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Sample records for axles

  1. Axle Shaft Optical Inspection System

    NASA Astrophysics Data System (ADS)

    Freese, Fritz; Geise, Philip; George, Eugene; Singh, Tom

    1980-11-01

    An electro-optical instrument to gauge automotive rear axle shafts is described. A high contrast image of the axle lug flange is projected via a high quality photographic lens on two self-scanning linear photodiode arrays. In one three-second rotation, a dedicated digital processor measures bolt circle location, hole diameter and separation. The unit automatically: compares each measurement with preset tolerances, computes the average bolt circle diameter, computes the bolt circle runout, makes a pass/fail decision, provides a digital readout, marks the axle shaft with colored ink and provides the operator a pass/fail light.

  2. Axle efficiency test procedure. SAE standard

    SciTech Connect

    1995-04-01

    Data from this SAE Recommended Practice permit mapping axle efficiency and/or waste energy over the operating range of passenger cars, trucks, buses, and other highway vehicles. The procedure can be applied to single axles, tandem axles as a system, or other systems, by combining separate tests, such as tests of the front axle and power divider and rear axle of tandem or tri-drive type.

  3. 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

  4. 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)...

  5. 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)...

  6. 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)...

  7. Generalised multi-axle vehicle handling

    NASA Astrophysics Data System (ADS)

    Williams, Daniel Eugene

    2012-01-01

    The familiar two-axle bicycle model and associated basic concepts of vehicle handling are reviewed and used to introduce minor changes in convention from the literature. The two-axle model is extended to a three-axle vehicle to illustrate the effectiveness of the notation combined with a simplifying mathematical identity found in the two-axle vehicle literature. A generalised model is then developed that produces dynamic equations of motion by inspection for a vehicle with an arbitrary number of steerable and non-steerable axles. Furthermore, the vehicle dynamic concepts of understeer and wheelbase are generalised and can be directly computed for various arbitrary vehicle configurations.

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

    SciTech Connect

    Kariolis, Mihalis S.; Miao, Yu Rebecca; Jones, Douglas S.; Kapur, Shiven; Mathews, Irimpan I.; Giaccia, Amato J.; Cochran, Jennifer R.

    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 to 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.

  9. 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. PMID:25136066

  10. 49 CFR 215.105 - Defective axle.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... conjunction with a plain bearing, has an end collar that is broken or cracked; (d) A journal on the car shows... plain bearing journal on the axle, or the fillet on the axle, has— (1) A ridge; (2) A depression; (3)...

  11. 49 CFR 215.105 - Defective axle.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... conjunction with a plain bearing, has an end collar that is broken or cracked; (d) A journal on the car shows... plain bearing journal on the axle, or the fillet on the axle, has— (1) A ridge; (2) A depression; (3)...

  12. Composite multi-axle suspension for vehicles

    SciTech Connect

    Sullivan, J.W.

    1986-09-30

    This patent describes a load dividing suspension system for vehicles comprising a chassis frame, a drive axle assembly supportively connected with the chassis frame, a fluid-pressure responsive spring means on the drive axle assembly and engaging the chassis frame and exerting a variable lifting force thereon. A tag axle assembly is attached to the chassis frame and includes a vertically swingable support structure for wheels of the tag axle assembly, a distribution valve means on the vehicle for pressurized fluid from an on-board supply of such fluid and having a connection with the supply, an outlet connection and a pressurized fluid line leading to and connected with the fluid-pressure responsive spring means, and an operating linkage for the valve means. The linkage is connected between a movable control element of the valve means and the vertically swingable support structure.

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

    DOE PAGESBeta

    Kariolis, Mihalis S.; Miao, Yu Rebecca; Jones, Douglas S.; Kapur, Shiven; Mathews, Irimpan I.; Giaccia, Amato J.; Cochran, Jennifer R.

    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

  14. 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

  15. 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

  16. Imaging Axl expression in pancreatic and prostate cancer xenografts

    SciTech Connect

    Nimmagadda, Sridhar; Pullambhatla, Mrudula; Lisok, Ala; Hu, Chaoxin; Maitra, Anirban; Pomper, Martin G

    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 radiolabeled 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 pancreatic

  17. Targeting Axl and Mer kinases in cancer.

    PubMed

    Verma, Anupam; Warner, Steven L; Vankayalapati, Hariprasad; Bearss, David J; Sharma, Sunil

    2011-10-01

    Receptor tyrosine kinases (RTK) are cell-surface transmembrane receptors that contain regulated kinase activity within their cytoplasmic domain and play an important role in signal transduction in both normal and malignant cells. The mammalian TAM RTK family includes 3 closely related members: Tyro-3, Axl, and Mer. Overexpression or ectopic expression of the TAM receptors has been detected in a wide array of human cancers. Growth arrest-specific gene 6 has been identified as the major ligand for these TAM RTKs, and its binding to the receptors has been shown to promote proliferation and survival of cancer cells in vitro. Abnormal expression and activation of Axl or Mer can provide a survival advantage for certain cancer cells. Inhibition of Axl and Mer may enhance the sensitivity of cancer cells to cytotoxic agents and would potentially be a therapeutic strategy to target cancer cells. This review elucidates the role of Axl and Mer in normal cellular function and their role in oncogenesis. In addition, we review the potential to inhibit these RTKs for the development of therapeutic targets in treatment of cancer. PMID:21933973

  18. On the equivalent wheelbase of a three-axle vehicle

    NASA Astrophysics Data System (ADS)

    Williams, Daniel Eugene

    2011-09-01

    The steady-state handling properties of a rigid vehicle with a tandem rear axle configuration are developed. This work uses conventions resulting in a parsimonious characterisation of steady-state handling of such three-axle vehicles that is shown to be a simple extension of the well-known two-axle bicycle model. Specifically the concepts of understeer and wheelbase are developed for a three-axle vehicle, and shown to play the same role in characterising vehicle handling as they do in the well-known two-axle vehicle model. An equivalent wheelbase of a three-axle vehicle is expressed in terms of vehicle geometry and cornering stiffness of each axle. The model developed in this work is reconciled with previous models that make use of simplifying assumptions found in the literature.

  19. Structural basis for Gas6–Axl signalling

    PubMed Central

    Sasaki, Takako; Knyazev, Pjotr G; Clout, Naomi J; Cheburkin, Yuri; Göhring, Walter; Ullrich, Axel; Timpl, Rupert; Hohenester, Erhard

    2006-01-01

    Receptor tyrosine kinases of the Axl family are activated by the vitamin K-dependent protein Gas6. Axl signalling plays important roles in cancer, spermatogenesis, immunity, and platelet function. The crystal structure at 3.3 Å resolution of a minimal human Gas6/Axl complex reveals an assembly of 2:2 stoichiometry, in which the two immunoglobulin-like domains of the Axl ectodomain are crosslinked by the first laminin G-like domain of Gas6, with no direct Axl/Axl or Gas6/Gas6 contacts. There are two distinct Gas6/Axl contacts of very different size, both featuring interactions between edge β-strands. Structure-based mutagenesis, protein binding assays and receptor activation experiments demonstrate that both the major and minor Gas6 binding sites are required for productive transmembrane signalling. Gas6-mediated Axl dimerisation is likely to occur in two steps, with a high-affinity 1:1 Gas6/Axl complex forming first. Only the minor Gas6 binding site is highly conserved in the other Axl family receptors, Sky/Tyro3 and Mer. Specificity at the major contact is suggested to result from the segregation of charged and apolar residues to opposite faces of the newly formed β-sheet. PMID:16362042

  20. Rear axle designed in oriented FRP

    SciTech Connect

    Not Available

    1982-08-01

    Using techniques of both synthesis and analysis, together with carefully defined goals, a team of investigators devised a major suspension member using oriented fiber reinforced plastic. A weight saving of 57% resulted for an innovative rear axle design estimate to increase cost about /1.20 per kilogram of weight saved. Only durability fell short of expectations, a factor which should improve with further refinements.

  1. 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

  2. AXL is an oncotarget in human colorectal cancer

    PubMed Central

    Martinelli, Erika; Troiani, Teresa; Liguori, Giuseppina; Vitagliano, Donata; Napolitano, Stefania; Morgillo, Floriana; Rinaldi, Barbara; Melillo, Rosa Marina; Liotti, Federica; Nappi, Anna; Bianco, Roberto; Berrino, Liberato; Ciuffreda, Loreta Pia; Ciardiello, Davide; Iaffaioli, Vincenzo; Botti, Gerardo; Ferraiolo, Fiorella; Ciardiello, Fortunato

    2015-01-01

    AXL is a tyrosine kinase receptor activated by GAS6 and regulates cancer cell proliferation migration and angiogenesis. We studied AXL as new therapeutic target in colorectal cancer (CRC). Expression and activation of AXL and GAS6 were evaluated in a panel of human CRC cell lines. AXL gene silencing or pharmacologic inhibition with foretinib suppressed proliferation, migration and survival in CRC cells. In an orthotopic colon model of human HCT116 CRC cells overexpressing AXL, foretinib treatment caused significant inhibition of tumour growth and peritoneal metastatic spreading. AXL and GAS6 overexpression by immunohistochemistry (IHC) were found in 76,7% and 73.5%, respectively, of 223 human CRC specimens, correlating with less differentiated histological grading. GAS6 overexpression was associated with nodes involvement and tumour stage. AXL gene was found amplified by Fluorescence in situ hybridization (FISH) in 8/146 cases (5,4%) of CRC samples. Taken together, AXL inhibition could represent a novel therapeutic approach in CRC. PMID:25966280

  3. AXL is an oncotarget in human colorectal cancer.

    PubMed

    Martinelli, Erika; Martini, Giulia; Cardone, Claudia; Troiani, Teresa; Liguori, Giuseppina; Vitagliano, Donata; Napolitano, Stefania; Morgillo, Floriana; Rinaldi, Barbara; Melillo, Rosa Marina; Liotti, Federica; Nappi, Anna; Bianco, Roberto; Berrino, Liberato; Ciuffreda, Loreta Pia; Ciardiello, Davide; Iaffaioli, Vincenzo; Botti, Gerardo; Ferraiolo, Fiorella; Ciardiello, Fortunato

    2015-09-15

    AXL is a tyrosine kinase receptor activated by GAS6 and regulates cancer cell proliferation migration and angiogenesis. We studied AXL as new therapeutic target in colorectal cancer (CRC). Expression and activation of AXL and GAS6 were evaluated in a panel of human CRC cell lines. AXL gene silencing or pharmacologic inhibition with foretinib suppressed proliferation, migration and survival in CRC cells. In an orthotopic colon model of human HCT116 CRC cells overexpressing AXL, foretinib treatment caused significant inhibition of tumour growth and peritoneal metastatic spreading. AXL and GAS6 overexpression by immunohistochemistry (IHC) were found in 76,7% and 73.5%, respectively, of 223 human CRC specimens, correlating with less differentiated histological grading. GAS6 overexpression was associated with nodes involvement and tumour stage. AXL gene was found amplified by Fluorescence in situ hybridization (FISH) in 8/146 cases (5,4%) of CRC samples. Taken together, AXL inhibition could represent a novel therapeutic approach in CRC. PMID:25966280

  4. Axl receptor blockade protects from invasive pulmonary aspergillosis in mice.

    PubMed

    Shibata, Takehiko; Habiel, David M; Coelho, Ana Lucia; Hogaboam, Cory M

    2014-10-01

    Aspergillus fumigatus is a sporulating fungus found ubiquitously in the environment, which is quickly contained in the immunocompetent host but can cause lethal invasive aspergillosis in the immunocompromised host. We have recently demonstrated that Axl (one member of the Tyro3, Axl, Mertk receptor family) is a key regulator of antiviral immune responses in the lung. In this study, we investigated the role of Axl in antifungal immunity in a model of invasive pulmonary aspergillosis (IPA). In this model, Aspergillus fumigatus conidia were administered into the lungs of neutrophil-depleted mice, and the mice were monitored for survival, lung inflammatory response, and fungal clearance. The lethal effect of IPA was significantly reduced in anti-Axl mAb-treated mice compared with IgG control-treated mice. Targeting Axl significantly inhibited pulmonary inflammation, including the expression of IL-1β, IL-6, TNF-α, and chitinase-like proteins in whole lung. Further, anti-Axl mAb treatment significantly increased M1 macrophages that highly expressed inducible NO synthase and decreased M2 macrophages that expressed Arginase 1 and were found in inflammatory zone protein (Fizz1). More importantly, anti-Axl mAb treatment significantly increased the number of IFN-γ-producing T cells and NK cells compared with the IgG control group during IPA. Together, our results demonstrate that the Axl mAb treatment is protective during invasive aspergillosis in neutropenic mice. Collectively, these data suggest a potential deleterious role for Axl during primary immune responses directed against A. fumigatus and novel therapeutic strategy for IPA. PMID:25156363

  5. Lane-keeping benefits of practical rear axle steer

    NASA Astrophysics Data System (ADS)

    Williams, Daniel Eugene

    2014-04-01

    The classic two-degree-of-freedom yaw-plane or 'bicycle' vehicle model is augmented with two additional states to describe lane-keeping behaviour and further augmented with an additional control input to steer the rear axle. A simple driver model is hypothesised where the driver closes a loop on a projected lateral lane position. The driver can select the preview distance to compensate driver/vehicle dynamics, consistent with the 'cross-over' model found in the literature. A rear axle steer control law is found to be a function of the front axle steering input and vehicle speed that exhibits stability similar to a positive-real system, while at the same time improving the ability of the driver/vehicle system to track a complex curved lane and improving steady-state manoeuvrability. The theoretically derived control law bears similarity to practical embodiments allowing a deeper understanding of the functional value of steering a rear axle.

  6. 13. DETAIL VIEW OF AXLE LATHE. Polishing journals on lathe. ...

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

    13. DETAIL VIEW OF AXLE LATHE. Polishing journals on lathe. Wilbur Johnston, operator. - Juniata Shops, Erecting Shop & Machine Shop, East of Fourth Avenue, between Fourth & Fifth Streets, Altoona, Blair County, PA

  7. 14. DETAIL VIEW OF AXLE LATHE. Polishing journals on lathe. ...

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

    14. DETAIL VIEW OF AXLE LATHE. Polishing journals on lathe. Wilbur Johnston, operator. - Juniata Shops, Erecting Shop & Machine Shop, East of Fourth Avenue, between Fourth & Fifth Streets, Altoona, Blair County, PA

  8. [2]Pseudorotaxane composed of heteroditopic macrobicycle and pyridine N-oxide based axle: recognition site dependent axle orientation.

    PubMed

    Saha, Subrata; Santra, Saikat; Ghosh, Pradyut

    2015-04-17

    A strategy for threading an axle having a hydrogen bond acceptor unit in the cavity of a C3v symmetric amido-amine macrobicycle is investigated. The macrobicycle acts as a wheel in its neutral as well as triprotonated states to form threaded architectures with a pyridine N-oxide derivative. The negative oxygen dipole of the axle is capable of [2]pseudorotaxane formation in two different orientations with the wheel in its neutral and triprotonated states. PMID:25825821

  9. Axl, a receptor tyrosine kinase, mediates flow-induced vascular remodeling.

    PubMed

    Korshunov, Vyacheslav A; Mohan, Amy M; Georger, Mary A; Berk, Bradford C

    2006-06-01

    Intima-media thickening (IMT) in response to hemodynamic stress is a physiological process that requires coordinated signaling among endothelial, inflammatory, and vascular smooth muscle cells (VSMC). Axl, a receptor tyrosine kinase, whose ligand is Gas6, is highly induced in VSMC after carotid injury. Because Axl regulates cell migration, phagocytosis and apoptosis, we hypothesized that Axl would play a role in IMT. Vascular remodeling in mice deficient in Axl (Axl(-/-)) and wild-type littermates (Axl(+/+)) was induced by ligation of the left carotid artery (LCA) branches maintaining flow via the left occipital artery. Both genotypes had similar baseline hemodynamic parameters and carotid artery structure. Partial ligation altered blood flow equally in both genotypes: increased by 60% in the right carotid artery (RCA) and decreased by 80% in the LCA. There were no significant differences in RCA remodeling between genotypes. However, in the LCA Axl(-/-) developed significantly smaller intima+media compared with Axl(+/+) (31+/-4 versus 42+/-6x10(-6) microm3, respectively). Quantitative immunohistochemistry of Axl(-/-) LCA showed increased apoptosis compared with Axl(+/+) (5-fold). As expected, p-Akt was decreased in Axl(-/-), whereas there was no difference in Gas6 expression. Cell composition also changed significantly, with increases in CD45+ cells and decreases in VSMC, macrophages, and neutrophils in Axl(-/-) compared with Axl(+/+). These data demonstrate an important role for Axl in flow-dependent remodeling by regulating vascular apoptosis and vascular inflammation. PMID:16627783

  10. Vehicle dynamics control using an active third-axle system

    NASA Astrophysics Data System (ADS)

    Soltani, Amir; Goodarzi, Avesta; Hassan Shojaeefard, Mohammad; Khajepour, Amir

    2014-11-01

    This paper introduces the active third-axle system as an innovative vehicle dynamic control method. This method can be applicable for different kinds of three-axle vehicles such as buses, trucks, or even three-axle passenger cars. In this system, an actuator on the middle axle actively applies an independent force on the suspension to improve the handling characteristics, and hence, its technology is similar to slow-active suspension systems. This system can change the inherent vehicle dynamic characteristics, such as under/over steering behaviour, in the linear handling region, as well as vehicle stability in the nonlinear, limit handling region. In this paper, our main focus is to show the potential capabilities of this method in enhancing vehicle dynamic performance. For this purpose, as the first step, the proposed method in both linear and nonlinear vehicle handling regions is studied mathematically. Next, a comprehensive, nonlinear, 10 degrees of freedom vehicle model with a fuzzy control strategy is used to evaluate the effectiveness of this system. The dynamic behaviour of a vehicle, when either uncontrolled or equipped with the active third axle is then compared. Simulation results show that this active system can be considered as an innovative method for vehicle dynamic control.

  11. Modeling operating weight and axle weight distributions for highway vehicles

    SciTech Connect

    Greene, D.L.; Liang, J.C.

    1988-07-01

    The estimation of highway cost responsibility requires detailed information on vehicle operating weights and axle weights by type of vehicle. Typically, 10--20 vehicle types must be cross-classified by 10--20 registered weight classes and again by 20 or more operating weight categories, resulting in 100--400 relative frequencies to be determined for each vehicle type. For each of these, gross operating weight must be distributed to each axle or axle unit. Given the rarity of many of the heaviest vehicle types, direct estimation of these frequencies and axle weights from traffic classification count statistics and truck weight data may exceed the reliability of even the largest (e.g., 250,000 record) data sources. An alternative is to estimate statistical models of operating weight distributions as functions of registered weight, and models of axle weight shares as functions of operating weight. This paper describes the estimation of such functions using the multinomial logit model (a log-linear model) and the implementation of the modeling framework as a PC-based FORTRAN program. Areas for further research include the addition of highway class and region as explanatory variables in operating weight distribution models, and the development of theory for including registration costs and costs of operating overweight in the modeling framework. 14 refs., 45 figs., 5 tabs.

  12. Eddy current system for inspection of train hollow axles

    SciTech Connect

    Chady, Tomasz; Psuj, Grzegorz; Sikora, Ryszard; Kowalczyk, Jacek; Spychalski, Ireneusz

    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.

  13. Axl Expression Stratifies Patients with Poor Prognosis after Hepatectomy for Hepatocellular Carcinoma

    PubMed Central

    Xia, Yong; Li, Jun; Shi, Lehua; Zou, Qifei; Wan, Xuying; Jiao, Binghua; Wang, Hongyang; Wu, Mengchao; Zhang, Yongjie; Shen, Feng

    2016-01-01

    Background Axl is a receptor tyrosine kinase which plays an important role in multiple human malignancies. Design The Axl expression was examined in several hepatocellular carcinoma(HCC) cell lines, paired tumor and nontumorous samples. Then, we examined cell growth curve, cell apoptosis and cell migration in SMMC-7721 cells over-expressed with Axl or siRNA against Axl, respectively. Finally, the prognostic value of Axl was investigated in a prospective cohort of 246 consecutive HCC patients undergoing curative hepatoectomy. Results We found Axl was positive in 22% of examined tumor tissues and all four cell lines. Over-expressing Axl in SMMC-7721 cells accelerated cell growth, cell migration and inhibited cell apoptosis, while knock-down of Axl exerted opposite effect. Axl expression was closely associated with serum AFP, multiple tumors, absence of encapsulation, microvascular invasion, and advanced BCLC or TNM stage. Patients with positive Axl staining had a higher 5-year recurrence rate (92% vs. 71%, P<0.001) and a lower 5-year survival rate (9% vs. 48%, P<0.001) than those with negative staining. The multivariate analyses showed that Axl expression was an independent factor for both tumor recurrence (HR: 1.725; 95% CI: 1.219–2.441) and survival (1.847; 1.291–2.642). Conclusion Axl expression suggests more aggressive tumor invasiveness and predicts worse prognosis for HCC patients undergoing resection. PMID:27182739

  14. Clinical, Pathological, and Molecular Features of Lung Adenocarcinomas with AXL Expression.

    PubMed

    Sato, Katsuaki; Suda, Kenichi; Shimizu, Shigeki; Sakai, Kazuko; Mizuuchi, Hiroshi; Tomizawa, Kenji; Takemoto, Toshiki; Nishio, Kazuto; Mitsudomi, Tetsuya

    2016-01-01

    The receptor tyrosine kinase AXL is a member of the Tyro3-Axl-Mer receptor tyrosine kinase subfamily. AXL affects several cellular functions, including growth and migration. AXL aberration is reportedly a marker for poor prognosis and treatment resistance in various cancers. In this study, we analyzed clinical, pathological, and molecular features of AXL expression in lung adenocarcinomas (LADs). We examined 161 LAD specimens from patients who underwent pulmonary resections. When AXL protein expression was quantified (0, 1+, 2+, 3+) according to immunohistochemical staining intensity, results were 0: 35%; 1+: 20%; 2+: 37%; and 3+: 7% for the 161 samples. AXL expression status did not correlate with clinical features, including smoking status and pathological stage. However, patients whose specimens showed strong AXL expression (3+) had markedly poorer prognoses than other groups (P = 0.0033). Strong AXL expression was also significantly associated with downregulation of E-cadherin (P = 0.025) and CD44 (P = 0.0010). In addition, 9 of 12 specimens with strong AXL expression had driver gene mutations (6 with EGFR, 2 with KRAS, 1 with ALK). In conclusion, we found that strong AXL expression in surgically resected LADs was a predictor of poor prognosis. LADs with strong AXL expression were characterized by mesenchymal status, higher expression of stem-cell-like markers, and frequent driver gene mutations. PMID:27100677

  15. Clinical, Pathological, and Molecular Features of Lung Adenocarcinomas with AXL Expression

    PubMed Central

    Suda, Kenichi; Shimizu, Shigeki; Sakai, Kazuko; Mizuuchi, Hiroshi; Tomizawa, Kenji; Takemoto, Toshiki; Nishio, Kazuto; Mitsudomi, Tetsuya

    2016-01-01

    The receptor tyrosine kinase AXL is a member of the Tyro3-Axl-Mer receptor tyrosine kinase subfamily. AXL affects several cellular functions, including growth and migration. AXL aberration is reportedly a marker for poor prognosis and treatment resistance in various cancers. In this study, we analyzed clinical, pathological, and molecular features of AXL expression in lung adenocarcinomas (LADs). We examined 161 LAD specimens from patients who underwent pulmonary resections. When AXL protein expression was quantified (0, 1+, 2+, 3+) according to immunohistochemical staining intensity, results were 0: 35%; 1+: 20%; 2+: 37%; and 3+: 7% for the 161 samples. AXL expression status did not correlate with clinical features, including smoking status and pathological stage. However, patients whose specimens showed strong AXL expression (3+) had markedly poorer prognoses than other groups (P = 0.0033). Strong AXL expression was also significantly associated with downregulation of E-cadherin (P = 0.025) and CD44 (P = 0.0010). In addition, 9 of 12 specimens with strong AXL expression had driver gene mutations (6 with EGFR, 2 with KRAS, 1 with ALK). In conclusion, we found that strong AXL expression in surgically resected LADs was a predictor of poor prognosis. LADs with strong AXL expression were characterized by mesenchymal status, higher expression of stem-cell-like markers, and frequent driver gene mutations. PMID:27100677

  16. 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

  17. 49 CFR 230.99 - Tender truck axles.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Tender truck axles. 230.99 Section 230.99 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Steam Locomotives...

  18. Manual Drivetrain and Axles Specialist. Teacher Edition. Automotive Service Series.

    ERIC Educational Resources Information Center

    Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

    This instructor's guide contains materials for teaching the manual drive trains and axle specialist component of a competency-based instructional program for students preparing for employment in the automotive service trade. It is based on National Institute of Automotive Service Excellence task lists. Six instructional units contain materials…

  19. Sunitinib activates Axl signaling in renal cell cancer.

    PubMed

    van der Mijn, Johannes C; Broxterman, Henk J; Knol, Jaco C; Piersma, Sander R; De Haas, Richard R; Dekker, Henk; Pham, Thang V; Van Beusechem, Victor W; Halmos, Balazs; Mier, James W; Jiménez, Connie R; Verheul, Henk M W

    2016-06-15

    Mass spectrometry-based phosphoproteomics provides a unique unbiased approach to evaluate signaling network in cancer cells. The tyrosine kinase inhibitor sunitinib is registered as treatment for patients with renal cell cancer (RCC). We investigated the effect of sunitinib on tyrosine phosphorylation in RCC tumor cells to get more insight in its mechanism of action and thereby to find potential leads for combination treatment strategies. Sunitinib inhibitory concentrations of proliferation (IC50) of 786-O, 769-p and A498 RCC cells were determined by MTT-assays. Global tyrosine phosphorylation was measured by LC-MS/MS after immunoprecipitation with the antiphosphotyrosine antibody p-TYR-100. Phosphoproteomic profiling of 786-O cells yielded 1519 phosphopeptides, corresponding to 675 unique proteins including 57 different phosphorylated protein kinases. Compared to control, incubation with sunitinib at its IC50 of 2 µM resulted in downregulation of 86 phosphopeptides including CDK5, DYRK3, DYRK4, G6PD, PKM and LDH-A, while 94 phosphopeptides including Axl, FAK, EPHA2 and p38α were upregulated. Axl- (y702), FAK- (y576) and p38α (y182) upregulation was confirmed by Western Blot in 786-O and A498 cells. Subsequent proliferation assays revealed that inhibition of Axl with a small molecule inhibitor (R428) sensitized 786-O RCC cells and immortalized endothelial cells to sunitinib up to 3 fold. In conclusion, incubation with sunitinib of RCC cells causes significant upregulation of multiple phosphopeptides including Axl. Simultaneous inhibition of Axl improves the antitumor activity of sunitinib. We envision that evaluation of phosphoproteomic changes by TKI treatment enables identification of new targets for combination treatment strategies. PMID:26815723

  20. Molecular Pathways: AXL, a Membrane Receptor Mediator of Resistance to Therapy

    PubMed Central

    Scaltriti, Maurizio; Elkabets, Moshe; Baselga, José

    2016-01-01

    AXL is a tyrosine kinase membrane receptor that signals via PI3K, MAPK, and protein kinase C (PKC), among other pathways. AXL has oncogenic potential and interacts with other membrane receptors, depending on their relative abundance and availability. The increased expression of AXL in cancer is often the result of pharmacologic selective pressure to a number of chemotherapies and targeted therapies and acts as a mechanism of acquired drug resistance. This resistance phenotype, frequently accompanied by epithelial-to-mesenchymal transition, can be reversed by AXL inhibition. In tumors with high levels of EGFR, including lung, head and neck, and triple-negative breast cancer, AXL dimerizes with this receptor and initiates signaling that circumvents the antitumor effects of anti-EGFR therapies. Likewise, AXL overexpression and dimerization with EGFR can overcome PI3K inhibition by activating the phospholipase C-γ-PKC cascade that, in turn, sustains mTORC1 activity. The causative role of AXL in inducing drug resistance is underscored by the fact that the suppression of AXL restores sensitivity to these agents. Hence, these observations indicate that AXL is selectively expressed in tumor cells refractory to therapy and that cotargeting AXL in this setting would potentially overcome drug resistance. The use of AXL inhibitors should be considered in the clinic. PMID:26763248

  1. Tyrosine kinase receptor Axl enhances entry of Zaire ebolavirus without direct interactions with the viral glycoprotein

    PubMed Central

    Brindley, Melinda A.; Hunt, Catherine L.; Kondratowicz, Andrew S.; Bowman, Jill; Sinn, Patrick L.; McCray, Paul B.; Quinn, Kathrina; Weller, Melodie L.; Chiorini, John A.; Maury, Wendy

    2011-01-01

    In a bioinformatics-based screen for cellular genes that enhance Zaire ebolavirus (ZEBOV) transduction, AXL mRNA expression strongly correlated with ZEBOV infection. A series of cell lines and primary cells were identified that require Axl for optimal ZEBOV entry. Using one of these cell lines, we identified ZEBOV entry events that are Axl-dependent. Interactions between ZEBOV-GP and the Axl ectodomain were not detected in immunoprecipitations and reduction of surface expressed Axl by RNAi did not alter ZEBOV-GP binding, providing evidence that Axl does not serve as a receptor for the virus. However, RNAi knock down of Axl reduced ZEBOV pseudovirion internalization and α-Axl antisera inhibited pseudovirion fusion with cellular membranes. Consistent with the importance of Axl for ZEBOV transduction, Axl transiently co-localized on the surface of cells with ZEBOV virus particles and was internalized during virion transduction. In total, these findings indicate that endosomal uptake of filoviruses is facilitated by Axl. PMID:21529875

  2. Molecular Pathways: AXL, a Membrane Receptor Mediator of Resistance to Therapy.

    PubMed

    Scaltriti, Maurizio; Elkabets, Moshe; Baselga, José

    2016-03-15

    AXL is a tyrosine kinase membrane receptor that signals via PI3K, MAPK, and protein kinase C (PKC), among other pathways. AXL has oncogenic potential and interacts with other membrane receptors, depending on their relative abundance and availability. The increased expression of AXL in cancer is often the result of pharmacologic selective pressure to a number of chemotherapies and targeted therapies and acts as a mechanism of acquired drug resistance. This resistance phenotype, frequently accompanied by epithelial-to-mesenchymal transition, can be reversed by AXL inhibition. In tumors with high levels of EGFR, including lung, head and neck, and triple-negative breast cancer, AXL dimerizes with this receptor and initiates signaling that circumvents the antitumor effects of anti-EGFR therapies. Likewise, AXL overexpression and dimerization with EGFR can overcome PI3K inhibition by activating the phospholipase C-γ-PKC cascade that, in turn, sustains mTORC1 activity. The causative role of AXL in inducing drug resistance is underscored by the fact that the suppression of AXL restores sensitivity to these agents. Hence, these observations indicate that AXL is selectively expressed in tumor cells refractory to therapy and that cotargeting AXL in this setting would potentially overcome drug resistance. The use of AXL inhibitors should be considered in the clinic. PMID:26763248

  3. Axl Phosphorylates Elmo Scaffold Proteins To Promote Rac Activation and Cell Invasion

    PubMed Central

    Abu-Thuraia, Afnan; Gauthier, Rosemarie; Chidiac, Rony; Fukui, Yoshinori; Screaton, Robert A.; Gratton, Jean-Philippe

    2014-01-01

    The receptor tyrosine kinase Axl contributes to cell migration and invasion. Expression of Axl correlates with metastatic progression in cancer patients, yet the specific signaling events promoting invasion downstream of Axl are poorly defined. Herein, we report Elmo scaffolds to be direct substrates and binding partners of Axl. Elmo proteins are established to interact with Dock family guanine nucleotide exchange factors to control Rac-mediated cytoskeletal dynamics. Proteomics and mutagenesis studies reveal that Axl phosphorylates Elmo1/2 on a conserved carboxyl-terminal tyrosine residue. Upon Gas6-dependent activation of Axl, endogenous Elmo2 becomes phosphorylated on Tyr-713 and enters into a physical complex with Axl in breast cancer cells. Interfering with Elmo2 expression prevented Gas6-induced Rac1 activation in breast cancer cells. Similarly to blocking of Axl, Elmo2 knockdown or pharmacological inhibition of Dock1 abolishes breast cancer cell invasion. Interestingly, Axl or Elmo2 knockdown diminishes breast cancer cell proliferation. Rescue of Elmo2 knockdown cells with the wild-type protein but not with Elmo2 harboring Tyr-713-Phe mutations restores cell invasion and cell proliferation. These results define a new mechanism by which Axl promotes cell proliferation and invasion and identifies inhibition of the Elmo-Dock pathway as a potential therapeutic target to stop Axl-induced metastases. PMID:25332238

  4. Axl phosphorylates Elmo scaffold proteins to promote Rac activation and cell invasion.

    PubMed

    Abu-Thuraia, Afnan; Gauthier, Rosemarie; Chidiac, Rony; Fukui, Yoshinori; Screaton, Robert A; Gratton, Jean-Philippe; Côté, Jean-François

    2015-01-01

    The receptor tyrosine kinase Axl contributes to cell migration and invasion. Expression of Axl correlates with metastatic progression in cancer patients, yet the specific signaling events promoting invasion downstream of Axl are poorly defined. Herein, we report Elmo scaffolds to be direct substrates and binding partners of Axl. Elmo proteins are established to interact with Dock family guanine nucleotide exchange factors to control Rac-mediated cytoskeletal dynamics. Proteomics and mutagenesis studies reveal that Axl phosphorylates Elmo1/2 on a conserved carboxyl-terminal tyrosine residue. Upon Gas6-dependent activation of Axl, endogenous Elmo2 becomes phosphorylated on Tyr-713 and enters into a physical complex with Axl in breast cancer cells. Interfering with Elmo2 expression prevented Gas6-induced Rac1 activation in breast cancer cells. Similarly to blocking of Axl, Elmo2 knockdown or pharmacological inhibition of Dock1 abolishes breast cancer cell invasion. Interestingly, Axl or Elmo2 knockdown diminishes breast cancer cell proliferation. Rescue of Elmo2 knockdown cells with the wild-type protein but not with Elmo2 harboring Tyr-713-Phe mutations restores cell invasion and cell proliferation. These results define a new mechanism by which Axl promotes cell proliferation and invasion and identifies inhibition of the Elmo-Dock pathway as a potential therapeutic target to stop Axl-induced metastases. PMID:25332238

  5. Tyrosine kinase receptor Axl enhances entry of Zaire ebolavirus without direct interactions with the viral glycoprotein

    SciTech Connect

    Brindley, Melinda A.; Hunt, Catherine L.; Kondratowicz, Andrew S.; Bowman, Jill; Sinn, Patrick L.; McCray, Paul B.; Quinn, Kathrina; Weller, Melodie L.; Chiorini, John A.; Maury, Wendy

    2011-07-05

    In a bioinformatics-based screen for cellular genes that enhance Zaire ebolavirus (ZEBOV) transduction, AXL mRNA expression strongly correlated with ZEBOV infection. A series of cell lines and primary cells were identified that require Axl for optimal ZEBOV entry. Using one of these cell lines, we identified ZEBOV entry events that are Axl-dependent. Interactions between ZEBOV-GP and the Axl ectodomain were not detected in immunoprecipitations and reduction of surface-expressed Axl by RNAi did not alter ZEBOV-GP binding, providing evidence that Axl does not serve as a receptor for the virus. However, RNAi knock down of Axl reduced ZEBOV pseudovirion internalization and {alpha}-Axl antisera inhibited pseudovirion fusion with cellular membranes. Consistent with the importance of Axl for ZEBOV transduction, Axl transiently co-localized on the surface of cells with ZEBOV virus particles and was internalized during virion transduction. In total, these findings indicate that endosomal uptake of filoviruses is facilitated by Axl.

  6. AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity.

    PubMed

    Schmid, Edward T; Pang, Iris K; Carrera Silva, Eugenio A; Bosurgi, Lidia; Miner, Jonathan J; Diamond, Michael S; Iwasaki, Akiko; Rothlin, Carla V

    2016-01-01

    The receptor tyrosine kinase (RTK) AXL is induced in response to type I interferons (IFNs) and limits their production through a negative feedback loop. Enhanced production of type I IFNs in Axl(-/-) dendritic cells (DCs) in vitro have led to speculation that inhibition of AXL would promote antiviral responses. Notwithstanding, type I IFNs also exert potent immunosuppressive functions. Here we demonstrate that ablation of AXL enhances the susceptibility to infection by influenza A virus and West Nile virus. The increased type I IFN response in Axl(-/-) mice was associated with diminished DC maturation, reduced production of IL-1β, and defective antiviral T cell immunity. Blockade of type I IFN receptor or administration of IL-1β to Axl(-/-) mice restored the antiviral adaptive response and control of infection. Our results demonstrate that AXL is essential for limiting the immunosuppressive effects of type I IFNs and enabling the induction of protective antiviral adaptive immunity. PMID:27350258

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

    SciTech Connect

    Xu, Fei; Li, Hongling; Sun, Yong

    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 effect 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.

  8. Passivation and Corrosion Behavior of Modified Ferritic-Pearlitic Railway Axle Steels

    NASA Astrophysics Data System (ADS)

    Moon, A. P.; Sangal, S.; Srivastav, Simant; Gajbhiye, N. S.; Mondal, K.

    2015-01-01

    Electrochemical polarization behavior of two newly developed ferritic-pearlitic railway axle steels (MS3 and MS6) and the standard Indian conventional axle steel has been studied in sodium borate buffer solution of pH 8.4 with and without the presence of NaCl. The polarization behavior of both the new axle steels shows close resemblance, whereas, different polarization behavior has been observed for the conventional axle steel. Electrochemical impedance spectroscopy measurements have clearly reflected significantly improved passivation behavior for the newly developed steels compared to that of the conventional axle steel. NaCl salt fog exposure tests have also shown superior corrosion resistance of the newly developed axle steels as compared to the conventional axle steel. Higher surface roughness on the corroded conventional axle steel has also been observed compared to the smoother surface in case of the new axle steels. Higher corrosion resistance of the new axle steels has been attributed to their finer microstructure and strongly adherent protective rusts.

  9. Axl receptor tyrosine kinase is up-regulated in metformin resistant prostate cancer cells

    PubMed Central

    Bansal, Nitu; Mishra, Prasun J.; Stein, Mark; DiPaola, Robert S.; Bertino, Joseph R.

    2015-01-01

    Recent epidemiological studies showed that metformin, a widely used anti-diabetic drug might prevent certain cancers. Metformin also has an anti-proliferative effect in preclinical studies of both hematologic malignancies as well as solid cancers and clinical studies testing metformin as an anti-cancer drug are in progress. However, all cancer types do not respond to metformin with the same effectiveness or acquire resistance. To understand the mechanism of acquired resistance and possibly its mechanism of action as an anti-proliferative agent, we developed metformin resistant LNCaP prostate cancer cells. Metformin resistant LNCaP cells had an increased proliferation rate, increased migration and invasion ability as compared to the parental cells, and expressed markers of epithelial-mesenchymal transition (EMT). A detailed gene expression microarray comparing the resistant cells to the wild type cells revealed that Edil2, Ereg, Axl, Anax2, CD44 and Anax3 were the top up-regulated genes and calbindin 2 and TPTE (transmembrane phosphatase with tensin homology) and IGF1R were down regulated. We focused on Axl, a receptor tyrosine kinase that has been shown to be up regulated in several drug resistance cancers. Here, we show that the metformin resistant cell line as well as castrate resistant cell lines that over express Axl were more resistant to metformin, as well as to taxotere compared to androgen sensitive LNCaP and CWR22 cells that do not overexpress Axl. Forced overexpression of Axl in LNCaP cells decreased metformin and taxotere sensitivity and knockdown of Axl in resistant cells increased sensitivity to these drugs. Inhibition of Axl activity by R428, a small molecule Axl kinase inhibitor, sensitized metformin resistant cells that overexpressed Axl to metformin. Inhibitors of Axl may enhance tumor responses to metformin and other chemotherapy in cancers that over express Axl. PMID:26036314

  10. Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma.

