; Possik, Patricia A; Cornelissen-Steijger, Paulien D M; Geukes Foppen, Marnix H; Kemper, Kristel; Goding, Colin R; McDermott, Ultan; Blank, Christian; Haanen, John; Graeber, Thomas G; Ribas, Antoni; Lo, Roger S; Peeper, Daniel S

    2014-12-15

    Increased expression of the Microphthalmia-associated transcription factor (MITF) contributes to melanoma progression and resistance to BRAF pathway inhibition. Here we show that the lack of MITF is associated with more severe resistance to a range of inhibitors, while its presence is required for robust drug responses. Both in primary and acquired resistance, MITF levels inversely correlate with the expression of several activated receptor tyrosine kinases, most frequently AXL. The MITF-low/AXL-high/drug-resistance phenotype is common among mutant BRAF and NRAS melanoma cell lines. The dichotomous behaviour of MITF in drug response is corroborated in vemurafenib-resistant biopsies, including MITF-high and -low clones in a relapsed patient. Furthermore, drug cocktails containing AXL inhibitor enhance melanoma cell elimination by BRAF or ERK inhibition. Our results demonstrate that a low MITF/AXL ratio predicts early resistance to multiple targeted drugs, and warrant clinical validation of AXL inhibitors to combat resistance of BRAF and NRAS mutant MITF-low melanomas.

  2. Impact of Surface Type, Wheelchair Weight, and Axle Position on Wheelchair Propulsion by Novice Older Adults

    PubMed Central

    Cowan, Rachel E.; Nash, Mark S.; Collinger, Jennifer L.; Koontz, Alicia M.; Boninger, Michael L.

    2009-01-01

    Objective To examine the impact of surface type, wheelchair weight, and rear axle position on older adult propulsion biomechanics. Design Crossover trial. Setting Biomechanics laboratory. Participants Convenience sample of 53 ambulatory older adults with minimal wheelchair experience (65−87y); men = 20, women = 33. Intervention Participants propelled 4 different wheelchair configurations over 4 surfaces; tile, low carpet, high carpet, and an 8% grade ramp (surface, chair order randomized). Chair configurations included: (1) unweighted chair with an anterior axle position, (2) 9.05kg weighted chair with an anterior axle position, (3) unweighted chair with a posterior axle position (Δ0.08m), and (4) 9.05kg weighted chair with a posterior axle position (Δ0.08m). Weight was added to a titanium folding chair, simulating the weight difference between very light and depot wheelchairs. Instrumented wheels measured propulsion kinetics. Main Outcome Measures Average self-selected velocity, push-frequency, stroke length, peak resultant and tangential force. Results Velocity decreased as surface rolling resistance or chair weight increased. Peak resultant and tangential forces increased as chair weight increased, surface resistance increased, and with a posterior axle position. The effect of a posterior axle position was greater on high carpet and the ramp. The effect of weight was constant, but more easily observed on high carpet and ramp. The effects of axle position and weight were independent of one another. Conclusion Increased surface resistance decreases self-selected velocity and increases peak forces. Increased weight decreases self-selected velocity and increases forces. Anterior axle positions decrease forces, more so on high carpet. Effects of weight and axle position are independent. Greatest reductions in peak forces occur in lighter chairs with anterior axle positions. PMID:19577019

  3. A promiscuous liaison between IL-15 receptor and Axl receptor tyrosine kinase in cell death control

    PubMed Central

    Budagian, Vadim; Bulanova, Elena; Orinska, Zane; Thon, Lutz; Mamat, Uwe; Bellosta, Paola; Basilico, Claudio; Adam, Dieter; Paus, Ralf; Bulfone-Paus, Silvia

    2005-01-01

    Discrimination between cytokine receptor and receptor tyrosine kinase (RTK) signaling pathways is a central paradigm in signal transduction research. Here, we report a ‘promiscuous liaison' between both receptors that enables interleukin (IL)-15 to transactivate the signaling pathway of a tyrosine kinase. IL-15 protects murine L929 fibroblasts from tumor necrosis factor α (TNFα)-induced cell death, but fails to rescue them upon targeted depletion of the RTK, Axl; however, Axl-overexpressing fibroblasts are TNFα-resistant. IL-15Rα and Axl colocalize on the cell membrane and co-immunoprecipitate even in the absence of IL-15, whereby the extracellular part of Axl proved to be essential for Axl/IL-15Rα interaction. Most strikingly, IL-15 treatment mimics stimulation by the Axl ligand, Gas6, resulting in a rapid tyrosine phosphorylation of both Axl and IL-15Rα, and activation of the phosphatidylinositol 3-kinase/Akt pathway. This is also seen in mouse embryonic fibroblasts from wild-type but not Axl−/− or IL-15Rα−/− mice. Thus, IL-15-induced protection from TNFα-mediated cell death involves a hitherto unknown IL-15 receptor complex, consisting of IL-15Rα and Axl RTK, and requires their reciprocal activation initiated by ligand-induced IL-15Rα. PMID:16308569

  4. 49 CFR 230.100 - Defects in tender truck axles and journals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Steam Locomotives and Tenders Running Gear § 230.100 Defects in tender truck axles and journals. (a... wheel seats that is more than 1/8 of an inch in depth. (b) Tender truck journal condemning defects... repaired : (1) Cut journals that cannot be made to run cool without turning; (2) Seams in axles causing...

  5. 49 CFR 230.100 - Defects in tender truck axles and journals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Defects in tender truck axles and journals. 230... Steam Locomotives and Tenders Running Gear § 230.100 Defects in tender truck axles and journals. (a... wheel seats that is more than 1/8 of an inch in depth. (b) Tender truck journal condemning defects...

  6. On condition evaluation of axle unit bearings of wheel pair

    NASA Astrophysics Data System (ADS)

    Glotov, V. V.; Romashchenko, M. A.; Ostroumov, I. V.; Kondratiev, Il V.

    2018-03-01

    At present, axle units of freight cars undergo a complete checkup with disassembling and visual inspection of the bearing parts every five years. During an annual interim checkup, external inspection of an axle box with removed cap is carried out and the lubricant condition is checked. The state of the rolling surfaces of bearings during an interim checkup should be assessed using the known methods of nondestructive testing.

  7. A rolling-sliding bench test for investigating rear axle lubrication

    DOE PAGES

    Stump, Benjamin C.; Zhou, Yan; Viola, Michael B.; ...

    2018-02-07

    An automotive rear axle is composed of a set of hypoid gears, whose contact surfaces experience a complex combination of rolling contact fatigue damage and sliding wear. Full-scale rear axle dynamometer tests are used in the industry for efficiency and durability assessment. Here, this study developed a bench-scale rolling-sliding test protocol by simulating the contact pressure, oil temperature, and lubrication regime experienced in a dynamometer duty cycle test. Initial bench results have demonstrated the ability of generating both rolling contact-induced micropitting and sliding wear and the feasibility of investigating the impact of slide-to-roll ratio, surface roughness, test duration, and oilmore » temperature on the friction behavior, vibration noise, and surface damage. Finally, this bench test will allow studying candidate rear axle lubricants and materials under relevant conditions.« less

  8. A rolling-sliding bench test for investigating rear axle lubrication

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stump, Benjamin C.; Zhou, Yan; Viola, Michael B.

    An automotive rear axle is composed of a set of hypoid gears, whose contact surfaces experience a complex combination of rolling contact fatigue damage and sliding wear. Full-scale rear axle dynamometer tests are used in the industry for efficiency and durability assessment. Here, this study developed a bench-scale rolling-sliding test protocol by simulating the contact pressure, oil temperature, and lubrication regime experienced in a dynamometer duty cycle test. Initial bench results have demonstrated the ability of generating both rolling contact-induced micropitting and sliding wear and the feasibility of investigating the impact of slide-to-roll ratio, surface roughness, test duration, and oilmore » temperature on the friction behavior, vibration noise, and surface damage. Finally, this bench test will allow studying candidate rear axle lubricants and materials under relevant conditions.« less

  9. Taking aim at Mer and Axl receptor tyrosine kinases as novel therapeutic targets in solid tumors

    PubMed Central

    Linger, Rachel M.A.; Keating, Amy K.; Earp, H. Shelton

    2010-01-01

    Importance of the field Axl and/or Mer expression correlates with poor prognosis in several cancers. Until recently, the specific role of these receptor tyrosine kinases (RTKs) in the development and progression of cancer remained unexplained. Studies demonstrating that Axl and Mer contribute to mechanisms of cell survival, migration, invasion, metastasis, and chemosensitivity justify further investigation of Axl and Mer as novel therapeutic targets in cancer. Areas covered in this review Axl and Mer signaling pathways in cancer cells are summarized and evidence validating these RTKs as therapeutic targets in glioblastoma multiforme, non-small cell lung cancer, and breast cancer is examined. A comprehensive discussion of Axl and/or Mer inhibitors in development is also provided. What the reader will gain Potential toxicities associated with Axl or Mer inhibition are addressed. We hypothesize that the probable action of Mer and Axl inhibitors on cells within the tumor microenvironment will provide a unique therapeutic opportunity to target both tumor cells and the stromal components which facilitate disease progression. Take home message Axl and Mer mediate multiple oncogenic phenotypes and activation of these RTKs constitutes a mechanism of chemoresistance in a variety of solid tumors. Targeted inhibition of these RTKs may be effective as anti-tumor and/or anti-metastatic therapy, particularly if combined with standard cytotoxic therapies. PMID:20809868

  10. AXL Inhibition Suppresses the DNA Damage Response and Sensitizes Cells to PARP Inhibition in Multiple Cancers

    PubMed Central

    Diao, Lixia; Tong, Pan; Fan, Youhong; Carey, Jason PW; Bui, Tuyen N.; Warner, Steve; Heymach, John V; Hunt, Kelly K; Wang, Jing

    2016-01-01

    Epithelial to mesenchymal transition (EMT) is associated with a wide range of changes in cancer cells, including stemness, chemo- and radio-resistance and metastasis. The mechanistic role of upstream mediators of EMT has not yet been well characterized. Recently, we showed that non-small cell lung cancers (NSCLCs) that have undergone EMT overexpress AXL, a receptor tyrosine kinase. AXL is also overexpressed in a subset of triple-negative breast cancers (TNBCs) and head and neck squamous cell carcinomas (HNSCCs) and its overexpression has been associated with more aggressive tumor behavior and linked to resistance to chemotherapy, radiation, and targeted therapy. Since the DNA repair pathway is also altered in patient tumor specimens overexpressing AXL, it is hypothesized that modulation of AXL in cells that have undergone EMT will sensitize them to agents targeting the DNA repair pathway. Downregulation or inhibition of AXL directly reversed the EMT phenotype, led to decreased expression of DNA repair genes and diminished efficiency of homologous recombination (HR) and RAD51 foci formation. As a result, AXL inhibition caused a state of HR-deficiency in the cells, making them sensitive to inhibition of the DNA repair protein, PARP1. AXL inhibition synergized with PARP inhibition, leading to apoptotic cell death. AXL expression also associated positively with markers of DNA repair across TNBC, HNSCC and NSCLC patient cohorts. PMID:27671334

  11. The AXL receptor tyrosine kinase is associated with adverse prognosis and distant metastasis in esophageal squamous cell carcinoma

    PubMed Central

    Wong, Li-Fan; Lee, Jang-Ming

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is a frequently recurrent deadly cancer for which no efficient targeted drug exists. AXL is an adverse prognostic factor in some cancers. Strong clinical evidence to support the prognostic role of AXL in ESCC is lacking. A total of 116 patients diagnosed with operable primary ESCC were enrolled. Both AXL and HER2 expression were detected by immunohistochemistry (IHC) in esophageal tissue and were correlated with the clinical outcome of patients. The efficacy of the AXL targeted drug foretinib was also evaluated in ESCC cells. Expression of AXL was found in about 80 % of ESCC tissue, and was significantly correlated with progression of tumor (P<0.001), increased risk of death (Hazard ratio HR [95 % CI=2.09[1.09-4.04], P=0.028], and distant metastasis (odds ratio OR [95 %CI]=3.96 (1.16-13.60), P=0.029). The adverse clinical impact of AXL was more evident when cumulatively expressed with HER2. In cell model, ESCC cells were more sensitive to AXL inhibitor foretinib than to the HER2 inhibitor lapatinib. Meanwhile, the AXL inhibitor foretinib showed a synergistic effect with HER2 inhibitors and the potential to overcome drug resistance to lapatinib. We thus concluded that AXL is a strong adverse prognostic factor for ESCC. Therapeutic agents targeting AXL have great potential to improve prognosis of ESCC patients. PMID:27172793

  12. Effect of Michigan multi-axle trucks on pavement distress and profile: volume 3.

    DOT National Transportation Integrated Search

    2009-02-01

    With the adoption of the new mechanistic-empirical pavement design method and the employment of axle load : spectra, the question of evaluating the pavement damage resulting from different axle and truck configurations has : become more relevant. In ...

  13. Effect of Michigan multi-axle trucks on pavement distress and profile : volume 1.

    DOT National Transportation Integrated Search

    2009-02-01

    With the adoption of the new mechanistic-empirical pavement design method and the employment of axle load : spectra, the question of evaluating the pavement damage resulting from different axle and truck configurations has : become more relevant. In ...

  14. Eddy current system for inspection of train hollow axles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chady, Tomasz; Psuj, Grzegorz; Sikora, Ryszard

    2014-02-18

    The structural integrity of wheelsets used in rolling stock is of great importance to the safety. In this paper, electromagnetic system with an eddy current transducer suitable for the inspection of hollow axles have been presented. The transducer was developed to detect surface braking defects having depth not smaller than 0.5 mm. Ultrasound technique can be utilized to inspect the whole axle, but it is not sufficiently sensitive to shallow defects located close to the surface. Therefore, the electromagnetic technique is proposed to detect surface breaking cracks that cannot be detected by ultrasonic technique.

  15. Influence of polygonal wear of railway wheels on the wheel set axle stress

    NASA Astrophysics Data System (ADS)

    Wu, Xingwen; Chi, Maoru; Wu, Pingbo

    2015-11-01

    The coupled vehicle/track dynamic model with the flexible wheel set was developed to investigate the effects of polygonal wear on the dynamic stresses of the wheel set axle. In the model, the railway vehicle was modelled by the rigid multibody dynamics. The wheel set was established by the finite element method to analyse the high-frequency oscillation and dynamic stress of wheel set axle induced by the polygonal wear based on the modal stress recovery method. The slab track model was taken into account in which the rail was described by the Timoshenko beam and the three-dimensional solid finite element was employed to establish the concrete slab. Furthermore, the modal superposition method was adopted to calculate the dynamic response of the track. The wheel/rail normal forces and the tangent forces were, respectively, determined by the Hertz nonlinear contact theory and the Shen-Hedrick-Elkins model. Using the coupled vehicle/track dynamic model, the dynamic stresses of wheel set axle with consideration of the ideal polygonal wear and measured polygonal wear were investigated. The results show that the amplitude of wheel/rail normal forces and the dynamic stress of wheel set axle increase as the vehicle speeds rise. Moreover, the impact loads induced by the polygonal wear could excite the resonance of wheel set axle. In the resonance region, the amplitude of the dynamic stress for the wheel set axle would increase considerably comparing with the normal conditions.

  16. Effect of Michigan multi-axle trucks on pavement distress and profile: volume 2.

    DOT National Transportation Integrated Search

    2009-02-01

    With the adoption of the new mechanistic-empirical pavement design method and the employment of axle load spectra, the question of evaluating the pavement damage resulting from different axle and truck configurations has become more relevant. In part...

  17. Deformation effect simulation and optimization for double front axle steering mechanism

    NASA Astrophysics Data System (ADS)

    Wu, Jungang; Zhang, Siqin; Yang, Qinglong

    2013-03-01

    This paper research on tire wear problem of heavy vehicles with Double Front Axle Steering Mechanism from the flexible effect of Steering Mechanism, and proposes a structural optimization method which use both traditional static structural theory and dynamic structure theory - Equivalent Static Load (ESL) method to optimize key parts. The good simulated and test results show this method has high engineering practice and reference value for tire wear problem of Double Front Axle Steering Mechanism design.

  18. Soluble Axl is an accurate biomarker of cirrhosis and hepatocellular carcinoma development: results from a large scale multicenter analysis

    PubMed Central

    Dengler, Mirko; Staufer, Katharina; Huber, Heidemarie; Stauber, Rudolf; Bantel, Heike; Weiss, Karl Heinz; Starlinger, Patrick; Pock, Hannelore; Klöters-Plachky, Petra; Gotthardt, Daniel N.; Rauch, Peter; Lackner, Carolin; Stift, Judith; Brostjan, Christine; Gruenberger, Thomas; Kumada, Takashi; Toyoda, Hidenori; Tada, Toshifumi; Weiss, Thomas S.; Trauner, Michael; Mikulits, Wolfgang

    2017-01-01

    Patients with chronic liver disease (CLD) and cirrhosis are at high risk for hepatocellular carcinoma (HCC). Current diagnostic tools for HCC detection include imaging techniques and serum biomarkers such as α-fetoprotein (AFP). Yet, these methods are limited in sensitivity and specificity to accurately detect early HCC. Here we focused on the potential of soluble Axl (sAxl) as a biomarker in CLD patients by analyzing serum samples of 1067 patients and healthy controls from centers in Europe and Asia. We show that serum concentrations of sAxl were significantly increased at early (82.57 ng/mL) and later stages of HCC (114.50 ng/mL) as compared to healthy controls (40.15 ng/mL). Notably, no elevated sAxl levels were detected in patients with CLD including chronic viral hepatitis, autoimmune hepatitis, cholestatic liver disease, or non-alcoholic fatty liver disease versus healthy controls. Furthermore, sAxl did not rise in liver adenomas or cholangiocarcinoma (CCA). Yet, patients with advanced fibrosis (F3) or cirrhosis (F4) showed enhanced sAxl concentrations (F3: 54.67 ng/mL; F4: 94.74 ng/mL). Hepatic myofibroblasts exhibited an increased release of sAxl, suggesting that elevated sAxl levels arise from these cells during fibrosis. Receiver operating characteristic curve analysis of sAxl displayed a strongly increased sensitivity and specificity to detect both cirrhosis (80.8%/92.0%) and HCC (83.3%/86.7%) with an area under the curve of 0.935/0.903 as compared to AFP. In conclusion, sAxl shows high diagnostic accuracy at early stage HCC as well as cirrhosis, thereby outperforming AFP. Importantly, sAxl remains normal in most common CLDs, liver adenomas and CCA. PMID:28526812

  19. Effective Crack Detection in Railway Axles Using Vibration Signals and WPT Energy.

    PubMed

    Gómez, María Jesús; Corral, Eduardo; Castejón, Cristina; García-Prada, Juan Carlos

    2018-05-17

    Crack detection for railway axles is key to avoiding catastrophic accidents. Currently, non-destructive testing is used for that purpose. The present work applies vibration signal analysis to diagnose cracks in real railway axles installed on a real Y21 bogie working on a rig. Vibration signals were obtained from two wheelsets with cracks at the middle section of the axle with depths from 5.7 to 15 mm, at several conditions of load and speed. Vibration signals were processed by means of wavelet packet transform energy. Energies obtained were used to train an artificial neural network, with reliable diagnosis results. The success rate of 5.7 mm defects was 96.27%, and the reliability in detecting larger defects reached almost 100%, with a false alarm ratio lower than 5.5%.

  20. Infection by Zika viruses requires the transmembrane protein AXL, endocytosis and low pH.

    PubMed

    Persaud, Mirjana; Martinez-Lopez, Alicia; Buffone, Cindy; Porcelli, Steven A; Diaz-Griffero, Felipe

    2018-05-01

    The recent Zika virus (ZIKV) outbreak in Brazil has suggested associations of this virus infection with neurological disorders, including microcephaly in newborn infants and Guillian-Barré syndrome in adults. Previous reports have shown that AXL, a transmembrane receptor tyrosine kinase protein, is essential for ZIKV infection of mammalian cells, but this remains controversial. Here, we have assessed the involvement of AXL in the ability of ZIKV to infect mammalian cells, and also the requirement for endocytosis and acidic pH. We demonstrated that AXL is essential for ZIKV infection of human fibroblast cell line HT1080 as the targeted deletion of the gene for AXL in HT1080 cells made them no longer susceptible to ZIKV infection. Our results also showed that infection was prevented by lysosomotropic agents such as ammonium chloride, chloroquine and bafilomycin A1, which neutralize the normally acidic pH of endosomal compartments. Infection by ZIKV was also blocked by chlorpromazine, indicating a requirement for clathrin-mediated endocytosis. Taken together, our findings suggest that AXL most likely serves as an attachment factor for ZIKV on the cell surface, and that productive infection requires endocytosis and delivery of the virus to acidified intracellular compartments. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Efficiency analysis of a multiple axle vehicle with hydrostatic transmission overcoming obstacles

    NASA Astrophysics Data System (ADS)

    Comellas, M.; Pijuan, J.; Nogués, M.; Roca, J.

    2018-01-01

    Transmission configurations in off-road vehicles with multiple driven axles can be a determining factor in the obstacle surmounting capacity and also in the vehicle efficiency. An off-road articulated vehicle with four driven axles, four bogies and two modules has been considered for the global hydrostatic transmission efficiency analysis and for the vehicle functional efficiency analysis. The power flow through the transmission system has been quantified from the combustion engine shaft to each axle of the wheels. It has been done for different the operating conditions and taking into account the wheel-terrain interaction and the transmission configuration, that could lead to a forced slippage of some of the wheels. Results show the influence of the different wheels' requirements, the transmission configuration limitations and the considered control strategy on the global transmission and vehicle functional efficiencies.

  2. Effect of Understress on Fretting Fatigue Crack Initiation of Press-Fitted Axle

    NASA Astrophysics Data System (ADS)

    Kubota, Masanobu; Niho, Sotaro; Sakae, Chu; Kondo, Yoshiyuki

    Axles are one of the most important components in railway vehicles with regard to safety, since a fail-safe design is not available. The problems of fretting fatigue crack initiation in a press-fitted axle have not been completely solved even though up-to-date fatigue design methods are employed. The objective of the present study is to clarify the effect of understress on fretting fatigue crack initiation behavior in the press-fitted axle. Most of the stress amplitude given to the axle in service is smaller than the fretting fatigue limit based on the stress to initiate cracks under a constant load σwf1. Rotating bending fatigue tests were performed using a 40mm-diameter press-fitted axle assembly. Two-step variable stresses consisting of σwf1 and half or one-third of σwf1 were used in the experiment. Crack initiation life was defined as the number of cycles when a fretting fatigue crack, which is longer than 30µm, was found using a metallurgical microscope. Fretting fatigue cracks were initiated even when the variable stress did not contain the stress above the fretting fatigue crack initiation limit. The crack initiation life varied from 4.0×107 to 1.2×108 depending on the stress frequency ratio nL/nH. The sum of the number of cycles of higher stress at crack initiation NH was much smaller than the number of cycles to initiate cracks estimated from the modified Miner's rule. The value of the modified Miner's damage ranged from 0.013 to 0.185. To clarify the effect of variable amplitude on the fretting fatigue crack initiation, a comprehensive investigation related to relative slip, tangential force and fretting wear is necessary.

  3. Train axle bearing fault detection using a feature selection scheme based multi-scale morphological filter

    NASA Astrophysics Data System (ADS)

    Li, Yifan; Liang, Xihui; Lin, Jianhui; Chen, Yuejian; Liu, Jianxin

    2018-02-01

    This paper presents a novel signal processing scheme, feature selection based multi-scale morphological filter (MMF), for train axle bearing fault detection. In this scheme, more than 30 feature indicators of vibration signals are calculated for axle bearings with different conditions and the features which can reflect fault characteristics more effectively and representatively are selected using the max-relevance and min-redundancy principle. Then, a filtering scale selection approach for MMF based on feature selection and grey relational analysis is proposed. The feature selection based MMF method is tested on diagnosis of artificially created damages of rolling bearings of railway trains. Experimental results show that the proposed method has a superior performance in extracting fault features of defective train axle bearings. In addition, comparisons are performed with the kurtosis criterion based MMF and the spectral kurtosis criterion based MMF. The proposed feature selection based MMF method outperforms these two methods in detection of train axle bearing faults.

  4. Autophagy induced by AXL receptor tyrosine kinase alleviates acute liver injury via inhibition of NLRP3 inflammasome activation in mice.

    PubMed

    Han, Jihye; Bae, Joonbeom; Choi, Chang-Yong; Choi, Sang-Pil; Kang, Hyung-Sik; Jo, Eun-Kyeong; Park, Jongsun; Lee, Young Sik; Moon, Hyun-Seuk; Park, Chung-Gyu; Lee, Myung-Shik; Chun, Taehoon

    2016-12-01

    Severe hepatic inflammation is a common cause of acute or chronic liver disease. Macrophages are one of the key mediators which regulate the progress of hepatic inflammation. Increasing evidence shows that the TAM (TYRO3, AXL and MERTK) family of RTKs (receptor tyrosine kinases), which is expressed in macrophages, alleviates inflammatory responses through a negative feedback loop. However, the functional contribution of each TAM family member to the progression of hepatic inflammation remains elusive. In this study, we explore the role of individual TAM family proteins during autophagy induction and evaluate their contribution to hepatic inflammation. Among the TAM family of RTKs, AXL (AXL receptor tyrosine kinase) only induces autophagy in macrophages after interaction with its ligand, GAS6 (growth arrest specific 6). Based on our results, autophosphorylation of 2 tyrosine residues (Tyr815 and Tyr860) in the cytoplasmic domain of AXL in mice is required for autophagy induction and AXL-mediated autophagy induction is dependent on MAPK (mitogen-activated protein kinase)14 activity. Furthermore, induction of AXL-mediated autophagy prevents CASP1 (caspase 1)-dependent IL1B (interleukin 1, β) and IL18 (interleukin 18) maturation by inhibiting NLRP3 (NLR family, pyrin domain containing 3) inflammasome activation. In agreement with these observations, axl -/- mice show more severe symptoms than do wild-type (Axl +/+ ) mice following acute hepatic injury induced by administration of lipopolysaccharide (LPS) or carbon tetrachloride (CCl 4 ). Hence, GAS6-AXL signaling-mediated autophagy induction in murine macrophages ameliorates hepatic inflammatory responses by inhibiting NLRP3 inflammasome activation.

  5. Rotation of artificial rotor axles in rotary molecular motors

    PubMed Central

    Baba, Mihori; Iwamoto, Kousuke; Ueno, Hiroshi; Hara, Mayu; Nakanishi, Atsuko; Kishikawa, Jun-ichi; Noji, Hiroyuki; Yokoyama, Ken

    2016-01-01

    F1- and V1-ATPase are rotary molecular motors that convert chemical energy released upon ATP hydrolysis into torque to rotate a central rotor axle against the surrounding catalytic stator cylinder with high efficiency. How conformational change occurring in the stator is coupled to the rotary motion of the axle is the key unknown in the mechanism of rotary motors. Here, we generated chimeric motor proteins by inserting an exogenous rod protein, FliJ, into the stator ring of F1 or of V1 and tested the rotation properties of these chimeric motors. Both motors showed unidirectional and continuous rotation, despite no obvious homology in amino acid sequence between FliJ and the intrinsic rotor subunit of F1 or V1. These results showed that any residue-specific interactions between the stator and rotor are not a prerequisite for unidirectional rotation of both F1 and V1. The torque of chimeric motors estimated from viscous friction of the rotation probe against medium revealed that whereas the F1-FliJ chimera generates only 10% of WT F1, the V1-FliJ chimera generates torque comparable to that of V1 with the native axle protein that is structurally more similar to FliJ than the native rotor of F1. This suggests that the gross structural mismatch hinders smooth rotation of FliJ accompanied with the stator ring of F1. PMID:27647891

  6. Curcumin-induced downregulation of Axl receptor tyrosine kinase inhibits cell proliferation and circumvents chemoresistance in non-small lung cancer cells.

    PubMed

    Kim, Kyung-Chan; Baek, Suk-Hwan; Lee, Chuhee

    2015-12-01

    Lung cancer is still in the first place in terms of both incidence and mortality. In the present study, we demonstrated the effect of curcumin, a phytochemical of the plant Curcuma longa, on expression and activation of Axl receptor tyrosine kinase (RTK) which plays an important role in cell survival, proliferation and anti-apoptosis. Curcumin treatment of non-small cell lung cancer (NSCLC) A549 and H460 cells, was found to decrease Axl protein as well as mRNA levels in a dose- and time-dependent manner. Axl promoter activity was also reduced by curcumin, indicating that curcumin downregulates Axl expression at the transcriptional level. Moreover, Axl phosphorylation in response to binding of its ligand, Gas6, was abrogated by curcumin, suggesting the inhibitory effect of curcumin on Gas6-induced Axl activation. We next found cytotoxic effect of cucumin on both the parental A549 and H460 cells, and their variants which are resistant to cisplatin (A549/CisR and H460/CisR) and paclitaxel (A549/TR and H460/TR). Exposure of these cells to curcumin resulted in dose-dependent decline of cell viability and clonogenic ability. It is further observed that the anti-proliferative effect of curcumin on A549 cells overexpressing Axl protein was reduced, while that on H460 cells transfected Axl specific siRNA was augmented, confirming that curcumin inhibits cell proliferation via downregulation of Axl expression. In addition, curcumin was found to cause the induction of p21, a cyclin-dependent kinase inhibitor, and reduction of X-linked inhibitor of apoptosis protein (XIAP), an anti-apoptotic molecule, in parental H460 cells as well as chemoresistant cells, H460/CisR and H460/TR. Taken together, our data imply that Axl RTK is a novel target of curcumin through which it exerts anti-proliferative effect in both parental and chemoresistant NSCLC cells.

  7. Research of 600C Grade Welding V-N Micro-Alloyed Steel Used on Truck Axle Housing After Thermal Forming

    NASA Astrophysics Data System (ADS)

    Quanli, Wang; Hui, Pan; Qingmei, Liu

    Automobile axle housing is the basic element to install the main reducing gear, differential mechanism, semi-axis, wheel hub and suspension. The main function of automobile axle housing is to support the automobile quality with driven axle, fix the driving wheel relative axial position and bear the driving wheel transmission force during the automobile running. Axle housing steel with the thickness of not less than 12mm is produced by the thermal forming method, which is to heat the plate to 830 degree and hold some time, then thermal forming, and cool to room temperature. The steel plate should maintain the original strength and good ductility and toughness requirements with thermal forming process.

  8. Axl is a novel target of withaferin A in the induction of apoptosis and the suppression of invasion.

    PubMed

    Woo, Seon Min; Min, Kyoung-jin; Kim, Shin; Park, Jong-Wook; Kim, Dong Eun; Kim, Sang Hyun; Choi, Yung Hyun; Kwon, Taeg Kyu

    2014-08-29

    Withaferin A, a withanolide derived from the medicinal plant Withania somnifera, has been reported to exhibit anti-tumorigenic activity against various cancer cells. In this study, we show that withaferin A inhibits the constitutive and recombinant human growth-arrest-specific protein 6 (rhGas6)-induced phosphorylation of Axl and STAT3. In addition, withaferin A also induces the down-regulation of Axl protein expression in a lysosome-dependent manner and inhibits rhGas6-induced wound healing and cell migration. Furthermore, the overexpression of Axl attenuates withaferin A-induced apoptosis. Taken together, the data from the present study indicate that the withaferin A-mediated down-regulation of the Gas6/Axl signaling pathway mediates the inhibition of cell migration and the induction of apoptosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. 21. VIEW OF AXLE AND WHEEL ASSEMBLY STORAGE AREA, adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    21. VIEW OF AXLE AND WHEEL ASSEMBLY STORAGE AREA, adjacent to Erecting Shop and Machine Shop. - Juniata Shops, Erecting Shop & Machine Shop, East of Fourth Avenue, between Fourth & Fifth Streets, Altoona, Blair County, PA

  10. Up-Regulation of Soluble Axl and Mer Receptor Tyrosine Kinases Negatively Correlates with Gas6 in Established Multiple Sclerosis Lesions

    PubMed Central

    Weinger, Jason G.; Omari, Kakuri M.; Marsden, Kurt; Raine, Cedric S.; Shafit-Zagardo, Bridget

    2009-01-01

    Multiple sclerosis is a disease that is characterized by inflammation, demyelination, and axonal damage; it ultimately forms gliotic scars and lesions that severely compromise the function of the central nervous system. Evidence has shown previously that altered growth factor receptor signaling contributes to lesion formation, impedes recovery, and plays a role in disease progression. Growth arrest-specific protein 6 (Gas6), the ligand for the TAM receptor tyrosine kinase family, consisting of Tyro3, Axl, and Mer, is important for cell growth, survival, and clearance of debris. In this study, we show that levels of membrane-bound Mer (205 kd), soluble Mer (∼150 kd), and soluble Axl (80 kd) were all significantly elevated in homogenates from established multiple sclerosis lesions comprised of both chronic active and chronic silent lesions. Whereas in normal tissue Gas6 positively correlated with soluble Axl and Mer, there was a negative correlation between Gas6 and soluble Axl and Mer in established multiple sclerosis lesions. In addition, increased levels of soluble Axl and Mer were associated with increased levels of mature ADAM17, mature ADAM10, and Furin, proteins that are associated with Axl and Mer solubilization. Soluble Axl and Mer are both known to act as decoy receptors and block Gas6 binding to membrane-bound receptors. These data suggest that in multiple sclerosis lesions, dysregulation of protective Gas6 receptor signaling may prolong lesion activity. PMID:19541935

  11. Heavy and Overweight Vehicle Brake Testing: Five-Axle Combination Tractor-Flatbed Final Report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lascurain, Mary Beth; Capps, Gary J; Franzese, Oscar

    The Federal Motor Carrier Safety Administration, in coordination with the Federal Highway Administration, sponsored the Heavy and Overweight Vehicle Brake Testing (HOVBT) program in order to provide information about the effect of gross vehicle weight (GVW) on braking performance. Because the Federal Motor Carrier Safety Regulations limit the number of braking system defects that may exist for a vehicle to be allowed to operate on the roadways, the examination of the effect of brake defects on brake performance for increased loads is also relevant. The HOVBT program seeks to provide relevant information to policy makers responsible for establishing load limits,more » beginning with providing test data for a combination tractor/trailer. This testing was conducted on a five-axle combination vehicle with tractor brakes meeting the Reduced Stopping Distance requirement rulemaking. This report provides a summary of the testing activities, the results of various analyses of the data, and recommendations for future research. Following a complete brake rebuild, instrumentation, and brake burnish, stopping tests were performed from 20 and 40 mph with various brake application pressures (15 psi, 25 psi, 35 psi, 45 psi, 55 psi, and full system pressure). These tests were conducted for various brake conditions at the following GVWs: 60,000, 80,000, 91,000, 97,000, 106,000, and 116,000 lb. The 80,000-lb GVWs included both balanced and unbalanced loads. The condition of the braking system was also varied. To introduce these defects, brakes (none, forward drive axle, or rear trailer axle) were made inoperative. In addition to the stopping tests, performance-based brake tests were conducted for the various loading and brake conditions. Analysis of the stopping test data showed the stopping distance to increase with load (as expected) and also showed that more braking force was generated by the drive axle brakes than the trailer axle brakes. The constant-pressure stopping test

  12. Cell- and Tissue-based Proteome Profiling and Bioimaging with the Probes Derived from a Potent AXL Kinase Inhibitor.

    PubMed

    Li, Zhengqiu; Zheng, Binbin; Guo, Haijun; Xu, Jiaqian; Ma, Nan; Ni, Yun; Li, Lin; Hao, Piliang; Ding, Ke

    2018-06-25

    AXL has been defined as a novel target for cancer therapeutics. However, only a few potent and selective inhibitors targeting AXL are available to date. Our group has developed a lead compound, 9im, capable of excellent inhibition against AXL. With the aim of understanding its cellular and tissue mechanism of actions and direct subsequent structure optimization, a study on competitive affinity-based proteome profiling and bioimaging was carried out. A series of unknown cellular and tissue targets, including RYK, PCK, ATP1A3, EIF4A, Ptprn and Cox5b were discovered. In addition, trans-cyclooctene (TCO) and acedan-containing probes were developed to image the binding between 9im and its target proteins inside live cells and tumor tissues. These probes would be useful tools in the detection of expression and activity of AXL. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. A Flexible Arrayed Eddy Current Sensor for Inspection of Hollow Axle Inner Surfaces.

    PubMed

    Sun, Zhenguo; Cai, Dong; Zou, Cheng; Zhang, Wenzeng; Chen, Qiang

    2016-06-23

    A reliable and accurate inspection of the hollow axle inner surface is important for the safe operation of high-speed trains. In order to improve the reliability of the inspection, a flexible arrayed eddy current sensor for non-destructive testing of the hollow axle inner surface was designed, fabricated and characterized. The sensor, consisting of two excitation traces and 28 sensing traces, was developed by using the flexible printed circuit board (FPCB) technique to conform the geometric features of the inner surfaces of the hollow axles. The main innovative aspect of the sensor was the new arrangement of excitation/sensing traces to achieve a differential configuration. Finite element model was established to analyze sensor responses and to determine the optimal excitation frequency. Experimental validations were conducted on a specimen with several artificial defects. Results from experiments and simulations were consistent with each other, with the maximum relative error less than 4%. Both results proved that the sensor was capable of detecting longitudinal and transverse defects with the depth of 0.5 mm under the optimal excitation frequency of 0.9 MHz.

  14. Examine impact to highways/structures : vehicles equipped with lift axles.

    DOT National Transportation Integrated Search

    2011-12-01

    "The main objective of this research study is to examine the effects of trucks equipped with lift axles on : pavement and bridge structures on Maryland roadways. In this report, the information presented intends to : meet the research objectives outl...

  15. Analysis of minimum rail size in heavy axle load environment

    DOT National Transportation Integrated Search

    2013-04-15

    The effects of increasing axle loads on rail integrity are examined in this paper. In the present context, rail integrity refers to the prevention and control of rail failures. Rail failures usually occur because cracks or defects develop and grow fr...

  16. A critical role of Gas6/Axl signal in allergic airway responses during RSV vaccine-enhanced disease.

    PubMed

    Shibata, Takehiko; Ato, Manabu

    2017-11-01

    Respiratory syncytial virus (RSV) is a common virus that causes lower respiratory infections across a wide range of ages. A licensed RSV vaccine is not available because vaccination with formalin-inactivated RSV (FI-RSV) and the subsequent RSV infection cause not only insufficient induction of neutralizing antibodies but also severe allergic airway responses, termed FI-RSV vaccine-enhanced disease (FI-RSV VED). However, the underlying mechanism has not been identified, although a Th2-biased immune response is known to be a hallmark of this disease. Our previous studies have shown that growth arrest-specific 6 (Gas6)/Axl signaling leads to Th2-biased immune responses during fungus-induced allergic airway inflammation. Here, we show that Gas6/Axl signaling also leads to FI-RSV VED and partially identify the mechanism in mice. Inhibiting Gas6/Axl signaling using Gas6-deficient mice, neutralizing antibodies, and a specific inhibitor of Axl attenuated allergic airway hyperresponsiveness, including airway inflammation, goblet cell hyperplasia, and Th2 cytokine production, in addition to increasing interferon-γ levels and the production of RSV-neutralizing IgG2a in FI-RSV VED. Gas6 was produced in lymph nodes during immunization with FI-RSV. Lymph node cells derived from immunized mice produced high levels of Gas6 and Th2 cytokines, but not IFN-γ, after restimulation with RSV. Finally, we found that dendritic cells stimulated with RSV-glycoprotein (G protein) produced Gas6 and that Axl signaling suppressed DC maturation and the induction of IL-12 production by the toll-like receptor 4 agonist RSV-fusion protein. Taken together, these results indicate that RSV-G protein-induced Gas6/Axl signaling causes allergic airway responses during FI-RSV VED.

  17. Molecular analysis of alternative transcripts of equine AXL receptor tyrosine kinase gene.

    PubMed

    Park, Jeong-Woong; Song, Ki-Duk; Kim, Nam Young; Choi, Jae-Young; Hong, Seul A; Oh, Jin Hyeog; Kim, Si Won; Lee, Jeong Hyo; Park, Tae Sub; Kim, Jin-Kyoo; Kim, Jong Geun; Cho, Byung-Wook

    2017-10-01

    Since athletic performance is a most importance trait in horses, most research focused on physiological and physical studies of horse athletic abilities. In contrast, the molecular analysis as well as the regulatory pathway studies remain insufficient for evaluation and prediction of horse athletic abilities. In our previous study, we identified AXL receptor tyrosine kinase ( AXL ) gene which was expressed as alternative spliced isoforms in skeletal muscle during exercise. In the present study, we validated two AXL alternative splicing transcripts (named as AXLa for long form and AXLb for short form) in equine skeletal muscle to gain insight(s) into the role of each alternative transcript during exercise. We validated two isoforms of AXL transcripts in horse tissues by reverse transcriptase polymerase chain reaction (RT-PCR), and then cloned the transcripts to confirm the alternative locus and its sequences. Additionally, we examined the expression patterns of AXLa and AXLb transcripts in horse tissues by quantitative RT-PCR (qRT-PCR). Both of AXLa and AXLb transcripts were expressed in horse skeletal muscle and the expression levels were significantly increased after exercise. The sequencing analysis showed that there was an alternative splicing event at exon 11 between AXLa and AXLb transcripts. 3-dimentional (3D) prediction of the alternative protein structures revealed that the structural distance of the connective region between fibronectin type 3 (FN3) and immunoglobin (Ig) domain was different between two alternative isoforms. It is assumed that the expression patterns of AXLa and AXLb transcripts would be involved in regulation of exercise-induced stress in horse muscle possibly through an NF-κB signaling pathway. Further study is necessary to uncover biological function(s) and significance of the alternative splicing isoforms in race horse skeletal muscle.

  18. Product Design and Production Practice of 700MPa High Strength Hot Rolled Strip for Auto Axle Tube

    NASA Astrophysics Data System (ADS)

    Hui, Pan; Zhao-dong, Wang; Ya-jun, Hui; Yang, Cui; Xiang-tao, Deng; Chun-lin, Bao

    According to the technical specifications of 700MPa high strength automotive axle tube steel, a low cost of 0.07%C+1.5%Mn+0.05%Nb+0.10%Ti was designed. The high strength mainly relies on grain refinement strengthening and precipitation strengthening. The recrystallization, precipitation, and CCT curves of the 700MPa grade axle tube steel were studied in order to determine a reasonable TMCP process. By controlling the low level segregation band, low level of C and N content, 700MPa grade high strength automotive axle tube steel is successfully developed with excellent mechanical property, welding property, flattening and flaring property, torsion fatigue property, static torsional property and surface quality.

  19. Differential activation of the Ras/extracellular-signal-regulated protein kinase pathway is responsible for the biological consequences induced by the Axl receptor tyrosine kinase.

    PubMed

    Fridell, Y W; Jin, Y; Quilliam, L A; Burchert, A; McCloskey, P; Spizz, G; Varnum, B; Der, C; Liu, E T

    1996-01-01

    To understand the mechanism of Axl signaling, we have initiated studies to delineate downstream components in interleukin-3-dependent 32D cells by using a chimeric receptor containing the recombinant epidermal growth factor (EGF) receptor extracellular and transmembrane domains and the Axl kinase domain (EAK [for EGF receptor-Axl kinase]). We have previously shown that upon exogenous EGF stimulation, 32D-EAK cells are capable of proliferation in the absence of interleukin-3. With this system, we determined that EAK-induced cell survival and mitogenesis are dependent upon the Ras/extracellular-signal-regulated protein kinase (ERK) cascade. Although the phosphatidylinositol-3 kinase pathway is activated upon EAK signaling, it appears to be dispensable for the biological actions of the Axl kinase. Furthermore, we demonstrated that different threshold levels of Ras/ERK activation are needed to induce a block to apoptosis or proliferation in 32D cells. Recently, we have identified an Axl ligand, GAS6. Surprisingly, GAS6-stimulated 32D-Axl cells exhibited no blockage to apoptosis or mitogenic response which is correlated with the absence of Ras/ERK activation. Taken together, these data suggest that different extracellular domains dramatically alter the intracellular response of the Axl kinase. Furthermore, our data suggest that the GAS6-Axl interaction does not induce mitogenesis and that its exact role remains to be determined.

  20. Task force report on the M-2 axle/bearing failure investigation.

    DOT National Transportation Integrated Search

    1983-01-31

    This investigation of the tubular-axle/roller-bearing failures experienced with M-2 multiple-unit cars of New York's Metropolitan Transportation Authority was aimed at establishing failure mechanisms, assessing the effectiveness of interim and long-t...

  1. The Axl kinase domain in complex with a macrocyclic inhibitor offers first structural insights into an active TAM receptor kinase.

    PubMed

    Gajiwala, Ketan S; Grodsky, Neil; Bolaños, Ben; Feng, Junli; Ferre, RoseAnn; Timofeevski, Sergei; Xu, Meirong; Murray, Brion W; Johnson, Ted W; Stewart, Al

    2017-09-22

    The receptor tyrosine kinase family consisting of Tyro3, Axl, and Mer (TAM) is one of the most recently identified receptor tyrosine kinase families. TAM receptors are up-regulated postnatally and maintained at high levels in adults. They all play an important role in immunity, but Axl has also been implicated in cancer and therefore is a target in the discovery and development of novel therapeutics. However, of the three members of the TAM family, the Axl kinase domain is the only one that has so far eluded structure determination. To this end, using differential scanning fluorimetry and hydrogen-deuterium exchange mass spectrometry, we show here that a lower stability and greater dynamic nature of the Axl kinase domain may account for its poor crystallizability. We present the first structural characterization of the Axl kinase domain in complex with a small-molecule macrocyclic inhibitor. The Axl crystal structure revealed two distinct conformational states of the enzyme, providing a first glimpse of what an active TAM receptor kinase may look like and suggesting a potential role for the juxtamembrane region in enzyme activity. We noted that the ATP/inhibitor-binding sites of the TAM members closely resemble each other, posing a challenge for the design of a selective inhibitor. We propose that the differences in the conformational dynamics among the TAM family members could potentially be exploited to achieve inhibitor selectivity for targeted receptors. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Plane hydroelastic beam vibrations due to uniformly moving one axle vehicle

    NASA Astrophysics Data System (ADS)

    Fleischer, D.; Park, S.-K.

    2004-06-01

    The hydroelastic vibrations of a beam with rectangular cross-section is analyzed under the effect of an uniformly moving single axle vehicle using modal analysis and two-dimensional potential flow theory of the fluid neglecting the effect of surface waves aside the beam. For the special case of homogeneous beam resting on the surface of a water filled prismatic basin, the normal modes are determined considering surface waves in beam direction under the condition of compensating the volume of the enclosed fluid. The way to determine the vertical acceleration of the single axle vehicle is shown, which governs the response of the system. As analysis results the course of wheel load, the surface waves along the beam and the flow velocity distribution of the fluid is demonstrated for a continuous floating bridge under the passage of a rolling mass moving with uniform speed.

  3. In brain, Axl recruits Grb2 and the p85 regulatory subunit of Pl3 kinase; in vitro mutagenesis defines th requisite binding sites for downstream Akt activation

    PubMed Central

    Weinger, Jason G.; Gohari, Pouyan; Yan, Ying; Backer, Jonathan M.; Varnum, Brian; Shafit-Zagardo, Bridget

    2010-01-01

    Axl is a receptor tyrosine kinase implicated in cell survival following growth factor withdrawal and other stressors. The binding of Axl's ligand, growth arrest-specific protein 6 (Gas6), results in Axl autophosphorylation, recruitment of signaling molecules, and activation of downstream survival pathways. Pull-down assays and immunoprecipitations using wildtype and mutant Axl transfected cells determined that Axl directly binds growth factor receptor-bound protein 2 (Grb2) at pYVN and the p85 subunit of phosphatidylinositol-3 kinase (PI3 kinase) at two pYXXM sites (pY779 and pY821). Also, p85 can indirectly bind to Axl via an interaction between p85's second proline-rich region and the N-terminal SH3 domain of Grb2. Further, Grb2 and p85 can compete for binding at the pY821VNM site. Gas6-stimulation of Axl-transfected COS7 cells recruited activated PI3 kinase and phosphorylated Akt. An interaction between Axl, p85 and Grb2 was confirmed in brain homogenates, enriched populations of O4+ oligodendrocytes, and O4– flow-through prepared from day 10 mouse brain, indicating that cells with active Gas6/Axl signal through Grb2 and the PI3 kinase/Akt pathways. PMID:18346204

  4. Overcoming drug-tolerant cancer cell subpopulations showing AXL activation and epithelial–mesenchymal transition is critical in conquering ALK-positive lung cancer

    PubMed Central

    Nakamichi, Shinji; Seike, Masahiro; Miyanaga, Akihiko; Chiba, Mika; Zou, Fenfei; Takahashi, Akiko; Ishikawa, Arimi; Kunugi, Shinobu; Noro, Rintaro; Kubota, Kaoru; Gemma, Akihiko

    2018-01-01

    Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) induce a dramatic response in non–small cell lung cancer (NSCLC) patients with the ALK fusion gene. However, acquired resistance to ALK-TKIs remains an inevitable problem. In this study, we aimed to discover novel therapeutic targets to conquer ALK-positive lung cancer. We established three types of ALK-TKI (crizotinib, alectinib and ceritinib)-resistant H2228 NSCLC cell lines by high exposure and stepwise methods. We found these cells showed a loss of ALK signaling, overexpressed AXL with epithelial-mesenchymal transition (EMT), and had cancer stem cell-like (CSC) properties, suggesting drug-tolerant cancer cell subpopulations. Similarly, we demonstrated that TGF-β1 treated H2228 cells also showed AXL overexpression with EMT features and ALK-TKI resistance. The AXL inhibitor, R428, or HSP90 inhibitor, ganetespib, were effective in reversing ALK-TKI resistance and EMT changes in both ALK-TKI-resistant and TGF-β1-exposed H2228 cells. Tumor volumes of xenograft mice implanted with established H2228-ceritinib-resistant (H2228-CER) cells were significantly reduced after treatment with ganetespib, or ganetespib in combination with ceritinib. Some ALK-positive NSCLC patients with AXL overexpression showed a poorer response to crizotinib therapy than patients with a low expression of AXL. ALK signaling-independent AXL overexpressed in drug-tolerant cancer cell subpopulations with EMT and CSC features may be commonly involved commonly involved in intrinsic and acquired resistance to ALK-TKIs. This suggests AXL and HSP90 inhibitors may be promising therapeutic drugs to overcome drug-tolerant cancer cell subpopulations in ALK-positive NSCLC patients for the reason that ALK-positive NSCLC cells do not live through ALK-TKI therapy. PMID:29930762

  5. Targeted Axl Inhibition Primes Chronic Lymphocytic Leukemia B Cells to Apoptosis and Shows Synergistic/Additive Effects in Combination with BTK Inhibitors.