    PubMed

    Zhou, L; Liu, X-D; Sun, M; Zhang, X; German, P; Bai, S; Ding, Z; Tannir, N; Wood, C G; Matin, S F; Karam, J A; Tamboli, P; Sircar, K; Rao, P; Rankin, E B; Laird, D A; Hoang, A G; Walker, C L; Giaccia, A J; Jonasch, E

    2016-05-01

    Antiangiogenic therapy resistance occurs frequently in patients with metastatic renal cell carcinoma (RCC). The purpose of this study was to understand the mechanism of resistance to sunitinib, an antiangiogenic small molecule, and to exploit this mechanism therapeutically. We hypothesized that sunitinib-induced upregulation of the prometastatic MET and AXL receptors is associated with resistance to sunitinib and with more aggressive tumor behavior. In the present study, tissue microarrays containing sunitinib-treated and untreated RCC tissues were stained with MET and AXL antibodies. The low malignant RCC cell line 786-O was chronically treated with sunitinib and assayed for AXL, MET, epithelial-mesenchymal transition (EMT) protein expression and activation. Co-culture experiments were used to examine the effect of sunitinib pretreatment on endothelial cell growth. The effects of AXL and MET were evaluated in various cell-based models by short hairpin RNA or inhibition by cabozantinib, the multi-tyrosine kinases inhibitor that targets vascular endothelial growth factor receptor, MET and AXL. Xenograft mouse models tested the ability of cabozantinib to rescue sunitinib resistance. We demonstrated that increased AXL and MET expression was associated with inferior clinical outcome in patients. Chronic sunitinib treatment of RCC cell lines activated both AXL and MET, induced EMT-associated gene expression changes, including upregulation of Snail and β-catenin, and increased cell migration and invasion. Pretreatment with sunitinib enhanced angiogenesis in 786-0/human umbilical vein endothelial cell co-culture models. The suppression of AXL or MET expression and the inhibition of AXL and MET activation using cabozantinib both impaired chronic sunitinib treatment-induced prometastatic behavior in cell culture and rescued acquired resistance to sunitinib in xenograft models. In summary, chronic sunitinib treatment induces the activation of AXL and MET signaling and

  11. Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma

    PubMed Central

    Zhou, Lijun; Liu, Xian-De; Sun, Mianen; Zhang, Xuesong; German, Peter; Bai, Shanshan; Ding, Zhiyong; Tannir, Nizar; Wood, Christopher G; Matin, Surena F; Karam, Jose A; Tamboli, Pheroze; Sircar, Kanishka; Rao, Priya; Rankin, Erinn B.; Laird, Douglas A; Hoang, Anh G; Walker, Cheryl L; Giaccia, Amato J; Jonasch, Eric

    2016-01-01

    Antiangiogenic therapy resistance occurs frequently in patients with metastatic renal cell carcinoma (RCC). The purpose of this study was to understand the mechanism of resistance to sunitinib, an antiangiogenic small molecule, and to exploit this mechanism therapeutically. We hypothesized that sunitinib-induced upregulation of the prometastatic MET and AXL receptors is associated with resistance to sunitinib and with more aggressive tumor behavior. In the present study, tissue microarrays containing sunitinib treated and untreated RCC tissues were stained with MET and AXL antibodies. The low malignant RCC cell line, 786-O, was chronically treated with sunitinib, and assayed for AXL, MET, epithelial mesenchymal transition (EMT) protein expression and activation. Co-culture experiments were used to examine the effect of sunitinib pretreatment on endothelial cell growth. The effects of AXL and MET were evaluated in various cell-based models by shRNA or inhibition by cabozantinib, the multi-tyrosine kinases inhibitor that targets VEGFR, MET and AXL. Xenograft mouse models tested the ability of cabozantinib to rescue sunitinib resistance. We demonstrated that increased AXL and MET expression was associated with inferior clinical outcome in patients. Chronic sunitinib treatment of RCC cell lines activated both AXL and MET, induced EMT associated gene expression changes including upregulation of Snail and β-catenin, and increased cell migration and invasion. Pretreatment with sunitinib enhanced angiogenesis in 786-0/HUVEC co-culture models. The suppression of AXL or MET expression, and the inhibition of AXL and MET activation using cabozantinib both impaired chronic sunitinib treatment-induced prometastatic behavior in cell culture, and rescued acquired resistance to sunitinib in xenograft models. In summary, chronic sunitinib treatment induces the activation of AXL and MET signaling and promotes pro-metastatic behavior and angiogenesis. The inhibition of AXL and MET

  12. 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

  13. 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... repaired : (1) Cut journals that cannot be made to run cool without turning; (2) Seams in axles causing journals to run hot; (3) Overheating, as evidenced by pronounced blue black discoloration; (4)...

  14. 49 CFR 230.100 - Defects in tender truck axles and journals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Steam Locomotives and Tenders Running Gear § 230.100 Defects in tender truck axles and journals. (a... repaired : (1) Cut journals that cannot be made to run cool without turning; (2) Seams in axles causing journals to run hot; (3) Overheating, as evidenced by pronounced blue black discoloration; (4)...

  15. 49 CFR 230.100 - Defects in tender truck axles and journals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Steam Locomotives and Tenders Running Gear § 230.100 Defects in tender truck axles and journals. (a... repaired : (1) Cut journals that cannot be made to run cool without turning; (2) Seams in axles causing journals to run hot; (3) Overheating, as evidenced by pronounced blue black discoloration; (4)...

  16. 49 CFR 230.100 - Defects in tender truck axles and journals.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Steam Locomotives and Tenders Running Gear § 230.100 Defects in tender truck axles and journals. (a... repaired : (1) Cut journals that cannot be made to run cool without turning; (2) Seams in axles causing journals to run hot; (3) Overheating, as evidenced by pronounced blue black discoloration; (4)...

  17. 49 CFR 230.100 - Defects in tender truck axles and journals.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Steam Locomotives and Tenders Running Gear § 230.100 Defects in tender truck axles and journals. (a... repaired : (1) Cut journals that cannot be made to run cool without turning; (2) Seams in axles causing journals to run hot; (3) Overheating, as evidenced by pronounced blue black discoloration; (4)...

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

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Driving, trailing, and engine truck axles. 230.98... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Steam Locomotives and Tenders Running Gear § 230.98 Driving, trailing, and engine truck axles. (a)...

  19. 49 CFR 230.98 - Driving, trailing, and engine truck axles.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Driving, trailing, and engine truck axles. 230.98... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Steam Locomotives and Tenders Running Gear § 230.98 Driving, trailing, and engine truck axles. (a)...

  20. 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... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Steam Locomotives and Tenders Running Gear § 230.98 Driving, trailing, and engine truck axles. (a)...

  1. 49 CFR 230.98 - Driving, trailing, and engine truck axles.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Driving, trailing, and engine truck axles. 230.98... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Steam Locomotives and Tenders Running Gear § 230.98 Driving, trailing, and engine truck axles. (a)...

  2. 49 CFR 230.98 - Driving, trailing, and engine truck axles.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Driving, trailing, and engine truck axles. 230.98... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Steam Locomotives and Tenders Running Gear § 230.98 Driving, trailing, and engine truck axles. (a)...

  3. Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET.

    PubMed

    Rankin, Erinn B; Fuh, Katherine C; Castellini, Laura; Viswanathan, Kartik; Finger, Elizabeth C; Diep, Anh N; LaGory, Edward L; Kariolis, Mihalis S; Chan, Andy; Lindgren, David; Axelson, Håkan; Miao, Yu R; Krieg, Adam J; Giaccia, Amato J

    2014-09-16

    Dysregulation of the von Hippel-Lindau/hypoxia-inducible transcription factor (HIF) signaling pathway promotes clear cell renal cell carcinoma (ccRCC) progression and metastasis. The protein kinase GAS6/AXL signaling pathway has recently been implicated as an essential mediator of metastasis and receptor tyrosine kinase crosstalk in cancer. Here we establish a molecular link between HIF stabilization and induction of AXL receptor expression in metastatic ccRCC. We found that HIF-1 and HIF-2 directly activate the expression of AXL by binding to the hypoxia-response element in the AXL proximal promoter. Importantly, genetic and therapeutic inactivation of AXL signaling in metastatic ccRCC cells reversed the invasive and metastatic phenotype in vivo. Furthermore, we define a pathway by which GAS6/AXL signaling uses lateral activation of the met proto-oncogene (MET) through SRC proto-oncogene nonreceptor tyrosine kinase to maximize cellular invasion. Clinically, AXL expression in primary tumors of ccRCC patients correlates with aggressive tumor behavior and patient lethality. These findings provide an alternative model for SRC and MET activation by growth arrest-specific 6 in ccRCC and identify AXL as a therapeutic target driving the aggressive phenotype in renal clear cell carcinoma. PMID:25187556

  4. Dominant-negative inhibition of the Axl receptor tyrosine kinase suppresses brain tumor cell growth and invasion and prolongs survival

    PubMed Central

    Vajkoczy, Peter; Knyazev, Pjotr; Kunkel, Andrea; Capelle, Hans-Holger; Behrndt, Sandra; von Tengg-Kobligk, Hendrik; Kiessling, Fabian; Eichelsbacher, Uta; Essig, Marco; Read, Tracy-Ann; Erber, Ralf; Ullrich, Axel

    2006-01-01

    Malignant gliomas remain incurable brain tumors because of their diffuse-invasive growth. So far, the genetic and molecular events underlying gliomagenesis are poorly understood. In this study, we have identified the receptor tyrosine kinase Axl as a mediator of glioma growth and invasion. We demonstrate that Axl and its ligand Gas6 are overexpressed in human glioma cell lines and that Axl is activated under baseline conditions. Furthermore, Axl is expressed at high levels in human malignant glioma. Inhibition of Axl signaling by overexpression of a dominant-negative receptor mutant (AXL-DN) suppressed experimental gliomagenesis (growth inhibition >85%, P < 0.05) and resulted in long-term survival of mice after intracerebral glioma cell implantation when compared with Axl wild-type (AXL-WT) transfected tumor cells (survival times: AXL-WT, 10 days; AXL-DN, >72 days). A detailed analysis of the distinct hallmarks of glioma pathology, such as cell proliferation, migration, and invasion and tumor angiogenesis, revealed that inhibition of Axl signaling interfered with cell proliferation (inhibition 30% versus AXL-WT), glioma cell migration (inhibition 90% versus mock and AXL-WT, P < 0.05), and invasion (inhibition 62% and 79% versus mock and AXL-WT, respectively; P < 0.05). This study describes the identification, functional manipulation, in vitro and in vivo validation, and preclinical therapeutic inhibition of a target receptor tyrosine kinase mediating glioma growth and invasion. Our findings implicate Axl in gliomagenesis and validate it as a promising target for the development of approaches toward a therapy of these highly aggressive but, as yet, therapy-refractory, tumors. PMID:16585512

  5. AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity

    PubMed Central

    Schmid, Edward T; Pang, Iris K; Carrera Silva, Eugenio A; Bosurgi, Lidia; Miner, Jonathan J; Diamond, Michael S; Iwasaki, Akiko; Rothlin, Carla V

    2016-01-01

    The receptor tyrosine kinase (RTK) AXL is induced in response to type I interferons (IFNs) and limits their production through a negative feedback loop. Enhanced production of type I IFNs in Axl-/-dendritic cells (DCs) in vitro have led to speculation that inhibition of AXL would promote antiviral responses. Notwithstanding, type I IFNs also exert potent immunosuppressive functions. Here we demonstrate that ablation of AXL enhances the susceptibility to infection by influenza A virus and West Nile virus. The increased type I IFN response in Axl-/- mice was associated with diminished DC maturation, reduced production of IL-1β, and defective antiviral T cell immunity. Blockade of type I IFN receptor or administration of IL-1β to Axl-/- mice restored the antiviral adaptive response and control of infection. Our results demonstrate that AXL is essential for limiting the immunosuppressive effects of type I IFNs and enabling the induction of protective antiviral adaptive immunity. DOI: http://dx.doi.org/10.7554/eLife.12414.001 PMID:27350258

  6. Activation of HER3 Interferes with Antitumor Effects of Axl Receptor Tyrosine Kinase Inhibitors: Suggestion of Combination Therapy1

    PubMed Central

    Torka, Robert; Pénzes, Kinga; Gusenbauer, Simone; Baumann, Christine; Szabadkai, István; Őrfi, Lászlȯ; Kéri, György; Ullrich, Axel

    2014-01-01

    The Axl receptor tyrosine kinase (RTK) has been established as a strong candidate for targeted therapy of cancer. However, the benefits of targeted therapies are limited due to acquired resistance and activation of alternative RTKs. Therefore, we asked if cancer cells are able to overcome targeted Axl therapies. Here, we demonstrate that inhibition of Axl by short interfering RNA or the tyrosine kinase inhibitor (TKI) BMS777607 induces the expression of human epidermal growth factor receptor 3 (HER3) and the neuregulin 1(NRG1)–dependent phosphorylation of HER3 in MDA-MB231 and Ovcar8 cells. Moreover, analysis of 20 Axl-expressing cancer cell lines of different tissue origin indicates a low basal phosphorylation of RAC-α serine/threonine-protein kinase (AKT) as a general requirement for HER3 activation on Axl inhibition. Consequently, phosphorylation of AKT arises as an independent biomarker for Axl treatment. Additionally, we introduce phosphorylation of HER3 as an independent pharmacodynamic biomarker for monitoring of anti-Axl therapy response. Inhibition of cell viability by BMS777607 could be rescued by NRG1-dependent activation of HER3, suggesting an escape mechanism by tumor microenvironment. The Axl-TKI MPCD84111 simultaneously blocked Axl and HER2/3 signaling and thereby prohibited HER3 feedback activation. Furthermore, dual inhibition of Axl and HER2/3 using BMS777607 and lapatinib led to a significant inhibition of cell viability in Axl-expressing MDA-MB231 and Ovcar8 cells. Therefore, we conclude that, in patient cohorts with expression of Axl and low basal activity of AKT, a combined inhibition of Axl and HER2/3 kinase would be beneficial to overcome acquired resistance to Axl-targeted therapies. PMID:24862757

  7. 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.

  8. Anion recognition in water by a rotaxane containing a secondary rim functionalised cyclodextrin stoppered axle.

    PubMed

    Řezanka, Michal; Langton, Matthew J; Beer, Paul D

    2015-03-14

    The synthesis of a water soluble [2]rotaxane is reported using hydrophilic secondary rim functionalised permethylated β-cyclodextrin derivatives as the axle stopper groups. The rotaxane recognises halide anions in pure water with impressive selectivity over sulfate. PMID:25682747

  9. The role of AXL and the in vitro activity of the receptor tyrosine kinase inhibitor BGB324 in Ewing sarcoma

    PubMed Central

    Fleuren, Emmy D.G.; Hillebrandt-Roeffen, Melissa H.S.; Flucke, Uta E.; te Loo, D. Maroeska W.M.; Boerman, Otto C.; van der Graaf, Winette T.A.; Versleijen-Jonkers, Yvonne M.H.

    2014-01-01

    New targets for Ewing sarcoma (ES) patients are urgently needed. Therefore, we investigated the expression and genetic aberrations of the oncogenic receptor tyrosine kinase (RTK) AXL in ES and determined the efficacy of AXL targeting on cell viability and migration. First, AXL and Gas6 (ligand) mRNA expression was determined by RT-PCR on 29 ES samples. Low, medium and high AXL mRNA expression was observed in 31% (n = 9), 48% (n = 14) and 21% (n = 6) of samples. Gas6 was abundantly present in all specimens. We next tested AXL protein expression immunohistochemically in 36 tumors (primary, post-chemotherapy, metastasized and relapsed samples) from 25 ES patients. Low, medium and high AXL protein expression was observed in 17% (n = 6), 19% (n = 7) and 36% (n = 13) of samples. In primary tumors (n = 15), high AXL expression correlated significantly with a worse overall survival compared to patients with lower expression (61 vs. 194 months, p = 0.026). No genetic aberrations were detected in the AXL RTK domain (n = 29). The AXL-inhibitor BGB324 affected viability (IC50 0.79–2.13 μmol/L) and migratory potential of all tested ES cell lines in vitro (n = 5–6). BGB324 chemosensitized chemotherapy-resistant ES-4 cells to vincristine and doxorubicin. These data suggest that AXL is a potential novel, druggable therapeutic target in ES. PMID:25528764

  10. Opposing Roles of Tyrosine Kinase Receptors Mer and Axl Determine Clinical Outcomes in Experimental Immune-Mediated Nephritis.

    PubMed

    Zhen, Yuxuan; Priest, Stephen O; Shao, Wen-Hai

    2016-09-15

    Glomerulonephritis is one of the most severe manifestations of systemic lupus erythematosus, with considerable morbidity and mortality. There remains a major unmet need for successful management of lupus nephritis. TAM family receptor tyrosine kinases (Mer and Axl) play an important role in the maintenance of immune homeostasis in the kidney. Mer is constitutively expressed in the glomeruli; Axl expression is inducible in glomeruli under inflammatory conditions. To investigate the distinct functions of Axl and Mer in lupus nephritis, we compared the severity of nephrotoxic serum glomerulonephritis in wild-type (WT), Axl-knockout (KO), Mer-KO, and Axl/Mer-KO mice. Mer-KO mice developed severe glomerulonephritis, with significantly decreased survival and increased blood urea nitrogen levels compared with WT mice given the same treatment. However, nephrotoxic serum-treated Axl-KO mice had significantly increased survival rates and improved renal function compared with similarly treated WT, Mer-KO, and Axl/Mer-KO mice. Interestingly, mice lacking both Axl and Mer developed kidney inflammation comparable to WT mice. Western blot analysis revealed significantly increased Stat3 phosphorylation and caspase-1 activation in the kidneys of nephritic Mer-KO mice. In contrast, Axl-deficient nephrotoxic serum-injected mice showed decreased Akt phosphorylation and Bcl-xL upregulation. Thus, the reciprocal activation of Axl and Mer receptor tyrosine kinases has a major impact on the outcome of renal inflammation. PMID:27527599

  11. 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.

  12. Two axles threaded using a single template site: active metal template macrobicyclic [3]rotaxanes.

    PubMed

    Goldup, Stephen M; Leigh, David A; McGonigal, Paul R; Ronaldson, Vicki E; Slawin, Alexandra M Z

    2010-01-13

    Template approaches to rotaxanes normally require at least n - 1 template sites to interlock n components. Here we describe the one-pot synthesis of [3]rotaxanes in which a single metal template site induces formation of axles through each cavity of a bicyclic macrocycle. Central to the approach is that a portion of the bicyclic molecule acts as a ligand for a transition metal ion that mediates covalent bond formation through one or other macrocyclic cavity, depending on the ligand's orientation, making a mechanical bond. The ligand can then rotate so that the transition metal can catalyze the formation of a second axle through the other macrocycle. Using this strategy with the Cu(I)-catalyzed azide-alkyne cycloaddition (the CuAAC reaction) generates a [3]rotaxane with two identical axles in up to 86% yield. [3]Rotaxanes with two different axles threaded through the macrobicyclic rings can also be created using a single template site, either by having copper(I) sequentially form both mechanical bonds (via the CuAAC reaction) using different sets of building blocks for each axle or by using two different reactions catalyzed by two different metal ions: a palladium(II)-mediated alkyne homocoupling to assemble the first thread through one cavity, followed by a copper(I)-mediated CuAAC reaction to form the second axle through the other ring. PMID:19968281

  13. 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.

  14. Mice lacking Axl and Mer tyrosine kinase receptors are susceptible to experimental autoimmune orchitis induction.

    PubMed

    Li, Nan; Liu, Zhenghui; Zhang, Yue; Chen, Qiaoyuan; Liu, Peng; Cheng, C Yan; Lee, Will M; Chen, Yongmei; Han, Daishu

    2015-03-01

    The mammalian testis is an immunoprivileged organ where male germ cell autoantigens are immunologically ignored. Both systemic immune tolerance to autoantigens and local immunosuppressive milieu contribute to the testicular immune privilege. Testicular immunosuppression has been intensively studied, but information on systemic immune tolerance to autoantigens is lacking. In the present study, we aimed to determine the role of Axl and Mer receptor tyrosine kinases in maintaining the systemic tolerance to male germ cell antigens using the experimental autoimmune orchitis (EAO) model. Axl and Mer double-knockout (Axl(-/-)Mer(-/-)) mice developed evident EAO after a single immunization with germ cell homogenates emulsified with complete Freund's adjuvant. EAO was characterized by the accumulation of macrophages and T lymphocytes in the testis. Damage to the seminiferous epithelium was also observed. EAO induction was associated with pro-inflammatory cytokine upregulation in the testes, impaired permeability of the blood-testis barrier and generation of autoantibodies against germ cell antigens in Axl(-/-)Mer(-/-) mice. Immunization also induced mild EAO in Axl or Mer single-gene-knockout mice. By contrast, a single immunization failed to induce EAO in wild-type mice. The results indicate that Axl and Mer receptors cooperatively regulate the systemic immune tolerance to male germ cell antigens. PMID:25403570

  15. The Axl receptor tyrosine kinase is a discriminator of macrophage function in the inflamed lung

    PubMed Central

    Kaur, Manminder; Bell, Thomas J; Fujino, Naoya; Cook, Peter C; Svedberg, Freya R; MacDonald, Andrew S; Maciewicz, Rose A; Singh, Dave; Hussell, Tracy

    2014-01-01

    Much of the biology surrounding macrophage functional specificity has arisen through examining inflammation-induced polarising signals, but this also occurs in homeostasis, requiring tissue-specific environmental triggers that influence macrophage phenotype and function. The TAM receptor family of receptor tyrosine kinases (Tyro3, Axl and MerTK) mediates the non-inflammatory removal of apoptotic cells by phagocytes through the bridging phosphatidylserine-binding molecules Gas6 or Protein S. We show that one such TAM receptor (Axl) is exclusively expressed on mouse airway macrophages, but not interstitial macrophages and other lung leukocytes, under homeostatic conditions and is constitutively ligated to Gas6. Axl expression is potently induced by GM-CSF expressed in the healthy and inflamed airway, and by type I interferon or TLR3 stimulation on human and mouse macrophages, indicating potential involvement of Axl in apoptotic cell removal under inflammatory conditions. Indeed, an absence of Axl does not cause sterile inflammation in health, but leads to exaggerated lung inflammatory disease upon influenza infection. These data imply that Axl allows specific identification of airway macrophages, and that its expression is critical for macrophage functional compartmentalisation in the airspaces or lung interstitium. We propose that this may be a critical feature to prevent excessive inflammation due to secondary necrosis of apoptotic cells that have not been cleared by efferocytosis. PMID:25603826

  16. Metrological approach to the force exerted by the axle of a road vehicle in motion carrying liquid

    NASA Astrophysics Data System (ADS)

    Faruolo, Luciano Bruno; de Noronha Castro Pinto, Fernando Augusto

    2016-01-01

    Weigh-in-motion (WIM) systems are used for identifying the dynamic force exerted on the ground by axles of a vehicle. These systems are important for monitoring the gross vehicle weight and the vehicle axle load. Overweighted trucks on the roads increase pavement damage and traffic accidents. Knowing the accuracy of WIM systems is necessary. In the case of liquid transport the ‘sloshing effect’ affects this accuracy. This paper aims to analyze the dynamic measurement of the axle forces in vehicles carrying liquid during WIM up to 6 km h-1. Laboratory experiments using one vehicle with six axles and liquid loads on different levels in weighing instruments are presented. A non-linear computational multi-mass-springs model was developed and laboratory experiments were carried out to show the acceleration influences on axle forces of vehicles with six axles and with and without baffles to vary the ‘sloshing effect’.

  17. axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase

    SciTech Connect

    O'Bryan, J.P.; Frye, R.A.; Cogswell, P.C.; Neubauer, A.; Kitch, B.; Prokop, C.; Earp, H.S.; Liu, E.T. ); Espinosa, R. III; Le Beau, M.M. )

    1991-10-01

    Using a sensitive transfection-tumorigenicity assay, the authors have isolated a novel transforming gene from the DNA of two patients with chronic myelogenous leukemia. Sequence analysis indicates that the product of this gene, axl, is a receptor tyrosine kinase. Overexpression of axl cDNA in NIH 3T3 cells induces neoplastic transformation with the concomitant appearance of a 140-kDa axl tyrosine-phosphorylated protein. Expression of axl cDNA in the baculovirus system results in the expression of the appropriate recombinant protein that is recognized by antophosphotyrosine antibodies, confirming that the axl protein is a tyrosine kinase. The juxtaposition of fibronectin type II and immunoglobulinlike repeats in the extracellular domain, as well as distinct amino acid sequences in the kinase domain, indicate that the axl protein represents a novel subclass of receptor tyrosine kinases.

  18. Reliability analysis of laser ultrasonics for train axle diagnostics based on model assisted POD curves

    NASA Astrophysics Data System (ADS)

    Malik, M. S.; Cavuto, A.; Martarelli, M.; Pandarese, G.; Revel, G. M.

    2014-05-01

    High speed train axles are integrated for a lifetime and it is time and resource consuming to conduct in service inspection with high accuracy. Laser ultrasonics is a proposed solution as a subset of non-contact measuring methods effective also for hard to reach areas and even recently proved to be effective using Laser Doppler Vibrometer (LDV) or air-coupled probes in reception. A reliability analysis of laser ultrasonics for this specific application is here performed. The research is mainly based on numerical study of the effect of high energy laser pulses on the surface of a steel axle and of the behavior of the ultrasonic waves in detecting possible defects. Probability of Detection (POD) concept is used as an estimated reliability of the inspection method. In particular Model Assisted Probability of Detection (MAPOD), a modified form of POD where models are used to infer results for making a decisive statistical approach of POD curve, is here adopted. This paper implements this approach by taking the inputs from limited experiments conducted on a high speed train axle using laser ultrasonics (source pulsed Nd:Yag, reception by high-frequency LDV) to calibrate a multiphysics FE model and by using the calibrated model to generate data samples statistically representative of damaged train axles. The simulated flaws are in accordance with the real defects present on the axle. A set of flaws of different depth has been modeled in order to assess the laser ultrasonics POD for this specific application.

  19. Heightened cleavage of Axl receptor tyrosine kinase by ADAM metalloproteases may contribute to disease pathogenesis in SLE.

    PubMed

    Orme, Jacob J; Du, Yong; Vanarsa, Kamala; Mayeux, Jessica; Li, Li; Mutwally, Azza; Arriens, Cristina; Min, Soyoun; Hutcheson, Jack; Davis, Laurie S; Chong, Benjamin F; Satterthwaite, Anne B; Wu, Tianfu; Mohan, Chandra

    2016-08-01

    Systemic lupus erythematosus (SLE) is characterized by antibody-mediated chronic inflammation in the kidney, lung, skin, and other organs to cause inflammation and damage. Several inflammatory pathways are dysregulated in SLE, and understanding these pathways may improve diagnosis and treatment. In one such pathway, Axl tyrosine kinase receptor responds to Gas6 ligand to block inflammation in leukocytes. A soluble form of the Axl receptor ectodomain (sAxl) is elevated in serum from patients with SLE and lupus-prone mice. We hypothesized that sAxl in SLE serum originates from the surface of leukocytes and that the loss of leukocyte Axl contributes to the disease. We determined that macrophages and B cells are a source of sAxl in SLE and in lupus-prone mice. Shedding of the Axl ectodomain from the leukocytes of lupus-prone mice is mediated by the matrix metalloproteases ADAM10 and TACE (ADAM17). Loss of Axl from lupus-prone macrophages renders them unresponsive to Gas6-induced anti-inflammatory signaling in vitro. This phenotype is rescued by combined ADAM10/TACE inhibition. Mice with Axl-deficient macrophages develop worse disease than controls when challenged with anti-glomerular basement membrane (anti-GBM) sera in an induced model of nephritis. ADAM10 and TACE also mediate human SLE PBMC Axl cleavage. Collectively, these studies indicate that increased metalloprotease-mediated cleavage of leukocyte Axl may contribute to end organ disease in lupus. They further suggest dual ADAM10/TACE inhibition as a potential therapeutic modality in SLE. PMID:27237127

  20. ALK inhibitor resistance in ALKF1174L-driven neuroblastoma is associated with AXL activation and induction of EMT

    PubMed Central

    Debruyne, D N; Bhatnagar, N; Sharma, B; Luther, W; Moore, N F; Cheung, N-K; Gray, N S; George, R E

    2016-01-01

    The crizotinib-resistant ALKF1174L mutation arises de novo in neuroblastoma (NB) and is acquired in ALK translocation-driven cancers, lending impetus to the development of novel anaplastic lymphoma kinase (ALK) inhibitors with different modes of action. The diaminopyrimidine TAE684 and its derivative ceritinib (LDK378), which are structurally distinct from crizotinib, are active against NB cells expressing ALKF1174L. Here we demonstrate acquired resistance to TAE684 and LDK378 in ALKF1174L-driven human NB cells that is linked to overexpression and activation of the AXL tyrosine kinase and epithelial-to-mesenchymal transition (EMT). AXL phosphorylation conferred TAE684 resistance to NB cells through upregulated extracellular signal-regulated kinase (ERK) signaling. Inhibition of AXL partly rescued TAE684 resistance, resensitizing these cells to this compound. AXL activation in resistant cells was mediated through increased expression of the active form of its ligand, GAS6, that also served to stabilize the AXL protein. Although ectopic expression of AXL and TWIST2 individually in TAE684-sensitive parental cells led to the elevated expression of mesenchymal markers and invasive capacity, only AXL overexpression induced resistance to TAE684 as well. TAE684-resistant cells showed greater sensitivity to HSP90 inhibition than did their parental counterparts, with downregulation of AXL and AXL-mediated ERK signaling. Our studies indicate that aberrant AXL signaling and development of an EMT phenotype underlie resistance of ALKF1174L-driven NB cells to TAE684 and its derivatives. We suggest that the combination of ALK and AXL or HSP90 inhibitors be considered to delay the emergence of such resistance. PMID:26616860

  1. Rational Design for Rotaxane Synthesis through Intramolecular Slippage: Control of Activation Energy by Rigid Axle Length.

    PubMed

    Masai, Hiroshi; Terao, Jun; Fujihara, Tetsuaki; Tsuji, Yasushi

    2016-05-01

    We describe a new concept for rotaxane synthesis through intramolecular slippage using π-conjugated molecules as rigid axles linked with organic soluble and flexible permethylated α-cyclodextrins (PM α-CDs) as macrocycles. Through hydrophilic-hydrophobic interactions and flipping of PM α-CDs, successful quantitative conversion into rotaxanes was achieved without covalent bond formation. The rotaxanes had high activation barrier for their de-threading, so that they were kinetically isolated and derivatized even under conditions unfavorable for maintaining the rotaxane structures. (1) H NMR spectroscopy experiments clearly revealed that the restricted motion of the linked macrocycle with the rigid axle made it possible to control the kinetic stability by adjusting the length of the rigid axle in the precursor structure rather than the steric bulkiness of the stopper unit. PMID:27027800

  2. 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

    .... 383.3(a)). Current Regulatory Guidance Question 14 to Sec. 390.5 (62 FR 16370, 16407, April 4, 1997..., but walks alongside it to use a wired or wireless remote control to steer the rear axle; sometimes the...'s design. In the self-steering mode, the axle automatically steers itself within a range...

  3. Finite element simulation on thermal mechanical expansion of the automobile rear axle housing

    NASA Astrophysics Data System (ADS)

    Liu, Hua-min; Zhao, Yufeng; Zhi, Fuxin

    2013-05-01

    Mechanical thermal expansion is a new metal processing method, which improved not only the properties of materials and the production efficiency, but also achieves better processing surface quality and comprehensive mechanical properties. Axle housing mechanical thermal expansion is simulated by DEFORM-3D, then by metal flow analysis, explored the deformation characteristics through stress-strain distribution and velocity, predicted possible forming defects types and locations and propose appropriate solutions. Through analysis of the influence of different process parameters on the axle housing mechanical thermal expansion, theoretical guidance for actual production is provided.

  4. 4-Oxo-1,4-dihydroquinoline-3-carboxamide Derivatives as New Axl Kinase Inhibitors.

    PubMed

    Tan, Li; Zhang, Zhang; Gao, Donglin; Luo, Jinfeng; Tu, Zheng-Chao; Li, Zhengqiu; Peng, Lijie; Ren, Xiaomei; Ding, Ke

    2016-07-28

    Axl is a new potential target for anticancer drug discovery. A series of 4-oxo-1,4-dihydroquinoline-3-carboxamides were designed and synthesized as highly potent Axl kinase inhibitors. One of the most promising compounds, 9im, tightly bound with Axl protein and potently inhibited its kinase function with a Kd value of 2.7 nM and an IC50 value of 4.0 nM, respectively, while was obviously less potent against most of the 403 wild-type kinases evaluated at a relatively high concentration. The compound dose-dependently inhibited the TGF-β1-induced epithelial-mesenchymal transition (EMT) and suppressed the migration and invasion of MDA-MB-231 breast cancer cells. In addition, 9im also demonstrated reasonable pharmacokinetics properties in rats and exhibited in vivo therapeutic effect on hepatic metastasis in a xenograft model of highly metastatic 4T1 murine breast cancer cells. Compound 9im may serve as a lead compound for new anticancer drug discovery and a valuable research probe for further biological investigation on Axl. PMID:27379978

  5. 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…

  6. In vitro and in vivo antiangiogenic activity of desacetylvinblastine monohydrazide through inhibition of VEGFR2 and Axl pathways

    PubMed Central

    Lei, Xueping; Chen, Minfeng; Nie, Qiulin; Hu, Jianyang; Zhuo, Zhenjian; Yiu, Anita; Chen, Heru; Xu, Nanhui; Huang, Maohua; Ye, Kaihe; Bai, Liangliang; Ye, Wencai; Zhang, Dongmei

    2016-01-01

    Tumor angiogenic process is regulated by multiple proangiogenic pathways, such as vascular endothelial growth factor receptor 2 (VEGFR2) and Axl receptor tyrosine kinase (Axl). Axl is one of many important factors involved in anti-VEGF resistance. Inhibition of VEGF/VEGFR2 signaling pathway alone fails to block tumor neovascularization. Therefore, discovery of novel agents targeting multiple angiogenesis pathways is in demand. Desacetylvinblastine monohydrazide (DAVLBH), a derivative of vinblastine (VLB), has been reported exhibit an anticancer activity via its cytotoxic effect. However, little attention has been paid to the antiangiogenic properties of DAVLBH. Here, we firstly reported that DAVLBH exerted a more potent antiangiogenic effect than VLB in vitro and in vivo, which was associated with inactivation of VEGF/VEGFR2 and Gas6/Axl signaling pathways. We found that DAVLBH inhibited VEGF- and Gas6-induced HUVECs proliferation, migration, tube formation and vessel sprouts formation in vitro and ex vivo. It significantly inhibited in vivo tumor angiogenesis and tumor growth in HeLa xenografts. It also inhibited Gas6-induced pericytes recruitment to endothelial tubes accompanied with a decrease in expression and activation of Axl. Besides, it could block the compensatory up-regulating expression and activation of Axl in response to bevacizumab treatment in HUVECs. Taken together, our results suggest that DAVLBH potently inhibits angiogenesis-mediated tumor growth through blockage of the activation of VEGF/VEGFR2 and Gas6/Axl pathways and it might serve as a promising antiangiogenic agent for the cancer therapy. PMID:27186435

  7. 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.

  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. PMID:25117439

  9. The novel receptor tyrosine kinase Axl is constitutively active in B-cell chronic lymphocytic leukemia and acts as a docking site of nonreceptor kinases: implications for therapy

    PubMed Central

    Secreto, Charla; Boysen, Justin; Sassoon, Traci; Shanafelt, Tait D.; Mukhopadhyay, Debabrata; Kay, Neil E.

    2011-01-01

    Recently, we detected that chronic lymphocytic leukemia (CLL) B-cell–derived microvesicles in CLL plasma carry a constitutively phosphorylated novel receptor tyrosine kinase (RTK), Axl, indicating that Axl was acquired from the leukemic B cells. To examine Axl status in CLL, we determined the expression of phosphorylated-Axl (P-Axl) in freshly isolated CLL B cells by Western blot analysis. We detected differential levels of P-Axl in CLL B cells, and further analysis showed that expression of P-Axl was correlated with the other constitutively phosphorylated kinases, including Lyn, phosphoinositide-3 kinase, SyK/ζ-associated protein of 70 kDa, phospholipase C γ2 in CLL B cells. We found that these intracellular signaling molecules were complexed with P-Axl in primary CLL B cells. When Axl and Src kinases were targeted by a Src/Abl kinase inhibitor, bosutinib (SKI-606), or a specific-inhibitor of Axl (R428), robust induction of CLL B-cell apoptosis was observed in both a dose- and time-dependent manner. Therefore, we have identified a novel RTK in CLL B cells which appears to work as a docking site for multiple non-RTKs and drives leukemic cell survival signals. These findings highlight a unique target for CLL treatment. PMID:21135257

  10. The tyrosine receptor kinase of Axl is an essential regulator of prostate cancer proliferation and tumor growth and represents a new therapeutic target

    PubMed Central

    Paccez, Juliano D; Vasques, Gabriela J; Correa, Ricardo G; Vasconcellos, Jaira F; Duncan, Kristal; Gu, Xuesong; Bhasin, Manoj; Libermann, Towia A; Zerbini, Luiz F

    2014-01-01

    Deregulation of the receptor tyrosine kinase Axl has been implicated in the progression of several human cancers. However, the role of Axl in prostate cancer remains poorly understood, and the therapeutic efficacy of Axl targeting remains untested. In this report we identified Axl as a new therapeutic target for prostate cancer. Axl is consistently overexpressed in prostate cancer cell lines and human prostate tumors. Interestingly, the blockage of Axl gene expression strongly inhibits proliferation, migration, invasion, and tumor growth. Furthermore, inhibition of Axl expression by small interfering RNA regulates a transcriptional program of genes involved in cell survival, strikingly all connected to the NF-κB pathway. Additionally, blockage of Axl expression leads to inhibition of Akt, IKKα and IκBα phosphorylation, increasing IκBα expression and stability. Furthermore, induction of Akt phosphorylation by IGF1 in Axl knockdown cells restores Akt activity and proliferation. Taken together our results establish an unambiguous role for Axl in prostate cancer tumorigenesis with implications for prostate cancer treatment. PMID:22410775

  11. Association between the expression levels of TAZ, AXL and CTGF and clinicopathological parameters in patients with colon cancer

    PubMed Central

    ZHANG, SHU-DONG; MCCRUDDEN, CIAN M.; YUEN, HIU-FUNG; LEUNG, KA LAI; HONG, WAN-JIN; KWOK, HANG FAI

    2016-01-01

    Colon cancer accounts for a large proportion of all the cancer-associated morbidities worldwide. Genetic analysis and stratification of patients based on survival may identify genetic signatures potentially useful for prognostic or treatment planning purposes. Previous studies have reported that the messenger (m)RNA expression levels of tafazzin (TAZ), AXL receptor tyrosine kinase (AXL) and connective tissue growth factor (CTGF) were able to predict the survival of patients with colon cancer in two independent colon cancer datasets. However, limited clinicopathological data were available from these two datasets. By contrast, a large colon cancer dataset comprising 566 patients has been recently published in the Gene Expression Omnibus database, which contains data regarding tumor stage and location, and genetic status of mismatch repair (MMR), Kirsten rat sarcoma viral oncogene homolog (KRAS), B-Raf proto-oncogene serine/threonine kinase (BRAF) and tumor protein p53 (TP53). In the present study, the mRNA expression levels of TAZ, AXL and CTGF were evaluated, and the TAZ-AXL-CTGF signature was correlated with the available pathological parameters and survival data. Overexpression of TAZ, AXL and CTGF was observed to be associated with severe pathological stage, deficiency in MMR, colon cancer subtype C4 and mutations in the BRAF gene. In addition, overexpression of TAZ-AXL-CTGF was associated with short overall survival in patients with mutations in the TP53 gene, colon cancer subtype C6, proficient MMR and wild-type status of the KRAS and BRAF genes. Furthermore, the prognostic value of TAZ-AXL-CTGF overexpression was observed to be independent of all the clinicopathological parameters and mutational statuses analyzed. The results of the present study confirm the previously reported findings, and suggest that the TAZ-AXL-CTGF mRNA signature is a potential prognostic indicator in colon cancer. PMID:26893723

  12. CBL controls a tyrosine kinase network involving AXL, SYK and LYN in nilotinib-resistant chronic myeloid leukaemia.

    PubMed

    Gioia, Romain; Trégoat, Claire; Dumas, Pierre-Yves; Lagarde, Valérie; Prouzet-Mauléon, Valérie; Desplat, Vanessa; Sirvent, Audrey; Praloran, Vincent; Lippert, Eric; Villacreces, Arnaud; Leconet, Wilhem; Robert, Bruno; Vigon, Isabelle; Roche, Serge; Mahon, François-Xavier; Pasquet, Jean-Max

    2015-09-01

    A tyrosine kinase network composed of the TAM receptor AXL and the cytoplasmic kinases LYN and SYK is involved in nilotinib-resistance of chronic myeloid leukaemia (CML) cells. Here, we show that the E3-ubiquitin ligase CBL down-regulation occurring during prolonged drug treatment plays a critical role in this process. Depletion of CBL in K562 cells increases AXL and LYN protein levels, promoting cell resistance to nilotinib. Conversely, forced expression of CBL in nilotinib-resistant K562 cells (K562-rn) dramatically reduces AXL and LYN expression and resensitizes K562-rn cells to nilotinib. A similar mechanism was found to operate in primary CML CD34(+) cells. Mechanistically, the E3-ligase CBL counteracts AXL/SYK signalling, promoting LYN transcription by controlling AXL protein stability. Surprisingly, the role of AXL in resistance was independent of its ligand GAS6 binding and its TK activity, in accordance with a scaffold activity for this receptor being involved in this cellular process. Collectively, our results demonstrate a pivotal role for CBL in the control of a tyrosine kinase network mediating resistance to nilotinib treatment in CML cells. PMID:25965880

  13. An AXL/LRP-1/RANBP9 complex mediates DC efferocytosis and antigen cross-presentation in vivo

    PubMed Central

    Subramanian, Manikandan; Hayes, Crystal D.; Thome, Joseph J.; Thorp, Edward; Matsushima, Glenn K.; Herz, Joachim; Farber, Donna L.; Liu, Kang; Lakshmana, Madepalli; Tabas, Ira

    2014-01-01

    The phagocytosis of apoptotic cells (ACs), or efferocytosis, by DCs is critical for self-tolerance and host defense. Although many efferocytosis-associated receptors have been described in vitro, the functionality of these receptors in vivo has not been explored in depth. Using a spleen efferocytosis assay and targeted genetic deletion in mice, we identified a multiprotein complex — composed of the receptor tyrosine kinase AXL, LDL receptor–related protein–1 (LRP-1), and RAN-binding protein 9 (RANBP9) — that mediates DC efferocytosis and antigen cross-presentation. We found that AXL bound ACs, but required LRP-1 to trigger internalization, in murine CD8α+ DCs and human-derived DCs. AXL and LRP-1 did not interact directly, but relied on RANBP9, which bound both AXL and LRP-1, to form the complex. In a coculture model of antigen presentation, the AXL/LRP-1/RANBP9 complex was used by DCs to cross-present AC-associated antigens to T cells. Furthermore, in a murine model of herpes simplex virus–1 infection, mice lacking DC-specific LRP-1, AXL, or RANBP9 had increased AC accumulation, defective viral antigen-specific CD8+ T cell activation, enhanced viral load, and decreased survival. The discovery of this multiprotein complex that mediates functionally important DC efferocytosis in vivo may have implications for future studies related to host defense and DC-based vaccines. PMID:24509082

  14. Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells.

    PubMed

    Nowakowski, Tomasz J; Pollen, Alex A; Di Lullo, Elizabeth; Sandoval-Espinosa, Carmen; Bershteyn, Marina; Kriegstein, Arnold R

    2016-05-01

    The recent outbreak of Zika virus (ZIKV) in Brazil has been linked to substantial increases in fetal abnormalities and microcephaly. However, information about the underlying molecular and cellular mechanisms connecting viral infection to these defects remains limited. In this study we have examined the expression of receptors implicated in cell entry of several enveloped viruses including ZIKV across diverse cell types in the developing brain. Using single-cell RNA-seq and immunohistochemistry, we found that the candidate viral entry receptor AXL is highly expressed by human radial glial cells, astrocytes, endothelial cells, and microglia in developing human cortex and by progenitor cells in developing retina. We also show that AXL expression in radial glia is conserved in developing mouse and ferret cortex and in human stem cell-derived cerebral organoids, highlighting multiple experimental systems that could be applied to study mechanisms of ZIKV infectivity and effects on brain development. PMID:27038591

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

    PubMed Central

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

    2016-01-01

    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. PMID:27347952

  16. Static rear stability of conventional and lightweight variable-axle-position wheelchairs.

    PubMed

    Loane, T D; Kirby, R L

    1985-03-01

    Wheelchair users with high or posteriorly placed centers of mass often complain of rear tipping on inclines or when accelerating. In this study we compared the rear stability of occupied conventional and lightweight wheelchairs and determined the effect of various rear axle positions. Ten normal subjects were studied in both a conventional (22.6 kg) and a lightweight (12.3 kg) wheelchair. Twenty-one experienced wheelchair users were also studied in their own wheelchairs. Stability points were determined with brakes unlocked on a tilt platform. Inter- and intraobserver test-retest reliabilities were 0.97 and 0.974, respectively. For the normal subjects the mean (+/- 1SD) stability point in the conventional chair was 28.6 (+/- 2.7) degrees. In the lightweight chair their mean stability points ranged from 21.7 (+/- 2.6) degrees to 9.4 (+/- 2.9) degrees, depending upon axle position. The mean difference between the conventional chair and the lightweight chair in its most stable position was 6.9 (+/- 1.7) degrees (t = 13.04, p less than 0.0001) and in its least stable position 19.3 (+/- 2.4) degrees (t = 24.97, p less than 0.0001). Experienced wheelchair users in their own lightweight wheelchairs were less stable than users of conventional chairs (t = 2.16, p less than 0.05) or chairs with posteriorly offset axles (t = 3.64, p less than 0.01). PMID:3977572

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

    PubMed

    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

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

    PubMed

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

    2016-01-01

    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. PMID:27347952

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

    SciTech Connect

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

    2013-10-01

    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, 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 data

  20. Sequential and Distinct Roles of the Cadherin Domain-containing Protein Axl2p in Cell Polarization in Yeast Cell Cycle

    PubMed Central

    Gao, Xiang-Dong; Sperber, Lauren M.; Kane, Steven A.; Tong, Zongtian; Tong, Amy Hin Yan; Boone, Charles

    2007-01-01

    Polarization of cell growth along a defined axis is essential for the generation of cell and tissue polarity. In the budding yeast Saccharomyces cerevisiae, Axl2p plays an essential role in polarity-axis determination, or more specifically, axial budding in MATa or α cells. Axl2p is a type I membrane glycoprotein containing four cadherin-like motifs in its extracellular domain. However, it is not known when and how Axl2p functions together with other components of the axial landmark, such as Bud3p and Bud4p, to direct axial budding. Here, we show that the recruitment of Axl2p to the bud neck after S/G2 phase of the cell cycle depends on Bud3p and Bud4p. This recruitment is mediated via an interaction between Bud4p and the central region of the Axl2p cytoplasmic tail. This region of Axl2p, together with its N-terminal region and its transmembrane domain, is sufficient for axial budding. In addition, our work demonstrates a previously unappreciated role for Axl2p. Axl2p interacts with Cdc42p and other polarity-establishment proteins, and it regulates septin organization in late G1 independently of its role in polarity-axis determination. Together, these results suggest that Axl2p plays sequential and distinct roles in the regulation of cellular morphogenesis in yeast cell cycle. PMID:17460121

  1. Combined inhibition of AXL, Lyn and p130Cas kinases block migration of triple negative breast cancer cells

    PubMed Central

    Pénzes, Kinga; Baumann, Christine; Szabadkai, István; Őrfi, László; Kéri, György; Ullrich, Axel; Torka, Robert

    2014-01-01

    Blocking the migration of metastatic cancer cells is a major goal in the therapy of cancer. The receptor tyrosine kinase AXL is one of the main triggers for cancer cell migration in neoplasia of breast, colon, skin, thyroid and prostate. In our study we analyzed the effect of AXL inhibition on cell motility and viability in triple negative breast cancer cell lines overexpressing AXL. Thereby we reveal that the compound BMS777607, exhibiting the lowest IC50 values for inhibition of AXL kinase activity in the studied cell lines, attenuates cell motility to a lower extent than the kinase inhibitors MPCD84111 and SKI606. By analyzing the target kinases of MPCD84111 and SKI606 with kinase profiling assays we identified Lyn, a Src family kinase, as a target of both compounds. Knockdown of Lyn and the migration-related CRK-associated substrate (p130Cas), had a significant inhibitory effect on cell migration. Taken together, our findings highlight the importance of combinatorial or multikinase inhibition of non-receptor tyrosine kinases and AXL receptor tyrosine kinase in the therapy of triple negative breast cancer. PMID:25482942

  2. Dethreading of a Photoactive Azobenzene-Containing Molecular Axle from a Crown Ether Ring: A Computational Investigation.

    PubMed

    Tabacchi, Gloria; Silvi, Serena; Venturi, Margherita; Credi, Alberto; Fois, Ettore

    2016-06-17

    Pseudorotaxanes formed by a dibenzo[24]crown-8 ring (R) and a dialkylammonium axle bearing either two E- or two Z-azobenzene units (EE-A or ZZ-A) revealed useful for the construction of light-powered molecular machines and motors, as they provide the opportunity of photocontrolling self-assembly/disassembly processes. The potential energies profiles for the dethreading of these complexes have been investigated by adopting a combination of first-principles molecular dynamics, metadynamics and quantum-chemical geometry optimization approaches. While the dethreading of the EE-A axle is associated with a monotonic energy increase, for that of the ZZ-A axle a transition state and an intermediate structure, in which the components are still threaded together, are found. The rate determining step for the dethreading of the ZZ axle has a higher energy barrier than that of the EE axle, in agreement with the experimental kinetic data. Moreover, the results suggest that the elliptic shape of the ring cavity is important for discriminating between the E and Z terminal azobenzene during dethreading. PMID:26918775

  3. ALK inhibitor resistance in ALK(F1174L)-driven neuroblastoma is associated with AXL activation and induction of EMT.

    PubMed

    Debruyne, D N; Bhatnagar, N; Sharma, B; Luther, W; Moore, N F; Cheung, N-K; Gray, N S; George, R E

    2016-07-14

    The crizotinib-resistant ALK(F1174L) mutation arises de novo in neuroblastoma (NB) and is acquired in ALK translocation-driven cancers, lending impetus to the development of novel anaplastic lymphoma kinase (ALK) inhibitors with different modes of action. The diaminopyrimidine TAE684 and its derivative ceritinib (LDK378), which are structurally distinct from crizotinib, are active against NB cells expressing ALK(F1174L). Here we demonstrate acquired resistance to TAE684 and LDK378 in ALK(F1174L)-driven human NB cells that is linked to overexpression and activation of the AXL tyrosine kinase and epithelial-to-mesenchymal transition (EMT). AXL phosphorylation conferred TAE684 resistance to NB cells through upregulated extracellular signal-regulated kinase (ERK) signaling. Inhibition of AXL partly rescued TAE684 resistance, resensitizing these cells to this compound. AXL activation in resistant cells was mediated through increased expression of the active form of its ligand, GAS6, that also served to stabilize the AXL protein. Although ectopic expression of AXL and TWIST2 individually in TAE684-sensitive parental cells led to the elevated expression of mesenchymal markers and invasive capacity, only AXL overexpression induced resistance to TAE684 as well. TAE684-resistant cells showed greater sensitivity to HSP90 inhibition than did their parental counterparts, with downregulation of AXL and AXL-mediated ERK signaling. Our studies indicate that aberrant AXL signaling and development of an EMT phenotype underlie resistance of ALK(F1174L)-driven NB cells to TAE684 and its derivatives. We suggest that the combination of ALK and AXL or HSP90 inhibitors be considered to delay the emergence of such resistance. PMID:26616860

  4. The receptor AXL diversifies EGFR signaling and limits the response to EGFR-targeted inhibitors in triple-negative breast cancer cells.

    PubMed

    Meyer, Aaron S; Miller, Miles A; Gertler, Frank B; Lauffenburger, Douglas A

    2013-08-01

    The relationship between drug resistance, changes in signaling, and emergence of an invasive phenotype is well appreciated, but the underlying mechanisms are not well understood. Using machine learning analysis applied to the Cancer Cell Line Encyclopedia database, we identified expression of AXL, the gene that encodes the epithelial-to-mesenchymal transition (EMT)-associated receptor tyrosine kinase (RTK) AXL, as exceptionally predictive of lack of response to ErbB family receptor-targeted inhibitors. Activation of EGFR (epidermal growth factor receptor) transactivated AXL, and this ligand-independent AXL activity diversified EGFR-induced signaling into additional downstream pathways beyond those triggered by EGFR alone. AXL-mediated signaling diversification was required for EGF (epidermal growth factor)-elicited motility responses in AXL-positive TNBC (triple-negative breast cancer) cells. Using cross-linking coimmunoprecipitation assays, we determined that AXL associated with EGFR, other ErbB receptor family members, MET (hepatocyte growth factor receptor), and PDGFR (platelet-derived growth factor receptor) but not IGF1R (insulin-like growth factor 1 receptor) or INSR (insulin receptor). From these AXL interaction data, we predicted AXL-mediated signaling synergy for additional RTKs and validated these predictions in cells. This alternative mechanism of receptor activation limits the use of ligand-blocking therapies and indicates against therapy withdrawal after acquired resistance. Further, subadditive interaction between EGFR- and AXL-targeted inhibitors across all AXL-positive TNBC cell lines may indicate that increased abundance of EGFR is principally a means to transactivation-mediated signaling. PMID:23921085

  5. MiR-34a suppresses ovarian cancer proliferation and motility by targeting AXL.

    PubMed

    Li, Rui; Shi, Xuejun; Ling, Fengyu; Wang, Chunguang; Liu, Junxia; Wang, Wei; Li, Ming

    2015-09-01

    Increasing evidence has suggested that dysregulation of microRNAs (miRNAs) could contribute to tumor progression. The miR-34 family is directly transactivated by tumor suppressor p53 which is frequently mutated in various cancers; however, the effect of miR-34a on the ovarian cancer cells remains unclear. The aim of the paper was to study the expression of miR-34a in ovarian cancer and miR-34a's relation to the cell proliferation and metastasis in ovarian cancer in vitro. miR-34a expression was determined by quantitative RT-PCR in a panel of 60 human ovarian cancer samples. Functional characterization of miR-34a was accomplished by reconstitution of miR-34a expression in ovarian cancer cells by determining changes in proliferation, migration, and invasion. Our results showed that miR-34a is downregulated in ovarian cancer tissues compared with the corresponding adjacent non-neoplastic tissues, and the expression level of miR-34a was significantly lower in ovarian cancer cell lines in comparison with normal human fallopian tube epithelial cell line. The 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide (MTT) assay revealed significant cell proliferation inhibition in miR-34a transfectant compared with the control from HO8910 and SKOV3 cells, which displayed lowest expressions of miR-34a. Furthermore, the transwell assay also showed significant cell migration inhibition in miR-34a transfectant, compared with cell lines transfected with NC. Overexpression of miR-34a led to the inhibition of AXL expression, indicating that AXL is a target gene for miR-34a. Our data suggest that miR-34a may function as a tumor suppressor through repression of oncogenic AXL in ovarian cancer. PMID:25895459

  6. Axle counter for high-speed railway based on fibre Bragg grating sensor and algorithm optimization for peak searching

    NASA Astrophysics Data System (ADS)

    Quan, Yu; He, Dawei; Wang, Yongsheng; Wang, Pengfei

    2014-08-01

    For the benefit of electrical isolation, corrosion resistance and quasi-distributed detecting, Fiber Bragg Grating Sensor has been studied for high-speed railway application progressively. Existing Axle counter system based on fiber Bragg grating sensor isn't appropriate for high-speed railway for the shortcoming of emplacement of fiber Bragg grating sensor, low Sampling rate and un-optimized algorithm for peak searching. We propose a new design for the Axle counter of high-speed railway based on high-speed fiber Bragg grating demodulating system. We also optimized algorithm for peak searching by synthesizing the three sensor data, bringing forward the time axle, Gaussian fitting and Finite Element Analysis. The feasibility was verified by field experiment.

  7. Axl mediates acquired resistance of head and neck cancer cells to the epidermal growth factor receptor inhibitor erlotinib.

    PubMed

    Giles, Keith M; Kalinowski, Felicity C; Candy, Patrick A; Epis, Michael R; Zhang, Priscilla M; Redfern, Andrew D; Stuart, Lisa M; Goodall, Gregory J; Leedman, Peter J

    2013-11-01

    Elevated expression and activity of the epidermal growth factor receptor (EGFR) is associated with development and progression of head and neck cancer (HNC) and a poor prognosis. Clinical trials with EGFR tyrosine kinase inhibitors (e.g., erlotinib) have been disappointing in HNC. To investigate the mechanisms mediating resistance to these agents, we developed an HNC cell line (HN5-ER) with acquired erlotinib resistance. In contrast to parental HN5 HNC cells, HN5-ER cells exhibited an epithelial-mesenchymal (EMT) phenotype with increased migratory potential, reduced E-cadherin and epithelial-associated microRNAs (miRNA), and elevated vimentin expression. Phosphorylated receptor tyrosine kinase profiling identified Axl activation in HN5-ER cells. Growth and migration of HN5-ER cells were blocked with a specific Axl inhibitor, R428, and R428 resensitized HN5-ER cells to erlotinib. Microarray analysis of HN5-ER cells confirmed the EMT phenotype associated with acquired erlotinib resistance, and identified activation of gene expression associated with cell migration and inflammation pathways. Moreover, increased expression and secretion of interleukin (IL)-6 and IL-8 in HN5-ER cells suggested a role for inflammatory cytokine signaling in EMT and erlotinib resistance. Expression of the tumor suppressor miR-34a was reduced in HN5-ER cells and increasing its expression abrogated Axl expression and reversed erlotinib resistance. Finally, analysis of 302 HNC patients revealed that high tumor Axl mRNA expression was associated with poorer survival (HR = 1.66, P = 0.007). In summary, our results identify Axl as a key mediator of acquired erlotinib resistance in HNC and suggest that therapeutic inhibition of Axl by small molecule drugs or specific miRNAs might overcome anti-EGFR therapy resistance. PMID:24026012

  8. The TRAIL receptor agonist drozitumab targets basal B triple-negative breast cancer cells that express vimentin and Axl.

    PubMed

    Dine, Jennifer L; O'Sullivan, Ciara C; Voeller, Donna; Greer, Yoshimi E; Chavez, Kathryn J; Conway, Catherine M; Sinclair, Sarah; Stone, Brandon; Amiri-Kordestani, Laleh; Merchant, Anand S; Hewitt, Stephen M; Steinberg, Seth M; Swain, Sandra M; Lipkowitz, Stanley

    2016-01-01

    Previously, we found that GST-tagged tumor necrosis factor-related apoptosis inducing ligand preferentially killed triple-negative breast cancer (TNBC) cells with a mesenchymal phenotype by activating death receptor 5 (DR5). The purpose of this study was to explore the sensitivity of breast cancer cell lines to drozitumab, a clinically tested DR5-specific agonist; identify potential biomarkers of drozitumab-sensitive breast cancer cells; and determine if those biomarkers were present in tumors from patients with TNBC. We evaluated viability, caspase activity, and sub-G1 DNA content in drozitumab-treated breast cancer cell lines and we characterized expression of potential biomarkers by immunoblot. Expression levels of vimentin and Axl were then explored in 177 TNBC samples from a publically available cDNA microarray dataset and by immunohistochemistry (IHC) in tumor tissue samples obtained from 53 African-American women with TNBC. Drozitumab-induced apoptosis in mesenchymal TNBC cell lines but not in cell lines from other breast cancer subtypes. The drozitumab-sensitive TNBC cell lines expressed the mesenchymal markers vimentin and Axl. Vimentin and Axl mRNA and protein were expressed in a subset of human TNBC tumors. By IHC, ~15 % of TNBC tumors had vimentin and Axl expression in the top quartile for both. These findings indicate that drozitumab-sensitive mesenchymal TNBC cells express vimentin and Axl, which can be identified in a subset of human TNBC tumors. Thus, vimentin and Axl may be useful to identify TNBC patients who would be most likely to benefit from a DR5 agonist. PMID:26759246

  9. Dicer Elicits Paclitaxel Chemosensitization and Suppresses Cancer Stemness in Breast Cancer by Repressing AXL.

    PubMed

    Chang, Ting-Yu; Chen, Hsin-An; Chiu, Ching-Feng; Chang, Yi-Wen; Kuo, Tsang-Chih; Tseng, Po-Chun; Wang, Weu; Hung, Mien-Chie; Su, Jen-Liang

    2016-07-01

    Paclitaxel is a standard-of-care chemotherapy for breast cancer, despite the increasing recognition of its poor effectiveness in the treatment of patients with advanced disease. Here, we report that adenovirus-type 5 E1A-mediated elevation of the miRNA-processing enzyme Dicer is sufficient to enhance paclitaxel sensitization and reduce cancer stem-like cell properties in this setting. Elevating Dicer expression increased levels of the AXL kinase targeting miRNA miR-494, thereby repressing AXL expression to increase paclitaxel sensitivity. We found that Dicer expression was regulated at the transcription level by E1A, through activation of an MAPK14/CEBPα pathway. Our findings define a mechanism of E1A-mediated chemosensitization for paclitaxel, which is based upon the suppression of breast cancer stem-like cells, with potential implications for the diagnosis and treatment of breast cancer patients. Cancer Res; 76(13); 3916-28. ©2016 AACR. PMID:27216190

  10. POD curves for non-maximizable ultrasonic responses: Statistical derivation and application to solid freight axles

    NASA Astrophysics Data System (ADS)

    Carboni, Michele; Cantini, Stefano

    2016-02-01

    The most relevant standards on ultrasonic testing, and an effective inspection practice, require the maximization of echo responses due to indications before their evaluation in terms of amplitude and size. This is achieved effectively pointing the acoustic axis of the sound beam to the indication, in a way to get back the maximum possible sound energy. Considering some operative cases, however, such a response maximization is not always feasible, mainly due to geometrical constraints impeding the inspection of the whole control area with a constant sensitivity. The traditional end inspection of solid railway axles by a rotating probe mounting conventional sensors falls back into this kind of inspections. In particular, inspection angles are fixed and the probe holder cannot move along the axle allowing response maximization of in-service damages located, for example, along the cylindrical body. It follows some control areas cannot be inspected using the maximum sound pressure. The present research shows how the derivation of "Probability of Detection" curves for non-maximizable ultrasonic responses cannot be carried out by the traditional statistical approach and a novel one, of the "Model-Assisted Probability of Detection" kind, is consequently proposed based on experiments and numerical simulations.

  11. Novel Axl-driven signaling pathway and molecular signature characterize high-grade ovarian cancer patients with poor clinical outcome

    PubMed Central

    Rea, Katia; Pinciroli, Patrizia; Sensi, Marialuisa; Alciato, Federica; Bisaro, Brigitte; Lozneanu, Ludmila; Raspagliesi, Francesco; Centritto, Floriana; Cabodi, Sara; Defilippi, Paola; Avanzi, Gian Carlo; Canevari, Silvana; Tomassetti, Antonella

    2015-01-01

    High-grade epithelial ovarian cancer (HGEOC) is a clinically diverse and molecularly heterogeneous disease comprising subtypes with distinct biological features and outcomes. The receptor tyrosine kinases, expressed by EOC cells, and their ligands, present in the microenvironment, activate signaling pathways, which promote EOC cells dissemination. Herein, we established a molecular link between the presence of Gas6 ligand in the ascites of HGEOCs, the expression and activation of its receptor Axl in ovarian cancer cell lines and biopsies, and the progression of these tumors. We demonstrated that Gas6/Axl signalling converges on the integrin β3 pathway in the presence of the adaptor protein p130Cas, thus inducing tumor cell adhesion to the extracellular matrix and invasion. Accordingly, Axl and p130Cas were significantly co-expressed in HGEOC samples. Clinically, we identified an Axl-associated signature of 62 genes able to portray the HGEOCs with the shortest overall survival. These data biologically characterize a group of HGEOCs and could help guide a more effective therapeutic approach to be taken for these patients. PMID:26356564

  12. Gas6/Axl is the sensor of arginine-auxotrophic response in targeted chemotherapy with arginine-depleting agents.

    PubMed

    Tsai, W-B; Long, Y; Park, J-R; Chang, J T; Liu, H; Rodriguez-Canales, J; Savaraj, N; Feun, L G; Davies, M A; Wistuba, I I; Kuo, M T

    2016-03-31

    Many human malignancies lack de novo biosynthesis of arginine (Arg) as the key enzyme argininosuccinate synthetase 1 (ASS1) is silenced. These tumors acquire ectopic Arg for survival, and depleting this source by Arg-depleting recombinant enzyme ADI-PEG20 results in cell death. Mechanisms underlying Arg auxotrophy in these tumors and how they respond to Arg-auxotrophic stress are poorly understood. Here, we report that an immediate-early event of Arg-auxotrophic response involves reactive oxygen species-mediated secretion of Gas6, which interacts with its receptor Axl and activates the downstream Ras/PI3K/Akt growth signal leading to accumulation of c-Myc by protein stabilization. Arg-auxotrophic challenge also transcriptionally upregulates c-Myc expression, which provides a feedback mechanism to enhance Axl expression. c-Myc is a positive regulator of ASS1, but elevated ASS1 provides a feedback mechanism to suppress c-Myc and Axl. Our results revealed multiple inter-regulatory pathways in Arg-auxotrophic response, consisting of Axl, c-Myc and ASS1, which regulate Arg homeostasis and ADI-PEG20 sensitivity. These pathways provide potential targets for improving the efficacy of treating Arg-auxotrophic tumors using Arg-deprivation strategies. PMID:26096933

  13. Protein kinase C α is involved in the regulation of AXL receptor tyrosine kinase expression in triple-negative breast cancer cells.

    PubMed

    Yue, Chia-Herng; Liu, Liang-Chih; Kao, Erl-Shyh; Lin, Ho; Hsu, Li-Sung; Hsu, Chih-Wei; Lin, Yu-Yu; Lin, Yi-Syuan; Liu, Jer-Yuh; Lee, Chia-Jen

    2016-08-01

    AXL receptor tyrosine kinase is overexpressed in triple-negative breast cancer (TNBC), and has a function in cancer progression and metastases. However, the mechanism underlying AXL gene regulation in TNBC remains unknown. In this study, the involvement of protein kinase C α (PKCα) in the expression of AXL was investigated in human TNBC cells. The microarray data from other studies showed that PKCα is significantly correlated with AXL expression in TNBC cell lines. Tissue array analysis also confirmed their correlation in TNBC. The PKCα inhibitor Go6976 was used to treat MDA‑MB‑231 and Hs578T TNBC cells, which resulted in decreased expression of AXL and epithelia-mesenchymal transition-related gene vimentin, and decreased cell proliferation. An MZF‑1 acidic domain fragment (MZF-1 peptide), which was designed to downregulate PKCα expression, was transfected into the cells and resulted in inhibition of AXL expression. This effect was reversed by co‑treatment with the constitutive form of PKCα. Moreover, the downregulation of PKCα was also confirmed by treatment with TAT‑fused MZF‑1 peptide. Thus, the current study proposes that AXL may be correlated with PKCα‑dependent TNBC cells, and could be modulated by MZF‑1 peptides. PMID:27357025

  14. 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

  15. Gas6/Axl Axis Contributes to Chemoresistance and Metastasis in Breast Cancer through Akt/GSK-3β/β-catenin Signaling

    PubMed Central

    Wang, Cun; Jin, Haojie; Wang, Ning; Fan, Shaohua; Wang, Yanyan; Zhang, Yurong; Wei, Lin; Tao, Xuemei; Gu, Dishui; Zhao, Fangyu; Fang, Jingyuan; Yao, Ming; Qin, Wenxin

    2016-01-01

    Chemoresistance in breast cancer has been of great interest in past studies. However, the development of rational therapeutic strategies targeting chemoresistant cells is still a challenge in clinical oncology. By integrating data from global differences of gene expression and phospho-receptor tyrosine kinases between sensitive parental cells (MCF-7) and doxorubicin-resistant cells (MCF-7/ADR), we identified Axl as a potential target for chemoresistance and metastasis in multidrug resistant breast cancer cells. We analyzed Axl expression in 57 breast cancer cell lines and detected a dramatic increase in its expression level in mesenchymal breast cancer cell lines. Axl silencing suppressed invasive and metastatic potentials of chemoresistant breast cancer cells as well as increased elimination of cancer cells when combined with doxorubicin. Furthermore, in preclinical assays, an Axl inhibitor R428 showed increased cell death upon doxorubicin treatment. Additionally, using phospho-kinase array based proteomic analysis, we identified that Akt/GSK-3β/β-catenin cascade was responsible for Axl-induced cell invasion. Nuclear translocation of β-catenin then induced transcriptional upregulation of ZEB1, which in turn regulated DNA damage repair and doxorubicin-resistance in breast cancer cells. Most importantly, Axl was correlated with its downstream targets in tumor samples and was associated with poor prognosis in breast cancer patients. These results demonstrate that Gas6/Axl axis confers aggressiveness in breast cancer and may represent a therapeutic target for chemoresistance and metastasis. PMID:27279912

  16. Testosterone delays vascular smooth muscle cell senescence and inhibits collagen synthesis via the Gas6/Axl signaling pathway.

    PubMed

    Chen, Yan-Qing; Zhao, Jing; Jin, Cheng-Wei; Li, Yi-Hui; Tang, Meng-Xiong; Wang, Zhi-Hao; Zhang, Wei; Zhang, Yun; Li, Li; Zhong, Ming

    2016-06-01

    Testosterone deficiency is associated with a higher incidence of cardiovascular diseases in men. However, its effect on cell senescence, which plays a causal role in vascular aging, remains unclear. Here, we tested the hypothesis that testosterone alleviated vascular smooth muscle cell (VSMC) senescence and collagen synthesis via growth arrest-specific protein 6 (Gas6)/Axl- and Akt/FoxO1a-dependent pathways. Testosterone significantly ameliorated angiotensin II-induced VSMC senescence and collagen overexpression. In addition, testosterone inhibited angiotensin II-induced matrix metalloproteinase-2 (MMP-2) activity, which played a pivotal role in facilitating age-related collagen deposition. Testosterone increased the expression of tissue inhibitor of metalloproteinase-2 but decreased the expression of MMP-2 and membrane type-1 metalloproteinase which contributed to increase MMP-2 activity. The effects on VSMCs senescence and collagen synthesis were mediated by restoration of angiotensin II-induced downregulation of Gas6 and Axl expression and a subsequent reduction of Akt and FoxO1a phosphorylation. The effects of testosterone were reversed by a Gas6 blocker, Axl-Fc, and a specific inhibitor of Axl, R428. Treatment of VSMCs with PI3K inhibitor LY294002 abrogated the downregulating effect of testosterone on MMP-2 activity. Furthermore, when FoxO1a expression was silenced by using a specific siRNA, the inhibitory effect of testosterone on MMP-2 activity was revered as well, that indicated this process was Akt/FoxO1a dependence. Taken together, Gas6/Axl and Akt/FoxO1a were involved in protective effects of testosterone on VSMCs senescence and collagen synthesis. Our results provide a novel mechanism underlying the protective effect of testosterone on vascular aging and may serve as a theoretical basis for testosterone replacement therapy. PMID:27206970

  17. 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

    2016-09-01

    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. PMID:27212383

  18. Inhibiting receptor tyrosine kinase AXL with small molecule inhibitor BMS-777607 reduces glioblastoma growth, migration, and invasion in vitro and in vivo

    PubMed Central

    Onken, Julia; Torka, Robert; Korsing, Sören; Radke, Josefine; Krementeskaia, Irina; Nieminen, Melina; Bai, Xi; Ullrich, Axel; Heppner, Frank; Vajkoczy, Peter

    2016-01-01

    Purpose Receptor tyrosine kinase AXL (RTK-AXL) is regarded as suitable target in glioma therapy. Here we evaluate the anti-tumoral effect of small molecule inhibitor BMS-777607 targeting RTK-AXL in a preclinical glioma model and provide evidence that RTK-AXL is expressed and phosphorylated in primary and recurrent glioblastoma multiforme (GBM). Experimental design We studied the impact of BMS-777607 targeting RTK-AXL in GBM models in vitro and in vivo utilizing glioma cells SF126 and U118MG. Impact on proliferation, apoptosis and angiogenesis was investigated by immunohistochemistry (IHC) and functional assays in vitro and in vivo. Tumor growth was assessed with MRI. Human GBM tissue was analyzed in terms of RTK-AXL phosphorylation by immunoprecipitation and immunohistochemistry. Results BMS-777607 displayed various anti-cancer effects dependent on increased apoptosis, decreased proliferation and migration in vitro and ex vivo in SF126 and U118 GBM cells. In vivo we observed a 56% tumor volume reduction in SF126 xenografts and remission in U118MG xenografts of more than 91%. The tube formation assay confirmed the anti-angiogenic effect of BMS-777607, which became also apparent in tumor xenografts. IHC of human GBM tissue localized phosphorylated RTK-AXL in hypercellular tumor regions, the migratory front of tumor cells in pseudo-palisades, and in vascular proliferates within the tumor. We further proved RTK-AXL phosphorylation in primary and recurrent disease state. Conclusion Collectively, these data strongly suggest that targeting RTK-AXL with BMS-777607 could represent a novel and potent regimen for the treatment of primary and recurrent GBM. PMID:26848524

  19. A new optical axle measuring instrument for wheel alignment in assembly-line production

    SciTech Connect

    Bruhn, H.; Felske, A.

    1985-01-01

    The newly developed optical measuring system allows adjustment of front and rear wheel angularities - toe, camber, caster - in assembly-line production. There is no need to align the car, since the measuring base for the angle alignment is formed by the car itself. Defined spring compression values and direct caster angle determination lead to higher accuracy. Adjustment is carried out directly on the assembly line. Measuring pits are not required. The working time for each car and the working area required, which are important cost factors, are markedly lower than with conventional instruments. The axle measuring system was developed for the VW Vanagon, but can also be used for passenger car chassis. The measuring principle, the optical and mechanical design of the device, and a statistical analysis of over 100 cars aligned by means of this system are described in comparison with conventional measuring instruments.

  20. Axle-less F1-ATPase rotates in the correct direction.

    PubMed

    Furuike, Shou; Hossain, Mohammad Delawar; Maki, Yasushi; Adachi, Kengo; Suzuki, Toshiharu; Kohori, Ayako; Itoh, Hiroyasu; Yoshida, Masasuke; Kinosita, Kazuhiko

    2008-02-15

    F1-adenosine triphosphatase (ATPase) is an ATP-driven rotary molecular motor in which the central gamma subunit rotates inside a cylinder made of three alpha and three beta subunits alternately arranged. The rotor shaft, an antiparallel alpha-helical coiled coil of the amino and carboxyl termini of the gamma subunit, deeply penetrates the central cavity of the stator cylinder. We truncated the shaft step by step until the remaining rotor head would be outside the cavity and simply sat on the concave entrance of the stator orifice. All truncation mutants rotated in the correct direction, implying torque generation, although the average rotary speeds were low and short mutants exhibited moments of irregular motion. Neither a fixed pivot nor a rigid axle was needed for rotation of F1-ATPase. PMID:18276891

  1. The Gas6-Axl Protein Interaction Mediates Endothelial Uptake of Platelet Microparticles.

    PubMed

    Happonen, Kaisa E; Tran, Sinh; Mörgelin, Matthias; Prince, Raja; Calzavarini, Sara; Angelillo-Scherrer, Anne; Dahlbäck, Björn

    2016-05-13

    Upon activation, platelets release plasma membrane-derived microparticles (PMPs) exposing phosphatidylserine on their surface. The functions and clearance mechanism of these microparticles are incompletely understood. As they are pro-coagulant and potentially pro-inflammatory, rapid clearance from the circulation is essential for prevention of thrombotic diseases. The tyrosine kinase receptors Tyro3, Axl, and Mer (TAMs) and their ligands protein S and Gas6 are involved in the uptake of phosphatidylserine-exposing apoptotic cells in macrophages and dendritic cells. Both TAMs and their ligands are expressed in the vasculature, the functional significance of which is poorly understood. In this study, we investigated how vascular TAMs and their ligands may mediate endothelial uptake of PMPs. PMPs, generated from purified human platelets, were isolated by ultracentrifugation and labeled with biotin or PKH67. The uptake of labeled microparticles in the presence of protein S and Gas6 in human aortic endothelial cells and human umbilical vein endothelial cells was monitored by flow cytometry, Western blotting, and confocal/electron microscopy. We found that both endothelial cell types can phagocytose PMPs, and by using TAM-blocking antibodies or siRNA knockdown of individual TAMs, we show that the uptake is mediated by endothelial Axl and Gas6. As circulating PMP levels were not altered in Gas6(-/-) mice compared with Gas6(+/+) mice, we hypothesize that the Gas6-mediated uptake is not a means to clear the bulk of circulating PMPs but may serve to locally phagocytose PMPs generated at sites of platelet activation and as a way to effect endothelial responses. PMID:27006397

  2. 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.

  3. AXL mediates resistance to PI3Kα inhibition by activating the EGFR/PKC/mTOR axis in head and neck and esophageal squamous cell carcinomas.

    PubMed

    Elkabets, Moshe; Pazarentzos, Evangelos; Juric, Dejan; Sheng, Qing; Pelossof, Raphael A; Brook, Samuel; Benzaken, Ana Oaknin; Rodon, Jordi; Morse, Natasha; Yan, Jenny Jiacheng; Liu, Manway; Das, Rita; Chen, Yan; Tam, Angela; Wang, Huiqin; Liang, Jinsheng; Gurski, Joseph M; Kerr, Darcy A; Rosell, Rafael; Teixidó, Cristina; Huang, Alan; Ghossein, Ronald A; Rosen, Neal; Bivona, Trever G; Scaltriti, Maurizio; Baselga, José

    2015-04-13

    Phosphoinositide-3-kinase (PI3K)-α inhibitors have shown clinical activity in squamous cell carcinomas (SCCs) of head and neck (H&N) bearing PIK3CA mutations or amplification. Studying models of therapeutic resistance, we have observed that SCC cells that become refractory to PI3Kα inhibition maintain PI3K-independent activation of the mammalian target of rapamycin (mTOR). This persistent mTOR activation is mediated by the tyrosine kinase receptor AXL. AXL is overexpressed in resistant tumors from both laboratory models and patients treated with the PI3Kα inhibitor BYL719. AXL dimerizes with and phosphorylates epidermal growth factor receptor (EGFR), resulting in activation of phospholipase Cγ (PLCγ)-protein kinase C (PKC), which, in turn, activates mTOR. Combined treatment with PI3Kα and either EGFR, AXL, or PKC inhibitors reverts this resistance. PMID:25873175

  4. AXL mediates resistance to PI3Kα inhibition by activating the EGFR/PKC/mTOR axis in head and neck and esophageal squamous cell carcinomas

    PubMed Central

    Elkabets, Moshe; Pazarentzos, Evangelos; Juric, Dejan; Sheng, Qing; Pelossof, Raphael A.; Brook, Samuel; Benzaken, Ana Oaknin; Rodon, Jordi; Morse, Natasha; Yan, Jenny Jiacheng; Liu, Manway; Das, Rita; Chen, Yan; Tam, Angela; Wang, Huiqin; Liang, Jinsheng; Gurski, Joseph M.; Kerr, Darcy A.; Rosell, Rafael; Teixidó, Cristina; Huang, Alan; Ghossein, Ronald A.; Rosen, Neal; Bivona, Trever G.; Scaltriti, Maurizio; Baselga, José

    2015-01-01

    Summary Phosphoinositide-3-kinase (PI3K)-α inhibitors have shown clinical activity in squamous carcinoma (SCC) of head and neck (H&N) bearing PIK3CA mutations or amplification. Studying models of therapeutic resistance we have observed that SCCs cells that become refractory to PI3Kα inhibition maintain PI3K-independent activation of the mammalian target of rapamycin (mTOR). This persistent mTOR activation is mediated by the tyrosine kinase receptor AXL. AXL is overexpressed in resistant tumors from both laboratory models and patients treated with the PI3Kα inhibitor BYL719. AXL dimerizes with and phosphorylates epidermal growth factor receptor (EGFR), resulting in activation of phospholipase Cγ (PLCγ)- protein kinase C (PKC), which in turn activates mTOR. Combined treatment with PI3Kα and either EGFR, AXL, or PKC inhibitors reverts this resistance. PMID:25873175

  5. Biodegradable interstitial release polymer loading a novel small molecule targeting Axl receptor tyrosine kinase and reducing brain tumour migration and invasion

    PubMed Central

    Yen, S-Y; Chen, S-R; Hsieh, J; Li, Y-S; Chuang, S-E; Chuang, H-M; Huang, M-H; Lin, S-Z; Harn, H-J; Chiou, T-W

    2016-01-01

    Glioblastoma multiforme (GBM) is the most common and aggressive brain tumour. The neoplasms are difficult to resect entirely because of their highly infiltration property and leading to the tumour edge is unclear. Gliadel wafer has been used as an intracerebral drug delivery system to eliminate the residual tumour. However, because of its local low concentration and short diffusion distance, patient survival improves non-significantly. Axl is an essential regulator in cancer metastasis and patient survival. In this study, we developed a controlled-release polyanhydride polymer loading a novel small molecule, n-butylidenephthalide (BP), which is not only increasing local drug concentration and extending its diffusion distance but also reducing tumour invasion, mediated by reducing Axl expression. First, we determined that BP inhibited the expression of Axl in a dose- and time-dependent manner and reduced the migratory and invasive capabilities of GBM cells. In addition, BP downregulated matrix metalloproteinase activity, which is involved in cancer cell invasion. Furthermore, we demonstrated that BP regulated Axl via the extracellular signal-regulated kinases pathway. Epithelial-to-mesenchymal transition (EMT) is related to epithelial cells in the invasive migratory mesenchymal cells that underlie cancer progression; we demonstrated that BP reduced the expression of EMT-related genes. Furthermore, we used the overexpression of Axl in GBM cells to prove that Axl is a crucial target in the inhibition of GBM EMT, migration and invasion. In an in vivo study, we demonstrated that BP inhibited tumour growth and suppressed Axl expression in a dose-dependent manner according to a subcutaneous tumour model. Most importantly, in an intracranial tumour model with BP wafer in situ treatment, we demonstrated that the BP wafer not only significantly increased the survival rate but also decreased Axl expression, and inhibited tumour invasion. These results contribute to the

  6. Reversible photoswitching of rotaxane character and interplay of thermodynamic stability and kinetic lability in a self-assembling ring-axle molecular system.

    PubMed

    Baroncini, Massimo; Silvi, Serena; Venturi, Margherita; Credi, Alberto

    2010-10-11

    We have designed, synthesized, and investigated a self-assembling system that can be reversibly interconverted between thermodynamically stable (pseudorotaxane) and kinetically inert (rotaxane) forms by light irradiation. The system is composed of a dibenzo[24]crown-8 ring and an axle comprised of a dibenzylammonium recognition site and two azobenzene end groups. The isomeric form of the azobenzene units of the axle has a little influence on the stability constants of the respective pseudorotaxanes but greatly affects the threading-dethreading rate constants. In fact, equilibration of the ring and the axle in its EE isomeric form occurs within seconds in acetonitrile at room temperature, whereas the ZZ axle threads-dethreads the ring at least four orders of magnitude slower. Moreover, we show that a change in the stability of the complex, achieved by deprotonating the dibenzylammonium recognition site on the axle, affects its kinetic behavior. We compare the results of these experiments with those observed upon dethreading the (pseudo)rotaxane by using a competitive guest for the ring, an approach which does not inherently destabilize the ring-axle interaction. This study outlines a general strategy for the reversible photochemical control of motion kinetics in threaded and interlocked compounds and constitutes a starting point for the construction of multicomponent structures that can behave as photochemically driven nanomachines. PMID:20842670

  7. Optic-electronic systems for measurement the three-dimension angular deformation of axles at the millimeter wave range radiotelescope

    NASA Astrophysics Data System (ADS)

    Konyakhin, Igor A.; Kopylova, Tatyana V.; Konyakhin, Alexsey I.; Smekhov, Andrey A.