    PubMed

    Sinha, Sutapa; Boysen, Justin; Nelson, Michael; Secreto, Charla; Warner, Steven L; Bearss, David J; Lesnick, Connie; Shanafelt, Tait D; Kay, Neil E; Ghosh, Asish K

    2015-05-01

    B-cell chronic lymphocytic leukemia (CLL) is an incurable disease despite aggressive therapeutic approaches. We previously found that Axl receptor tyrosine kinase (RTK) plays a critical role in CLL B-cell survival. Here, we explored the possibility of using a high-affinity Axl inhibitor as a single agent or in combination with Bruton's tyrosine kinase (BTK) inhibitors for future clinical trial to treat patients with CLL. Expression/activation status of other members of the TAM (e.g., Tyro3, Axl, and MER) family of RTKs in CLL B cells was evaluated. Cells were treated with a high-affinity orally bioavailable Axl inhibitor TP-0903 with or without the presence of CLL bone marrow stromal cells (BMSCs). Inhibitory effects of TP-0903 on the Axl signaling pathway were also evaluated in CLL B cells. Finally, cells were exposed to TP-0903 in combination with BTK inhibitors to determine any synergistic/additive effects of the combination. CLL B cells overexpress Tyro3, but not MER. Of interest, Tyro3 remains as constitutively phosphorylated and forms a complex with Axl in CLL B cells. TP-0903 induces massive apoptosis in CLL B cells with LD50 values of nanomolar ranges. Importantly, CLL BMSCs could not protect the leukemic B cells from TP-0903-induced apoptosis. A marked reduction of the antiapoptotic proteins Mcl-1, Bcl-2, and XIAP and upregulation of the proapoptotic protein BIM in CLL B cells was detected as a result of Axl inhibition. Finally, combination of TP-0903 with BTK inhibitors augments CLL B-cell apoptosis. Administration of TP-0903 either as a single agent or in combination with BTK inhibitors may be effective in treating patients with CLL. ©2015 American Association for Cancer Research.

  6. Integrated chassis control for a three-axle electric bus with distributed driving motors and active rear steering system

    NASA Astrophysics Data System (ADS)

    Liu, Wei; He, Hongwen; Sun, Fengchun; Lv, Jiangyi

    2017-05-01

    This paper describes an integrated chassis control framework for a novel three-axle electric bus with active rear steering (ARS) axle and four motors at the middle and rear wheels. The proposed integrated framework consists of four parts: (1) an active speed limiting controller is designed for anti-body slip control and rollover prevention; (2) an ARS controller is designed for coordinating the tyre wear between the driving wheels; (3) an inter-axle torque distribution controller is designed for optimal torque distribution between the axles, considering anti-wheel slip and battery power limitations and (4) a data acquisition and estimation module for collecting the measured and estimated vehicle states. To verify the performances, a simulation platform is established in Trucksim software combined with Simulink. Three test cases are particularly designed to show the performances. The proposed algorithm is compared with a simple even control algorithm. The test results show satisfactory lateral stability and rollover prevention performances under severe steering conditions. The desired tyre wear coordinating performance is also realised, and the wheel slip ratios are restricted within stable region during intensive driving and emergency braking with complicated road conditions.

  7. Part 1 : heavy axle load revenue service mega site testing 2005-2012.

    DOT National Transportation Integrated Search

    2014-06-01

    Since 2005, the Federal Railroad Administration : and the Association of American Railroads have : jointly funded a heavy axle load (HAL) revenue : service testing program with several objectives. : One objective is to determine the effects of HAL : ...

  8. Part 2 : heavy axle load revenue service mega site testing 2005-2012.

    DOT National Transportation Integrated Search

    2014-06-01

    Since 2005, the Federal Railroad Administration : and the Association of American Railroads have : jointly funded a heavy axle load (HAL) revenue : service testing program, with several objectives. : One objective is to determine the effects of HAL :...

  9. Normalization of TAM post-receptor signaling reveals a cell invasive signature for Axl tyrosine kinase.

    PubMed

    Kimani, Stanley G; Kumar, Sushil; Davra, Viralkumar; Chang, Yun-Juan; Kasikara, Canan; Geng, Ke; Tsou, Wen-I; Wang, Shenyan; Hoque, Mainul; Boháč, Andrej; Lewis-Antes, Anita; De Lorenzo, Mariana S; Kotenko, Sergei V; Birge, Raymond B

    2016-09-06

    Tyro3, Axl, and Mertk (TAMs) are a family of three conserved receptor tyrosine kinases that have pleiotropic roles in innate immunity and homeostasis and when overexpressed in cancer cells can drive tumorigenesis. In the present study, we engineered EGFR/TAM chimeric receptors (EGFR/Tyro3, EGFR/Axl, and EGF/Mertk) with the goals to interrogate post-receptor functions of TAMs, and query whether TAMs have unique or overlapping post-receptor activation profiles. Stable expression of EGFR/TAMs in EGFR-deficient CHO cells afforded robust EGF inducible TAM receptor phosphorylation and activation of downstream signaling. Using a series of unbiased screening approaches, that include kinome-view analysis, phosphor-arrays, RNAseq/GSEA analysis, as well as cell biological and in vivo readouts, we provide evidence that each TAM has unique post-receptor signaling platforms and identify an intrinsic role for Axl that impinges on cell motility and invasion compared to Tyro3 and Mertk. These studies demonstrate that TAM show unique post-receptor signatures that impinge on distinct gene expression profiles and tumorigenic outcomes.

  10. Impact of overweight vehicles (with heavy axle loads) on bridge deck deterioration.

    DOT National Transportation Integrated Search

    2012-03-01

    Bridge deck slabs develop compressive stresses from global flexural deformation and locally from high-level : wheel loads when it is subjected to overweight trucks. This study quantified the impact of overweight vehicles : with heavy axle loads on br...

  11. Vitamin K2 regression aortic calcification induced by warfarin via Gas6/Axl survival pathway in rats.

    PubMed

    Jiang, Xiaoyu; Tao, Huiren; Qiu, Cuiting; Ma, Xiaolei; Li, Shan; Guo, Xian; Lv, Anlin; Li, Huan

    2016-09-05

    The aim of this study was to investigate the effect of vitamin K2 on aortic calcification induced by warfarin via Gas6/Axl survival pathway in rats. A calcification model was established by administering 3mg/g warfarin to rats. Rats were divided into 9 groups: control group (0W, 4W, 6W and 12W groups), 4W calcification group, 6W calcification group, 12W calcification group, 6W calcification+6W normal group and 6W calcification+6W vitamin K2 group. Alizarin red S staining measured aortic calcium depositions; alkaline phosphatase activity in serum was measured by a kit; apoptosis was evaluated by TUNEL assay; protein expression levels of Gas6, Axl, phosphorylated Akt (p-Akt), and Bcl-2 were determined by western blotting. The calcium content, calcium depositions, ALP activity and apoptosis were significantly higher in the calcification groups than control group. Gas6, Axl, p-Akt and Bcl-2 expression was lower in the calcification group than control group. 100μg/g vitamin K2 treatment decreased calcium depositions, ALP activity and apoptosis significantly, but increased Gas6, Axl, p-Akt and Bcl-2 expression. 100μg/g vitamin K2 reversed 44% calcification. Pearson correlation analysis showed a positive correlation between formation calcification and apoptosis (R(2)=0.8853, P<0.0001). In conclusion, we established a warfarin-induced calcification model and showed vitamin K2 can inhibit warfarin-induced aortic calcification and apoptosis. The regression of aortic calcification by vitamin K2 involved the Gas6/Axl axis. This data may provide a theoretical basis for future clinical treatments for aortic calcification. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Fracture resistance and fatigue crack growth characteristics of railroad wheels and axles

    DOT National Transportation Integrated Search

    1977-11-30

    The effects of chemical composition, temperature and loading rates on the plane strain fracture toughness K sub I sub c of railroad wheels have been determined. Similarly, the effects of these variables were determined for grade U and F railroads axl...

  13. On the dynamic response at the wheel axle of a pneumatic tire

    NASA Astrophysics Data System (ADS)

    Kung, L. E.; Soedel, W.; Yang, T. Y.

    1986-06-01

    A method for calculating the steady state displacement response and force transmission at the wheel axle of a pneumatic tire-suspension system due to a steady state force or displacement excitation at the tire to ground contact point is developed. The method requires the frequency responses (or receptances)_of both tire-wheel and suspension units. The frequency response of the tire-wheel unit is obtained by using the modal expansion method. The natural frequencies and mode shapes of the tire-wheel unit are obtained by using a geometrically non-linear, ring type, thin shell finite element of laminate composite. The frequency response of the suspension unit is obtained analytically. These frequency responses are used to calculate the force-input and the displacement-input responses at the wheel axle. This method allows the freedom of designing a vehicle and its tires independently and still achieving optimum dynamic performance.

  14. Identification of the receptor tyrosine kinase AXL in breast cancer as a target for the human miR-34a microRNA

    PubMed Central

    Mackiewicz, Mark; Huppi, Konrad; Pitt, Jason J.; Dorsey, Tiffany H.; Ambs, Stefan

    2012-01-01

    The identification of molecular features that contribute to the progression of breast cancer can provide valuable insight into the pathogenesis of this disease. Deregulated microRNA expression represents one type of molecular event that has been associated with many different human cancers. In order to identify a miRNA/mRNA regulatory interaction that is biologically relevant to the triple-negative breast cancer genotype/phenotype, we initially conducted a miRNA profiling experiment to detect differentially expressed miRNAs in cell line models representing triple-negative (MDA-MB-231), ER+ (MCF7), and HER-2 over expressed (SK-BR-3) histotypes. We identified human miR-34a expression as being >3-fold down (from its median expression value across all cell lines) in MDA-MB-231 cells, and identified AXL as a putative mRNA target using multiple miRNA/target prediction algorithms. The miR-34a/AXL interaction was functionally characterized through ectopic over expression experiments with a miR-34a mimic in two independent triple-negative breast cancer cell lines. In reporter assays, miR-34a binds to its putative target site within the AXL 3′UTR to inhibit luciferase expression. We also observed degradation of AXL mRNA and decreased AXL protein levels, as well as cell signaling effects on AKT phosphorylation and phenotypic effects on cell migration. Finally, we present an inverse correlative trend in miR-34a and AXL expression for both cell line and patient tumor samples. PMID:21814748

  15. Identification of the soluble form of tyrosine kinase receptor Axl as a potential biomarker for intracranial aneurysm rupture.

    PubMed

    Xu, Jing; Ma, Feiqiang; Yan, Wei; Qiao, Sen; Xu, Shengquan; Li, Yi; Luo, Jianhong; Zhang, Jianmin; Jin, Jinghua

    2015-03-05

    Subarachnoid hemorrhage caused by a ruptured intracranial aneurysm (RIA) is a devastating condition with significant morbidity and mortality. Despite the fact that RIAs can be prevented by microsurgical clipping or endovascular coiling, there are no reliable means of effectively predicting IA patients at risk for rupture. The purpose of our study was to discover differentially-expressed glycoproteins in IAs with or without rupture as potential biomarkers to predict rupture. Forty age/gender-matched patients with RIA, unruptured IA (UIA), healthy controls (HCs) and disease controls (DCs) (discovery cohort, n = 10 per group) were recruited and a multiplex quantitative proteomic method, iTRAQ (isobaric Tagging for Relative and Absolute protein Quantification), was used to quantify relative changes in the lectin-purified glycoproteins in CSF from RIAs and UIAs compared to HCs and DCs. Then we verified the proteomic results in an independent set of samples (validation cohort, n = 20 per group) by enzyme-linked immunosorbent assay. Finally, we evaluated the specificity and sensitivity of the candidate marker with receiver operating characteristic (ROC) curve methods. The proteomic findings identified 294 proteins, 40 of which displayed quantitative changes unique to RIA, 13 to UIA, and 20 to IA. One of these proteins, receptor tyrosine kinase Axl, was significantly increased in RIA, as confirmed in CSF from the discovery cohort as well as in CSF and plasma from the validation cohort (p <0.05). Spearman's correlation analysis revealed that the CSF and plasma Axl levels were strongly correlated (r = 0.93, p <0.0001). The ROC curve indicated an optimal CSF Axl threshold of 0.12 nM for discriminating RIA from UIA with corresponding sensitivity/specificity of 73.33%/90% and an area under the curve (AUC) of 0.89 (95% CI: 0.80-0.97, p < 0.0001). The optimal threshold for plasma Axl was 1.7 nM with corresponding sensitivity/specificity of 50%/80% and an AUC of 0

  16. Effect of Michigan multi-axle trucks on pavement distress and profile: executive summary.

    DOT National Transportation Integrated Search

    2009-02-01

    Truck traffic is a major factor in pavement design because truck loads are the primary cause of : pavement distresses. Trucks have different axle configurations that cause different levels of : pavement damage. The American Association of State Highw...

  17. CONOCOPHILLIPS FUEL EFFICIENT HIGH-PERFORMANCE(FEHP) SAE 75W90 REAR AXLE GEAR LUBRICANT

    EPA Science Inventory

    This report is on the Environmental Verification Test of a ConocoPhillips real axle gear lubricant to determine whether it could save vehicle fuel. It determined that a verifyable fuel savings could be measured.

  18. Faults Diagnostics of Railway Axle Bearings Based on IMF’s Confidence Index Algorithm for Ensemble EMD

    PubMed Central

    Yi, Cai; Lin, Jianhui; Zhang, Weihua; Ding, Jianming

    2015-01-01

    As train loads and travel speeds have increased over time, railway axle bearings have become critical elements which require more efficient non-destructive inspection and fault diagnostics methods. This paper presents a novel and adaptive procedure based on ensemble empirical mode decomposition (EEMD) and Hilbert marginal spectrum for multi-fault diagnostics of axle bearings. EEMD overcomes the limitations that often hypothesize about data and computational efforts that restrict the application of signal processing techniques. The outputs of this adaptive approach are the intrinsic mode functions that are treated with the Hilbert transform in order to obtain the Hilbert instantaneous frequency spectrum and marginal spectrum. Anyhow, not all the IMFs obtained by the decomposition should be considered into Hilbert marginal spectrum. The IMFs’ confidence index arithmetic proposed in this paper is fully autonomous, overcoming the major limit of selection by user with experience, and allows the development of on-line tools. The effectiveness of the improvement is proven by the successful diagnosis of an axle bearing with a single fault or multiple composite faults, e.g., outer ring fault, cage fault and pin roller fault. PMID:25970256

  19. The influence of axle position and the use of accessories on the activity of upper limb muscles during manual wheelchair propulsion.

    PubMed

    Bertolaccini, Guilherme da Silva; Carvalho Filho, Idinei Francisco Pires de; Christofoletti, Gustavo; Paschoarelli, Luis Carlos; Medola, Fausto Orsi

    2018-06-01

    Wheelchair configuration is an important factor influencing the ergonomics of the user-device interface and, from a biomechanical point of view, small changes in chair setup may have a positive influence on the demand on the upper limbs during manual propulsion. This study aimed to investigate the influence of the position of the rear wheels' axle and the use of accessories on the activity of upper limb muscles during manual wheelchair propulsion. Electromyography signals of the biceps, triceps, anterior deltoids and pectoralis major were collected for 11 able-bodied subjects in a wheelchair propulsion protocol with four different wheelchair configurations (differing in axle position and the use of accessories) on a straightforward sprint and a slalom course. With accessories, moving the axle forward led to a decrease in the activity of all muscles in both the straightforward sprint (significant differences in triceps, anterior deltoids and biceps) and the slalom course (significant difference in anterior deltoids and biceps). However, when propelling the chair without accessories, no difference was found related to axle position. Changes in wheelchair configuration can influence the ergonomics of manual wheelchair propulsion. Reducing the biomechanical loads may benefit users' mobility, independence and social participation.

  20. Off-road axle detection sensor (ORADS) : occlusion feasibility study, executive summary, 27 August, 1997.

    DOT National Transportation Integrated Search

    1997-08-27

    The work accomplished under this initiative is in direct relation to the development effort proposed by Spectra Research, Inc. (S*R) for an "Off-Road Axle Detection Sensor (ORADS)". The feasibility study was performed to investigate potential occlusi...

  1. Off-road axle detection sensor (ORADS) : occlusion feasibility study, final technical report, 27 August, 1997.

    DOT National Transportation Integrated Search

    1997-08-27

    The work accomplished under this initiative is in direct relation to the development effort proposed by Spectra : Research, Inc. (S*R) for an "Off-Road Axle Detection Sensor (ORADS)". The feasibility study was performed to : investigate potential occ...

  2. EEMD-Based Steady-State Indexes and Their Applications to Condition Monitoring and Fault Diagnosis of Railway Axle Bearings

    PubMed Central

    Fan, Wei; Tsui, Kwok-Leung; Lin, Jianhui

    2018-01-01

    Railway axle bearings are one of the most important components used in vehicles and their failures probably result in unexpected accidents and economic losses. To realize a condition monitoring and fault diagnosis scheme of railway axle bearings, three dimensionless steadiness indexes in a time domain, a frequency domain, and a shape domain are respectively proposed to measure the steady states of bearing vibration signals. Firstly, vibration data collected from some designed experiments are pre-processed by using ensemble empirical mode decomposition (EEMD). Then, the coefficient of variation is introduced to construct two steady-state indexes from pre-processed vibration data in a time domain and a frequency domain, respectively. A shape function is used to construct a steady-state index in a shape domain. At last, to distinguish normal and abnormal bearing health states, some guideline thresholds are proposed. Further, to identify axle bearings with outer race defects, a pin roller defect, a cage defect, and coupling defects, the boundaries of all steadiness indexes are experimentally established. Experimental results showed that the proposed condition monitoring and fault diagnosis scheme is effective in identifying different bearing health conditions. PMID:29495446

  3. Development and characterization of K562 cell clones expressing BCL11A-XL: Decreased hemoglobin production with fetal hemoglobin inducers and its rescue with mithramycin

    PubMed Central

    Finotti, Alessia; Gasparello, Jessica; Breveglieri, Giulia; Cosenza, Lucia Carmela; Montagner, Giulia; Bresciani, Alberto; Altamura, Sergio; Bianchi, Nicoletta; Martini, Elisa; Gallerani, Eleonora; Borgatti, Monica; Gambari, Roberto

    2015-01-01

    Induction of fetal hemoglobin (HbF) is considered a promising strategy in the treatment of β-thalassemia, in which production of adult hemoglobin (HbA) is impaired by mutations affecting the β-globin gene. Recent results indicate that B-cell lymphoma/leukemia 11A (BCL11A) is a major repressor of γ-globin gene expression. Therefore, disrupting the binding of the BCL11A transcriptional repressor complex to the γ-globin gene promoter provides a novel approach for inducing expression of the γ-globin genes. To develop a cellular screening system for the identification of BCL11A inhibitors, we produced K562 cell clones with integrated copies of a BCL11A-XL expressing vector. We characterized 12 K562 clones expressing different levels of BCL11A-XL and found that a clear inverse relationship does exist between the levels of BCL11A-XL and the extent of hemoglobinization induced by a panel of HbF inducers. Using mithramycin as an inducer, we found that this molecule was the only HbF inducer efficient in rescuing the ability to differentiate along the erythroid program, even in K562 cell clones expressing high levels of BCL11A-XL, suggesting that BCL11A-XL activity is counteracted by mithramycin. PMID:26342260

  4. Development and characterization of K562 cell clones expressing BCL11A-XL: Decreased hemoglobin production with fetal hemoglobin inducers and its rescue with mithramycin.

    PubMed

    Finotti, Alessia; Gasparello, Jessica; Breveglieri, Giulia; Cosenza, Lucia Carmela; Montagner, Giulia; Bresciani, Alberto; Altamura, Sergio; Bianchi, Nicoletta; Martini, Elisa; Gallerani, Eleonora; Borgatti, Monica; Gambari, Roberto

    2015-12-01

    Induction of fetal hemoglobin (HbF) is considered a promising strategy in the treatment of β-thalassemia, in which production of adult hemoglobin (HbA) is impaired by mutations affecting the β-globin gene. Recent results indicate that B-cell lymphoma/leukemia 11A (BCL11A) is a major repressor of γ-globin gene expression. Therefore, disrupting the binding of the BCL11A transcriptional repressor complex to the γ-globin gene promoter provides a novel approach for inducing expression of the γ-globin genes. To develop a cellular screening system for the identification of BCL11A inhibitors, we produced K562 cell clones with integrated copies of a BCL11A-XL expressing vector. We characterized 12 K562 clones expressing different levels of BCL11A-XL and found that a clear inverse relationship does exist between the levels of BCL11A-XL and the extent of hemoglobinization induced by a panel of HbF inducers. Using mithramycin as an inducer, we found that this molecule was the only HbF inducer efficient in rescuing the ability to differentiate along the erythroid program, even in K562 cell clones expressing high levels of BCL11A-XL, suggesting that BCL11A-XL activity is counteracted by mithramycin. Copyright © 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  5. 75 FR 52981 - Chrysler, LLC, Detroit Axle Plant, Including On-Site Leased Workers from Caravan Knight...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-30

    ... certification for workers of the subject firm. The workers are engaged in the production of automotive axles, a... automotive vehicles. New information shows that workers leased from Syncreon were employed on-site at the...

  6. Vitamin K2 inhibits rat vascular smooth muscle cell calcification by restoring the Gas6/Axl/Akt anti-apoptotic pathway.

    PubMed

    Qiu, Cuiting; Zheng, Haijun; Tao, Huiren; Yu, Wenjun; Jiang, Xiaoyu; Li, Aiqin; Jin, Hui; Lv, Anlin; Li, Huan

    2017-09-01

    Vascular calcification is associated with cardiovascular disease as a complication of hypertension, hyperlipidemia, diabetes mellitus, and chronic kidney disease. Vitamin K2 (VK2) delays vascular calcification by an unclear mechanism. Moreover, apoptosis modulates vascular smooth muscle cell (VSMC) calcification. This paper aimed to study VK2-modified VSMC calcification and survival cell signaling mediated by growth arrest-specific gene 6 (Gas6) and its tyrosine kinase receptor Axl. Primary-cultured VSMCs were dose-dependently treated with VK2 in the presence of calcification medium for 8 days, or pre-treated for 1 h with/without the Axl inhibitor R428 (2 μmol/L) or the caspase inhibitor Z-VAD-fmk (20 μmol/L) followed by treatment with VK2 (10 μmol/L) or rmGas6 (200 nmol/L) in calcification medium for 8 days. Calcium deposition was determined by the o-cresolphthalein complexone assay and Alizarin Red S staining. Apoptosis was determined by TUNEL and flow cytometry using Annexin V-FITC and propidium iodide staining. Western blotting detected the expressions of Axl, Gas6, p-Akt, Akt, and Bcl2. VK2 significantly inhibited CaCl 2 - and β-sodium glycerophosphate (β-GP)-induced VSMC calcification and apoptosis, which was dependent on restored Gas6 expression and activated downstream signaling by Axl, p-Akt, and Bcl2. Z-VAD-fmk significantly inhibited CaCl 2 - and β-GP-induced VSMC calcification and apoptosis. Augmented recombinant mouse Gas6 protein (rmGas6) expression significantly reduced VSMC calcification and apoptosis. Furthermore, the Gas6/Axl interaction was inhibited by R428, which abolished the preventive effect of VK2 on CaCl 2 - and β-GP-induced apoptosis and calcification. These results suggest that Gas6 is critical in VK2-mediated functions that attenuate CaCl 2 - and β-GP-induced VSMC calcification by blocking apoptosis.

  7. Heat-affected zone microstructure and mechanical properties evolution for laser remanufacturing 35CrMoA axle steel

    NASA Astrophysics Data System (ADS)

    Feng, Xiangyi; Dong, Shiyun; Yan, Shixing; Liu, Xiaoting; Xu, Binshi; Pan, Fusheng

    2018-03-01

    In this article, by using orthogonal test the technological test was conducted and the optimum processing of the remanufacturing35CrMoA axle were obtained. The evolution of microstructure and mechanical property of HAZ were investigated. The microstructure of HAZ was characterized by means of OM and SEM. Meanwhile hardness distribution in HAZ and tensile property of cladding-HAZ-substrate samples were measured. The microstructure of cladding and HAZ were observed. The microsturcture evoltion and the mechanism of harden in the HAZ was discussed and revealed. The results indicated that the remanufacturing part has excellent strength due to grain refining and dispersive distribution of nanoscale cementite. The remanufacturing part will have uniform microstructure and hardness matching with that of 35CrMoA axle by using stress-relieving annealing at 580°.

  8. Trackside acoustic diagnosis of axle box bearing based on kurtosis-optimization wavelet denoising

    NASA Astrophysics Data System (ADS)

    Peng, Chaoyong; Gao, Xiaorong; Peng, Jianping; Wang, Ai

    2018-04-01

    As one of the key components of railway vehicles, the operation condition of the axle box bearing has a significant effect on traffic safety. The acoustic diagnosis is more suitable than vibration diagnosis for trackside monitoring. The acoustic signal generated by the train axle box bearing is an amplitude modulation and frequency modulation signal with complex train running noise. Although empirical mode decomposition (EMD) and some improved time-frequency algorithms have proved to be useful in bearing vibration signal processing, it is hard to extract the bearing fault signal from serious trackside acoustic background noises by using those algorithms. Therefore, a kurtosis-optimization-based wavelet packet (KWP) denoising algorithm is proposed, as the kurtosis is the key indicator of bearing fault signal in time domain. Firstly, the geometry based Doppler correction is applied to signals of each sensor, and with the signal superposition of multiple sensors, random noises and impulse noises, which are the interference of the kurtosis indicator, are suppressed. Then, the KWP is conducted. At last, the EMD and Hilbert transform is applied to extract the fault feature. Experiment results indicate that the proposed method consisting of KWP and EMD is superior to the EMD.

  9. Improved characterization of truck traffic volumes and axle loads for mechanistic-empirical pavement design : [executive summary report].

    DOT National Transportation Integrated Search

    2012-12-01

    Traffic is one of the primary inputs in pavement design. Traditional pavement design procedures account for traffic using the equivalent single axle loads (ESALs) accumulated during the life of the pavement structure. This procedure is based on co...

  10. 75 FR 11914 - Chrysler, LLC, Detroit Axle Plant, Including On-Site Leased Workers From Caravan Knight...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-12

    ... shipped to an affiliated plant where they are used in the assembly of automotive vehicles. New information... Detroit, Michigan location of Chrysler, LLC, Detroit Axle Plant. The Department has determined that these... Knight Facilities Management LLC working on-site at the Detroit, Michigan location of Chrysler, LLC...

  11. Development of truck axle spectra from Oregon weigh-in-motion data for use in pavement design and analysis.

    DOT National Transportation Integrated Search

    2008-01-01

    (ADTT) volumes, were selected to characterize axle weight and spacing spectra on Oregon state highways. : Seasonal variations were considered by investigating data occurring over the four seasons: winter, spring, summer, : and fall. WIM data were cle...

  12. Wheeled Vehicle Drive Lines, Axles, and Suspension Systems. Military Curriculum Materials for Vocational and Technical Education.

    ERIC Educational Resources Information Center

    Army Ordnance Center and School, Aberdeen Proving Ground, MD.

    This course is one of several subcourses that make up the entire Army correspondence course on wheeled vehicle maintenance. The subcourse is designed to provide the student with information about the operation, malfunction diagnosis, maintenance, and repair of wheeled vehicle drive lines, axles, and suspension systems. It provides the basic…

  13. 76 FR 32327 - Regulatory Guidance on the Designation of Steerable Rear Axle Operators (Tillermen) as Drivers of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-06

    ..., to ``tillerman,'' a person exercising control over the movement of a steerable rear axle on a CMV... Riggers Association, asking about other circumstances under which a person exercising control over a CMV's... AND PENALTIES Section 383.3, ``Applicability.'' ``Question 34: Would a tillerman, a person exercising...

  14. Army Excellence in Leadership (AXL): A Multimedia Approach to Building Tacit Knowledge and Cultural Reasoning

    DTIC Science & Technology

    2007-01-01

    response options were randomly arranged for both the pretest and posttest . Additionally, one of the " pretest " items was given prior to watching the film...After selecting a topic, the AXL system presents the goals of the module to the group . The group then watches the associated filmed case on the...questionnaires and focus group interviews were used to create measures to assess learning from Tripwire modules. ARI then pilot tested one of the new

  15. AUTOMOTIVE DIESEL MAINTENANCE 1. UNIT XIX, I--ENGINE TUNE-UP--CUMMINS DIESEL ENGINE, II--FRONT END SUSPENSION AND AXLES.

    ERIC Educational Resources Information Center

    Minnesota State Dept. of Education, St. Paul. Div. of Vocational and Technical Education.

    THIS MODULE OF A 30-MODULE COURSE IS DESIGNED TO DEVELOP AN UNDERSTANDING OF DIESEL ENGINE TUNE-UP PROCEDURES AND THE DESIGN OF FRONT END SUSPENSION AND AXLES USED ON DIESEL ENGINE EQUIPMENT. TOPICS ARE (1) PRE-TUNE-UP CHECKS, (2) TIMING THE ENGINE, (3) INJECTOR PLUNGER AND VALVE ADJUSTMENTS, (4) FUEL PUMP ADJUSTMENTS ON THE ENGINE (PTR AND PTG),…

  16. Development of a new time domain-based algorithm for train detection and axle counting

    NASA Astrophysics Data System (ADS)

    Allotta, B.; D'Adamio, P.; Meli, E.; Pugi, L.

    2015-12-01

    This paper presents an innovative train detection algorithm, able to perform the train localisation and, at the same time, to estimate its speed, the crossing times on a fixed point of the track and the axle number. The proposed solution uses the same approach to evaluate all these quantities, starting from the knowledge of generic track inputs directly measured on the track (for example, the vertical forces on the sleepers, the rail deformation and the rail stress). More particularly, all the inputs are processed through cross-correlation operations to extract the required information in terms of speed, crossing time instants and axle counter. This approach has the advantage to be simple and less invasive than the standard ones (it requires less equipment) and represents a more reliable and robust solution against numerical noise because it exploits the whole shape of the input signal and not only the peak values. A suitable and accurate multibody model of railway vehicle and flexible track has also been developed by the authors to test the algorithm when experimental data are not available and in general, under any operating conditions (fundamental to verify the algorithm accuracy and robustness). The railway vehicle chosen as benchmark is the Manchester Wagon, modelled in the Adams VI-Rail environment. The physical model of the flexible track has been implemented in the Matlab and Comsol Multiphysics environments. A simulation campaign has been performed to verify the performance and the robustness of the proposed algorithm, and the results are quite promising. The research has been carried out in cooperation with Ansaldo STS and ECM Spa.

  17. Dynamic axle and wheel loads identification: laboratory studies

    NASA Astrophysics Data System (ADS)

    Zhu, X. Q.; Law, S. S.

    2003-12-01

    Two methods have been reported by Zhu and Law to identify moving loads on the top of a bridge deck. One is based on the exact solution (ESM) and the other is based on the finite element formulation (FEM). Simulation studies on the effect of different influencing factors have been reported previously. This paper comparatively studies the performances of these two methods with experimental measurements obtained from a bridge/vehicle system in the laboratory. The strains of the bridge deck are measured when a model car moves across the bridge deck along different paths. The moving loads on the bridge deck are identified from the measured strains using these two methods, and the responses are reconstructed from the identified loads for comparison with the measured responses to verify the performances of these methods. Studies on the identification accuracy due to the effect of the number of vibration mode used, the number of measuring points and eccentricities of travelling paths are performed. Results show that the ESM could identify the moving loads individually or as axle loads when they are travelling at an eccentricity with the sensors located close to the travelling path of the forces. And the accuracy of the FEM is dependent on the amount of measured information used in the identification.

  18. Screening and identification of novel compounds with potential anti-proliferative effects on gallium-resistant lung cancer through an AXL kinase pathway.

    PubMed

    Oyewumi, Moses O; Alazizi, Adnan; Liva, Sophia; Lin, Li; Geldenhuys, Werner J

    2014-09-15

    The clinical application of gallium compounds as anticancer agents is hampered by development of resistance. As a potential strategy to overcome the limitation, eight series of compounds were identified through virtual screening of AXL kinase homology model. Anti-proliferative studies were carried using gallium-sensitive (S) and gallium-resistant (R) human lung adenocarcinoma (A549) cells. Compounds 5476423 and 7919469 were identified as leads. The IC50 values from treating R-cells showed compounds 5476423 and 7919469 had 80 fold and 13 fold increased potency, respectively, compared to gallium acetylacetonate (GaAcAc). The efficacy of GaAcAc against R-cells was increased 2 fold and 1.2 fold when combined with compounds 5476423 and 7919469, respectively. Compared with S-cells, R-cells showed elevated expression of AXL protein, which was significantly suppressed through treatments with the lead compounds. It is anticipated that the lead compounds could be applied in virtual screening programs to identify novel scaffolds for new therapeutic agents as well as combinatorial therapy agents in gallium resistant lung cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. The Design and Performance Evaluation of Hydroformed Tubular Torsion Beam Axle

    NASA Astrophysics Data System (ADS)

    Kim, Jaehyun; Oh, Jinho; Choi, Hanho

    2010-06-01

    Suspensions for vehicles are structural devices used for suspending a vehicle body and absorbing shocks from the road. Thus, the suspensions must be designed such that they can attenuate shocks from a road and make passengers feel comfortable despite the shocks, and improve steering stability, determined by the ground contact force of tires during running of vehicles. Another important factor to be considered while designing suspensions is that the suspensions must maintain desired stiffness and desired durability despite the repeated application of shocks from roads thereto. The present relates, in general, to a tubular torsion beam for rear suspensions of vehicles and a manufacturing method thereof and, more particularly, to the provision of tubular torsion beams having excellent roll stiffness and excellent roll strength, produced through hydroforming. The hydroforming technology has a lot of benefit which is shape accuracy, good durability caused by compressive pressure, and good forming quality. In this study, the performance evaluation of the hydroformed tubular torsion beam axle is evaluated.

  20. Synthesis of the adaptive continuous system for the multi-axle wheeled vehicle body oscillation damping

    NASA Astrophysics Data System (ADS)

    Zhileykin, M. M.; Kotiev, G. O.; Nagatsev, M. V.

    2018-02-01

    In order to meet the growing mobility requirements for the wheeled vehicles on all types of terrain the engineers have to develop a large number of specialized control algorithms for the multi-axle wheeled vehicle (MWV) suspension improving such qualities as ride comfort, handling and stability. The authors have developed an adaptive algorithm of the dynamic damping of the MVW body oscillations. The algorithm provides high ride comfort and high mobility of the vehicle. The article discloses a method for synthesis of an adaptive dynamic continuous algorithm of the MVW body oscillation damping and provides simulation results proving high efficiency of the developed control algorithm.

  1. Track train dynamics analysis and test program: Methodology development for the derailment safety analysis of six-axle locomotives

    NASA Technical Reports Server (NTRS)

    Marcotte, P. P.; Mathewson, K. J. R.

    1982-01-01

    The operational safety of six axle locomotives is analyzed. A locomotive model with corresponding data on suspension characteristics, a method of track defect characterization, and a method of characterizing operational safety are used. A user oriented software package was developed as part of the methodology and was used to study the effect (on operational safety) of various locomotive parameters and operational conditions such as speed, tractive effort, and track curvature. The operational safety of three different locomotive designs was investigated.

  2. A receptor tyrosine kinase, UFO/Axl, and other genes isolated by a modified differential display PCR are overexpressed in metastatic prostatic carcinoma cell line DU145.

    PubMed

    Jacob, A N; Kalapurakal, J; Davidson, W R; Kandpal, G; Dunson, N; Prashar, Y; Kandpal, R P

    1999-01-01

    We have used a modified differential display PCR protocol for isolating 3' restriction fragments of cDNAs specifically expressed or overexpressed in metastatic prostate carcinoma cell line DU145. Several cDNA fragments were identified that matched to milk fat globule protein, UFO/Axl, a receptor tyrosine kinase, human homologue of a Xenopus maternal transcript, laminin and laminin receptor, human carcinoma-associated antigen, and some expressed sequence tags. The transcript for milk fat globule protein, a marker protein shown to be overexpressed in breast tumors, was elevated in DU145 cells. The expression of UFO/Axl, a receptor tyrosine kinase, was considerably higher in DU145 cells as compared to normal prostate cells and prostatic carcinoma cell line PC-3. The overexpression of UFO oncogene in DU145 cells is discussed in the context of prostate cancer metastasis.

  3. Serial analysis of gene expression reveals differential expression between endometriosis and normal endometrium. Possible roles for AXL and SHC1 in the pathogenesis of endometriosis

    PubMed Central

    Honda, Hiroshi; Barrueto, Fermin F; Gogusev, Jean; Im, Dwight D; Morin, Patrice J

    2008-01-01

    Background Endometriosis is a clinical condition that affects up to 10% of the women of reproductive age. Endometriosis is characterized by the presence of endometrial tissues outside the uterine cavity and can lead to chronic pelvic pain, infertility and, in some cases, to ovarian cancer. Methods In order to better understand the pathogenesis of endometriosis, we have used Serial Analysis of Gene Expression (SAGE) to identify genes differentially in this disease by studying three endometriotic tissues and a normal endometrium sample. Promising candidates (AXL, SHC1, ACTN4, PI3KCA, p-AKT, p-mTOR, and p-ERK) were independently validated by immunohistochemistry in additional normal and endometriotic tissues. Results We identified several genes differentially expressed between endometriosis and normal endometrium. IGF2, ACTN4, AXL, and SHC1 were among the most upregulated genes. Comparison of the endometriosis gene expression profiles with the gene expression patterns observed in normal human tissues allowed the identification of endometriosis-specific genes, which included several members of the MMP family (MMP1,2,3,10,11,14). Immunohistochemical analysis of several candidates confirmed the SAGE findings, and suggested the involvement of the PI3K-Akt and MAPK signaling pathways in endometriosis. Conclusion In human endometriosis, the PI3K-Akt and MAPK signaling pathways may be activated via overexpression of AXL and SHC1, respectively. These genes, as well as others identified as differentially expressed in this study, may be useful for the development of novel strategies for the detection and/or therapy of endometriosis. PMID:19055724

  4. Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site.

    PubMed

    Braunger, J; Schleithoff, L; Schulz, A S; Kessler, H; Lammers, R; Ullrich, A; Bartram, C R; Janssen, J W

    1997-06-05

    Ufo/Axl belongs to a new family of receptor tyrosine kinases with an extracellular structure similar to that of neural cell adhesion molecules. In order to elucidate intracellular signaling, the cytoplasmic moiety of Ufo/Axl was used to screen an expression library according to the CORT (cloning of receptor targets) method. Three putative Ufo substrates were identified: phospholipase Cgamma1 (PLCgamma), as well as p85alpha and p85beta subunits of phosphatidylinositol 3'-kinase (PI3-kinase). Subsequently, chimeric EGFR/Ufo receptors consisting of the extracellular domains of the epidermal growth factor receptor (EGFR) and the transmembrane and intracellular moiety of Ufo were engineered. Using different far-Western blot analyses and coimmunoprecipitation assays, receptor binding of PLCgamma and p85 proteins as well as GRB2, c-src and lck was examined in vitro and in vivo. Competitive inhibition of substrate binding and mutagenesis experiments with EGFR/Ufo constructs revealed C-terminal tyrosine 821 (EILpYVNMDEG) as a docking site for multiple effectors, namely PLCgamma, p85 proteins, GRB2, c-src and lck. Tyrosine 779 (DGLpYALMSRC) demonstrated an additional, but lower binding affinity for the p85 proteins in vitro. In addition, binding of PLCgamma occurred through tyrosine 866 (AGRpYVLCPST). Moreover, our in vivo data indicate that further direct or indirect binding sites for PLCgamma, GRB2, c-src and lck on the human Ufo receptor may exist.

  5. ORNL-GM: Development of Ionic Liquid-Additized, GF-5/6 Compatible Low-Viscosity Oils for Automotive Engine and Rear Axle Lubrication for 4% Improved Fuel Economy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Qu, Jun; Zhou, Yan; Luo, Huimin

    The overall objective of this project are as follows: Further develop ionic liquid (IL)-additized lowviscosity engine oils meeting the GF-5/6 specifications and possessing superior lubricating characteristics; Expand the IL additive technology to rear axle lubricants; and Seek a combined improvement in the vehicle fuel economy

  6. Common Co-activation of AXL and CDCP1 in EGFR-mutation-positive Non-smallcell Lung Cancer Associated With Poor Prognosis.

    PubMed

    Karachaliou, Niki; Chaib, Imane; Cardona, Andres Felipe; Berenguer, Jordi; Bracht, Jillian Wilhelmina Paulina; Yang, Jie; Cai, Xueting; Wang, Zhigang; Hu, Chunping; Drozdowskyj, Ana; Servat, Carles Codony; Servat, Jordi Codony; Ito, Masaoki; Attili, Ilaria; Aldeguer, Erika; Capitan, Ana Gimenez; Rodriguez, July; Rojas, Leonardo; Viteri, Santiago; Molina-Vila, Miguel Angel; Ou, Sai-Hong Ignatius; Okada, Morihito; Mok, Tony S; Bivona, Trever G; Ono, Mayumi; Cui, Jean; Cajal, Santiago Ramón Y; Frias, Alex; Cao, Peng; Rosell, Rafael

    2018-03-01

    Epidermal growth factor receptor (EGFR)-mutation-positive non-smallcell lung cancer (NSCLC) is incurable, despite high rates of response to EGFR tyrosine kinase inhibitors (TKIs). We investigated receptor tyrosine kinases (RTKs), Src family kinases and focal adhesion kinase (FAK) as genetic modifiers of innate resistance in EGFR-mutation-positive NSCLC. We performed gene expression analysis in two cohorts (Cohort 1 and Cohort 2) of EGFR-mutation-positive NSCLC patients treated with EGFR TKI. We evaluated the efficacy of gefitinib or osimertinib with the Src/FAK/Janus kinase 2 (JAK2) inhibitor, TPX0005 in vitro and in vivo. In Cohort 1, CUB domain-containing protein-1 (CDCP1) was an independent negative prognostic factor for progression-free survival (hazard ratio of 1.79, p=0.0407) and overall survival (hazard ratio of 2.23, p=0.0192). A two-gene model based on AXL and CDCP1 expression was strongly associated with the clinical outcome to EGFR TKIs, in both cohorts of patients. Our preclinical experiments revealed that several RTKs and non-RTKs, were up-regulated at baseline or after treatment with gefitinib or osimertinib. TPX-0005 plus EGFR TKI suppressed expression and activation of RTKs and downstream signaling intermediates. Co-expression of CDCP1 and AXL is often observed in EGFR-mutation-positive tumors, limiting the efficacy of EGFR TKIs. Co-treatment with EGFR TKI and TPX-0005 warrants testing. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  7. First-in-human phase I study of oral S49076, a unique MET/AXL/FGFR inhibitor, in advanced solid tumours.

    PubMed

    Rodon, Jordi; Postel-Vinay, Sophie; Hollebecque, Antoine; Nuciforo, Paolo; Azaro, Analia; Cattan, Valérie; Marfai, Lucie; Sudey, Isabelle; Brendel, Karl; Delmas, Audrey; Malasse, Stéphanie; Soria, Jean-Charles

    2017-08-01

    S49076 is a novel ATP-competitive tyrosine kinase inhibitor of MET, AXL and FGFR with a unique selectivity profile. A phase I open-label study was undertaken to establish the tolerability profile and determine the recommended dose (RD) and administration schedule. Patients with advanced solid tumours received S49076 orally once-daily (qd) or twice-daily (bid) in continuous 21-day cycles at escalating doses guided by a 3 + 3 design and followed by an expansion phase at the RD. Pharmacokinetic (PK) parameters were assessed and pharmacodynamic end-points were evaluated in pre- and post-treatment tumour biopsies. Preliminary anti-tumour activity was evaluated as per the Response Evaluation Criteria In Solid Tumours 1.1 criteria. A total of 103 patients were treated: 79 in the dose-escalation and 24 in the expansion. Doses from 15 to 900 mg were evaluated. Dose-limiting toxicities were reported in 9 patients and occurred at 30, 760 and 900 mg in the qd arm and at 180, 225 and 285 mg in the bid arm. The RD was defined at 600 mg qd. Adverse events (AEs) occurred with similar frequency in both regimens at an equivalent total daily dose. Overall, 83 patients (81.4%) had drug-related AEs, the majority (93%) of which were grade I-II (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0) and only 3% led to drug discontinuation. Intratumoural PK analysis at the RD suggested hitting of MET, AXL and FGFR. S49076 demonstrated a tolerable safety profile with limited single-agent activity. PK/pharmacodynamic readouts of S49076 are encouraging for further investigation of S49076 in combination therapies. ISRCTN00759419. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Nitroxoline shows antimyeloma activity by targeting the TRIM25/p53 axle.

    PubMed

    Mao, Hongwu; Du, Yanyun; Zhang, Zubin; Cao, Biyin; Zhao, Jun; Zhou, Haibin; Mao, Xinliang

    2017-04-01

    The aim of this study was to identify the most potent quinoline-based anti-infectives for the treatment of multiple myeloma (MM) and to understand the molecular mechanisms. A small-scale screen against a panel of marketed quinoline-based drugs was performed in MM cell lines. Cell apoptosis was examined by flow cytometry. Anti-MM activity was also evaluated in nude mice. Western blotting was performed to investigate mechanisms. Nitroxoline (NXQ) was the most effective in suppressing MM cell proliferation. NXQ induced more than 40% MM cell apoptosis within 24 h and potentiated anti-MM activities of current major drugs including doxorubicin and lenalidomide. This finding was shown by activation of caspase-3, a major executive apoptotic enzyme, and by inactivation of PARP, a major enzyme in DNA damage repair. NXQ also suppressed prosurvival proteins Bcl-xL and Mcl-1. Moreover, NXQ suppressed the growth of myeloma xenografts in nude mice models. In the mechanistic study, NXQ was found to downregulate TRIM25, a highly expressed ubiquitin ligase in MM. Notably, NXQ upregulated tumor suppressor p53, but not PTEN. Furthermore, overexpression of TRIM25 decreased p53 protein. This study indicated that the long-term use of anti-infective NXQ has potential for MM treatment by targeting the TRIM25/p53 axle.

  9. Thermal Property Analysis of Axle Load Sensors for Weighing Vehicles in Weigh-in-Motion System

    PubMed Central

    Burnos, Piotr; Gajda, Janusz

    2016-01-01

    Systems which permit the weighing of vehicles in motion are called dynamic Weigh-in-Motion scales. In such systems, axle load sensors are embedded in the pavement. Among the influencing factors that negatively affect weighing accuracy is the pavement temperature. This paper presents a detailed analysis of this phenomenon and describes the properties of polymer, quartz and bending plate load sensors. The studies were conducted in two ways: at roadside Weigh-in-Motion sites and at a laboratory using a climate chamber. For accuracy assessment of roadside systems, the reference vehicle method was used. The pavement temperature influence on the weighing error was experimentally investigated as well as a non-uniform temperature distribution along and across the Weigh-in-Motion site. Tests carried out in the climatic chamber allowed the influence of temperature on the sensor intrinsic error to be determined. The results presented clearly show that all kinds of sensors are temperature sensitive. This is a new finding, as up to now the quartz and bending plate sensors were considered insensitive to this factor. PMID:27983704

  10. An integrated control strategy for the composite braking system of an electric vehicle with independently driven axles

    NASA Astrophysics Data System (ADS)

    Sun, Fengchun; Liu, Wei; He, Hongwen; Guo, Hongqiang

    2016-08-01

    For an electric vehicle with independently driven axles, an integrated braking control strategy was proposed to coordinate the regenerative braking and the hydraulic braking. The integrated strategy includes three modes, namely the hybrid composite mode, the parallel composite mode and the pure hydraulic mode. For the hybrid composite mode and the parallel composite mode, the coefficients of distributing the braking force between the hydraulic braking and the two motors' regenerative braking were optimised offline, and the response surfaces related to the driving state parameters were established. Meanwhile, the six-sigma method was applied to deal with the uncertainty problems for reliability. Additionally, the pure hydraulic mode is activated to ensure the braking safety and stability when the predictive failure of the response surfaces occurs. Experimental results under given braking conditions showed that the braking requirements could be well met with high braking stability and energy regeneration rate, and the reliability of the braking strategy was guaranteed on general braking conditions.