    2013-01-01

    Researches in the millimetre wave range require the high accuracy for position of the mirror components of the radiotelescope. A mirror weight is the cause of the three-dimension angular deformation of the elevation axle and azimuth axle relatively bearings. At result the elevation angle and azimuth angle of a parabolic mirror axis orientation is not equal to the set values. For the measuring roll, pitch and yaw angular deformations the autocollimation system with new type of the reflector are used. Reflector for autocollimation measurements as compositions of the anamorphic prism and special tetrahedral reflector is described. New methods for roll, pitch, yaw angles measuring are discussed. Optical scheme for the measurement system, structure the anamorphic prism and tetrahedral reflector are proposed. Equations for the static characteristic of the measuring system are shown.

  8. 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.

  9. Effect of Quenching Rate on Distortion and Residual Stresses During Induction Hardening of a Full-Float Truck Axle Shaft

    NASA Astrophysics Data System (ADS)

    Li, Zhichao; Ferguson, B. Lynn; Nemkov, Valentin; Goldstein, Robert; Jackowski, John; Fett, Greg

    2014-12-01

    Computer simulation is used to predict the residual stresses and distortion of a full-float truck axle shaft that has been induction scan hardened. Flux2D® is used to model the electromagnetic behavior and the power distributions inside the axle shaft in terms of time. The power distributions are imported and mapped into DANTE® model for thermal, phase transformation, and stress analysis. The truck axle shaft has three main geometrical regions: the flange/filet, the shaft, and the spline. Both induction heating and spray quenching processes have significant effect on the quenching results: distortion and residual stress distributions. In this study, the effects of spray quenching severity on residual stresses and distortion are investigated using modeling. The spray quenching rate can be adjusted by spray nozzle design, ratio of polymer solution, and quenchant flow rate. Different quenching rates are modeled by assigning different heat transfer coefficients as thermal boundary conditions during spray quenching. In this paper, three heat transfer coefficients, 5, 12, and 25 kW/(m2 °C), are applied while keeping all other conditions constant. With the understanding of effects of heating and quenching on residual stresses and distortion of induction hardened parts, the induction hardening process can be optimized for improved part performance.

  10. Fault Prognosis and Diagnosis of an Automotive Rear Axle Gear Using a RBF-BP Neural Network

    NASA Astrophysics Data System (ADS)

    Shao, Yimin; Liang, Jie; Gu, Fengshou; Chen, Zaigang; Ball, Andrew

    2011-07-01

    The rear axle gear is one of the key parts of transmission system for automobiles. Its healthy state directly influences the security and reliability of the automotives. However, non-stationary and nonlinear characteristics of gear vibration due to load and speed fluctuations, makes it difficult to detect and diagnosis the faults from the transmission gear. To solve this problem a fault prognosis and diagnosis method based on a combination of radial basis function(RBF) and back-propagation (BP) neural networks is proposed in this paper. Firstly, a moving average pretreatment is used to suppress the time series fluctuation of vibration characteristic parameter tie series and reduce the interference of random noise. Then, the RBF network is applied to the pretreated parameter sequences for fault prognosis. Furthermore, based on self-learning ability of neural networks, characteristic parameters for different common faults are learned by a BP network. Then the trained BP neural network is utilized for fault diagnosis of the rear axle gear. The results show that the proposed method has a good performance in prognosing and diagnosing different faults from the rear axle gear.

  11. 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

  12. 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.

  13. Tyro3, Axl, and Mertk Receptor Signaling in Inflammatory Bowel Disease and Colitis-associated Cancer

    PubMed Central

    Rothlin, Carla V.; Leighton, Jonathan A.; Ghosh, Sourav

    2015-01-01

    Three receptor tyrosine kinases, Tyro3, Axl, and Mertk (TAM) and their ligands Gas6 and Protein S, have emerged as potent negative regulators of innate immune responses. A number of studies using genetic ablation of TAM loci in mice have elucidated the mechanism of TAM engagement and function during the immune response and removal of apoptotic cells. Following phagocytosis of apoptotic cells or the induction of T-cell dependent adaptive immune responses, ligand-induced TAM signaling dampens proinflammatory cytokine production and thus prevents exaggerated or prolonged inflammation. It is believed that the TAM pathway may play an important role in the pathogenesis of inflammatory bowel disease. Suppression of inflammation and removal of apoptotic cells followed by tissue repair are essential processes for disease remission and the successful management of inflammatory bowel disease. In light of the key role of TAMs in controlling inflammatory responses, here, we review the recent advances on TAM research vis-à-vis the resolution of intestinal inflammation. Targeted activation of TAM receptor tyrosine kinases may represent a potent therapeutic opportunity in inflammatory bowel disease. PMID:24846720

  14. 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.

  15. Axl Inhibition Primes Chronic Lymphocytic Leukemia B-Cells to Apoptosis and Show Synergistic/Additive Effects in Combination with BTK inhibitors

    PubMed Central

    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.

    2015-01-01

    Purpose 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 CLL patients. Experimental Design Expression/activation status of other members of the TAM (Tyro3, Axl, 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 presence of CLL bone marrow stromal cells (BMSCs). Inhibitory effects of TP-0903 on Axl signaling pathway was 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. Results CLL B-cells overexpress Tyro3, but not MER. Of interest, Tyro3 remains as constitutively phosphorylated and form 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 anti-apoptotic proteins Mcl-1, Bcl-2, XIAP and upregulation of the pro-apoptotic protein BIM in CLL B-cells were detected as a result of Axl inhibition. Finally, combination of TP-0903 with BTK inhibitors augments CLL B-cell apoptosis. Conclusion Administration of TP-0903 either as a single agent or in combination with BTK inhibitors may be effective in treating CLL patients. PMID:25673699

  16. Control of A Five-axle, Three-steering Coupled-vehicle System

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Hiroaki; Mori, Masato; Kawakami, Atsushi

    This paper presents a new type of coupled-vehicle system: a five-axle, three-steering coupled-vehicle system and its path following feedback control law. The coupled-vehicle system consists of two car-like mobile robots, two carriers and a steering system. One of the two car-like mobile robots is coupled by one of the two carriers via a revolute joint passively rotating and the other car-like mobile robot is also coupled by one remaining carrier via a passive revolute joint, and the two carriers are coupled via another passive revolute joint. The steering system is attached to one of the carriers and its steering axis is located at the same position of the rotating axis of the passive revolute joint coupling the two carriers. We first show that, by assuming virtual mechanical elements, it is possible to convert the kinematical equation of the coupled-vehicle system into three-chain, single-generator chained form in a coordinate system in which a path two times differentiable is an axis and a straight line perpendicular to the tangent of the path is another axis. Based on chained form, we secondly derive the path following feedback control law which enables the orientations of the two carriers relative to the tangent of the path to be controllable. By the feedback control law, it is possible to cause the two carriers to form a line-shaped composed carrier or a V-shaped composed carrier and to cause them to keep such shapes while performing a path following behavior, which means that the coupled-vehicle system is able to adapt the shape of the composed carrier to the shape of a transported object. The validity of the mechanical design of the coupled-vehicle system and its path following feedback control law has been verified experimentally.

  17. Vibration control of bridge subjected to multi-axle vehicle using multiple tuned mass friction dampers

    NASA Astrophysics Data System (ADS)

    Pisal, Alka Y.; Jangid, R. S.

    2016-06-01

    The effectiveness of tuned mass friction damper (TMFD) in reducing undesirable resonant response of the bridge subjected to multi-axle vehicular load is investigated. A Taiwan high-speed railway (THSR) bridge subjected to Japanese SKS (Salkesa) train load is considered. The bridge is idealized as a simply supported Euler-Bernoulli beam with uniform properties throughout the length of the bridge, and the train's vehicular load is modeled as a series of moving forces. Simplified model of vehicle, bridge and TMFD system has been considered to derive coupled differential equations of motion which is solved numerically using the Newmark's linear acceleration method. The critical train velocities at which the bridge undergoes resonant vibration are investigated. Response of the bridge is studied for three different arrangements of TMFD systems, namely, TMFD attached at mid-span of the bridge, multiple tuned mass friction dampers (MTMFD) system concentrated at mid-span of the bridge and MTMFD system with distributed TMFD units along the length of the bridge. The optimum parameters of each TMFD system are found out. It has been demonstrated that an optimized MTMFD system concentrated at mid-span of the bridge is more effective than an optimized TMFD at the same place with the same total mass and an optimized MTMFD system having TMFD units distributed along the length of the bridge. However, the distributed MTMFD system is more effective than an optimized TMFD system, provided that TMFD units of MTMFD system are distributed within certain limiting interval and the frequency of TMFD units is appropriately distributed.

  18. Kinome-wide shRNA Screen Identifies the Receptor Tyrosine Kinase AXL as a Key Regulator for Mesenchymal Glioblastoma Stem-like Cells

    PubMed Central

    Cheng, Peng; Phillips, Emma; Kim, Sung-Hak; Taylor, David; Hielscher, Thomas; Puccio, Laura; Hjelmeland, Anita B.; Lichter, Peter; Nakano, Ichiro; Goidts, Violaine

    2015-01-01

    Summary Glioblastoma is a highly lethal cancer for which novel therapeutics are urgently needed. Two distinct subtypes of glioblastoma stem-like cells (GSCs) were recently identified: mesenchymal (MES) and proneural (PN). To identify mechanisms to target the more aggressive MES GSCs, we combined transcriptomic expression analysis and kinome-wide short hairpin RNA screening of MES and PN GSCs. In comparison to PN GSCs, we found significant upregulation and phosphorylation of the receptor tyrosine kinase AXL in MES GSCs. Knockdown of AXL significantly decreased MES GSC self-renewal capacity in vitro and inhibited the growth of glioblastoma patient-derived xenografts. Moreover, inhibition of AXL with shRNA or pharmacologic inhibitors also increased cell death significantly more in MES GSCs. Clinically, AXL expression was elevated in the MES GBM subtype and significantly correlated with poor prognosis in multiple cancers. In conclusion, we identified AXL as a potential molecular target for novel approaches to treat glioblastoma and other solid cancers. PMID:25921812

  19. Prostaglandin E₂ induces oncostatin M expression in human chronic wound macrophages through Axl receptor tyrosine kinase pathway.

    PubMed

    Ganesh, Kasturi; Das, Amitava; Dickerson, Ryan; Khanna, Savita; Parinandi, Narasimham L; Gordillo, Gayle M; Sen, Chandan K; Roy, Sashwati

    2012-09-01

    Monocytes and macrophages (m) are plastic cells whose functions are governed by microenvironmental cues. Wound fluid bathing the wound tissue reflects the wound microenvironment. Current literature on wound inflammation is primarily based on the study of blood monocyte-derived macrophages, cells that have never been exposed to the wound microenvironment. We sought to compare pair-matched monocyte-derived macrophages with m isolated from chronic wounds of patients. Oncostatin M (OSM) was differentially overexpressed in pair-matched wound m. Both PGE₂ and its metabolite 13,14-dihydro-15-keto-PGE₂ (PGE-M) were abundant in wound fluid and induced OSM in wound-site m. Consistently, induction of OSM mRNA was observed in m isolated from PGE₂-enriched polyvinyl alcohol sponges implanted in murine wounds. Treatment of human THP-1 cell-derived m with PGE₂ or PGE-M caused dose-dependent induction of OSM. Characterization of the signal transduction pathways demonstrated the involvement of EP4 receptor and cAMP signaling. In human m, PGE₂ phosphorylated Axl, a receptor tyrosine kinase (RTK). Axl phosphorylation was also induced by a cAMP analogue demonstrating interplay between the cAMP and RTK pathways. PGE₂-dependent Axl phosphorylation led to AP-1 transactivation, which is directly implicated in inducible expression of OSM. Treatment of human m or mice excisional wounds with recombinant OSM resulted in an anti-inflammatory response as manifested by attenuated expression of endotoxin-induced TNF-α and IL-1β. OSM treatment also improved wound closure during the early inflammatory phase of healing. In summary, this work recognizes PGE₂ in the wound fluid as a potent inducer of m OSM, a cytokine with an anti-inflammatory role in cutaneous wound healing. PMID:22844123

  20. Comparative analysis into the tractor-trailer braking dynamics: tractor with single axle brakes, tractor with all wheel brakes

    NASA Astrophysics Data System (ADS)

    Nastasoiu, Mircea; Ispas, Nicolae

    2014-06-01

    The paper elaborates a mathematical model in order to conduct a study into the dynamics of tractor-trailer systems during braking. The braking dynamics is analyzed by considering two versions for the braking system: 1) braking applied on the rear axle and 2) braking applied on all four wheels. In both versions the trailer is braked on all wheels. The mathematical model enables us to determine and graphically illustrate the evolution of the following parameters: braking deceleration, braking speed and the distance traveled by the tractor during braking. The mathematical model elaborated is applied on a tractor-trailer system completing transportation works.

  1. 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

  2. On "impact of surface type, wheelchair weight, and axle position on wheelchair propulsion by novice older adults".

    PubMed

    Sprigle, Stephen

    2009-07-01

    The mechanical efficiency of propelling manual wheelchairs is a very important topic. Wheelchair users, clinicians, manufacturers and payers would all benefit from better understanding of mechanical efficiency. However, the measurement of the mechanical efficiency is a nontrivial challenge. Cowan et al deserve a lot of credit for tackling such a difficult problem in their article "Impact of surface type, wheelchair weight, and axle position on wheelchair propulsion by novice older adults." The study demonstrated good internal validity in detecting a 4% difference in peak propulsion forces in wheelchairs that differed in mass by 9.1 kg. However, the instrumentation used to measure forces altered both the mass and inertia of the wheelchair-occupant system--2 factors that directly affect system energy. This approach, therefore, affects external validity, and the results cannot be extended to infer differences across wheelchair codes. That said, this study adds important information to the body of work into mechanical efficiency of wheelchairs. We now have evidence to suggest that addition of 9 kg and an 8 cm posterior displacement of axle position adversely affects propulsion biomechanics in an elderly cohort. Improved methodology can lead to mechanical efficiency measurement of different wheelchair models and different wheelchair options. PMID:19577018

  3. Evaluation of pitch up of two-axle solid waste collection compactor trucks in the static condition.

    PubMed

    Souza, Rosilene Viana de Freitas; Pinto, João Mário Andrade; Cimini, Carlos Alberto; Pereira, Sérgio Luiz de Souza

    2011-03-01

    The study of pitch up limit for solid waste collection compactor trucks in tilted public roads is of great relevance both for the planning of waste collection, mainly in cities with very uneven street gradient, or for use as a design parameter in projects involving public roads. Considering the typical construction and use of rear loader waste compactor equipment, the centre of gravity moves towards the rear of the vehicle as it is loaded, resulting in overload in the rear axle at the end of the waste collection period. In the city of Belo Horizonte (Brazil), several cases of pitch up have been reported for this type of vehicle, in streets with different inclinations and with loading situations in which the load box was not completely full. The present study investigated the variation of the imminence pitch up angles of the two-axle, rear-loading, solid waste collection compactor truck in a static condition, determined by the variation of its centre of gravity coordinates, which were obtained experimentally by means of a testing programme for different loading situations. The critical inclination angle was 0.347 rad (19.89°), which corresponds to a ramp inclination of 36.17%, for the condition of total weight of 157.06 kN (16 027 kgf) with payload of 63.42 kN (6472 kgf). PMID:20406754

  4. Receptor Tyrosine Kinases, TYRO3, AXL, and MER, Demonstrate Distinct Patterns and Complex Regulation of Ligand-induced Activation*

    PubMed Central

    Tsou, Wen-I; Nguyen, Khanh-Quynh N.; Calarese, Daniel A.; Garforth, Scott J.; Antes, Anita L.; Smirnov, Sergey V.; Almo, Steve C.; Birge, Raymond B.; Kotenko, Sergei V.

    2014-01-01

    TYRO3, AXL, and MER receptors (TAMs) are three homologous type I receptor-tyrosine kinases that are activated by endogenous ligands, protein S (PROS1) and growth arrest-specific gene 6 (GAS6). These ligands can either activate TAMs as soluble factors, or, in turn, opsonize phosphatidylserine (PS) on apoptotic cells (ACs) and serve as bridging molecules between ACs and TAMs. Abnormal expression and activation of TAMs have been implicated in promoting proliferation and survival of cancer cells, as well as in suppressing anti-tumor immunity. Despite the fact that TAM receptors share significant similarity, little is known about the specificity of interaction between TAM receptors and their ligands, particularly in the context of ACs, and about the functional diversity of TAM receptors. To study ligand-mediated activation of TAMs, we generated a series of reporter cell lines expressing chimeric TAM receptors. Using this system, we found that each TAM receptor has a unique pattern of interaction with and activation by GAS6 and PROS1, which is also differentially affected by the presence of ACs, PS-containing lipid vesicles and enveloped virus. We also demonstrated that γ-carboxylation of ligands is essential for the full activation of TAMs and that soluble immunoglobulin-like TAM domains act as specific ligand antagonists. These studies demonstrate that, despite their similarity, TYRO3, AXL, and MER are likely to perform distinct functions in both immunoregulation and the recognition and removal of ACs. PMID:25074926

  5. 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),…

  6. Non-contacting fluid ring seal systems for railcar axle bearing systems: Quarterly progress report No. 1, June 15 to September 15, 1987

    SciTech Connect

    Not Available

    1987-01-01

    The main objectives of this DOE contract is the technical development of a practical, cost effective Fluid Ring seal system capable of: Drastically reducing locomotive drawbar traction power requirements by lowering seal friction losses prevalent in present railcar axle bearing systems; increasing reliability and safety of railroad cars by minimizing bearing lubricant leakage and minimizing bearing ''hot boxes''; and improving the productivity of the railway transportation systems by reducing rolling stock ''outages'' due to long seal life. 14 refs.

  7. Potential of Active-Steering Bogie for Reducing Lateral Axle Load Caused at Worn Welded Joints of Outer Rail in Curved Track

    NASA Astrophysics Data System (ADS)

    Iizuka, Tatsuya; Tanifuji, Katsuya; Soma, Hitoshi

    This paper deals with the potential of an active-steering bogie to reduce the large lateral axle load that arises at worn welded joints of the outer rail in a curved track when high-speed trains pass. The shape of the worn joint, called lateral ‘angular bent’, is modeled on the basis of the measured irregularity shape of actual joints. Then, numerical simulation of running on a curved track is carried out for a two-axle bogie vehicle to compare an active-steering bogie and a conventional nonsteering bogie. The behavior of the vehicle negotiating the curve is evaluated from the viewpoints of decreasing the peak value of lateral axle load within the allowance limit and maintaining the running stability. To satisfy the requirements, wheelset-supporting parameters and feedback gains for active-steering are optimized on a curved section of 400 m radius by the Genetic Algorithm. On the basis of the optimized wheelset-supporting parameter values, additional sets of feedback gains, which are adjusted for the curves of different radii, are proposed. The numerical simulation shows that the operation speed of a vehicle with active-steering bogies having the optimized parameter values has the potential to be raised to the possible speed for tilting trains while satisfying the criterion of riding comfort.

  8. In-service parametric modelling a rail vehicle's axle-box hydraulic damper for high-speed transit problems

    NASA Astrophysics Data System (ADS)

    Wang, W. L.; Yu, D. S.; Zhou, Z.

    2015-10-01

    Due to the high-speed operation of modern rail vehicles and severe in-service environment of their hydraulic dampers, it has become important to establish more practical and accurate damper models and apply those models in high-speed transit problem studies. An improved full parametric model with actual in-service parameters, such as variable viscous damping, comprehensive stiffness and small mounting clearance was established for a rail vehicle's axle-box hydraulic damper. A subtle variable oil property model was built and coupled to the modelling process, which included modelling of the dynamic flow losses and the relief-valve system dynamics. The experiments validated the accuracy and robustness of the established full in-service parametric model and simulation which captured the damping characteristics over an extremely wide range of excitation speeds. Further simulations were performed using the model to uncover the effects of key in-service parameter variations on the nominal damping characteristics of the damper. The obtained in-service parametric model coupled all of the main factors that had significant impacts on the damping characteristics, so that the model could be useful in more extensive parameter effects analysis, optimal specification and product design optimisation of hydraulic dampers for track-friendliness, ride comfort and other high-speed transit problems.

  9. Chemical bonding and dynamic fluxionality of a B15(+) cluster: a nanoscale double-axle tank tread.

    PubMed

    Wang, Ying-Jin; You, Xue-Rui; Chen, Qiang; Feng, Lin-Yan; Wang, Kang; Ou, Ting; Zhao, Xiao-Yun; Zhai, Hua-Jin; Li, Si-Dian

    2016-06-21

    A planar, elongated B15(+) cationic cluster is shown to be structurally fluxional and functions as a nanoscale tank tread on the basis of electronic structure calculations, bonding analyses, and molecular dynamics simulations. The outer B11 peripheral ring behaves like a flexible chain gliding around an inner B4 rhombus core, almost freely at the temperature of 500 K. The rotational energy barrier is only 1.37 kcal mol(-1) (0.06 eV) at the PBE0/6-311+G* level, further refined to 1.66 kcal mol(-1) (0.07 eV) at the single-point CCSD(T)/6-311G*//CCSD/6-311G* level. Two soft vibrational modes of 166.3 and 258.3 cm(-1) are associated with the rotation, serving as double engines for the system. Bonding analysis suggests that the "island" electron clouds, both σ and π, between the peripheral ring and inner core flow and shift continuously during the intramolecular rotation, facilitating the dynamic fluxionality of the system with a small rotational barrier. The B15(+) cluster, roughly 0.6 nm in dimension, is the first double-axle nanoscale tank tread equipped with two engines, which expands the concepts of molecular wheels, Wankel motors, and molecular tanks. PMID:27229290

  10. GAS6/AXL Axis Regulates Prostate Cancer Invasion, Proliferation, and Survival in the Bone Marrow Niche12

    PubMed Central

    Shiozawa, Yusuke; Pedersen, Elisabeth A; Patel, Lalit R; Ziegler, Anne M; Havens, Aaron M; Jung, Younghun; Wang, Jingcheng; Zalucha, Stephanie; Loberg, Robert D; Pienta, Kenneth J; Taichman, Russell S

    2010-01-01

    Our recent studies have shown that annexin II, expressed on the cell surface of osteoblasts, plays an important role in the adhesion of hematopoietic stem cells (HSCs) to the endosteal niche. Similarly, prostate cancer (PCa) cells express the annexin II receptor and seem to use the stem cell niche for homing to the bone marrow. The role of the niche is thought to be the induction and sustenance of HSC dormancy. If metastatic PCa cells occupy a similar or the same ecological niche as HSCs, then it is likely that the initial role of the HSC niche will be to induce dormancy in metastatic cells. In this study, we demonstrate that the binding of PCa to annexin II induces the expression of the growth arrest-specific 6 (GAS6) receptors AXL, Sky, and Mer, which, in the hematopoietic system, induce dormancy. In addition, GAS6 produced by osteoblasts prevents PCa proliferation and protects PCa from chemotherapy-induced apoptosis. Our results suggest that the activation of GAS6 receptors on PCa in the bone marrow environment may play a critical role as a molecular switch, establishing metastatic tumor cell dormancy. PMID:20126470

  11. MicroRNA-432 functions as a tumor suppressor gene through targeting E2F3 and AXL in lung adenocarcinoma

    PubMed Central

    Chen, Ling; Kong, Guangming; Zhang, Chuantao; Dong, Hongyan; Yang, Cuicui; Song, Guanhua; Guo, Chengye; Wang, Lin; Yu, Hongsheng

    2016-01-01

    Abnormal proliferation and drug resistance are the hallmarks of lung adenocarcinoma (LAD). Dispite the advances in diagnosis and therapy, the 5-year survival remains low. Increasing studies regarding its pathological mechanism have been focused on microRNA (miRNA) due to its nodal regulatory properties. This study aims to characterize the expression of miR-432 in LAD and investigate its effects on the proliferation and sensitivity of lung cancer cells to cisplatin. Here, we report that downregulation of miR-432 in LAD tissues was correlated with a higher clinical stage (p = 0.03) and poor prognosis (p = 0.036). Additionally, miR-432 expression was negative correlated with high Ki67 labeling index (p = 0.016) in our cohorts. Functionally, over-expression of miR-432 inhibits cell proliferation through arresting cell cycle and sensitizes tumor cells to cisplatin. Mechanistically, miR-432 functions by directly targeting E2F3 and AXL, and they, in turn, mediate the regulation of miR-432 towards cell proliferation and cisplatin sensitivity. Importantly, miR-432 levels are negatively correlated with the levels of E2F3 and AXL in human LAD tissues. These results demonstrated that miR-432 functions as a tumor-suppressive miRNA and may represent a prognostic parameter and therapeutic target for LAD. PMID:26942465

  12. Nonlinearity-induced time-varying harmonic dynamic axle load and its impact on dynamic stability of car-trailer combinations

    NASA Astrophysics Data System (ADS)

    Zhang, Ning; Xiao, Hong; Winner, Hermann

    2016-06-01

    A nonlinearity-induced time-varying harmonic dynamic axle load is found in the road test of a car-trailer combination. To understand its influence on system dynamic stability, a corresponding linear single-track model (STM) is proposed. System dynamic stability is described and sensitivity analysis for the system parameters is achieved. The contribution of the harmonic force is quantified by a derived effective axle load. Because the harmonic effect might be time varying in practice, a time-frequency analysis-based parameter identification method is introduced. Experimental study shows that a time-varying harmonic effect really exists. A yaw-rate-based simulation method is designed to simulate this behaviour. The sensitivity analysis of the influence of the harmonic amplitude or phase on dynamic stability is performed with a simulation study. With appropriate modification of the harmonic amplitude and phase shift applied in selected time windows, the time-varying system characteristics in the road test can be simulated very well.

  13. Structural studies on inclusion compounds and solvent sorption behavior of gradually elongated wheel-and-axle-type diol hosts featuring lateral benzo[b]thiophene units

    NASA Astrophysics Data System (ADS)

    Katzsch, Felix; Gruber, Tobias; Weber, Edwin

    2016-06-01

    Based on the wheel-and-axle design strategy, a series of six new clathrate hosts featuring two di(benzo[b]thien-2-yl)hydroxymethyl units attached to both ends of a central linear building element of varying length have been synthesized and their capability to form crystalline inclusion compounds with a fixed range of organic solvents are reported. X-ray crystal structures of relevant inclusion compounds have been determined and are comparatively discussed involving structural modification of the host molecules. Organic vapor sorption behavior of the host compounds coated as solid films on the quartz crystal of a QCM device has been studied. Significant differences in the affinities towards solvent vapors dependent both on structural and polarity properties of host and solvent are observed, indicating potential application as mass sensitive materials.

  14. 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.

  15. Transfer case with inter-axle dual-planetary differential

    SciTech Connect

    Eastman, R.E.; Williams, R.C.

    1987-07-07

    A transfer case apparatus is described adapted for driving a four wheel drive motor vehicle having front and rear ground engaging wheels. The apparatus includes a housing, an input shaft adapted for connection to a transmission of the motor vehicle, a pair of first and second output shafts supported for rotation in the housing, the first output shaft adapted for driving connection to the rear ground engaging wheels and the second output shaft adapted for driving connection to the front ground engaging wheels. A dual helical planetary differential gear assembly is arranged in a compact manner for proportioning torque between the first and second output shafts. The dual planetary differential helical gear assembly comprises a dual planetary carrier including first and second longitudinally spaced carrier rings rotatable about the central axis of the first output shaft. The first carrier ring has a central opening formed with internal splines concentrically disposed about the first output shaft. First and second juxtaposed toothed helical gun gears are concentrically disposed about the first output shaft. The first sun gear is fixed to the first output shaft and has its teeth at a first uniform radius. The second sun gear is journalled on the first output shaft and has its teeth at a second uniform radius a predetermined distance less than the first sun gear teeth radius.

  16. Evaluation of the 30 Ton CHA Crane Wheel Axle Modification

    SciTech Connect

    RICH, J.W.

    2002-06-04

    An existing design for eccentric bushings was utilized and updated as necessary to accommodate minor adjustment as required to correct wheel alignment on the North West Idler wheel. The design is revised to install eccentric bushings on only one end.

  17. Will the Requirement by the US FDA to Simultaneously Co-Develop Companion Diagnostics (CDx) Delay the Approval of Receptor Tyrosine Kinase Inhibitors for RTK-Rearranged (ROS1-, RET-, AXL-, PDGFR-α-, NTRK1-) Non-Small Cell Lung Cancer Globally?

    PubMed

    Ou, Sai-Hong Ignatius; Soo, Ross A; Kubo, Akihito; Kawaguchi, Tomoya; Ahn, Myung-Ju

    2014-01-01

    The discovery of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC) in 2007 and the approval of crizotinib for the treatment of advanced ALK-rearranged NSCLC in 2011 represents a landmark in the development of targeted oncology therapy. The approval of crizotinib was accompanied simultaneously by the approval of the Vysis (Abbott Molecular) break-apart fluorescence in situ hybridization (FISH) test as the companion diagnostic (CDx) test to detect ALK rearrangement. Pfizer, the manufacturer of crizotinib, sponsored the screening of thousands of patients and the standardization of the ALK FISH test as part of the approval process for crizotinib, a first in class ALK inhibitor. Many pharmaceutical companies are now using the Food and Drug Administration (FDA)-approved ALK FISH assay to enroll patients onto trials for their own respective ALK inhibitors. In essence they are "piggybacking" on the FDA-approved ALK FISH assay without having to pay for the development of a CDx, nor screening for ALK-rearranged NSCLC patients in the protocols because screening for ALK rearrangement is now the standard of care in NSCLC after the approval of crizotinib. Since 2007, rearrangement in more receptor tyrosine kinases (RTKs) such as ROS1, RET, AXL, PDGFR-α, and NTRK1 have been discovered in NSCLC but the incidence of each subtype of RTK-rearranged NSCLC is quite rare. Crizotinib has now demonstrated significant clinical activity in ROS1-rearranged NSCLC patients. Whether crizotinib will gain official FDA approval for use in ROS1-rearranged NSCLC, on the other hand, remains unclear as there is no test for ROS1-rearrangement currently being developed to support US FDA approval as a CDx. This may be due in part to the fact that the full cost associated with the development of a pre-market approved-approved CDx must be borne by the company seeking the first drug approval in a new indication. Given the low incidence of ROS1-rearrangement in NSCLC, and

  18. 75 FR 76036 - American Axle & Manufacturing Detroit Manufacturing Complex Holbrook Avenue and Saint Aubin...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-07

    ... December 10, 2008 (73 FR 75137). The Department's Notice was amended on January 8, 2009 to clarify that the... (subject firm). The Department's Notice was published in the Federal Register on January 15, 2009 (74 FR... Avenue and Saint Aubin Including On-Site Leased Workers From Paint Tech International Detroit,...

  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. Algorithm of orthogonal bi-axle for auto-separating of watermelon seeds

    NASA Astrophysics Data System (ADS)

    Sun, Yong; Guan, Miao; Yu, Daoqin; Wang, Jing

    2007-11-01

    During the process of watermelon seeds characteristic extraction as well as separation, watermelon seeds' major and minor axes, the length and width ratio have played a very important role in appearance regulating degree evaluation. It is quite difficult to find the answer of orthogonal bi-axes because the watermelon seeds are flat and irregular in shape and what's more there is no rule to follow. After a lot of experiments and research, the author proposed the algorithm of orthogonal bi-axes algorithm for granulated object. It has been put into practice and proved in the application of auto-separation system for watermelon seeds. This algorithm has the advantage of lower time complexity and higher precision compared with other algorithms. The algorithm can be used in the solution of other similar granulated objects, and has the widespread application value.

  1. 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

    ... the Federal Register on February 2, 2009 (74 FR 5870). At the request of the State agency, the... From Caravan Knight Facilities Management LLC; Detroit, MI; Amended Certification Regarding Eligibility... Caravan Knight Facilities Management LLC were employed on-site at the Detroit, Michigan location...

  2. 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

    ... from Caravan Knight Facilities Management LLC, and Syncreon, Detroit, MI; Amended Certification... was published in the Federal Register on February 2, 2009 (74 FR 5870). The notice was amended on March 4, 2010 to include on-site leased workers from Caravan Knight Facilities Management LLC....

  3. Influence of wheel and rail profile shape on the initiation of rolling contact fatigue cracks at high axle loads

    NASA Astrophysics Data System (ADS)

    Spangenberg, Ulrich; Desmond Fröhling, Robert; Schalk Els, Pieter

    2016-05-01

    The influence of wheel and rail profile shape features on the initiation of rolling contact fatigue (RCF) cracks is evaluated based on the results of multi-body vehicle dynamics simulations. The damage index and surface fatigue index are used as two damage parameters to assess the influence of the different features. The damage parameters showed good agreement to one another and to in-field observations. The wheel and rail profile shape features showed a correlation to the predicted RCF damage. The RCF damage proved to be most sensitive to the position of hollow wear and thus bogie tracking. RCF initiation and crack growth can be reduced by eliminating unwanted shape features through maintenance and design and by improving bogie tracking.

  4. AUTOMOTIVE DIESEL MAINTENANCE 1. UNIT XVIII, I--UNDERSTAND ENGINE GEARS AND GEARING PRINCIPLES, II--MACK INTER-AXLE POWER DIVIDER.

    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 GEARS AND GEARING PRINCIPLES AND THE OPERATING PRINCIPLES AND MAINTENANCE OF POWER DIVIDERS (GEAR BOXES) USED IN DIESEL ENGINE POWER TRANSMISSION. TOPICS ARE (1) THE PURPOSE OF THE ENGINE GEARS, (2) INSPECTING FOR GEAR FAILURES, (3) INSPECTING FOR SHAFT…

  5. Increased roll stability suspension system

    SciTech Connect

    Giese, L.

    1987-05-26

    A suspension system is described for suspending an elongated chassis of a vehicle, such as a heavy duty truck, above the front axle and rear axle of a transversely extending tandem axle combination. The suspension system comprises: means for locating the roll center of the vehicle at an elevation below the elevation of the axles; and a stabilizer unit for providing roll stability to the vehicle. The stabilizer unit is mounted to the vehicle chassis at a pivot point longitudinally intermediate the front axle and the rear axle of the tandem axle combination for rotation in a generally horizontal plane. The stabilizer unit includes a pair of linkage members, each linkage member extending generally longitudinally outward from the pivot point in a direction opposite from the other linkage member and toward a corresponding axle.

  6. Axial length in unilateral idiopathic central serous chorioretinopathy

    PubMed Central

    Moon, Hoseok; Lee, Dae Yeong; Nam, Dong Heun

    2016-01-01

    AIM To evaluate the axial length (AXL) in unilateral idiopathic central serous chorioretinopathy (CSC). METHODS This retrospective case-control study was comprised of a consecutive case series of 35 patients with acute unilateral idiopathic CSC, and age- and sex-matched 50 control eyes. AXL of both eyes of unilateral CSC patients and the control eyes were investigated. AXL was measured by ultrasonic biometry, and the adjusted AXL was calculated for CSC eyes as measured AXL plus differences of foveal thickness between CSC and normal fellow eyes in millimeters. The main outcome measures were comparison of AXL between CSC, fellow and control eyes. RESULTS The mean age of 35 CSC patients was 45.5y, and 31 males were included. The adjusted AXL of CSC eyes was 23.52 mm, and the AXL of fellow eyes was 23.46 mm, and of control eyes 23.94 mm. The AXL of both CSC and fellow eyes were significantly shorter than control eyes (CSC vs control, P=0.044; fellow vs control, P=0.026). There was no statistically significant difference in AXL between CSC and fellow eyes. CONCLUSION In unilateral idiopathic CSC, the AXL of CSC and fellow eyes are shorter than that of control eyes. Short AXL may be related with choroidal circulation abnormality in CSC. PMID:27275428

  7. A Molecular Rotor Possessing an H-M-H "Spoke" on a P-M-P "Axle": A Platinum(II) trans-Dihydride Spins Rapidly Even at 75 K.

    PubMed

    Prack, Ernest; O'Keefe, Christopher A; Moore, Jeremy K; Lai, Angel; Lough, Alan J; Macdonald, Peter M; Conradi, Mark S; Schurko, Robert W; Fekl, Ulrich

    2015-10-28

    A new class of low-barrier molecular rotors, metal trans-dihydrides, is suggested here. To test whether rapid rotation can be achieved, the known complex trans-H2Pt(P(t)Bu3)2 was experimentally studied by (2)H and (195)Pt solid-state NMR spectroscopy (powder pattern changes with temperature) and computationally modeled as a (t)Bu3P-Pt-P(t)Bu3 stator with a spinning H-Pt-H rotator. Whereas the related chloro-hydride complex, trans-H(Cl)Pt(P(t)Bu3)2, does not show rotational behavior at room temperature, the dihydride trans-H2Pt(P(t)Bu3)2 rotates fast on the NMR time scale, even at low temperatures down to at least 75 K. The highest barrier to rotation is estimated to be ∼3 kcal mol(-1), for the roughly 3 Å long rotator in trans-H2Pt(P(t)Bu3)2. PMID:26448538

  8. Effect of Component Mobility on the Properties of Macromolecular [2]Rotaxanes.

    PubMed

    Chen, Zhen; Aoki, Daisuke; Uchida, Satoshi; Marubayashi, Hironori; Nojima, Shuichi; Takata, Toshikazu

    2016-02-18

    Macromolecular [2]rotaxanes comprising a polymer axle and crown ether wheel were synthesized to evaluate the effect of component mobility on the properties of the axle polymer, especially its crystallinity. Living ring-opening polymerization of δ-valerolactone with a pseudorotaxane initiator with a hydroxy group at the axle terminus was followed by end-capping with a bulky isocyanate. This yielded macromolecular [2]rotaxanes (M2Rs) possessing polyester axles of varying molecular weights. The crystallinity of the axle polymers of two series of M2Rs, with either fixed and movable components, was evaluated by differential scanning calorimetry. The results revealed that the effect of component mobility was significant in the fixed and movable M2Rs with a certain axle length, thus suggesting that the properties of the axle polymer depend on the mobility of the polyrotaxane components. PMID:26806916

  9. 49 CFR 537.7 - Pre-model year and mid-model year reports.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... resulting data to the Environmental Protection Agency under 40 CFR 600.509. (c) Model type and configuration... accordance with subpart D of 40 CFR part 600, (2) Body style, (3) Beginning model year 2010, base tire as defined in 49 CFR 523.2, (4) Beginning model year 2010, front axle, rear axle and average track width...

  10. 49 CFR 537.7 - Pre-model year and mid-model year reports.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... CFR 523.2, (B) Beginning model year 2013, front axle, rear axle and average track width as defined in 49 CFR 523.2, (C) Beginning model year 2013, wheelbase as defined in 49 CFR 523.2, and (D) Beginning model year 2013, footprint as defined in 49 CFR 523.2. (E) Optionally, beginning model year 2013,...

  11. 49 CFR 537.7 - Pre-model year and mid-model year reports.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... resulting data to the Environmental Protection Agency under 40 CFR 600.509. (c) Model type and configuration... accordance with subpart D of 40 CFR part 600, (2) Body style, (3) Beginning model year 2010, base tire as defined in 49 CFR 523.2, (4) Beginning model year 2010, front axle, rear axle and average track width...

  12. 49 CFR 537.7 - Pre-model year and mid-model year reports.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... CFR 523.2, (B) Beginning model year 2013, front axle, rear axle and average track width as defined in 49 CFR 523.2, (C) Beginning model year 2013, wheelbase as defined in 49 CFR 523.2, and (D) Beginning model year 2013, footprint as defined in 49 CFR 523.2. (E) Optionally, beginning model year 2013,...

  13. 49 CFR 393.48 - Brakes to be operative.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... motor vehicles provided the speed at which the combination of vehicles will be operated does not exceed... within 12.2 meters (40 feet) from the speed at which the vehicle is being operated or 32 km/hour (20 mph), whichever is less. (6) Raised lift axles. Brakes on lift axles need not be capable of being operated...

  14. 40 CFR 86.602-84 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... defined herein have the meaning given them in the Act. (1) Acceptable Quality Level (AQL) means the... satisfactory as a process average. (2) Axle Ratio means all ratios within ±3% of the axle ratio specified in the configuration in the test order. (3) Configuration means a subclassification of an...

  15. 40 CFR 86.602-84 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... defined herein have the meaning given them in the Act. (1) Acceptable Quality Level (AQL) means the... satisfactory as a process average. (2) Axle Ratio means all ratios within ±3% of the axle ratio specified in the configuration in the test order. (3) Configuration means a subclassification of an...

  16. Mode Orientation Control For Sapphire Dielectric Ring Resonator

    NASA Technical Reports Server (NTRS)

    Santiago, David G.; Dick, G. John; Prata, Aluizio

    1996-01-01

    Small sapphire tuning wedge used in technique for solving mode-purity problem associated with sapphire dielectric-ring resonator part of cryogenic microwave frequency discriminator. Breaks quasi-degeneracy of two modes and allows selective coupling to just one mode. Wedge mounted on axle entering resonator cavity and rotated while resonator cryogenically operating in vacuum. Furthermore, axle moved vertically to tune resonant frequency.

  17. 23 CFR Appendix B to Part 658 - Grandfathered Semitrailer Lengths

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... a kingpin-to-rearmost axle distance of 38 feet. Semitrailers that are consistent with 23 CFR 658.13... 23 CFR 658.13(g) may operate without a permit provided the distance from the kingpin to the center of the rear axle is 46 feet or less. 3 Semitrailers up to 53 feet in length may operate without a...

  18. 23 CFR Appendix B to Part 658 - Grandfathered Semitrailer Lengths

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... a kingpin-to-rearmost axle distance of 38 feet. Semitrailers that are consistent with 23 CFR 658.13... 23 CFR 658.13(g) may operate without a permit provided the distance from the kingpin to the center of the rear axle is 46 feet or less. 3 Semitrailers up to 53 feet in length may operate without a...

  19. 23 CFR Appendix B to Part 658 - Grandfathered Semitrailer Lengths

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... a kingpin-to-rearmost axle distance of 38 feet. Semitrailers that are consistent with 23 CFR 658.13... 23 CFR 658.13(g) may operate without a permit provided the distance from the kingpin to the center of the rear axle is 46 feet or less. 3 Semitrailers up to 53 feet in length may operate without a...

  20. All-terrain vehicle

    SciTech Connect

    Somerton-Rayner, M.

    1986-12-16

    This patent describes an all-terrain vehicle comprising: a chassis; four road wheel axles equally spaced along the chassis; suspension means mounting the axles on the chassis; wheels mounted adjacent both ends of each of the axles, the wheels on the foremost and the rearmost axles being steerably mounted; propulsion and driving means including a single internal combustion engine and gearbox, and first and second transfer boxes both coupled to be driven by the engine through the gearbox; the first transfer box driving the first and third axles and the second transfer box driving the second and fourth axles; means for driving in the alternative all four wheels and only the center two wheels; power-assisted steering gear means operatively connected to the steerably-mounted wheels of the foremost axle; and steering coupling means extending between the steerably-mounted wheels on the foremost and rearmost axles so dimensioned that upon steering of the front wheels, the rear wheels perform castoring constrained to a smaller turning angle and a lower rate of angular movement than the front wheels.

  1. 49 CFR 571.7 - Applicability.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... engine, transmission, and drive axle(s) (as a minimum) of the assembled vehicle are not new, and at least..., DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR VEHICLE SAFETY STANDARDS General § 571.7 Applicability. (a... B of this part applies according to its terms to all motor vehicles or items of motor...

  2. 49 CFR 571.7 - Applicability.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... engine, transmission, and drive axle(s) (as a minimum) of the assembled vehicle are not new, and at least..., DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR VEHICLE SAFETY STANDARDS General § 571.7 Applicability. (a... B of this part applies according to its terms to all motor vehicles or items of motor...

  3. 14 CFR 29.497 - Ground loading conditions: landing gear with tail wheels.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ....471 through 29.475; (2) The vertical load at each axle must be combined with a drag load at that axle... drag load must be applied, at the ground contact point, of not less than the lesser of— (i) 0.8...

  4. 14 CFR 27.497 - Ground loading conditions: landing gear with tail wheels.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ....471 through 27.475; (2) The vertical load at each axle must be combined with a drag load at that axle... drag load must be applied, at the ground contact point, of not less than the lesser of— (i) 0.8...

  5. 49 CFR 229.63 - Lateral motion.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Lateral motion. 229.63 Section 229.63....63 Lateral motion. (a) Except as provided in paragraph (b), the total uncontrolled lateral motion... powered axles. (b) The total uncontrolled lateral motion may not exceed 11/4 inches on the center axle...

  6. Mount for continuously orienting a collector dish in a system adapted to perform both diurnal and seasonal solar tracking

    NASA Technical Reports Server (NTRS)

    Brantley, L. W., Jr.; Lawson, B. D. (Inventor)

    1977-01-01

    A collector dish is continuously oriented toward the sun in a system adapted to perform both diurnal and seasonal solar tracking. The mount is characterized by a rigid, angulated axle having a linear midportion supporting a collector dish, and oppositely extended end portions normally related to the midportion of the axle and received in spaced journals. The longitudinal axis of symmetry for the midportion of the axle is coincident with a seasonal axis while the axes of the journals are coincident with a diurnal axis paralleling the earth's polar axis. Drive means are provided for periodically displacing the axle about the diurnal axis at a substantially constant rate, while other drive means are provided for periodically indexing the dish through 1 deg about the seasonal axis whereby the position of the dish relative to the axle is varied for accommodating seasonal tracking as changes in the angle of inclination of the polar axis occurs.

  7. A piston-rotaxane with two potential stripes: force transitions and yield stresses.

    PubMed

    Sevick, Edith M; Williams, David R M

    2013-01-01

    We examine a rod piston-rotaxane system, where the positions of several mobile rings on the axle are controlled by an external force acting on one of the rings. This allows us to access the translational entropy of the rings. For a simple rotaxane molecule with an axle that has uniform ring-axle interactions along its length, the molecule behaves like a miniature piston filled with a one-dimensional ideal gas. We then examine the effect of two stripes on the axle, having different ring-axle interactions with the mobile rings, so that one section is of high energy (repulsive) for the rings and another section is of lower energy (or attractive). This kind of rotaxane can exhibit rapid changes in displacement or force, and in particular, this molecule can exhibit a yield stress in which the piston suddenly compresses under a small increase in the applied force. PMID:24177696

  8. Rear wheel suspension and steering system

    SciTech Connect

    Ewen, J.G.

    1990-07-17

    This patent describes an improvement in a rear wheel support and driving system. The system comprises a rack-type dead axle adapted to support a vehicle body thereupon through suitable spring means, a pair of wheels rotatably supported upon the dead axle, a differential drive mechanism adapted to be supported upon the vehicle body movable with the body relative to the dead axle, the differential mechanism including a power input shaft and power output shafts, a pair of live axles drivingly connecting the output shafts with the wheels. The dead axle being generally rectilinear in shape and having a first pair of longitudinal beams respectively transversely spaced outboard of the differential mechanism, a second pair of cross beams respectively spaced fore and aft of the differential mechanism and secured to the first pair of beams.

  9. Frame structure for a four-wheel drive vehicle

    SciTech Connect

    Yamanaka, I.

    1986-09-30

    A frame is described for a four-wheel drive vehicle of the type where the rider straddles the vehicle, comprising a front axle support structure extending transversely of the vehicle; an upper frame structure including two downtubes extending upwardly, rearwardly and inwardly from the axle support structure and two main body tubes extending rearwardly from the downtubes; a lower frame structure extending rearwardly from the axle support structure, the lower frame structure including two lower frame tubes mutually spaced and extending rearwardly from the axle support structure. The lower frame structure is laterally inward of the downtubes at the axle support structure and laterally outward of the main body tubes; and each of the downtubes, main body tubes and lower frame tubes being formed from a continuous tube, the main body tube and the lower frame tube forming a continuous U-bend at the rear of the vehicle.

  10. 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.

  11. 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.

  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. 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.

  14. 49 CFR 393.48 - Brakes to be operative.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... a three-axle truck or truck tractor manufactured before March 1, 1975, a device to remove the front... braking effort may only be used on buses, trucks, and truck tractors manufactured before March 1,...

  15. Daisy Chain Rotaxanes Made from Interlocked DNA Nanostructures

    PubMed Central

    Weigandt, Johannes; Chung, Chia‐Ling; Jester, Stefan‐S.

    2016-01-01

    Abstract We report the stepwise assembly of supramolecular daisy chain rotaxanes (DCR) made of double‐stranded DNA: Small dsDNA macrocycles bearing an axle assemble into a pseudo‐DCR precursor that was connected to rigid DNA stoppers to form DCR with the macrocycles hybridized to the axles. In presence of release oligodeoxynucleotides (rODNs), the macrocycles are released from their respective hybridization sites on the axles, leading to stable mechanically interlocked DCRs. Besides the expected threaded DCRs, certain amounts of externally hybridized structures were observed, which dissociate into dumbbell structures in presence of rODNs. We show that the genuine DCRs have significantly higher degrees of freedom in their movement along the thread axle than the hybridized DCR precursors. Interlocking of DNA in DCRs might serve as a versatile principle for constructing functional DNA nanostructures where the movement of the subunits is restricted within precisely confined tolerance ranges. PMID:27010370

  16. 14 CFR 25.509 - Towing loads.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... towing fittings and must act parallel to the ground. In addition— (1) A vertical load factor equal to 1.0...) A reaction with a maximum value equal to the vertical reaction must be applied at the axle of...

  17. 14 CFR 25.509 - Towing loads.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... towing fittings and must act parallel to the ground. In addition— (1) A vertical load factor equal to 1.0...) A reaction with a maximum value equal to the vertical reaction must be applied at the axle of...

  18. 14 CFR 25.509 - Towing loads.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... towing fittings and must act parallel to the ground. In addition— (1) A vertical load factor equal to 1.0...) A reaction with a maximum value equal to the vertical reaction must be applied at the axle of...

  19. 14 CFR 25.509 - Towing loads.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... towing fittings and must act parallel to the ground. In addition— (1) A vertical load factor equal to 1.0...) A reaction with a maximum value equal to the vertical reaction must be applied at the axle of...

  20. 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.

  1. Daisy Chain Rotaxanes Made from Interlocked DNA Nanostructures.

    PubMed

    Weigandt, Johannes; Chung, Chia-Ling; Jester, Stefan-S; Famulok, Michael

    2016-04-25

    We report the stepwise assembly of supramolecular daisy chain rotaxanes (DCR) made of double-stranded DNA: Small dsDNA macrocycles bearing an axle assemble into a pseudo-DCR precursor that was connected to rigid DNA stoppers to form DCR with the macrocycles hybridized to the axles. In presence of release oligodeoxynucleotides (rODNs), the macrocycles are released from their respective hybridization sites on the axles, leading to stable mechanically interlocked DCRs. Besides the expected threaded DCRs, certain amounts of externally hybridized structures were observed, which dissociate into dumbbell structures in presence of rODNs. We show that the genuine DCRs have significantly higher degrees of freedom in their movement along the thread axle than the hybridized DCR precursors. Interlocking of DNA in DCRs might serve as a versatile principle for constructing functional DNA nanostructures where the movement of the subunits is restricted within precisely confined tolerance ranges. PMID:27010370

  2. Educational Materials Development in Primary Science: Simple Machines

    ERIC Educational Resources Information Center

    Franks, Frank L.; Butterfield, Lawrence H., Jr.

    1977-01-01

    Evaluated was the ability of 27 legally blind elementary students to identify and manipulate the parts of the following adapted simple machines: lever, inclined plane, wheel and axle, and pulley. (SBH)

  3. Cart Wheels

    ERIC Educational Resources Information Center

    Peck, Edson R.

    1978-01-01

    This paper draws attention to cart wheels, two wheels rotating freely about a common axle and rolling on an inclined plane, both as a demonstration and as a satisfying application of dynamical analysis. (BB)

  4. Simple Machines Simply Put.

    ERIC Educational Resources Information Center

    Kirkwood, James J.

    1994-01-01

    Students explore the workings of the lever, wheel and axle, and the inclined plane as they build simple toys--a bulldozer and a road grader. The project takes four weeks. Diagrams and procedures are included. (PR)

  5. Instability of Vibration of a Moving-Train Coupling System

    NASA Astrophysics Data System (ADS)

    Zheng, D. Y.; Fan, S. C.

    2002-08-01

    This paper presents the derivation of the governing equations for the stability of vibration of an integrated system comprising a moving train and the railway track. The train consists of a convoy of articulated two-axle wagons. The equations are applicable to any arbitrary number of axles at arbitrary spacing. Each axle is modelled as a mass-spring-damper vibration unit. The railway track is an infinitely long Euler beam subjected to an axial compressive force and rests on a visco-elastic foundation. The governing equations for the integrated system are coupled differential equations, which can be transformed to algebraic equations by Fourier and Laplace transforms. Subsequent inverse Fourier transform and contour integration yield the instability equation. Critical parameter is identified. It follows by parametric studies on the instability of vibration due to different train configurations. Illustrative examples for trains having up to 20 wagons or 40 axles are given.

  6. Improvement of the directional stability of passenger car trailer couplings with actively controlled steering

    NASA Astrophysics Data System (ADS)

    Desens, Jens

    The stabilization of pendulum oscillations of passenger car trailer couplings, using active steering, was examined. A linear model of the couplings was presented. Each axle was provided with a controller. The controllers were optimized, with regard to necessary sensors, in order to minimize costs. The rear and the front axles were provided with a control unit in order to compute the potential prevailing in the active steering of several axles. It was shown that the passenger car rear axle was the most suitable for coupling stabilization. The experiment was simulated, using a complex coupling model. The developed controller allowed the passenger car trailer to be driven at a speed higher than 150 km per hour.

  7. All wheel drive vehicle

    SciTech Connect

    Watanabe, M.; Yagasaki, A.; Kawashima, Y.

    1986-07-15

    An all-wheel-drive vehicle is described which consists of: (a) a body; (b) an engine mounted on the body and having an output shaft; (c) front and rear pairs of wheels drivable by power from the engine, the front and rear wheels being vertically movably suspended from the body; (d) axles coupled to the front and rear wheels; (e) first power transmitting means for transmitting power from the output shaft of the engine to one of the axles of the front and rear wheels; (f) a power output unit mounted on the one axle; and (g) second power transmitting means for transmitting power from the power output unit to the other of the axles of the front and rear wheels.

  8. Planning Torque Distribution Control of Rolling Stock for Fine Anti-slip/skid Re-adhesion Control

    NASA Astrophysics Data System (ADS)

    Imai, Kazutomi; Ohishi, Kiyoshi; Sano, Takashi; Makishima, Shingo; Yasukawa, Shinobu

    Generally, under a wet railway track condition, the axle adhesion coefficient of a train gradually increases from the head of a rolling stock. The improvement of adhesion characteristics is important in an electric motor coach. In order to suppress the slip/skid phenomenon, we have already proposed an anti-slip/skid re-adhesion control system based on a disturbance observer and sensor-less vector control. Moreover, we have confirmed that this system drives the train with the high adhesion force utilization ratio. This paper discusses the theoretical characteristic of the axle adhesion coefficient distribution of a rolling stock, which is based on the axle adhesion coefficient data of Shinkansen. In order to maintain the desired driving force performance, this paper proposes a new planning torque distribution control based on the axle adhesion coefficient distribution. This paper points out that the proposed method well maintains the desired driving force performance by the numerical simulation results.

  9. 75 FR 38081 - Notice of Scope Rulings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-01

    ... Scope Rulings, 75 FR 14138 (March 24, 2010). This current notice covers all scope rulings and... from the People's Republic of China Requestor: Northern Tool & Equipment Co.; whether a high-axle...

  10. Track train dynamics analysis and test program: Locomotive dynamic characterization summary

    NASA Technical Reports Server (NTRS)

    Berry, R. L.

    1982-01-01

    Locomotive mechanical characteristics, track perturbations, and operational characteristics involving experimentally determined suspension system parameters are analyzed. Suspension bearings, shock absorbers, pads, and two- and three- axle trucks are comparatively evaluated with respect to locomotive design.

  11. 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)...

  12. 49 CFR 587.6 - General description.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... the ballast installation and details concerning the ballast plate are provided in drawings shown in... center of gravity: X=44.2 inches rear of front axle Y=0.3 inches left of longitudinal center line...

  13. 49 CFR 587.6 - General description.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... the ballast installation and details concerning the ballast plate are provided in drawings shown in... center of gravity: X=44.2 inches rear of front axle Y=0.3 inches left of longitudinal center line...

  14. 49 CFR 587.6 - General description.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... the ballast installation and details concerning the ballast plate are provided in drawings shown in... center of gravity: X=44.2 inches rear of front axle Y=0.3 inches left of longitudinal center line...

  15. 49 CFR 393.42 - Brakes required on all wheels.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... axles and manufactured before July 25, 1980, are not required to have brakes on the front wheels... driveaway-towaway operation (including the last truck of triple saddle-mount combinations (see §...

  16. 49 CFR 393.42 - Brakes required on all wheels.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... axles and manufactured before July 25, 1980, are not required to have brakes on the front wheels... driveaway-towaway operation (including the last truck of triple saddle-mount combinations (see §...

  17. 49 CFR 393.42 - Brakes required on all wheels.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... axles and manufactured before July 25, 1980, are not required to have brakes on the front wheels... driveaway-towaway operation (including the last truck of triple saddle-mount combinations (see §...

  18. 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.

  19. Facile and efficient formation and dissociation of a pseudo[2]rotaxane by a slippage approach using pillar[5]arene-based cyclic host liquid and solvent.

    PubMed

    Ogoshi, Tomoki; Tamura, Yuko; Yamafuji, Daiki; Aoki, Takamichi; Yamagishi, Tada-Aki

    2016-08-11

    A pillar[5]arene-based pseudo[2]rotaxane was synthesized using a slippage method by only heating an axle with bulky valine derivative ends in a cyclic host liquid (CHL), which is liquid at room temperature. The pseudo[2]rotaxane synthesized in a CHL can be converted back to the starting components, i.e., the pillar[5]arene wheel and the axle, by heating in a solvent. PMID:27471989

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

    PubMed

    Robertson, L S

    1993-08-01

    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

  1. 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

  2. Global phosphotyrosine survey in triple-negative breast cancer reveals activation of multiple tyrosine kinase signaling pathways

    PubMed Central

    Ma, Binyun; Liu, Ren; Renuse, Santosh; Sahasrabuddhe, Nandini A.; Chen, Lily; Chaerkady, Raghothama; Kim, Min-Sik; Zhong, Jun; Jelinek, Christine; Barbhuiya, Mustafa A.; Leal-Rojas, Pamela; Yang, Yi; Kashyap, Manoj Kumar; Marimuthu, Arivusudar; Ling, Min; Fackler, Mary Jo; Merino, Vanessa; Zhang, Zhen; Zahnow, Cynthia A.; Gabrielson, Edward; Stearns, Vered; Roa, Juan Carlos; Sukumar, Saraswati; Gill, Parkash S.; Pandey, Akhilesh

    2015-01-01

    Breast cancer is the most prevalent cancer in women worldwide. About 15–20% of all breast cancers are triple negative breast cancer (TNBC) and are often highly aggressive when compared to other subtypes of breast cancers. To better characterize the biology that underlies the TNBC phenotype, we profiled the phosphotyrosine proteome of a panel of twenty-six TNBC cell lines using quantitative high resolution Fourier transform mass spectrometry. A heterogeneous pattern of tyrosine kinase activation was observed based on 1,789 tyrosine-phosphorylated peptides identified from 969 proteins. One of the tyrosine kinases, AXL, was found to be activated in a majority of aggressive TNBC cell lines and was accompanied by a higher level of AXL expression. High levels of AXL expression are correlated with a significant decrease in patient survival. Treatment of cells bearing activated AXL with a humanized AXL antibody inhibited cell proliferation and migration in vitro, and tumor growth in mice. Overall, our global phosphoproteomic analysis provided new insights into the heterogeneity in the activation status of tyrosine kinase pathways in TNBCs. Our approach presents an effective means of identifying important novel biomarkers and targets for therapy such as AXL in TNBC. PMID:26356563

  3. Shaft-driven motor vehicle

    SciTech Connect

    Imaizumi, M.; Akai, H.; Irie, T.; Inagaki, T.

    1987-03-03

    A motor vehicle is described comprising: a frame; a rear fork composed of first and second rear fork members having front ends pivotally mounted on the fame and rear ends supporting rear wheels, respectively; an axle housing having first and second axial ends, the first axial end having an attachment flange joined to the rear end of the first rear fork member; a rear axle rotatably supported in the axle housing; a gear case coupled between the rear end of the second rear fork member and the second axial end of the axial housing and accommodating a gear mechanism for driving the rear axle; at least one cross member extending between and joined to the first and second rear fork members; the rear end of the first rear fork member having a first joining surface having at least one attachment hole defined therein and directed transversely of the frame; the attachment flange of the axle housing having a second joining surface having at least one attachment hole defined therein and facing the first joining surface; at least one of the attachment holes in the first and second joining surfaces being elongate; and fastener means for joining the first rear fork member and the axle housing through the attachment holes.

  4. Off-the-road four-wheel drive vehicle

    SciTech Connect

    Foote, D.C.; Grinde, J.E.

    1987-03-17

    An off-road recreational vehicle is described comprising, in combination: (a) a frame; (b) front and rear pairs of wheels, each having relatively wide, ultra-low pressure tires mounted thereon, each of the wheel being secured to an axle member; (c) a limited slip differential means including a drive input disposed between the axle members of the front pair of wheels; (d) driving means drivenly connected to the axle members of the rear pair of wheels; (e) means for independently suspending the frame relative to the axle members of the front pair of wheels and for resiliently securing the frame to the driving means connected to the axle members of the rear pair of wheels; (f) an engine supported on the frame between the front and rear pairs of wheels, the engine having an output shaft directly coupled to the drive means connected to the rear axle member; and (g) over-running clutch means operatively coupled to the output shaft of the engine and interposed between the output shaft of the engine and the drive input of the limited slip differential for applying a driving force to the front pair of wheels only when slipage exists between the rear pair of wheels and the ground.

  5. Efficacy and Safety of Ambroxol Lozenges in the Treatment of Acute Uncomplicated Sore Throat - a Pooled Analysis.

    PubMed

    de Mey, C; Koelsch, S; Richter, E; Pohlmann, T; Sousa, R

    2016-07-01

    A pooled analysis is presented of 7 placebo-controlled RCT that investigated lozenges containing ambroxol for pain relief in acute sore throat.2 242 patients were treated with different ambroxol doses or control treatments, 2 183 were evaluable for efficacy. The present analysis is focused on the recommended dose of 20 mg (AXL20): 856 patients were treated with AXL20, 847 with matched placebo lozenges (PL).The average reduction in pain intensity over the first 3 h after the first AXL20 ranged from 38% to 52% of the maximum achievable effect (MAE). The overall treatment difference between AXL20 and PL was 11% (95% CI: 8-13%) of the MAE (post-hoc meta-analysis). The corresponding NNT was 6.0 (CI: 4.7-8.4) for an average pain reduction from baseline of 33% of the MAE over the first 3 h.71.9, 79.0, and 85.3% of the AXL20-patients scored the efficacy as "very good or good" at the end of the 1(st), 2(nd) and 3(rd) day, respectively, vs. 57.5, 64.4, and 70.4% of the PL-patients resulting in odds ratios of 1.9 (CI: 1.5-2.3) for the 1(st), 2.1 (CI: 1.7-2.6) for the 2(nd) and 2.43 (CI: 1.8-3.3) for the 3(rd) day.At the end of treatment 'no redness' or 'slightly red' was scored on pharyngeal inspection in 84.4% and 77.3% of AXL20- and PL-patients (OR: 1.6, CI: 1.3-1.9).AXL20-treatment was well tolerated and is safe and efficacious for acute uncomplicated sore throat of recent onset in adolescent and adult patients. PMID:27281448

  6. 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

  7. Kinetic Study of [2]Pseudorotaxane Formation with an Asymmetrical Thread.

    PubMed

    Quiroga, Miguel; Parajó, Mercedes; Rodríguez-Dafonte, Pedro; García-Río, Luis

    2016-06-28

    Kinetic and thermodynamic studies on cyclodextrin (CD)-based [2]pseudorotaxane formation have been carried out by a combination of NMR and calorimetric techniques using bolaform surfactants as axles. Experimental evidence of the formation of an external complex between the trimethylammonium head groups of the axle and the external hydrogen atoms of α-cyclodextrin (α-CD) is reported. Inclusion of this external complex in the reaction pathway allows us to explain the kinetic behavior as well as the nonlinear dependence of the observed rate constant on CD concentrations. The equilibrium constant for [2]pseudorotaxane formation is strongly affected by the spacer length of the axle. This effect is a consequence of increasing rotaxane stability because the threading rate constant is almost independent of the spacer length, but dethreading strongly decreases on increasing the axle size. Using a nonsymmetrical axle with tripropyl and trimethylammonium cations precludes CD threading by the large head side. CDs will thread this asymmetrical bolaform by both their wide and narrow sides, yielding two isomeric [2]pseudorotaxanes. Threading by the wide side of the CD is 60% more favorable than that by the narrow one, but dethreading rate constants are the same for both isomers. PMID:27232769

  8. Analysis of Semi-Active and Passive Suspensions System for Off-Road Vehicles

    NASA Astrophysics Data System (ADS)

    BenLahcene, Zohir; Faris, Waleed F.; Khan, M. D. Raisuddin

    2009-03-01

    The speed of off-road vehicles over rough terrain is generally determined by the ride quality not by the engine power. For this reason, researches are currently being undertaking to improve the ride dynamics of these vehicles using an advanced suspension system. This study intends to provide a preliminary evaluation of whether semi-active suspensions are beneficial to improving ride and handling in off-road vehicles. One of the greatest challenges in designing off-road vehicle suspension system is maintaining a good balance between vehicle ride and handling. Three configurations of these vehicles; 2-axle, 3-xle and 4-axles have been studied and their performances are compared. The application of several control policies of semi-active suspension system, namely skyhook; ground-hook and hybrid controls have been analyzed and compared with passive systems. The results show that the hybrid control policy yields better comfort than a passive suspension, without reducing the road-holding quality or increasing the suspension displacement. The hybrid control policy is also shown to be a better compromise between comfort, road-holding and suspension displacement than the skyhook and ground-hook control policies. Results show an improvement in ride comfort and vehicle handling using 4-axle over 3-axle and 2-axle when emphasis is placed on the response of the vehicle body acceleration, suspension and tyre deflection.

  9. Combination vehicle assembly

    SciTech Connect

    Silverman, M.J. Sr.

    1987-03-17

    A combination recreational vehicle assembly is described comprising: two vehicles of a different type, the vehicles comprising a first, leading vehicle having a steering mechanism for maneuvering the assembly and a drivable axle mechanism for propelling the assembly; an independently drivable second vehicle trailing the first vehicle comprising a standard road vehicle having a motor, and an axle mechanism for connecting the motor to the wheels of the second vehicle for providing power to the wheels of the vehicle. A gear means for selectively disconnecting the motor from the axle mechanism to place the vehicle in neutral, and a steering means for maneuvering the second vehicle when driven independently of the first vehicle are included; and a releasable mechanical drive connection between the second vehicle motor and the first vehicle axle mechanism to provide power for driving the assembly. The drive connection comprises a drive pinion projecting from the second vehicle motor to the front of the second vehicle, and a drive shaft projecting from the first vehicle axle mechanism to the rear of the first vehicle.

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

    SciTech Connect

    Lee, Yunhee; Lee, Mira; Kim, Semi

    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 signaling 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.

  11. 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

  12. Dual roadside seismic sensor for moving road vehicle detection and characterization.

    PubMed

    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

  13. 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

  14. 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

  15. Driving device for a mining machine

    SciTech Connect

    Blazewicz, A.; Cyrulo, J.; Krutki, M.; Sedlaczek, J.; Wozniak, T.

    1980-11-18

    The invention solves a problem of transferring the combined weight onto a conveyor through a railing, instead of through a link chain. For the aforesaid purpose a slide skid is provided, at both sides, with riding wheels. During operation of the combine the riding wheels roll on a railing; the riding wheels are mounted in a slide skid on a cranked axle. The cranked axle is protected against turning by means of a cover provided with a splined hole fixed on a splined pin of the cranked axle. The cover is fixed to the slide skid by means of screws. The design of the present device prevents deformation and tightening of vertical links of a chain between a rack and a slide skid in case of fouling of the rack with fine coal.

  16. Synthesis of multivalent host and guest molecules for the construction of multithreaded diamide pseudorotaxanes

    PubMed Central

    Kaufmann, Lena; Franzmann, Elisa; Maison, Wolfgang; Brandt, Emily; Aicher, Daniel; Wiehe, Arno

    2012-01-01

    Summary A series of di-, tri- and tetravalent axles and wheels for the synthesis of pseudorotaxanes bearing the tetralactam macrocycle/diamide axle binding motif was prepared. Starting from iodinated monovalent precursors, Sonogashira cross-coupling reactions were utilized to couple the binding sites to appropriate spacer groups. Through this “Lego” or “toolbox” approach, the convergent synthesis of host and guests with a well-defined number of the binding sites is possible. In addition, the spatial arrangement of the binding sites can be controlled through the quite rigid connections between linker and binding sites. Although a quantitative assessment of binding strengths was not possible by NMR titration experiments, typical and significant shifts of the signals of the diamide moiety indicate qualitatively the formation of pseudorotaxanes from the axle and wheel precursors. PMID:22423290

  17. Antibody-mediated neutralization of autocrine Gas6 inhibits the growth of pancreatic ductal adenocarcinoma tumors in vivo.

    PubMed

    Moody, Gordon; Belmontes, Brian; Masterman, Stephanie; Wang, Wei; King, Chadwick; Murawsky, Chris; Tsuruda, Trace; Liu, Shuying; Radinsky, Robert; Beltran, Pedro J

    2016-09-15

    Gas6 and its receptors Axl, Mer and Tyro-3 (TAM) are highly expressed in human malignancy suggesting that signaling through this axis may be tumor-promoting. In pancreatic ductal adenocarcinoma (PDAC), Gas6 and the TAM receptor Axl are frequently co-expressed and their co-expression correlates with poor survival. A strategy was devised to generate fully human neutralizing antibodies against Gas6 using XenoMouse® technology. Hybridoma supernatants were selected based on their ability to inhibit Gas6 binding to the receptor Axl and block Gas6-induced Axl phosphorylation in human cells. Two purified antibodies isolated from the screened hybridomas, GMAB1 and GMAB2, displayed optimal cellular potency which was comparable to that of the soluble extracellular domain of the receptor Axl (Axl-Fc). In vivo characterization of GMAB1 was conducted using a pharmacodynamic assay that measured inhibition of Gas6-induced Akt activation in the mouse spleen. Treatment of mice with a single dose (100-1000 µg) of GMAB1 led to greater than 90% inhibition of Gas6-induced phosphorylated Akt (pAkt) for up to 72 hr. Based on the target coverage observed in the PD assay, the efficacy of GMAB1 was tested against human pancreatic adenocarcinoma xenografts. At doses of 50 µg and 150 µg, twice weekly, GMAB1 was able to inhibit 55% and 76% of tumor growth, respectively (p < 0.001 for both treatments vs. control Ig). When combined with gemcitabine, GMAB1 significantly inhibited tumor growth compared to either agent alone (p < 0.001). Together, the data suggest that Gas6 neutralization may be important as a potential strategy for the treatment of PDAC. PMID:27170265

  18. Adhesion-related kinase induction of migration requires phosphatidylinositol-3-kinase and ras stimulation of rac activity in immortalized gonadotropin-releasing hormone neuronal cells.

    PubMed

    Nielsen-Preiss, Sheila M; Allen, Melissa P; Xu, Mei; Linseman, Daniel A; Pawlowski, John E; Bouchard, R J; Varnum, Brian C; Heidenreich, Kim A; Wierman, Margaret E

    2007-06-01

    GnRH neurons migrate into the hypothalamus during development. Although migratory defects may result in disordered activation of the reproductive axis and lead to delayed or absent sexual maturation, specific factors regulating GnRH neuronal migration remain largely unknown. The receptor tyrosine kinase, adhesion-related kinase (Ark) (also known as Axl, UFO, and Tyro7), has been implicated in the migration of GnRH neuronal cells. Binding of its ligand, growth arrest-specific gene 6 (Gas6), promotes cytoskeletal remodeling and migration of NLT GnRH neuronal cells via Rac and p38 MAPK. Here, we examined the Axl effectors proximal to Rac in the signaling pathway. Gas6/Axl-induced lamellipodia formation and migration were blocked after phosphatidylinositol-3-kinase (PI3K) inhibition in GnRH neuronal cells. The p85 subunit of PI3K coimmunoprecipitated with Axl and was phosphorylated in a Gas6-sensitive manner. In addition, PI3K inhibition in GnRH neuronal cells diminished Gas6-induced Rac activation. Exogenous expression of a dominant-negative form of Ras also decreased GnRH neuronal lamellipodia formation, migration, and Rac activation. PI3K inhibition blocked Ras in addition to Rac activation and migration. In contrast, pharmacological blockade of the phospholipase C gamma effectors, protein kinase C or calcium/calmodulin protein kinase II, had no effect on Gas6/Axl signaling to promote Rac activation or stimulate cytoskeletal reorganization and migration. Together, these data show that the PI3K-Ras pathway is a major mediator of Axl actions upstream of Rac to induce GnRH neuronal cell migration. PMID:17332061

  19. Vision-based industrial automatic vehicle classifier

    NASA Astrophysics Data System (ADS)

    Khanipov, Timur; Koptelov, Ivan; Grigoryev, Anton; Kuznetsova, Elena; Nikolaev, Dmitry

    2015-02-01

    The paper describes the automatic motor vehicle video stream based classification system. The system determines vehicle type at payment collection plazas on toll roads. Classification is performed in accordance with a preconfigured set of rules which determine type by number of wheel axles, vehicle length, height over the first axle and full height. These characteristics are calculated using various computer vision algorithms: contour detectors, correlational analysis, fast Hough transform, Viola-Jones detectors, connected components analysis, elliptic shapes detectors and others. Input data contains video streams and induction loop signals. Output signals are vehicle enter and exit events, vehicle type, motion direction, speed and the above mentioned features.

  20. Timing mechanism for wind motors

    SciTech Connect

    White, H.O.

    1980-09-23

    A plate is carried by the blade support shaft journalled within the frame of a wind motor. The axle shaft of the blade is securable to the plate at variable distances relative the support shaft to selectively vary the offset of the blade. A primary drive element, gear or sprocket, coaxial with the axle shaft and rotatable in response to rotation of the blade, drivingly engages a driven idler element, gear or sprocket, respectively, carried by an idler shaft journalled within the plate. A planetary gear rotatable in response to the driven idler element, drivingly engages a sun gear fixed to the frame coaxial with the support shaft.

  1. Side mounted V-type 4-cycle engine

    SciTech Connect

    Asano, A.; Kato, K.

    1987-06-09

    This patent describes a V-type four-cycle engine having overhead camshafts and a crankshaft, comprising: idle gear trains, the idle gear tram extending between the crankshaft and a camshaft and including idle gears; a gear retainer having first and second axles for rotatably mounting the idle gears; the first axle including a journal portion having a cylindrical surface about a first axial centerline and mounting portions having a cylindrical surface about a second axial centerline displaced from the first axial centerline; the mounting portions being supported by the gear retainer; and means for retaining the journal portion in selectable angular orientation with respect to the gear retainer.

  2. Molecular machinery: synthesis of a "nanodragster".

    PubMed

    Vives, Guillaume; Kang, Jungho; Kelly, Kevin F; Tour, James M

    2009-12-17

    The synthesis and imaging by scanning tunneling microscopy of a mixed wheeled nanovehicle composed of a p-carborane small-wheeled short front axle and a C(60) large-wheeled long rear axle that has been termed a nanodragster due to the structural relation to a dragster are reported. This nanodragster is expected to exhibit motion at a lower temperature than pure C(60)-wheeled nanocars and should allow the investigation of the role played by p-carborane wheels in directional motion. PMID:20000442

  3. Method of measurement and analysis of the extent of wear of rope wheel bearings in Bogdanka coal mine

    SciTech Connect

    Mazurkiewicz, D.; Galinski, M.

    2007-03-15

    This paper presents the method of assessing rope wheel bearing wear, developed for the special case of a shaft hoist in the Bogdanka coal mine. The diagnosis method presented here may also be used for inspecting the bearings of direction rope wheels with movable axles and bearings placed outside the axle in bodies, of the type that prevail in Polish coal mining. The superiority of this method in comparison to those used so far consists in limiting the testing time, as well as in the fact that no extra workers are needed. Nor does it require special availability of the shaft equipment for performing the test.

  4. 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…

  5. 23 CFR Appendix B to Part 658 - Grandfathered Semitrailer Lengths

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... a kingpin-to-rearmost axle distance of 38 feet. Semitrailers that are consistent with 23 CFR 658.13... 23 CFR 658.13(g) may operate without a permit provided the distance from the kingpin to the center of... tandem assembly. Semitrailers that are consistent with 23 CFR 658.13(g) may operate without a...

  6. 26 CFR 1.593-11 - Qualifying real property loan and nonqualifying loan defined.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 7 2012-04-01 2012-04-01 false Qualifying real property loan and nonqualifying... and axles removed, affixed to the ground by means of straps, and connected to water, sewer, gas, and... Qualifying real property loan and nonqualifying loan defined. (a) Loan defined. For purposes of this...

  7. 26 CFR 1.593-11 - Qualifying real property loan and nonqualifying loan defined.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 7 2014-04-01 2013-04-01 true Qualifying real property loan and nonqualifying... and axles removed, affixed to the ground by means of straps, and connected to water, sewer, gas, and... Qualifying real property loan and nonqualifying loan defined. (a) Loan defined. For purposes of this...

  8. 26 CFR 1.593-11 - Qualifying real property loan and nonqualifying loan defined.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 7 2013-04-01 2013-04-01 false Qualifying real property loan and nonqualifying... and axles removed, affixed to the ground by means of straps, and connected to water, sewer, gas, and... Qualifying real property loan and nonqualifying loan defined. (a) Loan defined. For purposes of this...

  9. 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…

  10. 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

  11. 49 CFR 571.110 - Tire selection and rims and motor home/recreation vehicle trailer load carrying capacity...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... GAWR of the axle system as specified on the vehicle's certification label required by 49 CFR part 567... certification label specified in 49 CFR part 567. Additionally, each trailer must on its placard contain a cargo... citations affecting § 571.111 see the List of CFR Sections Affected, which appears in the Finding...

  12. 49 CFR 571.110 - Tire selection and rims and motor home/recreation vehicle trailer load carrying capacity...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... GAWR of the axle system as specified on the vehicle's certification label required by 49 CFR part 567... certification label specified in 49 CFR part 567. Additionally, each trailer must on its placard contain a cargo... citations affecting § 571.111 see the List of CFR Sections Affected, which appears in the Finding...

  13. 49 CFR 396.3 - Inspection, repair, and maintenance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 5 2014-10-01 2014-10-01 false Inspection, repair, and maintenance. 396.3 Section... of the vehicle including company number, if so marked, make, serial number, year, and tire size. In..., axles and attaching parts, wheels and rims, and steering systems. (2) Pushout windows, emergency...

  14. 49 CFR 396.3 - Inspection, repair, and maintenance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 5 2012-10-01 2012-10-01 false Inspection, repair, and maintenance. 396.3 Section... of the vehicle including company number, if so marked, make, serial number, year, and tire size. In..., axles and attaching parts, wheels and rims, and steering systems. (2) Pushout windows, emergency...

  15. 49 CFR 396.3 - Inspection, repair, and maintenance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 5 2013-10-01 2013-10-01 false Inspection, repair, and maintenance. 396.3 Section... of the vehicle including company number, if so marked, make, serial number, year, and tire size. In..., axles and attaching parts, wheels and rims, and steering systems. (2) Pushout windows, emergency...

  16. 49 CFR 396.3 - Inspection, repair, and maintenance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 5 2011-10-01 2011-10-01 false Inspection, repair, and maintenance. 396.3 Section... of the vehicle including company number, if so marked, make, serial number, year, and tire size. In..., axles and attaching parts, wheels and rims, and steering systems. (2) Pushout windows, emergency...

  17. 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…

  18. 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…

  19. 49 CFR 537.4 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... weight is used as defined in subpart A of 40 CFR part 86. (2) The terms axle ratio, base level, body..., inertia weight, transmission class, and vehicle configuration are used as defined in subpart A of 40 CFR... are used as defined in subpart A of 40 CFR part 600. (4) The terms automobile, automobile capable...

  20. 49 CFR 537.4 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... weight is used as defined in subpart A of 40 CFR part 86. (2) The terms axle ratio, base level, body..., inertia weight, transmission class, and vehicle configuration are used as defined in subpart A of 40 CFR... are used as defined in subpart A of 40 CFR part 600. (4) The terms automobile, automobile capable...

  1. How to lighten trucks to haul bigger payloads

    SciTech Connect

    Smiley, C.H.

    1981-07-01

    New truck models are lighter and permit greater payloads. Weight distribution and axle loading must be considered to determine if an individual weight reduction can be transformed into a potentially profitable one. It should also be determined if the actual dollar value of increased payload compares favorably with the investment.

  2. Selective and effective binding of pillar[5,6]arenes toward secondary ammonium salts with a weakly coordinating counteranion.

    PubMed

    Li, Chunju; Shu, Xiaoyan; Li, Jian; Fan, Jiazeng; Chen, Zhenxia; Weng, Linhong; Jia, Xueshun

    2012-08-17

    The selective and effective binding of secondary ammoniums with a weakly coordinating tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BArF) counteranion by per-ethylated pillar[5,6]arenes is reported. The construction of a first pillararene-based self-sorting system consisting of two wheels and two axles is also described. PMID:22866893

  3. 40 CFR 85.2230 - Steady state test dynamometer-EPA 91.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... not drift more than ±0.5 horsepower (hp) during any single test mode. (3) Roll weight capacity. The dynamometer must be capable of supporting a driving axle weight up to four thousand (4,000) pounds or greater... lifting a minimum of four thousand (4,000) pounds. (5) Roll brakes. Rolls must be locked when the...

  4. 76 FR 9717 - Parts and Accessories Necessary for Safe Operation; Saddle-Mount Braking Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-22

    ... complete Privacy Act Statement in the Federal Register notice published on April 11, 2000 (65 FR 19476). II... after March 1, 1998.\\5\\ (70 FR 48008, Aug. 15, 2005). The axle weight of an unladen dolly is so low that... stated in its final rule: \\5\\ FMCSA noted that with NHTSA's March 10, 1995, final rule on ABS (60...