  11. Modelling and characteristic analysis of tri-axle trucks with hydraulically interconnected suspensions

    NASA Astrophysics Data System (ADS)

    Ding, Fei; Han, Xu; Luo, Zhen; Zhang, Nong

    2012-12-01

    In this paper, a new hydraulically interconnected suspension (HIS) system is proposed for the implementation of a resistance control for the pitch and bounce modes of tri-axle heavy trucks. A lumped-mass half-truck model is established using the free-body diagram method. The equations of motion of a mechanical and hydraulic coupled system are developed by incorporating the hydraulic strut forces into the mechanical subsystem as externally applied forces. The transfer matrix method (TMM) is used to evaluate the impedance matrix of the hydraulic subsystem consisting of models of fluid pipes, damper valves, accumulators, and three-way junctions. The TMM is further applied to find the quantitative relationships between the hydraulic strut forces and boundary flow of the mechanical-fluid interactive subsystem. The modal analysis method is employed to perform the vibration analysis between the trucks with the conventional suspension and the proposed HIS. Comparison analysis focuses on free vibration with identified eigenvalues and eigenvectors, isolation vibration capacity, and force vibration in terms of the power spectrum density responses. The obtained results show the effectiveness of the proposed HIS system in reducing the pitch motion of sprung mass and simultaneously maintaining the ride comfort. The pitch stiffness is increased while the bounce stiffness is slightly softened. The peak values of sprung mass and wheel hop motions are greatly reduced, and the vibration decay rate of sprung mass is also significantly increased.

  12. The Effect of Flexible Pavement Mechanics on the Accuracy of Axle Load Sensors in Vehicle Weigh-in-Motion Systems.

    PubMed

    Burnos, Piotr; Rys, Dawid

    2017-09-07

    Weigh-in-Motion systems are tools to prevent road pavements from the adverse phenomena of vehicle overloading. However, the effectiveness of these systems can be significantly increased by improving weighing accuracy, which is now insufficient for direct enforcement of overloaded vehicles. Field tests show that the accuracy of Weigh-in-Motion axle load sensors installed in the flexible (asphalt) pavements depends on pavement temperature and vehicle speeds. Although this is a known phenomenon, it has not been explained yet. The aim of our study is to fill this gap in the knowledge. The explanation of this phenomena which is presented in the paper is based on pavement/sensors mechanics and the application of the multilayer elastic half-space theory. We show that differences in the distribution of vertical and horizontal stresses in the pavement structure are the cause of vehicle weight measurement errors. These studies are important in terms of Weigh-in-Motion systems for direct enforcement and will help to improve the weighing results accuracy.

  13. The Effect of Flexible Pavement Mechanics on the Accuracy of Axle Load Sensors in Vehicle Weigh-in-Motion Systems

    PubMed Central

    Rys, Dawid

    2017-01-01

    Weigh-in-Motion systems are tools to prevent road pavements from the adverse phenomena of vehicle overloading. However, the effectiveness of these systems can be significantly increased by improving weighing accuracy, which is now insufficient for direct enforcement of overloaded vehicles. Field tests show that the accuracy of Weigh-in-Motion axle load sensors installed in the flexible (asphalt) pavements depends on pavement temperature and vehicle speeds. Although this is a known phenomenon, it has not been explained yet. The aim of our study is to fill this gap in the knowledge. The explanation of this phenomena which is presented in the paper is based on pavement/sensors mechanics and the application of the multilayer elastic half-space theory. We show that differences in the distribution of vertical and horizontal stresses in the pavement structure are the cause of vehicle weight measurement errors. These studies are important in terms of Weigh-in-Motion systems for direct enforcement and will help to improve the weighing results accuracy. PMID:28880215

  14. Differential expression of the ufo/axl oncogene in human leukemia-lymphoma cell lines.

    PubMed

    Challier, C; Uphoff, C C; Janssen, J W; Drexler, H G

    1996-05-01

    The ufo protein (also termed axl) is a member of a new family of receptor tyrosine kinases and is encoded by a transforming gene that was initially isolated from primary human myeloid leukemia cells by DNA-mediated transformation of NIH/3T3 cells. The ligand, Gas6, a protein S-related molecule lacking any known function yet, has recently been identified. We report the expression pattern of ufo mRNA in a panel of 76 human continuous leukemia-lymphoma cell lines. The gene was not expressed in cell lines derived from lymphoid malignancies (n=28), but transcription was seen in 3/11 myeloid, 0/6 monocytic, 9/13 erythroid and 11/18 megakaryocytic cell lines. Several cell lines were treated with phorbol ester leading to significant upregulation of the ufo message in constitutively positive cells. An apparent ufo mRNA overexpression was not found in any of the positive leukemia cell lines, but was identified in the drug-resistant subclones of the cervix carcinoma cell line HeLa. Southern blot analysis of restriction enzyme-digested genomic DNA did not provide evidence for gene amplification, but the HeLa subclones showed banding patterns suggestive of gene rearrangement. Two main ufo mRNA bands of 3.2 and 5.0 kb were identified; no differences in the half-lives (t1/2 = 2.5 h) of these two mRNA species could be identified. In summary, ufo, representing a novel type of receptor tyrosine kinase, is expressed solely in myeloid and erythro-megakaryocytic leukemias but not in lymphoid malignancies. These and previous data suggest an involvement of the ufo receptor tyrosine kinase in normal and malignant myelopoiesis; however, its exact role, if any, and mode of operation in leukemogenesis remains to be determined.

  15. Extended-Kalman-filter-based regenerative and friction blended braking control for electric vehicle equipped with axle motor considering damping and elastic properties of electric powertrain

    NASA Astrophysics Data System (ADS)

    Lv, Chen; Zhang, Junzhi; Li, Yutong

    2014-11-01

    Because of the damping and elastic properties of an electrified powertrain, the regenerative brake of an electric vehicle (EV) is very different from a conventional friction brake with respect to the system dynamics. The flexibility of an electric drivetrain would have a negative effect on the blended brake control performance. In this study, models of the powertrain system of an electric car equipped with an axle motor are developed. Based on these models, the transfer characteristics of the motor torque in the driveline and its effect on blended braking control performance are analysed. To further enhance a vehicle's brake performance and energy efficiency, blended braking control algorithms with compensation for the powertrain flexibility are proposed using an extended Kalman filter. These algorithms are simulated under normal deceleration braking. The results show that the brake performance and blended braking control accuracy of the vehicle are significantly enhanced by the newly proposed algorithms.

  16. Comparative analysis of the operation efficiency of the continuous and relay control systems of a multi-axle wheeled vehicle suspension

    NASA Astrophysics Data System (ADS)

    Zhileykin, M. M.; Kotiev, G. O.; Nagatsev, M. V.

    2018-02-01

    In order to improve the efficiency of the multi-axle wheeled vehicles (MWV) automotive engineers are increasing their cruising speed. One of the promising ways to improve ride comfort of the MWV is the development of the dynamic active suspension systems and control laws for such systems. Here, by the dynamic control systems we mean the systems operating in real time mode and using current (instantaneous) values of the state variables. The aim of the work is to develop the MWV suspension optimal control laws that would reduce vibrations on the driver’s seat at kinematic excitation. The authors have developed the optimal control laws for damping the oscillations of the MWV body. The developed laws allow reduction of the vibrations on the driver’s seat and increase in the maximum speed of the vehicle. The laws are characterized in that they allow generating the control inputs in real time mode. The authors have demonstrated the efficiency of the proposed control laws by means of mathematical simulation of the MWV driving over unpaved road with kinematic excitation. The proposed optimal control laws can be used in the MWV suspension control systems with magnetorheological shock absorbers or controlled hydropneumatic springs. Further evolution of the research line can be the development of the energy-efficient MWV suspension control systems with continuous control input on the vehicle body.

  17. 23 CFR 658.17 - Weight.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... weight limits of less than 20,000 pounds on a single axle, 34,000 pounds on a tandem axle, or the weights.... States may not limit tire loads to less than 500 pounds per inch of tire or tread width, except that such limits may not be applied to tires on the steering axle. States may not limit steering axle weights to...

  18. 23 CFR 658.17 - Weight.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... weight limits of less than 20,000 pounds on a single axle, 34,000 pounds on a tandem axle, or the weights.... States may not limit tire loads to less than 500 pounds per inch of tire or tread width, except that such limits may not be applied to tires on the steering axle. States may not limit steering axle weights to...

  19. rse, a novel receptor-type tyrosine kinase with homology to Axl/Ufo, is expressed at high levels in the brain.

    PubMed

    Mark, M R; Scadden, D T; Wang, Z; Gu, Q; Goddard, A; Godowski, P J

    1994-04-08

    We have isolated cDNA clones that encode the human and murine forms of a novel receptor-type tyrosine kinase termed Rse. Sequence analysis indicates that human Rse contains 890 amino acids, with an extracellular region composed of two immunoglobulin-like domains followed by two fibronectin type III domains. Murine Rse contains 880 amino acids and shares 90% amino acid identity with its human counterpart. Rse is structurally similar to the receptor-type tyrosine kinase Axl/Ufo, and the two proteins have 35 and 63% sequence identity in their extracellular and intracellular domains, respectively. To study the synthesis and activation of this putative receptor-type tyrosine kinase, we constructed a version of Rse (termed gD-Rse, where gD represents glycoprotein D) that contains an NH2-terminal epitope tag. NIH3T3 cells were engineered to express gD-Rse, which could be detected at the cell surface by fluorescence-activated cell sorting. Moreover, gD-Rse was rapidly phosphorylated on tyrosine residues upon incubation of the cells with an antibody directed against the epitope tag, suggesting that rse encodes an active tyrosine kinase. In the human tissues we examined, the highest level of expression of rse mRNA was observed in the brain; rse mRNA was also detected in the premegakaryocytopoietic cell lines CMK11-5 and Dami. The gene for rse was localized to human chromosome 15.

  20. qPCR in gastrointestinal stromal tumors: Evaluation of reference genes and expression analysis of KIT and the alternative receptor tyrosine kinases FLT3, CSF1-R, PDGFRB, MET and AXL

    PubMed Central

    2010-01-01

    Background Gastrointestinal stromal tumors (GIST) represent the most common mesenchymal tumors of the gastrointestinal tract. About 85% carry an activating mutation in the KIT or PDGFRA gene. Approximately 10% of GIST are so-called wild type GIST (wt-GIST) without mutations in the hot spots. In the present study we evaluated appropriate reference genes for the expression analysis of formalin-fixed, paraffin-embedded and fresh frozen samples from gastrointestinal stromal tumors. We evaluated the gene expression of KIT as well as of the alternative receptor tyrosine kinase genes FLT3, CSF1-R, PDGFRB, AXL and MET by qPCR. wt-GIST were compared to samples with mutations in KIT exon 9 and 11 and PDGFRA exon 18 in order to evaluate whether overexpression of these alternative RTK might contribute to the pathogenesis of wt-GIST. Results Gene expression variability of the pooled cDNA samples is much lower than the single reverse transcription cDNA synthesis. By combining the lowest variability values of fixed and fresh tissue, the genes POLR2A, PPIA, RPLPO and TFRC were chosen for further analysis of the GIST samples. Overexpression of KIT compared to the corresponding normal tissue was detected in each GIST subgroup except in GIST with PDGFRA exon 18 mutation. Comparing our sample groups, no significant differences in the gene expression levels of FLT3, CSF1R and AXL were determined. An exception was the sample group with KIT exon 9 mutation. A significantly reduced expression of CSF1R, FLT3 and PDGFRB compared to the normal tissue was detected. GIST with mutations in KIT exon 9 and 11 and in PDGFRA exon 18 showed a significant PDGFRB downregulation. Conclusions As the variability of expression levels for the reference genes is very high comparing fresh frozen and formalin-fixed tissue there is a strong need for validation in each tissue type. None of the alternative receptor tyrosine kinases analyzed is associated with the pathogenesis of wild-type or mutated GIST. It

  1. The MET/AXL/FGFR Inhibitor S49076 Impairs Aurora B Activity and Improves the Antitumor Efficacy of Radiotherapy.

    PubMed

    Clémenson, Céline; Chargari, Cyrus; Liu, Winchygn; Mondini, Michele; Ferté, Charles; Burbridge, Mike F; Cattan, Valérie; Jacquet-Bescond, Anne; Deutsch, Eric

    2017-10-01

    Several therapeutic agents targeting HGF/MET signaling are under clinical development as single agents or in combination, notably with anti-EGFR therapies in non-small cell lung cancer (NSCLC). However, despite increasing data supporting a link between MET, irradiation, and cancer progression, no data regarding the combination of MET-targeting agents and radiotherapy are available from the clinic. S49076 is an oral ATP-competitive inhibitor of MET, AXL, and FGFR1-3 receptors that is currently in phase I/II clinical trials in combination with gefitinib in NSCLC patients whose tumors show resistance to EGFR inhibitors. Here, we studied the impact of S49076 on MET signaling, cell proliferation, and clonogenic survival in MET-dependent (GTL16 and U87-MG) and MET-independent (H441, H460, and A549) cells. Our data show that S49076 exerts its cytotoxic activity at low doses on MET-dependent cells through MET inhibition, whereas it inhibits growth of MET-independent cells at higher but clinically relevant doses by targeting Aurora B. Furthermore, we found that S49076 improves the antitumor efficacy of radiotherapy in both MET-dependent and MET-independent cell lines in vitro and in subcutaneous and orthotopic tumor models in vivo In conclusion, our study demonstrates that S49076 has dual antitumor activity and can be used in combination with radiotherapy for the treatment of both MET-dependent and MET-independent tumors. These results support the evaluation of combined treatment of S49076 with radiation in clinical trials without patient selection based on the tumor MET dependency status. Mol Cancer Ther; 16(10); 2107-19. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. MEPDG Traffic Loading Defaults Derived from Traffic Pooled Fund Study

    DOT National Transportation Integrated Search

    2016-04-01

    As part of traffic loading inputs, the Mechanistic-Empirical Pavement Design Guide (MEPDG), Interim Edition: A Manual of Practice requires detailed axle loading information in the form of normalized axle load spectra (NALS), number of axle per truck ...

  3. 77 FR 12812 - Steel Wheels From the People's Republic of China: Notice of Preliminary Affirmative Determination...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-02

    ... separately. These products are used with both tubed and tubeless tires. Steel wheels, whether or not attached to tires or axles, are included. However, if the steel wheels are imported as an assembly attached to tires or axles, the tire or axle is not covered by the scope. The scope includes steel wheels, discs...

  4. 23 CFR 658.17 - Weight.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... maximum gross vehicle weight shall be 80,000 pounds except where lower gross vehicle weight is dictated by... of axles, or a vehicle is 20,000 pounds. (d) The maximum gross weight on tandem axles is 34,000... first and last axle is 36 feet or more. In no case shall the total gross weight of a vehicle exceed 80...

  5. 49 CFR 393.42 - Brakes required on all wheels.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... subject to this part is not required to be equipped with brakes if the axle weight of the towed vehicle does not exceed 40 percent of the sum of the axle weights of the towing vehicle. (4) Any full trailer... of the towed vehicle does not exceed 40 percent of the sum of the axle weights of the towing vehicle...

  6. TAZ Expression as a Prognostic Indicator in Colorectal Cancer

    PubMed Central

    Tham, Jill M.; Zhang, Xiaoqian; Zeng, Qi; Zhang, Shu-Dong; Hong, WanJin

    2013-01-01

    The Hippo pathway restricts the activity of transcriptional coactivators TAZ (WWTR1) and YAP. TAZ and YAP are reported to be overexpressed in various cancers, however, their prognostic significance in colorectal cancers remains unstudied. The expression levels of TAZ and YAP, and their downstream transcriptional targets, AXL and CTGF, were extracted from two independent colon cancer patient datasets available in the Gene Expression Omnibus database, totaling 522 patients. We found that mRNA expressions of both TAZ and YAP were positively correlated with those of AXL and CTGF (p<0.05). High level mRNA expression of TAZ, AXL or CTGF significantly correlated with shorter survival. Importantly, patients co-overexpressing all 3 genes had a significantly shorter survival time, and combinatorial expression of these 3 genes was an independent predictor for survival. The downstream target genes for TAZ-AXL-CTGF overexpression were identified by Java application MyStats. Interestingly, genes that are associated with colon cancer progression (ANTXR1, EFEMP2, SULF1, TAGLN, VCAN, ZEB1 and ZEB2) were upregulated in patients co-overexpressing TAZ-AXL-CTGF. This TAZ-AXL-CTGF gene expression signature (GES) was then applied to Connectivity Map to identify small molecules that could potentially be utilized to reverse this GES. Of the top 20 small molecules identified by connectivity map, amiloride (a potassium sparing diuretic,) and tretinoin (all-trans retinoic acid) have shown therapeutic promise in inhibition of colon cancer cell growth. Using MyStats, we found that low level expression of either ANO1 or SQLE were associated with a better prognosis in patients who co-overexpressed TAZ-AXL-CTGF, and that ANO1 was an independent predictor of survival together with TAZ-AXL-CTGF. Finally, we confirmed that TAZ regulates Axl, and plays an important role in clonogenicity and non-adherent growth in vitro and tumor formation in vivo. These data suggest that TAZ could be a therapeutic

  7. Differential TAM receptor-ligand-phospholipid interactions delimit differential TAM bioactivities.

    PubMed

    Lew, Erin D; Oh, Jennifer; Burrola, Patrick G; Lax, Irit; Zagórska, Anna; Través, Paqui G; Schlessinger, Joseph; Lemke, Greg

    2014-09-29

    The TAM receptor tyrosine kinases Tyro3, Axl, and Mer regulate key features of cellular physiology, yet the differential activities of the TAM ligands Gas6 and Protein S are poorly understood. We have used biochemical and genetic analyses to delineate the rules for TAM receptor-ligand engagement and find that the TAMs segregate into two groups based on ligand specificity, regulation by phosphatidylserine, and function. Tyro3 and Mer are activated by both ligands but only Gas6 activates Axl. Optimal TAM signaling requires coincident TAM ligand engagement of both its receptor and the phospholipid phosphatidylserine (PtdSer): Gas6 lacking its PtdSer-binding 'Gla domain' is significantly weakened as a Tyro3/Mer agonist and is inert as an Axl agonist, even though it binds to Axl with wild-type affinity. In two settings of TAM-dependent homeostatic phagocytosis, Mer plays a predominant role while Axl is dispensable, and activation of Mer by Protein S is sufficient to drive phagocytosis.

  8. Validating Future Force Performance Measures (Army Class): Reclassification Test and Criterion Development

    DTIC Science & Technology

    2009-09-01

    Replace CV boot assembly. 11 Replace propeller shafts , universal joints, and center bearings. 11 Replace front axle spindle . 5 Replace...propeller shafts , universal joints, and center bearings. (SL1/2) 12 Troubleshoot axles. (SL1/2) 11 Replace front axle spindle . (SL1/2) 6...Social Sciences. NOTE: The findings in this report are not to be construed as an official Department of the Army position, unless so designated by

  9. GAS6-expressing and self-sustaining cancer cells in 3D spheroids activate the PDK-RSK-mTOR pathway for survival and drug resistance.

    PubMed

    Baumann, Christine; Ullrich, Axel; Torka, Robert

    2017-10-01

    AXL receptor tyrosine kinase (RTK) inhibition presents a promising therapeutic strategy for aggressive tumor subtypes, as AXL signaling is upregulated in many cancers resistant to first-line treatments. Furthermore, the AXL ligand growth arrest-specific gene 6 (GAS6) has recently been linked to cancer drug resistance. Here, we established that challenging conditions, such as serum deprivation, divide AXL-overexpressing tumor cell lines into non-self-sustaining and self-sustaining subtypes in 3D spheroid culture. Self-sustaining cells are characterized by excessive GAS6 secretion and TAM-PDK-RSK-mTOR pathway activation. In 3D spheroid culture, the activation of the TAM-PDK-RSK-mTOR pathway proves crucial following treatment with AXL/MET inhibitor BMS777607, when the self-sustaining tumor cells react with TAM-RSK hyperactivation and enhanced SRC-AKT-mTOR signaling. Thus, bidirectional activated mTOR leads to enhanced proliferation and counteracts the drug effect. mTOR activation is accompanied by an enhanced AXL expression and hyperphosphorylation following 24 h of treatment with BMS777607. Therefore, we elucidate a double role of AXL that can be assigned to RSK-mTOR as well as SRC-AKT-mTOR pathway activation, specifically through AXL Y779 phosphorylation. This phosphosite fuels the resistance mechanism in 3D spheroids, alongside further SRC-dependent EGFR Y1173 and/or MET Y1349 phosphorylation which is defined by the cell-specific addiction. In conclusion, self-sustenance in cancer cells is based on a signaling synergy, individually balanced between GAS6 TAM-dependent PDK-RSK-mTOR survival pathway and the AXLY779/EGFR/MET-driven SRC-mTOR pathway. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  10. Magnetic Fields of the Cerebral Cortex,

    DTIC Science & Technology

    1980-06-15

    with worm gears on two separate horizontal shafts . One shaft (the declination axle ) near the end of the frame rotates the dewar. The other near the...carriage is fabricated from fiberglass or wood wherever possible. Vertical movement of the dewar is permitted by a 6 cm diameter cylindrical axle of...hardwood that runs between sets of aluminum rollers having double conical shape. The axle is supported by four strands of nylon parachute cord, each

  11. 77 FR 56172 - Airworthiness Directives; Airbus Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-12

    ... high tensile standing stress, resulting from dry fit axle assembly method. Improvement has been introduced subsequently with a grease fit axle assembly method. Fatigue and damage tolerance analyses were...

  12. Method and appartus for converting static in-ground vehicle scales into weigh-in-motion systems

    DOEpatents

    Muhs, Jeffrey D.; Scudiere, Matthew B.; Jordan, John K.

    2002-01-01

    An apparatus and method for converting in-ground static weighing scales for vehicles to weigh-in-motion systems. The apparatus upon conversion includes the existing in-ground static scale, peripheral switches and an electronic module for automatic computation of the weight. By monitoring the velocity, tire position, axle spacing, and real time output from existing static scales as a vehicle drives over the scales, the system determines when an axle of a vehicle is on the scale at a given time, monitors the combined weight output from any given axle combination on the scale(s) at any given time, and from these measurements automatically computes the weight of each individual axle and gross vehicle weight by an integration, integration approximation, and/or signal averaging technique.

  13. Differential TAM receptor–ligand–phospholipid interactions delimit differential TAM bioactivities

    PubMed Central

    Lew, Erin D; Oh, Jennifer; Burrola, Patrick G; Lax, Irit; Zagórska, Anna; Través, Paqui G; Schlessinger, Joseph; Lemke, Greg

    2014-01-01

    The TAM receptor tyrosine kinases Tyro3, Axl, and Mer regulate key features of cellular physiology, yet the differential activities of the TAM ligands Gas6 and Protein S are poorly understood. We have used biochemical and genetic analyses to delineate the rules for TAM receptor–ligand engagement and find that the TAMs segregate into two groups based on ligand specificity, regulation by phosphatidylserine, and function. Tyro3 and Mer are activated by both ligands but only Gas6 activates Axl. Optimal TAM signaling requires coincident TAM ligand engagement of both its receptor and the phospholipid phosphatidylserine (PtdSer): Gas6 lacking its PtdSer-binding ‘Gla domain’ is significantly weakened as a Tyro3/Mer agonist and is inert as an Axl agonist, even though it binds to Axl with wild-type affinity. In two settings of TAM-dependent homeostatic phagocytosis, Mer plays a predominant role while Axl is dispensable, and activation of Mer by Protein S is sufficient to drive phagocytosis. DOI: http://dx.doi.org/10.7554/eLife.03385.001 PMID:25265470

  14. Comparison of anterior segment parameters and axial length measurements performed on a Scheimpflug device with biometry function and a reference optical biometer.

    PubMed

    Muzyka-Woźniak, Maria; Oleszko, Adam

    2018-04-26

    To compare measurements of axial length (AL), corneal curvature (K), anterior chamber depth (ACD) and white-to-white (WTW) distance on a new device combining Scheimpflug camera and partial coherence interferometry (Pentacam AXL) with a reference optical biometer (IOL Master 500). To evaluate differences between IOL power calculations based on the two biometers. Ninety-seven eyes of 97 consecutive cataract or refractive lens exchange patients were examined preoperatively on IOL Master 500 and Pentacam AXL units. Comparisons between two devices were performed for AL, K, ACD and WTW. Intraocular lens (IOL) power targeting emmetropia was calculated with SRK/T and Haigis formulas on both devices and compared. There were statistically significant differences between two devices for all measured parameters (P < 0.05), except ACD (P = 0.36). Corneal curvature measured with Pentacam AXL was significantly flatter then with IOL Master. The mean difference in AL was clinically insignificant (0.01 mm; 95% LoA 0.16 mm). Pentacam AXL yielded higher IOL power in 75% of eyes for Haigis formula and in 62% of eyes for SRK/T formula, with a mean difference within ± 0.5 D for 72 and 86% of eyes, respectively. There were statistically significant differences between AL, K and WTW measurements obtained with the compared biometers. Flatter corneal curvature measurements on Pentacam AXL necessitate formulas optimisation for Pentacam AXL.

  15. A deformable spherical planet exploration robot

    NASA Astrophysics Data System (ADS)

    Liang, Yi-shan; Zhang, Xiu-li; Huang, Hao; Yang, Yan-feng; Jin, Wen-tao; Sang, Zhong-xun

    2013-03-01

    In this paper, a deformable spherical planet exploration robot has been introduced to achieve the task of environmental detection in outer space or extreme conditions. The robot imitates the morphology structure and motion mechanism of tumbleweeds. The robot is wind-driven. It consists of an axle, a spherical steel skeleton and twelve airbags. The axle is designed as two parts. The robot contracts by contracting the two-part axle. The spherical robot installs solar panels to provide energy for its control system.

  16. Anticancer effect of luteolin is mediated by downregulation of TAM receptor tyrosine kinases, but not interleukin-8, in non-small cell lung cancer cells.

    PubMed

    Lee, Youn Ju; Lim, Taeho; Han, Min Su; Lee, Sun-Hwa; Baek, Suk-Hwan; Nan, Hong-Yan; Lee, Chuhee

    2017-02-01

    TAM receptor tyrosine kinases (RTKs), Tyro3, Axl and MerTK, transduce diverse signals responsible for cell survival, growth, proliferation and anti-apoptosis. In the present study, we demonstrated the effect of luteolin, a flavonoid with antioxidant, anti-inflammatory and anticancer activities, on the expression and activation of TAM RTKs and the association with its cytotoxicity in non-small cell lung cancer (NSCLC) cells. We observed the cytotoxic effect of luteolin in parental A549 and H460 cells as well as in cisplatin-resistant A549/CisR and H460/CisR cells. Exposure of these cells to luteolin also resulted in a dose‑dependent decrease in clonogenic ability. Next, luteolin was found to decrease the protein levels of all three TAM RTKs in the A549 and A549/CisR cells in a dose‑dependent manner. In a similar manner, in H460 and H460/CisR cells, the protein levels of Axl and Tyro3 were decreased following luteolin treatment. In addition, Axl promoter activity was decreased by luteolin, indicating that luteolin suppresses Axl expression at the transcriptional level. We next found that luteolin abrogated Axl phosphorylation in response to growth arrest-specific 6 (Gas6), its ligand, implying the inhibitory effect of luteolin on Gas6-induced Axl activation. Ectopic expression of Axl was observed to attenuate the antiproliferative effect of luteolin, while knockdown of the Axl protein level using a gold nanoparticle-assisted gene delivery system increased its cytotoxicity. In contrast to the inhibitory effect of luteolin on the expression of TAM RTKs, interleukin-8 (IL-8) production was not decreased by luteolin in H460 and H460/CisR cells, while IL-8 production/cell was increased. Collectively, our data suggest that TAM RTKs, but not IL-8, are promising therapeutic targets of luteolin to abrogate cell proliferation and to overcome chemoresistance in NSCLC cells.

  17. Space allowance during commercial long distance transport of cattle in North America.

    PubMed

    González, L A; Schwartzkopf-Genswein, K S; Bryan, M; Silasi, R; Brown, F

    2012-10-01

    The objective of the present work was to study space allowance in cattle during commercial long haul transport (≥400 km; n = 6,152 journeys). Surveys, delivered to livestock transport carriers, gathered information on the number, BW, and distribution of cattle by trailer compartment as well as the characteristics of the transport vehicles used. Space allowance (SA; m(2)/animal), allometric coefficient (k = SA / BW(0.6667)), and the percentage of deviation from recommended SA (DRSA; %) in the Canadian Codes of Practice were calculated for each compartment of the trailers. All quad-axle (77%) and tri-axle (23%) cattle trailers were reported with 5 compartments (nose, deck, belly, back, and doghouse). Sixty percent of all animals were carried in the middle compartments (deck and belly), 30% in the rear (back and doghouse), and 10% in the front or nose. Approximately 30% of the journeys required that the cattle be redistributed at the Canada-USA border to comply with different axle weight regulations, and most journeys moved them between the deck and the doghouse. Total loaded weight increased and the number of animals decreased with increasing BW of the animals. space allowance, k-value, and DRSA were least for calves and feeders compared with fat and cull cattle (p < 0.01). Both total loaded weight and number of animals increased with the number of axles in the trailer, being greatest in quad-axle trailers pulled by push tractors, which were most frequently used. Space allowance (k-value) was least in vehicles with greater number of axles and transporting the lightest cattle (i.e., quad-axles trailers transporting calves and feeders). Space allowance, k-value, and variability among journeys were least in the middle compartments (belly and deck), followed by the back, then doghouse and nose compartments of the trailers showing the largest values (p < 0.05). Many factors contributed to the variability in SA such as body size (smaller animals are placed more densely

  18. Protective Effects of Pterostilbene Against Myocardial Ischemia/Reperfusion Injury in Rats.

    PubMed

    Wu, Miao; Lu, Shijuan; Zhong, Jianghua; Huang, Kang; Zhang, Saidan

    2017-04-01

    Pterostilbene (PTB) has been suggested to protect against myocardial ischemia/reperfusion (MI/R) injury. Gas6/Axl signaling has been suggested to play an important role in cell survival. However, the interaction between PTB and Gas6/Axl signaling in MI/R remains unclear. This study aims to evaluate the role of Gas6/Axl signaling in the protective effects of PTB against MI/R injury. In experiment 1, the rats were subjected to 30 min of ischemia, followed by 3, 6, and 12 h of reperfusion, respectively. In experiment 2, the rats were administered intraperitoneally with PTB or vehicle and subjected to MI/R injury. The results suggested that the expression of Gas6 and Axl decreased significantly after MI/R injury. PTB treatment conferred a cardioprotective effect with an improved post-ischemic cardiac function, a reduced myocardial infarct size, and decreased lactate dehydrogenase and creatine kinase-MB in the serum, a decreased oxidative stress and inflammation, and a reduced number of apoptotic cardiomyocytes. Moreover, PTB treatment up-regulated the expression of Gas6, Axl, and Bcl-2 and down-regulated Bax expression. Our findings suggest that PTB treatment exerts cardioprotection against MI/R injury via attenuating inflammatory response, oxidative stress, and apoptosis and up-regulating the expression of Gas6 and Axl. The application of PTB may be a new strategy for the treatment of MI/R injury.

  19. Development of gage widening projection parameter for the deployable gage restraint measurement system

    DOT National Transportation Integrated Search

    2006-10-01

    Recent gage restraint measurement system (GRMS) developments include the redesign of GRMS vehicles to conduct testing from a deployable axle instead of using freight truck mounted axle and GRMS on hi-rail vehicles. This new test configuration results...

  20. Air actuated clutch for four wheel drive vehicles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Clohessy, K.E.

    1986-12-09

    A control system is described for selectively engaging and disengaging a vehicle wheel and a vehicle drive mechanism comprising; a spindle having inside and outside rotative support surfaces, the spindle adapted to be mounted to a vehicle frame, an axle portion rotatably supported on the inside support surface, and drive means for selectively and rotatively driving the axle portion relative to the spindle; a wheel hub assembly adapted to carry a vehicle wheel, the hub assembly rotatively supported on the outside support surface of the spindle; a sealed expansion chamber defined in part by the spindle, the axle portion, themore » hub assembly and a movable wall carried by the hub assembly, venting means venting the outer side of the movable wall to atmospheric pressure, the clutch ring engaged by the movable wall for movement of the clutch ring with movement of the movable wall as induced by a pressure difference generated within the chamber, and pressurizing means for selectively pressurizing and depressurizing the expansion chamber to thereby selectively shift the clutch ring between the positions of interlocking the axle portion and hub assembly and unlocking the axle portion and hub assembly.« less

  1. In-line drivetrain and four wheel drive work machine using same

    DOEpatents

    Hoff, Brian

    2008-08-05

    A four wheel drive articulated mine loader is powered by a fuel cell and propelled by a single electric motor. The drivetrain has the first axle, second axle, and motor arranged in series on the work machine chassis. Torque is carried from the electric motor to the back differential via a pinion meshed with the ring gear of the back differential. A second pinion oriented in an opposite direction away from the ring gear is coupled to a drive shaft to transfer torque from the ring gear to the differential of the front axle. Thus, the ring gear of the back differential acts both to receive torque from the motor and to transfer torque to the forward axle. The in-line drive configuration includes a single electric motor and a single reduction gear to power the four wheel drive mine loader.

  2. Surface--micromachined rotatable member having a low-contact-area hub

    DOEpatents

    Rodgers, M. Steven; Sniegowski, Jeffry J.

    2002-01-01

    A surface-micromachined rotatable member formed on a substrate and a method for manufacturing thereof are disclosed. The surface-micromachined rotatable member, which can be a gear or a rotary stage, has a central hub, and an annulus connected to the central hub by an overarching bridge. The hub includes a stationary axle support attached to the substrate and surrounding an axle. The axle is retained within the axle support with an air-gap spacing therebetween of generally 0.3 .mu.m or less. The rotatable member can be formed by alternately depositing and patterning layers of a semiconductor (e.g. polysilicon or a silicon-germanium alloy) and a sacrificial material and then removing the sacrificial material, at least in part. The present invention has applications for forming micromechanical or microelectromechanical devices requiring lower actuation forces, and providing improved reliability.

  3. Surface-micromachined rotatable member having a low-contact-area hub

    DOEpatents

    Rodgers, M. Steven; Sniegowski, Jeffry J.; Krygowski, Thomas W.

    2003-11-18

    A surface-micromachined rotatable member formed on a substrate and a method for manufacturing thereof are disclosed. The surface-micromachined rotatable member, which can be a gear or a rotary stage, has a central hub, and an annulus connected to the central hub by an overarching bridge. The hub includes a stationary axle support attached to the substrate and surrounding an axle. The axle is retained within the axle support with an air-gap spacing therebetween of generally 0.3 .mu.m or less. The rotatable member can be formed by alternately depositing and patterning layers of a semiconductor (e.g. polysilicon or a silicon-germanium alloy) and a sacrificial material and then removing the sacrificial material, at least in part. The present invention has applications for forming micromechanical or microelectromechanical devices requiring lower actuation forces, and providing improved reliability.

  4. Characterization and development of truck load spectra and growth factors for current and future pavement design practices in Louisiana : technical summary report.

    DOT National Transportation Integrated Search

    2011-07-01

    Current roadway pavement design practices follow the standards set by the American Society of State : Highway and Transportation Officials (AASHTO), which require the use of an equivalent single axle load : (ESAL-18 kip single axle load) for design t...

  5. 49 CFR 661.11 - Rolling stock procurements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Devices; (21) Car Axle Counters; (22) Communication Based Train Control (CBTC). (u) Communication... components of a bus. This list is not all-inclusive. Car body shells, egines, transmissions, front axle... assemblies, air compressor and pneumatic systems, generator/alternator and electrical systems, steering...

  6. 49 CFR 661.11 - Rolling stock procurements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Devices; (21) Car Axle Counters; (22) Communication Based Train Control (CBTC). (u) Communication... components of a bus. This list is not all-inclusive. Car body shells, egines, transmissions, front axle... assemblies, air compressor and pneumatic systems, generator/alternator and electrical systems, steering...

  7. Estimation of 18-kip equivalent on primary and interstate road systems in Virginia.

    DOT National Transportation Integrated Search

    1972-01-01

    For pavement design purposes, the Virginia Department of Highways uses the AASHO method of determining the 18-kip equivalent single axle load (EWL-18). The evaluation of the EWL-18 is based on on-location truck axle weight studies that usually are ca...

  8. Electronic differential for tramcar bogies: system development and performance evaluation by means of numerical simulation

    NASA Astrophysics Data System (ADS)

    Barbera, Andrea N.; Bucca, Giuseppe; Corradi, Roberto; Facchinetti, Alan; Mapelli, Ferdinando

    2014-05-01

    The dynamic behaviour of railway vehicles depends on the wheelset configuration, i.e. solid axle wheelset or independently rotating wheels (IRWs). The self-centring behaviour, peculiar of the solid axle wheelset, makes this kind of wheelset very suitable for tangent track running at low speed: the absence of the self-centring mechanism in the IRWs may lead to anomalous wheel/rail wear, reduced vehicle safety and passengers' discomfort. On the contrary, during negotiation of the sharp curves typical of urban tramways, solid axle wheelsets produce lateral contact forces higher than those of IRWs. This paper illustrates an electronic differential system to be applied to tramcar bogies equipped with wheel-hub motors which allows switching from solid axle in tangent track to IRWs in sharp curve (and vice versa). An electro-mechanical vehicle model is adopted for the design of the control system and for the evaluation of the vehicle dynamic performances.

  9. Axle Lubricant Efficiency

    DTIC Science & Technology

    2014-05-09

    state or reflect those of the United States Government or the DoA, and shall not be used for advertising or product endorsement purposes...Engine Control Module FMTV Family of Medium Tactical Vehicles GO Gear Oil GPS Global Positioning System GVW Gross Vehicle Weight HDO Heavy Duty Oil

  10. Updating the school bus standard vehicle for load rating Alabama bridges.

    DOT National Transportation Integrated Search

    2010-06-01

    The objective of this project is to identify a representative school bus (weight and axle spacing) for load rating highway bridges. The ALDOT Bridge Rating and Load Test Section currently uses a 12.5-ton school bus (four tons on the front axle and 8....

  11. Effect of weight-mile tax on road damage in Oregon

    DOT National Transportation Integrated Search

    1999-09-01

    Oregon's weight-mile tax was amended in 1990 to provide for a lower tax rate for trucks weighing more than 80,000 pounds if they added axles. The additional axles within a weight class reduce the amount of road damage. The tax break was largely based...

  12. Tyro3 Family-Mediated Cell Entry of Ebola and Marburg Viruses

    PubMed Central

    Shimojima, Masayuki; Takada, Ayato; Ebihara, Hideki; Neumann, Gabriele; Fujioka, Kouki; Irimura, Tatsuro; Jones, Steven; Feldmann, Heinz; Kawaoka, Yoshihiro

    2006-01-01

    Filoviruses, represented by the genera Ebolavirus and Marburgvirus, cause a lethal hemorrhagic fever in humans and in nonhuman primates. Although filovirus can replicate in various tissues or cell types in these animals, the molecular mechanisms of its broad tropism remain poorly understood. Here we show the involvement of members of the Tyro3 receptor tyrosine kinase family—Axl, Dtk, and Mer—in cell entry of filoviruses. Ectopic expression of these family members in lymphoid cells, which otherwise are highly resistant to filovirus infection, enhanced infection by pseudotype viruses carrying filovirus glycoproteins on their envelopes. This enhancement was reduced by antibodies to Tyro3 family members, Gas6 ligand, or soluble ectodomains of the members. Live Ebola viruses infected both Axl- and Dtk-expressing cells more efficiently than control cells. Antibody to Axl inhibited infection of pseudotype viruses in a number of Axl-positive cell lines. These results implicate each Tyro3 family member as a cell entry factor in filovirus infection. PMID:17005688

  13. GAS6 Receptor Status Is Associated with Dormancy and Bone Metastatic Tumor Formation

    PubMed Central

    Taichman, Russell S.; Patel, Lalit R.; Bedenis, Rachel; Wang, Jingcheng; Weidner, Savannah; Schumann, Taibriana; Yumoto, Kenji; Berry, Janice E.; Shiozawa, Yusuke; Pienta, Kenneth J.

    2013-01-01

    Disseminated tumor cells (DTCs) are believed to lie dormant in the marrow before they can be activated to form metastases. How DTCs become dormant in the marrow and how dormant DTCs escape dormancy remains unclear. Recent work has shown that prostate cancer (PCa) cell lines express the growth-arrest specific 6 (GAS6) receptors Axl, Tyro3, and Mer, and become growth arrested in response to GAS6. We therefore hypothesized that GAS6 signaling regulates the proliferative activity of DTCs in the marrow. To explore this possibility, in vivo studies were performed where it was observed that when Tyro3 expression levels exceed Axl expression, the PCa cells exhibit rapid growth. When when Axl levels predominate, PCa cells remain largely quiescent. These findings suggest that a balance between the expression of Axl and Tyro3 is associated with a molecular switch between a dormant and a proliferative phenotype in PCa metastases. PMID:23637920

  14. Chassis stabilization system

    DOEpatents

    Claxton, Gerald L.

    1999-01-01

    A stabilizing suspension system is provided for vehicles carrying telescopic booms or aerial work platforms having a fixed axle and a oscillating axle. Hydraulic cylinders are connected to each end of the oscillating axle, each cylinder being capable of extending and retracting. An off level sensor senses the angle of tilt of the chassis in both left and right directions and, when a predetermined threshold of tilt has been detected, the hydraulic cylinder on the downhill side of the chassis is locked against retracting, but is free to move in the downhill direction to allow the downhill wheel to remain in contact with the ground.

  15. Response of reinforced concrete and corrugated steel pipes to surface load

    NASA Astrophysics Data System (ADS)

    Lay, Geoff R.

    Full-scale simulated live load tests were conducted in a controlled laboratory setting using a single-axle frame on 600-mm-inner-diameter reinforced concrete pipe (RCP) and corrugated steel pipe (CSP) when buried in dense, well-graded sand and gravel. Measurements of the RCP at nominal and working forces and beyond are reported for 0.3, 0.6 and 0.9 m of soil cover above the pipe crown. The RCP experienced no cracking when buried at 0.3 m under nominal and working CL-625 and CL-800 single-axle design loads. At these loads, the vertical contraction of the pipe diameter was less than 0.08 and 0.10 mm and the largest tensile strains in the pipe were 75 and 100 muepsilon (50-60% of the cracking strain), respectively. A 0.15 (+/-0.05)-mm-wide axial crack developed at the inner crown in the presence of a 6 kNm/m circumferential bending moment (70% of the theoretical ultimate moment capacity) at the fully factored CL-625 load. This crack did not propagate or widen from 3 series of cyclic load-unload tests. At 1300 kN of applied load the change in pipe diameter was less than 3.5 mm. Increasing soil cover from 0.3 to 0.6 to 0.9 m reduced the circumferential crown bending moment from 6.0 to 3.9 to 2.1 kNm/m, respectively, at 400 kN of axle load. A 1.6- and a 2.8-mm-thick CSP were also subjected to axle loading. No yielding or limit states occurred in the 1.6-mm-thick CSP when buried 0.9-m-deep. However, at 0.6 m of cover a 300 kN axle load caused local yielding at the pipe crown. Increasing soil cover from 0.6 to 0.9 m decreased the vertical diameter change from -3.0 to -1.2 mm and the crown bending moment from 0.7 to 0.2 kNm/m (75% and 20% of the yield moment), respectively, at a 250 kN axle load. Deflections of the thicker CSP were less than the thinner pipe below the CL-625 single-axle load, however further increases in applied load produced a greater response in the thicker pipe, likely due to a haunch support issue. Shallow axle loading produced a greater 3-dimensional

  16. 49 CFR 393.207 - Suspension systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... bar. No torsion bar or torsion bar suspension shall be cracked or broken. (f) Air suspensions. The air... the controls are either located on the trailer, or the power unit and trailer combination are not....207 Suspension systems. (a) Axles. No axle positioning part shall be cracked, broken, loose or missing...

  17. 49 CFR 393.207 - Suspension systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ....207 Suspension systems. (a) Axles. No axle positioning part shall be cracked, broken, loose or missing... locking pins missing or disengaged. (c) Leaf springs. No leaf spring shall be cracked, broken, or missing nor shifted out of position. (d) Coil springs. No coil spring shall be cracked or broken. (e) Torsion...

  18. String and Sticky Tape Experiments: Simple Self-Lubricated Electric Motor for Elementary Physics Lab.

    ERIC Educational Resources Information Center

    Entrikin, Jerry; Griffiths, David

    1983-01-01

    The main problem in constructing functioning electric motors from simple parts is the mounting of the axle (which is too flimsy to maintain good electrical contacts or too tight, imposing excessive friction at the supports). This problem is solved by using a pencil sharpened at both ends as the axle. (JN)

  19. Gas6 induces cancer cell migration and epithelial–mesenchymal transition through upregulation of MAPK and Slug

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Yunhee; Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon; Lee, Mira

    2013-04-26

    Highlights: •We investigated the molecular mechanisms underlying Gas6-mediated cancer cell migration. •Gas6 treatment and subsequent Axl activation induce cell migration and EMT via upregulation of Slug. •Slug expression mediated by Gas6 is mainly through c-Jun and ATF-2 in an ERK1/2 and JNK-dependent manner. •The Gas6/Axl-Slug axis may be exploited as a target for anti-cancer metastasis therapy. -- Abstract: Binding of Gas6 to Axl (Gas6/Axl axis) alters cellular functions, including migration, invasion, proliferation, and survival. However, the molecular mechanisms underlying Gas6-mediated cell migration remain poorly understood. In this study, we found that Gas6 induced the activation of JNK and ERK1/2 signalingmore » in cancer cells expressing Axl, resulting in the phosphorylation of activator protein-1 (AP-1) transcription factors c-Jun and ATF-2, and induction of Slug. Depletion of c-Jun or ATF-2 by siRNA attenuated the Gas6-induced expression of Slug. Slug expression was required for cell migration and E-cadherin reduction/vimentin induction induced by Gas6. These results suggest that Gas6 induced cell migration via Slug upregulation in JNK- and ERK1/2-dependent mechanisms. These data provide an important insight into the molecular mechanisms mediating Gas6-induced cell migration.« less

  20. 77 FR 3505 - Investigations Regarding Certifications of Eligibility To Apply for Worker Adjustment Assistance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-24

    ... 01/06/12 01/05/12 81218 Ballantyne Strong, Inc. Omaha, NE 01/06/12 01/05/12 (Company). 81219 Deloitte.../12 (Company). 81207 American Axle & Detroit, MI 01/03/12 01/02/12 Manufacturing (Company). 81208 American Axle & Cheektowaga, NY....... 01/03/12 12/30/11 Manufacturing, Inc. (AAM) (Company). 81209 TriNet...

  1. 23 CFR 658.17 - Weight.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... the bridge formula. (c) The maximum gross weight upon any one axle, including any one axle of a group... following formula, referred to as the Bridge Gross Weight Formula: EC14OC91.012 except that two consecutive... derived from the Bridge Formula, up to a maximum of 80,000 pounds, including all enforcement tolerances...

  2. 23 CFR 658.17 - Weight.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... the bridge formula. (c) The maximum gross weight upon any one axle, including any one axle of a group... following formula, referred to as the Bridge Gross Weight Formula: EC14OC91.012 except that two consecutive... derived from the Bridge Formula, up to a maximum of 80,000 pounds, including all enforcement tolerances...

  3. Radiometric, Spectral and Effectiveness Equipment

    DTIC Science & Technology

    1993-09-24

    modified Contraves Kineto Tracking Mount (KTM) Model 443. The KTM is a self-contained trailer and mount. The trailer is a four wheel duel-axle bed with...measurement system also uses the Contraves (KTM) Model 433. The KTM is a self-contained trailer and mount. The trailer is a four wheel duel-axle bed with

  4. 26 CFR 48.4061(a)-1 - Imposition of tax; exclusion for light-duty trucks, etc.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... chassis frame, the axle capacity and placement, and the spring, brake, rim, and tire capacities. The... weight. If the capacity of any of the readily attachable components (springs, brakes, rims, or tires... solely on the basis of the chassis frame or the total of the axle ratings is 12,000 pounds or less. (vi...

  5. 26 CFR 48.4061(a)-1 - Imposition of tax; exclusion for light-duty trucks, etc.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... chassis frame, the axle capacity and placement, and the spring, brake, rim, and tire capacities. The... weight. If the capacity of any of the readily attachable components (springs, brakes, rims, or tires... solely on the basis of the chassis frame or the total of the axle ratings is 12,000 pounds or less. (vi...

  6. 26 CFR 48.4061(a)-1 - Imposition of tax; exclusion for light-duty trucks, etc.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... chassis frame, the axle capacity and placement, and the spring, brake, rim, and tire capacities. The... weight. If the capacity of any of the readily attachable components (springs, brakes, rims, or tires... solely on the basis of the chassis frame or the total of the axle ratings is 12,000 pounds or less. (vi...