  5. 40 CFR 86.084-2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the smallest angle in a plan side view of an automobile, formed by the level surface on which the... smallest angle, in a plan side view of an automobile, formed by the level surface on which the automobile... level surface on which an automobile is standing to the lowest point on the axle differential of...

  6. 40 CFR 86.084-2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the smallest angle in a plan side view of an automobile, formed by the level surface on which the... smallest angle, in a plan side view of an automobile, formed by the level surface on which the automobile... level surface on which an automobile is standing to the lowest point on the axle differential of...

  7. 40 CFR 86.084-2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the smallest angle in a plan side view of an automobile, formed by the level surface on which the... smallest angle, in a plan side view of an automobile, formed by the level surface on which the automobile... level surface on which an automobile is standing to the lowest point on the axle differential of...

  8. 78 FR 7394 - Foreign-Trade Zone 41-Milwaukee, WI; Notification of Proposed Production Activity; CNH America...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-01

    ... Activity; CNH America, LLC, Subzone 41I (Tractors and Tractor/Combine Components), Racine, WI The Port of... are used for the production of tractors and tractor/combine components. Pursuant to 15 CFR 400.14(b)4...; differential axles; transmissions for combines and agricultural tractors; track-laying agricultural...

  9. Teaching Tips: For What Purpose?

    ERIC Educational Resources Information Center

    Hedges, Lowell E.; And Others

    1985-01-01

    Suggestions for teachers are presented, involving audiovisual materials, magazines, worksheets, safety reports, computers, bulletin boards, storage, problem solving, computer-assisted job searches, visual aids, motivating techniques, visual communications, engine valve display, computer printouts for stencils, wheel alignment for tractor axles,…

  10. 49 CFR 571.110 - Tire selection and rims and motor home/recreation vehicle trailer load carrying capacity...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... vehicle with standard equipment including the maximum capacity of fuel, oil, and coolant, and, if so... GAWR of the axle system as specified on the vehicle's certification label required by 49 CFR part 567... certification label specified in 49 CFR part 567. Additionally, each trailer must on its placard contain a...

  11. 49 CFR 585.61 - Scope.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...,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 requirements of Standard No. 138, Tire pressure monitoring systems (49 CFR 571.138)....

  12. 49 CFR 585.61 - Scope.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...,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 requirements of Standard No. 138, Tire pressure monitoring systems (49 CFR 571.138)....

  13. 49 CFR 585.61 - Scope.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...,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 requirements of Standard No. 138, Tire pressure monitoring systems (49 CFR 571.138)....

  14. 49 CFR 585.61 - Scope.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...,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 requirements of Standard No. 138, Tire pressure monitoring systems (49 CFR 571.138)....

  15. 49 CFR 585.61 - Scope.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...,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 requirements of Standard No. 138, Tire pressure monitoring systems (49 CFR 571.138)....

  16. 49 CFR 571.110 - Tire selection and rims and motor home/recreation vehicle trailer load carrying capacity...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... at the vehicle manufacturer's recommended cold inflation pressure for that tire. S4.2.2Tire load... GAWR of the axle system as specified on the vehicle's certification label required by 49 CFR part 567... of the derated load rating at the vehicle manufacturer's recommended cold inflation pressure for...

  17. 14 CFR 23.509 - Towing loads.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    .... In addition: (1) A vertical load factor equal to 1.0 must be considered acting at the center of... main gear must be reacted as follows: (i) A reaction with a maximum value equal to the vertical reaction must be applied at the axle of the wheel to which the load is applied. Enough airplane inertia...

  18. 14 CFR 23.509 - Towing loads.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    .... In addition: (1) A vertical load factor equal to 1.0 must be considered acting at the center of... main gear must be reacted as follows: (i) A reaction with a maximum value equal to the vertical reaction must be applied at the axle of the wheel to which the load is applied. Enough airplane inertia...

  19. 14 CFR 23.509 - Towing loads.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    .... In addition: (1) A vertical load factor equal to 1.0 must be considered acting at the center of... main gear must be reacted as follows: (i) A reaction with a maximum value equal to the vertical reaction must be applied at the axle of the wheel to which the load is applied. Enough airplane inertia...

  20. 14 CFR 23.509 - Towing loads.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    .... In addition: (1) A vertical load factor equal to 1.0 must be considered acting at the center of... main gear must be reacted as follows: (i) A reaction with a maximum value equal to the vertical reaction must be applied at the axle of the wheel to which the load is applied. Enough airplane inertia...

  1. 16 CFR 1512.9 - Requirements for protective guards.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... cover the top strand of the chain and at least 90° of the perimeter where the drive chain contacts the... in.) forward of the centerline of the rear axle. The minimum width of the top area of the chain guard... the top area may be tapered. The minimum width at the rear of the guard shall be one-half the...

  2. Simple Machines Made Simple.

    ERIC Educational Resources Information Center

    St. Andre, Ralph E.

    Simple machines have become a lost point of study in elementary schools as teachers continue to have more material to cover. This manual provides hands-on, cooperative learning activities for grades three through eight concerning the six simple machines: wheel and axle, inclined plane, screw, pulley, wedge, and lever. Most activities can be…

  3. Teaching Simple Machines.

    ERIC Educational Resources Information Center

    Atwater, Mary M.

    1988-01-01

    Presents several fun activities and teacher demonstrations which simplify terms and condense science concepts for teaching about the lever, wedge, wheel and axle, screw, pulley, and the inclined plane. Includes objectives, materials, procedures, suggested follow-up assignments, and diagrams. (RT)

  4. 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,…

  5. 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…

  6. 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…

  7. 14 CFR 25.733 - Tires.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Tires. 25.733 Section 25.733 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Landing Gear § 25.733 Tires. (a) When a landing gear axle is fitted with a single wheel...

  8. 49 CFR 537.4 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... are used as defined in subpart A of 40 CFR part 600. (4) The terms automobile, automobile capable of... weight is used as defined in subpart A of 40 CFR part 86. (2) The terms axle ratio, base level, body..., inertia weight, transmission class, and vehicle configuration are used as defined in subpart A of 40...

  9. Soil structural changes caused by agricultural machinery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Effects of tractor traffic with high axle load on the aggregate size distribution, the total soil porosity, and the aggregate porosity were studied in a field experiment on a silty clay loam Greyzem soil. One and three tractors passes were made at pre-irrigated and non-irrigated 10x10 m plots. The v...

  10. 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...

  11. 49 CFR 537.4 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... are used as defined in subpart A of 40 CFR part 600. (4) The terms automobile, automobile capable of... weight is used as defined in subpart A of 40 CFR part 86. (2) The terms axle ratio, base level, body..., inertia weight, transmission class, and vehicle configuration are used as defined in subpart A of 40...

  12. 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.

  13. Rear-heavy car control by adaptive linear optimal preview

    NASA Astrophysics Data System (ADS)

    Thommyppillai, M.; Evangelou, S.; Sharp, R. S.

    2010-05-01

    Adaptive linear optimal preview control theory is applied to a simple but non-linear car model, with parameters chosen to make the rear axle saturate first in any quasi-steady manoeuvre. The tendency of such a car to spin above a critical speed, which is a function of its running state, causes control to be especially difficult when operating near to the limit of the rear-axle force system. As in previous work, trim states and optimal gains are computed off-line for a given speed and a full range of lateral accelerations. Gain-scheduling with interpolation over trims and gain sets is used to keep the control appropriate to the running conditions, as they change. Simulations of manoeuvres are used to test and demonstrate the system capability. It is shown that utilising the rear-axle lateral-slip ratio as the scheduling variable, in the case of this rear-heavy car, gives excellent tracking, even when the tyres are run close to full saturation. It is implied by this and previous work that the general case can be treated effectively by monitoring both front- and rear-axle slips and scheduling on a worst-case basis.

  14. 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…

  15. 49 CFR 570.60 - Steering system.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... steering axle wheels in the straight ahead position, turn the steering wheel in one direction until there... are correctly adjusted. Grasp the front and rear of a tire and attempt to turn the tire and wheel assemble left and right. If the free movement at the front or rear tread of the tire exceeds the...

  16. 49 CFR 238.15 - Movement of passenger equipment with power brake defects.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... by the total number of TBUs in the train. (iii) Each cut-out axle on a locomotive that weighs more... restrictions on passenger trains with inoperative power brakes on the front or rear unit. If the power brakes on the front or rear unit in any passenger train are completely inoperative the following shall...

  17. Electrical drive for automobile

    SciTech Connect

    Fobbs, H.

    1980-09-16

    Electrical apparatus for driving an automobile is described that is comprised of a dc motor operationally connected to the rear axle through a drive shaft with the motor energized from storage batteries and recharged from alternators coupled to the drive shaft adjacent a clutch at the rear end of the automobile through an auxiliary drive shaft.

  18. Accurate and portable weigh-in-motion system for manifesting air cargo

    SciTech Connect

    Nodine, R.N.; Scudiere, M.B.; Jordan, J.K.

    1995-12-01

    An automated and portable weigh-in-motion system has been developed at Oak Ridge National Laboratory for the purpose of manifesting cargo onto aircraft. The system has an accuracv range of {plus_minus} 3.0% to {plus_minus} 6.0% measuring gross vehicle weight and locating the center of balance of moving vehicles at speeds of 1 to 5 mph. This paper reviews the control/user interface system and weight determination algorithm developed to acquire, process, and interpret multiple sensor inputs. The development effort resulted in a self-zeroing, user-friendly system capable of weighing a wide range of vehicles in any random order. The control system is based on the STANDARD (STD) bus and incorporates custom-designed data acquisition and sensor fusion hardware controlled by a personal computer (PC) based single-board computer. The user interface is written in the ``C`` language to display number of axles, axle weight, axle spacing, gross weight, and center of balance. The weighing algorithm developed will function with any linear weight sensor and a set of four axle switches per sensor.

  19. 77 FR 60169 - Safety Advisory 2012-04; Worn Rail Conditions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-02

    ... under repeated loading. In practice, the growth rate of rail defects is considered highly variable and unpredictable. Moreover, heavy axle loading on worn rail can lead to the accelerated development of rail surface... on the rail head running surface from wheel/rail interaction during cyclical loading. The...

  20. 49 CFR 537.4 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., inertia weight, transmission class, and vehicle configuration are used as defined in subpart A of 40 CFR... are used as defined in subpart A of 40 CFR part 600. (4) The terms automobile, automobile capable of... weight is used as defined in subpart A of 40 CFR part 86. (2) The terms axle ratio, base level,...

  1. 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…

  2. 78 FR 65759 - Notice of Receipt of Petition for Decision That Nonconforming 2012 Ahlm SBT 16-25 Trailers Are...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-01

    ... complete Privacy Act Statement in the Federal Register published on April 11, 2000 (65 FR 19477-78). How to... manner conforming to the standard. Standard No. 119 New Pneumatic Tires for Vehicles Other Than Passenger... Brake Systems: The vehicle was manufactured with an integrated axle, suspension, and brake...

  3. 23 CFR 500.204 - TMS components for highway traffic data.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... provide information on the numbers of single-trailer combination trucks, multiple-trailer combination... persons per automobile, light two-axle truck, and bus. The duration, geographic extent, and level of... during a monitoring session, as well as information on the date(s) and hour(s) of monitoring, will...

  4. 23 CFR 500.204 - TMS components for highway traffic data.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... provide information on the numbers of single-trailer combination trucks, multiple-trailer combination... persons per automobile, light two-axle truck, and bus. The duration, geographic extent, and level of... during a monitoring session, as well as information on the date(s) and hour(s) of monitoring, will...

  5. 23 CFR 500.204 - TMS components for highway traffic data.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... provide information on the numbers of single-trailer combination trucks, multiple-trailer combination... persons per automobile, light two-axle truck, and bus. The duration, geographic extent, and level of... during a monitoring session, as well as information on the date(s) and hour(s) of monitoring, will...

  6. 23 CFR 500.204 - TMS components for highway traffic data.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... provide information on the numbers of single-trailer combination trucks, multiple-trailer combination... persons per automobile, light two-axle truck, and bus. The duration, geographic extent, and level of... during a monitoring session, as well as information on the date(s) and hour(s) of monitoring, will...

  7. 49 CFR 230.112 - Wheels and tires.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Wheels and tires. 230.112 Section 230.112... Tenders Wheels and Tires § 230.112 Wheels and tires. (a) Mounting. Wheels shall be securely mounted on... wheels mounted on the same axle shall not vary more than 1/4 inch. (d) Tire thickness. Wheels may...

  8. 49 CFR 230.112 - Wheels and tires.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Wheels and tires. 230.112 Section 230.112... Tenders Wheels and Tires § 230.112 Wheels and tires. (a) Mounting. Wheels shall be securely mounted on... wheels mounted on the same axle shall not vary more than 1/4 inch. (d) Tire thickness. Wheels may...

  9. 49 CFR 230.112 - Wheels and tires.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Wheels and tires. 230.112 Section 230.112... Tenders Wheels and Tires § 230.112 Wheels and tires. (a) Mounting. Wheels shall be securely mounted on... wheels mounted on the same axle shall not vary more than 1/4 inch. (d) Tire thickness. Wheels may...

  10. 49 CFR 230.112 - Wheels and tires.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Wheels and tires. 230.112 Section 230.112... Tenders Wheels and Tires § 230.112 Wheels and tires. (a) Mounting. Wheels shall be securely mounted on... wheels mounted on the same axle shall not vary more than 1/4 inch. (d) Tire thickness. Wheels may...

  11. An Instructor's Guide for a Program in Drive Line Services.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Bureau of Secondary Curriculum Development.

    The Drive Line Services guide is designed to prepare students for employment in a specialized area of automotive services. The six units outlined are: an introduction (a course overview and a discussion of eye safety devices and the relevant legislation); clutches; drive lines; manual transmissions; overdrive units; and rear axle assemblies. Each…

  12. 40 CFR 86.1102-87 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the basis of engine code, inertia weight class, transmission type and gear ratios, rear axle ratio, or... of heavy-duty vehicles based on such factors as gross vehicle weight rating, fuel usage (gasoline-, diesel-, and methanol-fueled), vehicle usage, engine horsepower or additional criteria that...

  13. 40 CFR 86.602-84 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the basis of engine code, inertia weight class, transmission type and gear ratios, axle ratio, and... numbers associated with a particular sampling plan. (6) Vehicle means any new production light-duty vehicle as defined in subpart A of this part. (7) Test Vehicle means a vehicle in a test sample. (8)...

  14. Learning Activity Packets for Auto Mechanics II. Section C--Drive Train.

    ERIC Educational Resources Information Center

    Oklahoma State Board of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

    Five learning activity packets (LAPs) are provided for the instructional area of drive train in the auto mechanics II program. They accompany an instructor's guide available separately. The LAPs outline the study activities and performance tasks for these five units: (1) clutch assembly, (2) standard transmission, (3) drive lines, (4) rear axle,…

  15. 40 CFR 86.602-84 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... combination on the basis of engine code, inertia weight class, transmission type and gear ratios, axle ratio... pass and fail numbers associated with a particular sampling plan. (6) Vehicle means any new production light-duty vehicle as defined in subpart A of this part. (7) Test Vehicle means a vehicle in a...

  16. 40 CFR 86.602-84 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... combination on the basis of engine code, inertia weight class, transmission type and gear ratios, axle ratio... pass and fail numbers associated with a particular sampling plan. (6) Vehicle means any new production light-duty vehicle as defined in subpart A of this part. (7) Test Vehicle means a vehicle in a...

  17. 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.

  18. 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

  19. LAMOST fiber unit positional precision passive detection exploiting the technique of template matching

    NASA Astrophysics Data System (ADS)

    Wang, Mengxin; Zhao, Yongheng; Luo, Ali

    2012-09-01

    The large sky area multi-object fiber spectroscopic telescope (LAMOST) is an innovative reflecting schmidt telescope, promising a very high spectrum acquiring rate of several ten-thousands of spectra per night. By using the parallel controllable fiber positioning technique, LAMOST makes reconfiguration of fibers accurately according to the positions of objects in minutes and fine adjusting the fibers. As a key problem, High precision positioning detection of LAMOST fiber positioning unit has always been highly regarded and some detection schemes have been proposed. Among these, active detection method, which determines the final accurate position of optical fiber end with the help of lighting the fiber, has been most widely researched, but this kind of method could not be applied in LAMOST real-time observation because it needs projecting light into fiber. A novel detection idea exploiting the technique of template matching is presented in this paper. As we know, final position of a specific fiber end can be easily inferred by its corresponding revolving angles of the central revolving axle and bias revolving axle in double revolving style, so the key point in this problem is converted to the accurate determination of these revolving angles. Template matching technique are explored to acquire the matching parameters for its real-time collected imagery, and thus determine the corresponding revolving angle of the central revolving axle and bias revolving axle respectively. Experiments results obtained with data acquired from LAMOST site are used to verify the feasibility and effectiveness of this novel method.

  20. 49 CFR 571.110 - Tire selection and rims and motor home/recreation vehicle trailer load carrying capacity...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... GAWR of the axle system as specified on the vehicle's certification label required by 49 CFR part 567... certification label specified in 49 CFR part 567. Additionally, each trailer must on its placard contain a cargo... citations affecting § 571.111 see the List of CFR Sections Affected which appears in the Finding...

  1. 78 FR 49290 - Oshkosh Defense, a Division of Oshkosh Corporation, Including On-Site Leased Workers From...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-13

    ... IT Services, LLC, Landmark Staffing Resources, Inc., Larsen and Toubro Limited, MRI Network/Manta..., S-Series Front Discharge Cement Mixers and AARF axles), including component parts. The workers are... Services, LLC, Landmark Staffing Resources, Inc., Larsen and Toubro Limited, MRI Network/Manta...

  2. 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

  3. 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…

  4. 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,…

  5. 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,…

  6. Preliminary Assessment of Overweight Mainline Vehicles

    SciTech Connect

    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 vehicles 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 trailer

  7. Assessment of Open-Angle Glaucoma Peripapillary and Macular Choroidal Thickness Using Swept-Source Optical Coherence Tomography (SS-OCT)

    PubMed Central

    Song, Yong Ju; Kim, Young Kook; Jeoung, Jin Wook; Park, Ki Ho

    2016-01-01

    Objective To compare peripapillary and macular choroidal thickness (PCT and MCT) between open-angle glaucoma (OAG) and normal controls using swept-source optical coherence tomography (SS-OCT), and to evaluate global and localized relationships between choroidal thickness and various factors in OAG, also using SS-OCT. Methods In this cross-sectional comparative study, 134 OAG patients and 73 normal controls were examined. PCT (global, 12 clock-hour sectors), MCT (global, six sectors) were measured by SS-OCT. The difference in choroidal thickness between the OAG patients and the normal controls was analyzed. The relationships between choroidal thickness and various factors including age, sex, spherical equivalent (SE), axial length (AXL), central corneal thickness (CCT), intraocular pressure (IOP), peripapillary retinal nerve fiber layer thickness (pRNFLT), visual field mean deviation (MD), ganglion cell-inner plexiform layer thickness (GCIPLT), and disc area were analyzed by univariate and multivariate linear regression. Global and regional analyses were performed in 12 segments of the peripapillary circle and in six sectors of the macula. Results There were significant differences in global PCT and MCT between the OAG patients and the normal controls (115.22±41.17 vs. 138.89±44.70, P<0.001), (184.36±57.15 vs. 209.25±61.11, P = 0.004). The difference in global PCT remained, both after adjusting for age, AXL (117.08±3.45 vs. 135.47±4.70, P = 0.002) and also after adjusting for age, AXL, disc area (117.46±3.46 vs. 135.67±4.67, P = 0.002). But the difference in global MCT did not remain after adjusting for age, AXL, SE (188.18±4.46 vs. 202.25±6.08, P = 0.066). PCT showed significant differences between the groups in all of the 12 clock-hour sectors. These differences remained after adjusting for age, AXL and for age, AXL, disc area, with the exception of the 10 o’clock (o/c) sector. MCT in six sectors showed differences between the two groups, but they did

  8. Structural Changes of a Doubly Spin-Labeled Chemically Driven Molecular Shuttle Probed by PELDOR Spectroscopy.

    PubMed

    Franchi, Paola; Bleve, Valentina; Mezzina, Elisabetta; Schäfer, Christian; Ragazzon, Giulio; Albertini, Marco; Carbonera, Donatella; Credi, Alberto; Di Valentin, Marilena; Lucarini, Marco

    2016-06-20

    Gaining detailed information on the structural rearrangements associated with stimuli-induced molecular movements is of utmost importance for understanding the operation of molecular machines. Pulsed electron-electron double resonance (PELDOR) was employed to monitor the geometrical changes arising upon chemical switching of a [2]rotaxane that behaves as an acid-base-controlled molecular shuttle. To this aim, the rotaxane was endowed with stable nitroxide radical units in both the ring and axle components. The combination of PELDOR data and molecular dynamic calculations indicates that in the investigated rotaxane, the ring displacement along the axle, caused by the addition of a base, does not alter significantly the distance between the nitroxide labels, but it is accompanied by a profound change in the geometry adopted by the macrocycle. PMID:27123774

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

    PubMed

    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

  10. Solar concentrator

    SciTech Connect

    Smyth, J.S.

    1982-06-08

    A solar concentrator having an open framework formed as a geodesic dome. A rotatable support axle extends substantially diametrically across the dome and has the opposite ends thereof supported on the framework. The support axle defines a first rotational axis which is oriented to extend substantially parallel with the earth's north-south axis. A support post is hingedly mounted on the support shaft substantially at the midpoint thereof for permitting angular displacement of the support post relative to the support shaft about a second rotational axis which is perpendicular to the first axis. A dishshaped reflector assembly is positioned within the interior of the framework and fixedly secured to the support post. First and second drives effect angular displacement of the reflector assembly about the first and second axes, respectively, to permit tracking of the solar position.

  11. Glider kits cut truck ownership costs

    SciTech Connect

    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 high 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.

  12. Tetranitro-oxacalix[4]crown-Based Host-Guest Recognition Motif and a Related [2]Rotaxane-Based Molecular Switch.

    PubMed

    Liu, Hua; Hu, Wen-Jing; Liu, Yahu A; Li, Jiu-Sheng; Jiang, Biao; Wen, Ke

    2016-08-01

    Different from so far reported oxacalix[4]crown-based host-guest motifs in which oxacalix[4]crowns act only as hydrogen bond acceptors, a [2]pseudorotaxane-type tetranitro-oxacalix[4]crown/urea host-guest recognition motif was developed in which tetranitro-oxacalix[4]crown played a role as both a hydrogen bond donor and an acceptor to stabilize the resulting supramolecular complex. Furthermore, on the basis of a [2]pseudorotaxane complex formed from a tetranitro-oxacalix[4]crown and an axle containing a secondary ammonium ion and a urea group, a [2]rotaxane-based molecular switch was created, in which the oxacalix[4]crown wheel was able to reversibly translocate between the secondary ammonium binding site and the urea binding site of the axle under acid-base stimulation. PMID:27384815

  13. 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

  14. Predicting pavement distress in oil field areas

    SciTech Connect

    Mason, J.M.; Scullion, T.; Stampley, B.E.

    1984-05-01

    A study on oil field traffic characteristics was performed and a procedure was developed for assessing current and future effects of oil field truck traffic on surface-treated (stage construction type) pavements. A computer program calculates several types of pavement distress and serviceability parameters to evaluate pavement performance under various axle load repetitions. Stepwise regression analysis of 132 surface-treated pavement sections led to the development of individual distress equations for rutting, raveling, flushing, alligator cracking, patching, longitudinal and transverse cracking, and failures (potholes). The versatility of the program provides a means of anticipating early pavement failures due to increased axle load repetitions. The program also provides the basic framework for computing the effects of other ''special-use'' truck traffic demands.

  15. Predicting pavement distress in oil field areas

    SciTech Connect

    Mason, J.M.; Scullion, T.; Stampley, B.E.

    1983-05-01

    A study on oil field traffic characteristics was performed and a procedure was developed for assessing current and future effects of oil field truck traffic on surface-treated (stage construction type) pavements. A computer program calculates several types of pavement distress and serviceability parameters to evaluate pavement performance under various axle load repetitions. Stepwise regression analysis of 132 surface-treated pavement sections led to the development of individual distress equations for rutting, raveling, flushing, alligator cracking, patching, longitudinal and transverse cracking, and failures (potholes). The versatility of the program provides a means of anticipating early pavement failures due to increased axle load repetitions. The program also provides the basic framework for computing the effects of other ''special-use'' truck traffic demands.

  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. 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

  18. Long-range movement of large mechanically interlocked DNA nanostructures

    PubMed Central

    List, Jonathan; Falgenhauer, Elisabeth; Kopperger, Enzo; Pardatscher, Günther; Simmel, Friedrich C.

    2016-01-01

    Interlocked molecules such as catenanes and rotaxanes, connected only via mechanical bonds have the ability to perform large-scale sliding and rotational movements, making them attractive components for the construction of artificial molecular machines and motors. We here demonstrate the realization of large, rigid rotaxane structures composed of DNA origami subunits. The structures can be easily modified to carry a molecular cargo or nanoparticles. By using multiple axle modules, rotaxane constructs are realized with axle lengths of up to 355 nm and a fuel/anti-fuel mechanism is employed to switch the rotaxanes between a mobile and a fixed state. We also create extended pseudo-rotaxanes, in which origami rings can slide along supramolecular DNA filaments over several hundreds of nanometres. The rings can be actively moved and tracked using atomic force microscopy. PMID:27492061

  19. 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

    2016-09-01

    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. PMID:27436297

  20. Fast tracking using edge histograms

    NASA Astrophysics Data System (ADS)

    Rokita, Przemyslaw

    1997-04-01

    This paper proposes a new algorithm for tracking objects and objects boundaries. This algorithm was developed and applied in a system used for compositing computer generated images and real world video sequences, but can be applied in general in all tracking systems where accuracy and high processing speed are required. The algorithm is based on analysis of histograms obtained by summing along chosen axles pixels of edge segmented images. Edge segmentation is done by spatial convolution using gradient operator. The advantage of such an approach is that it can be performed in real-time using available on the market hardware convolution filters. After edge extraction and histograms computation, respective positions of maximums in edge intensity histograms, in current and previous frame, are compared and matched. Obtained this way information about displacement of histograms maximums, can be directly converted into information about changes of target boundaries positions along chosen axles.

  1. Acoustofluidic actuation of in situ fabricated microrotors.

    PubMed

    Kaynak, Murat; Ozcelik, Adem; Nama, Nitesh; Nourhani, Amir; Lammert, Paul E; Crespi, Vincent H; Huang, Tony Jun

    2016-09-21

    We have demonstrated in situ fabricated and acoustically actuated microrotors. A polymeric microrotor with predefined oscillating sharp-edge structures is fabricated in situ by applying a patterned UV light to polymerize a photocrosslinkable polyethylene glycol solution inside a microchannel around a polydimethylsiloxane axle. To actuate the microrotors by oscillating the sharp-edge structures, we employed piezoelectric transducers which generate tunable acoustic waves. The resulting acoustic streaming flows rotate the microrotors. The rotation rate is tuned by controlling the peak-to-peak voltage applied to the transducer. A 6-arm microrotor can exceed 1200 revolutions per minute. Our technique is an integration of single-step microfabrication, instant assembly around the axle, and easy acoustic actuation for various applications in microfluidics and microelectromechanical systems (MEMS). PMID:27466140

  2. [Traffic medicine expert opinions in otorhinolaryngology: current aspects].

    PubMed

    Waldfahrer, F; Iro, H; von Brevern, M; Fetter, M; Hamann, K-F; Holube, I; Lenarz, T; Lesinski-Schiedat, A; Stoll, W; von Stuckradt-Barre, S; Westhofen, M

    2010-02-01

    According to German law granting of driving licenses depends on the proof of an adequate driving capability. The corresponding guidelines are at present in the process of being revised. At the moment bilateral deafness and high-grade hearing loss (> or = 60% in pure tone audiometry) are not exclusion criteria for driving licenses grades A, B and C, while driving licenses grade D and licenses for public transport are generally excluded. In the forthcoming revised edition of the guidelines it has been suggested that the latter group will also not be excluded. The regulations concerning dizziness are wide-sweeping at the moment as no driving license will be granted if dizziness is present but will be more specific in the next issue. In particular a division will be made between single axle and two axle vehicles. An expert assessment about driving suitability can only be made by a certified specialist with qualifications in traffic medicine. PMID:20111915

  3. 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.

  4. [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. PMID:17380942

  5. Motor vehicle differential gear housing

    SciTech Connect

    Bitcon, L.L.

    1990-06-12

    This patent describes a motor vehicle differential gear housing. It comprises: a substantially box shaped casing having an interior and exterior defined by front, rear, top, bottom and two side panels, the front and rear panels each having an aperture, the apertures being at least partially in axial alignment; first bearing means cooperating with the apertures and demountably secured to each of the front and rear panels. The first bearing means is aligned coaxially with the aligned portions of the apertures; the side panels each having an opening, the openings being at least partially in axial alignment; axle support bearing housings aligned coaxially with the aligned portions of the openings on the side panels and threadedly mounted therein and adapted to have driving axles journaled in second bearing means in the bearing housings; and at least the front and rear panels being removably attached to the side panels.

  6. Longitudinal velocity and road slope estimation in hybrid electric vehicles employing early detection of excessive wheel slip

    NASA Astrophysics Data System (ADS)

    Klomp, Matthijs; Gao, Yunlong; Bruzelius, Fredrik

    2014-05-01

    Vehicle speed is one of the important quantities in vehicle dynamics control. Estimation of the slope angle is in turn a necessity for correct dead reckoning from vehicle acceleration. In the present work, estimation of vehicle speed is applied to a hybrid vehicle with an electric motor on the rear axle and a combustion engine on the front axle. The wheel torque information, provided by electric motor, is used to early detect excessive wheel slip and improve the accuracy of the estimate. A best-wheel selection approach is applied as the observation variable of a Kalman filter which reduces the influence of slipping wheels as well as reducing the computational effort. The performance of the proposed algorithm is illustrated on a test data recorded at a winter test ground with excellent results, even for extreme conditions such as when all four wheels are spinning.

  7. Noncircular rolling joints for vibrational reduction in slewing maneuvers

    NASA Technical Reports Server (NTRS)

    Chew, Meng-Sang (Inventor); Juang, Jer-Nan (Inventor); Yang, Li-Farn (Inventor)

    1992-01-01

    A rolling joint is provided for obtaining slewing maneuvers for various apparatus including space structures, space vehicles, robotic manipulators, and simulators. Two noncircular cylinders, namely a drive and a driven cylinder, are provided in driving contact with one another. This contact is maintained by two pairs of generally S-shaped bands, each pair forming a generally 8-shaped coupling tightly about the circumferential periphery of the noncircular drive and driven cylinders. A stationarily fixed arm extends between and is rotatably journalled with a drive axle and a spindle axle respectively extending through selected rotational points of the drive cylinder and of the driven cylinder. The noncircular cylinders are profiled to obtain the desired varying gear ratio. The novelty of the present invention resides in using specifically profiled noncircular cylinders to obtain a desired varying gear ratio.

  8. Apparatus for raising or tilting a micromechanical structure

    DOEpatents

    Allen, James J.

    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.

  9. 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.

  10. Noncircular rolling joints for vibrational reduction in slewing maneuvers

    NASA Astrophysics Data System (ADS)

    Chew, Meng-Sang; Juang, Jer-Nan; Yang, Li-Farn

    1992-09-01

    A rolling joint is provided for obtaining slewing maneuvers for various apparatus including space structures, space vehicles, robotic manipulators, and simulators. Two noncircular cylinders, namely a drive and a driven cylinder, are provided in driving contact with one another. This contact is maintained by two pairs of generally S-shaped bands, each pair forming a generally 8-shaped coupling tightly about the circumferential periphery of the noncircular drive and driven cylinders. A stationarily fixed arm extends between and is rotatably journalled with a drive axle and a spindle axle respectively extending through selected rotational points of the drive cylinder and of the driven cylinder. The noncircular cylinders are profiled to obtain the desired varying gear ratio. The novelty of the present invention resides in using specifically profiled noncircular cylinders to obtain a desired varying gear ratio.

  11. Laithwaite's Heavy Spinning Disk Demonstration

    NASA Astrophysics Data System (ADS)

    Cross, Rod

    2014-09-01

    In 1974, Professor Eric Laithwaite demonstrated an unusually heavy gyroscope at a Royal Institution lecture in London. The demonstration was televised and can be viewed on YouTube.1 A recent version of the same experiment, together with partial explanations, attracted two million YouTube views in the first few months.2 In both cases, the gyroscope consisted of a 40-lb (18-kg) spinning disk on the end of a 3-ft (0.91-m) long axle. The most remarkable feature of the demonstration was that Laithwaite was able to lift the disk over his head with one hand, holding onto the far end of the axle. The impression was given that the 40-lb disk was almost weightless, or "as light as a feather" according to Laithwaite.

  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. Long-range movement of large mechanically interlocked DNA nanostructures

    NASA Astrophysics Data System (ADS)

    List, Jonathan; Falgenhauer, Elisabeth; Kopperger, Enzo; Pardatscher, Günther; Simmel, Friedrich C.

    2016-08-01

    Interlocked molecules such as catenanes and rotaxanes, connected only via mechanical bonds have the ability to perform large-scale sliding and rotational movements, making them attractive components for the construction of artificial molecular machines and motors. We here demonstrate the realization of large, rigid rotaxane structures composed of DNA origami subunits. The structures can be easily modified to carry a molecular cargo or nanoparticles. By using multiple axle modules, rotaxane constructs are realized with axle lengths of up to 355 nm and a fuel/anti-fuel mechanism is employed to switch the rotaxanes between a mobile and a fixed state. We also create extended pseudo-rotaxanes, in which origami rings can slide along supramolecular DNA filaments over several hundreds of nanometres. The rings can be actively moved and tracked using atomic force microscopy.

  14. 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

  15. 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.

  16. 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…

  17. Light-powered, artificial molecular pumps: a minimalistic approach.

    PubMed

    Ragazzon, Giulio; Baroncini, Massimo; Silvi, Serena; Venturi, Margherita; Credi, Alberto

    2015-01-01

    The realization of artificial molecular motors capable of converting energy into mechanical work is a fascinating challenge of nanotechnology and requires reactive systems that can operate away from chemical equilibrium. This article describes the design and construction of a simple, supramolecular ensemble in which light irradiation causes the directional transit of a macrocycle along a nonsymmetric molecular axle, thus forming the basis for the development of artificial molecular pumps. PMID:26665081

  18. Rotating stool mounted on a low-friction hub

    NASA Astrophysics Data System (ADS)

    Bryant, Arthur

    2000-11-01

    The rotating stool for angular momentum described in this article uses a hub removed from the rear axle of a salvaged Geo automobile. The bearings of this hub are sealed and will not require any additional preparation. This rotating stool weighs 18 pounds, is 18 inches high, and will conform to an uneven floor. The seat and stand can easily be removed from the base for storage and transportation.

  19. A computer program (HEVSIM) for heavy duty vehicle fuel economy and performance simulation. Volume I: Description and analysis. Final report Mar-Oct 80

    SciTech Connect

    Buck, R.E.

    1981-09-01

    This report presents a description of a vehicle simulation program, which can determine the fuel economy and performance of a specified motor vehicle over a defined route as it executes a given driving schedule. Vehicle input accommodated by HEVSIM include accessories, engine, rear axle, converter, transmission, tires, aerodynamic drag coefficient, and shift logic. The report consists of three volumes. Volume I presents a description of the numerical approach and equations, Volume II is a user's manual, and Volume III contains the program listings.

  20. Wind turbine apparatus with fluidic rotation indicator

    SciTech Connect

    Machin, T.H.

    1993-06-22

    A wind turbine apparatus, comprising, an impeller housing, the housing including a front torroidal plate spaced from a rear solid uninterrupted plate, wherein the front plate is parallel, and spaced from the rear plate in a coaxially aligned relationship, and an axle shaft fixedly mounted to the rear plate and to the front plate extending rearward of the rear plate, and a plurality of arcuate vanes mounted between the rear plate and front plate adjacent an outer periphery of the housing, wherein the outer periphery of the housing is defined by a rear plate outer periphery and a front plate outer periphery, and each arcuate vane includes an outer edge adjacent the outer periphery, and an inner edge spaced from the outer periphery, wherein the inner edge and outer edge are arranged in a parallel relationship, and a central cone, the central cone including a cone base, wherein the cone base is fixedly mounted to a forward surface of the rear plate, and a cone apex positioned to extend at least to the front plate, wherein the cone is arranged coaxially relative to the axle shaft, and the arcuate vanes are positioned between the central cone and the outer periphery, and a plurality of radial brace legs mounted to an outer surface of the front plate extending radially of the front plate terminating in a central bearing ring, with a forward terminal end of the axle shaft mounted within the bearing ring, and a plurality of arcuate liquid chambers mounted to the forward surface of the front plate, each liquid chamber spaced an equal radial distance relative to the axle shaft and equally spaced about the front plate, with each chamber containing a first fluid and a second fluid, each first fluid defined by a first coloration and a first specific gravity, and each second fluid defined by a second coloration and second specific gravity, whereupon rotation of the impeller hosing, the first fluid and second fluid are intermixed to define a third coloration.

  1. 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.

  2. 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.

  3. 40 CFR 600.507-08 - Running change data requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... under §§ 86.079-32, 86.079-33, or 86.082-34 or 86.1842-01 as applicable, which: (1) Creates a new base level or, (2) Affects an existing base level by: (i) Adding an axle ratio which is at least 10 percent... 10 percent increase using the originally certified road-load horsepower as a base). (iii) Adding...

  4. Light-powered, artificial molecular pumps: a minimalistic approach

    PubMed Central

    Ragazzon, Giulio; Baroncini, Massimo; Silvi, Serena; Venturi, Margherita

    2015-01-01

    Summary The realization of artificial molecular motors capable of converting energy into mechanical work is a fascinating challenge of nanotechnology and requires reactive systems that can operate away from chemical equilibrium. This article describes the design and construction of a simple, supramolecular ensemble in which light irradiation causes the directional transit of a macrocycle along a nonsymmetric molecular axle, thus forming the basis for the development of artificial molecular pumps. PMID:26665081

  5. 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.

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

    SciTech Connect

    Woolley, R.D.

    1996-12-31

    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.

  7. 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. PMID:27049947

  8. Quantitative phosphoproteomics revealed interplay between Syk and Lyn in the resistance to nilotinib in chronic myeloid leukemia cells.

    PubMed

    Gioia, Romain; Leroy, Cédric; Drullion, Claire; Lagarde, Valérie; Etienne, Gabriel; Dulucq, Stéphanie; Lippert, Eric; Roche, Serge; Mahon, François-Xavier; Pasquet, Jean-Max

    2011-08-25

    In this study, we have addressed how Lyn kinase signaling mediates nilotinib-resistance by quantitative phospho-proteomics using Stable Isotope Labeling with Amino acid in Cell culture. We have found an increased tyrosine phosphorylation of 2 additional tyrosine kinases in nilotinib-resistant cells: the spleen tyrosine kinase Syk and the UFO family receptor tyrosine kinase Axl. This increased tyrosine phosphorylation involved an interaction of these tyrosine kinases with Lyn. Inhibition of Syk by the inhibitors R406 or BAY 61-3606 or by RNA interference restored the capacity of nilotinib to inhibit cell proliferation. Conversely, coexpression of Lyn and Syk were required to fully induce resistance to nilotinib in drug-sensitive cells. Surprisingly, the knockdown of Syk also strongly decreased tyrosine phosphorylation of Lyn and Axl, thus uncovering interplay between Syk and Lyn. We have shown the involvement of the adaptor protein CDCP-1 in resistance to nilotinib. Interestingly, the expression of Axl and CDCP1 were found increased both in a nilotinib-resistant cell line and in nilotinib-resistant CML patients. We conclude that an oncogenic signaling mediated by Lyn and Syk can bypass the need of Bcr-Abl in CML cells. Thus, targeting these kinases may be of therapeutic value to override imatinib or nilotinib resistance in CML. PMID:21730355

  9. Solar collector mounting and support apparatus

    SciTech Connect

    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 on 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.

  10. Suppressing Vertical Vibration in Railway Vehicles through Primary Suspension Damping Force Control

    NASA Astrophysics Data System (ADS)

    Sugahara, Yoshiki; Takigami, Tadao; Sampei, Mitsuji

    Suppression of the vertical bending vibration of carbodies has recently become essential in improving the riding comfort of railway vehicles. In many cases, the resonant frequency of the system (consisting of a bogie frame and axle springs) is close to that of the first mode bending vibration of the carbody, so suppressing the vibration of bogie frames near their resonant frequency effectively reduces carbody vibration. In this paper, we propose a method of suppressing such vibration by controlling the damping force of axle dampers installed between bogie frames and wheel sets. The design of the semi-active controller applied to determine the optimal damping force is based on the sky hook control theory. Numerical simulations using a vehicle model with 16 degrees of freedom as well as excitation tests using a carbody with variable axle dampers at a rolling stock test plant were carried out. The results show that this control method effectively reduces the power spectral density (PSD) of acceleration on the floor and that the riding comfort level (LT) can be improved by about 3 dB.