  7. TAM Receptors Are Not Required for Zika Virus Infection in Mice.

    PubMed

    Hastings, Andrew K; Yockey, Laura J; Jagger, Brett W; Hwang, Jesse; Uraki, Ryuta; Gaitsch, Hallie F; Parnell, Lindsay A; Cao, Bin; Mysorekar, Indira U; Rothlin, Carla V; Fikrig, Erol; Diamond, Michael S; Iwasaki, Akiko

    2017-04-18

    Tyro3, Axl, and Mertk (TAM) receptors are candidate entry receptors for infection with the Zika virus (ZIKV), an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we used several routes of viral inoculation and compared viral replication in wild-type versus Axl -/- , Mertk -/- , Axl -/- Mertk -/- , and Axl -/- Tyro3 -/- mice in various organs. Pregnant and non-pregnant mice treated with interferon-α-receptor (IFNAR)-blocking (MAR1-5A3) antibody and infected subcutaneously with ZIKV showed no reliance on TAMs for infection. In the absence of IFNAR-blocking antibody, adult female mice challenged intravaginally with ZIKV showed no difference in mucosal viral titers. Similarly, in young mice that were infected with ZIKV intracranially or intraperitoneally, ZIKV replication occurred in the absence of TAM receptors, and no differences in cell tropism were observed. These findings indicate that, in mice, TAM receptors are not required for ZIKV entry and infection. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Fault detection method for railway wheel flat using an adaptive multiscale morphological filter

    NASA Astrophysics Data System (ADS)

    Li, Yifan; Zuo, Ming J.; Lin, Jianhui; Liu, Jianxin

    2017-02-01

    This study explores the capacity of the morphology analysis for railway wheel flat fault detection. A dynamic model of vehicle systems with 56 degrees of freedom was set up along with a wheel flat model to calculate the dynamic responses of axle box. The vehicle axle box vibration signal is complicated because it not only contains the information of wheel defect, but also includes track condition information. Thus, how to extract the influential features of wheels from strong background noise effectively is a typical key issue for railway wheel fault detection. In this paper, an algorithm for adaptive multiscale morphological filtering (AMMF) was proposed, and its effect was evaluated by a simulated signal. And then this algorithm was employed to study the axle box vibration caused by wheel flats, as well as the influence of track irregularity and vehicle running speed on diagnosis results. Finally, the effectiveness of the proposed method was verified by bench testing. Research results demonstrate that the AMMF extracts the influential characteristic of axle box vibration signals effectively and can diagnose wheel flat faults in real time.

  9. Small molecule inhibitors block Gas6-inducible TAM activation and tumorigenicity.

    PubMed

    Kimani, Stanley G; Kumar, Sushil; Bansal, Nitu; Singh, Kamalendra; Kholodovych, Vladyslav; Comollo, Thomas; Peng, Youyi; Kotenko, Sergei V; Sarafianos, Stefan G; Bertino, Joseph R; Welsh, William J; Birge, Raymond B

    2017-03-08

    TAM receptors (Tyro-3, Axl, and Mertk) are a family of three homologous type I receptor tyrosine kinases that are implicated in several human malignancies. Overexpression of TAMs and their major ligand Growth arrest-specific factor 6 (Gas6) is associated with more aggressive staging of cancers, poorer predicted patient survival, acquired drug resistance and metastasis. Here we describe small molecule inhibitors (RU-301 and RU-302) that target the extracellular domain of Axl at the interface of the Ig-1 ectodomain of Axl and the Lg-1 of Gas6. These inhibitors effectively block Gas6-inducible Axl receptor activation with low micromolar IC 50s in cell-based reporter assays, inhibit Gas6-inducible motility in Axl-expressing cell lines, and suppress H1299 lung cancer tumor growth in a mouse xenograft NOD-SCIDγ model. Furthermore, using homology models and biochemical verifications, we show that RU301 and 302 also inhibit Gas6 inducible activation of Mertk and Tyro3 suggesting they can act as pan-TAM inhibitors that block the interface between the TAM Ig1 ectodomain and the Gas6 Lg domain. Together, these observations establish that small molecules that bind to the interface between TAM Ig1 domain and Gas6 Lg1 domain can inhibit TAM activation, and support the further development of small molecule Gas6-TAM interaction inhibitors as a novel class of cancer therapeutics.

  10. ATLAS 60’ Fording Study

    DTIC Science & Technology

    1992-03-03

    crack. Carbon steel stress cracks in the presence of sodium hydroxide (" caustic embrittlement"), whereas austenitic stainless steels stress crack in...transmission life. - Outboard planetary axle design reduces stresses on differential, drive shafts and axle shaft U-joints. . Enclosed oil disc brakes on... Stress Corrosion Crevice Pitting Erosion Corrosion Uniform Corrosion Intergranular Selective Leaching Page 19 Caterpflar Inc. ATLAS Fording Study Q The

  11. Learning the Lessons of Leadership: Case Method Teaching with Interactive Computer-Based Tools and Film-Based Cases

    DTIC Science & Technology

    2008-03-01

    report describes how the AXL system capitalizes on the best practices of traditional case method instruction and addresses some of the limitations of...system were addressed in the AXL system, producing an innovative technology solution for delivering case method instruction. Several case method best ...approaches for addressing such problems. The report also documents how case method best practices in traditional classroom environments can be translated into

  12. Promiscuity and selectivity of small-molecule inhibitors across TAM receptor tyrosine kinases in pediatric leukemia.

    PubMed

    Liu, Mao-Hua; Chen, Shi-Bing; Yu, Juan; Liu, Cheng-Jun; Zhang, Xiao-Jing

    2017-08-01

    The TAM receptor tyrosine kinase family member Mer has been recognized as an attractive therapeutic target for pediatric leukemia. Beside Mer the family contains other two kinases, namely, Tyro3 and Axl, which are highly homologues with Mer and thus most existing small-molecule inhibitors show moderate or high promiscuity across the three kinases. Here, the structural basis and energetic property of selective binding of small-molecule inhibitors to the three kinases were investigated at molecular level. It is found that the selectivity is primarily determined by the size, shape and configuration of kinase's ATP-binding site; the Mer and Axl possess a small, closed active pocket as compared to the bulky, open pocket of Tyro3. The location and conformation of active-site residues of Mer and Axl are highly consistent, suggesting that small-molecule inhibitors generally have a low Mer-over-Axl selectivity and a high Mer-over-Tyro3 selectivity. We demonstrated that the difference in ATP binding potency to the three kinases is also responsible for inhibitor selectivity. We also found that the long-range interactions and allosteric effect arising from rest of the kinase's active site can indirectly influence inhibitor binding and selectivity. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Analysis of Rail Vehicle Suspension Spring with Special Emphasis on Curving, Tracking and Tractive Efforts

    NASA Astrophysics Data System (ADS)

    Kumbhalkar, M. A.; Bhope, D. V.; Vanalkar, A. V.

    2016-09-01

    The dynamics of the rail vehicle represents a balance between the forces acting between wheel and rail, the inertia forces and the forces exerted by suspension and articulation. Axial loading on helical spring causes vertical deflection at straight track but failures calls to investigate for lateral and longitudinal loading at horizontal and vertical curves respectively. Goods carrying vehicle has the frequent failures of middle axle inner suspension spring calls for investigation. The springs are analyzed for effect of stress concentration due to centripetal force and due to tractive and breaking effort. This paper also discusses shear failure analysis of spring at curvature and at uphill at various speeds for different loading condition analytically and by finite element analysis. Two mass rail vehicle suspension systems have been analyzed for vibration responses analytically using mathematical tool Matlab Simulink and the same will be evaluated using FFT vibration analyzer to find peak resonance in vertical, lateral and longitudinal direction. The results prove that the suspension acquires high repeated load in vertical and lateral direction due to tracking and curving causes maximum stress concentration on middle axle suspension spring as height of this spring is larger than end axle spring in primary suspension system and responsible for failure of middle axle suspension spring due to high stress acquisition.

  14. Dollar Summary of Federal Supply Classification and Service Category by Company, FY84, Part 1 (1005-2610).

    DTIC Science & Technology

    1984-01-01

    350 STATE TOTAL 377 NEBRASKA ARMY TRACTORS WHEELED 111 CONTRACTOR TOTAL 488 PINE BUSH EQUIPMENT CO INC NEW YORK ARMY TRACTORS WHEELED 49 PSI MOBILE...ARMY VEHICULAR FURNITURE AND ACCESSORIES 48- AURORA CORD a CABLE CO INC ILLINOIS ARMY VEHICULAR FURNITURE AND ACCESSORIES 211 BARREN RV MTL HTH/MTL...MICHIGAN ARMY VEHICULAR BRAKE STEERING AXLE WHEEL COMP 702 PENN ARMY VEHICULAR BRAKE STEERING AXLE WHEEL COMP 32 CONTRACTOR TOTAL 734 RYAN CHRYSLER PLYMOUTH

  15. Fatal car fires from rear-end crashes: the effects of fuel tank placement before and after regulation.

    PubMed Central

    Robertson, L S

    1993-01-01

    A federal standard for fuel tank integrity in cars was applied to 1977 and subsequent models. National data indicate that fatalities per 10,000 occupants in rear-end crashes of small cars, where fire was the most harmful event, were reduced by approximately 57% if the fuel tank was located behind the rear axle and 77% if the tank was situated directly above or in front of the rear axle. PMID:8342730

  16. An Automatic Vehicle Classification System.

    DTIC Science & Technology

    1981-07-01

    addi- tion, various portions of the system design can be used by other vehicle study projects, e.g. for projects concerned with vehicle speed or for...traffic study projects that require an axle counter or vehicle height indicator. A *4 UNCLASSIFIED SECURITY CLASSIFICATION OF THIS PAGE(W1en Data Enrerod...optoelectronic components as the basis for detection. Factors of vehicle length, height, and number of axles are used as identification characteristics. In

  17. Aircraft Operations on Repaired Runways (L’Exploitation des Aeronefs sur les Pistes Refaites)

    DTIC Science & Technology

    1990-08-01

    of this Section and investigations to be the force 0-y apply to the axle . Under the influence of that reported later - in Sections 6 and 7 and...upward axle movement;For the formersince the length of unacceptably extensive programme cc calculations to tile ratmp will often be comparable to the...outsidethat range would necessitatecither general discussion we need not be concerned.) The a full analysis or thtir exclusion from the aircraft’s maximum

  18. Preliminary Assessment of Overweight Mainline Vehicles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Siekmann, Adam; Capps, Gary J; Lascurain, Mary Beth

    2011-11-01

    The Federal Motor Carrier Safety Administration requested information regarding overweight and oversized vehicle traffic entering inspection stations (ISs) in order to develop strategies for future research efforts and possibly help guide regulatory issues involving overweight commercial motor vehicles (CMVs). For a period of one month, inspection stations in Knox County and Greene County, Tennessee, recorded overweight and oversized vehicles that entered these ISs. During this period, 435 CMVs were recorded using an electronic form filled out by enforcement personnel at the IS. Of the 435 CMVs recorded, 381 had weight information documented with them. The majority (52.2%) of the vehiclesmore » recorded were five-axle combination vehicles, and 50.6% of all the vehicles were permitted to operate above the legal weight limit in Tennessee, which is 80,000 lb for vehicles with five or more axles. Only 16.8% of the CMVs recorded were overweight gross (11.5% of permitted vehicles) and 54.1% were overweight on an axle group. The low percentage of overweight gross CMVs was because only 45 of the vehicles over 80,000 lb. were not permitted. On average, axles that were overweight were 2,000 lb. over the legal limit for an axle or group of axles. Of the vehicles recorded, 172 vehicles were given a North American Standard (NAS) inspection during the assessment. Of those, 69% of the inspections were driver-only inspections (Level III) and only 25% of the inspections had a vehicle component (such as a Level I or Level II). The remaining 6% of inspections did not have valid Aspen numbers; the type of was inspection unknown. Data collected on the types of trailers of each vehicle showed that about half of the recorded CMVs could realistically be given a Level I (full vehicle and driver) inspection; this estimate was solely based on trailer type. Enforcement personnel at ISs without an inspection pit have difficulty fully inspecting certain vehicles due to low clearance below the

  19. Role of phosphatidylserine receptors in enveloped virus infection.

    PubMed

    Morizono, Kouki; Chen, Irvin S Y

    2014-04-01

    We recently demonstrated that a soluble protein, Gas6, can facilitate viral entry by bridging viral envelope phosphatidylserine to Axl, a receptor tyrosine kinase expressed on target cells. The interaction between phosphatidylserine, Gas6, and Axl was originally shown to be a molecular mechanism through which phagocytes recognize phosphatidylserine exposed on dead cells. Since our initial report, several groups have confirmed that Axl/Gas6, as well as other phosphatidylserine receptors, facilitate entry of dengue, West Nile, and Ebola viruses. Virus binding by viral envelope phosphatidylserine is now a viral entry mechanism generalized to many families of viruses. In addition to Axl/Gas6, various molecules are known to recognize phosphatidylserine; however, the effects of these molecules on virus binding and entry have not been comprehensively evaluated and compared. In this study, we examined most of the known human phosphatidylserine-recognizing molecules, including MFG-E8, TIM-1, -3, and -4, CD300a, BAI1, and stabilin-1 and -2, for their abilities to facilitate virus binding and infection. Using pseudotyped lentiviral vectors, we found that a soluble phosphatidylserine-binding protein, MFG-E8, enhances transduction. Cell surface receptors TIM-1 and -4 also enhance virus binding/transduction. The extent of enhancement by these molecules varies, depending on the type of pseudotyping envelope proteins. Mutated MFG-E8, which binds viral envelope phosphatidylserine without bridging virus to cells, but, surprisingly, not annexin V, which has been used to block phagocytosis of dead cells by concealing phosphatidylserine, efficiently blocks these phosphatidylserine-dependent viral entry mechanisms. These results provide insight into understanding the role of viral envelope phosphatidylserine in viral infection. Envelope phosphatidylserine has previously been shown to be important for replication of various envelope viruses, but details of this mechanism(s) were unclear

  20. Self-Rappelling Robot System for Inspection and Reconnaissance in Search and Rescue Applications

    DTIC Science & Technology

    2009-07-01

    of at least 12 hours • Be capable of carrying crucial sensor- modalities (visual, chemical, etc.) • Be capable of accessing and climbing up/down...endure abuse and be light and low cost to reproduce or replace. The shell is split into a fixed- axle rear compartment and an actively postureable front...feet locomotors on the rear axle for those types of motions, but with an increased leg-length (effective diameter), so they stick out beyond the rear

  1. Aircraft Operations on Repaired Runways (l’Exploitation des Aeronefs sur les Pistes Refaites)

    DTIC Science & Technology

    1990-08-01

    further compressed, so increasingThe discussions of this Section and investigations to be the force they’ apply to the axle . Under the intlucrncc of that...structural location the differLnce between the ratio of the For analysis the aircraft may be regarded as a system having stress corresponding to ultimate load...determine the rcliof of the loadingdIC initially be specified would probably require an to upward axle movement. For the former, since the length of

  2. Identification of Cell Surface Molecules Involved in Dystroglycan-Independent Lassa Virus Cell Entry

    PubMed Central

    Ströher, Ute; Ebihara, Hideki; Feldmann, Heinz

    2012-01-01

    Although O-mannosylated dystroglycan is a receptor for Lassa virus, a causative agent of Lassa fever, recent findings suggest the existence of an alternative receptor(s). Here we identified four molecules as receptors for Lassa virus: Axl and Tyro3, from the TAM family, and dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and liver and lymph node sinusoidal endothelial calcium-dependent lectin (LSECtin), from the C-type lectin family. These molecules enhanced the binding of Lassa virus to cells and mediated infection independently of dystroglycan. Axl- or Tyro3-mediated infection required intracellular signaling via the tyrosine kinase activity of Axl or Tyro3, whereas DC-SIGN- or LSECtin-mediated infection and binding were dependent on a specific carbohydrate and on ions. The identification of these four molecules as Lassa virus receptors advances our understanding of Lassa virus cell entry. PMID:22156524

  3. Changes in Somatosensory Responsiveness in Behaving Monkeys and Human Sub

    DTIC Science & Technology

    1991-08-30

    OFFICE SYMBOL 7a. NAME OF MONITORING ORGANIZATION University of Tennessee, Memphis f Air Force Office of Scientific Research/NL Sc. ADDRESS (City, State...wrist and at the elbow with velcro straps. Each animal palm manipulated a smooth aluminum plate attached at one end to the axle of a brushless DC...display are described above. The subject’s hand rested on a flat aluminum handle coupled at one end to the axle of a brushless DC torque motor while the

  4. Kinetic Shapes: Analysis, Verification, and Applications.

    PubMed

    Handz̆ić, Ismet; Reed, Kyle B

    2014-06-01

    A circular shape placed on an incline will roll; similarly, an irregularly shaped object, such as the Archimedean spiral, will roll on a flat surface when a force is applied to its axle. This rolling is dependent on the specific shape and the applied force (magnitude and location). In this paper, we derive formulas that define the behavior of irregular 2D and 3D shapes on a flat plane when a weight is applied to the shape's axle. These kinetic shape (KS) formulas also define and predict shapes that exert given ground reaction forces when a known weight is applied at the axle rotation point. Three 2D KS design examples are physically verified statically with good correlation to predicted values. Motion simulations of unrestrained 2D KS yielded expected results in shape dynamics and self-stabilization. We also put forth practical application ideas and research for 2D and 3D KS such as in robotics and gait rehabilitation.

  5. TAM receptors regulate multiple features of microglial physiology.

    PubMed

    Fourgeaud, Lawrence; Través, Paqui G; Tufail, Yusuf; Leal-Bailey, Humberto; Lew, Erin D; Burrola, Patrick G; Callaway, Perri; Zagórska, Anna; Rothlin, Carla V; Nimmerjahn, Axel; Lemke, Greg

    2016-04-14

    Microglia are damage sensors for the central nervous system (CNS), and the phagocytes responsible for routine non-inflammatory clearance of dead brain cells. Here we show that the TAM receptor tyrosine kinases Mer and Axl regulate these microglial functions. We find that adult mice deficient in microglial Mer and Axl exhibit a marked accumulation of apoptotic cells specifically in neurogenic regions of the CNS, and that microglial phagocytosis of the apoptotic cells generated during adult neurogenesis is normally driven by both TAM receptor ligands Gas6 and protein S. Using live two-photon imaging, we demonstrate that the microglial response to brain damage is also TAM-regulated, as TAM-deficient microglia display reduced process motility and delayed convergence to sites of injury. Finally, we show that microglial expression of Axl is prominently upregulated in the inflammatory environment that develops in a mouse model of Parkinson's disease. Together, these results establish TAM receptors as both controllers of microglial physiology and potential targets for therapeutic intervention in CNS disease.

  6. Hierarchical Control Strategy for the Cooperative Braking System of Electric Vehicle.

    PubMed

    Peng, Jiankun; He, Hongwen; Liu, Wei; Guo, Hongqiang

    2015-01-01

    This paper provides a hierarchical control strategy for cooperative braking system of an electric vehicle with separated driven axles. Two layers are defined: the top layer is used to optimize the braking stability based on two sliding mode control strategies, namely, the interaxle control mode and signal-axle control strategies; the interaxle control strategy generates the ideal braking force distribution in general braking condition, and the single-axle control strategy can ensure braking safety in emergency braking condition; the bottom layer is used to maximize the regenerative braking energy recovery efficiency with a reallocated braking torque strategy; the reallocated braking torque strategy can recovery braking energy as much as possible in the premise of meeting battery charging power. The simulation results show that the proposed hierarchical control strategy is reasonable and can adapt to different typical road surfaces and load cases; the vehicle braking stability and safety can be guaranteed; furthermore, the regenerative braking energy recovery efficiency can be improved.

  7. Dual Roadside Seismic Sensor for Moving Road Vehicle Detection and Characterization

    PubMed Central

    Wang, Hua; Quan, Wei; Wang, Yinhai; Miller, Gregory R.

    2014-01-01

    This paper presents a method for using a dual roadside seismic sensor to detect moving vehicles on roadway by installing them on a road shoulder. Seismic signals are split into fixed time intervals in recording. In each interval, the time delay of arrival (TDOA) is estimated using a generalized cross-correlation approach with phase transform (GCC-PHAT). Various kinds of vehicle characterization information, including vehicle speed, axle spacing, detection of both vehicle axles and moving direction, can also be extracted from the collected seismic signals as demonstrated in this paper. The error of both vehicle speed and axle spacing detected by this approach has been shown to be less than 20% through the field tests conducted on an urban street in Seattle. Compared to most existing sensors, this new design of dual seismic sensor is cost effective, easy to install, and effective in gathering information for various traffic management applications. PMID:24526304

  8. Hierarchical Control Strategy for the Cooperative Braking System of Electric Vehicle

    PubMed Central

    Peng, Jiankun; He, Hongwen; Guo, Hongqiang

    2015-01-01

    This paper provides a hierarchical control strategy for cooperative braking system of an electric vehicle with separated driven axles. Two layers are defined: the top layer is used to optimize the braking stability based on two sliding mode control strategies, namely, the interaxle control mode and signal-axle control strategies; the interaxle control strategy generates the ideal braking force distribution in general braking condition, and the single-axle control strategy can ensure braking safety in emergency braking condition; the bottom layer is used to maximize the regenerative braking energy recovery efficiency with a reallocated braking torque strategy; the reallocated braking torque strategy can recovery braking energy as much as possible in the premise of meeting battery charging power. The simulation results show that the proposed hierarchical control strategy is reasonable and can adapt to different typical road surfaces and load cases; the vehicle braking stability and safety can be guaranteed; furthermore, the regenerative braking energy recovery efficiency can be improved. PMID:26236772

  9. Vibration reduction on automotive shafts using piezoceramics

    NASA Astrophysics Data System (ADS)

    Kunze, Holger; Riedel, Mathias; Schmidt, Knut; Bianchini, Emanuele

    2003-08-01

    This paper reports an experimental study on active vibration reduction for automotive shafts with the use of piezoelectric material. The work focuses on an axle of an Audi A2. The demand in the automobile sector for higher comfort in the vehicle is of a great importance alongside the requirements of lighter weight and low fuel consumption. These requirements are typically in conflict with each other. One solution is the use of intelligent materials instead of viscoelastic materials and proof mass absorbers. These solutions are quite heavy especially at low frequencies. Active vibration control and piezoelectric devices are advantageous in this application due to their low mass to performance ratio. Our research study explores the use of such piezoelectric devices for an axle. In conjunction with electronics it will reduce vibrations in the first natural bending mode of the axle. Laboratory tests simulated the condition present in the road. At first a stationary set up was used, then a simulated disturbance was input at the attachment points of the shaft. Finally, a test with rotating shaft was performed. Piezoelectric devices (custom QuickPacks from ACX, a Division of Cymer) were used as sensors and as actuators to properly control the axle during the different operating conditions. The power consumption of each actuator pair was less than 20W. The work described here details the test setup, the control strategy, the hardware implementation as well as the test results obtained.

  10. Schwann cells use TAM receptor-mediated phagocytosis in addition to autophagy to clear myelin in a mouse model of nerve injury.

    PubMed

    Brosius Lutz, Amanda; Chung, Won-Suk; Sloan, Steven A; Carson, Glenn A; Zhou, Lu; Lovelett, Emilie; Posada, Sean; Zuchero, J Bradley; Barres, Ben A

    2017-09-19

    Ineffective myelin debris clearance is a major factor contributing to the poor regenerative ability of the central nervous system. In stark contrast, rapid clearance of myelin debris from the injured peripheral nervous system (PNS) is one of the keys to this system's remarkable regenerative capacity, but the molecular mechanisms driving PNS myelin clearance are incompletely understood. We set out to discover new pathways of PNS myelin clearance to identify novel strategies for activating myelin clearance in the injured central nervous system, where myelin debris is not cleared efficiently. Here we show that Schwann cells, the myelinating glia of the PNS, collaborate with hematogenous macrophages to clear myelin debris using TAM (Tyro3, Axl, Mer) receptor-mediated phagocytosis as well as autophagy. In a mouse model of PNS nerve crush injury, Schwann cells up-regulate TAM phagocytic receptors Axl and Mertk following PNS injury, and Schwann cells lacking both of these phagocytic receptors exhibit significantly impaired myelin phagocytosis both in vitro and in vivo. Autophagy-deficient Schwann cells also display reductions in myelin clearance after mouse nerve crush injury, as has been recently shown following nerve transection. These findings add a mechanism, Axl/Mertk-mediated myelin clearance, to the repertoire of cellular machinery used to clear myelin in the injured PNS. Given recent evidence that astrocytes express Axl and Mertk and have previously unrecognized phagocytic potential, this pathway may be a promising avenue for activating myelin clearance after CNS injury.

  11. Growth Arrest-Specific 6 (Gas6) and TAM Receptors in Mouse Platelets.

    PubMed

    Uras, Fikriye; Küçük, Burhanettin; Bingöl Özakpınar, Özlem; Demir, Ahmet Muzaffer

    2015-03-05

    Growth arrest-specific 6 (Gas6) is a newly discovered vitamin K-dependent protein, which is a ligand for TAM receptors [Tyro3 (Sky), Axl, and Mer] from the tyrosine kinase family. Gas6 knockout mice were resistant to venous and arterial thrombosis. There are contradictory reports on the presence of Gas6 and its receptors in mouse platelets. The objective of this study was to investigate whether Gas6 and its receptors were present in mouse platelets or not. Specific pathogen-free BALB/c male and female mice of 8-10 weeks old and 25-30 g in weight were anesthetized under light ether anesthesia and blood samples were taken from their hearts. RNAs were isolated from isolated platelets, and then mRNAs encoding Gas6 and TAM receptors were detected by reverse transcription-polymerase chain reaction (RT-PCR). Protein concentrations of Gas6 and TAM receptors in platelets were measured by ELISA, but not those of Mer, because of the absence of any commercial ELISA kit for mouse specimens. RT-PCR results indicated the presence of mRNAs encoding Gas6 and Mer in mouse platelets. However, although RT-PCR reactions were performed at various temperatures and cycles, we could not detect the presence of mRNAs encoding Axl and Tyro3 (Sky). Receptor protein levels of Axl and Tyro3 were below the detection limits of the ELISA method. We found the presence of mRNAs encoding Gas6 and the receptor Mer in mouse platelets, but not Axl and Tyro3. Gas6, Axl, and Tyro3 protein levels were below the detection limits of the ELISA. The presence of mRNA is not obvious evidence of protein expression in platelets that have no nucleus or DNA. Further studies are required to clarify the presence of Gas6/TAM receptors in platelets using real-time PCR and more sensitive immunological methods, and future studies on mechanisms will indicate whether the Gas6/TAM pathway is a strategy for treatment of disorders.

  12. Solar collector mounting and support apparatus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hutchison, J.A.

    1981-12-22

    A solar collector system is described of the type having a movable surface for receiving solar radiation having improved means for rotatably supporting the movable surface and for rotating the collector surface. A support axle for the collector includes a ball at one end which is carried within a cylindrical sleeve in the solar collector to support the weight of the collector. A torque transmitting arm comprising a flexible flat strip is connected at one end to the axle and at the other end to the collector surface. An improved rotational drive mechanism includes a first sprocket wheel carried onmore » the axle and a second sprocket wheel supported on a support pylon with a drive chain engaging both sprockets. A double acting piston also supported by the pylon is coupled to the chain so that the chain may be driven by a hydraulic control system to rotate the collector surfaces as required. An improved receiver tube support ring is also provided for use with the improved mounting and support apparatus to improve overall efficiency by reducing thermal losses.« less

  13. HBEGF promotes gliomagenesis in the context of Ink4a/Arf and Pten loss.

    PubMed

    Shin, C H; Robinson, J P; Sonnen, J A; Welker, A E; Yu, D X; VanBrocklin, M W; Holmen, S L

    2017-08-10

    Heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF) is a ligand for the EGF receptor (EGFR), one of the most commonly amplified receptor tyrosine kinases (RTKs) in glioblastoma (GBM). While HBEGF has been found to be expressed in a subset of malignant gliomas, its sufficiency for glioma initiation has not been evaluated. In this study, we demonstrate that HBEGF can initiate GBM in mice in the context of Ink4a/Arf and Pten loss, and that these tumors are similar to the classical GBM subtype observed in patients. Isogenic astrocytes from these mice showed activation not only of Egfr but also the RTK Axl in response to HBEGF stimulation. Deletion of either Egfr or Axl decreased the tumorigenic properties of HBEGF-transformed cells; however, only EGFR was able to rescue the phenotype in cells lacking both RTKs indicating that Egfr is required for activation of Axl in this context. Silencing of HBEGF in vivo resulted in tumor regression and significantly increased survival, suggesting that HBEGF may be a clinically relevant target.

  14. HBEGF promotes gliomagenesis in the context of Ink4a/Arf and Pten loss

    PubMed Central

    Shin, Clifford H.; Robinson, James P.; Sonnen, Joshua A.; Welker, Adam E.; Yu, Diana X.; VanBrocklin, Matthew W.; Holmen, Sheri L.

    2017-01-01

    Heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF) is a ligand for the epidermal growth factor receptor (EGFR), one of the most commonly amplified receptor tyrosine kinases (RTK) in glioblastoma. While HBEGF has been found to be expressed in a subset of malignant gliomas, its sufficiency for glioma initiation has not been evaluated. In this study, we demonstrate that HBEGF can initiate glioblastoma (GBM) in mice in the context of Ink4a/Arf and Pten loss, and that these tumors are similar to the classical GBM subtype observed in patients. Isogenic astrocytes from these mice showed activation not only of Egfr but also the RTK Axl in response to HBEGF stimulation. Deletion of either Egfr or Axl decreased the tumorigenic properties of HBEGF transformed cells; however only EGFR was able to rescue the phenotype in cells lacking both RTKs indicating that Egfr is required for activation of Axl in this context. Silencing of HBEGF in vivo resulted in tumor regression and significantly increased survival suggesting that HBEGF may be a clinically relevant target. PMID:28368403

  15. Coal combine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Krutki, M.; Olender, K.; Sedlaczek, J.

    1981-03-24

    The invention solves the problem of eliminating the transfer of the combine weight onto a conveyor through a chain instead of through a railing, in the combines which are advanced by means of a link chain meshing with a rack fixed alongside of the conveyor. To this end the slide skid (7) forcing the chain (1) to mesh with the rack (8) is provided with a tubular slipper (10). The tubular slipper (10) encloses a railing (11) situated in the gates of the conveyor (9) close to the rack (8). The tubular slipper (10) is mounted on a cranked axlemore » (12). The cranked axle (12) has - on the end of the pin embedded in the slide skid (7) a splined tip (16) embedded in a grooved hole (17) which has a common geometrical axis (15) with the pin of the cranked axle (12), the said pin being embedded in the slide skid (7). The tubular slipper (10) mounted on the pin (14) of the cranked axle (12) is protected against slipping off into the tubular slipper (10).« less

  16. Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears.

    PubMed

    Miner, Jonathan J; Sene, Abdoulaye; Richner, Justin M; Smith, Amber M; Santeford, Andrea; Ban, Norimitsu; Weger-Lucarelli, James; Manzella, Francesca; Rückert, Claudia; Govero, Jennifer; Noguchi, Kevin K; Ebel, Gregory D; Diamond, Michael S; Apte, Rajendra S

    2016-09-20

    Zika virus (ZIKV) is an emerging flavivirus that causes congenital abnormalities and Guillain-Barré syndrome. ZIKV infection also results in severe eye disease characterized by optic neuritis, chorioretinal atrophy, and blindness in newborns and conjunctivitis and uveitis in adults. We evaluated ZIKV infection of the eye by using recently developed mouse models of pathogenesis. ZIKV-inoculated mice developed conjunctivitis, panuveitis, and infection of the cornea, iris, optic nerve, and ganglion and bipolar cells in the retina. This phenotype was independent of the entry receptors Axl or Mertk, given that Axl(-/-), Mertk(-/-), and Axl(-/-)Mertk(-/-) double knockout mice sustained levels of infection similar to those of control animals. We also detected abundant viral RNA in tears, suggesting that virus might be secreted from lacrimal glands or shed from the cornea. This model provides a foundation for studying ZIKV-induced ocular disease, defining mechanisms of viral persistence, and developing therapeutic approaches for viral infections of the eye. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. Evaluation of engineering plastic for rollover protective structure (ROPS) mounting.

    PubMed

    Comer, R S; Ayers, P D; Liu, J

    2007-04-01

    Agriculture has one of the highest fatality rates of any industry in America. Tractor rollovers are a significant contributor to the high death rate. Rollover protective structures (ROPS) have helped lower these high fatality rates on full-size tractors. However, a large number of older tractors still do not use ROPS due to the difficulty of designing and creating a mounting structure. To help reduce this difficulty, engineering plastics were evaluated for use in a ROPS mounting structure on older tractors. The use of engineering plastics around axle housings could provide a uniform mounting configuration as well as lower costs for aftermarket ROPS. Various plastics were examined through shear testing, scale model testing, and compressive strength testing. Once a material was chosen based upon strength and cost, full-scale testing of the plastic's strength on axle housings was conducted. Finally, a mounting structure was tested in static ROPS tests, and field upset tests were performed in accordance with SAE Standard J2194. Initial tests revealed that the ROPS mounting structure and axle housing combination had higher torsional strength with less twisting than the axle housing alone. An engineering plastic ROPS mounting structure was easily successful in withstanding the forces applied during the static longitudinal and lateral ROPS tests. Field upset testing revealed that the mounting structure could withstand the impact loads seen during actual upsets without a failure. During both static testing and field upset testing, no permanent twisting of the mounting structure was found. Engineering plastic could therefore be a viable option for a universal ROPS mounting structure for older tractors.

  18. The role of TAM family receptors and ligands in the nervous system: From development to pathobiology.

    PubMed

    Shafit-Zagardo, Bridget; Gruber, Ross C; DuBois, Juwen C

    2018-03-04

    Tyro3, Axl, and Mertk, referred to as the TAM family of receptor tyrosine kinases, are instrumental in maintaining cell survival and homeostasis in mammals. TAM receptors interact with multiple signaling molecules to regulate cell migration, survival, phagocytosis and clearance of metabolic products and cell debris called efferocytosis. The TAMs also function as rheostats to reduce the expression of proinflammatory molecules and prevent autoimmunity. All three TAM receptors are activated in a concentration-dependent manner by the vitamin K-dependent growth arrest-specific protein 6 (Gas6). Gas6 and the TAMs are abundantly expressed in the nervous system. Gas6, secreted by neurons and endothelial cells, is the sole ligand for Axl. ProteinS1 (ProS1), another vitamin K-dependent protein functions mainly as an anti-coagulant, and independent of this function can activate Tyro3 and Mertk, but not Axl. This review will focus on the role of the TAM receptors and their ligands in the nervous system. We highlight studies that explore the function of TAM signaling in myelination, the visual cortex, neural cancers, and multiple sclerosis (MS) using Gas6 -/- and TAM mutant mice models. Copyright © 2018. Published by Elsevier Inc.

  19. Monocyte and plasma expression of TAM ligand and receptor in renal failure: Links to unregulated immunity and chronic inflammation.

    PubMed

    Lee, Iris J; Hilliard, Brendan A; Ulas, Mehriban; Yu, Daohai; Vangala, Chandan; Rao, Swati; Lee, Jean; Gadegbeku, Crystal A; Cohen, Philip L

    2015-06-01

    Chronic inflammation is increased in patients with chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality. Specific immune mechanisms and pathways that drive and maintain chronic inflammation in CKD are not well described. The TAM ligands (Gas6 and protein S) and receptors (Axl and Mer) have been recently recognized as playing a prominent role in immune regulation. The receptors exist in both soluble and cell-bound forms; the soluble receptors (sAxl and sMer) are believed to compete with the bound receptors and thus inhibit their function. In this study, we determined the expression of cell-bound and soluble TAM proteins in patients with CKD. CKD patients had significantly lower expression of Mer in monocytes, yet increased expression of soluble TAM receptors sAxl and sMer in plasma compared to controls. The metalloproteinase ADAM 17, responsible for cleavage of Mer to its soluble form, was increased in patient monocytes. Elevated levels of soluble TAM receptors were more evident in patients with progressive renal failure. These observations suggest that functional deficiency of TAM receptor-mediated regulation of inflammation may contribute to chronic inflammation in patients with CKD. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Targeting of TAM Receptors Ameliorates Fibrotic Mechanisms in Idiopathic Pulmonary Fibrosis.

    PubMed

    Espindola, Milena S; Habiel, David M; Narayanan, Rohan; Jones, Isabelle; Coelho, Ana L; Murray, Lynne A; Jiang, Dianhua; Noble, Paul W; Hogaboam, Cory M

    2018-06-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung remodeling, which progressively abolishes lung function in an RTK (receptor tyrosine kinase)-dependent manner. Gas6 (growth arrest-specific 6) ligand, Tyro3 (TYRO3 protein tyrosine kinase 3), and Axl (anexelekto) RTK expression and activity are increased in IPF. To determine if targeting these RTK pathways would inhibit fibroblast activation and the development of pulmonary fibrosis. Quantitative genomic, proteomic, and functional analyses were used to determine Gas6/TAM (Tyro3, Axl, and Mertk [MER proto-oncogene, tyrosine kinase]) RTK expression and activation in tissues and fibroblasts from normal and IPF lungs. The profibrotic impact of these RTK pathways were also examined in bleomycin-induced pulmonary fibrosis and in SCID/Bg mice that developed pulmonary fibrosis after the intravenous administration of primary IPF fibroblasts. Gas6, Axl, and Tyro3 were increased in both rapidly and slowly progressive IPF compared with normal lung samples and fibroblasts. Targeting these pathways with either specific antibodies directed at Gas6 or Axl, or with small-molecule TAM inhibitors indicated that the small molecule-mediated targeting approach was more efficacious in both in vitro and in vivo studies. Specifically, the TAM receptor inhibitor R428 (also known as BGB324) significantly inhibited the synthetic, migratory, and proliferative properties of IPF fibroblasts compared with the other Gas6/TAM receptor targeting agents. Finally, loss of Gas6 expression decreased lung fibrotic responses to bleomycin and treatment with R428 inhibited pulmonary fibrosis in humanized SCID/Bg mice. Gas6/TAM receptor activity contributes to the activation of pulmonary fibroblasts in IPF, suggesting that targeting this RTK pathway might be an effective antifibrotic strategy in this disease.

  1. Soluble TAM receptor tyrosine kinases in rheumatoid arthritis: correlation with disease activity and bone destruction.

    PubMed

    Xu, L; Hu, F; Zhu, H; Liu, X; Shi, L; Li, Y; Zhong, H; Su, Y

    2018-04-01

    The TAM receptor tyrosine kinases (TAM RTK) are a subfamily of receptor tyrosine kinases, the role of which in autoimmune diseases such as systemic lupus erythematosus has been well explored, while their functions in rheumatoid arthritis (RA) remain largely unknown. In this study, we investigated the role of soluble TAM receptor tyrosine kinases (sAxl/sMer/sTyro3) in patients with RA. A total of 306 RA patients, 100 osteoarthritis (OA) patients and 120 healthy controls (HCs) were enrolled into this study. The serum concentrations of sAxl/sMer/sTyro3 were measured by enzyme-linked immunosorbent assay (ELISA), then the associations between sAxl/sMer/sTyro3 levels and clinical features of RA patients were analysed. We also investigated whether sTyro3 could promote osteoclast differentiation in vitro in RA patients. The results showed that compared with healthy controls (HCs), sTyro3 levels in the serum of RA patients were elevated remarkably and sMer levels were decreased significantly, whereas there was no difference between HCs and RA patients on sAxl levels. The sTyro3 levels were correlated weakly but positively with white blood cells (WBC), immunoglobulin (Ig)M, rheumatoid factor (RF), swollen joint counts, tender joint counts, total sharp scores and joint erosion scores. Conversely, there were no significant correlations between sMer levels and the above indices. Moreover, RA patients with high disease activity also showed higher sTyro3 levels. In-vitro osteoclast differentiation assay showed further that tartrate-resistant acid phosphatase (TRAP) + osteoclasts were increased significantly in the presence of sTyro3. Collectively, our study indicated that serum sTyro3 levels were elevated in RA patients and correlated positively with disease activity and bone destruction, which may serve as an important participant in RA pathogenesis. © 2017 British Society for Immunology.

  2. Peripheral Retinal Vascular Patterns in Patients with Rhegmatogenous Retinal Detachment in Taiwan

    PubMed Central

    Chen, San-Ni; Hwang, Jiunn-Feng; Wu, Wen-Chuan

    2016-01-01

    This is an observational study of fluorescein angiography (FA) in consecutive patients with rhegmatogenous retinal detachment (RRD) in Changhua Christian Hospital to investigate the peripheral retinal vascular patterns in those patients. All patients had their age, sex, axial length (AXL), and refraction status (RF) recorded. According to the findings in FA of the peripheral retina, the eyes were divided into 4 groups: in group 1, there was a ramified pattern of peripheral retinal vasculature with gradual tapering; in group 2, there was an abrupt ending of peripheral vasculature with peripheral non-perfusion; in group 3, there was a curving route of peripheral vasculature forming vascular arcades or anastomosis; and in group 4, the same as in group 3, but with one or more wedge-shaped avascular notches. Comparisons of age, sex, AXL, and RF, association of breaks with lattice degeneration and retinal non-perfusion, surgical procedures utilized, and mean numbers of operations were made among the four groups. Of the 73 eyes studied, there were 13 eyes (17.8%) in group 1, 3 eyes (4.1%) in group 2, 40 eyes (54.8%) in group 3 and 17 eyes (23.3%) in group 4. Significant differences in age, AXL and RF, and association of retinal breaks to non-perfusion were noted among the four groups. Patients in group 1 had older ages, while younger ages were noted in groups 3 and 4. Eyes in group 1 had the shortest average AXL and were least myopic in contrast to the eyes in groups 3 and 4. Association of retinal breaks and retinal non-perfusion was significantly higher in groups 2, 3 and 4 than in group 1. In conclusion, peripheral vascular anomalies are common in cases with RRD. Patients with peripheral non-perfusion tend to be younger, with longer axial length and have the breaks associated with retinal non-perfusion. PMID:26909812

  3. System and method for weighing and characterizing moving or stationary vehicles and cargo

    DOEpatents

    Beshears, David L [Knoxville, TN; Scudiere, Matthew B [Oak Ridge, TN; White, Clifford P [Seymour, TN

    2008-05-20

    A weigh-in-motion device and method having at least one transducer pad, each transducer pad having at least one transducer group with transducers positioned essentially perpendicular to the direction of travel. At least one pad microcomputer is provided on each transducer pad having a means for calculating first output signal indicative of weight, second output signal indicative of time, and third output signal indicative of speed. At least one host microcomputer is in electronic communication with each pad microcomputer, and having a means for calculating at least one unknown selected from the group consisting of individual tire weight, individual axle weight, axle spacing, speed profile, longitudinal center of balance, and transverse center of balance.

  4. Variations of archived static-weight data and WIM

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Elliott, C.J.; Gillmann, R.; Kent, P.M.

    1998-12-01

    Using seven-card archived, static-weight and weigh-in-motion (WIM), truck data received by FHWA for 1966--1992, the authors examine the fluctuations of four fiducial weight measures reported at weight sites in the 50 states. The reduced 172 MB Class 9 (332000) database was prepared and ordered from 2 CD-ROMS with duplicate records removed. Front-axle weight and gross-vehicle weight (GVW) are combined conceptually by determining the front axle weight in four-quartile GVW categories. The four categories of front axle weight from the four GVW categories are combined in four ways. Three linear combinations are with fixed-coefficient fiducials and one is that optimal linearmore » combination producing the smallest standard deviation to mean value ratio. The best combination gives coefficients of variation of 2--3% for samples of 100 trucks, below the expected accuracy of single-event WIM measurements. Time tracking of data shows some high-variation sites have seasonal variations, or linear variations over the time-ordered samples. Modeling of these effects is very site specific but provides a way to reduce high variations. Some automatic calibration schemes would erroneously remove such seasonal or linear variations were they static effects.« less

  5. Changes in inertia and effect on turning effort across different wheelchair configurations.

    PubMed

    Caspall, Jayme J; Seligsohn, Erin; Dao, Phuc V; Sprigle, Stephen

    2013-01-01

    When executing turning maneuvers, manual wheelchair users must overcome the rotational inertia of the wheelchair system. Differences in wheelchair rotational inertia can result in increases in torque required to maneuver, resulting in greater propulsion effort and stress on the shoulder joints. The inertias of various configurations of an ultralightweight wheelchair were measured using a rotational inertia-measuring device. Adjustments in axle position, changes in wheel and tire type, and the addition of several accessories had various effects on rotational inertias. The configuration with the highest rotational inertia (solid tires, mag wheels with rearward axle) exceeded the configuration with the lowest (pneumatic tires, spoke wheels with forward axle) by 28%. The greater inertia requires increased torque to accelerate the wheelchair during turning. At a representative maximum acceleration, the reactive torque spanned the range of 11.7 to 15.0 N-m across the wheelchair configurations. At higher accelerations, these torques exceeded that required to overcome caster scrub during turning. These results indicate that a wheelchair's rotational inertia can significantly influence the torque required during turning and that this influence will affect active users who turn at higher speeds. Categorizing wheelchairs using both mass and rotational inertia would better represent differences in effort during wheelchair maneuvers.

  6. Integrative DNA methylome analysis of pan-cancer biomarkers in cancer discordant monozygotic twin-pairs.

    PubMed

    Roos, Leonie; van Dongen, Jenny; Bell, Christopher G; Burri, Andrea; Deloukas, Panos; Boomsma, Dorret I; Spector, Tim D; Bell, Jordana T

    2016-01-01

    A key focus in cancer research is the discovery of biomarkers that accurately diagnose early lesions in non-invasive tissues. Several studies have identified malignancy-associated DNA methylation changes in blood, yet no general cancer biomarker has been identified to date. Here, we explore the potential of blood DNA methylation as a biomarker of pan-cancer (cancer of multiple different origins) in 41 female cancer discordant monozygotic (MZ) twin-pairs sampled before or after diagnosis using the Illumina HumanMethylation450 BeadChip. We analysed epigenome-wide DNA methylation profiles in 41 cancer discordant MZ twin-pairs with affected individuals diagnosed with tumours at different single primary sites: the breast, cervix, colon, endometrium, thyroid gland, skin (melanoma), ovary, and pancreas. No significant global differences in whole blood DNA methylation profiles were observed. Epigenome-wide analyses identified one novel pan-cancer differentially methylated position at false discovery rate (FDR) threshold of 10 % (cg02444695, P = 1.8 × 10(-7)) in an intergenic region 70 kb upstream of the SASH1 tumour suppressor gene, and three suggestive signals in COL11A2, AXL, and LINC00340. Replication of the four top-ranked signals in an independent sample of nine cancer-discordant MZ twin-pairs showed a similar direction of association at COL11A2, AXL, and LINC00340, and significantly greater methylation discordance at AXL compared to 480 healthy concordant MZ twin-pairs. The effects at cg02444695 (near SASH1), COL11A2, and LINC00340 were the most promising in biomarker potential because the DNA methylation differences were found to pre-exist in samples obtained prior to diagnosis and were limited to a 5-year period before diagnosis. Gene expression follow-up at the top-ranked signals in 283 healthy individuals showed correlation between blood methylation and gene expression in lymphoblastoid cell lines at PRL, and in the skin tissue at AXL. A significant

  7. Metal-organic and supramolecular architectures based on mechanically interlocked molecules

    NASA Astrophysics Data System (ADS)

    Fernando, Isurika Rosini

    The focus of this work is on mechanically interlocked molecules (MIMs), which have unusual physicochemical and mechanical properties with potential applications in nano-scale/molecular devices and high strength materials. Rotaxanes, for example, consist of an axle-like molecule threaded through a wheel-like molecule, with bulky groups at the two ends of the axle preventing the wheel from dissociating. The position of the wheel along the axle can be switched in a controllable and reversible manner by applying external stimuli, a feature that might lead to the next generation of computers. Molecularly woven materials (MWMs), another example of molecules with mechanically interlocked features, are predicted to be unprecedentedly strong while being lightweight and flexible. With the ultimate goal of achieving control over the functioning of molecular devices in the solid state, a variety of pseudorotaxane building blocks were prepared and characterized, including a novel, rare blue-colored motif. The temperature-dependent assembly/disassembly of pseudorotaxanes was exploited for the construction of single-wavelength colorimetric temperature sensors over a 100 °C window. Pseudorotaxanes based on aromatic crown ether wheels and disubstituted 4,4'-bipyridinium axles were converted into rotaxanes upon binding to metal complexes (zinc, cadmium, mercury, copper, cobalt), and the formation of ordered crystalline arrays was studied in the solid state. The columnar organization of pseudorotaxanes by Hg2X6 2-- complexes (X = Cl, Br, I), leading to unprecedented dichroic (blue/red) rotaxane crystals, was demonstrated for the first time. From the crystal structures studied it became apparent that negatively charged metal complexes are needed for successful assembly with the positively charged pseudorotaxane units. To be able to use the more common, positively charged metal ions for rotaxane framework construction, neutral and negatively charged pseudorotaxanes were synthesized

  8. 23 CFR 500.204 - TMS components for highway traffic data.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... persons per automobile, light two-axle truck, and bus. The duration, geographic extent, and level of... methods include roadside monitoring, traveler surveys, the use of administrative records (e.g., accident...

  9. 23 CFR 500.204 - TMS components for highway traffic data.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... persons per automobile, light two-axle truck, and bus. The duration, geographic extent, and level of... methods include roadside monitoring, traveler surveys, the use of administrative records (e.g., accident...

  10. 23 CFR 500.204 - TMS components for highway traffic data.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... persons per automobile, light two-axle truck, and bus. The duration, geographic extent, and level of... methods include roadside monitoring, traveler surveys, the use of administrative records (e.g., accident...

  11. 23 CFR 500.204 - TMS components for highway traffic data.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... persons per automobile, light two-axle truck, and bus. The duration, geographic extent, and level of... methods include roadside monitoring, traveler surveys, the use of administrative records (e.g., accident...

  12. Apparatus for raising or tilting a micromechanical structure

    DOEpatents

    Allen, James J [Albuquerque, NM

    2008-09-09

    An active hinge apparatus is disclosed which can be used to raise a micromechanical structure (e.g. a plate or micromirror) on a substrate. The active hinge apparatus utilizes one or more of teeth protruding outward from an axle which also supports the micromechanical structure on one end thereof. A rack is used to engage the teeth and rotate the axle to raise the micromechanical structure and tilt the structure at an angle to the substrate. Motion of the rack is provided by an actuator which can be a mechanically-powered actuator, or alternately an electrostatic comb actuator or a thermal actuator. A latch can be optionally provided in the active hinge apparatus to lock the micromechanical structure in an "erected" position.

  13. Adaptive video-based vehicle classification technique for monitoring traffic : [executive summary].

    DOT National Transportation Integrated Search

    2015-08-01

    Federal Highway Administration (FHWA) recommends axle-based classification standards to map : passenger vehicles, single unit trucks, and multi-unit trucks, at Automatic Traffic Recorder (ATR) stations : statewide. Many state Departments of Transport...

  14. Three-dimensional derailment analysis of crashed freight trains

    NASA Astrophysics Data System (ADS)

    Zhou, Hechao; Zhang, Jimin; Hecht, Markus

    2014-03-01

    In this paper, the collision-induced derailment of freight trains was investigated. The collision between two identical freight trains occurring on a curved path rather than along a straight line was investigated. This is because from the point of view of safety against derailment this collision scenario is thought to be more critical than the scenarios defined in the European standard EN 15227. In this work, one of the trains is stationary and the other moving train collides at 36 km/h. Two kinds of container wagons were simulated. One is the two-axle freight wagon Kls 442. Another is the freight wagon Rmms 662 with two Y25 bogies. Simulation results demonstrate that in terms of safety against derailment the bogie wagon Rmms 662 was found to have better behaviour than the two-axle wagon Kls 442. In addition, this study points out that there are many contributory factors to the responses of freight wagons during a collision, such as curve radius, distance between bogie pivots and loading mass. The derailment phenomenon is less likely to occur, when freight trains collide on the curve with a larger radius. Besides that the characteristics of freight wagons with large axle loads, low centre of gravity of car body and appropriate static strength are favourable for the collided wagons in reducing the risk of derailment.

  15. Improved Apparatus for Measuring Distance Between Axles

    NASA Technical Reports Server (NTRS)

    Willard, Douglas E.; Townsend, Ivan I., III

    2003-01-01

    An improved version of an optoelectronic apparatus for measuring distances of the order of tens of feet with an error no larger than a small fraction of an inch (a few millimeters) has been built. Like the previous version, the present improved version of the apparatus is designed to measure the distance approximately equal to 66 ft (approximately equal to 20 m) between the axes of rotation of the front and rear tires of the space shuttle orbiter as it rests in a ground-based processing facility. Like the previous version, the present version could also be adapted for similar purposes in other settings: Examples include measuring perpendicular distance from a wall in a building, placement of architectural foundations, and general alignment and measurement operations.

  16. Glider kits cut truck ownership costs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Smiley, C.H.

    1983-06-01

    A glider kit consists of a new truck without the power train, with the customer supplying the engine, transmission, clutch, driveline and rear axles for mounting in a new frame and cab complete with steering axle, wiring harnesses, exhaust system and cooling system. Glider kits have long been regarded as a cost effective means of replacing accident or fire damaged late model vehicles. The financial advantages, assembly and remanufacturing are discussed. Points out that at a basic cost about one third of a new truck, a glider kit offers lower cost of borrowed capital, tax savings, and elimination of highmore » maintenance and downtime costs. The paper concludes that use of glider kits as an alternative to major repair or reconditioning or outright replacement of coal haulers presents some interesting options.« less

  17. Adaptive video-based vehicle classification technique for monitoring traffic.

    DOT National Transportation Integrated Search

    2015-08-01

    This report presents a methodology for extracting two vehicle features, vehicle length and number of axles in order : to classify the vehicles from video, based on Federal Highway Administration (FHWA)s recommended vehicle : classification scheme....

  18. Control of rolling contact fatigue on premium rails in revenue service.

    DOT National Transportation Integrated Search

    2014-11-01

    Effective rail maintenance strategies are : essential for controlling rolling contact fatigue : (RCF) and reducing wear of rails under heavy : axle load (HAL) operations. In an effort to : optimize rail maintenance strategies in revenue : service, Tr...

  19. Development of standardized component\\0x2010based equipment specifications and transition plan into a predictive maintenance strategy : final report.

    DOT National Transportation Integrated Search

    2015-12-01

    This project investigated INDOT equipment records and equipment industry standards to produce standard equipment specifications : and a predictive maintenance schedule for the more than 1100 single and tandem axle trucks in use at INDOT. The research...

  20. Rural ITS user needs

    DOT National Transportation Integrated Search

    1999-07-01

    The Truck Characteristics Study seeks to develop a better understanding of the physical characteristics of the national truck fleet. With automatic vehicle classifiers (AVC) and weigh-in-motion devices (WIM), only axle spacing and weight information ...

  1. Idaho AASHTOWare pavement ME design user's guide, version 1.1.

    DOT National Transportation Integrated Search

    2014-03-01

    The AASHTOWare Pavement ME Design procedure is based on mechanistic-empirical (M-E) design concepts. This means that the design procedure calculates pavement responses such as stresses, strains, and deflections under axle loads and climatic condition...

  2. Development of standardized component\\0x2010based equipment specifications and transition plan into a predictive maintenance strategy.

    DOT National Transportation Integrated Search

    2015-12-01

    This project investigated INDOT equipment records and equipment industry standards to produce standard equipment specifications : and a predictive maintenance schedule for the more than 1100 single and tandem axle trucks in use at INDOT. The research...

  3. 14 CFR 23.509 - Towing loads.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... reaction must be applied at the axle of the wheel to which the load is applied. Enough airplane inertia to achieve equilibrium must be applied. (ii) The loads must be reacted by airplane inertia. (d) The...

  4. 14 CFR 23.509 - Towing loads.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... reaction must be applied at the axle of the wheel to which the load is applied. Enough airplane inertia to achieve equilibrium must be applied. (ii) The loads must be reacted by airplane inertia. (d) The...

  5. 14 CFR 23.509 - Towing loads.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... reaction must be applied at the axle of the wheel to which the load is applied. Enough airplane inertia to achieve equilibrium must be applied. (ii) The loads must be reacted by airplane inertia. (d) The...

  6. 14 CFR 23.509 - Towing loads.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... reaction must be applied at the axle of the wheel to which the load is applied. Enough airplane inertia to achieve equilibrium must be applied. (ii) The loads must be reacted by airplane inertia. (d) The...

  7. Heavy truck data in Virginia : collection, uses, and needs.

    DOT National Transportation Integrated Search

    1988-01-01

    This report describes the collection and uses of heavy truck data by Virginia agencies. Data categories include: (I) classification counts, (2) accidents; (3) off-tracking; (4) passenger car equivalents (PCE), (5) equivalent axle load (EAL), (6) spee...

  8. Traffic load spectra for implementing and using the mechanistic-empirical pavement design guide in Georgia.

    DOT National Transportation Integrated Search

    2014-02-01

    The GDOT is preparing for implementation of the Mechanistic-Empirical Pavement Design : Guide (MEPDG). As part of this preparation, a statewide traffic load spectra program is being : developed for gathering truck axle loading data. This final report...

  9. International Guide to Highway Transportation Information: Volume 2 - Websites

    DOT National Transportation Integrated Search

    2013-10-01

    "This guide addresses the selection and use of axle loading defaults for Mechanistic-Empirical Pavement Design Guide (MEPDG) applications. The defaults were developed based on weigh-in-motion (WIM) data from the Long- Term Pavement Performance (LTPP)...

  10. Assessment of data collection for ESAL determinations for the Kentucky Transportation Cabinet, Division of Planning.

    DOT National Transportation Integrated Search

    2004-06-01

    The Kentucky Transportation Cabinet Cabinets Division of Planning collects weight data, traffic volume data, and vehicle classification data. These data are used as inputs to determine ESALs (equivalent single axle loads). ESALs are used in the pa...

  11. Hybrid organic-inorganic rotaxanes and molecular shuttles.

    PubMed

    Lee, Chin-Fa; Leigh, David A; Pritchard, Robin G; Schultz, David; Teat, Simon J; Timco, Grigore A; Winpenny, Richard E P

    2009-03-19

    The tetravalency of carbon and its ability to form covalent bonds with itself and other elements enables large organic molecules with complex structures, functions and dynamics to be constructed. The varied electronic configurations and bonding patterns of inorganic elements, on the other hand, can impart diverse electronic, magnetic, catalytic and other useful properties to molecular-level structures. Some hybrid organic-inorganic materials that combine features of both chemistries have been developed, most notably metal-organic frameworks, dense and extended organic-inorganic frameworks and coordination polymers. Metal ions have also been incorporated into molecules that contain interlocked subunits, such as rotaxanes and catenanes, and structures in which many inorganic clusters encircle polymer chains have been described. Here we report the synthesis of a series of discrete rotaxane molecules in which inorganic and organic structural units are linked together mechanically at the molecular level. Structural units (dialkyammonium groups) in dumb-bell-shaped organic molecules template the assembly of essentially inorganic 'rings' about 'axles' to form rotaxanes consisting of various numbers of rings and axles. One of the rotaxanes behaves as a 'molecular shuttle': the ring moves between two binding sites on the axle in a large-amplitude motion typical of some synthetic molecular machine systems. The architecture of the rotaxanes ensures that the electronic, magnetic and paramagnetic characteristics of the inorganic rings-properties that could make them suitable as qubits for quantum computers-can influence, and potentially be influenced by, the organic portion of the molecule.

  12. Gas6 Induces Growth, β-Catenin Stabilization, and T-Cell Factor Transcriptional Activation in Contact-Inhibited C57 Mammary Cells

    PubMed Central

    Goruppi, Sandro; Chiaruttini, Cristina; Ruaro, Maria Elisabetta; Varnum, Brian; Schneider, Claudio

    2001-01-01

    Gas6 is a growth factor related to protein S that was identified as the ligand for the Axl receptor tyrosine kinase (RTK) family. In this study, we show that Gas6 induces a growth response in a cultured mammalian mammary cell line, C57MG. The presence of Gas6 in the medium induces growth after confluence and similarly causes cell cycle reentry of density-inhibited C57MG cells. We show that Axl RTK but not Rse is efficiently activated by Gas6 in density-inhibited C57MG cells. We have analyzed the signaling required for the Gas6 proliferative effect and found a requirement for PI3K-, S6K-, and Ras-activated pathways. We also demonstrate that Gas6 activates Akt and concomitantly inhibits GSK3 activity in a wortmannin-dependent manner. Interestingly, Gas6 induces up-regulation of cytosolic β-catenin, while membrane-associated β-catenin remains unaffected. Stabilization of β-catenin in C57MG cells is correlated with activation of a T-cell factor (TCF)-responsive transcriptional element. We thus provide evidence that Gas6 is mitogenic and induces β-catenin proto-oncogene stabilization and subsequent TCF/Lef transcriptional activation in a mammary system. These results suggest that Gas6-Axl interaction, through stabilization of β-catenin, may have a role in mammary development and/or be involved in the progression of mammary tumors. PMID:11154277

  13. The TAM-family receptor Mer mediates production of HGF through the RhoA-dependent pathway in response to apoptotic cells.

    PubMed

    Park, Hyun-Jung; Baen, Ji-Yeon; Lee, Ye-Ji; Choi, Youn-Hee; Kang, Jihee Lee

    2012-08-01

    The TAM receptor protein tyrosine kinases Tyro3, Axl, and Mer play important roles in macrophage function. We investigated the roles of the TAM receptors in mediating the induction of hepatocyte growth factor (HGF) during the interaction of macrophages with apoptotic cells. Mer-specific neutralizing antibody, small interfering RNA (siRNA), and a recombinant Mer protein (Mer/Fc) inhibited HGF mRNA and protein expression, as well as activation of RhoA, Akt, and specific mitogen-activated protein (MAP) kinases in response to apoptotic cells. Inhibition of Axl or Tyro3 with specific antibodies, siRNA, or Fc-fusion proteins did not prevent apoptotic cell-induced HGF mRNA and protein expression and did not inhibit activation of the postreceptor signaling molecules RhoA and certain MAP kinases, including extracellular signal-regulated protein kinase and c-Jun NH(2)-terminal kinase. However, Axl- and Tyro3-specific blockers did inhibit the activation of Akt and p38 MAP kinase in response to apoptotic cells. In addition, none of the TAM receptors mediated the effects of apoptotic cells on transforming growth factor-β or epidermal growth factor mRNA expression. However, they were involved in the induction of vascular endothelial growth factor mRNA expression. Our data provide evidence that when macrophages interact with apoptotic cells, only Mer of the TAM-family receptors is responsible for mediating transcriptional HGF production through a RhoA-dependent pathway.

  14. Method and apparatus for steady-state magnetic measurement of poloidal magnetic field near a tokamak plasma

    DOEpatents

    Woolley, R.D.

    1998-09-08

    A method and apparatus are disclosed for the steady-state measurement of poloidal magnetic field near a tokamak plasma, where the tokamak is configured with respect to a cylindrical coordinate system having z, phi (toroidal), and r axes. The method is based on combining the two magnetic field principles of induction and torque. The apparatus includes a rotor assembly having a pair of inductive magnetic field pickup coils which are concentrically mounted, orthogonally oriented in the r and z directions, and coupled to remotely located electronics which include electronic integrators for determining magnetic field changes. The rotor assembly includes an axle oriented in the toroidal direction, with the axle mounted on pivot support brackets which in turn are mounted on a baseplate. First and second springs are located between the baseplate and the rotor assembly restricting rotation of the rotor assembly about its axle, the second spring providing a constant tensile preload in the first spring. A strain gauge is mounted on the first spring, and electronic means to continually monitor strain gauge resistance variations is provided. Electronic means for providing a known current pulse waveform to be periodically injected into each coil to create a time-varying torque on the rotor assembly in the toroidal direction causes mechanical strain variations proportional to the torque in the mounting means and springs so that strain gauge measurement of the variation provides periodic magnetic field measurements independent of the magnetic field measured by the electronic integrators. 6 figs.

  15. Method and apparatus for steady-state magnetic measurement of poloidal magnetic field near a tokamak plasma

    DOEpatents

    Woolley, Robert D.

    1998-01-01

    A method and apparatus for the steady-state measurement of poloidal magnetic field near a tokamak plasma, where the tokamak is configured with respect to a cylindrical coordinate system having z, phi (toroidal), and r axes. The method is based on combining the two magnetic field principles of induction and torque. The apparatus includes a rotor assembly having a pair of inductive magnetic field pickup coils which are concentrically mounted, orthogonally oriented in the r and z directions, and coupled to remotely located electronics which include electronic integrators for determining magnetic field changes. The rotor assembly includes an axle oriented in the toroidal direction, with the axle mounted on pivot support brackets which in turn are mounted on a baseplate. First and second springs are located between the baseplate and the rotor assembly restricting rotation of the rotor assembly about its axle, the second spring providing a constant tensile preload in the first spring. A strain gauge is mounted on the first spring, and electronic means to continually monitor strain gauge resistance variations is provided. Electronic means for providing a known current pulse waveform to be periodically injected into each coil to create a time-varying torque on the rotor assembly in the toroidal direction causes mechanical strain variations proportional to the torque in the mounting means and springs so that strain gauge measurement of the variation provides periodic magnetic field measurements independent of the magnetic field measured by the electronic integrators.

  16. 49 CFR 571.212 - Standard No. 212; Windshield mounting.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... forward control vehicles, walk-in van-type vehicles, or to open-body type vehicles with fold-down or... so that the weight on each axle as measured at the tire-ground interface is in proportion to its GAWR...

  17. 49 CFR 571.219 - Standard No. 219; Windshield zone intrusion.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... forward control vehicles, walk-in van-type vehicles, or to open-body-type vehicles with fold-down or... tire-ground interface is in proportion to its GAWR. If the mass on any axle when the vehicle is loaded...

  18. 49 CFR 571.212 - Standard No. 212; Windshield mounting.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... forward control vehicles, walk-in van-type vehicles, or to open-body type vehicles with fold-down or... so that the weight on each axle as measured at the tire-ground interface is in proportion to its GAWR...

  19. 49 CFR 571.219 - Standard No. 219; Windshield zone intrusion.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... forward control vehicles, walk-in van-type vehicles, or to open-body-type vehicles with fold-down or... tire-ground interface is in proportion to its GAWR. If the mass on any axle when the vehicle is loaded...

  20. 49 CFR 571.212 - Standard No. 212; Windshield mounting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... forward control vehicles, walk-in van-type vehicles, or to open-body type vehicles with fold-down or... so that the weight on each axle as measured at the tire-ground interface is in proportion to its GAWR...

  1. 49 CFR 571.219 - Standard No. 219; Windshield zone intrusion.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... forward control vehicles, walk-in van-type vehicles, or to open-body-type vehicles with fold-down or... tire-ground interface is in proportion to its GAWR. If the mass on any axle when the vehicle is loaded...

  2. 49 CFR 571.212 - Standard No. 212; Windshield mounting.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... forward control vehicles, walk-in van-type vehicles, or to open-body type vehicles with fold-down or... so that the weight on each axle as measured at the tire-ground interface is in proportion to its GAWR...

  3. 49 CFR 571.212 - Standard No. 212; Windshield mounting.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... forward control vehicles, walk-in van-type vehicles, or to open-body type vehicles with fold-down or... so that the weight on each axle as measured at the tire-ground interface is in proportion to its GAWR...

  4. 49 CFR 571.219 - Standard No. 219; Windshield zone intrusion.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... forward control vehicles, walk-in van-type vehicles, or to open-body-type vehicles with fold-down or... tire-ground interface is in proportion to its GAWR. If the mass on any axle when the vehicle is loaded...

  5. Use of permanent traffic recorder data to develop factors for traffic and truck variations

    DOT National Transportation Integrated Search

    2002-10-01

    This project entailed the development of the following four traffic volume adjustment factors from 1995 and 1996 permanent traffic recorder data: (1) A truck (axle) adjustment factor for single pneumatic tube counters; (2) A factor for estimating Des...

  6. Tie-ballast interaction.

    DOT National Transportation Integrated Search

    2015-09-28

    Improvements in railroad efficiency in the future may likely require higher passenger train speeds and heavier freight axle loads. As the demand for more efficient rail transportation grows, so does the need for higher performance and lower maintenan...

  7. Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy

    PubMed Central

    Angelillo-Scherrer, Anne; Burnier, Laurent; Flores, Nathalie; Savi, Pierre; DeMol, Maria; Schaeffer, Paul; Herbert, Jean-Marc; Lemke, Greg; Goff, Stephen P.; Matsushima, Glenn K.; Earp, H. Shelton; Vesin, Christian; Hoylaerts, Marc F.; Plaisance, Stéphane; Collen, Désiré; Conway, Edward M.; Wehrle-Haller, Bernhard; Carmeliet, Peter

    2005-01-01

    Mechanisms regulating thrombus stabilization remain largely unknown. Here, we report that loss of any 1 of the Gas6 receptors (Gas6-Rs), i.e., Tyro3, Axl, or Mer, or delivery of a soluble extracellular domain of Axl that traps Gas6 protects mice against life-threatening thrombosis. Loss of a Gas6-R does not prevent initial platelet aggregation but impairs subsequent stabilization of platelet aggregates, at least in part by reducing “outside-in” signaling and platelet granule secretion. Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the β3 integrin, thereby amplifying outside-in signaling via αIIbβ3. Blocking the Gas6-R–αIIbβ3 integrin cross-talk might be a novel approach to the reduction of thrombosis. PMID:15650770

  8. Motorizing fibres with geometric zero-energy modes

    NASA Astrophysics Data System (ADS)

    Baumann, Arthur; Sánchez-Ferrer, Antoni; Jacomine, Leandro; Martinoty, Philippe; Le Houerou, Vincent; Ziebert, Falko; Kulić, Igor M.

    2018-06-01

    Responsive materials1-3 have been used to generate structures with built-in complex geometries4-6, linear actuators7-9 and microswimmers10-12. These results suggest that complex, fully functional machines composed solely from shape-changing materials might be possible13. Nonetheless, to accomplish rotary motion in these materials still relies on the classical wheel and axle motifs. Here we explore geometric zero-energy modes to elicit rotary motion in elastic materials in the absence of a rigid wheel travelling around an axle. We show that prestrained polymer fibres closed into rings exhibit self-actuation and continuous motion when placed between two heat baths due to elastic deformations that arise from rotational-symmetry breaking around the rod's axis. Our findings illustrate a simple but robust model to create active motion in mechanically prestrained objects.

  9. Structural elucidation of the DFG-Asp in and DFG-Asp out states of TAM kinases and insight into the selectivity of their inhibitors.

    PubMed

    Messoussi, Abdellah; Peyronnet, Lucile; Feneyrolles, Clémence; Chevé, Gwénaël; Bougrin, Khalid; Yasri, Aziz

    2014-10-10

    Structural elucidation of the active (DFG-Asp in) and inactive (DFG-Asp out) states of the TAM family of receptor tyrosine kinases is required for future development of TAM inhibitors as drugs. Herein we report a computational study on each of the three TAM members Tyro-3, Axl and Mer. DFG-Asp in and DFG-Asp out homology models of each one were built based on the X-ray structure of c-Met kinase, an enzyme with a closely related sequence. Structural validation and in silico screening enabled identification of critical amino acids for ligand binding within the active site of each DFG-Asp in and DFG-Asp out model. The position and nature of amino acids that differ among Tyro-3, Axl and Mer, and the potential role of these residues in the design of selective TAM ligands, are discussed.

  10. [Atypical injury pattern of a pedestrian run over by an unimog in the epigastric region].

    PubMed

    Guddat, Saskia Sabrina; Müller-Rakow, Peter; Wiedmann, Peter; Püschel, Klaus; Tsokos, Michael

    2007-01-01

    Strongly intoxicated, a 37-year-old man fell in front of the right back wheel of an emergency vehicle (MB Unimog) and was run over according to eye witnesses. He died in hospital shortly afterwards. The autopsy revealed that he bled to death from a traumatic liver rupture (bursting of the right hepatic lobe and severing of a piece of tissue measuring 17 x 8 x 4 cm). There were no injuries classicaly seen in victims run over by a car. The atypical injury findings in this case are due to the special features of the accident vehicle: The Unimog (an all-wheel vehicle with a fixed rear axle and flat coils) struck the right side of the body lying on the street with its rear wheel and was then lifted over the body by its fixed axle without touching the left side.

  11. Traffic-load forecasting using weigh-in-motion data

    DOT National Transportation Integrated Search

    1997-03-01

    Vehicular traffic loading is a crucial consideration for the design and maintenance of pavements. With the help of weigh-in-motion (WIM) systems, the information about date, time, speed, lane of travel, lateral lane position, axle spacing, and wheel ...

  12. Truck Traffic Iowa : 2010

    DOT National Transportation Integrated Search

    2011-01-01

    Truck volumes represented on this map are Annual Average Daily Traffic Volumes between major traffic generators: i.e., Highway Junctions and Cities. : Truck volumes include 6-Tire and 3 Axle single unit trucks, buses and all multiple unit trucks.

  13. Verification, refinement, and applicability of long-term pavement performance vehicle classification rules.

    DOT National Transportation Integrated Search

    2014-11-01

    The Long-Term Pavement Performance (LTPP) project has developed and deployed a set of rules for converting axle spacing and weight data into estimates of a vehicles classification. These rules are being used at Transportation Pooled Fund Study (TP...

  14. Continuous vehicle classification data : how good is it?

    DOT National Transportation Integrated Search

    2000-08-01

    Florida has a lengthy history of trying to obtain continuous vehicle classification data. They installed their first piezoelectric axle sensors at a continuous count site in October of 1988. At that time, they had 86 continuous count sites operating ...

  15. Bridge Approach Remedies Implemented at Western Mega Site

    DOT National Transportation Integrated Search

    2017-09-01

    As part of the heavy axle load (HAL) revenue service mega site testing program, the Transportation Technology Center, Inc. (TTCI) has worked closely with the Union Pacific Railroad (UP) to address bridge approach problems under HAL operations. The te...

  16. Evaluation of adjacent AC and CRC pavement lanes : final report.

    DOT National Transportation Integrated Search

    1995-02-01

    On some of Oregon's highways, particularly on the interstate freeways in Eastern Oregon, most of the heavy trucks travel in the outside lane (right lane). With this kind of truck traffic pattern, the right lane experiences significantly higher axle l...

  17. Measurement of dowel bar response in rigid pavement

    DOT National Transportation Integrated Search

    1999-01-01

    The effectiveness of load transfer between adjacent slabs is an important component of long term rigid pavement performance. When load transfer is minimal or non-existent, concrete slabs must carry the full weight of truck axles across their entire l...

  18. Impact of increasing freight loads on rail substructure from fracking sand transportation.

    DOT National Transportation Integrated Search

    2014-03-01

    In this report the effect of surface infiltration of frac sand and heavy axle loads (HALs) were studied for their impact on the ballast layer. : Different combinations of ballast and fracking sand were constructed to observe long term trends of defor...

  19. Field and modeling framework and case study of truck weigh station operations

    DOT National Transportation Integrated Search

    2002-01-01

    Weigh-in-Motion (WIM) systems improve the capacity of weigh station operations significantly by screening trucks while traveling at high speeds and only requiring trucks within a threshold of a maximum permissible gross of axle weight to be weighed o...

  20. Statistical analysis of heavy truck loads using Wisconsin weigh-in-motion data

    DOT National Transportation Integrated Search

    2009-09-01

    This study involved statistical evaluation of heavy truck loads that were recorded in 2007 using Weigh-In-Motion : stations located throughout the State of Wisconsin. The heaviest 5% of all trucks in each class and axle groupings were : selected for ...

  1. Case study guidelines.

    DOT National Transportation Integrated Search

    2017-03-01

    In TxDOT project 0-6817, Review and Evaluation of Current Gross Vehicle Weights and Axle : Load Limits, the project team reviewed the estimated costs imposed by use of overweight (OW) : vehicles and ways to allocate costs to different vehicle classes...

  2. An investigation of site effeects on roadside measurement of truck noise

    DOT National Transportation Integrated Search

    1977-01-31

    Multi-microphone measurements of the passby noise emissions from three dedicated multi-axle trucks and from transient trucking were made at nine highway sites and one standard (SAE-J366b) measuring site. Measurements were made in and around Fort Wayn...

  3. Heavy Haul Access to U.S. Ports.

    DOT National Transportation Integrated Search

    2017-10-01

    Texas exporters are increasingly concerned that current overweight regulations do not allow for the full use of the capacity of oceangoing containers. Even with an over-axle/over-gross weight tolerance permit (also known as the HB 2060 permit), the o...

  4. Characterization of ocular biometrics and aqueous humor dynamics in primary angle closure suspects.

    PubMed

    Guo, Li; Deng, Yuan; Fang, Li; Liu, Chaoqi; Guo, Tao

    2017-02-01

    Detailed characterizations of ocular biometrics and parameters of aqueous humor dynamics are lacking in primary angle closure suspect (PACS) patients. This study aims to characterize these parameters and compare them with age-matched healthy volunteers.Elderly healthy volunteers (60.6 ± 7.2 years of age, mean ± SD, n = 28) and PACS patients (64.1 ± 11.6 years, n = 30) completed the study. Parameters investigated were axial length (AXL), anterior chamber depth (ACD), anterior chamber volume (ACV), central cornea thickness (CCT), intraocular pressure (IOP), aqueous flow (Fa), outflow facility (C), episcleral venous pressure (EVP), and uveoscleral outflow (Fu). Comparisons and correlations were made between and within groups.In healthy volunteers, ocular biometric parameters, IOP, and EVP correlated very well between the 2 eyes of each individual, but Fa, C, and Fu were not significantly correlated. Biometric parameters of the PACS group significantly (P < 0.001) differed from those of the healthy controls: AXL (23.31 ± 1.03 mm [PACS] vs 22.39 ± 1.04 mm [Control]; mean ± SD), ACD (2.44 ± 0.33 mm [PACS] vs 1.86 ± 0.25 mm [Control]), ACV (136.0 ± 36.1 μL [PACS] vs 81.4 ± 21.8 μL [Control]), CCT (526.9 ± 37.0 μm [PACS] vs 556.1 ± 28.4 μm [Control]). There was no significant change in IOP, Fa, C, EVP, or Fu between Control and PACS. Furthermore, IOP showed no significant correlations with AXL, ACD, ACV, CCT, or C in both groups.The PACS eyes had a shorter AXL, a shallower ACD, and a smaller ACV, but a thicker CCT. Despite these morphological changes, the PACS eyes did not have any significant changes in IOP, and aqueous humor dynamics parameters. This is consistent with the findings that IOP did not show significant correlations with biometrics, or C.

  5. Wind data from Kennedy Airport

    DOT National Transportation Integrated Search

    1997-06-01

    A 700-foot array of horizontal and vertical single-axle anemometers was installed at New York's Kennedy Airport on 30-foot poles under the approach to Runway 31R. One-minute average measurements were recorded continuously, with a few breaks, from Sep...

  6. Evaluation of the Viking-Cives towplow for winter maintenance.

    DOT National Transportation Integrated Search

    2014-01-01

    To maximize efficiency while minimizing costs within ODOTs winter maintenance budget, ODOT is : evaluating new methods of snow and ice removal. One method is the use of the Viking-Cives TowPlow. The : TowPlow is pulled behind a tandem axle truck a...

  7. UGV Interoperability Profile (IOP) - Overarching Profile JAUS Profiling Rules, Version 0

    DTIC Science & Technology

    2011-12-21

    negative values indicate pivot counter clockwise. - Multi- axle steering vehicles are not supported. Acceleration Limit A SetAcceleration limit...obtained from a Global Positioning Sensor (GPS), but may also be a combination of multiple sensor modalities that lead to a global pose referenced

  8. Quantifying the effects of on-the-fly changes of seating configuration on the stability of a manual wheelchair.

    PubMed

    Thomas, Louise; Borisoff, Jaimie; Sparrey, Carolyn J

    2017-07-01

    In general, manual wheelchairs are designed with a fixed frame, which is not optimal for every situation. Adjustable on the fly seating allow users to rapidly adapt their wheelchair configuration to suit different tasks. These changes move the center of gravity (CoG) of the system, altering the wheelchair stability and maneuverability. To assess these changes, a computer simulation of a manual wheelchair was created with adjustable seat, backrest, rear axle position and user position, and validated with experimental testing. The stability of the wheelchair was most affected by the position of the rear axle, but adjustments to the backrest and seat angles also result in stability improvements that could be used when wheeling in the community. These findings describe the most influential parameters for wheelchair stability and maneuverability, as well as provide quantitative guidelines for the use of manual wheelchairs with on the fly adjustable seats.

  9. Targeting Pediatric Glioma with Apoptosis and Autophagy Manipulation

    DTIC Science & Technology

    2012-08-01

    Task 2:  Evaluate autophagic flux following RTK inhibition.      2a.  Measure  p62  and BHMT levels. [Months 1‐3 and 16‐18]  Update Aug 2012‐‐‐ We have...inhibition in several different glioma cell lines  [Figure  3].   We  are  also  beginning  to  evaluate  p62   by  immunoblot  also.      ‐tubulin...P ar en ta l G FP M er 1 A M er 1 B M er 4 B Mer Axl CQ: LC3 ‐I LC3 ‐II U251WT shGFP shMer1A shAxl

  10. Selective Nitrate Recognition by a Halogen‐Bonding Four‐Station [3]Rotaxane Molecular Shuttle

    PubMed Central

    Barendt, Timothy A.; Docker, Andrew; Marques, Igor; Félix, Vítor

    2016-01-01

    Abstract The synthesis of the first halogen bonding [3]rotaxane host system containing a bis‐iodo triazolium‐bis‐naphthalene diimide four station axle component is reported. Proton NMR anion binding titration experiments revealed the halogen bonding rotaxane is selective for nitrate over the more basic acetate, hydrogen carbonate and dihydrogen phosphate oxoanions and chloride, and exhibits enhanced recognition of anions relative to a hydrogen bonding analogue. This elaborate interlocked anion receptor functions via a novel dynamic pincer mechanism where upon nitrate anion binding, both macrocycles shuttle from the naphthalene diimide stations at the periphery of the axle to the central halogen bonding iodo‐triazolium station anion recognition sites to form a unique 1:1 stoichiometric nitrate anion–rotaxane sandwich complex. Molecular dynamics simulations carried out on the nitrate and chloride halogen bonding [3]rotaxane complexes corroborate the 1H NMR anion binding results. PMID:27436297

  11. Distinguishing Two Ammonium and Triazolium Sites of Interaction in a Three-Station [2]Rotaxane Molecular Shuttle.

    PubMed

    Waelès, Philip; Fournel-Marotte, Karine; Coutrot, Frédéric

    2017-08-25

    This paper reports on the synthesis of a tri-stable [2]rotaxane molecular shuttle, in which the motion of the macrocycle is triggered by either selective protonation/deprotonation or specific carbamoylation/decarbamoylation of an alkylbenzylamine. The threaded axle is surrounded by a dibenzo[24]crown[8] (DB24C8) macrocycle and contains three sites of different binding affinities towards the macrocycle. An N-methyltriazolium moiety acts as a molecular station that has weak affinity for the DB24C8 macrocycle and is located in the centre of the molecular axle. Two other molecular stations, arylammonium and alkylbenzylammonium moieties, sit on either side of the triazolium moiety along the molecular axle and have stronger affinities for the DB24C8 macrocycle. These two ammonium moieties are covalently linked to two different stopper groups at each extremity of the thread: a tert-butylphenyl group and a substituted DB24C8 unit. Owing to steric hindrance, the former does not allow any π-π stacking interactions with the encircling DB24C8 macrocycle, whereas the latter residue does; therefore, this allows the discrimination of the two ammonium stations by the surrounding DB24C8 macrocycle in the fully protonated state. In the deprotonated state, the contrasting reactivity of the amine functional groups, as either a base or a nucleophile, allows for selective reactions that trigger the controlled shuttling of the macrocycle around the three molecular stations. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Traffic Feasibility Study for a Grade Separator at a Busy Intersection in Vellore

    NASA Astrophysics Data System (ADS)

    Vasantha Kumar, S.; Gulati, Himanshu; Arora, Shivam

    2017-11-01

    One of the byproduct of urbanization is traffic congestion and before suggesting any solutions to reduce congestion, understanding the present context becomes very important. Study of traffic volumes at busy intersections to find the percentage composition of different vehicle types, directional distribution and peak hour traffic volume is a first step towards understanding the present context of traffic. Hence in the present study, one of the busy intersections in Vellore, namely, Gandhi nagar intersection in Vellore-Katpadi road was selected and traffic flow data was collected using video surveys. It was found that at the selected intersection, the two wheelers and three wheelers alone share 80% of the total traffic when compared to other vehicle types. Nearly 700 trucks and multi axle trailers were observed to pass through the intersection during the analysis period of five hours. That is, on an average 2 trucks/multi axle trailers were passing through the intersection in each minute. As like in other major cities, entry of trucks and other heavy vehicles such as multi axle trailers into the city needs to be banned during peak hours for smooth flow of traffic within city limits. A highest hourly volume of 6939 PCU’s was observed between 4 and 5 pm at the selected intersection. By assuming a 10% uniform traffic growth every year, it was found that after about 4 years, i.e., in 2019, the traffic volume at the intersection may reach 10,000 PCU’s and may warrant for a grade separator or interchange at the intersection.

  13. Sparsity guided empirical wavelet transform for fault diagnosis of rolling element bearings

    NASA Astrophysics Data System (ADS)

    Wang, Dong; Zhao, Yang; Yi, Cai; Tsui, Kwok-Leung; Lin, Jianhui

    2018-02-01

    Rolling element bearings are widely used in various industrial machines, such as electric motors, generators, pumps, gearboxes, railway axles, turbines, and helicopter transmissions. Fault diagnosis of rolling element bearings is beneficial to preventing any unexpected accident and reducing economic loss. In the past years, many bearing fault detection methods have been developed. Recently, a new adaptive signal processing method called empirical wavelet transform attracts much attention from readers and engineers and its applications to bearing fault diagnosis have been reported. The main problem of empirical wavelet transform is that Fourier segments required in empirical wavelet transform are strongly dependent on the local maxima of the amplitudes of the Fourier spectrum of a signal, which connotes that Fourier segments are not always reliable and effective if the Fourier spectrum of the signal is complicated and overwhelmed by heavy noises and other strong vibration components. In this paper, sparsity guided empirical wavelet transform is proposed to automatically establish Fourier segments required in empirical wavelet transform for fault diagnosis of rolling element bearings. Industrial bearing fault signals caused by single and multiple railway axle bearing defects are used to verify the effectiveness of the proposed sparsity guided empirical wavelet transform. Results show that the proposed method can automatically discover Fourier segments required in empirical wavelet transform and reveal single and multiple railway axle bearing defects. Besides, some comparisons with three popular signal processing methods including ensemble empirical mode decomposition, the fast kurtogram and the fast spectral correlation are conducted to highlight the superiority of the proposed method.

  14. The economics of potential reduction of the rural road system in Kansas : technical summary.

    DOT National Transportation Integrated Search

    2011-11-01

    The increasing size of farms in Kansas has led to increasing farm vehicle size as well. Tractor and combine weight and width has increased and the majority of farmers deliver their grain in semi-trucks. Tandem axle trucks are used to deliver farm sup...

  15. 10. 22'X34' original blueprint, VariableAngle Launcher, 'SIDE VIEW CAMERA CARSTEEL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. 22'X34' original blueprint, Variable-Angle Launcher, 'SIDE VIEW CAMERA CAR-STEEL FRAME AND AXLES' drawn at 1/2'=1'-0'. (BOURD Sketch # 209124). - Variable Angle Launcher Complex, Camera Car & Track, CA State Highway 39 at Morris Reservior, Azusa, Los Angeles County, CA

  16. 77 FR 60285 - Airworthiness Directives; The Boeing Company Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-03

    ... the MLG for chicken- wire cracks, corrosion, and chrome plate distress; repetitive magnetic particle... center axles of the MLG for chicken-wire cracks, corrosion, and chrome plate distress; repetitive... the MLG for chicken- wire cracks, corrosion, and chrome plate distress; do a magnetic particle...

  17. 24 CFR 3280.902 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... provides a platform for securement of the running gear assembly, the drawbar and coupling mechanism. (d) Running gear assembly means the subsystem consisting of suspension springs, axles, bearings, wheels, hubs... mechanism, frame, running gear assembly, and lights. (b) Drawbar and coupling mechanism means the rigid...

  18. Procedures for controlling the effect of increased tire pressure on asphalt concrete pavement damage.

    DOT National Transportation Integrated Search

    1988-06-01

    As the axle load increases, higher tire pressures become more popular for long-haul truck operators. To collect data on tire pressures and the types of tires in use, a survey was carried out at a weigh station located on Interstate 5 in Oregon during...

  19. Axle equivalent transverse loading on segmental bridge decks.

    DOT National Transportation Integrated Search

    2014-04-01

    For a prestressed concrete segmental box girder bridge, both design and load rating are determined by : longitudinal and transverse analyses. A transverse analysis is performed for the top slab, typically by : using Homberg charts (an engineers de...

  20. A loading study of older highway bridges in Virginia. Pt. 2, Concrete slab and steel beam bridge in Clarke County.

    DOT National Transportation Integrated Search

    1976-01-01

    A 60-foot non-composite steel beam and concrete deck highway bridge span over the Shenandoah River on Route 7 in Clarke County was tested with a 23-ton, tandem axle test vehicle in July1975. Strain gages were placed near midspan on the lower flanges,...

  1. Every Day a New 3D Printing Material

    ERIC Educational Resources Information Center

    Hughes, Bill; Mona, Lynn; Wilson, Greg; Seamans, Jeff; McAninch, Steve; Stout, Heath

    2017-01-01

    A handful of technological episodes: fire, wheel and axle, Industrial Revolution, Faraday's discovery of electromagnetic induction, the transistor, and the digital age, have historically altered humanity. We are now witnessing/participating in the next transformational technology: 3D printing. Although dating back nearly 30 years, the technology…

  2. Quantifying the effects of conservation practice implementation on predicted runoff and chemical losses under climate change

    USDA-ARS?s Scientific Manuscript database

    The Soil and Water Assessment Tool with downscaled weather data generated using the MarkSim weather file generator was used to evaluate the impact of long-term conservation practice implementation on runoff, sediment, atrazine, nitrogen (N) and phosphorus (P) losses in the AXL Watershed located in n...

  3. Evaluating the Effects of Restraint Systems on 4WD Testing Methodologies: A Collaborative Effort between the NVFEL and ANL

    EPA Science Inventory

    Testing vehicles for emissions and fuel economy has traditionally been conducted with a single-axle chassis dynamometer. The 2006 SAE All Wheel Drive Symposium cited four wheel drive (4WD) and all wheel drive (AWD) sales as climbing from 20% toward 30% of a motor vehicle mar...

  4. 78 FR 72861 - Foreign-Trade Zone (FTZ) 20-Suffolk, Virginia, Notification of Proposed Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-04

    ... status components used in export production. On its domestic sales, GEC would be able to choose the duty...; winches; axles; tire-rim assemblies; clips; pins; brackets; bolts; junction plates; tower masts; shaped springs; shaped pipes; brackets; mufflers; stabilizer legs; locks; top covers; air springs; door plates...

  5. Long-Term Performance Evaluation of Asphalt Surface Treatments: Product Placement

    DTIC Science & Technology

    2010-02-01

    20 Wheeler-Sack Army Airfield, Fort Drum , New York ...............................................................28 4...Grip Tester underside view ................................................................................ 6 Figure 3. Rotating disc of Dynamic...measures pavement friction using the braked -wheel, fixed-slip principle. Two wheels support the Grip Tester on a drive axle, while a measuring wheel with

  6. Better Seals for Vacuum Bags

    NASA Technical Reports Server (NTRS)

    Penn, B.; Clemons, J. M.

    1983-01-01

    Roller tool spreads even layer of adhesive. Tool easily constructed from metal, plastic, or wood. Sewing-thread spool serves as roller, nail as axle, and jigsawed block of wood as handle. Tool rolled and pressed against plastic film to assure even layer of adhesive around periphery.

  7. 49 CFR 585.63 - Applicability.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... passenger cars, multipurpose passenger vehicles, trucks, and buses with a gross vehicle weight rating of 4,536 kilograms (10,000 pounds) or less, except those vehicles with dual wheels on an axle. However, this subpart does not apply to manufacturers whose production consists exclusively of vehicles...

  8. Performance of a logging truck with a central tire inflation system.

    Treesearch

    John A. Sturos; Douglas B. Brumm; Andrew Lehto

    1995-01-01

    Describes the performance of an 11-axle logging truck with a central tire inflation system. Results included reduced damages to roads, improved ride of the truck, improved drawbar pull, and reduced rolling resistance. Road construction costs were reduced 62%, primarily due to using 33% less gravel.

  9. 40 CFR 86.085-37 - Production vehicles and engines.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .... (d) The following definitions apply to this section: (1) Model type means a unique combination of car..., inertia weight, and transmission class. (3) Vehicle configuration means a unique combination of basic engine, engine code, inertia weight, transmission configuration, and axle ratio within a base level. [48...

  10. 40 CFR 86.085-37 - Production vehicles and engines.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    .... (d) The following definitions apply to this section: (1) Model type means a unique combination of car..., inertia weight, and transmission class. (3) Vehicle configuration means a unique combination of basic engine, engine code, inertia weight, transmission configuration, and axle ratio within a base level. [48...

  11. Dynamic Measurement for the Diameter of A Train Wheel Based on Structured-Light Vision

    PubMed Central

    Gong, Zheng; Sun, Junhua; Zhang, Guangjun

    2016-01-01

    Wheels are very important for the safety of a train. The diameter of the wheel is a significant parameter that needs regular inspection. Traditional methods only use the contact points of the wheel tread to fit the rolling round. However, the wheel tread is easily influenced by peeling or scraping. Meanwhile, the circle fitting algorithm is sensitive to noise when only three points are used. This paper proposes a dynamic measurement method based on structured-light vision. The axle of the wheelset and the tread are both employed. The center of the rolling round is determined by the axle rather than the tread only. Then, the diameter is calculated using the center and the contact points together. Simulations are performed to help design the layout of the sensors, and the influences of different noise sources are also analyzed. Static and field experiments are both performed, and the results show it to be quite stable and accurate. PMID:27104543

  12. Traction drive automatic transmission for gas turbine engine driveline

    DOEpatents

    Carriere, Donald L.

    1984-01-01

    A transaxle driveline for a wheeled vehicle has a high speed turbine engine and a torque splitting gearset that includes a traction drive unit and a torque converter on a common axis transversely arranged with respect to the longitudinal centerline of the vehicle. The drive wheels of the vehicle are mounted on a shaft parallel to the turbine shaft and carry a final drive gearset for driving the axle shafts. A second embodiment of the final drive gearing produces an overdrive ratio between the output of the first gearset and the axle shafts. A continuously variable range of speed ratios is produced by varying the position of the drive rollers of the traction unit. After starting the vehicle from rest, the transmission is set for operation in the high speed range by engaging a first lockup clutch that joins the torque converter impeller to the turbine for operation as a hydraulic coupling.

  13. Dynamic Measurement for the Diameter of A Train Wheel Based on Structured-Light Vision.

    PubMed

    Gong, Zheng; Sun, Junhua; Zhang, Guangjun

    2016-04-20

    Wheels are very important for the safety of a train. The diameter of the wheel is a significant parameter that needs regular inspection. Traditional methods only use the contact points of the wheel tread to fit the rolling round. However, the wheel tread is easily influenced by peeling or scraping. Meanwhile, the circle fitting algorithm is sensitive to noise when only three points are used. This paper proposes a dynamic measurement method based on structured-light vision. The axle of the wheelset and the tread are both employed. The center of the rolling round is determined by the axle rather than the tread only. Then, the diameter is calculated using the center and the contact points together. Simulations are performed to help design the layout of the sensors, and the influences of different noise sources are also analyzed. Static and field experiments are both performed, and the results show it to be quite stable and accurate.

  14. Lateral dynamic interaction analysis of a train girder pier system

    NASA Astrophysics Data System (ADS)

    Xia, H.; Guo, W. W.; Wu, X.; Pi, Y. L.; Bradford, M. A.

    2008-12-01

    A dynamic model of a coupled train-girder-pier system is developed in this paper. Each vehicle in a train is modeled with 27 degrees-of-freedom for a 4-axle passenger coach or freight car, and 31 for a 6-axle locomotive. The bridge model is applicable to straight and curved bridges. The centrifugal forces of moving vehicles on curved bridges are considered in both the vehicle model and the bridge model. The dynamic interaction between the bridge and train is realized through an assumed wheel-hunting movement. A case study is performed for a test train traversing two straight and two curved multi-span bridges with high piers. The histories of the train traversing the bridges are simulated and the dynamic responses of the piers and the train vehicles are calculated. A field experiment is carried out to verify the results of the analysis, by which the lateral resonant train speed inducing the peak pier-top amplitudes and some other observations are validated.

  15. The TAM receptor Mertk protects against neuroinvasive viral infection by maintaining blood-brain barrier integrity.

    PubMed

    Miner, Jonathan J; Daniels, Brian P; Shrestha, Bimmi; Proenca-Modena, Jose L; Lew, Erin D; Lazear, Helen M; Gorman, Matthew J; Lemke, Greg; Klein, Robyn S; Diamond, Michael S

    2015-12-01

    The TAM receptors Tyro3, Axl and Mertk are receptor tyrosine kinases that dampen host innate immune responses following engagement with their ligands Gas6 and Protein S, which recognize phosphatidylserine on apoptotic cells. In a form of apoptotic mimicry, many enveloped viruses display phosphatidylserine on the outer leaflet of their membranes, enabling TAM receptor activation and downregulation of antiviral responses. Accordingly, we hypothesized that a deficiency of TAM receptors would enhance antiviral responses and protect against viral infection. Unexpectedly, mice lacking Mertk and/or Axl, but not Tyro3, exhibited greater vulnerability to infection with neuroinvasive West Nile and La Crosse encephalitis viruses. This phenotype was associated with increased blood-brain barrier permeability, which enhanced virus entry into and infection of the brain. Activation of Mertk synergized with interferon-β to tighten cell junctions and prevent virus transit across brain microvascular endothelial cells. Because TAM receptors restrict pathogenesis of neuroinvasive viruses, these findings have implications for TAM antagonists that are currently in clinical development.

  16. Helical screw viscometer

    DOEpatents

    Aubert, J.H.; Chapman, R.N.; Kraynik, A.M.

    1983-06-30

    A helical screw viscometer for the measurement of the viscosity of Newtonian and non-Newtonian fluids comprising an elongated cylindrical container closed by end caps defining a circular cylindrical cavity within the container, a cylindrical rotor member having a helical screw or ribbon flight carried by the outer periphery thereof rotatably carried within the cavity whereby the fluid to be measured is confined in the cavity filling the space between the rotor and the container wall. The rotor member is supported by axle members journaled in the end caps, one axle extending through one end cap and connectable to a drive source. A pair of longitudinally spaced ports are provided through the wall of the container in communication with the cavity and a differential pressure meter is connected between the ports for measuring the pressure drop caused by the rotation of the helical screw rotor acting on the confined fluid for computing viscosity.