  11. Single-Stranded Tile Stoppers for Interlocked DNA Architectures.

    PubMed

    Valero, Julián; Lohmann, Finn; Keppner, Daniel; Famulok, Michael

    2016-06-16

    Interlocked DNA architectures are useful for DNA nanotechnology because of their mechanically bonded components, which can move relative to one another without disassembling. We describe the design, synthesis, and characterization of novel single-stranded tile (SST) stoppers for the assembly of interlocked DNA architectures. SST stoppers are shown to self-assemble into a square-shaped rigid structure upon mixing 97 oligodeoxynucleotide (ODN) strands. The structures are equipped with a sticky end that is designed for hybridization with the sticky ends of a dsDNA axle of a DNA rotaxane. Because the diameter of the macrocycle threaded onto the axle is 14 nm, the dimension of the square-shaped stopper was designed to be bulky enough to prevent the dethreading of the macrocycle. An asymmetric rotaxane with a SST- and a ring-shaped stopper featuring two stations for hybridization of the macrocycle to the axle was assembled. The macrocycle can be directed towards one or the other station upon triggering with fuel ODNs. PMID:26972112

  12. 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.

  13. 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.

  14. Vehicle with magnetic engine

    SciTech Connect

    Wortham, C.

    1993-06-15

    A vehicle is described comprising a vehicle frame fitted with axles and wheels rotatably carried by the axles; an engine block mounted on the frame; a plurality of magnetic cylinders provided in the engine block and a plurality of magnetic pistons disposed in the magnetic cylinders, respectively, in reciprocating relationship, the magnetic cylinders having a first magnetic polarity in one end and a second magnetic polarity in the opposite end for alternately attracting and repelling the magnetic pistons, respectively; a crankshaft journalled for rotation in the engine block; power transmission means connecting the crankshaft to at least one of the axles in driving relationship; and connecting rods connecting the crankshaft to the magnetic pistons, respectively, whereby reciprocation of the magnetic pistons in the magnetic cylinders effects rotation of the crankshaft; a cylinder head provided on the engine block and piston electromagnetic means provided in the cylinder head above the magnetic cylinders and the magnetic pistons, respectively for alternately attracting and repelling the magnetic pistons; at least one battery carried by the frame; and polarity timing means electrically connected to the battery and the piston electromagnetic means, for alternating the polarity of the piston electromagnet means, whereby electric current is supplied to the piston electromagnetic means in current-reversing relationship to alternately attract and repel the magnetic pistons in reciprocating relationship responsive to operation of the polarity timing means.

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

    PubMed Central

    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. PMID:26236772

  16. Effect of stationary guiding vanes on improvement of the washout behind the rotor in centrifugal blood pumps.

    PubMed

    Schima, H; Huber, L; Melvin, D; Trubel, W; Prodinger, A; Losert, U; Thoma, H; Wolner, E

    1992-01-01

    In centrifugal pumps, there always exists an area of stagnation between the rear of the rotor and the rear housing wall that promotes thrombus formation around the axle. Some current devices overcome the problem by using holes in the rotor plane, leading to increased hydrodynamic losses and shear stress. In this study, a simple apparatus was developed to overcome this problem. Guiding vanes were fixed to the rear housing wall. These vanes decrease the tangential velocity of the fluid and thus the centrifugal force, leading to an increased secondary flow toward the axle. The effect of such vanes was studied in videographic and ultrasound studies. An increase of washout and mixing between the flow layers could be demonstrated (stay time < 200 msec versus several seconds without vanes). In the first animal experiment using nonoptimized vanes, there was no thrombus at the back plane or the seal, and only a small thrombus at the transition between axle and rotor. Hemolysis was slightly elevated (3.2 mg/dl versus 2.5 mg/dl in control experiments). In conclusion, it is highly likely that this simple system will improve the flow characteristics in centrifugal pumps. PMID:1457852

  17. Miner's rule revisited

    NASA Astrophysics Data System (ADS)

    Schuetz, W.; Heuler, P.

    1994-03-01

    In the first sections, the requirements to be met by hypotheses for fatigue life prediction (including those for the crack initiation and crack propagation phases) are discussed in detail. These requirements are shown to be different for 'scientific' and for 'industrial' fatigue life prediction. Aspects with regard to an assessment of fatigue life prediction hypotheses are discussed. The last section presents the results of a large cooperative program between IABG and several automobile manufacturers, in which Miner's Rule in several versions was assessed against spectrum tests with five different actual automobile components: forged steel stub axle; forged steel stub axle, induction hardened; sheet steel welded rear axle (front wheel drive car); cast aluminum wheel; and welded sheet steel wheel. Since up to 80 components each were available, and two different, but typical, automotive stress-time histories were employed, the assessment was very thorough, avoiding many of the drawbacks of previous assessments. It is shown that damage sums to failure were usually far below 1.0; they also depended on the component in question, the aluminum wheel resulting in the lowest damage sums to failure; the damage sums to failure where always lower for a mild spectrum than for a severe one; and the influence of spectrum variation was predicted best - among the hypotheses tested - by use of a recent proposal of Zenner and Liu.

  18. Automatic power transmission mechanism for a four wheel drive vehicle

    SciTech Connect

    Garrett, R.J.

    1987-11-17

    In a transmission for a vehicle having two forward traction wheels and two rear traction wheels, this patent describes a multiple ratio transaxle having an input shaft adapted to be connected to an engine and arranged on a first axis and planetary gearing coaxially disposed relative to the input shaft and an output shaft; a first differential gear mechanism forming a part of the transaxle and having a torque output gear and side gears adapted to be connected to axle shafts for the forward wheels; a torque transfer drive means connecting the output shaft with the torque output gear including a first drive gear coaxially mounted relative to the torque output gear; an interaxle geared differential having a differential carrier and a pair of side gears, an interaxle torque input shaft having a third axis parallel to the second axis; a rear axle drive means connected to one of the interaxle differential side gears; a second drive gear and a third drive gear coaxially mounted with respect to the interaxle differential side gears; and first, second, third and fourth clutch means coaxially arranged with respect to the interaxle torque input shaft and independently actuatable for selectively connecting respectively (i) the third drive gear with the second drive gear, (ii) the second drive gear with the intermediate shaft, (iii) the third drive gear with the other side gear of the interaxle differential and (iv) the rear axle drive means with the carrier of the interaxle differential.

  19. 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. PMID:26236772

  20. Estrogen promotes Leydig cell engulfment by macrophages in male infertility

    PubMed Central

    Yu, Wanpeng; Zheng, Han; Lin, Wei; Tajima, Astushi; Zhang, Yong; Zhang, Xiaoyan; Zhang, Hongwen; Wu, Jihua; Han, Daishu; Rahman, Nafis A.; Korach, Kenneth S.; Gao, George Fu; Inoue, Ituro; Li, Xiangdong

    2014-01-01

    Male infertility accounts for almost half of infertility cases worldwide. A subset of infertile men exhibit reduced testosterone and enhanced levels of estradiol (E2), though it is unclear how increased E2 promotes deterioration of male fertility. Here, we utilized a transgenic mouse strain that overexpresses human CYP19, which encodes aromatase (AROM+ mice), and mice with knockout of Esr1, encoding estrogen receptor α (ERαKO mice), to analyze interactions between viable Leydig cells (LCs) and testicular macrophages that may lead to male infertility. In AROM+ males, enhanced E2 promoted LC hyperplasia and macrophage activation via ERα signaling. E2 stimulated LCs to produce growth arrest–specific 6 (GAS6), which mediates phagocytosis of apoptotic cells by bridging cells with surface exposed phosphatidylserine (PS) to macrophage receptors, including the tyrosine kinases TYRO3, AXL, and MER. Overproduction of E2 increased apoptosis-independent extrusion of PS on LCs, which in turn promoted engulfment by E2/ERα-activated macrophages that was mediated by AXL-GAS6-PS interaction. We further confirmed E2-dependant engulfment of LCs by real-time 3D imaging. Furthermore, evaluation of molecular markers in the testes of patients with nonobstructive azoospermia (NOA) revealed enhanced expression of CYP19, GAS6, and AXL, which suggests that the AROM+ mouse model reflects human infertility. Together, these results suggest that GAS6 has a potential as a clinical biomarker and therapeutic target for male infertility. PMID:24762434

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

    PubMed Central

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

    2015-01-01

    Objective: 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. Materials and Methods: 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. Results: 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. Conclusion: 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. PMID:25805676

  2. 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

  3. Prototype Weigh-In-Motion Performance

    SciTech Connect

    Abercrombie, Robert K; Beshears, David L; Hively, Lee M; Scudiere, Matthew B; Sheldon, Frederick T

    2006-10-01

    Oak Ridge National Laboratory (ORNL) has developed and patented methods to weigh slowly moving vehicles. We have used this technology to produce a portable weigh-in-motion system that is robust and accurate. This report documents the performance of the second-generation portable weigh-in-motion prototype (WIM Gen II). The results of three modes of weight determination are compared in this report: WIM Gen II dynamic mode, WIM Gen II stop-and-go mode, and static (parked) mode on in-ground, static scales. The WIM dynamic mode measures axle weights as the vehicle passes over the system at speeds of 3 to 7 miles per hour (1.3 to 3.1 meters/second). The WIM stop-and-go mode measures the weight of each axle of the vehicle as the axles are successively positioned on a side-by-side pair of WIM measurement pads. In both measurement modes the center of balance (CB) and the total weight are obtained by a straight-forward calculation from axle weights and axle spacings. The performance metric is measurement error (in percent), which is defined as 100 x (sample standard deviation)/(average); see Appendix A for details. We have insufficient data to show that this metric is predictive. This report details the results of weight measurements performed in May 2005 at two sites using different types of vehicles at each site. In addition to the weight measurements, the testing enabled refinements to the test methodology and facilitated an assessment of the influence of vehicle speed on the dynamic-mode measurements. The initial test at the National Transportation Research Center in Knoxville, TN, involved measurements of passenger and light-duty commercial vehicles. A subsequent test at the Arrival/Departure Airfield Control Group (A/DACG) facility in Ft. Bragg, NC, involved military vehicles with gross weights between 3,000 and 75,000 pounds (1,356 to 33,900 kilograms) with a 20,000-pound (9,040 kilograms) limit per axle. For each vehicle, four or more separate measurements were done

  4. Case depth verification of hardened samples with Barkhausen noise sweeps

    SciTech Connect

    Santa-aho, Suvi; Vippola, Minnamari; Lepistö, Toivo; Hakanen, Merja; Sorsa, Aki; Leiviskä, Kauko

    2014-02-18

    An interesting topic of recent Barkhausen noise (BN) method studies is the application of the method to case depth evaluation of hardened components. The utilization of BN method for this purpose is based on the difference in the magnetic properties between the hardened case and the soft core. Thus, the detection of case depth with BN can be achieved. The measurements typically have been carried out by using low magnetizing frequencies which have deeper penetration to the ferromagnetic samples than the conventional BN measurement. However, the penetration depth is limited due to eddy current damping of the signal. We introduce here a newly found sweep measurement concept for the case depth evaluation. In this study sweep measurements were carried out with various magnetizing frequencies and magnetizing voltages to detect the effect of different frequency and voltage and their correspondence to the actual case depth values verified from destructive characterization. Also a BN measurement device that has an implemented sweep analysis option was utilised. The samples were either induction or case-hardened samples and sample geometry contained both rod samples and gear axle samples with different case depth values. Samples were also further characterized with Xray diffraction to study the residual stress state of the surface. The detailed data processing revealed that also other calculated features than the maximum slope division of the 1st derivative of the BN signal could hold the information about the case depth value of the samples. The sweep method was able to arrange the axles into correct order according to the case depth value even though the axles were used.

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

    PubMed Central

    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. PMID:26924277

  6. Signal pathways in up-regulation of chemokines by tyrosine kinase MER/NYK in prostate cancer cells.

    PubMed

    Wu, Yi-Mi; Robinson, Dan R; Kung, Hsing-Jien

    2004-10-15

    The AXL/UFO family of tyrosine kinases is characterized by a common N-CAM (neural adhesion molecule)-related extracellular domain and a common ligand, GAS6 (growth arrest-specific protein 6). Family members are prone to transcriptional regulation and carry out diverse functions including the regulation of cell adhesion, migration, phagocytosis, and survival. In this report, we describe a new role of MER/N-CAM-related kinase (NYK), a member of the AXL family of kinases, in the up-regulation of chemokines in prostate cancer cells. We show that NYK has elevated expression in a subset of tumor specimens and prostate cancer cell lines. Activation of NYK in the prostate cancer cell line DU145 does not cause a mitogenic effect; instead, it causes a differentiation phenotype. Microarray analysis revealed that NYK is a strong inducer of endocrine factors including interleukin (IL)-8 and several other angiogenic CXC chemokines as well as bone morphogenic factors. The dramatic increase of IL-8 expression is seen at both transcriptional and posttranscriptional levels. The downstream signals engaged by NYK were characterized, and those responsible for the up-regulation of IL-8 transcription were defined. In contrast to IL-1alpha, NYK-induced up-regulation of IL-8 in DU145 depends on the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase/Jun/Fos pathway, but not phosphoinositide 3'-kinase/nuclear factor-kappaB. These data define a new function of the AXL family of kinases and suggest a potential role of NYK in prostate cancer progression. PMID:15492251

  7. 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.

  8. Case depth verification of hardened samples with Barkhausen noise sweeps

    NASA Astrophysics Data System (ADS)

    Santa-aho, Suvi; Hakanen, Merja; Sorsa, Aki; Vippola, Minnamari; Leiviskä, Kauko; Lepistö, Toivo

    2014-02-01

    An interesting topic of recent Barkhausen noise (BN) method studies is the application of the method to case depth evaluation of hardened components. The utilization of BN method for this purpose is based on the difference in the magnetic properties between the hardened case and the soft core. Thus, the detection of case depth with BN can be achieved. The measurements typically have been carried out by using low magnetizing frequencies which have deeper penetration to the ferromagnetic samples than the conventional BN measurement. However, the penetration depth is limited due to eddy current damping of the signal. We introduce here a newly found sweep measurement concept for the case depth evaluation. In this study sweep measurements were carried out with various magnetizing frequencies and magnetizing voltages to detect the effect of different frequency and voltage and their correspondence to the actual case depth values verified from destructive characterization. Also a BN measurement device that has an implemented sweep analysis option was utilised. The samples were either induction or case-hardened samples and sample geometry contained both rod samples and gear axle samples with different case depth values. Samples were also further characterized with Xray diffraction to study the residual stress state of the surface. The detailed data processing revealed that also other calculated features than the maximum slope division of the 1st derivative of the BN signal could hold the information about the case depth value of the samples. The sweep method was able to arrange the axles into correct order according to the case depth value even though the axles were used.

  9. Growth arrest-specific gene 6 (Gas6) levels are elevated in patients with chronic renal failure

    PubMed Central

    Lee, Iris J.; Hilliard, Brendan; Swami, Abhishek; Madara, John C.; Rao, Swati; Patel, Tapan; Gaughan, John P.; Lee, Jean; Gadegbeku, Crystal A.; Choi, Eric T.; Cohen, Philip L.

    2012-01-01

    Background The TAM receptors (tyro3, axl and mer) and their ligands (vitamin K-dependent proteins—Gas6 and Protein S) are crucial modulators of inflammation, which may be relevant in chronic kidney disease (CKD). Gas6 and axl have multiple roles in mediating vascular atherosclerosis and injury, thrombosis and inflammation, yet nothing is known about the Gas6–axl pathway in humans with CKD. Given the prevalence of chronic inflammation and vascular disease in this population, we measured TAM ligands in patients with various levels of renal function. Methods Gas6 and protein S were quantified in the plasma by ELISA in three patient groups: end-stage renal disease on chronic hemodialysis (HD), CKD and normal controls. Results Significantly increased levels of Gas6 and protein S were found in CKD patients compared with normal controls (P < 0.01 and <0.001, respectively). In HD patients, Gas6 levels were elevated compared with controls (P < 0.001) and positively associated with low albumin (r= 0.33; P = 0.01), dialysis vintage (r= 0.36; P = 0.008) and IV iron administration (r= 0.33; P = 0.01). The levels of Gas6 rose with CKD stage and were inversely associated with estimated GFR (P < 0.0001). Conclusions Dysregulation of circulating Gas6 is associated with renal disease and inversely proportional to renal function. Low albumin and higher IV iron administration were associated with higher Gas6 levels, suggesting a possible connection between inflammation and oxidative stress mediated by iron. Protein S levels were also elevated in CKD patients, but the relevance of this finding needs to be further investigated. PMID:22907951

  10. Power transfer device for four-wheel drive

    SciTech Connect

    Sasaki, K.; Takimura, K.; Katayama, N.

    1987-10-06

    A power transfer device is described for four-wheel drive in combination with a power transmission having a transmission casing, an input shaft rotatably mounted, an output shaft rotatably mounted, a change-speed gearing mounted on the input and output shafts, and an output gear mounted on the output shaft for rotation therewith. The power transfer device comprises: a transfer casing detachably secured at one side to the transmission casing; a first differential gear unit including an input element in the form of a first gear casing rotatably mounted within the transmission casing and drivingly connected to the output gear, and an air of first output elements rotatably mounted within the first gear casing respectively for front-wheel drive and rear-wheel drive; a second differential gear unit arranged coaxially with the first differential gear unit and including a second input member in the form of a second gear casing; a carrier member rotatably mounted within the transfer casing and arranged coaxially with the first and second differential gear units; a first wheel axle drivingly connected at an inner end; a second wheel axle drivingly connected at an inner end with the other second output element of the second differential gear unit and extending outwardly from the transfer casing through the carrier member; a hollow shaft arranged with the second wheel axle; and a clutch sleeve; an output gearing assembled within the transfer casing and arranged to be driven by the carrier member; and means for axially slidably coupling an end of the clutch sleeve with one end of the carrier member in such a manner that the clutch sleeve is positioned relative to the carrier member in a predetermined radial and circumferential direction.

  11. 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.

  12. Registrations and vehicle miles of travel of light duty vehicles, 1985--1995

    SciTech Connect

    Hu, P.S.; Davis, S.C.; Schmoyer, R.L.

    1998-02-01

    To obtain vehicle registration data that consistently and accurately reflect the distinction between automobiles and light-duty trucks, Oak Ridge National Laboratory (ORNL) was asked by FHWA to estimate the current and historical vehicle registration numbers of automobiles and of other two-axle four-tire vehicles (i.e., light-duty trucks), and their associated travel. The term automobile is synonymous with passenger car. Passenger cars are defined as all sedans, coupes, and station wagons manufactured primarily for the purpose of carrying passengers. This includes taxicabs, rental cars, and ambulances and hearses on an automobile chassis. Light-duty trucks refer to all two-axle four-tire vehicles other than passenger cars. They include pickup trucks, panel trucks, delivery and passenger vans, and other vehicles such as campers, motor homes, ambulances on a truck chassis, hearses on a truck chassis, and carryalls. In this study, light-duty trucks include four major types: (1) pickup truck, (2) van, (3) sport utility vehicle, and (4) other 2-axle 4-tire truck. Specifically, this project re-estimates statistics that appeared in Tables MV-1 and MV-9 of the 1995 Highway Statistics. Given the complexity of the approach developed in this effort and the incompleteness and inconsistency of the state-submitted data, it is recommended that alternatives be considered by FHWA to obtain vehicle registration data. One alternative is the Polk`s NVPP data (via the US Department of Transportation`s annual subscription to Polk). The second alternative is to obtain raw registration files from individual states` Departments of Motor Vehicles and to decode individual VINs.

  13. 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. PMID:26924277

  14. CSF protein biomarkers predicting longitudinal reduction of CSF β-amyloid42 in cognitively healthy elders

    PubMed Central

    Mattsson, N; Insel, P; Nosheny, R; Zetterberg, H; Trojanowski, J Q; Shaw, L M; Tosun, D; Weiner, M

    2013-01-01

    β-amyloid (Aβ) plaque accumulation is a hallmark of Alzheimer's disease (AD). It is believed to start many years prior to symptoms and is reflected by reduced cerebrospinal fluid (CSF) levels of the peptide Aβ1–42 (Aβ42). Here we tested the hypothesis that baseline levels of CSF proteins involved in microglia activity, synaptic function and Aβ metabolism predict the development of Aβ plaques, assessed by longitudinal CSF Aβ42 decrease in cognitively healthy people. Forty-six healthy people with three to four serial CSF samples were included (mean follow-up 3 years, range 2–4 years). There was an overall reduction in Aβ42 from a mean concentration of 211–195 pg ml−1 after 4 years. Linear mixed-effects models using longitudinal Aβ42 as the response variable, and baseline proteins as explanatory variables (n=69 proteins potentially relevant for Aβ metabolism, microglia or synaptic/neuronal function), identified 10 proteins with significant effects on longitudinal Aβ42. The most significant proteins were angiotensin-converting enzyme (ACE, P=0.009), Chromogranin A (CgA, P=0.009) and Axl receptor tyrosine kinase (AXL, P=0.009). Receiver-operating characteristic analysis identified 11 proteins with significant effects on longitudinal Aβ42 (largely overlapping with the proteins identified by linear mixed-effects models). Several proteins (including ACE, CgA and AXL) were associated with Aβ42 reduction only in subjects with normal baseline Aβ42, and not in subjects with reduced baseline Aβ42. We conclude that baseline CSF proteins related to Aβ metabolism, microglia activity or synapses predict longitudinal Aβ42 reduction in cognitively healthy elders. The finding that some proteins only predict Aβ42 reduction in subjects with normal baseline Aβ42 suggest that they predict future development of the brain Aβ pathology at the earliest stages of AD, prior to widespread development of Aβ plaques. PMID:23962923

  15. Antibody-Array-Based Proteomic Screening of Serum Markers in Systemic Lupus Erythematosus: A Discovery Study.

    PubMed

    Wu, Tianfu; Ding, Huihua; Han, Jie; Arriens, Cristina; Wei, Chungwen; Han, Weilu; Pedroza, Claudia; Jiang, Shan; Anolik, Jennifer; Petri, Michelle; Sanz, Ignacio; Saxena, Ramesh; Mohan, Chandra

    2016-07-01

    A discovery study was carried out where serum samples from 22 systemic lupus erythematosus (SLE) patients and matched healthy controls were hybridized to antibody-coated glass slide arrays that interrogated the level of 274 human proteins. On the basis of these screens, 48 proteins were selected for ELISA-based validation in an independent cohort of 28 SLE patients. Whereas AXL, ferritin, and sTNFRII were significantly elevated in patients with active lupus nephritis (LN) relative to SLE patients who were quiescent, other molecules such as OPN, sTNFRI, sTNFRII, IGFBP2, SIGLEC5, FAS, and MMP10 exhibited the capacity to distinguish SLE from healthy controls with ROC AUC exceeding 90%, all with p < 0.001 significance. These serum markers were next tested in a cohort of 45 LN patients, where serum was obtained at the time of renal biopsy. In these patients, sTNFRII exhibited the strongest correlation with eGFR (r = -0.50, p = 0.0014) and serum creatinine (r = 0.57, p = 0.0001), although AXL, FAS, and IGFBP2 also correlated with these clinical measures of renal function. When concurrent renal biopsies from these patients were examined, serum FAS, IGFBP2, and TNFRII showed significant positive correlations with renal pathology activity index, while sTNFRII displayed the highest correlation with concurrently scored renal pathology chronicity index (r = 0.57, p = 0.001). Finally, in a longitudinal cohort of seven SLE patients examined at ∼3 month intervals, AXL, ICAM-1, IGFBP2, SIGLEC5, sTNFRII, and VCAM-1 demonstrated the ability to track with concurrent disease flare, with significant subject to subject variation. In summary, serum proteins have the capacity to identify patients with active nephritis, flares, and renal pathology activity or chronicity changes, although larger longitudinal cohort studies are warranted. PMID:27211902

  16. Evaluation of choroidal thickness changes after phacoemulsification surgery

    PubMed Central

    Aslan Bayhan, Seray; Bayhan, Hasan Ali; Muhafiz, Ersin; Kırboğa, Kadir; Gürdal, Canan

    2016-01-01

    Purpose The aim of the study was to analyze the effects of uneventful phacoemulsification surgery on choroidal thickness (CT) using spectral domain optical coherence tomography (SD-OCT). Methods In this prospective study, 38 eyes of 38 patients having phacoemulsification surgery were included. All patients underwent detailed ophthalmologic examination, including preoperative axial length (AXL) measurement with optical biometry and intraocular pressure (IOP) measurement preoperatively and 1 month postoperatively. The CT was measured perpendicularly at the fovea and 1.5 mm temporal, 3.0 mm temporal, 1.5 mm nasal, and 3.0 mm nasal using SD-OCT preoperatively and 1 month postoperatively. Changes in the CT after surgery and correlation of this change with age, AXL, preoperative IOP, and IOP change were evaluated. Results There was a statistically significant increase in the CT at all regions evaluated. This increment was more prominent in the nasal and subfoveal regions. The IOP decreased significantly 1 month after surgery (16.14±4.94 mmHg vs 13.91±4.86 mmHg; P<0.001). The change in IOP was correlated with the CT changes at all regions, whereas age, AXL, and preoperative IOP had no significant correlations with the changes in CT. Conclusion Phacoemulsification surgery may cause significant increase in CT, which is correlated with surgery-induced IOP change in the short term. Long-term follow-up of eyes having phacoemulsification surgery may provide further insight into the effects of cataract surgery on the choroid. PMID:27307699

  17. Beyond Scheme F

    SciTech Connect

    Elliott, C.J.; Fisher, H.; Pepin, J.; Gillmann, R.

    1996-07-01

    Traffic classification techniques were evaluated using data from a 1993 investigation of the traffic flow patterns on I-20 in Georgia. First we improved the data by sifting through the data base, checking against the original video for questionable events and removing and/or repairing questionable events. We used this data base to critique the performance quantitatively of a classification method known as Scheme F. As a context for improving the approach, we show in this paper that scheme F can be represented as a McCullogh-Pitts neural network, oar as an equivalent decomposition of the plane. We found that Scheme F, among other things, severely misrepresents the number of vehicles in Class 3 by labeling them as Class 2. After discussing the basic classification problem in terms of what is measured, and what is the desired prediction goal, we set forth desirable characteristics of the classification scheme and describe a recurrent neural network system that partitions the high dimensional space up into bins for each axle separation. the collection of bin numbers, one for each of the axle separations, specifies a region in the axle space called a hyper-bin. All the vehicles counted that have the same set of in numbers are in the same hyper-bin. The probability of the occurrence of a particular class in that hyper- bin is the relative frequency with which that class occurs in that set of bin numbers. This type of algorithm produces classification results that are much more balanced and uniform with respect to Classes 2 and 3 and Class 10. In particular, the cancellation of errors of classification that occurs is for many applications the ideal classification scenario. The neural network results are presented in the form of a primary classification network and a reclassification network, the performance matrices for which are presented.

  18. State-of-the-art of small molecule inhibitors of the TAM family: the point of view of the chemist.

    PubMed

    Baladi, Tom; Abet, Valentina; Piguel, Sandrine

    2015-11-13

    The TAM family of tyrosine kinases receptors (Tyro3, Axl and Mer) is implicated in cancer development, autoimmune reactions and viral infection and is therefore emerging as an effective and attractive therapeutic target. To date, only a few small molecules have been intentionally designed to block the TAM kinases, while most of the inhibitors were developed for blocking different protein kinases and then identified through selectivity profile studies. This minireview will examine in terms of chemical structure the different compounds able to act on either one, two or three TAM kinases with details about structure-activity relationships, drug-metabolism and pharmacokinetics properties where they exist. PMID:26498569

  19. Hidden Markov Modeling for Weigh-In-Motion Estimation

    SciTech Connect

    Abercrombie, Robert K; Ferragut, Erik M; Boone, Shane

    2012-01-01

    This paper describes a hidden Markov model to assist in the weight measurement error that arises from complex vehicle oscillations of a system of discrete masses. Present reduction of oscillations is by a smooth, flat, level approach and constant, slow speed in a straight line. The model uses this inherent variability to assist in determining the true total weight and individual axle weights of a vehicle. The weight distribution dynamics of a generic moving vehicle were simulated. The model estimation converged to within 1% of the true mass for simulated data. The computational demands of this method, while much greater than simple averages, took only seconds to run on a desktop computer.

  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. 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

  2. Manganese-Aluminum-Based Magnets: Nanocrystalline t-MnAI Permanent Magnets

    SciTech Connect

    2012-01-01

    REACT Project: Dartmouth is developing specialized alloys with magnetic properties superior to the rare earths used in today’s best magnets. EVs and renewable power generators typically use rare earths to turn the axles in their electric motors due to the magnetic strength of these minerals. However, rare earths are difficult and expensive to refine. Dartmouth will swap rare earths for a manganese-aluminum alloy that could demonstrate better performance and cost significantly less. The ultimate goal of this project is to develop an easily scalable process that enables the widespread use of low-cost and abundant materials for the magnets used in EVs and renewable power generators.

  3. Low-Noise Spiral Bevel Gears

    NASA Technical Reports Server (NTRS)

    Lewicki, David G.; Handschuh, Robert F.; Coy, John J.; Henry, Zachary; Thomas, John; Litvin, Faydor L.

    1994-01-01

    Modified spiral bevel gears that generate relatively little noise and vibration designed and fabricated for use in U.S. Army OH-58D helicopter. Noise reduced by 12 to 19 dB. Similar low-noise, low-vibration spiral bevel gears used in other helicopters, with consequent benefits in comfort and health of pilots and passengers, enhancement of pilots' performance and safety through reduction of audible distraction, and reduction in cost and weight of helicopters through reduction in amount of sound-proofing material. Low-noise, low-vibration spiral bevel gears also used in drive axles of cars and trucks for smoother, quieter rides.

  4. Emerging role of CD300 receptors in regulating myeloid cell efferocytosis

    PubMed Central

    Voss, Oliver H; Tian, Linjie; Murakami, Yousuke; Coligan, John E; Krzewski, Konrad

    2015-01-01

    Engulfment of apoptotic cells is predominantly executed by phagocytes via the recognition of “eat me” signals like phosphatidylserine (PS). Various PS-specific receptors exist on phagocytes, including Tyro3, Axl, and MerTK receptor tyrosine kinases (TAMs), T-cell immunoglobulin and mucin domain containing 1 and 4 (TIM1/4), and the newly identified CD300 family. The aim of the present auto-commentary is to highlight recent findings regarding the Cd300lf and Cd300lb receptors and their emerging roles in the development of autoimmune disease. PMID:27308512

  5. Emerging role of CD300 receptors in regulating myeloid cell efferocytosis.

    PubMed

    Voss, Oliver H; Tian, Linjie; Murakami, Yousuke; Coligan, John E; Krzewski, Konrad

    2015-01-01

    Engulfment of apoptotic cells is predominantly executed by phagocytes via the recognition of "eat me" signals like phosphatidylserine (PS). Various PS-specific receptors exist on phagocytes, including Tyro3, Axl, and MerTK receptor tyrosine kinases (TAMs), T-cell immunoglobulin and mucin domain containing 1 and 4 (TIM1/4), and the newly identified CD300 family. The aim of the present auto-commentary is to highlight recent findings regarding the Cd300lf and Cd300lb receptors and their emerging roles in the development of autoimmune disease. PMID:27308512

  6. Active-Metal Template Synthesis of a Halogen-Bonding Rotaxane for Anion Recognition.

    PubMed

    Langton, Matthew J; Xiong, Yaoyao; Beer, Paul D

    2015-12-21

    The synthesis of an all-halogen-bonding rotaxane for anion recognition is achieved by using active-metal templation. A flexible bis-iodotriazole-containing macrocycle is exploited for the metal-directed rotaxane synthesis. Endotopic binding of a Cu(I) template facilitates an active-metal CuAAC iodotriazole axle formation reaction that captures the interlocked rotaxane product. Following copper-template removal, exotopic coordination of a more sterically demanding rhenium(I) complex induces an inversion in the conformation of the macrocycle component, directing the iodotriazole halogen-bond donors into the rotaxane's interlocked binding cavity to facilitate anion recognition. PMID:26500150

  7. Weight Control for Highway Trucking

    NASA Technical Reports Server (NTRS)

    1984-01-01

    LODEC, Inc. scales use load cell technology, a spinoff from aerospace technology, in manufacturing electronic axle scales for weighing trucks and trailers to insure that they are within legal highway limits. The scales trace their origin to the space program of the 1960's when ELDEC Corporation, then LODEC parent company, acquired advanced electronic technology as a subcontractor on such projects as Apollo and Saturn launch vehicles. LODEC scales come in both permanent and portable versions with accuracy of within one percent and frequently better.

  8. Active‐Metal Template Synthesis of a Halogen‐Bonding Rotaxane for Anion Recognition

    PubMed Central

    Langton, Matthew J.; Xiong, Yaoyao

    2015-01-01

    Abstract The synthesis of an all‐halogen‐bonding rotaxane for anion recognition is achieved by using active‐metal templation. A flexible bis‐iodotriazole‐containing macrocycle is exploited for the metal‐directed rotaxane synthesis. Endotopic binding of a CuI template facilitates an active‐metal CuAAC iodotriazole axle formation reaction that captures the interlocked rotaxane product. Following copper‐template removal, exotopic coordination of a more sterically demanding rhenium(I) complex induces an inversion in the conformation of the macrocycle component, directing the iodotriazole halogen‐bond donors into the rotaxane’s interlocked binding cavity to facilitate anion recognition. PMID:26500150

  9. Light-powered autonomous and directional molecular motion of a dissipative self-assembling system.

    PubMed

    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. PMID:25420035

  10. 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.

  11. 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.

  12. Structural analysis in real time using continuous monitoring

    NASA Astrophysics Data System (ADS)

    Braunstein, Juergen; Viano, Charles; Hodac, Bernard

    2005-05-01

    OSMOS developed a completely automatic monitoring-system, which is ideal for the determination and monitoring of the structural state of civil engineering structures. Static and dynamic data are recorded as needed and are available via internet for further analysis. In case of bridges, automatic calculation of the axle load of the flowing traffic is implemented, a weigh in motion system (WIMS). When configurable thresholds are exceeded alarms are sent by SMS, e-mail, SNMP-trap for facility-management-systems or by fax.

  13. 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.

  14. 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

  15. Power transmission casing apparatus in motorized two-wheeled vehicle

    SciTech Connect

    Kurata, N.; Miyazaki, K.; Yamamoto, K.

    1985-02-12

    A power transmission casing apparatus in a motorized two-wheeled vehicle which comprises a case main body extending from one lateral side of an internal combustion engine to one lateral side of a rear wheel in rear thereof and supporting rotatably a wheel axle of the rear wheel. The case main body is applied with a cover member for containing therein liquid-tightly a reduction gear means, and is applied with another cover member for containing therein a V-belt means.

  16. Fatalities associated with improper hitching to farm tractors--New York, 1991-1995.

    PubMed

    1996-04-19

    Approximately half of all injury-related fatalities in the agricultural industry are associated with farm tractors (1). Since April 1991, the New York State Department of Health's Occupational Health Nurses in Agricultural Communities (OHNAC) program has investigated 27 incidents of sudden rear rollover of farm tractors (i.e., incidents in which the tractor flips backward, rotating around its rear axle); these incidents resulted in 15 fatalities. This report describes four of these incidents, summarizes the characteristics of the 16 incidents that involved improper hitching, and outlines strategies for reducing the risk for their occurrence. PMID:8602129

  17. Effect of molybdenum-containing, oil-soluble friction modifiers on engine fuel economy and gear oil efficiency

    SciTech Connect

    Greene, A.B.; Risdon, T.J.

    1981-01-01

    A selection of molybdenum-containing, oil-soluble friction modifier additives was tested comparatively in engine dynamometer tests on gasoline and diesel engines; the tests measured variations in brake specific fuel consumption with speed. A similar selection of molybdenum-containing additives was evaluated in terms of transmission efficiency in a hypoid-gear, rear-axle test rig; the baseline oil was a formulated SAE-75W gear oil. Bench-scale friction tests utilizing the Press-Fit, Timken and Four-Ball test devices were employed to establish a correlation between small-scale rigs and full-scale engine tests. 13 refs.

  18. Tank truck vehicle for transporting fluid or pulverous material, particularly oil

    SciTech Connect

    Hirvonen, R.

    1982-04-20

    A tank truck vehicle for transporting fluid or pulverous material, such as oil, comprises in one embodiment a longitudinally extending tubular shell whose length is substantially that of the truck vehicle and which is formed so as to be sufficiently rigid so as to function both as the wall of the transporting container of the vehicle and, simultaneously, as the supporting frame for the vehicle so that there is no need for a supporting beam frame separate from the supporting tank as is conventional. The front and rear wheels are mounted on axle assemblies which are substantially directly connected to the tubular shell.

  19. 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.

  20. EXT-II: a second generation advanced ac propulsion system

    SciTech Connect

    Bates, B.; Patil, P.B.; Ciccarelli, M.F.

    1986-01-01

    This paper discusses the characteristics of the concept and includes discussion of the system constraints, including traction battery constraints, and brief descriptions of the major subsystems being developed. The components discussed include: the system controller, dc to ac inverter, an internal permanent magnet ac motor and a two-speed automatic transmission with an integral final drive and differential. The motor and transmission are on a common axis and are integrated into one compact unit that is integral with the rear axle of the vehicle.

  1. 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.

  2. Reliability-based robust design optimization of vehicle components, Part II: Case studies

    NASA Astrophysics Data System (ADS)

    Zhang, Yimin

    2015-06-01

    The reliability-based optimization, the reliability- based sensitivity analysis and robust design method are employed to propose an effective approach for reliability-based robust design optimization of vehicle components in Part I. Applications of the method are further discussed for reliability-based robust optimization of vehicle components in this paper. Examples of axles, torsion bar, coil and composite springs are illustrated for numerical investigations. Results have shown the proposed method is an efficient method for reliability-based robust design optimization of vehicle components.

  3. 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

  4. [Life and work at the petroleum industry in Campos Basin].

    PubMed

    Leite, Rose Mery dos Santos Costa

    2009-01-01

    In this paper we detach the subject of confinement as a central axle in the activity at maritime oil platforms of Campos Basin, in north region of the Rio de Janeiro state. This work reality that determines for offshore workers, as they are known, a rupture between two different moments in there lives: the period of fourteen days in the sea and the life in land per twenty one days. We adopt as material empiricist, the research carried out on this universe, detaching here the way as these professionals understand the conditions of confined work in which they are submitted. PMID:20069186

  5. Photovoltaic panel clamp

    DOEpatents

    Mittan, Margaret Birmingham; Miros, Robert H. J.; Brown, Malcolm P.; Stancel, Robert

    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.

  6. 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.

  7. 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.

  8. Review of some results of the author's fatigue investigations with applications in engineering and material science

    NASA Astrophysics Data System (ADS)

    Buch, A.

    1994-04-01

    This document deals with research results mainly connected with the problem of fatigue calculations and various aspects of fatigue. It contains the following topics: Correlation between fatigue limits and ultimate tensile strength, Fatigue properties of pure metals, Analytical approach to notch-size effects in fatigue of aircraft sheet materials, Torsional fatigue life of axle shafts under program loading, Fatigue properties of aircraft lugs with interference fit, Comparison of various aircraft loading test results with the aid of Relative-Miner-Rule, The Relative Method in the case of Local-Strain-Approach, and Prediction of fatigue life.

  9. Automated-In-Motion Vehicle Evaluation Environment (AIMVEE)

    Energy Science and Technology Software Center (ESTSC)

    2006-05-04

    The AIMVEE/WIM system electronically retrieves deployment information, identifies vehicle automatically, and determines total weight, individual wheel weight, individual axle weights, axle spacing, and center-of-balance for any wheeled vehicle in motion. The AIMVEE/WIM system can also perform these functions statically for both wheel vehicles and cargo with information. The AIMVEE/WIM system incorporates digital images and applies cubing algorithms to determine length, width, height for cubic dimensions of both vehicle and cargo. Once all this information ismore » stored, it electronically links to data collection and dissemination systems to provide “actual” weight and measurement information for planning, deployment, and in-transit visibility. The Static Scale Conversion (SSC) system is an unique enhancement to the AIMVEE/WIM system. It enables a SSC to weigh and measure vehicles and cargo dynamically (i.e., as they pass over the large scale and is included in the AIMVEE computer code base. The material to be copyrighted is the Automated-In-Motion Vehicle Evaluation Environment (AIMVEE)/Weigh-In-Motion User Training and Testing material. It includes instructional material in the set-up, operation and tear-down of the AIMVEE/WIM system. It also includes a final exam associated with the training.« less

  10. Automated-In-Motion Vehicle Evaluation Environment (AIMVEE) Weigh-In Motion (WIM) User Training and Testing

    Energy Science and Technology Software Center (ESTSC)

    2006-05-04

    The AIMVEE/WIM system electronically retrieves deployment information, identifies vehicle automatically, and determines total weight, individual wheel weight, individual axle weights, axle spacing, and center-of-balance for any wheeled vehicle in motion. The AIMVEE/WIM system can also perform these functions statically for both wheel vehicles and cargo with information. The AIMVEE/WIM system incorporates digital images and applies cubing algorithms to determine length, width, height for cubic dimensions of both vehicle and cargo. Once all this information ismore » stored, it electronically links to data collection and dissemination systems to provide “actual” weight and measurement information for planning, deployment, and in-transit visibility. The Static Scale Conversion (SSC) system is an unique enhancement to the AIMVEE/WIM system. It enables a SSC to weigh and measure vehicles and cargo dynamically (i.e., as they pass over the large scale and is included in the AIMVEE computer code base. The material to be copyrighted is the Automated-In-Motion Vehicle Evaluation Environment (AIMVEE)/Weigh-In-Motion User Training and Testing material. It includes instructional material in the set-up, operation and tear-down of the AIMVEE/WIM system. It also includes a final exam associated with the training.« less

  11. ORNL Automated-In-Motion Evaluation Environment (AIMVEE) User Training and Testing Materials - U.S. Copyright TXu 1-797-273

    SciTech Connect

    Abercrombie, Robert K; Sheldon, Frederick T

    2012-01-01

    The AIMVEE/WIM system electronically retrieves deployment information, identifies vehicle automatically, and determines total weight, individual wheel weight, individual axle weights, axle spacing, and center-of-balance for any wheeled vehicle in motion. The AIMVEE/WIM system can also perform these functions statically for both wheel vehicles and cargo with information. The AIMVEE/WIM system incorporates digital images and applies cubing algorithms to determine length, width, height for cubic dimensions of both vehicle and cargo. Once all this information is stored, it electronically links to data collection and dissemination systems to provide actual weight and measurement information for planning, deployment, and in-transit visibility. The Static Scale Conversion (SSC) system is an unique enhancement to the AIMVEE/WIM system. It enables a SSC to weigh and measure vehicles and cargo dynamically (i.e., as they pass over the large scale and is included in the AIMVEE computer code base. The material copyrighted is the ORNL Automated-In-Motion Vehicle Evaluation Environment (AIMVEE)/Weigh-In-Motion User Training and Testing material. It includes instructional material in the set-up, operation and tear-down of the AIMVEE/WIM system. It also includes a final exam associated with the training.