  17. Principle of maximum entropy for reliability analysis in the design of machine components

    NASA Astrophysics Data System (ADS)

    Zhang, Yimin

    2018-03-01

    We studied the reliability of machine components with parameters that follow an arbitrary statistical distribution using the principle of maximum entropy (PME). We used PME to select the statistical distribution that best fits the available information. We also established a probability density function (PDF) and a failure probability model for the parameters of mechanical components using the concept of entropy and the PME. We obtained the first four moments of the state function for reliability analysis and design. Furthermore, we attained an estimate of the PDF with the fewest human bias factors using the PME. This function was used to calculate the reliability of the machine components, including a connecting rod, a vehicle half-shaft, a front axle, a rear axle housing, and a leaf spring, which have parameters that typically follow a non-normal distribution. Simulations were conducted for comparison. This study provides a design methodology for the reliability of mechanical components for practical engineering projects.

  18. Selective Nitrate Recognition by a Halogen-Bonding Four-Station [3]Rotaxane Molecular Shuttle.

    PubMed

    Barendt, Timothy A; Docker, Andrew; Marques, Igor; Félix, Vítor; Beer, Paul D

    2016-09-05

    The synthesis of the first halogen bonding [3]rotaxane host system containing a bis-iodo triazolium-bis-naphthalene diimide four station axle component is reported. Proton NMR anion binding titration experiments revealed the halogen bonding rotaxane is selective for nitrate over the more basic acetate, hydrogen carbonate and dihydrogen phosphate oxoanions and chloride, and exhibits enhanced recognition of anions relative to a hydrogen bonding analogue. This elaborate interlocked anion receptor functions via a novel dynamic pincer mechanism where upon nitrate anion binding, both macrocycles shuttle from the naphthalene diimide stations at the periphery of the axle to the central halogen bonding iodo-triazolium station anion recognition sites to form a unique 1:1 stoichiometric nitrate anion-rotaxane sandwich complex. Molecular dynamics simulations carried out on the nitrate and chloride halogen bonding [3]rotaxane complexes corroborate the (1) H NMR anion binding results. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  19. Vehicle systems: coupled and interactive dynamics analysis

    NASA Astrophysics Data System (ADS)

    Vantsevich, Vladimir V.

    2014-11-01

    This article formulates a new direction in vehicle dynamics, described as coupled and interactive vehicle system dynamics. Formalised procedures and analysis of case studies are presented. An analytical consideration, which explains the physics of coupled system dynamics and its consequences for dynamics of a vehicle, is given for several sets of systems including: (i) driveline and suspension of a 6×6 truck, (ii) a brake mechanism and a limited slip differential of a drive axle and (iii) a 4×4 vehicle steering system and driveline system. The article introduces a formal procedure to turn coupled system dynamics into interactive dynamics of systems. A new research direction in interactive dynamics of an active steering and a hybrid-electric power transmitting unit is presented and analysed to control power distribution between the drive axles of a 4×4 vehicle. A control strategy integrates energy efficiency and lateral dynamics by decoupling dynamics of the two systems thus forming their interactive dynamics.

  20. A novel serrated columnar phased array ultrasonic transducer

    NASA Astrophysics Data System (ADS)

    Zou, Cheng; Sun, Zhenguo; Cai, Dong; Song, Hongwei; Chen, Qiang

    2016-02-01

    Traditionally, wedges are required to generate transverse waves in a solid specimen and mechanical rotation device is needed for interrogation of a specimen with a hollow bore, such as high speed railway locomotive axles, turbine rotors, etc. In order to eliminate the mechanical rotation process, a novel array pattern of phased array ultrasonic transducers named as serrated columnar phased array ultrasonic transducer (SCPAUT) is designed. The elementary transducers are planar rectangular, located on the outside surface of a cylinder. This layout is aimed to generate electrically rotating transverse waveforms so as to inspect the longitudinal cracks on the outside surface of a specimen which has a hollow bore at the center, such as the high speed railway locomotive axles. The general geometry of the SCPAUT and the inspection system are illustrated. A FEM model and mockup experiment has been carried out. The experiment results are in good agreement with the FEM simulation results.

  1. Design and development of split-parallel through-the road retrofit hybrid electric vehicle with in-wheel motors

    NASA Astrophysics Data System (ADS)

    Zulkifli, S. A.; Syaifuddin Mohd, M.; Maharun, M.; Bakar, N. S. A.; Idris, S.; Samsudin, S. H.; Firmansyah; Adz, J. J.; Misbahulmunir, M.; Abidin, E. Z. Z.; Syafiq Mohd, M.; Saad, N.; Aziz, A. R. A.

    2015-12-01

    One configuration of the hybrid electric vehicle (HEV) is the split-axle parallel hybrid, in which an internal combustion engine (ICE) and an electric motor provide propulsion power to different axles. A particular sub-type of the split-parallel hybrid does not have the electric motor installed on board the vehicle; instead, two electric motors are placed in the hubs of the non-driven wheels, called ‘hub motor’ or ‘in-wheel motor’ (IWM). Since propulsion power from the ICE and IWM is coupled through the vehicle itself, its wheels and the road on which it moves, this particular configuration is termed ‘through-the-road’ (TTR) hybrid. TTR configuration enables existing ICE-powered vehicles to be retrofitted into an HEV with minimal physical modification. This work describes design of a retrofit- conversion TTR-IWM hybrid vehicle - its sub-systems and development work. Operating modes and power flow of the TTR hybrid, its torque coupling and resultant traction profiles are initially discussed.

  2. Correlation of track irregularities and vehicle responses based on measured data

    NASA Astrophysics Data System (ADS)

    Karis, Tomas; Berg, Mats; Stichel, Sebastian; Li, Martin; Thomas, Dirk; Dirks, Babette

    2018-06-01

    Track geometry quality and dynamic vehicle response are closely related, but do not always correspond with each other in terms of maximum values and standard deviations. This can often be seen to give poor results in analyses with correlation coefficients or regression analysis. Measured data from both the EU project DynoTRAIN and the Swedish Green Train (Gröna Tåget) research programme is used in this paper to evaluate track-vehicle response for three vehicles. A single degree of freedom model is used as an inspiration to divide track-vehicle interaction into three parts, which are analysed in terms of correlation. One part, the vertical axle box acceleration divided by vehicle speed squared (?) and the second spatial derivative of the vertical track irregularities (?), is shown to be the weak link with lower correlation coefficients than the other parts. Future efforts should therefore be directed towards investigating the relation between axle box accelerations and track irregularity second derivatives.

  3. The Effect of Friction in Pulleys on the Tension in Cables and Strings

    NASA Astrophysics Data System (ADS)

    Martell, Eric C.; Martell, Verda Beth

    2013-02-01

    Atwood's machine is used in countless introductory physics classes as an illustration of Newton's second law. Initially, the analysis is performed assuming the pulley and string are massless and the axle is frictionless. Although the mass of the pulley is often included when the problem is revisited later in the context of rotational dynamics, the mass of the string and the friction associated with the axle are less frequently discussed. Two questions then arise: 1) If we are ignoring these effects, how realistic is our model? and 2) How can we determine when or if we need to incorporate these effects in order to make our model match up with reality? These questions are connected to fundamental issues faced by physics teachers, namely the frustration students sometimes feel when they do not see how they can use the results of the problems they have been working on and how we can help our students develop effective models for physical systems.

  4. 40 CFR 1066.210 - Dynamometers.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... to recreate the mechanical inertia and frictional forces that a vehicle exerts on road surfaces... drive axles may share a single drive roll. Use good engineering judgment to ensure that the dynamometer... engineering judgment. (3) The load applied by the dynamometer simulates forces acting on the vehicle during...

  5. A loading study of older highway bridges in Virginia. Pt. 3, Concrete tee-beam bridge in Nelson County.

    DOT National Transportation Integrated Search

    1977-01-01

    A 40-foot clear span, standard reinforced tee-beam bridge over the Tye River in Nelson County was tested with a 23-ton, tandem axle test vehicle in July 1976. The test span was one of four identical spans making a total bridge length of 170 feet. Str...

  6. Serum sex hormone and growth arrest-specific protein 6 levels in male patients with coronary heart disease.

    PubMed

    Zhao, Rui; Li, Yan; Dai, Wen

    2016-01-01

    Epidemiological studies have shown a high prevalence of low serum testosterone levels in men with cardiovascular disease. Moreover, the tyrosine kinase receptor Axl, the ligand of which is growth arrest-specific protein 6 (GAS6), is expressed in the vasculature, and serum GAS6 levels are associated with endothelial dysfunction and cardiovascular events. Testosterone regulates GAS6 gene transcription directly, which inhibits calcification of vascular smooth muscle cells and provides a mechanistic insight into the cardioprotective action of androgens. This study was designed to determine the correlation between serum GAS6 and testosterone levels in male patients with coronary heart disease (CHD). We recruited 225 patients with CHD and 102 apparently healthy controls. Serum concentrations of GAS6 and soluble Axl were quantified by an enzyme-linked immunosorbent assay. Levels of high-sensitivity C-reactive protein, testosterone, estradiol, and other routine biochemical markers were also measured. Testosterone decreased from 432.69 ± 14.40 to 300.76 ± 6.23 ng dl-1 (P < 0.001) and GAS6 decreased from 16.20 ± 0.31 to 12.51 ± 0.19 ng ml-1 (P < 0.001) in patients with CHD, compared with control subjects. Multiple linear regression analysis showed that serum testosterone and GAS6 levels were positively associated in male patients with CHD. Alterations in GAS6 levels may influence the development of CHD. Downregulation of GAS6/Axl signaling in the presence of low sex hormone levels during disease progression is a potential mechanism by which GAS6 affects CHD. This study provides novel results regarding the influence of sex hormones on serum GAS6 levels in patients with CHD.

  7. Increased Circulating and Urinary Levels of Soluble TAM Receptors in Diabetic Nephropathy.

    PubMed

    Ochodnicky, Peter; Lattenist, Lionel; Ahdi, Mohamed; Kers, Jesper; Uil, Melissa; Claessen, Nike; Leemans, Jaklien C; Florquin, Sandrine; Meijers, Joost C M; Gerdes, Victor E A; Roelofs, Joris J T H

    2017-09-01

    TAM receptors (Tyro3, Axl, and Mer) have been implicated in innate immunity. Circulating TAM receptor soluble forms (sTyro3, sAxl, sMer) are related to autoimmune disorders. We investigated TAM and their ligand protein S in patients with diabetes. Urinary and plasma levels of protein S, sTyro3, sAxl, and sMer were determined in 126 patients with diabetes assigned to a normoalbuminuric or macroalbuminuric (urinary albumin excretion <30 mg/24 hours and >300 mg/24 hours, respectively) study group and 18 healthy volunteers. TAM and protein S immunostaining was performed on kidney biopsy specimens from patients with diabetic nephropathy (n = 9) and controls (n = 6). TAM expression and shedding by tubular epithelial cells were investigated by PCR and enzyme-linked immunosorbent assay in an in vitro diabetes model. Patients with macroalbuminuria diabetes had higher circulating levels of sMer and more urinary sTyro3 and sMer than normoalbuminuric diabetics. Increased clearance of sTyro3 and sMer was associated with loss of tubular Tyro3 and Mer expression in diabetic nephropathy tissue and glomerular depositions of protein S. During in vitro diabetes, human kidney cells had down-regulation of Tyro3 and Mer mRNA and increased shedding of sTyro3 and sMer. Renal injury in diabetes is associated with elevated systemic and urine levels of sMer and sTyro3. This is the first study reporting excretion of sTAM receptors in urine, identifying the kidney as a source of sTAM. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  8. 77 FR 25647 - Airworthiness Directives; The Boeing Company Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-01

    ... inspections of the outer diameter chrome on the center axles of the MLG for cracks; and related investigative... MLG for cracks; and related investigative and corrective actions if necessary. The related... operators Lubrication of MLG pivot joints.. 4 work-hours x $85 $0 $340 per $54,400 per per hour = $340...

  9. Why Wheels Work.

    ERIC Educational Resources Information Center

    Stepp, Richard D.

    1982-01-01

    Discusses how the wheel works. The inherent mechanical advantage of wheel-and-axle system is that it reduced the distance the load-bearing surfaces have to slip relative to one another when the whole apparatus advances some given distance reducing (with leverage) the force needed to propel the system. (Author/JN)

  10. 76 FR 68306 - Airworthiness Directives; Bombardier, Inc. Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ... another country to identify and correct an unsafe condition on an aviation product. The MCAI describes the... axle thrust face, damage to the protective coating and consequent stress corrosion. In both cases, the... coating and consequent stress corrosion. In both cases, the MLG did not collapse. In order to avoid future...

  11. Snowmobile Repair. Teacher Edition.

    ERIC Educational Resources Information Center

    Hennessy, Stephen S.; Conrad, Rex

    This teacher's guide contains 14 units on snowmobile repair: (1) introduction to snowmobile repair; (2) skis, front suspension, and steering; (3) drive clutch; (4) drive belts; (5) driven clutch; (6) chain drives; (7) jackshafts and axles; (8) rear suspension; (9) tracks; (10) shock absorbers; (11) brakes; (12) engines; (13) ignition and…

  12. 76 FR 31354 - Notice of Issuance of Final Determination Concerning the Transit Connect Electric Vehicle

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-31

    ... base without a powertrain or exhaust components, and consists of a frame, body, axles, and wheels. The... substantially transformed in the U.S. and considered products of the U.S. The U.S. assembly occurs at various stations. The assembly stations at AM General, the manufacturing subcontractor, are described as follows...

  13. 49 CFR 393.47 - Brake actuators, slack adjusters, linings/pads and drums/rotors.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Brake actuators, slack adjusters, linings/pads and..., slack adjusters, linings/pads and drums/rotors. (a) General requirements. Brake components must be... same size. (c) Slack adjusters. The effective length of the slack adjuster on each end of an axle must...

  14. 40 CFR 86.1702-99 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... to a point of first sale in the All States Trading Region. Axle ratio means the number of times the... is below the applicable fleet average NMOG standard, times the applicable production for a given... average NMOG standard, times the applicable production for a given model year. NMOG debits have units of g...

  15. 40 CFR 86.1702-99 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... to a point of first sale in the All States Trading Region. Axle ratio means the number of times the... is below the applicable fleet average NMOG standard, times the applicable production for a given... average NMOG standard, times the applicable production for a given model year. NMOG debits have units of g...

  16. 49 CFR 585.61 - Scope.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... passenger cars, multipurpose passenger vehicles, trucks, and buses with a gross vehicle weight rating of 4,536 kilograms (10,000 pounds) or less, except those vehicles with dual wheels on an axle, to submit a report, and maintain records related to the report, concerning the number of such vehicles that meet the...

  17. 40 CFR 86.602-98 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 19 2011-07-01 2011-07-01 false Definitions. 86.602-98 Section 86.602... Auditing of New Light-Duty Vehicles, Light-Duty Trucks, and Heavy-Duty Vehicles § 86.602-98 Definitions..., inertia weight class, transmission type and gear ratios, axle ratio, and other parameters which may be...

  18. 40 CFR 86.602-98 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 19 2010-07-01 2010-07-01 false Definitions. 86.602-98 Section 86.602... Auditing of New Light-Duty Vehicles, Light-Duty Trucks, and Heavy-Duty Vehicles § 86.602-98 Definitions..., inertia weight class, transmission type and gear ratios, axle ratio, and other parameters which may be...

  19. 40 CFR 86.602-98 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 20 2012-07-01 2012-07-01 false Definitions. 86.602-98 Section 86.602... Auditing of New Light-Duty Vehicles, Light-Duty Trucks, and Heavy-Duty Vehicles § 86.602-98 Definitions..., inertia weight class, transmission type and gear ratios, axle ratio, and other parameters which may be...

  20. 40 CFR 86.1102-87 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 19 2014-07-01 2014-07-01 false Definitions. 86.1102-87 Section 86....1102-87 Definitions. (a) The definitions in this section apply to this subpart. (b) As used in this..., inertia weight class, transmission type and gear ratios, rear axle ratio, or other parameters which may be...

  1. 40 CFR 86.602-98 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 20 2013-07-01 2013-07-01 false Definitions. 86.602-98 Section 86.602... Auditing of New Light-Duty Vehicles, Light-Duty Trucks, and Heavy-Duty Vehicles § 86.602-98 Definitions..., inertia weight class, transmission type and gear ratios, axle ratio, and other parameters which may be...

  2. 40 CFR 86.602-98 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 19 2014-07-01 2014-07-01 false Definitions. 86.602-98 Section 86.602... New Light-Duty Vehicles, Light-Duty Trucks, and Heavy-Duty Vehicles § 86.602-98 Definitions. Section..., inertia weight class, transmission type and gear ratios, axle ratio, and other parameters which may be...

  3. Influence of tunnel and soil parameters on vibrations from underground railways

    NASA Astrophysics Data System (ADS)

    Gupta, S.; Stanus, Y.; Lombaert, G.; Degrande, G.

    2009-10-01

    A parametric study is performed to identify the key parameters which have an important influence on the generation and propagation of vibrations from underground railways. In this paper, the parameters related to the tunnel and the soil are considered and their influence on the free field response is studied. The coupled periodic finite element-boundary element model and the pipe-in-pipe model have been used for this study. Both models account for the dynamic interaction between the train, the track, the tunnel and the soil. A general analytical formulation is used to compute the response of three-dimensional invariant or periodic media that are excited by moving loads. The response to moving loads is written in terms of the axle loads and the transfer functions. The parametric study can be carried out by separately analyzing the variations in the axle loads and the transfer functions. The axle loads are mainly influenced by the parameters related to the vehicle and the track, while the transfer functions are influenced by the properties of the track, the tunnel and the soil. In the present paper, the parameters related to the tunnel and soil are investigated. It is observed that the material damping and the shear modulus of the soil have an important influence on the propagation of vibrations. The influence of structural changes to the tunnel as well as geometrical properties such as the size and shape of the tunnel is investigated. It is observed that a larger tunnel results in a smaller response above the tunnel as more energy is radiated downwards. Moreover, it is demonstrated that the tunnel geometry has a considerable influence on the response closer to the tunnel.

  4. High BIM mRNA levels are associated with longer survival in advanced gastric cancer.

    PubMed

    Wu, Nandie; Huang, Ying; Zou, Zhengyun; Gimenez-Capitan, Ana; Yu, Lixia; Hu, Wenjing; Zhu, Lijing; Sun, Xia; Sanchez, Jose Javier; Guan, Wenxian; Liu, Baorui; Rosell, Rafael; Wei, Jia

    2017-03-01

    Chemotherapy drugs, including 5-fluorouracil (5-FU), oxaliplatin and docetaxel, are commonly used in the treatment of gastric cancer (GC). Apoptosis-relevant genes may be associated with drug resistance. In the present study, the messenger RNA (mRNA) expression levels of B-cell lymphoma 2 interacting mediator of cell death (BIM), astrocyte elevated gene-1 (AEG-1) and AXL receptor tyrosine kinase (AXL) were investigated in 131 advanced GC samples, and the expression levels of these genes were correlated with patients' overall survival (OS). All 131 patients received first-line FOLFOX combination chemotherapy with folinic acid and 5-FU, in which 56 patients were further treated with second-line docetaxel-based chemotherapy. A correlation between the mRNA expression levels of BIM and AEG-1 was observed ( r s =0.30; P=0.002). There was no association between the mRNA expression levels of any of the individual genes analyzed and OS in patients only receiving first-line FOLFOX chemotherapy. In a subgroup of patients receiving docetaxel-based second-line chemotherapy, those with high or intermediate levels of BIM exhibited a median OS of 18.2 months [95% confidence interval (CI), 12.8-23.6], compared with 9.6 months (95% CI, 8.9-10.3) in patients with low BIM levels (P=0.008). However, there was no correlation between the mRNA expression levels of AEG-1 or AXL and OS. The risk of mortality was higher in patients with low BIM mRNA levels than in those with high or intermediate BIM mRNA levels (hazard ratio, 2.61; 95% CI, 1.21-5.62; P=0.010). Therefore, BIM may be considered as a biomarker to identify whether patients could benefit from docetaxel-based second-line chemotherapy in GC.

  5. Development of the electromagnetic technology for broken rail detection from a mobil platform

    NASA Astrophysics Data System (ADS)

    Plotnikov, Yuri; Raghunathan, Arun; Kumar, Ajith; Noffsinger, Joseph; Fries, Jeffrey; Ehret, Steven; Frangieh, Tannous; Palanganda, Samhitha

    2016-02-01

    Timely detection of breaks in running rails remains a topic of significant importance for the railroad industry. GE has been investigating new ideas of the Rail Integrity Monitoring or RIM technology that can be implemented on a wide range of the rolling stock platforms including locomotives, passenger and freight cars. The focus of the project is to establish a simple, non-contact, and inexpensive means of nondestructive inspection by fusion of known solutions with new technology development that can result in detection with high reliability. A scaled down model of a typical locomotive-track system has been developed at GE Global research for detailed study of the detection process. In addition, a finite element model has been established and used to understand distribution of the magnetic field and currents in such a system. Both models have been using the rails and wheel-axles geometry to establish a realistic model that would provide the electric current and magnetic field distribution close to the real world phenomenon. Initial magnetic field maps were obtained by scanning a 1:15 model constructed of steel bars using a 3D scanner and an inductive coil. Sensitivity to a broken rail located between two locomotive axles simulated by an opening in this metallic frame was demonstrated. Further investigation and optimization was conducted on a larger, 1:3 scale, physical model and by running mathematical simulations. Special attention was paid to consistency between the finite element and physical model results. The obtained results allowed establishment of a working frequency range, inductive current injection into the rail-wheel-axle loop and measuring the electromagnetic response to a broken rail. The verification and full scale system prototype tests are following the laboratory experiments and mathematical simulations.

  6. 49 CFR Appendix G to Subchapter B... - Minimum Periodic Inspection Standards

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... or broken cable strands. (b) Improper clamps or clamping. f. Saddle-Mounts. (1) Method of attachment... axle. (6) A tube-type radial tire without radial tube stem markings. These markings include a red band around the tube stem, the word “radial” embossed in metal stems, or the word “radial” molded in rubber...

  7. The Effect of Friction in Pulleys on the Tension in Cables and Strings

    ERIC Educational Resources Information Center

    Martell, Eric C.; Martell, Verda Beth

    2013-01-01

    Atwood's machine is used in countless introductory physics classes as an illustration of Newton's second law. Initially, the analysis is performed assuming the pulley and string are massless and the axle is frictionless. Although the mass of the pulley is often included when the problem is revisited later in the context of rotational dynamics, the…

  8. Automotive Power Flow System; Auto Mechanics I: 9043.04.

    ERIC Educational Resources Information Center

    Dade County Public Schools, Miami, FL.

    This automotive power flow system course sets the foundation in the theory of operation of the standard and automatic transmission, clutch assemblies, drive-line and rear axle assemblies. This is a one or two quinmester credit course covering 45 clock hours. In the fourth quinmester course in the tenth year, instruction consists of lectures,…

  9. Why Does the Motorbike Feather?

    ERIC Educational Resources Information Center

    Ruocco, A.; De Luca, R.

    2007-01-01

    The problem of motorbike feathering has been analysed by writing the angular momentum theorem for non-inertial reference systems. The acceleration, for which the ideal line joining the median points of the axles of the two wheels makes an angle [theta] with the horizontal, has been calculated neglecting air friction and considering that the…

  10. 49 CFR 230.114 - Wheel centers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., following the repair, the crankpin and axle shall remain tight in the wheel. Banding of the hub is permitted... 49 Transportation 4 2013-10-01 2013-10-01 false Wheel centers. 230.114 Section 230.114... Tenders Wheels and Tires § 230.114 Wheel centers. (a) Filling blocks and shims. Driving and trailing wheel...

  11. 49 CFR 230.114 - Wheel centers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., following the repair, the crankpin and axle shall remain tight in the wheel. Banding of the hub is permitted... 49 Transportation 4 2014-10-01 2014-10-01 false Wheel centers. 230.114 Section 230.114... Tenders Wheels and Tires § 230.114 Wheel centers. (a) Filling blocks and shims. Driving and trailing wheel...

  12. 49 CFR 230.114 - Wheel centers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., following the repair, the crankpin and axle shall remain tight in the wheel. Banding of the hub is permitted... 49 Transportation 4 2012-10-01 2012-10-01 false Wheel centers. 230.114 Section 230.114... Tenders Wheels and Tires § 230.114 Wheel centers. (a) Filling blocks and shims. Driving and trailing wheel...

  13. 49 CFR 230.114 - Wheel centers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., following the repair, the crankpin and axle shall remain tight in the wheel. Banding of the hub is permitted... 49 Transportation 4 2011-10-01 2011-10-01 false Wheel centers. 230.114 Section 230.114... Tenders Wheels and Tires § 230.114 Wheel centers. (a) Filling blocks and shims. Driving and trailing wheel...

  14. 49 CFR 230.114 - Wheel centers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., following the repair, the crankpin and axle shall remain tight in the wheel. Banding of the hub is permitted... 49 Transportation 4 2010-10-01 2010-10-01 false Wheel centers. 230.114 Section 230.114... Tenders Wheels and Tires § 230.114 Wheel centers. (a) Filling blocks and shims. Driving and trailing wheel...

  15. 40 CFR 86.1102-87 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 19 2011-07-01 2011-07-01 false Definitions. 86.1102-87 Section 86... § 86.1102-87 Definitions. (a) The definitions in this section apply to this subpart. (b) As used in... the basis of engine code, inertia weight class, transmission type and gear ratios, rear axle ratio, or...

  16. 40 CFR 86.1102-87 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 20 2013-07-01 2013-07-01 false Definitions. 86.1102-87 Section 86... § 86.1102-87 Definitions. (a) The definitions in this section apply to this subpart. (b) As used in... the basis of engine code, inertia weight class, transmission type and gear ratios, rear axle ratio, or...

  17. 40 CFR 86.1102-87 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 20 2012-07-01 2012-07-01 false Definitions. 86.1102-87 Section 86... § 86.1102-87 Definitions. (a) The definitions in this section apply to this subpart. (b) As used in... the basis of engine code, inertia weight class, transmission type and gear ratios, rear axle ratio, or...

  18. Analysis of Ebola Virus Entry Into Macrophages

    PubMed Central

    Dahlmann, Franziska; Biedenkopf, Nadine; Babler, Anne; Jahnen-Dechent, Willi; Karsten, Christina B.; Gnirß, Kerstin; Schneider, Heike; Wrensch, Florian; O'Callaghan, Christopher A.; Bertram, Stephanie; Herrler, Georg; Becker, Stephan; Pöhlmann, Stefan; Hofmann-Winkler, Heike

    2015-01-01

    Ebolaviruses constitute a public health threat, particularly in Central and Western Africa. Host cell factors required for spread of ebolaviruses may serve as targets for antiviral intervention. Lectins, TAM receptor tyrosine kinases (Tyro3, Axl, Mer), T cell immunoglobulin and mucin domain (TIM) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruses into certain cellular systems. However, the factors used by ebolaviruses to invade macrophages, major viral targets, are poorly defined. Here, we show that mannose-specific lectins, TIM-1 and Axl augment entry into certain cell lines but do not contribute to Ebola virus (EBOV)-glycoprotein (GP)–driven transduction of macrophages. In contrast, expression of Mer, integrin αV, and NPC1 was required for efficient GP-mediated transduction and EBOV infection of macrophages. These results define cellular factors hijacked by EBOV for entry into macrophages and, considering that Mer and integrin αV promote phagocytosis of apoptotic cells, support the concept that EBOV relies on apoptotic mimicry to invade target cells. PMID:25877552

  19. Apparatus for weighing and identifying characteristics of a moving vehicle

    DOEpatents

    Muhs, Jeffrey D.; Jordan, John K.; Tobin, Jr., Kenneth W.; LaForge, John V.

    1993-01-01

    Apparatus for weighing a vehicle in motion is provided by employing a plurality of elongated fiber-optic sensors defined by an optical fiber embedded in an encasement of elastomeric material and disposed parallel to each other on the roadway in the path of moving vehicles. Each fiber-optic sensor is provided with contact grid means which can be selectively altered to provide the fiber-optic sensors with sensitivities to vehicular weight different from each other for weighing vehicles in an extended weight range. Switch means are used in conjunction with the fiber-optic sensors to provide signals indicative of the speed of the moving vehicle, the number of axles on the vehicle, weight distribution, tire position, and the wheelbase of the vehicle. The use of a generally N-shaped configuration of switch means also provides a determination of the number of tires on each axle and the tire footprint. When switch means in this configuration are formed of optical fibers, the extent of light transmission through the fibers during contact with the tires of the vehicle is indicative of the vehicle weight.

  20. REDOX-SWITCHABLE CALIX[6]ARENE-BASED ISOMERIC ROTAXANES.

    PubMed

    Zanichelli, Valeria; Bazzoni, Margherita; Arduini, Arturo; Franchi, Paola; Lucarini, Marco; Ragazzon, Giulio; Secchi, Andrea; Silvi, Serena

    2018-04-16

    Operating molecular machines are based on switchable systems, whose components can be set in motion in a controllable fashion. The presence of non-symmetric elements is a mandatory requirement to obtain and demonstrate the unidirectionality of motion. Calixarene-based macrocycles have proven very efficient hosts in the design of oriented rotaxanes and of pseudorotaxanes with a strict control on the direction of complexation. We have synthesized and characterized a series of two-station rotaxanes based on bypiridinium-ammonium axles. We have exploited a recently reported supramolecular-assisted strategy for the synthesis of different orientational isomers and we identified the ammonium unit as a proper secondary station for the calixarene. We were able to trigger the displacement of the macrocycle upon electrochemical reduction of the bipyridinium primary station and we demonstrated that the shuttling is influenced both by the length of the chain of the axle component and by the position of the secondary station with respect to the calixarene rims. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Road profile estimation of city roads using DTPS

    NASA Astrophysics Data System (ADS)

    Wang, Qi; McDaniel, J. Gregory; Sun, Nian X.; Wang, Ming L.

    2013-04-01

    This work presents a non-destructive and non-contact acoustic sensing approach for measuring road profile of road and bridge deck with vehicles running at normal speed without stopping traffic. This approach uses an instantaneous and real-time dynamic tire pressure sensor (DTPS) that can measure dynamic response of the tire-road interaction and increases the efficiency of currently used road profile measuring systems with vehicle body-mounted profilers and axle-mounted accelerometers. In this work, a prototype of real-time DTPS system has been developed and demonstrated on a testing van at speeds from 5 to 80 miles per hour (mph). A data analysis algorithm has been developed to remove axle dynamic motions from the measured DTPS data and to find the transfer function between dynamic tire pressure change and the road profile. Field test has been performed to estimate road profiles. The road profile resolution is approximately 5 to 10 cm in width and sensitivity is 0. 3 cm for the height road surface features at driving speeds of 5 to 80 mph.

  2. Curve squeal of urban rolling stock—Part 1: State of the art and field measurements

    NASA Astrophysics Data System (ADS)

    Vincent, N.; Koch, J. R.; Chollet, H.; Guerder, J. Y.

    2006-06-01

    This is the first part of a series of three papers dealing with curve squeal of urban rolling stock such as metros and trams. After a brief review of the present state of the art, the key parameters involved in curve squeal generation are discussed. Then, some results of field measurement campaigns, on metro and on tramway systems, are presented. A specific measurement methodology is applied for both campaigns in order to record the main key parameters: rolling speed, axle angle of attack, wheel/rail lateral position and modal damping of relevant wheel modes. On-board microphones are mounted close to each wheel of the instrumented bogies in order to locate the squealing wheels. No squeal occurs on the outer wheel of the leading axle in flange contact with the rail. The highest squeal levels are generally found on the front inner wheel. Pure tone frequencies are related to wheel axial modes for metro (undamped steel wheel) and for tramway (resilient wheels). Squeal occurrence is also observed on a bogie with independent wheels.

  3. Numerical prediction on static and dynamic properties for rotating mirror of ultra-high-speed photography

    NASA Astrophysics Data System (ADS)

    Huang, Hongbin; Li, Jingzhen; Gong, Xiangdong; Sun, Fengshan; He, Tiefeng

    2007-01-01

    The methods of numerical analysis for the strength and vibration modals of rotating mirrors were presented based respectively on the three-dimensional elastic mechanics and dynamics. On strength computation, the finite element models of rotating mirror were established according to the real structure of mirror, and the rotating three-faced aluminous and beryllium mirrors were analysed contrastively. Results display that the surface deformation quantity of the aluminous mirror is approximately 20 times as large as beryllium one, and the maximum stress is 1.6 times against the latter. Then, the three-faced aluminous mirrors were analyzed at variedly fit between shaft and axle hole. One conclusion is gotten out that the mirror strength is foreign to fits, but it is weaken by the axle hole obviously. On the modal analysis of vibration, this method can simulates accurately the natural frequencies and corresponding modalities of mirror. And the results from three-face aluminous mirror indicate that the resonance points of a new mirror may be guaranteed existing in selected speed range.

  4. Flexibility within the rotor and stators of the vacuolar H+-ATPase.

    PubMed

    Song, Chun Feng; Papachristos, Kostas; Rawson, Shaun; Huss, Markus; Wieczorek, Helmut; Paci, Emanuele; Trinick, John; Harrison, Michael A; Muench, Stephen P

    2013-01-01

    The V-ATPase is a membrane-bound protein complex which pumps protons across the membrane to generate a large proton motive force through the coupling of an ATP-driven 3-stroke rotary motor (V1) to a multistroke proton pump (Vo). This is done with near 100% efficiency, which is achieved in part by flexibility within the central rotor axle and stator connections, allowing the system to flex to minimise the free energy loss of conformational changes during catalysis. We have used electron microscopy to reveal distinctive bending along the V-ATPase complex, leading to angular displacement of the V1 domain relative to the Vo domain to a maximum of ~30°. This has been complemented by elastic network normal mode analysis that shows both flexing and twisting with the compliance being located in the rotor axle, stator filaments, or both. This study provides direct evidence of flexibility within the V-ATPase and by implication in related rotary ATPases, a feature predicted to be important for regulation and their high energetic efficiencies.

  5. Wireless sensor node for detection of freight train derailment

    NASA Astrophysics Data System (ADS)

    Costa, Andrea; Milani, Damiano; Resta, Ferruccio; Tomasini, Gisella

    2016-04-01

    The target of the research activity presented in this paper is to design, to realize and to test an autonomous sensor node able to measure the accelerations in correspondence of the axle box of a freight train. The final goal of the sensor is to identify the derailment conditions by observing the variations in the spectra of the box accelerations, around the frequencies associated to the wheel revolution and its multiples. The sensor node embeds an accelerometer, a microprocessor, a transmission system, a piezoelectric bimorph energy harvester and an integrated circuit for managing the power distribution to each component of the node. In particular, a mechanical filter to be applied to the node was specifically designed to increment the energy recovered by the harvester and to filter out the high frequency components of the axle-box acceleration, allowing the use of a more sensitive accelerometer. The harvesting system was setup by means of laboratory tests carried out with an electromechanical shaker and the sensor node was finally tested through field tests on freight trains.

  6. Off-road axle detection sensor (ORADS) : research implementation plan.

    DOT National Transportation Integrated Search

    2001-04-01

    To collect various types of traffic data to meet the Federal Requirements, field technicians have to enter : the roadway to anchor the road sensors while traffic is moving at highway speeds. On high volumes : routes this can be a very time consuming ...

  7. Identification of Vehicle Axle Loads from Bridge Dynamic Responses

    NASA Astrophysics Data System (ADS)

    ZHU, X. Q.; LAW, S. S.

    2000-09-01

    A method is presented to identify moving loads on a bridge deck modelled as an orthotropic rectangular plate. The dynamic behavior of the bridge deck under moving loads is analyzed using the orthotropic plate theory and modal superposition principle, and Tikhonov regularization procedure is applied to provide bounds to the identified forces in the time domain. The identified results using a beam model and a plate model of the bridge deck are compared, and the conditions under which the bridge deck can be simplified as an equivalent beam model are discussed. Computation simulation and laboratory tests show the effectiveness and the validity of the proposed method in identifying forces travelling along the central line or at an eccentric path on the bridge deck.

  8. 14 CFR 23.499 - Supplementary conditions for nose wheels.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., the application of 1.33 times the full steering torque combined with a vertical reaction equal to 1.33 times the maximum static reaction on the nose gear must be assumed. However, if a torque limiting device... components at the axle must be— (1) A vertical component of 2.25 times the static load on the wheel; and (2...

  9. 14 CFR 23.499 - Supplementary conditions for nose wheels.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., the application of 1.33 times the full steering torque combined with a vertical reaction equal to 1.33 times the maximum static reaction on the nose gear must be assumed. However, if a torque limiting device... components at the axle must be— (1) A vertical component of 2.25 times the static load on the wheel; and (2...

  10. 14 CFR 23.499 - Supplementary conditions for nose wheels.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., the application of 1.33 times the full steering torque combined with a vertical reaction equal to 1.33 times the maximum static reaction on the nose gear must be assumed. However, if a torque limiting device... components at the axle must be— (1) A vertical component of 2.25 times the static load on the wheel; and (2...

  11. AUTOMOTIVE DIESEL MAINTENANCE 1. UNIT XXI, I--MAINTAINING THE AIR SYSTEM--CATERPILLAR DIESEL ENGINE, II--UNDERSTANDING REAR END SUSPENSION.

    ERIC Educational Resources Information Center

    Minnesota State Dept. of Education, St. Paul. Div. of Vocational and Technical Education.

    THIS MODULE OF A 30-MODULE COURSE IS DESIGNED TO DEVELOP AN UNDERSTANDING OF THE OPERATION AND MAINTENANCE OF THE DIESEL ENGINE AIR SYSTEM AND REAR AXLE SUSPENSION USED ON DIESEL POWERED VEHICLES. TOPICS ARE (1) AIR INDUCTION AND EXHAUST SYSTEM, (2) VALVE MECHANISM, (3) TROUBLESHOOTING THE AIR SYSTEM, (4) PURPOSE OF VEHICLE SUSPENSION, (5) TANDEM…

  12. The Fluid Foil: The Seventh Simple Machine

    ERIC Educational Resources Information Center

    Mitts, Charles R.

    2012-01-01

    A simple machine does one of two things: create a mechanical advantage (lever) or change the direction of an applied force (pulley). Fluid foils are unique among simple machines because they not only change the direction of an applied force (wheel and axle); they convert fluid energy into mechanical energy (wind and Kaplan turbines) or vice versa,…

  13. Rolling Friction on a Wheeled Laboratory Cart

    ERIC Educational Resources Information Center

    Mungan, Carl E.

    2012-01-01

    A simple model is developed that predicts the coefficient of rolling friction for an undriven laboratory cart on a track that is approximately independent of the mass loaded onto the cart and of the angle of inclination of the track. The model includes both deformation of the wheels/track and frictional torque at the axles/bearings. The concept of…

  14. 49 CFR 230.112 - Wheels and tires.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... wheels mounted on the same axle shall not vary more than 1/4 inch. (d) Tire thickness. Wheels may not have tires with a minimum thickness less than that indicated in the table in this paragraph (d). When... the minimum thickness of tires may be as much below the limits specified earlier in this paragraph (d...

  15. Fun with Physics in the Elementary School.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    Primary grade pupils can become fascinated with simple machines. This paper suggests that teachers have simple machines in the classroom for a unit of study. It proposes some guidelines to create a unit of study for six simple machines that include the fulcrum, inclined plane, pulley, wheel and axle, wedge, and screw. Friction, gravity, force, and…

  16. Basic Machines. Navy Training Course.

    ERIC Educational Resources Information Center

    Bureau of Naval Personnel, Washington, DC.

    This document is a reference for the enlisted men in the Navy whose duties require knowledge of the fundamentals of machinery. Beginning with the simplest of machines--the lever--the book proceeds with the discussion of block and tackle, wheel and axle, inclined plane, screw and gears. It explains the concepts of work and power, and differentiates…

  17. Simple Machine Junk Cars

    ERIC Educational Resources Information Center

    Herald, Christine

    2010-01-01

    During the month of May, the author's eighth-grade physical science students study the six simple machines through hands-on activities, reading assignments, videos, and notes. At the end of the month, they can easily identify the six types of simple machine: inclined plane, wheel and axle, pulley, screw, wedge, and lever. To conclude this unit,…

  18. 6. VIEW OF BORING MILL. Chuck action of locomotive wheel ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. VIEW OF BORING MILL. Chuck action of locomotive wheel Wheel weight 1200 pounds, 3'-0' diameter. Table 53' in diameter Wheel is 48'. Largest hole that can be bored is 9-1/2' plus (GE axle is 10'). - Juniata Shops, Erecting Shop & Machine Shop, East of Fourth Avenue, between Fourth & Fifth Streets, Altoona, Blair County, PA

  19. Alternative Fuels Data Center

    Science.gov Websites

    vehicles equipped with idle reduction technology may exceed the state's gross and axle weight limits by up vehicle primarily powered by natural gas may exceed the state's gross vehicle weight limits by a weight maximum gross weight may not exceed 82,000 lbs. (Reference New Mexico Statutes 66-7-4

  20. Alternative Fuels Data Center

    Science.gov Websites

    vehicles equipped with idle reduction technology may exceed the state's gross and axle weight limits by up vehicle primarily powered by natural gas may exceed the state's gross vehicle weight limits by a weight and the weight of a comparable vehicle with a diesel tank and fueling system. The NGV maximum gross

  1. Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans

    DTIC Science & Technology

    2013-10-01

    2012 – 19 Sept 2013 4 biopsies from cancer group. Right cluster is consisting of rest of the high risk and cancer biopsies. Upregulation of Notch3 ...classifiers from bronchial biopsy specimen comparing non-smoker versus smoker with top 5 markers, Notch3 , EGFR.pY1173, LCN2, AXL and Rb.pS807.811 (right

  2. 29 CFR 1910.177 - Servicing multi-piece and single piece rim wheels.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... rim wheel onto a vehicle axle hub. Removing means the opposite of installing. Mounting a tire means... 29 Labor 5 2011-07-01 2011-07-01 false Servicing multi-piece and single piece rim wheels. 1910.177... § 1910.177 Servicing multi-piece and single piece rim wheels. (a) Scope. (1) This section applies to the...

  3. 29 CFR 1910.177 - Servicing multi-piece and single piece rim wheels.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... means the transfer and attachment of an assembled rim wheel onto a vehicle axle hub. Removing means the... 29 Labor 5 2014-07-01 2014-07-01 false Servicing multi-piece and single piece rim wheels. 1910.177... § 1910.177 Servicing multi-piece and single piece rim wheels. (a) Scope. (1) This section applies to the...

  4. 29 CFR 1910.177 - Servicing multi-piece and single piece rim wheels.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... rim wheel onto a vehicle axle hub. Removing means the opposite of installing. Mounting a tire means... 29 Labor 5 2010-07-01 2010-07-01 false Servicing multi-piece and single piece rim wheels. 1910.177... § 1910.177 Servicing multi-piece and single piece rim wheels. (a) Scope. (1) This section applies to the...

  5. 29 CFR 1910.177 - Servicing multi-piece and single piece rim wheels.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... means the transfer and attachment of an assembled rim wheel onto a vehicle axle hub. Removing means the... 29 Labor 5 2013-07-01 2013-07-01 false Servicing multi-piece and single piece rim wheels. 1910.177... § 1910.177 Servicing multi-piece and single piece rim wheels. (a) Scope. (1) This section applies to the...

  6. 29 CFR 1910.177 - Servicing multi-piece and single piece rim wheels.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... means the transfer and attachment of an assembled rim wheel onto a vehicle axle hub. Removing means the... 29 Labor 5 2012-07-01 2012-07-01 false Servicing multi-piece and single piece rim wheels. 1910.177... § 1910.177 Servicing multi-piece and single piece rim wheels. (a) Scope. (1) This section applies to the...

  7. A theory of wheelchair wheelie performance.

    PubMed

    Kauzlarich, J J; Thacker, J G

    1987-01-01

    The results of this analytical study of wheelchair wheelie performance can be summarized into two wheelchair design equations, or rules of thumb, as developed in the paper. The equation containing the significant parameters involved in popping a wheelie for curb climbing is: fh = 0.8 mg theta c.g. [A] where fh is handrim force, m is the mass of the wheelchair + user less rear wheels, g is acceleration of gravity (9.807 m/s2), and theta c.g. is "c.g. angle," i.e., the angle between the vertical through the rear axle and a line connecting the rear axle and the system center-of-gravity. Equation [A] shows that reducing the mass and/or the c.g. angle will make it easier to pop a wheelie. The c.g. angle is reduced by moving the rear axle position forward on the wheelchair. Wheelie balance is the other aspect of performance considered; where the user balances the wheelchair on the rear wheels for going down curbs or just for fun. The ease with which a system can be controlled (balanced) is related to the static stability of the system. The static stability is defined as: omega 2 = mgl/J [B] where J is the mass moment of inertia at the center of gravity of the system about the direction perpendicular to the sideframe. For better wheelchair control during wheelchair balance the static stability should be reduced. Measurements of the value for the polar mass moment of inertia for a typical wheelchair + user of m = 90 kg was found to be J = 8.7 kg-m2. In order to decrease the value of the static stability, Equation [B], one can increase J or decrease m and/or l, where l is the distance from the rear axle to the c.g. of the system. It is also shown that balancing a rod in the palm of the hand (inverted pendulum) is a mathematical problem similar to the wheelie balance problem, and a rod of length 1.56 meters is similar to a wheelchair + user system mass of 90 kg. However, balancing a rod is done primarily by using visual perception, whereas wheelie balance involves human

  8. Can a String's Tension Exert a Torque on a Pulley?

    ERIC Educational Resources Information Center

    Krause, Dennis E.; Sun, Yifei

    2011-01-01

    A typical textbook problem in rotational dynamics involves calculating the angular acceleration of a massive pulley due to a string, such as in the example shown in Fig. 1. The string is assumed to be massless and to move without slipping over the pulley, which is mounted on a frictionless axle. If T[subscript L] and T[subscript R] are the…

  9. Carbon Nanotube Aluminum Matrix Composites

    DTIC Science & Technology

    2010-08-01

    from nanoscale transistors (2) and interconnects (3), supercapacitors (4), artificial muscle fibers (5), and even as axles in molecular vehicles (6...anything other than basic architectures. This problem is compounded for nanomaterials such as CNTs, where homogeneous dispersion (not to mention any form...Microelectronic Engineering 2002, 64, 399–408. 4. Frackowiak, E.; Metenier, K.; Bertagna, V.; Beguin, F. Supercapacitor Electrodes From Multiwalled

  10. Verge and Foliot Clock Escapement: A Simple Dynamical System

    ERIC Educational Resources Information Center

    Denny, Mark

    2010-01-01

    The earliest mechanical clocks appeared in Europe in the 13th century. From about 1250 CE to 1670 CE, these simple clocks consisted of a weight suspended from a rope or chain that was wrapped around a horizontal axle. To tell time, the weight must fall with a slow uniform speed, but, under the action of gravity alone, such a suspended weight would…

  11. A Nontoxic Barlow's Wheel

    ERIC Educational Resources Information Center

    Daffron, John A.; Greenslade, Thomas B., Jr.

    2015-01-01

    Barlow's wheel has been a favorite demonstration since its invention by Peter Barlow (1776-1862) in 1822. In the form shown in Fig. 1, it represents the first electric motor. The interaction between the electric current passing from the axle of the wheel to the rim and the magnetic field produced by the U-magnet produces a torque that turns…

  12. Vehicle Concept Model Abstractions For Integrated Geometric, Inertial ,Rigid Body, Powertrain and FE Analysis

    DTIC Science & Technology

    2011-06-17

    structure through quantitative assessment of stiffness and modal parameter changes resulting from modifications to the beam geometries and positions...power transmission assembly. If the power limit at a wheel exceeds the traction limit, then depending on the type of differential placed on the axle ...components with appropriate model connectivity instead to determine the free modal response of powertrain type components, without abstraction

  13. Safe Operations of Unmanned Systems for Reconnaissance in Complex Environments Army Technology Objective (SOURCE ATO)

    DTIC Science & Technology

    2011-04-25

    must adapt its planning to vehicle size, shape, wheelbase, wheel and axle configuration, the specific obstacle-crossing capabilities of the vehicle...scalability of the ANS is a consequence of making each sensing modality capable of performing reasonable perception tasks while allowing a wider...autonomous system design achieves flexibility by exploiting redundant sensing modalities where possible, and by a decision-making process that

  14. Vehicle Concept Model Abstractions for Integrated Geometric, Inertial, Rigid Body, Powertrain, and FE Analysis

    DTIC Science & Technology

    2011-01-01

    refinement of the vehicle body structure through quantitative assessment of stiffness and modal parameter changes resulting from modifications to the beam...differential placed on the axle , adjustment of the torque output to the opposite wheel may be required to obtain the correct solution. Thus...represented by simple inertial components with appropriate model connectivity instead to determine the free modal response of powertrain type

  15. Charles River Crossing

    DTIC Science & Technology

    2012-04-06

    48 MODAL ANALYSIS...2. Lateral Loads 3. Non-uniform Loads 4. Modal Analysis 5. Seismic Analysis 6. Moving Load Analysis All of these analyses were conducted with...Tandem c onsisting of a t wo a xle ve hicle with 25 kips on each axle spaced by 4 ft Self-Weight Dead Load: Steel density of 0.49 kips per cubic foot

  16. Exploratory methods for truck re-identification in a statewide network based on axle weight and axle spacing data to enhance freight metrics : phase II.

    DOT National Transportation Integrated Search

    2012-05-01

    Vehicle re-identification methods can be used to anonymously match vehicles crossing two different locations based on vehicle attribute data. : This research builds upon a previous study and investigates different methods for solving the re-identific...

  17. Driver assistance system for passive multi-trailer vehicles with haptic steering limitations on the leading unit.

    PubMed

    Morales, Jesús; Mandow, Anthony; Martínez, Jorge L; Reina, Antonio J; García-Cerezo, Alfonso

    2013-04-03

    Driving vehicles with one or more passive trailers has difficulties in both forward and backward motion due to inter-unit collisions, jackknife, and lack of visibility. Consequently, advanced driver assistance systems (ADAS) for multi-trailer combinations can be beneficial to accident avoidance as well as to driver comfort. The ADAS proposed in this paper aims to prevent unsafe steering commands by means of a haptic handwheel. Furthermore, when driving in reverse, the steering-wheel and pedals can be used as if the vehicle was driven from the back of the last trailer with visual aid from a rear-view camera. This solution, which can be implemented in drive-by-wire vehicles with hitch angle sensors, profits from two methods previously developed by the authors: safe steering by applying a curvature limitation to the leading unit, and a virtual tractor concept for backward motion that includes the complex case of set-point propagation through on-axle hitches. The paper addresses system requirements and provides implementation details to tele-operate two different off- and on-axle combinations of a tracked mobile robot pulling and pushing two dissimilar trailers.

  18. Analysis of Ebola Virus Entry Into Macrophages.

    PubMed

    Dahlmann, Franziska; Biedenkopf, Nadine; Babler, Anne; Jahnen-Dechent, Willi; Karsten, Christina B; Gnirß, Kerstin; Schneider, Heike; Wrensch, Florian; O'Callaghan, Christopher A; Bertram, Stephanie; Herrler, Georg; Becker, Stephan; Pöhlmann, Stefan; Hofmann-Winkler, Heike

    2015-10-01

    Ebolaviruses constitute a public health threat, particularly in Central and Western Africa. Host cell factors required for spread of ebolaviruses may serve as targets for antiviral intervention. Lectins, TAM receptor tyrosine kinases (Tyro3, Axl, Mer), T cell immunoglobulin and mucin domain (TIM) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruses into certain cellular systems. However, the factors used by ebolaviruses to invade macrophages, major viral targets, are poorly defined. Here, we show that mannose-specific lectins, TIM-1 and Axl augment entry into certain cell lines but do not contribute to Ebola virus (EBOV)-glycoprotein (GP)-driven transduction of macrophages. In contrast, expression of Mer, integrin αV, and NPC1 was required for efficient GP-mediated transduction and EBOV infection of macrophages. These results define cellular factors hijacked by EBOV for entry into macrophages and, considering that Mer and integrin αV promote phagocytosis of apoptotic cells, support the concept that EBOV relies on apoptotic mimicry to invade target cells. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  19. Correlations of the instantaneous carrying force and pressure distribution in the case of the narrow sliding radial bearing under hard shocks

    NASA Astrophysics Data System (ADS)

    Alexandrescu, I. M.; Coteţiu, R.; Darabă, D.

    2017-02-01

    We present the determining relationship of carriage in non-dimensional form for narrow radial bearings subjected to shocks and vibrations, as well as the determining relationships of the lubricant minimum thickness in relation to the dynamic loading. Due to the very short time of loading radial bearings subjected to shocks and vibrations, of about 0.5-1 ms, we consider only the approaching motion between spindle/axle and bushing on the direction of the centre line, without the rotation of the spindle/axle (the case of the non-rotating bearing), so that the effect of the lubricant expulsion be prevalent in the achieving of the self-carrying film. The paper is focused on determining relationship of carriage in dimensional form for narrow radial bearings exposed to shocks and vibrations, as well as the determining relationships of the pressure distribution from the film to be lubricated in various places of the bearing’s body. It is showed the details during the measuring accomplishments and the experimental results are registered in a record of obtained results. This paper was accepted for publication in Proceedings after double peer reviewing process but was not presented at the Conference ROTRIB’16

  20. Fisetin, a dietary phytochemical, overcomes Erlotinib-resistance of lung adenocarcinoma cells through inhibition of MAPK and AKT pathways.

    PubMed

    Zhang, Liang; Huang, Yi; Zhuo, Wenlei; Zhu, Yi; Zhu, Bo; Chen, Zhengtang

    2016-01-01

    Erlotinib (Tarceva) is a selective epidermal growth factor receptor tyrosine kinase inhibitor for treatment of non-small cell lung cancer (NSCLC). However, its efficacy is usually reduced by the occurrence of drug resistance. Our recent study showed that a flavonoid found in many plants, Fisetin, might have a potential to reverse the acquired Cisplatin-resistance of lung adenocarcinoma. In the present study, we aimed to test whether Fisetin could have the ability to reverse Erlotinib-resistance of lung cancer cells. Erlotinib-resistant lung adenocarcinoma cells, HCC827-ER, were cultured from the cell line HCC827, and the effects of Fisetin and Erlotinib on the cell viability and apoptosis were evaluated. The possible signaling pathways in this process were also detected. As expected, the results showed that Fisetin effectively increased sensitivity of Erlotinib-resistant lung cancer cells to Erlotinib, possibly by inhibiting aberrant activation of MAPK and AKT signaling pathways resulted from AXL suppression. In conclusion, Fisetin was a potential agent for reversing acquired Erlotinib-resistance of lung adenocarcinoma. Inactivation of AXL, MAPK and AKT pathways might play a partial role in this process.

  1. Fisetin, a dietary phytochemical, overcomes Erlotinib-resistance of lung adenocarcinoma cells through inhibition of MAPK and AKT pathways

    PubMed Central

    Zhang, Liang; Huang, Yi; Zhuo, Wenlei; Zhu, Yi; Zhu, Bo; Chen, Zhengtang

    2016-01-01

    Erlotinib (Tarceva) is a selective epidermal growth factor receptor tyrosine kinase inhibitor for treatment of non-small cell lung cancer (NSCLC). However, its efficacy is usually reduced by the occurrence of drug resistance. Our recent study showed that a flavonoid found in many plants, Fisetin, might have a potential to reverse the acquired Cisplatin-resistance of lung adenocarcinoma. In the present study, we aimed to test whether Fisetin could have the ability to reverse Erlotinib-resistance of lung cancer cells. Erlotinib-resistant lung adenocarcinoma cells, HCC827-ER, were cultured from the cell line HCC827, and the effects of Fisetin and Erlotinib on the cell viability and apoptosis were evaluated. The possible signaling pathways in this process were also detected. As expected, the results showed that Fisetin effectively increased sensitivity of Erlotinib-resistant lung cancer cells to Erlotinib, possibly by inhibiting aberrant activation of MAPK and AKT signaling pathways resulted from AXL suppression. In conclusion, Fisetin was a potential agent for reversing acquired Erlotinib-resistance of lung adenocarcinoma. Inactivation of AXL, MAPK and AKT pathways might play a partial role in this process. PMID:27904686

  2. The expression of inflammatory cytokines, TAM tyrosine kinase receptors and their ligands is upregulated in venous leg ulcer patients: a novel insight into chronic wound immunity.

    PubMed

    Filkor, Kata; Németh, Tibor; Nagy, István; Kondorosi, Éva; Urbán, Edit; Kemény, Lajos; Szolnoky, Győző

    2016-08-01

    The systemic host defence mechanisms, especially innate immunity, in venous leg ulcer patients are poorly investigated. The aim of the current study was to measure Candida albicans killing activity and gene expressions of pro- and anti-inflammatory cytokines and innate immune response regulators, TAM receptors and ligands of peripheral blood mononuclear cells separated from 69 venous leg ulcer patients and 42 control probands. Leg ulcer patients were stratified into responder and non-responder groups on the basis of wound healing properties. No statistical differences were found in Candida killing among controls, responders and non-responders. Circulating blood mononuclear cells of patients overexpress pro-inflammatory (IL-1α, TNFα, CXCL-8) and anti-inflammatory (IL-10) cytokines as well as TAM receptors (Tyro, Axl, MerTK) and their ligands Gas6 and Protein S compared with those of control individuals. IL-1α is notably overexpressed in venous leg ulcer treatment non-responders; in contrast, Axl gene expression is robustly stronger among responders. These markers may be considered as candidates for the prediction of treatment response among venous leg ulcer patients. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  3. Functions of TAM RTKs in regulating spermatogenesis and male fertility in mice.

    PubMed

    Chen, Yongmei; Wang, Huizhen; Qi, Nan; Wu, Hui; Xiong, Weipeng; Ma, Jing; Lu, Qingxian; Han, Daishu

    2009-10-01

    Mice lacking TYRO3, AXL and MER (TAM) receptor tyrosine kinases (RTKs) are male sterile. The mechanism of TAM RTKs in regulating male fertility remains unknown. In this study, we analyzed in more detail the testicular phenotype of TAM triple mutant (TAM(-/-)) mice with an effort to understand the mechanism. We demonstrate that the three TAM RTKs cooperatively regulate male fertility, and MER appears to be more important than AXL and TYRO3. TAM(-/-) testes showed a progressive loss of germ cells from elongated spermatids to spermatogonia. Young adult TAM(-/-) mice exhibited oligo-astheno-teratozoospermia and various morphological malformations of sperm cells. As the mice aged, the germ cells were eventually depleted from the seminiferous tubules. Furthermore, we found that TAM(-/-) Sertoli cells have an impaired phagocytic activity and a large number of differentially expressed genes compared to wild-type controls. By contrast, the function of Leydig cells was not apparently affected by the mutation of TAM RTKs. Therefore, we conclude that the suboptimal function of Sertoli cells leads to the impaired spermatogenesis in TAM(-/-) mice. The results provide novel insight into the mechanism of TAM RTKs in regulating male fertility.

  4. Use of Finite Elements Analysis for a Weigh-in-Motion Sensor Design

    PubMed Central

    Opitz, Rigobert; Goanta, Viorel; Carlescu, Petru; Barsanescu, Paul-Doru; Taranu, Nicolae; Banu, Oana

    2012-01-01

    High speed weigh-in-motion (WIM) sensors are utilized as components of complex traffic monitoring and measurement systems. They should be able to determine the weights on wheels, axles and vehicle gross weights, and to help the classification of vehicles (depending on the number of axles). WIM sensors must meet the following main requirements: good accuracy, high endurance, low price and easy installation in the road structure. It is not advisable to use cheap materials in constructing these devices for lower prices, since the sensors are normally working in harsh environmental conditions such as temperatures between −40 °C and +70 °C, dust, temporary water immersion, shocks and vibrations. Consequently, less expensive manufacturing technologies are recommended. Because the installation cost in the road structure is high and proportional to the WIM sensor cross section (especially with its thickness), the device needs to be made as flat as possible. The WIM sensor model presented and analyzed in this paper uses a spring element equipped with strain gages. Using Finite Element Analysis (FEA), the authors have attempted to obtain a more sensitive, reliable, lower profile and overall cheaper elastic element for a new WIM sensor. PMID:22969332

  5. Re-Evaluation of the AASHTO-Flexible Pavement Design Equation with Neural Network Modeling

    PubMed Central

    Tiğdemir, Mesut

    2014-01-01

    Here we establish that equivalent single-axle loads values can be estimated using artificial neural networks without the complex design equality of American Association of State Highway and Transportation Officials (AASHTO). More importantly, we find that the neural network model gives the coefficients to be able to obtain the actual load values using the AASHTO design values. Thus, those design traffic values that might result in deterioration can be better calculated using the neural networks model than with the AASHTO design equation. The artificial neural network method is used for this purpose. The existing AASHTO flexible pavement design equation does not currently predict the pavement performance of the strategic highway research program (Long Term Pavement Performance studies) test sections very accurately, and typically over-estimates the number of equivalent single axle loads needed to cause a measured loss of the present serviceability index. Here we aimed to demonstrate that the proposed neural network model can more accurately represent the loads values data, compared against the performance of the AASHTO formula. It is concluded that the neural network may be an appropriate tool for the development of databased-nonparametric models of pavement performance. PMID:25397962

  6. Re-evaluation of the AASHTO-flexible pavement design equation with neural network modeling.

    PubMed

    Tiğdemir, Mesut

    2014-01-01

    Here we establish that equivalent single-axle loads values can be estimated using artificial neural networks without the complex design equality of American Association of State Highway and Transportation Officials (AASHTO). More importantly, we find that the neural network model gives the coefficients to be able to obtain the actual load values using the AASHTO design values. Thus, those design traffic values that might result in deterioration can be better calculated using the neural networks model than with the AASHTO design equation. The artificial neural network method is used for this purpose. The existing AASHTO flexible pavement design equation does not currently predict the pavement performance of the strategic highway research program (Long Term Pavement Performance studies) test sections very accurately, and typically over-estimates the number of equivalent single axle loads needed to cause a measured loss of the present serviceability index. Here we aimed to demonstrate that the proposed neural network model can more accurately represent the loads values data, compared against the performance of the AASHTO formula. It is concluded that the neural network may be an appropriate tool for the development of databased-nonparametric models of pavement performance.

  7. Driver Assistance System for Passive Multi-Trailer Vehicles with Haptic Steering Limitations on the Leading Unit

    PubMed Central

    Morales, Jesús; Mandow, Anthony; Martínez, Jorge L.; Reina, Antonio J.; García-Cerezo, Alfonso

    2013-01-01

    Driving vehicles with one or more passive trailers has difficulties in both forward and backward motion due to inter-unit collisions, jackknife, and lack of visibility. Consequently, advanced driver assistance systems (ADAS) for multi-trailer combinations can be beneficial to accident avoidance as well as to driver comfort. The ADAS proposed in this paper aims to prevent unsafe steering commands by means of a haptic handwheel. Furthermore, when driving in reverse, the steering-wheel and pedals can be used as if the vehicle was driven from the back of the last trailer with visual aid from a rear-view camera. This solution, which can be implemented in drive-by-wire vehicles with hitch angle sensors, profits from two methods previously developed by the authors: safe steering by applying a curvature limitation to the leading unit, and a virtual tractor concept for backward motion that includes the complex case of set-point propagation through on-axle hitches. The paper addresses system requirements and provides implementation details to tele-operate two different off- and on-axle combinations of a tracked mobile robot pulling and pushing two dissimilar trailers. PMID:23552102

  8. Apparatus for weighing and identifying characteristics of a moving vehicle

    DOEpatents

    Muhs, J.D.; Jordan, J.K.; Tobin, K.W. Jr.; LaForge, J.V.

    1993-11-09

    Apparatus for weighing a vehicle in motion is provided by employing a plurality of elongated fiber-optic sensors defined by an optical fiber embedded in an encasement of elastomeric material and disposed parallel to each other on the roadway in the path of moving vehicles. Each fiber-optic sensor is provided with contact grid means which can be selectively altered to provide the fiber-optic sensors with sensitivities to vehicular weight different from each other for weighing vehicles in an extended weight range. Switch means are used in conjunction with the fiber-optic sensors to provide signals indicative of the speed of the moving vehicle, the number of axles on the vehicle, weight distribution, tire position, and the wheelbase of the vehicle. The use of a generally N-shaped configuration of switch means also provides a determination of the number of tires on each axle and the tire footprint. When switch means in this configuration are formed of optical fibers, the extent of light transmission through the fibers during contact with the tires of the vehicle is indicative of the vehicle weight. 15 figures.

  9. Quantification of uncertainty in the prediction of railway induced ground vibration due to the use of statistical track unevenness data

    NASA Astrophysics Data System (ADS)

    Lombaert, G.; Galvín, P.; François, S.; Degrande, G.

    2014-09-01

    Environmental vibrations due to railway traffic are predominantly due to dynamic axle loads caused by wheel and track unevenness and impact excitation by rail joints and wheel flats. Because of its irregular character, track unevenness is commonly processed statistically and represented by its power spectral density function or its root mean square (RMS) value in one-third octave bands. This statistical description does not uniquely define the track unevenness at a given site, however, and different track unevenness profiles matching the statistical description will lead to different predictions of dynamic axle loads and resulting ground vibration. This paper presents a methodology that allows quantifying the corresponding variability in ground vibration predictions. The procedure is derived assuming the geometry of the track and soil to be homogeneous along the track. The procedure is verified by means of Monte Carlo simulations and its usefulness for assessing the mismatch between predicted and measured ground vibrations is demonstrated in a case study. The results show that the response in time domain and its narrow band spectrum exhibit significant variability which is reduced when the running RMS value or the one-third octave band spectrum of the response is considered.

  10. An Annotated Selective Bibliography on Human Performance in Fault Diagnosis Tasks

    DTIC Science & Technology

    1980-01-01

    and automated fault diagnosis has been omitted from this bibliography. Where possible, we used the abstract that accompanied an item. However, we...system failure, ignition system failure, drive, transmission, and rear axle trouble, and power brake and power steering failure. 98 pages Howard W. Sams...knowledge. The second section discusses some of the pedagogical issues that have emerged from the use of diagnostic models within an instructional

  11. Catalog of components for electric and hybrid vehicle propulsion systems

    NASA Technical Reports Server (NTRS)

    Eissler, H. C.

    1981-01-01

    This catalog of commercially available electric and hybrid vehicle propulsion system components is intended for designers and builders of these vehicles and contains 50 categories of components. These categories include those components used between the battery terminals and the output axle hub, as well as some auxiliary equipment. An index of the components and a listing of the suppliers and their addresses and phone numbers are included.

  12. A Saturation Balancing Control Method for Enhancing Dynamic Vehicle Stability (PREPRINT)

    DTIC Science & Technology

    2011-03-01

    force estimation; axle saturation level; independent drive; torque biasing; 1. Introduction Vehicle stability control ( VSC ) systems have widely been...shown to reduce accidents by minimizing driver’s loss of control during aggressive emergency maneuvers. VSC systems manipulate one or more of the... VSC (also referred to as vehicle dynamics control (VDC)) systems available on the market today are brake-based systems which extend the functionality

  13. Qualitative Maintenance Experience Handbook. P-3C/S-3A Supplement.

    DTIC Science & Technology

    1977-06-15

    axle which automatically assists in disc alignment, a positive feature, in easing maintenance and preventing casual damage. Brake assemblies should...Reverse Of Removal Use brake tool to align brake discs . After Installation Actions: _ Bleed _ Rig _ Adjust X Service Lubricate - Boresight. _ Other...Hydraulic I Access Required: Test Equipment Required: Actions: 1. Check clearance of discs after brakes are put on. 2. Apply brakes . 8 ANALYST’S COMMENTS

  14. None of the Rotor Residues of F1-ATPase Are Essential for Torque Generation

    PubMed Central

    Chiwata, Ryohei; Kohori, Ayako; Kawakami, Tomonari; Shiroguchi, Katsuyuki; Furuike, Shou; Adachi, Kengo; Sutoh, Kazuo; Yoshida, Masasuke; Kinosita, Kazuhiko

    2014-01-01

    F1-ATPase is a powerful rotary molecular motor that can rotate an object several hundred times as large as the motor itself against the viscous friction of water. Forced reverse rotation has been shown to lead to ATP synthesis, implying that the mechanical work against the motor’s high torque can be converted into the chemical energy of ATP. The minimal composition of the motor protein is α3β3γ subunits, where the central rotor subunit γ turns inside a stator cylinder made of alternately arranged α3β3 subunits using the energy derived from ATP hydrolysis. The rotor consists of an axle, a coiled coil of the amino- and carboxyl-terminal α-helices of γ, which deeply penetrates the stator cylinder, and a globular protrusion that juts out from the stator. Previous work has shown that, for a thermophilic F1, significant portions of the axle can be truncated and the motor still rotates a submicron sized bead duplex, indicating generation of up to half the wild-type (WT) torque. Here, we inquire if any specific interactions between the stator and the rest of the rotor are needed for the generation of a sizable torque. We truncated the protruding portion of the rotor and replaced part of the remaining axle residues such that every residue of the rotor has been deleted or replaced in this or previous truncation mutants. This protrusionless construct showed an unloaded rotary speed about a quarter of the WT, and generated one-third to one-half of the WT torque. No residue-specific interactions are needed for this much performance. F1 is so designed that the basic rotor-stator interactions for torque generation and control of catalysis rely solely upon the shape and size of the rotor at very low resolution. Additional tailored interactions augment the torque to allow ATP synthesis under physiological conditions. PMID:24853745

  15. Off-road axle detection sensor (ORADS) : executive summary, April 2001.

    DOT National Transportation Integrated Search

    2001-04-01

    Spectra Research has developed a non-intrusive lane monitoring sensor which can be used to measure and classify vehicular traffic over multiple lane roadways. This sensor employs dual beam laser radar (LADAR) that accurately measures location and pas...

  16. Off-road axle detection sensor (ORADS) : final report, April 2001.

    DOT National Transportation Integrated Search

    2001-04-01

    Spectra Research has developed a non-intrusive lane monitoring sensor which can be used to measure and classify vehicular traffic over multiple lane roadways. This sensor employs dual beam laser radar (LADAR) that accurately measures location and pas...

  17. M1078 Hybrid Hydraulic Vehicle Fuel Economy Evaluation

    DTIC Science & Technology

    2012-09-01

    intermediate starts and stops on a dry concrete surface free from any lose material without stalling, slipping , overheating, or upsetting. 6.93...speed, lockable transfer case, which transmits power via driveshafts to the front and rear ring and pinion sets, differentials, and axles. Wheel hub...of transmission housing and turbine shaft to hydraulically orient and seal the transmission and provide attachment to the input pump motor. With the

  18. Siah1/2 Ubiquitin Ligases in ER Stress Signaling in Melanoma

    DTIC Science & Technology

    2015-10-01

    expression of RTK including EGFR, PDGFR and AXL , which were shown to be important in melanoma resistance phenotypes. This study was published few months ago...year will establish novel therapeutic modality for treatment of cancer, focused on melanoma. Major Task 3: Determine the effect of Siah1/2 and ER...foundation for novel stratification methods and therapeutic modalities for BCa. Specific Aims: (1) Identify RNF5-dependent and -independent

  19. Reliability and validity of the Microsoft Kinect for assessment of manual wheelchair propulsion.

    PubMed

    Milgrom, Rachel; Foreman, Matthew; Standeven, John; Engsberg, Jack R; Morgan, Kerri A

    2016-01-01

    Concurrent validity and test-retest reliability of the Microsoft Kinect in quantification of manual wheelchair propulsion were examined. Data were collected from five manual wheelchair users on a roller system. Three Kinect sensors were used to assess test-retest reliability with a still pose. Three systems were used to assess concurrent validity of the Kinect to measure propulsion kinematics (joint angles, push loop characteristics): Kinect, Motion Analysis, and Dartfish ProSuite (Dartfish joint angles were limited to shoulder and elbow flexion). Intraclass correlation coefficients revealed good reliability (0.87-0.99) between five of the six joint angles (neck flexion, shoulder flexion, shoulder abduction, elbow flexion, wrist flexion). ICCs suggested good concurrent validity for elbow flexion between the Kinect and Dartfish and between the Kinect and Motion Analysis. Good concurrent validity was revealed for maximum height, hand-axle relationship, and maximum area (0.92-0.95) between the Kinect and Dartfish and maximum height and hand-axle relationship (0.89-0.96) between the Kinect and Motion Analysis. Analysis of variance revealed significant differences (p < 0.05) in maximum length between Dartfish (mean 58.76 cm) and the Kinect (40.16 cm). Results pose promising research and clinical implications for propulsion assessment and overuse injury prevention with the application of current findings to future technology.

  20. Vertical and pitching resonance of train cars moving over a series of simple beams

    NASA Astrophysics Data System (ADS)

    Yang, Y. B.; Yau, J. D.

    2015-02-01

    The resonant response, including both vertical and pitching motions, of an undamped sprung mass unit moving over a series of simple beams is studied by a semi-analytical approach. For a sprung mass that is very small compared with the beam, we first simplify the sprung mass as a constant moving force and obtain the response of the beam in closed form. With this, we then solve for the response of the sprung mass passing over a series of simple beams, and validate the solution by an independent finite element analysis. To evaluate the pitching resonance, we consider the cases of a two-axle model and a coach model traveling over rough rails supported by a series of simple beams. The resonance of a train car is characterized by the fact that its response continues to build up, as it travels over more and more beams. For train cars with long axle intervals, the vertical acceleration induced by pitching resonance dominates the peak response of the train traveling over a series of simple beams. The present semi-analytical study allows us to grasp the key parameters involved in the primary/sub-resonant responses. Other phenomena of resonance are also discussed in the exemplar study.

  1. TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation.

    PubMed

    Ji, Rui; Tian, Shifu; Lu, Helen J; Lu, Qingjun; Zheng, Yan; Wang, Xiaomin; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

    2013-12-15

    TAM tyrosine kinases play multiple functional roles, including regulation of the target genes important in homeostatic regulation of cytokine receptors or TLR-mediated signal transduction pathways. In this study, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impairs hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAPK and NF-κB activation and elevated production of proinflammatory cytokines that are detrimental to neuron stem cell proliferation and neuronal differentiation. Injection of LPS causes even more severe inhibition of BrdU incorporation in the Tyro3(-/-)Axl(-/-)Mertk(-/-) triple-knockout (TKO) brains, consistent with the LPS-elicited enhanced expression of proinflammatory mediators, for example, IL-1β, IL-6, TNF-α, and inducible NO synthase, and this effect is antagonized by coinjection of the anti-inflammatory drug indomethacin in wild-type but not TKO brains. Conditioned medium from TKO microglia cultures inhibits neuron stem cell proliferation and neuronal differentiation. IL-6 knockout in Axl(-/-)Mertk(-/-) double-knockout mice overcomes the inflammatory inhibition of neurogenesis, suggesting that IL-6 is a major downstream neurotoxic mediator under homeostatic regulation by TAM receptors in microglia. Additionally, autonomous trophic function of the TAM receptors on the proliferating neuronal progenitors may also promote progenitor differentiation into immature neurons.

  2. Risk of large-scale evacuation based on the effectiveness of rescue strategies under different crowd densities.

    PubMed

    Wang, Jinghong; Lo, Siuming; Wang, Qingsong; Sun, Jinhua; Mu, Honglin

    2013-08-01

    Crowd density is a key factor that influences the moving characteristics of a large group of people during a large-scale evacuation. In this article, the macro features of crowd flow and subsequent rescue strategies were considered, and a series of characteristic crowd densities that affect large-scale people movement, as well as the maximum bearing density when the crowd is extremely congested, were analyzed. On the basis of characteristic crowd densities, the queuing theory was applied to simulate crowd movement. Accordingly, the moving characteristics of the crowd and the effects of typical crowd density-which is viewed as the representation of the crowd's arrival intensity in front of the evacuation passageways-on rescue strategies was studied. Furthermore, a "risk axle of crowd density" is proposed to determine the efficiency of rescue strategies in a large-scale evacuation, i.e., whether the rescue strategies are able to effectively maintain or improve evacuation efficiency. Finally, through some rational hypotheses for the value of evacuation risk, a three-dimensional distribution of the evacuation risk is established to illustrate the risk axle of crowd density. This work aims to make some macro, but original, analysis on the risk of large-scale crowd evacuation from the perspective of the efficiency of rescue strategies. © 2012 Society for Risk Analysis.

  3. Influence of AC system design on the realisation of tractive efforts by high adhesion locomotives

    NASA Astrophysics Data System (ADS)

    Spiryagin, Maksym; Wolfs, Peter; Cole, Colin; Stichel, Sebastian; Berg, Mats; Manfred, Plöchl

    2017-08-01

    The main task for heavy haul railway operators is to reduce the cost of exported minerals and enhance the long-term viability of rail transport operations through increasing productivity by running longer and heavier trains. The common opinion is that this is achievable by means of implementation of high adhesion locomotives with advanced AC traction technologies. Modern AC high adhesion locomotives are very complex mechatronic systems and can be designed with two alternative traction topologies of either bogie or individual axle controls. This paper describes a modelling approach for these two types of AC traction systems with the application of an advanced co-simulation methodology, where an electrical system and a traction algorithm are modelled in Matlab/Simulink, and a mechanical system is modelled in a multibody software package. Although the paper concentrates on the analysis of the functioning for these two types of traction control systems, the choice of reference slip values also has an influence on the performance of both systems. All these design variations and issues have been simulated for various adhesion conditions at the wheel-rail interface and their influence on the high traction performance of a locomotive equipped with two three-axle bogies has been discussed.

  4. Facing rim cavities fluctuation modes

    NASA Astrophysics Data System (ADS)

    Casalino, Damiano; Ribeiro, André F. P.; Fares, Ehab

    2014-06-01

    Cavity modes taking place in the rims of two opposite wheels are investigated through Lattice-Boltzmann CFD simulations. Based on previous observations carried out by the authors during the BANC-II/LAGOON landing gear aeroacoustic study, a resonance mode can take place in the volume between the wheels of a two-wheel landing gear, involving a coupling between shear-layer vortical fluctuations and acoustic modes resulting from the combination of round cavity modes and wheel-to-wheel transversal acoustic modes. As a result, side force fluctuations and tonal noise side radiation take place. A parametric study of the cavity mode properties is carried out in the present work by varying the distance between the wheels. Moreover, the effects due to the presence of the axle are investigated by removing the axle from the two-wheel assembly. The azimuthal properties of the modes are scrutinized by filtering the unsteady flow in narrow bands around the tonal frequencies and investigating the azimuthal structure of the filtered fluctuation modes. Estimation of the tone frequencies with an ad hoc proposed analytical formula confirms the observed modal properties of the filtered unsteady flow solutions. The present study constitutes a primary step in the description of facing rim cavity modes as a possible source of landing gear tonal noise.

  5. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dowdy, M.W.; Couch, M.D.

    A vehicle comparison methodology based on the Otto-Engine Equivalent (OEE) vehicle concept is described. As an illustration of this methodology, the concept is used to make projections of the fuel economy potential of passenger cars using various alternative power systems. Sensitivities of OEE vehicle results to assumptions made in the calculational procedure are discussed. Factors considered include engine torque boundary, rear axle ratio, performance criteria, engine transient response, and transmission shift logic.

  6. The Otto-engine-equivalent vehicle concept

    NASA Technical Reports Server (NTRS)

    Dowdy, M. W.; Couch, M. D.

    1978-01-01

    A vehicle comparison methodology based on the Otto-Engine Equivalent (OEE) vehicle concept is described. As an illustration of this methodology, the concept is used to make projections of the fuel economy potential of passenger cars using various alternative power systems. Sensitivities of OEE vehicle results to assumptions made in the calculational procedure are discussed. Factors considered include engine torque boundary, rear axle ratio, performance criteria, engine transient response, and transmission shift logic.

  7. Procedures for One-Pass Vehicle Cone Index (VCI1) Determination for Acquisition Support

    DTIC Science & Technology

    2013-08-01

    the VCI of tracked vehicles can be directly compared to that of wheeled vehicles; Priddy and Willoughby, 2006). Measurement of the minimum soil...of the wheel , or number of revolutions per unit time divided by 2π for a track v = forward velocity of vehicle or wheel axle. 12. Trafficability...be tested at the expected gross vehicle weight (GVW) and, for wheeled vehicles, at an appropriate soft-soil tire pressure. For wheeled vehicles

  8. Theoretical and experimental research on the phenomenon of stick-slip at traction railway vehicles

    NASA Astrophysics Data System (ADS)

    Sebesan, Ioan; Manea, Ion; Spiroiu, Marius Adrian; Arsene, Sorin

    2018-01-01

    The stick-slip phenomenon may occur when the limit adhesion force is exceeded at one of the motor axles of the vehicle. In the present paper is analysed the physical phenomenon stick-slip, the conditions for its occurrence and the mechanical model recommended for the study of the phenomenon. Regarding the experimental research, it is presented the stand built in the laboratory of the Rolling Stock Department at Politehnica University of Bucharest.

  9. Wheel brakes and their application to aircraft

    NASA Technical Reports Server (NTRS)

    Dowty, G H

    1928-01-01

    The advantages to be gained from braking have not been ignored, and in the search for a suitable method many schemes have been suggested and tried. Some of the methods discussed in this paper include: 1) increasing the height of the landing gear; 2) air brakes of various forms; 3) sprags on tail skid and axle; and 4) wheel brakes. This report focuses on the design of wheel brakes and wheel brake controls.

  10. SeaFrame: Innovation Leads to Superior Warfighting Capability. Volume 4, Issue 1, 2008

    DTIC Science & Technology

    2008-01-01

    U” stands for utility, “K” stands for front wheel drive, and “W” indicates two rear-driving axles .) AMPHIBIOUS FORCE LOGISTIC SUPPORT...using the very latest state-of-the-art instrumentation and analysis techniques,” says Gabor Karafiath, one of the project’s principal investigators. “I...first with standard bladed propulsors with struts and shafting . Then, the model was modified to accom- modate four waterjets, the nozzles of which were

  11. Proceedings of the ISTVS (International Society for Terrain-Vehicle Systems) Workshop on Measurement and Evaluation of Tire Performance under Winter Conditions, Alta, Utah, 11-14 April 1983.

    DTIC Science & Technology

    1985-09-01

    Transducers capable of measuring electro-hydraulic control system which fore-aft and vertical load on a driven controls the brake system to deactivate tire...power. * axle allows design of all load-carrying - System logic power. ENGINE I EXTERNAL COMPARTMENT COMPONENTS CAB Brake Levelin system I trans... brake con- The TWS DAS was designed to 1) pro- trol system . vide onboard data sampling and filtering, A simplified truck operational flow chart 2) make

  12. Indirect Tire Monitoring System - Machine Learning Approach

    NASA Astrophysics Data System (ADS)

    Svensson, O.; Thelin, S.; Byttner, S.; Fan, Y.

    2017-10-01

    The heavy vehicle industry has today no requirement to provide a tire pressure monitoring system by law. This has created issues surrounding unknown tire pressure and thread depth during active service. There is also no standardization for these kind of systems which means that different manufacturers and third party solutions work after their own principles and it can be hard to know what works for a given vehicle type. The objective is to create an indirect tire monitoring system that can generalize a method that detect both incorrect tire pressure and thread depth for different type of vehicles within a fleet without the need for additional physical sensors or vehicle specific parameters. The existing sensors that are connected communicate through CAN and are interpreted by the Drivec Bridge hardware that exist in the fleet. By using supervised machine learning a classifier was created for each axle where the main focus was the front axle which had the most issues. The classifier will classify the vehicles tires condition and will be implemented in Drivecs cloud service where it will receive its data. The resulting classifier is a random forest implemented in Python. The result from the front axle with a data set consisting of 9767 samples of buses with correct tire condition and 1909 samples of buses with incorrect tire condition it has an accuracy of 90.54% (0.96%). The data sets are created from 34 unique measurements from buses between January and May 2017. This classifier has been exported and is used inside a Node.js module created for Drivecs cloud service which is the result of the whole implementation. The developed solution is called Indirect Tire Monitoring System (ITMS) and is seen as a process. This process will predict bad classes in the cloud which will lead to warnings. The warnings are defined as incidents. They contain only the information needed and the bandwidth of the incidents are also controlled so incidents are created within an

  13. Rolling Friction on a Wheeled Laboratory Cart

    DTIC Science & Technology

    2012-01-01

    by gravity, and a vehicle (such as a car or bicycle) accelerating along a level road is driven by a motor or by pedalling. In such cases, static...is slowing down, its acceleration a points downhill). The normal force N, frictional force f and axle torque four wheels. θ υ N a θ ω τ ƒ mg...friction force pointed backward (to translationally decelerate the object), then it would simultaneously rotationally accelerate the cylinder about its

  14. Hydrodynamic Forces on Composite Structures

    DTIC Science & Technology

    2014-06-01

    and placed under a vacuum of 10 mmHg overnight. The vacuum set up over the composite sample is shown in Figure 13, the hose in upper left leads to...pulley system, one of which drives the carriage via a braided steel cable. Although the pulley connection between the motor and the drive axle may...slip this system contains a tensioner device. More likely, the braided steel cable is slipping against the drive pulley which has a quarter-inch

  15. Posture Report.

    DTIC Science & Technology

    1980-01-01

    TON M871 22-1/2 Ton Semitrailer The M871 is a flatbed semitrailer, 30 feet long2- and 5 TON COMMERCIAL with tandem axle suspension, capable of TRUCK...It attenuates the peak blast impact im- SUSPENSION celerometers, developemnt of laminate stack pulses to the interior mounted equipment and bonding...and Carl .,nkley Patent No 4,180,599 issued 25 Dec 79 COMPOSITE LAMINATED VEHICLE ARMOR OF LASER SCANNER to Dr. Stephen M. Wolpert and Gustav J

  16. Tracked Vehicle Road Wheel Puller

    DTIC Science & Technology

    2009-02-01

    employed for removing smaller-size components, such as bolts and the like. U.S. Patent No. 5,410,792, issued to Freeman (3), discloses a caster wheel ...separation of the rubberized annular layer from the outer annular surface of the wheel . Figure 5 further illustrates a modification of the wheel puller...2001. 2. Rubino et al. Pulling Tool. U.S. Patent 5,479,688, 1996. 3. Freeman. Caster Wheel Axle Extraction Apparatus. U.S. Patent 5,410,792

  17. Analysis of Stress Distributions Under Lightweight Wheeled Vehicles

    DTIC Science & Technology

    2013-10-09

    For a balanced analysis it is important at examine the full scale error ε f . Sinkage error, although large in a relative sense is typically on the...director of the Edgerton Center at MIT, to Thuan Doan, and to Meccanotecnica Riesi SRL for collaborating on manufacturing the custom sensing array...a pulling/braking force at the vehicle axle. Fx = T −Rc (33) The importance of drawbar force is obvious, since a positive drawbar force implies that

  18. Diagnostic Health Monitoring System Development for Army Vehicle Reliability

    DTIC Science & Technology

    2011-07-01

    19-24 3.4 Receiver Operator Characteristics for fault detection ……………………….. 24-28 3.5 Extended diagnostic speed bump modal data analysis...extended diagnostic speed bump was akin to the use of modal impact testing for exciting broadband frequency ranges in mechanical systems for use in...for a front axle wheel crossing measured using long cleat for ( ) first 30, ( ) second 11, ( ) third 11, ( ) fourth 11, and ( ) fifth 11 data series

  19. The CRREL Instrumented Vehicle: Hardware and Software.

    DTIC Science & Technology

    1983-01-01

    rear axle torque are meas- ured. The vehicle is equipped for front-wheel, rear-wheel or four-wheel drive. A dual brake system allows front-, rear- or...four-wheel braking . A minicomputer- based data acquisition system is installed in the vehicle to control data gather ing and to process the data. The...o..o...o 4 4. Dual brake system control valves . ........ 5 5. Schematic of modified brake system ...... .... st 5 6. Air-shock-absorber regulator

  20. Heavy and overweight vehicle brake testing : combination six-axle, final report.

    DOT National Transportation Integrated Search

    2017-05-01

    The Heavy and Overweight Vehicle Brake Testing (HOVBT) program exists in order to provide information about the effect of gross vehicle weight (GVW) and on braking performance testing included service brake stopping distance tests, constant-pressure ...

  1. Risk appraisal of passing zones on two-lane rural highways and policy applications.

    PubMed

    Mwesige, Godfrey; Farah, Haneen; Koutsopoulos, Haris N

    2016-05-01

    Passing on two-lane rural highways is associated with risks of head-on collision resulting from unsafe completion of passing maneuvers in the opposite traffic lane. In this paper, we explore the use of time-to-collision (TTC) as a surrogate safety measure of the risk associated with passing maneuvers. Logistic regression models to predict the probability to end the passing maneuver with TTC less than 2 or 3s-threshold were developed with the time-gap from initiation of the maneuver to arrival of the opposite vehicle (effective accepted gap), and the passing duration as explanatory variables. The data used for model estimation was collected using stationary tripod-mounted camcorders at 19 passing zones in Uganda. Results showed that passing maneuvers completed with TTC less than 3s are unsafe and often involved sudden speed reduction, flashing headlights, and lateral shift to shoulders. Model sensitivity analysis was conducted for observed passing durations involving passenger cars or short trucks (2-3 axles), and long trucks (4-7 axles) as the passed vehicles for 3s TTC-threshold. Three risk levels were proposed based on the probability to complete passing maneuvers with TTC less than 3s for a range of opposite direction traffic volumes. Applications of the results for safety improvements of two-lane rural highways are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Toward a four-toothed molecular bevel gear with C2-symmetrical rotors.

    PubMed

    Kao, Chen-Yi; Hsu, Ya-Ting; Lu, Hsiu-Feng; Chao, Ito; Huang, Shou-Ling; Lin, Ying-Chih; Sun, Wei-Ting; Yang, Jye-Shane

    2011-07-15

    The design, synthesis, conformational analysis, and variable-temperature NMR studies of pentiptycene-based molecular gears Pp(2)X, where Pp is the unlabeled (in 1H) or methoxy groups-labeled (in 1OM) pentiptycene rotor and X is the phenylene stator containing ortho-bridged ethynylene axles, are reported. The approach of using shape-persistent rotors of four teeth but C(2) symmetry for constructing four-toothed molecular gears is unprecedented. In addition, the first example of enantioresolution of chiral pentiptycene scaffolds is demonstrated. Density functional theory (DFT) and AM1 calculations on these Pp(2)X systems suggest two possible correlated torsional motions, geared rocking and four-toothed geared rotations, which compete with the uncorrelated gear slippage. The DFT-derived torsional barriers in 1H for rocking, four-toothed rotation, and gear slippage are approximately 2.9, 5.5, and 4.7 kcal mol(-1), respectively. The low energy barriers for these torsional motions result from the low energy cost of bending the ethynylene axles. Comparison of the NMR spectra of 1OM in a mixture of stereoisomers (1OM-mix) and in an enantiopure form (1OM-op) confirms a fast gear slippage in these Pp(2)X systems. The effect of the methoxy labels on rotational potential energy surface and inter-rotor dynamics is also discussed.

  3. Engine classification using vibrations measured by Laser Doppler Vibrometer on different surfaces

    NASA Astrophysics Data System (ADS)

    Wei, J.; Liu, Chi-Him; Zhu, Zhigang; Vongsy, Karmon; Mendoza-Schrock, Olga

    2015-05-01

    In our previous studies, vehicle surfaces' vibrations caused by operating engines measured by Laser Doppler Vibrometer (LDV) have been effectively exploited in order to classify vehicles of different types, e.g., vans, 2-door sedans, 4-door sedans, trucks, and buses, as well as different types of engines, such as Inline-four engines, V-6 engines, 1-axle diesel engines, and 2-axle diesel engines. The results are achieved by employing methods based on an array of machine learning classifiers such as AdaBoost, random forests, neural network, and support vector machines. To achieve effective classification performance, we seek to find a more reliable approach to pick authentic vibrations of vehicle engines from a trustworthy surface. Compared with vibrations directly taken from the uncooperative vehicle surfaces that are rigidly connected to the engines, these vibrations are much weaker in magnitudes. In this work we conducted a systematic study on different types of objects. We tested different types of engines ranging from electric shavers, electric fans, and coffee machines among different surfaces such as a white board, cement wall, and steel case to investigate the characteristics of the LDV signals of these surfaces, in both the time and spectral domains. Preliminary results in engine classification using several machine learning algorithms point to the right direction on the choice of type of object surfaces to be planted for LDV measurements.

  4. Interlocking Molecular Gear Chains Built on Surfaces.

    PubMed

    Zhao, Rundong; Qi, Fei; Zhao, Yan-Ling; Hermann, Klaus E; Zhang, Rui-Qin; Van Hove, Michel A

    2018-05-17

    Periodic chains of molecular gears in which molecules couple with each other and rotate on surfaces have been previously explored by us theoretically using ab initio simulation tools. On the basis of the knowledge and experience gained about the interactions between neighboring molecular gears, we here explore the transmission of rotational motion and energy over larger distances, namely, through a longer chain of gear-like passive "slave" molecules. Such microscopic gears exhibit quite different behaviors compared to rigid cogwheels in the macroscopic world due to their structural flexibility affecting intermolecular interaction. Here, we investigate the capabilities of such gear chains and reveal the mechanisms of the transmission process in terms of both quantum-level density functional theory (DFT) and simple classical mechanics. We find that the transmission of rotation along gear chains depends strongly on the gear-gear distance: short distances can cause tilting of gears and even irregular "creep-then-jump" (or "stick-slip") motion or expulsion of gears; long gear-gear distances cause weak coupling between gears, slipping and skipping. More importantly, for transmission of rotation at intermediate gear-gear distances, our modeling clearly exhibits the relative roles of several important factors: flexibility of gear arms, axles, and supports, as well as resulting rotational delays, slippages, and thermal and other effects. These studies therefore allow better informed design of future molecular machine components involving motors, gears, axles, etc.

  5. Further study on the wheel-rail impact response induced by a single wheel flat: the coupling effect of strain rate and thermal stress

    NASA Astrophysics Data System (ADS)

    Jing, Lin; Han, Liangliang

    2017-12-01

    A comprehensive dynamic finite-element simulation method was proposed to study the wheel-rail impact response induced by a single wheel flat based on a 3-D rolling contact model, where the influences of the structural inertia, strain rate effect of wheel-rail materials and thermal stress due to the wheel-rail sliding friction were considered. Four different initial conditions (i.e. pure mechanical loading plus rate-independent, pure mechanical loading plus rate-dependent, thermo-mechanical loading plus rate-independent, and thermo-mechanical loading plus rate-dependent) were involved into explore the corresponding impact responses in term of the vertical impact force, von-Mises equivalent stress, equivalent plastic strain and shear stress. Influences of train speed, flat length and axle load on the flat-induced wheel-rail impact response were discussed, respectively. The results indicate that the maximum thermal stresses are occurred on the tread of the wheel and on the top surface of the middle rail; the strain rate hardening effect contributes to elevate the von-Mises equivalent stress and restrain the plastic deformation; and the initial thermal stress due to the sliding friction will aggravate the plastic deformation of wheel and rail. Besides, the wheel-rail impact responses (i.e. impact force, von-Mises equivalent stress, equivalent plastic strain, and XY shear stress) induced by a flat are sensitive to the train speed, flat length and axle load.

  6. A hub dynamometer for measurement of wheel forces in off-road bicycling.

    PubMed

    De Lorenzo, D S; Hull, M L

    1999-02-01

    A dynamometric hubset that measures the two ground contact force components acting on a bicycle wheel in the plane of the bicycle during off-road riding while either coasting or braking was designed, constructed, and evaluated. To maintain compatibility with standard mountain bike construction, the hubs use commercially available shells with modified, strain gage-equipped axles. The axle strain gages are sensitive to forces acting in the radial and tangential directions, while minimizing sensitivity to transverse forces, steering moments, and variations in the lateral location of the center of pressure. Static calibration and a subsequent accuracy check that computed differences between applied and apparent loads developed during coasting revealed root mean squared errors of 1 percent full-scale or less (full-scale load = 4500 N). The natural frequency of the rear hub with the wheel attached exceeded 350 Hz. These performance capabilities make the dynamometer useful for its intended purpose during coasting. To demonstrate this usefulness, sample ground contact forces are presented for a subject who coasted downhill over rough terrain. The dynamometric hubset can also be used to determine ground contact forces during braking providing that the brake reaction force components are known. However, compliance of the fork can lead to high cross-sensitivity and corresponding large (> 5 percent FS) measurement errors at the front wheel.

  7. Research of cost aspects of cement pavements construction

    NASA Astrophysics Data System (ADS)

    Bezuglyi, Artem; Illiash, Sergii; Tymoshchuk, Oleksandr

    2017-09-01

    The tendency to increasing traffic volume on public roads and to increased axle loads of vehicles makes the road scientists to develop scientifically justified methods for preserving the existing and developing the new transport network of Ukraine. One of the options for solving such issues is the construction of roads with rigid (cement concrete) pavement. However, any solution must be justified considering technical and economic components. This paper presents the results of the research of cost aspects of cement pavements construction.

  8. 26. SOUTH TO CIRCA 1865 METALTURNING LATHE (POSSIBLY MADE BY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    26. SOUTH TO CIRCA 1865 METAL-TURNING LATHE (POSSIBLY MADE BY AMES MFG. CO., CHICOPEE, MASS.) WITH PARTS/TOOL BINS ALONG EAST INTERIOR WALL OF FACTORY. BENEATH THE LATHE ON THE FLOOR IS A STACK OF AUTOMOBILE AXLES AS 'RAW MATERIAL' FOR FABRICATING REPAIR PARTS FOR PUMPS AND WATER SUPPLY EQUIPMENT. ON THE POST BEHIND THE MACHINE IS ONE OF THE HISTORIC ELECTRICAL FUSE/SWITCH BOXES FOR THE FACTORY. - Kregel Windmill Company Factory, 1416 Central Avenue, Nebraska City, Otoe County, NE

  9. Objectification of Public Bus Stop's Pavement Surface Morphology

    NASA Astrophysics Data System (ADS)

    Decký, Martin; Kováč, Matúš; Mužík, Juraj; Mičechová, Lenka; Ďuriš, Lukáš

    2018-06-01

    The article deals with the road pavement surface morphology objectification in term of the surface unevenness degradation during the life cycle of bus stop pavements. The article presents the results of long-term rut depth measurements performed during 25 years on selected bus stops which were intended to determine correlation dependences of pavement rut depth on a number of design axles. The article also presents different methods for rut depth measurements including the straightedge test, Profilograph GE, TRIMBLE CX, and dynamic Road Scanner.

  10. Review and Evaluation of Contingency Plans for Oil and Hazardous Substances in the Upper Great Lakes Region

    DTIC Science & Technology

    1986-11-15

    reproduced photographically and laminated to a format 35 cm wide by 42 cm high. Maps were enclosed in a binder with each individual map being removable for...FLATBDS, TRACT1V 40 Ft. Flatbed w/Tractor 12 Ton Lowboy w/Tractor 35 Ton Lowboy w/Tractor 50 Ton Lowboy w/Tractor Over-The-Road Tractor Rig Tandem Axle...Mechanics Van All-terrain vehicle Flatbeds (4) (with tarp covers) Emergency Air Supply Van Tractors (4) (2 equipped with gear pumps) 20 yard Rolloff boxes

  11. Hybrid Soft Soil Tire Model (HSSTM). Part 1: Tire Material and Structure Modeling

    DTIC Science & Technology

    2015-04-28

    commercially available vehicle simulation packages. Model parameters are obtained using a validated finite element tire model, modal analysis, and other...design of experiment matrix. This data, in addition to modal analysis data were used to validate the tire model. Furthermore, to study the validity...é ë ê ê ê ê ê ê ê ù û ú ú ú ú ú ú ú (78) The applied forces to the rim center consist of the axle forces and suspension forces: FFF Gsuspension G

  12. Drop and Flight Tests on NY-2 Landing Gears Including Measurements of Vertical Velocities at Landing

    NASA Technical Reports Server (NTRS)

    Peck, W D; Beard, A P

    1933-01-01

    This investigation was conducted to obtain quantitative information on the effectiveness of three landing gears for the NY-2 (consolidated training) airplane. The investigation consisted of static, drop, and flight tests on landing gears of the oleo-rubber-disk and the mercury rubber-chord types, and flight tests only on a landing gear of the conventional split-axle rubber-cord type. The results show that the oleo gear is the most effective of the three landing gears in minimizing impact forces and in dissipating the energy taken.

  13. Combat Squadrons of the Air Force, World War II,

    DTIC Science & Technology

    1982-01-01

    1952. Inactivated on 1 Jul 1957. Redes- of a paddle wheel river boat, Air Force ignated 7o2d Troop Carrier Squadron blue, the windows lighted Air Force ...782d Bombard- hitched to a red wagon with wheels red, ment Squadron (Heavy) on 19 May hub yellow, tires and axles black, the 1943. Activated on 1 Aug...AD-A128 026 COMBAT SQUADRONS OF TOE AIR FORCE WORLD WAR IU) 1OFFICEOF AIR FORCE HISTORY WASHINGTON DC M MAURER UNCLASSIFIED F/G 15/7 NL

  14. The mechanics of gyroscope ball bearings

    NASA Astrophysics Data System (ADS)

    Zhuravlev, V. F.; Balmont, V. B.

    Various aspects of the mechanics of gyroscopes are examined with emphasis on the elastic properties of the radial thrust ball bearings of the main axle and of the radial ball bearings of the gimbal suspension, covers, and flanges. Particular attention is given to the statics, kinematics, and dynamics of imperfect bearings. A stiffnes model convenient for engineering calculations is developed. A gyroscope vibration theory is proposed, and methods for reducing and preventing vibration are analyzed. The validity of the models proposed here is supported by experimental data.

  15. An implantable seal-less centrifugal pump with integrated double-disk motor.

    PubMed

    Schima, H; Schmallegger, H; Huber, L; Birgmann, I; Reindl, C; Schmidt, C; Roschal, K; Wieselthaler, G; Trubel, W; Losert, U

    1995-07-01

    Thrombus formation and sealing problems at the shaft as well as the compact and efficient design of the driving unit have been major difficulties in the construction of a long-term implantable centrifugal pump. To eliminate the problems of the seal, motor size, and efficiency, two major steps were taken by modifying the Vienna implantable centrifugal pump. First, a special driving unit was developed, in which the permanent magnets of the motor themselves are used for coupling the force into the rotor. Second, the rotor shaft in the pumping chamber was eliminated by adopting a concept recently presented by Ohara. The rotor is supported by 3 pins, which run on a carbon disk, whose concave shape leads to stabilization. The device has the following specifications: size: 65 mm (diameter) by 35 mm (height), 101 cm3; priming volume 30 cm3, 240 g; and a 6-pole brushless double disk DC motor. The required input power of the described prototype is 15 W at 150 mm Hg, 5 L/min (overall eta = 11%), and has an in vitro index of hemolysis (IH) of 0.0046 g/100 L. The test for in vitro thrombus growth exhibited far less thrombus formation in the new design than in designs with axles. In conclusion, the design of a special driving unit and the elimination of the axle led to the construction of a small pump with very low blood traumatization.

  16. CSF protein changes associated with hippocampal sclerosis risk gene variants highlight impact of GRN/PGRN.

    PubMed

    Fardo, David W; Katsumata, Yuriko; Kauwe, John S K; Deming, Yuetiva; Harari, Oscar; Cruchaga, Carlos; Nelson, Peter T

    2017-04-01

    Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs). Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes. The GRN risk SNP (rs5848) status correlated with variation in CSF proteins, with the risk allele (T) associated with increased levels of AXL Receptor Tyrosine Kinase (AXL), TNF-Related Apoptosis-Inducing Ligand Receptor 3 (TRAIL-R3), Vascular Cell Adhesion Molecule-1 (VCAM-1) and clusterin (CLU) (all p<0.05 after Bonferroni correction). The TRAIL-R3 correlation was significant in meta-analysis with an additional dataset (p=5.05×10 -5 ). Further, the rs5848 SNP status was associated with increased CSF tau protein - a marker of neurodegeneration (p=0.015). These data are remarkable since this GRN SNP has been found to be a risk factor for multiple types of dementia-related brain pathologies. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Army Excellence in Leadership (AXL): Educating Army Leaders with the Tripwire Film

    DTIC Science & Technology

    2007-03-01

    after being placed into your DVD- ROM drive. Once open, you have the choice of playing the film or viewing the trailer . If, after inserting the DVD...8217 suggestions, he himself was not receptive to feedback, and he failed to delegate responsibilities. Questions to facilitate the discussion of establishing trust...about leadership: Mentoring with movies and interactive characters. Proceedings of the 15th Innovative Applications of Artificial Intelligence

  18. Photovoltaic panel clamp

    DOEpatents

    Mittan, Margaret Birmingham [Oakland, CA; Miros, Robert H. J. [Fairfax, CA; Brown, Malcolm P [San Francisco, CA; Stancel, Robert [Loss Altos Hills, CA

    2012-06-05

    A photovoltaic panel clamp includes an upper and lower section. The interface between the assembled clamp halves and the module edge is filled by a flexible gasket material, such as EPDM rubber. The gasket preferably has small, finger like protrusions that allow for easy insertion onto the module edge while being reversed makes it more difficult to remove them from the module once installed. The clamp includes mounting posts or an integral axle to engage a bracket. The clamp also may include a locking tongue to secure the clamp to a bracket.

  19. Photovoltaic panel clamp

    DOEpatents

    Brown, Malcolm P.; Mittan, Margaret Birmingham; Miros, Robert H. J.; Stancel, Robert

    2013-03-19

    A photovoltaic panel clamp includes an upper and lower section. The interface between the assembled clamp halves and the module edge is filled by a flexible gasket material, such as EPDM rubber. The gasket preferably has small, finger like protrusions that allow for easy insertion onto the module edge while being reversed makes it more difficult to remove them from the module once installed. The clamp includes mounting posts or an integral axle to engage a bracket. The clamp also may include a locking tongue to secure the clamp to a bracket.

  20. Workout Machine

    NASA Technical Reports Server (NTRS)

    1995-01-01

    The Orbotron is a tri-axle exercise machine patterned after a NASA training simulator for astronaut orientation in the microgravity of space. It has three orbiting rings corresponding to roll, pitch and yaw. The user is in the middle of the inner ring with the stomach remaining in the center of all axes, eliminating dizziness. Human power starts the rings spinning, unlike the NASA air-powered system. Marketed by Fantasy Factory (formerly Orbotron, Inc.), the machine can improve aerobic capacity, strength and endurance in five to seven minute workouts.

  1. Design of power-transmitting shifts

    NASA Technical Reports Server (NTRS)

    Loewenthal, S. H.

    1984-01-01

    Power transmission shafting which is a vital element of all rotating machinery is discussed. Design methods, based on strength considerations for sizing shafts and axles to withstand both steady and fluctuating loads are summarized. The effects of combined bending, torsional, and axial loads are considered along with many application factors that are known to influence the fatigue strength of shafting materials. Methods are presented to account for variable amplitude loading histories and their influence on limited life designs. The influences of shaft rigidity, materials, and vibration on the design are discussed.

  2. BLAISDELL SLOW SAND FILTER WASHING MACHINE. VIEW LOOKING SOUTH. THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    BLAISDELL SLOW SAND FILTER WASHING MACHINE. VIEW LOOKING SOUTH. THE SUCTION (INTAKE) HOSE IS SEEN AT THE LEFT RESTING ON THE FILTER BED SURFACE; THE DISCHARGE HOSE IS AT THE RIGHT, RUNNING FROM THE BOTTOM OF THE CENTRAL VERTICAL AXLE TO THE CENTRIFUGAL PUMP. FROM THE PUMP WATER IS DISCHARGED THROUGH THE HORIZONTAL PIPE LOCATED UNDER THE EDGE OF PLATFORM DECK INTO THE WASTE-WATER TROUGH (NOT SEEN IN THIS VIEW). - Yuma Main Street Water Treatment Plant, Blaisdell Slow Sand Filter Washing Machine, Jones Street at foot of Main Street, Yuma, Yuma County, AZ

  3. Chinese-English Electronics and Telecommunications Dictionary. Volume 2

    DTIC Science & Technology

    1976-11-01

    cA fS] i^ W ^- bearing pin 01 axial 02 axial symmetry; rotational 03 synmetry axle weight 0« shaft clip 05 collar; burr CM axial ...terminal strips 07 J<A# three-way Joint ; triple Joint 08 K#frtt three-wattmeter method. 09 *t*Ü«f*f* three-dimensional wave propagation 10...design load ; assumed load ; 29 load rating 1040 •hejl genju wttt mm •hejl gongahl sir«* •h«Ji jlauan Äjtrt» •hejl Jlsuanblao ■ it it * /< •h«Jl

  4. Study on Standard Fatigue Vehicle Load Model

    NASA Astrophysics Data System (ADS)

    Huang, H. Y.; Zhang, J. P.; Li, Y. H.

    2018-02-01

    Based on the measured data of truck from three artery expressways in Guangdong Province, the statistical analysis of truck weight was conducted according to axle number. The standard fatigue vehicle model applied to industrial areas in the middle and late was obtained, which adopted equivalence damage principle, Miner linear accumulation law, water discharge method and damage ratio theory. Compared with the fatigue vehicle model Specified by the current bridge design code, the proposed model has better applicability. It is of certain reference value for the fatigue design of bridge in China.

  5. Finite element, modal co-ordinate analysis of structures subjected to moving loads

    NASA Astrophysics Data System (ADS)

    Olsson, M.

    1985-03-01

    Some of the possibilities of the finite element method in the moving load problem are demonstrated. The bridge-vehicle interaction phenomenon is considered by deriving a general bridge-vehicle element which is believed to be novel. This element may be regarded as a finite element with time-dependent and unsymmetric element matrices. The bridge response is formulated in modal co-ordinates thereby reducing the number of equations to be solved within each time step. Illustrative examples are shown for the special case of a beam bridge model and a one-axle vehicle model.

  6. Acoustic and Linguistic Interdependencies of Irregular Phonation

    DTIC Science & Technology

    2010-05-01

    duration in the word ’year’ for a specific TIMIT case. ’ axl " refers to the phonated portion of the ’ I" in ’year’ and ’q’ refers to the inegularly phonated...and trans glottal pressure. Different configurations of the 19 system can lead not only to modal voiced speech and 1I11~oiced speech (the "regular...irregular phonation, despite the fact that they have much more divergent ranges during modal phonation. Males Females Group Range ofIrregular Region 7 -78

  7. Age‐related alterations in immune responses to West Nile virus infection

    PubMed Central

    2016-01-01

    Summary West Nile virus (WNV) is the most important causative agent of viral encephalitis worldwide and an important public health concern in the United States due to its high prevalence, severe disease, and the absence of effective treatments. Infection with WNV is mainly asymptomatic, but some individuals develop severe, possibly fatal, neurological disease. Individual host factors play a role in susceptibility to WNV infection, including genetic polymorphisms in key anti‐viral immune genes, but age is the most well‐defined risk factor for susceptibility to severe disease. Ageing is associated with distinct changes in immune cells and a decline in immune function leading to increased susceptibility to infection and reduced responses to vaccination. WNV is detected by pathogen recognition receptors including Toll‐like receptors (TLRs), which show reduced expression and function in ageing. Neutrophils, monocyte/macrophages and dendritic cells, which first recognize and respond to infection, show age‐related impairment of many functions relevant to anti‐viral responses. Natural killer cells control many viral infections and show age‐related changes in phenotype and functional responses. A role for the regulatory receptors Mertk and Axl in blood–brain barrier permeability and in facilitating viral uptake through phospholipid binding may be relevant for susceptibility to WNV, and age‐related up‐regulation of Axl has been noted previously in human dendritic cells. Understanding the specific immune parameters and mechanisms that influence susceptibility to symptomatic WNV may lead to a better understanding of increased susceptibility in elderly individuals and identify potential avenues for therapeutic approaches: an especially relevant goal, as the world's populating is ageing. PMID:27612657

  8. Microcystin-leucine arginine mediates apoptosis and engulfment of Leydig cell by testicular macrophages resulting in reduced serum testosterone levels.

    PubMed

    Chen, Yabing; Wang, Jing; Chen, Xiang; Li, Dongmei; Han, Xiaodong

    2018-06-01

    Microcystin-leucine arginine (MC-LR) causes decline of serum testosterone levels resulting in impaired spermatogenesis; however, the underlying molecular mechanisms are not fully understood. In this study, we aimed to investigate the effects of MC-LR exposure on the number of Leydig cells (LCs) in testis. Following chronic low dose exposure to MC-LR, the number of LCs was markedly decreased while macrophages were significantly increased. Then, we established a co-culture system to study the interaction between macrophages and LCs in the presence of MC-LR. No significant apoptosis of LCs cultured alone was observed after MC-LR (< 5 000 nM) treatment; however, apoptosis was robustly increased when LCs were co-cultured with macrophages in the presence of MC-LR. Further studies identified that MC-LR could stimulate macrophage to produce TNF-α, and secreted TNF-α induced LC apoptosis by binding to the tumor necrosis factor receptor 1 (TNFR1) on the LCs and thus activating reactive oxygen species (ROS)-p38MAPK signaling pathway. Furthermore, we also examined increased expression of Axl receptor and growth arrest-specific 6 (Gas6) in macrophages after MC-LR treatment. GAS6 mediates phagocytosis of apoptotic LCs by binding to the Axl receptor on macrophages and phosphatidylserine (PtdSer) on apoptotic LCs. Together, these results suggested that reduced serum testosterone levels may be associated with decrease of LCs as a result of LC apoptosis and phagocytosis by immune cells in MC-LR-treated mice. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Reconfiguration of the upper extremity relative to the pushrim affects load distribution during wheelchair propulsion.

    PubMed

    Munaretto, Joseph M; McNitt-Gray, Jill L; Flashner, Henryk; Requejo, Philip S

    2013-08-01

    Repetitive loading during manual wheelchair propulsion (WCP) is associated with overuse injury to the upper extremity (UE). The aim of this study was to determine how RF redirection and load distribution are affected by changes upper extremity kinematic modifications associated with modifications in seat positions during a WCP task. The aim of this study was to determine how RF redirection and load distribution are affected by upper extremity kinematic changes associated with seat position adjustment during a WCP task. Dynamic simulations using an experiment-based multi-link inverse dynamics model were used to generate solutions for redistributing UE mechanical load in different seating positions without decrements in WCP task performance. Experimental RF and kinematic data were collected for one subject propelling at a self-selected speed and used as input into the model. Shoulder/axle distance, wrist angular position, and RF direction were systematically modified to simulate how the mechanical demand imposed on the upper extremity (elbow and shoulder net joint moments (NJMs) and net joint forces) may vary. Load distribution depended on UE orientation relative to the wheel. At peak force, lower shoulder/axle distances and more anterior wrist positions on the pushrim allowed for more extended elbow positions and reduced total NJM load. Simulation results incorporating subject-specific data may provide mechanically based information to guide clinical interventions that aim to maintain WCP performance and redistribute load by modifying RF direction, seat configuration and hand/rim interaction. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved.

  10. Experimental investigation into the mechanism of the polygonal wear of electric locomotive wheels

    NASA Astrophysics Data System (ADS)

    Tao, Gongquan; Wang, Linfeng; Wen, Zefeng; Guan, Qinghua; Jin, Xuesong

    2018-06-01

    Experiments were conducted at field sites to investigate the mechanism of the polygonal wear of electric locomotive wheels. The polygonal wear rule of electric locomotive wheels was obtained. Moreover, two on-track tests have been carried out to investigate the vibration characteristics of the electric locomotive's key components. The measurement results of wheels out-of-round show that most electric locomotive wheels exhibit polygonal wear. The main centre wavelength in the 1/3 octave bands is 200 mm and/or 160 mm. The test results of vibration characteristics indicate that the dominating frequency of the vertical acceleration measured on the axle box is approximately equal to the passing frequency of a polygonal wheel, and does not vary with the locomotive speed during the acceleration course. The wheelset modal analysis using the finite element method (FEM) indicates that the first bending resonant frequency of the wheelset is quite close to the main vibration frequency of the axle box. The FEM results are verified by the experimental modal analysis of the wheelset. Moreover, different plans were designed to verify whether the braking system and the locomotive's adhesion control have significant influence on the wheel polygon or not. The test results indicate that they are not responsible for the initiation of the wheel polygon. The first bending resonance of the wheelset is easy to be excited in the locomotive operation and it is the root cause of wheel polygon with centre wavelength of 200 mm in the 1/3 octave bands.

  11. Prediction of Ground Vibration from Freight Trains

    NASA Astrophysics Data System (ADS)

    Jones, C. J. C.; Block, J. R.

    1996-05-01

    Heavy freight trains emit ground vibration with predominant frequency components in the range 4-30 Hz. If the amplitude is sufficient, this may be felt by lineside residents, giving rise to disturbance and concern over possible damage to their property. In order to establish the influence of parameters of the track and rolling stock and thereby enable the design of a low vibration railway, a theoretical model of both the generation and propagation of vibration is required. The vibration is generated as a combination of the effects of dynamic forces, due to the unevenness of the track, and the effects of the track deformation under successive axle loads. A prediction scheme, which combines these effects, has been produced. A vehicle model is used to predict the dynamic forces at the wheels. This includes the non-linear effects of friction damped suspensions. The loaded track profile is measured by using a track recording coach. The dynamic loading and the effects of the moving axles are combined in a track response model. The predicted track vibration is compared to measurements. The transfer functions from the track to a point in the ground can be calculated by using a coupled track and a three-dimensional layered ground model. The propagation effects of the ground layers are important but the computation of the transfer function from each sleeper, which would be required for a phase coherent summation of the vibration in the ground, would be prohibitive. A compromise summation is used and results are compared with measurements.

  12. Evaluation of powertrain solutions for future tactical truck vehicle systems

    NASA Astrophysics Data System (ADS)

    Pisu, Pierluigi; Cantemir, Codrin-Gruie; Dembski, Nicholas; Rizzoni, Giorgio; Serrao, Lorenzo; Josephson, John R.; Russell, James

    2006-05-01

    The article presents the results of a large scale design space exploration for the hybridization of two off-road vehicles, part of the Future Tactical Truck System (FTTS) family: Maneuver Sustainment Vehicle (MSV) and Utility Vehicle (UV). Series hybrid architectures are examined. The objective of the paper is to illustrate a novel design methodology that allows for the choice of the optimal values of several vehicle parameters. The methodology consists in an extensive design space exploration, which involves running a large number of computer simulations with systematically varied vehicle design parameters, where each variant is paced through several different mission profiles, and multiple attributes of performance are measured. The resulting designs are filtered to choose the design tradeoffs that better satisfy the performance and fuel economy requirements. At the end, few promising vehicle configuration designs will be selected that will need additional detailed investigation including neglected metrics like ride and drivability. Several powertrain architectures have been simulated. The design parameters include the number of axles in the vehicle (2 or 3), the number of electric motors per axle (1 or 2), the type of internal combustion engine, the type and quantity of energy storage system devices (batteries, electrochemical capacitors or both together). An energy management control strategy has also been developed to provide efficiency and performance. The control parameters are tunable and have been included into the design space exploration. The results show that the internal combustion engine and the energy storage system devices are extremely important for the vehicle performance.

  13. [Occupational health administrative coordination a propos of a case: brake linings with asbestos in a company].

    PubMed

    García Gómez, Montserrat; Alonso Urreta, Iciar; Antón Tomey, Carlos; Bosque Peralta, Isabel; García-Gutierrez, María Jesús; Luna Lacarta, Francisco José; Martínez Arguisuelas, Nieves; Mena Marín, María Luisa; Vázquez Cortizo, Margarita

    2018-04-10

    The current structure of the Spanish State of Autonomies is characterized by institutional pluralism and the autonomy of the different public administrations. In this context, the principle of coordination is fundamental for the cohesion of the system, but experience shows that its implementation is difficult. This paper examines the set of actions carried out by the administrations in relation to an occupational and public health problem raised in March 2016. The Public Health General Direction of Aragon's Government was informed of a possible use of brake linings with asbestos to manufacture axles for agricultural machinery by a Company from Zaragoza; the collaboration from Aragon's Institute of Occupational Safety and Health, the Industry Department and the Labour and Social Security Inspectorate were asked; the joint action of these administrations detected the use of several models of brake linings with a content of 2-5% of Chrysotile. The brake linings came from a Chinese company. The axles nated are sold in several Spanish Autonomous Communities. A national alert was activated by the SIRIPQ (System of Rapid Exchange of Information on Chemical Products) which is coordinated by the Ministry of Health, Social Services and Equality. Several measures were taken including: ceasing the work with the brake linings, the replacement of brake linings with asbestos, the immobilization of brake linings in the company by application of the REACH Reglament, etc. This case shows that the cooperation and co-responsibility of public administrations from different territorial, sectoral and competence areas allows improving the occupational risks prevention and the public health.

  14. Relation of anthropometric measurements to ocular biometric changes and refractive error in children with thalassemia.

    PubMed

    Elkitkat, Rania S; El-Shazly, Amany A; Ebeid, Weam M; Deghedy, Marwa R

    2018-03-01

    To evaluate and correlate anthropometric, biometric, and refractive error changes in thalassemia major (TM). One hundred children with TM and another hundred healthy controls were recruited. Height, weight, body mass index (BMI), and occipitofrontal circumference (OFC) were the anthropometric parameters recorded. Full ophthalmologic examination was performed, including best-corrected visual acuity, cycloplegic refraction, slit-lamp examination, Goldmann applanation tonometry, indirect ophthalmoscopy, keratometry (K readings), and ocular biometry. Compared to controls, children with TM were shorter and lighter, with a smaller BMI (p<0.001); however, no significant difference existed in OFC. Regarding ocular biometric data, patients with thalassemia had steeper mean K readings (p = 0.03), shorter axial length (AXL) (p = 0.005), shorter vitreous chamber depth (p<0.001), and thicker crystalline lens (p<0.001) than controls. Patients with thalassemia had a significant myopic shift (p = 0.003). Multiple regression analyses only showed a significant correlation between corneal astigmatism and both weight and height (β = -0.05 and p = 0.03 and β = 0.06 and p = 0.04, respectively). Spherical equivalent was significantly correlated to K readings, lens thickness, and anterior chamber depth (p<0.0001 for all parameters). Compared to controls, children with TM have significant retardation in general and ocular growth (smaller BMI and shorter AXL). Ocular growth changes probably resulted in compensatory biometric changes (steeper corneas and thicker lenses) to reach emmetropization, with an exaggerated response and subsequent myopic shift. However, growth retardation is not directly related to ocular growth changes, myopic shift, or variations in biometric parameters.

  15. TAM receptors in apoptotic cell clearance, autoimmunity, and cancer.

    PubMed

    Nguyen, Khanh-Quynh; Tsou, Wen-I; Kotenko, Sergei; Birge, Raymond B

    2013-08-01

    Receptor tyrosine kinases, Tyro-3, Axl and Mer, collectively designated as TAM, are involved in the clearance of apoptotic cells. TAM ligands, Gas6 and Protein S, bind to the surfaces of apoptotic cells, and at the same time, interact directly with TAM expressed on phagocytes, impacting the engulfment and clearance of apoptotic cells and debris. The well-tuned and balanced actions of TAM may affect a variety of human pathologies including autoimmunity, retinal degeneration, and cancer. This article emphasizes some of the emerging findings and mechanistic insights into TAM functions that are clinically relevant and possibly therapeutically targeted.

  16. Rotatable non-circular forebody flow controller

    NASA Technical Reports Server (NTRS)

    Moskovitz, Cary A. (Inventor)

    1991-01-01

    The invention is a rotatable, non-circular forebody flow controller. The apparatus comprises a small geometric device located at a nose of a forebody of an aircraft and a non-circular cross-sectional area that extends toward the apex of the aircraft. The device is symmetrical about a reference plane and preferably attaches to an axle which in turn attaches to a rotating motor. The motor rotates the device about an axis of rotation. Preferably, a control unit connected to an aircraft flight control computer signals to the rotating motor the proper rotational positioning of the geometric device.

  17. A Nontoxic Barlow's Wheel

    NASA Astrophysics Data System (ADS)

    Daffron, John A.; Greenslade, Thomas B.

    2015-01-01

    Barlow's wheel has been a favorite demonstration since its invention by Peter Barlow (1776-1862) in 1822.1 In the form shown in Fig. 1, it represents the first electric motor. The interaction between the electric current passing from the axle of the wheel to the rim and the magnetic field produced by the U-magnet produces a torque that turns the wheel. The original device used mercury to provide electrical contact to the rim, and the dangers involved with the use of this heavy metal have caused the apparatus to disappear from the lecture hall.

  18. Drag reduction obtained by modifying a standard truck

    NASA Technical Reports Server (NTRS)

    Sheridan, A. E.; Grier, S. J.

    1978-01-01

    A standard two-axle truck with a box-shaped cargo compartment was tested to determine whether significant reductions in aerodynamic drag could be obtained by modifying the front of the cargo compartment. The coastdown method was used to determine the total drag of the baseline vehicle, which had a square-cornered cargo box, and of several modified configurations. Test velocities ranged from 56.3 to 94.6 kilometers per hour (35 to 60 miles per hour). At 88.5 kilometers per hour (55 miles per hour), the aerodynamic drag reductions obtained with the modified configurations ranged from 8 to 30 percent.

  19. Manual Drive Train and Axles. Auto Mechanics Curriculum Guide Module 7. Instructor's Guide.

    ERIC Educational Resources Information Center

    Colesworthy, Robert; Donovan, Roger

    This document is one of a series of modules in the Missouri Auto Mechanics Curriculum Guide, which is based on 144 basic auto mechanics competencies identified on the Missouri Auto Mechanics Competency Profile. The instructor's materials in this document are for a 13-unit secondary education course. The following units are included: (1)…

  20. Heavy and overweight vehicle brake testing : combination five-axle tractor-flatbed, final report

    DOT National Transportation Integrated Search

    2017-05-01

    The Federal Motor Carrier Safety Administration (FMCSA), in coordination with the Federal Highway Administration (FHWA), sponsored the Heavy and Overweight Vehicle Brake Testing (HOVBT) program in order to provide information about the effect of gros...

  1. Gas6 Deficiency Increases Oligodendrocyte Loss and Microglial Activation in Response to Cuprizone-Induced Demyelination

    PubMed Central

    Binder, Michele D.; Cate, Holly S.; Prieto, Anne L.; Kemper, Dennis; Butzkueven, Helmut; Gresle, Melissa M.; Cipriani, Tania; Jokubaitis, Vilija G.; Carmeliet, Peter

    2008-01-01

    The TAM family of receptor protein tyrosine kinases comprises three known members, namely Tyro3, Axl, and Mer. These receptors are widely expressed in the nervous system, including by oligodendrocytes, the cell type responsible for myelinating the CNS. We examined the potential role of the TAM family and of their principle cognate ligand, Gas6 (growth arrest gene 6), in modulating the phenotype of the cuprizone model of demyelination. We found that the expression profiles of Axl, Mer, and Gas6 mRNA were increased in the corpus callosum in a temporal profile correlating with the increased migration and proliferation of microglia/macrophages in this model. In contrast, expression of Tyro3 decreased, correlating with the loss of oligodendrocytes. Gas6 both promoted in vitro survival of oligodendrocytes (39.3 ± 3.1 vs 11.8 ± 2.4%) and modulated markers of activation in purified cultures of microglia (tumor necrosis factor α mRNA expression was reduced ∼48%). In Gas6−/− mice subjected to cuprizone-challenge, demyelination was greater than in control mice, within the rostral region of the corpus callosum, as assessed by luxol fast blue staining (myelination reduced by 36%) and by ultrastructural analysis. An increased loss of Gst-π (glutathione S-transferase-π)-positive oligodendrocytes was also identified throughout the corpus callosum of Gas6−/− mice. Microglial marker expression (ionized calcium-binding adapter molecule 1) was increased in Gas6−/− mice but was restricted to the rostral corpus callosum. Therefore, TAM receptor activation and regulation can independently influence both oligodendrocyte survival and the microglial response after CNS damage. PMID:18480276

  2. Protein S Protects against Podocyte Injury in Diabetic Nephropathy.

    PubMed

    Zhong, Fang; Chen, Haibing; Xie, Yifan; Azeloglu, Evren U; Wei, Chengguo; Zhang, Weijia; Li, Zhengzhe; Chuang, Peter Y; Jim, Belinda; Li, Hong; Elmastour, Firas; Riyad, Jalish M; Weber, Thomas; Chen, Hongyu; Wang, Yongjun; Zhang, Aihua; Jia, Weiping; Lee, Kyung; He, John C

    2018-05-01

    Background Diabetic nephropathy (DN) is a leading cause of ESRD in the United States, but the molecular mechanisms mediating the early stages of DN are unclear. Methods To assess global changes that occur in early diabetic kidneys and to identify proteins potentially involved in pathogenic pathways in DN progression, we performed proteomic analysis of diabetic and nondiabetic rat glomeruli. Protein S (PS) among the highly upregulated proteins in the diabetic glomeruli. PS exerts multiple biologic effects through the Tyro3, Axl, and Mer (TAM) receptors. Because increased activation of Axl by the PS homolog Gas6 has been implicated in DN progression, we further examined the role of PS in DN. Results In human kidneys, glomerular PS expression was elevated in early DN but suppressed in advanced DN. However, plasma PS concentrations did not differ between patients with DN and healthy controls. A prominent increase of PS expression also colocalized with the expression of podocyte markers in early diabetic kidneys. In cultured podocytes, high-glucose treatment elevated PS expression, and PS knockdown further enhanced the high-glucose-induced apoptosis. Conversely, PS overexpression in cultured podocytes dampened the high-glucose- and TNF- α -induced expression of proinflammatory mediators. Tyro3 receptor was upregulated in response to high glucose and mediated the anti-inflammatory response of PS. Podocyte-specific PS loss resulted in accelerated DN in streptozotocin-induced diabetic mice, whereas the transient induction of PS expression in glomerular cells in vivo attenuated albuminuria and podocyte loss in diabetic OVE26 mice. Conclusions Our results support a protective role of PS against glomerular injury in DN progression. Copyright © 2018 by the American Society of Nephrology.

  3. The AP-1 transcription factor FOSL1 causes melanocyte reprogramming and transformation.

    PubMed

    Maurus, K; Hufnagel, A; Geiger, F; Graf, S; Berking, C; Heinemann, A; Paschen, A; Kneitz, S; Stigloher, C; Geissinger, E; Otto, C; Bosserhoff, A; Schartl, M; Meierjohann, S

    2017-09-07

    The MAPK pathway is activated in the majority of melanomas and is the target of therapeutic approaches. Under normal conditions, it initiates the so-called immediate early response, which encompasses the transient transcription of several genes belonging to the AP-1 transcription factor family. Under pathological conditions, such as continuous MAPK pathway overactivation due to oncogenic alterations occurring in melanoma, these genes are constitutively expressed. The consequences of a permanent expression of these genes are largely unknown. Here, we show that FOSL1 is the main immediate early AP-1 member induced by melanoma oncogenes. We first examined its role in established melanoma cells. We found that FOSL1 is involved in melanoma cell migration as well as cell proliferation and anoikis-independent growth, which is mediated by the gene product of its target gene HMGA1, encoding a multipotent chromatin modifier. As FOSL1 expression is increased in patient melanoma samples compared to nevi, we investigated the effect of enhanced FOSL1 expression on melanocytes. Intriguingly, we found that FOSL1 acts oncogenic and transforms melanocytes, enabling subcutaneous tumor growth in vivo. During the process of transformation, FOSL1 reprogrammed the melanocytes and downregulated MITF in a HMGA1-dependent manner. At the same time, AXL was upregulated, leading to a shift in the MITF/AXL balance. Furthermore, FOSL1 re-enforced pro-tumorigenic transcription factors MYC, E2F3 and AP-1. Together, this led to the enhancement of several growth-promoting processes, such as ribosome biogenesis, cellular detachment and pyrimidine metabolism. Overall, we demonstrate that FOSL1 is a novel reprogramming factor for melanocytes with potent tumor transformation potential.

  4. Optimal implementation of best management practices to improve agricultural hydrology and water quality

    NASA Astrophysics Data System (ADS)

    Liu, Y.; Engel, B.; Collingsworth, P.; Pijanowski, B. C.

    2017-12-01

    Nutrient loading from the Maumee River watershed is a significant reason for the harmful algal blooms (HABs) problem in Lake Erie. Strategies to reduce nutrient loading from agricultural areas in the Maumee River watershed need to be explored. Best management practices (BMPs) are popular approaches for improving hydrology and water quality. Various scenarios of BMP implementation were simulated in the AXL watershed (an agricultural watershed in Maumee River watershed) using Soil and Water Assessment Tool (SWAT) and a new BMP cost tool to explore the cost-effectiveness of the practices. BMPs of interest included vegetative filter strips, grassed waterways, blind inlets, grade stabilization structures, wetlands, no-till, nutrient management, residue management, and cover crops. The following environmental concerns were considered: streamflow, Total Phosphorous (TP), Dissolved Reactive Phosphorus (DRP), Total Kjeldahl Nitrogen (TKN), and Nitrate+Nitrite (NOx). To obtain maximum hydrological and water quality benefits with minimum cost, an optimization tool was developed to optimally select and place BMPs by connecting SWAT, the BMP cost tool, and optimization algorithms. The optimization tool was then applied in AXL watershed to explore optimization focusing on critical areas (top 25% of areas with highest runoff volume/pollutant loads per area) vs. all areas of the watershed, optimization using weather data for spring (March to July, due to the goal of reducing spring phosphorus in watershed management plan) vs. full year, and optimization results of implementing BMPs to achieve the watershed management plan goal (reducing 2008 TP levels by 40%). The optimization tool and BMP optimization results can be used by watershed groups and communities to solve hydrology and water quality problems.

  5. In-Service Evaluation of HVOF Coated Main Landing Gear on Navy P-3 Aircraft

    NASA Technical Reports Server (NTRS)

    Devereaux, jon L.; Forrest, Clint

    2008-01-01

    Due to the environmental and health concerns with Electroplated Hard Chrome (EHC), the Hard Chrome Alternatives Team (HCAT) has been working to provide an alternative wear coating for EHC. The US Navy selected Tungsten-Carbide Cobalt (WC- 17Co) High Velocity Oxy-Fuel (HVOF) thermal spray coating for this purpose and completed service evaluations on select aircraft components to support the HCAT charter in identifying an alternative wear coating for chrome plating. Other benefits of WC-Co thermal spray coatings over EHC are enhanced corrosion resistance, improved durability, and exceptional wear properties. As part of the HCAT charter and to evaluate HVOF coatings on operational Navy components, the P-3 aircraft was selected for a service evaluation to determine the coating durability as compared to chrome plating. In April 1999, a VP-30 P-3 aircraft was outfitted with a right-hand Main Landing Gear (MLG) shock strut coated with WCCo HYOF thermal spray applied to the piston barrel and four axle journals. The HVOF coating on the piston barrel and axle journals was applied by Southwest United Industries, Inc. This HVOF coated strut assembly has since completed 6,378 landings. Teardown analysis .for this WC-Co HVOF coated MLG asset is significant in assessing the durability of this wear coating in service relative to EHC and to substantiate Life Cycle Cost (LCC) data to support a retrograde transition from EHC to HVOF thermal spray coatings. Findings from this teardown analysis may also benefit future transitions to HVOF thermal spray coatings by identifying enhancements to finishing techniques, mating bearing and liner material improvements, improved seal materials, and improvements in HVOF coating selection.

  6. An investigation into the mechanism of the polygonal wear of metro train wheels and its effect on the dynamic behaviour of a wheel/rail system

    NASA Astrophysics Data System (ADS)

    Jin, Xuesong; Wu, Lei; Fang, Jianying; Zhong, Shuoqiao; Ling, Liang

    2012-12-01

    This paper presents a detailed investigation conducted into the mechanism of the polygonal wear of metro train wheels through extensive experiments conducted at the sites. The purpose of the experimental investigation is to determine from where the resonant frequency that causes the polygonal wear of the metro train wheels originates. The experiments include the model tests of a vehicle and its parts and the tracks, the dynamic behaviour test of the vehicle in operation and the observation test of the polygonal wear development of the wheels. The tracks tested include the viaducts and the tunnel tracks. The structure model tests show that the average passing frequency of a polygonal wheel is approximately close to the first bending resonant frequency of the wheelset that is found by the wheelset model test and verified by the finite element analysis of the wheelset. Also, the dynamic behaviour test of the vehicle in operation indicates the main frequencies of the vertical acceleration vibration of the axle boxes, which are dominant in the vertical acceleration vibration of the axle boxes and close to the passing frequency of a polygonal wheel, which shows that the first bending resonant frequency of the wheelset is very exciting in the wheelset operation. The observation test of the polygonal wear development of the wheels indicates an increase in the rate of the polygonal wear of the wheels after their re-profiling. This paper also describes the dynamic models used for the metro vehicle coupled with the ballasted track and the slab track to analyse the effect of the polygonal wear of the wheels on the wheel/rail normal forces.

  7. Total dynamic response of a PSS vehicle negotiating asymmetric road excitations

    NASA Astrophysics Data System (ADS)

    Zhu, Jian Jun; Khajepour, Amir; Esmailzadeh, Ebrahim

    2012-12-01

    A planar suspension system (PSS) is a novel automobile suspension system in which an individual spring-damper strut is implemented in both the vertical and longitudinal directions, respectively. The wheels in a vehicle with such a suspension system can move back and forth relative to the chassis. When a PSS vehicle experiences asymmetric road excitations, the relative longitudinal motion of wheels with respect to the chassis in two sides of the same axle are not identical, and thus the two wheels at one axle will not be aligned in the same axis. The total dynamic responses, including those of the bounce, pitch and the roll of the PSS vehicle, to the asymmetric road excitation may exhibit different characteristics from those of a conventional vehicle. This paper presents an investigation into the comprehensive dynamic behaviour of a vehicle with the PSS, in such a road condition, on both the straight and curved roads. The study was carried out using an 18 DOF full-car model incorporating a radial-spring tyre-ground contact model and a 2D tyre-ground dynamic friction model. Results demonstrate that the total dynamic behaviour of a PSS vehicle is generally comparable with that of the conventional vehicle, while PSS exhibits significant improvement in absorbing the impact forces along the longitudinal direction when compared to the conventional suspension system. The PSS vehicle is found to be more stable than the conventional vehicle in terms of the directional performance against the disturbance of the road potholes on a straight line manoeuvre, while exhibiting a very similar handling performance on a curved line.

  8. The excitation of ground vibration by rail traffic: theory of vehicle track soil interaction and measurements on high-speed lines

    NASA Astrophysics Data System (ADS)

    Auersch, L.

    2005-06-01

    This article presents an integrated model for the computation of vehicle-track interaction and the ground vibrations of passing trains. A combined finite element and boundary element method is used to calculate the dynamic compliance of the track on realistic soil whereas multi-body models are used for the vehicle. The dynamic stiffness of the vehicle and that of the track are combined to calculate the dynamic axle loads due to the irregularities of the vehicle and the track as well as those due to sleeper passing excitation. These loads serve as input for the calculation of ground vibration near railway lines in the time and frequency domains. The theoretical methods and results have been proven by experiments in several respects and at several instances. First, on the occasion of the test and record runs of the Intercity Experimental, there was a very good quality of the vehicle and of the newly built track so that the deterministic parts of the excitation—the static load and the sleeper-passing component—could clearly be identified, the first being of minor importance apart from the track. Second, simultaneous measurements of the vehicle, the track and the soil at three different track situations were performed where we could verify the different parts of the stochastic excitation and their importance for the ground vibrations. The irregularities of the vehicle are dominant at high frequencies whereas the irregularities of the track are more important at lower frequencies. The comparison of the theory and the measurements also points to the phenomena of the vehicle-track resonance and the scattering of the quasi-static axle impulses by randomly varying soil.

  9. Engine Lubricant

    NASA Technical Reports Server (NTRS)

    1993-01-01

    PS 212, a plasma-sprayed coating developed by NASA, is used to coat valves in a new rotorcam engine. The coating eliminates the need for a liquid lubricant in the rotorcam, which has no crankshaft, flywheel, distributor or water pump. Developed by Murray United Development Corporation, it is a rotary engine only 10 inches long with four cylinders radiating outward from a central axle. Company officials say the engine will be lighter, more compact and cheaper to manufacture than current engines and will feature cleaner exhaust emissions. A licensing arrangement with a manufacturer is under negotiation. Primary applications are for automobiles, but the engine may also be used in light aircraft.

  10. Kidney cancer: current and novel treatment options.

    PubMed

    Jonasch, Eric

    2015-05-01

    Antiangiogenic therapies remain the standard of care in the front-line setting for renal cell carcinoma, although vascular endothelial growth factor (VEGF) blockade is not sufficient, and many patients do not respond to such treatment. With a host of approved agents, questions arise as to how best to use them in both initial and secondary treatments. Optimal sequences are currently being tested in various clinical trials. Because approximately 20% of patients exhibiting primary resistance to these anti-VEGF therapies, new therapies are needed. Novel therapies such as MET and AXL inhibitors as well as checkpoint antibodies hold promise for the future. Copyright © 2015 by the National Comprehensive Cancer Network.

  11. Fractography of induction-hardened steel fractured in fatigue and overload

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Santos, C.G.; Laird, C.

    1997-07-01

    The fracture surfaces of induction-hardened steel specimens obtained from an auto axle were characterized, macroscopically and microscopically, after being fractured in fatigue and monotonic overload. Specimens were tested in cyclic three-point bending under load control, and the S-N curve was established for specimens that had been notched by spark machining to facilitate fractography. Scanning electron microscopy of the fractured surfaces obtained for lives spanning the range 17,000 to 418,000 cycles revealed diverse fracture morphologies, including intergranular fracture and transgranular fatigue fracture. The results are being offered to assist in the analysis of complex field failures in strongly hardened steel.

  12. TAM receptor tyrosine kinase function and the immunopathology of liver disease.

    PubMed

    Mukherjee, S K; Wilhelm, A; Antoniades, C G

    2016-06-01

    Tyro3, Axl, MERTK (TAM) receptor tyrosine kinases are implicated in the regulation of the innate immune response through clearance of apoptotic cellular debris and control of cytokine signaling cascades. As a result they are pivotal in regulating the inflammatory response to tissue injury. Within the liver, immune regulatory signaling is employed to prevent the overactivation of innate immunity in response to continual antigenic challenge from the gastrointestinal tract. In this review we appraise current understanding of the role of TAM receptor function in the regulation of both innate and adaptive immunity, with a focus on its impact upon hepatic inflammatory pathology. Copyright © 2016 the American Physiological Society.

  13. Line scanning time-of-flight laser sensor for intelligent transport systems, combining wide field-of-view optics of 30 deg, high scanning speed of 0.9 ms/line, and simple sensor configuration

    NASA Astrophysics Data System (ADS)

    Imaki, Masaharu; Kameyama, Shumpei; Ishimura, Eitaro; Nakaji, Masaharu; Yoshinaga, Hideo; Hirano, Yoshihito

    2017-03-01

    We developed a line scanning time-of-flight (TOF) laser sensor for an intelligent transport system (ITS), which combines wide field-of-view (FOV) receiving optics of 30 deg and a high-speed microelectro mechanical system scanner of 0.9 ms/line with a simple sensor configuration. The newly developed high-aspect ratio photodiode realizes the scanless and wide FOV receiver. The sinusoidal wave intensity modulation method is used for the TOF measurement. This enables the noise reduction of the trans-impedance amplifier by applying the LC-resonant method. The vehicle detection and axle counting, which are the important functions in ITS, are also demonstrated.

  14. Light-powered autonomous and directional molecular motion of a dissipative self-assembling system

    NASA Astrophysics Data System (ADS)

    Ragazzon, Giulio; Baroncini, Massimo; Silvi, Serena; Venturi, Margherita; Credi, Alberto

    2015-01-01

    Biomolecular motors convert energy into directed motion and operate away from thermal equilibrium. The development of dynamic chemical systems that exploit dissipative (non-equilibrium) processes is a challenge in supramolecular chemistry and a premise for the realization of artificial nanoscale motors. Here, we report the relative unidirectional transit of a non-symmetric molecular axle through a macrocycle powered solely by light. The molecular machine rectifies Brownian fluctuations by energy and information ratchet mechanisms and can repeat its working cycle under photostationary conditions. The system epitomizes the conceptual and practical elements forming the basis of autonomous light-powered directed motion with a minimalist molecular design.

  15. Influence of switches and crossings on wheel profile evolution in freight vehicles

    NASA Astrophysics Data System (ADS)

    Casanueva, Carlos; Doulgerakis, Emmanouil; Jönsson, Per-Anders; Stichel, Sebastian

    2014-05-01

    Wheel reprofiling costs for freight vehicles are a major issue in Sweden, reducing the profitability of freight traffic operations and therefore hindering the modal shift needed for achieving reduced emissions. In order to understand the damage modes in freight vehicles, uniform wear prediction with Archard's wear law has been studied in a two-axle timber transport wagon, and simulation results have been compared to measurements. Challenges of wheel wear prediction in freight wagons are discussed, including the influence of block brakes and switches and crossings. The latter have a major influence on the profile evolution of this case study, so specific simulations are performed and a thorough discussion is carried out.

  16. Improved characterization of truck traffic volumes and axle loads for mechanistic-empirical pavement design.

    DOT National Transportation Integrated Search

    2012-12-01

    The recently developed mechanistic-empirical pavement design guide (MEPDG) requires a multitude of traffic : inputs to be defined for the design of pavement structures, including the initial two-way annual average daily truck : traffic (AADTT), direc...

  17. AXL.Net: Web-Enabled Case Method Instruction for Accelerating Tacit Knowledge Acquisition in Leaders

    DTIC Science & Technology

    2006-11-01

    individuals. Officers watched Tripwire as a group on a laptop computer and then independently completed a set of measures. After completing the measures...judgment posttest score (r = .33, p < .05). Positive affect was not, however, correlated with the behavioral judgment pretest score (r = .10, p = ns... Pretest .10 .05 Behavioral Judgment Posttest .33* .13 Emphasized Cultural Issues (T1) a .48** .21 Emphasized Cultural Issues (T2) a .29 .22 Note. * p

  18. DEVELOPMENT OF AN ARMY STATIONARY AXLE TEST STAND FOR LUBRICANT EFFICIENCY EVALUATION-PART II

    DTIC Science & Technology

    2017-01-13

    value was estimated based on the engines maximum peak torque output, multiplied by the transmissions 1st gear ratio, high range transfer case ratio...efficiency test stand to allow for laboratory based investigation of Fuel Efficient Gear Oils (FEGO) and their impact on vehicle efficiency. Development...their impact on vehicle efficiency. The test stand was designed and developed with the following goals: • Provide a lower cost alternative for

  19. Development of an Army Stationary Axle Efficiency Test Stand - Interim Report TFLRF No. 471

    DTIC Science & Technology

    2015-09-01

    Santena 1 10029 Villastellone (TO) Italy 31-Jul-18 PRI GL 0632 Tutela Transmission X-Road SAE 75W-90 Petronas Lubrificantes Brasil S.A. Avenida Trajano de...Araujo Viana 2500 Contagem - MG Brasil 30-Nov-19 PRI GL 0703 Tutela TRD 85W-140 SAE 85W-140 Phillips 66 (previously known as ConocoPhillips prior to

  20. 75 FR 76036 - American Axle & Manufacturing Detroit Manufacturing Complex Holbrook Avenue and Saint Aubin...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-07

    ... From Paint Tech International Detroit, MI; Amended Certification Regarding Eligibility To Apply for... firm. New information revealed that workers leased from Paint Tech International were employed on-site... certification to include workers leased from Paint Tech International working on-site at the Detroit, Michigan...