  12. 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

  13. Multifunctional Aptamer-miRNA Conjugates for Targeted Cancer Therapy

    PubMed Central

    Esposito, Carla L; Cerchia, Laura; Catuogno, Silvia; De Vita, Gennaro; Dassie, Justin P; Santamaria, Gianluca; Swiderski, Piotr; Condorelli, Gerolama; Giangrande, Paloma H; de Franciscis, Vittorio

    2014-01-01

    While microRNAs (miRNAs) clearly regulate multiple pathways integral to disease development and progression, the lack of safe and reliable means for specific delivery of miRNAs to target tissues represents a major obstacle to their broad therapeutic application. Our objective was to explore the use of nucleic acid aptamers as carriers for cell-targeted delivery of a miRNA with tumor suppressor function, let-7g. Using an aptamer that binds to and antagonizes the oncogenic receptor tyrosine kinase Axl (GL21.T), here we describe the development of aptamer-miRNA conjugates as multifunctional molecules that inhibit the growth of Axl-expressing tumors. We conjugated the let-7g miRNA to GL21.T and demonstrate selective delivery to target cells, processing by the RNA interference machinery, and silencing of let-7g target genes. Importantly, the multifunctional conjugate reduced tumor growth in a xenograft model of lung adenocarcinoma. Therefore, our data establish aptamer-miRNA conjugates as a novel tool for targeted delivery of miRNAs with therapeutic potential. PMID:24441398

  14. 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. PMID:23126453

  15. 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.

  16. 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

  17. Ride dynamic evaluations and design optimisation of a torsio-elastic off-road vehicle suspension

    NASA Astrophysics Data System (ADS)

    Pazooki, Alireza; Cao, Dongpu; Rakheja, Subhash; Boileau, Paul-Émile

    2011-09-01

    The ride dynamic characteristics of a novel torsio-elastic suspension for off-road vehicle applications are investigated through field measurements and simulations. A prototype suspension was realised and integrated within the rear axle of a forestry skidder for field evaluations. Field measurements were performed on forestry terrains at a constant forward speed of 5 km/h under the loaded and unloaded conditions, and the ride responses were acquired in terms of accelerations along the vertical, lateral, roll, longitudinal and pitch axes. The measurements were also performed on a conventional skidder to investigate the relative ride performance potentials of the proposed suspension. The results revealed that the proposed suspension could yield significant reductions in magnitudes of transmitted vibration to the operator seat. Compared with the unsuspended vehicle, the prototype suspended vehicle resulted in nearly 35%, 43% and 57% reductions in the frequency-weighted rms accelerations along the x-, y- and z-axis, respectively. A 13-degree-of-freedom ride dynamic model of the vehicle with rear-axle torsio-elastic suspension was subsequently derived and validated in order to study the sensitivity of the ride responses to suspension parameters. Optimal suspension parameters were identified using the Pareto technique based on the genetic algorithm to obtain minimal un-weighted and frequency-weighted rms acceleration responses. The optimal solutions resulted in further reduction in the pitch acceleration in the order of 20%, while the reductions in roll and vertical accelerations ranged from 3.5 to 6%.

  18. Automated-In-Motion Vehicle Evaluation Environment (AIMVEE)

    SciTech Connect

    Abercrombie, Robert K.; Sheldon, Frederick T.

    2006-05-04

    The AIMVEE/WIM system electronically retrieves deployment information, identifies vehicle automatically, and determines total weight, individual wheel weight, individual axle weights, axle spacing, and center-of-balance for any wheeled vehicle in motion. The AIMVEE/WIM system can also perform these functions statically for both wheel vehicles and cargo with information. The AIMVEE/WIM system incorporates digital images and applies cubing algorithms to determine length, width, height for cubic dimensions of both vehicle and cargo. Once all this information is stored, it electronically links to data collection and dissemination systems to provide “actual” weight and measurement information for planning, deployment, and in-transit visibility. The Static Scale Conversion (SSC) system is an unique enhancement to the AIMVEE/WIM system. It enables a SSC to weigh and measure vehicles and cargo dynamically (i.e., as they pass over the large scale and is included in the AIMVEE computer code base. The material to be copyrighted is the Automated-In-Motion Vehicle Evaluation Environment (AIMVEE)/Weigh-In-Motion User Training and Testing material. It includes instructional material in the set-up, operation and tear-down of the AIMVEE/WIM system. It also includes a final exam associated with the training.

  19. Automated-In-Motion Vehicle Evaluation Environment (AIMVEE) Weigh-In Motion (WIM) User Training and Testing

    SciTech Connect

    2006-05-04

    The AIMVEE/WIM system electronically retrieves deployment information, identifies vehicle automatically, and determines total weight, individual wheel weight, individual axle weights, axle spacing, and center-of-balance for any wheeled vehicle in motion. The AIMVEE/WIM system can also perform these functions statically for both wheel vehicles and cargo with information. The AIMVEE/WIM system incorporates digital images and applies cubing algorithms to determine length, width, height for cubic dimensions of both vehicle and cargo. Once all this information is stored, it electronically links to data collection and dissemination systems to provide “actual” weight and measurement information for planning, deployment, and in-transit visibility. The Static Scale Conversion (SSC) system is an unique enhancement to the AIMVEE/WIM system. It enables a SSC to weigh and measure vehicles and cargo dynamically (i.e., as they pass over the large scale and is included in the AIMVEE computer code base. The material to be copyrighted is the Automated-In-Motion Vehicle Evaluation Environment (AIMVEE)/Weigh-In-Motion User Training and Testing material. It includes instructional material in the set-up, operation and tear-down of the AIMVEE/WIM system. It also includes a final exam associated with the training.

  20. 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.

  1. Vorticity amplification near the stagnation point of landing gear wheels: effect of the orientation of the impinging vorticity

    NASA Astrophysics Data System (ADS)

    Gu, Mingyao; Feltham, Graham; Ekmekci, Alis

    2014-11-01

    When oncoming streams of weak vorticity aligned with the axle axis of a two-wheel landing gear impinge near the forward stagnation point of the wheels, a mechanism for vorticity collection, growth, amplification into discrete large-scale vortices, and shedding was formerly shown to exist. In the current study, the impinging vorticity streams are perpendicular to the axle axis, i.e. in a vertical orientation as opposed to the horizontal orientation before. Experiments are conducted in a recirculating water channel using hydrogen bubble visualization and particle image velocimetry at a Reynolds number of 32,500 (based on the wheel diameter). As with the horizontal orientation, vorticity collection and amplification are observed, but the large-scale vortices thus formed are stretched around the wheel circumference in contrast to being stretched around the wheel sides, as observed for the horizontal orientation. This flow behavior varies with the impingement location of the vorticity streams across the wheel width. Maximum vorticity amplification occurs at a critical impingement location and drastically alters the flow separation along the wheel circumference. In addition, the instantaneous vortical structures are identified and tracked using a Galilean-invariant criterion.

  2. Flow Visualization around a Simplified Two-Wheel Landing Gear

    NASA Astrophysics Data System (ADS)

    Ekmekci, Alis; Feltham, Graham

    2013-11-01

    The flow topology around a simplified two-wheel landing gear model is investigated experimentally by employing the hydrogen bubble flow visualization technique in a recirculating water channel. The landing gear test model consists of two identical wheels, an axle, a main strut and a support strut. The flow Reynolds number based on wheel diameter is 31,500 and wheels with varying geometric details are considered. Flow structures have been identified through analysis of long-time video recordings and linked to the model geometry. In the flow region above the wheels (wing side), the flow in the inter-wheel region either separates prematurely from the inner surfaces of the wheels and forms slant vortices in the near-wake, or remains attached till the aft wheel perimeter. Inclusion of interior wheel wells are found to result in a jet-like ejection as a result of the interaction with the axle and main strut. In the flow region below the wheels (ground side) the near wake contains periodically forming, complex, large-scale structures.

  3. Landing-gear noise prediction using high-order finite difference schemes

    NASA Astrophysics Data System (ADS)

    Liu, Wen; Wook Kim, Jae; Zhang, Xin; Angland, David; Caruelle, Bastien

    2013-07-01

    Aerodynamic noise from a generic two-wheel landing-gear model is predicted by a CFD/FW-H hybrid approach. The unsteady flow-field is computed using a compressible Navier-Stokes solver based on high-order finite difference schemes and a fully structured grid. The calculated time history of the surface pressure data is used in an FW-H solver to predict the far-field noise levels. Both aerodynamic and aeroacoustic results are compared to wind tunnel measurements and are found to be in good agreement. The far-field noise was found to vary with the 6th power of the free-stream velocity. Individual contributions from three components, i.e. wheels, axle and strut of the landing-gear model are also investigated to identify the relative contribution to the total noise by each component. It is found that the wheels are the dominant noise source in general. Strong vortex shedding from the axle is the second major contributor to landing-gear noise. This work is part of Airbus LAnding Gear nOise database for CAA validatiON (LAGOON) program with the general purpose of evaluating current CFD/CAA and experimental techniques for airframe noise prediction.

  4. Analysis of bifurcation and stability for a tractor semi-trailer in planar motion

    NASA Astrophysics Data System (ADS)

    Ding, Nenggen; Shi, Xiaobo; Zhang, Yipeng; Chen, Wen

    2014-12-01

    This paper is intended for bifurcation analysis of a nonlinear tractor semi-trailer vehicle model in planar motion and for investigating its stability under constant running conditions. Bifurcation analysis shows that bifurcation diagrams of a tractor semi-trailer are quite different from those of a single-unit vehicle. Some instability phenomena of the vehicle system such as jackknifing, sideslip, and spinning are explained by correlating them with the behaviour in the neighbourhood of unstable fixed points based on analysis of eigenvectors, phase trajectories, and status of lateral tyre force saturation. It is also found that yaw planar instability of a tractor semi-trailer is caused by lateral tyre force saturation of the tractor's rear axles and/or the trailer's axles. Moreover, the stability region in the state space is demarcated, and a stability index for evaluating size of the stability region in a feasible domain is proposed. Yaw stability under constant driving conditions is analysed by using the proposed stability index.

  5. 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

    2013-01-01

    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

  6. Top-of-Rail lubricant

    SciTech Connect

    Alzoubi, M. F.; Fenske, G. R.; Erck, R. A.; Boparai, A. S.

    2000-07-14

    Analysis of the volatile and semivolatile fractions collected after use of the TOR lubricant indicated that other than contaminants in the collection laboratory, no compounds on the EPA's Target Compound Lists (Tables 2 and 5) were detected in these fractions. The data of these qualitative analyses, given in the various tables in the text, indicate only the relative amounts of the tentatively identified compounds. The authors recommend that quantitative analysis be performed on the volatile and semivolatile fractions to allow confirmation of the tentatively identified compounds and to obtain absolute amounts of the detected compounds. Additionally, the semivolatile fraction should be analyzed by liquid chromatography/mass spectrometry to identify compounds that are not chromatographable under the temperature program used for determination of semivolatile compounds. Introducing the top-of-rail (TOR) lubricant into the wheel/rail interface results in a reduction of almost 60% of lateral friction force over the forces encountered under dry conditions. This reveals good potential for energy savings, as well as wear reduction, for railroad companies. In TOR lubrication, an increase in the angle of attack and axle load results in increased lateral friction and rate of lubricant consumption. The most efficient TOR lubricant quantity to be used in the wheel/rail interface must be calculated precisely according to the number of cars, axle loads, train speed, and angle of attack.

  7. 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. PMID:26523970

  8. 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.

  9. Mesenchymal Cancer Cell-Stroma Crosstalk Promotes Niche Activation, Epithelial Reversion, and Metastatic Colonization

    PubMed Central

    del Pozo Martin, Yaiza; Park, Danielle; Ramachandran, Anassuya; Ombrato, Luigi; Calvo, Fernando; Chakravarty, Probir; Spencer-Dene, Bradley; Derzsi, Stefanie; Hill, Caroline S.; Sahai, Erik; Malanchi, Ilaria

    2015-01-01

    Summary During metastatic colonization, tumor cells must establish a favorable microenvironment or niche that will sustain their growth. However, both the temporal and molecular details of this process remain poorly understood. Here, we found that metastatic initiating cells (MICs) exhibit a high capacity for lung fibroblast activation as a result of Thrombospondin 2 (THBS2) expression. Importantly, inhibiting the mesenchymal phenotype of MICs by blocking the epithelial-to-mesenchymal transition (EMT)-associated kinase AXL reduces THBS2 secretion, niche-activating ability, and, consequently, metastatic competence. Subsequently, disseminated metastatic cells revert to an AXL-negative, more epithelial phenotype to proliferate and decrease the phosphorylation levels of TGF-β-dependent SMAD2-3 in favor of BMP/SMAD1-5 signaling. Remarkably, newly activated fibroblasts promote this transition. In summary, our data reveal a crosstalk between cancer cells and their microenvironment whereby the EMT status initially triggers and then is regulated by niche activation during metastatic colonization. PMID:26670048

  10. 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.

  11. Static Scale Conversion (SSC)

    SciTech Connect

    2007-01-19

    The Static Scale Conversion (SSC) software is a unique enhancement to the AIMVEE system. It enables a SSC to weigh and measure vehicles and cargo dynamically (i.e., as they pass over the large scale. Included in the software is the AIMVEE computer code base. The SSC and AIMVEE computer system electronically continue to retrieve deployment information, identify vehicle automatically and determine total weight, individual axle weights, axle spacing and center-of-balance for any wheeled vehicle in motion. The AIMVEE computer code system can also perform these functions statically for both wheel vehicles and cargo with information. The AIMVEE computer code system incorporates digital images and applies cubing algorithms to determine length, width, height for cubic dimensions of both vehicle and cargo. Once all this information is stored, it electronically links to data collection and dissemination systems to provide “actual” weight and measurement information for planning, deployment, and in-transit visibility.

  12. Waveband Analysis of Track Irregularities in High-Speed Railway from On-Board Acceleration Measurement

    NASA Astrophysics Data System (ADS)

    Lee, Jun Seok; Choi, Sunghoon; Kim, Sang-Soo; Kim, Young Guk; Kim, Seog Won; Park, Choonsoo

    This paper is focused on waveband analysis of the lateral and vertical track irregularities from the on-board acceleration measurement of in-service high-speed trains. The track irregularities play important roles to determine dynamic stability of vehicles and ride quality of passengers, so that their amplitude and wavelength should be monitored continuously and carefully. Measuring acceleration at the axle-box or bogie of the trains has been under consideration for low-cost implementation and robust to a harsh railway environment. To estimate the track irregularities, lateral and vertical vibration caused by the wheel/track interaction is measured by the axle-box and bogie mounted accelerometers of an in-service high-speed train. A Kalman filter is used to prevent unrealistic drifts in the estimation. By applying the waveband-pass and compensation filters to the estimated displacement, it is possible to estimate the track irregularities. A distance-wavelength representation is used to identify their waveband in an intuitive way. It is verified by comparing with a commercial track geometry measurement system. From their comparison, it confirms that the representation can produce a satisfactory result.

  13. Receptor tyrosine kinase expression of circulating tumor cells in small cell lung cancer

    PubMed Central

    Hamilton, Gerhard; Rath, Barbara; Klameth, Lukas; Hochmair, Maximilian

    2015-01-01

    Small cell lung cancer (SCLC) has a poor prognosis and is found disseminated at first presentation in the majority of cases. The cell biological mechanisms underlying metastasis and drug resistance are not clear. SCLC is characterized by high numbers of circulating tumor cells (CTCs) and we were able to expand several CTC lines ex vivo and to relate chitinase-3-like-1/YKL-40 (CHI3L1) as marker. Availability of expanded SCLC CTC cells allowed for a screening of receptor tyrosine kinases (RTKs) expressed. The metastatic CHI3L1-negative SCLC cell line SCLC26A, established from a pleural effusion was used for comparison. The CTC cell line BHGc10 was found to exhibit increased expression of RYK, AXL, Tie-1, Dtk, ROR1/2, several ephrins (Eph) and FGF/EGF receptors compared to SCLC26A. All of these RTKs have been associated with cell motility, invasion and poor prognosis in diverse cancer entities without knowledge of their association with CTCs. The identification of RYK, AXL and ROR1/2 as pseudokinases, lacking activity, seems to be related to the observed failure of RTK inhibitors in SCLC. These kinases are involved in the noncanonical WNT pathway and their expression in SCLC CTCs represents a cancer stem cell-like phenotype. PMID:26328272

  14. Flexibility within the Rotor and Stators of the Vacuolar H+-ATPase

    PubMed Central

    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. PMID:24312643

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

    PubMed Central

    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.

    2015-01-01

    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 down-regulation 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 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 IFN-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. PMID:26523970

  16. Mechanically Interlocked Linkers inside Metal-Organic Frameworks: Effect of Ring Size on Rotational Dynamics.

    PubMed

    Vukotic, V Nicholas; O'Keefe, Christopher A; Zhu, Kelong; Harris, Kristopher J; To, Christine; Schurko, Robert W; Loeb, Stephen J

    2015-08-01

    A series of metal-organic framework (MOF) materials has been prepared, each containing a mechanically interlocked molecule (MIM) as the linker and a copper(II) paddlewheel as the secondary building unit (SBU). The MIM linkers are [2]rotaxanes with varying sizes of crown ether macrocycles ([22]crown-6, 22C6; [24]crown-6, 24C6; [26]crown-6, 26C6; benzo[24]crown-6, B24C6) and an anilinium-based axle containing four carboxylate donor groups. Herein, the X-ray structures of MOFs UWCM-1 (no crown) and UWDM-1(22) are compared and demonstrate the effect of including a macrocycle around the axle of the linker. The rotaxane linkers are linear and result in nbo-type MOFs with void space that allows for motion of the interlocked macrocycle inside the MOF pores, while the macrocycle-free linker is bent and yields a MOF with a novel 12-connected bcc structure. Variable temperature (2)H solid-state nuclear magnetic resonance showed that the macrocycles in UWDM-1(22), UWDM-1(24), and UWDM-1(B24) undergo different degrees and rates of rotation depending on the size and shape of the macrocycle. PMID:26175343

  17. 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. PMID:25877552

  18. Organic Nanofibers Embedding Stimuli-Responsive Threaded Molecular Components

    PubMed Central

    2014-01-01

    While most of the studies on molecular machines have been performed in solution, interfacing these supramolecular systems with solid-state nanostructures and materials is very important in view of their utilization in sensing components working by chemical and photonic actuation. Host polymeric materials, and particularly polymer nanofibers, enable the manipulation of the functional molecules constituting molecular machines and provide a way to induce and control the supramolecular organization. Here, we present electrospun nanocomposites embedding a self-assembling rotaxane-type system that is responsive to both optical (UV–vis light) and chemical (acid/base) stimuli. The system includes a molecular axle comprised of a dibenzylammonium recognition site and two azobenzene end groups and a dibenzo[24]crown-8 molecular ring. The dethreading and rethreading of the molecular components in nanofibers induced by exposure to base and acid vapors, as well as the photoisomerization of the azobenzene end groups, occur in a similar manner to what observed in solution. Importantly, however, the nanoscale mechanical function following external chemical stimuli induces a measurable variation of the macroscopic mechanical properties of nanofibers aligned in arrays, whose Young’s modulus is significantly enhanced upon dethreading of the axles from the rings. These composite nanosystems show therefore great potential for application in chemical sensors, photonic actuators, and environmentally responsive materials. PMID:25264943

  19. Portable walking beam pump jack

    SciTech Connect

    Laney, R.N.

    1986-02-25

    This patent describes a portable walking beam pump jack for use in pumping liquids from an oil well. This jack consists of: an elongated frame having a longitudinal axis and front and rear ends, the frame also including first and second support seats; a towing receptacle, an axle connected transversely across the frame; ground engaging wheels connected to the axle for supporting the frame for rolling transportation; stabilizing means for securing the frame with respect to a ground location; a walking beam having a first end, a midportion and a second end, the second end being adapted for connection to a pumping rod; an engine mounted on the frame; a pair of arms counterweighted for balancing a pumping rod connected to the walking beam, a drive yoke, a support assembly foldably mounted on the frame and upon which the midportion of the walking beam is pivotally connected, the support assembly the arms and the drive yoke being foldable together, from a first, fixed position in which the walking beam arms and yoke are supported in a raised position for rocking in a pumping motion to a second, fixed position disposed downwardly and forwardly from the first fixed position and in which the walking beam arms and yoke are held in a lowered position for transportation; a front support and a hydraulic cylinder connected between the frame and the support assembly for moving the support assembly between the first, fixed position and the second fixed position.

  20. Dynamic pavement deflection

    NASA Astrophysics Data System (ADS)

    Rand, D. W.; Jacobs, K. M.

    1981-06-01

    Dynamic pavement deflection measurements for bituminous concrete pavements of two and three-quarter, five and seven-eights, and seven and one-half inches in thickness under moving axle loads of 15,000, 18,000, and 22,000 pounds were obtained at speeds of 10, 25 and 45 miles per hour. The results were analyzed and compared to Benkelman beam measurements. The data indicate that slow moving loads have greater adverse effect (larger deflections) on the pavement than the high speed loads. The results also show that the bituminous pavement undergoes numerous vertical fluctuations and bending as the front and rear axles approached the point of measurement. The magnitude of the vertical displacement was measured via the means of an accelerometer and double integrator. When values of the dynamic deflections were in the magnitude of 0.07 through 0.10 inches, there was evidence of pavement failure. When the deflection values were above 0.10 inches pavement failures were distinct.

  1. 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. PMID:10080099

  2. Optimal design of active and semi-active suspensions including time delays and preview

    NASA Astrophysics Data System (ADS)

    Hac', A.; Youn, I.

    1993-10-01

    Several control laws for active and semi-active suspension based on a linear half car model are derived and investigated. The strategies proposed take full advantage of the fact that the road input to the rear wheels is a delayed version of that to the front wheels, which in turn can be obtained either from the measurements of the front wheels and body motions or by direct preview of road irregularities if preview sensors are available. The suspension systems are optimized with respect to ride comfort, road holding and suspension rattle space as expressed by the mean-square-values of body acceleration (including effects of heave and pitch), tire deflections and front and rear suspension travels. The optimal control laws that minimize the given performance index and include passivity constraints in the semi-active case are derived using calculus of variation. The optimal semi-active suspension becomes piecewise linear, varying between passive and fully active systems and combinations of them. The performances of active and semi-active systems with and without preview were evaluated by numerical simulation in the time and frequency domains. The results show that incorporation of time delay between the front and rear axles in controller design improves the dynamic behavior of the rear axle and control of body pitch motion, while additional preview improves front wheel dynamics and body heave.

  3. Viscous coupling apparatus for on-demand four wheel drive system

    SciTech Connect

    Eastman, R.E.; Varma, S.K.

    1987-03-17

    A viscous fluid rear axle coupling apparatus is described for a front engine drive vehicle having front and rear pairs of road wheels. The vehicle has a front transaxle including differential means drivingly interconnected to the front pair of wheels; and a longitudinally extending propeller shaft having its forward end drivingly connected to the transaxle differential means. The propeller shaft has right-angle power transfer means adjacent to its aft end adapted to receive engine torque from the front differential, the right angle power transfer means comprising in part a crown gear fixedly secured to a viscous coupling apparatus. The improvement described here is wherein the apparatus comprises a viscous coupling casing having a pair of right and left outboard end cover plates closing the ends of a cylindrical outer drum defining a sealed viscous fluid chamber, one of the cover plates removably fastened to the crown gear. The power transfer means is adapted to convert the rotation of the propeller shaft into rotation of the outer drum about a transverse axis coincident with rear axle means, the outer drum concentrically surrounding a pair of coaxial right and left inner drums. The right and left inner drums are fixedly connected to respective coaxial right and left transverse output shafts such that the inner drums rotate relative to each other and to the outer drum.

  4. 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.

  5. Static Scale Conversion (SSC)

    Energy Science and Technology Software Center (ESTSC)

    2007-01-19

    The Static Scale Conversion (SSC) software is a unique enhancement to the AIMVEE system. It enables a SSC to weigh and measure vehicles and cargo dynamically (i.e., as they pass over the large scale. Included in the software is the AIMVEE computer code base. The SSC and AIMVEE computer system electronically continue to retrieve deployment information, identify vehicle automatically and determine total weight, individual axle weights, axle spacing and center-of-balance for any wheeled vehicle inmore » motion. The AIMVEE computer code system can also perform these functions statically for both wheel vehicles and cargo with information. The AIMVEE computer code system incorporates digital images and applies cubing algorithms to determine length, width, height for cubic dimensions of both vehicle and cargo. Once all this information is stored, it electronically links to data collection and dissemination systems to provide “actual” weight and measurement information for planning, deployment, and in-transit visibility.« less

  6. 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.

  7. The idiosyncrasies of (BBIM-alkane)DB30C10 MIMs

    NASA Astrophysics Data System (ADS)

    Ghosh, Sabari; Chaudhuri, Tandrima; Padmanaban, E.; Mukhopadhyay, Chhanda

    2015-10-01

    In this present study we explore the mechanically interlocked molecules (MIMs) resulting from the combination of the BBIM(bis-benzimidazolium)-alkane systems with DB30C10 (Dibenzo-30-crown-10) in solvent acetonitrile. The (BBIM-alkane)DB30C10 systems chosen for the study are (BBIM)DB30C10, (BBIM-methane)DB30C10, (BBIM-ethane)DB30C10, (BBIM-propane)DB30C10 and (BBIM-butane)DB30C10. 1H NMR, 2D-NMR (COSY and NOESY), Monte Carlo calculations and HRMS have been done on the studied assemblies. Even though (BBIM)DB30C10 and (BBIM-methane)DB30C10 form normal threaded structures, in (BBIM-ethane)DB30C10, (BBIM-propane)DB30C10 and (BBIM-butane)DB30C10 systems the respective axles are cradled inside the crown ether. That is, the axles BBIM-ethane, BBIM-propane and BBIM-butane are cradled inside the boat-like cavity of DB30C10.

  8. Verification of residual stresses in flash-butt-weld rails using neutron diffraction

    NASA Astrophysics Data System (ADS)

    Tawfik, David; Kirstein, Oliver; Mutton, Peter John; Chiu, Wing Kong

    2006-11-01

    Residual stresses developed during flash-butt welding may play a crucial role in prolonging the fatigue life of the welded tracks under service loading conditions. The finished welds typically exhibit high levels of tensile residual stresses in the web region of the weld. Moreover, the surface condition of the web may contain shear drag or other defects resulting from the shearing process which may lead to the initiation and propagation of fatigue cracks in a horizontal split web failure mode under high axle loads. However, a comprehensive understanding into the residual stress behaviour throughout the complex weld geometry remains unclear and is considered necessary to establish the correct localised post-weld heat treatment modifications intended to lower tensile residual stresses. This investigation used the neutron diffraction technique to analyse residual stresses in an AS60 flash-butt-welded rail cooled under normal operating conditions. The findings will ultimately contribute to developing modifications to the flash-butt-welding procedure to lower tensile residual stresses which may then improve rail performance under high axle load.

  9. 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.

  10. 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. PMID:26192232

  11. 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

  12. Star/linear polymer topology transformation facilitated by mechanical linking of polymer chains.

    PubMed

    Aoki, Daisuke; Uchida, Satoshi; Takata, Toshikazu

    2015-06-01

    Topology transformation of a star polymer to a linear polymer is demonstrated for the first time. A three-armed star polymer possessing a mechanical linking of two polymer chains was synthesized by the living ring-opening polymerization of δ-valerolactone initiated by a pseudo[2]rotaxane having three hydroxy groups as the initiator sites on the wheel component and at both axle termini. The polymerization was followed by the propagation end-capping reaction with a bulky isocyanate not only to prevent the wheel component deslippage but also to introduce the urethane moiety at the axle terminal. The resulting rotaxane-linked star polymer with a fixed rotaxane linkage based on the ammonium/crown ether interaction was subjected to N-acetylation of the ammonium moiety, which liberated the components from the interaction to move the wheel component to the urethane terminal as the interaction site, eventually affording the linear polymer. The physical property change caused by the present topology transformation was confirmed by the hydrodynamic volume and viscosity. PMID:25892579

  13. 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

  14. Detection of rail corrugation based on fiber laser accelerometers

    NASA Astrophysics Data System (ADS)

    Huang, Wenzhu; Zhang, Wentao; Du, Yanliang; Sun, Baochen; Ma, Huaixiang; Li, Fang

    2013-09-01

    Efficient inspection methods are necessary for detection of rail corrugation to improve the safety and ride quality of railway operations. This paper presents a novel fiber optic technology for detection of rail corrugation based on fiber laser accelerometers (FLAs), tailored to the measurement of surface damage on rail structures. The principle of detection of rail corrugation using double integration of axle-box acceleration is presented. Then we present the theoretical model and test results of FLAs which are installed on the bogie to detect the vertical axle-box acceleration of the train. Characteristics of high sensitivity and large dynamic range are achieved when using fiber optic interferometric demodulation. A flexible inertial algorithm based on double integration and the wavelet denoising method is proposed to accurately estimate the rail corrugation. A field test is carried out on the Datong-Qinhuangdao Railway in north China. The test results are compared with the results of a rail inspection car, which shows that the fiber laser sensing system has a good performance in monitoring rail corrugation.

  15. Active flow control on a 1:4 car model

    NASA Astrophysics Data System (ADS)

    Heinemann, Till; Springer, Matthias; Lienhart, Hermann; Kniesburges, Stefan; Othmer, Carsten; Becker, Stefan

    2014-05-01

    Lift and drag of a passenger car are strongly influenced by the flow field around its rear end. The bluff body geometry produces a detached, transient flow which induces fluctuating forces on the body, affecting the rear axle, which may distress dynamic stability and comfort significantly. The investigations presented here deal with a 1:4 scale model of a simplified test car geometry that produces fluctuating lift and drag due to its strongly rounded rear geometry. To examine the influence of active flow control on this behavior, steady air jets were realized to exhaust from thin slots across the rear in three different configurations. Investigations were performed at and included the capturing of effective integral lift and drag, velocity measurements in the surrounding flow field with Laser Doppler Anemometry, surface pressure measurements and surface oil flow visualization on the rear. The flow field was found to be dominated by two longitudinal vortices, developing from the detachment of the flow at the upper C-pillar positions, and a recirculating, transverse vortex above the rear window. With an air jet emerging from a slot across the surface right below the rear window section, tangentially directed upstream toward the roof section, total lift could be reduced by more than 7 %, with rear axle lift reduction of about 5 % and negligible drag affection (1 %).

  16. 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. PMID:26874293

  17. Understanding the apparent stator-rotor connections in the rotary ATPase family using coarse-grained computer modeling.

    PubMed

    Richardson, Robin A; Papachristos, Konstantinos; Read, Daniel J; Harlen, Oliver G; Harrison, Michael; Paci, Emanuele; Muench, Stephen P; Harris, Sarah A

    2014-12-01

    Advances in structural biology, such as cryo-electron microscopy (cryo-EM) have allowed for a number of sophisticated protein complexes to be characterized. However, often only a static snapshot of a protein complex is visualized despite the fact that conformational change is frequently inherent to biological function, as is the case for molecular motors. Computer simulations provide valuable insights into the different conformations available to a particular system that are not accessible using conventional structural techniques. For larger proteins and protein complexes, where a fully atomistic description would be computationally prohibitive, coarse-grained simulation techniques such as Elastic Network Modeling (ENM) are often employed, whereby each atom or group of atoms is linked by a set of springs whose properties can be customized according to the system of interest. Here we compare ENM with a recently proposed continuum model known as Fluctuating Finite Element Analysis (FFEA), which represents the biomolecule as a viscoelastic solid subject to thermal fluctuations. These two complementary computational techniques are used to answer a critical question in the rotary ATPase family; implicit within these motors is the need for a rotor axle and proton pump to rotate freely of the motor domain and stator structures. However, current single particle cryo-EM reconstructions have shown an apparent connection between the stators and rotor axle or pump region, hindering rotation. Both modeling approaches show a possible role for this connection and how it would significantly constrain the mobility of the rotary ATPase family. PMID:25174610

  18. Modeling on energy harvesting from a railway system using piezoelectric transducers

    NASA Astrophysics Data System (ADS)

    Wang, Jianjun; Shi, Zhifei; Xiang, Hongjun; Song, Gangbing

    2015-10-01

    Theoretical models of piezoelectric energy harvesting from railway systems using patch-type and stack-type piezoelectric transducers are studied. An infinite Euler-Bernoulli beam on a Winkler foundation subjected to moving multi-loads is adopted to describe the dynamic behavior of railway track. The voltage and electric power of piezoelectric transducers installed at the bottom of a steel rail are derived analytically. Comparisons with earlier works and experimental results are given, indicating that the present solutions are reliable. Additionally, a parametric study is conducted to discuss the effects of axle loads, running velocity and load resistors on the solutions. The numerical results show that patch-type and stack-type piezoelectric transducers can harvest the available energy from track vibration to supply power for a wireless sensor network node and can also serve as sensors to monitor basic train information, such as the running velocity, the location and the axle load. The present investigations provide a theoretical guide in the design of piezoelectric patch and stack energy harvesters used in railway systems, which can serve as power sources for distributed wireless sensor networks in remote areas. The research results also demonstrate the potential of piezoelectric patches and stack harvesters in designing self-powered wireless sensor networks used in railway systems to ensure train operation safety.

  19. 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.

  20. 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.

  1. Biology of Zika Virus Infection in Human Skin Cells

    PubMed Central

    Hamel, Rodolphe; Dejarnac, Ophélie; Wichit, Sineewanlaya; Ekchariyawat, Peeraya; Neyret, Aymeric; Luplertlop, Natthanej; Perera-Lecoin, Manuel; Surasombatpattana, Pornapat; Talignani, Loïc; Thomas, Frédéric; Cao-Lormeau, Van-Mai; Choumet, Valérie; Briant, Laurence; Desprès, Philippe; Amara, Ali; Yssel, Hans

    2015-01-01

    ABSTRACT Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family, which includes dengue, West Nile, yellow fever, and Japanese encephalitis viruses, that causes a mosquito-borne disease transmitted by the Aedes genus, with recent outbreaks in the South Pacific. Here we examine the importance of human skin in the entry of ZIKV and its contribution to the induction of antiviral immune responses. We show that human dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells are permissive to the most recent ZIKV isolate, responsible for the epidemic in French Polynesia. Several entry and/or adhesion factors, including DC-SIGN, AXL, Tyro3, and, to a lesser extent, TIM-1, permitted ZIKV entry, with a major role for the TAM receptor AXL. The ZIKV permissiveness of human skin fibroblasts was confirmed by the use of a neutralizing antibody and specific RNA silencing. ZIKV induced the transcription of Toll-like receptor 3 (TLR3), RIG-I, and MDA5, as well as several interferon-stimulated genes, including OAS2, ISG15, and MX1, characterized by strongly enhanced beta interferon gene expression. ZIKV was found to be sensitive to the antiviral effects of both type I and type II interferons. Finally, infection of skin fibroblasts resulted in the formation of autophagosomes, whose presence was associated with enhanced viral replication, as shown by the use of Torin 1, a chemical inducer of autophagy, and the specific autophagy inhibitor 3-methyladenine. The results presented herein permit us to gain further insight into the biology of ZIKV and to devise strategies aiming to interfere with the pathology caused by this emerging flavivirus. IMPORTANCE Zika virus (ZIKV) is an arbovirus belonging to the Flaviviridae family. Vector-mediated transmission of ZIKV is initiated when a blood-feeding female Aedes mosquito injects the virus into the skin of its mammalian host, followed by infection of permissive cells via specific receptors. Indeed, skin immune

  2. A rapid in vivo screen for pancreatic ductal adenocarcinoma therapeutics.

    PubMed

    Ocal, Ozhan; Pashkov, Victor; Kollipara, Rahul K; Zolghadri, Yalda; Cruz, Victoria H; Hale, Michael A; Heath, Blake R; Artyukhin, Alex B; Christie, Alana L; Tsoulfas, Pantelis; Lorens, James B; Swift, Galvin H; Brekken, Rolf A; Wilkie, Thomas M

    2015-10-01

    Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related deaths in the United States, and is projected to be second by 2025. It has the worst survival rate among all major cancers. Two pressing needs for extending life expectancy of affected individuals are the development of new approaches to identify improved therapeutics, addressed herein, and the identification of early markers. PDA advances through a complex series of intercellular and physiological interactions that drive cancer progression in response to organ stress, organ failure, malnutrition, and infiltrating immune and stromal cells. Candidate drugs identified in organ culture or cell-based screens must be validated in preclinical models such as KIC (p48(Cre);LSL-Kras(G12D);Cdkn2a(f/f)) mice, a genetically engineered model of PDA in which large aggressive tumors develop by 4 weeks of age. We report a rapid, systematic and robust in vivo screen for effective drug combinations to treat Kras-dependent PDA. Kras mutations occur early in tumor progression in over 90% of human PDA cases. Protein kinase and G-protein coupled receptor (GPCR) signaling activates Kras. Regulators of G-protein signaling (RGS) proteins are coincidence detectors that can be induced by multiple inputs to feedback-regulate GPCR signaling. We crossed Rgs16::GFP bacterial artificial chromosome (BAC) transgenic mice with KIC mice and show that the Rgs16::GFP transgene is a Kras(G12D)-dependent marker of all stages of PDA, and increases proportionally to tumor burden in KIC mice. RNA sequencing (RNA-Seq) analysis of cultured primary PDA cells reveals characteristics of embryonic progenitors of pancreatic ducts and endocrine cells, and extraordinarily high expression of the receptor tyrosine kinase Axl, an emerging cancer drug target. In proof-of-principle drug screens, we find that weanling KIC mice with PDA treated for 2 weeks with gemcitabine (with or without Abraxane) plus inhibitors of Axl signaling

  3. Does diverse grazing behavior of suckler cows have an impact on predicted methane emissions?

    PubMed

    Ricci, P; Umstätter, C; Holland, J P; Waterhouse, A

    2014-03-01

    A modeling study based on a dataset from a large-scale grazing study was used to identify the potential impact of grazing behavior and performance of diverse cow genotypes on predicted methane (CH4) emissions. Lactating cows grazing extensive seminatural grassland and heath vegetation were monitored with Global Positioning System collars and activity sensors. The diet selected by cows of 3 different genotypes, Aberdeen Angus cross Limousin (AxL), Charolais (CHA), and Luing (LUI), was simulated by matching their locations during active periods with hill vegetation maps. Measured performance and activity were used to predict energy requirements, DMI, and CH4 output. The cumulative effect of actual performance, diet selection, and actual physical activity on potential CH4 output and yield was estimated. Sensitivity analyses were performed for the digestibility of intake, energy cost of activity, proportion of milk consumed by calves, and reproductive efficiency. Although with a better performance (P < 0.05), LUI required less total energy than the other genotypes (P < 0.001) as the other 2 spent more energy for maintenance (P < 0.001) and activity (P < 0.001). By selecting a better quality diet (P < 0.03), estimated CH4 of CHA cow-calf pairs was lower than AxL (P = 0.001) and slightly lower than LUI (P = 0.08). Energy lost as CH4 was 0.17 and 0.58% lower for LUI than AxL and CHA (P < 0.002). This study suggests for the first time that measured activity has a major impact on estimated CH4 outputs. A 15% difference of the cow-calf pair CH4 was estimated when using different coefficients to convert actual activity into energy. Predicted CH4 was highly sensitive to small changes in diet quality, suggesting the relative importance of diet selection on heterogeneous rangelands. Extending these results to a farm systems scale, CH4 outputs were also highly sensitive to reductions in weaning rates, illustrating the impact on CH4 at the farm-system level of using poorly adapted

  4. A rapid in vivo screen for pancreatic ductal adenocarcinoma therapeutics

    PubMed Central

    Ocal, Ozhan; Pashkov, Victor; Kollipara, Rahul K.; Zolghadri, Yalda; Cruz, Victoria H.; Hale, Michael A.; Heath, Blake R.; Artyukhin, Alex B.; Christie, Alana L.; Tsoulfas, Pantelis; Lorens, James B.; Swift, Galvin H.; Brekken, Rolf A.; Wilkie, Thomas M.

    2015-01-01

    ABSTRACT Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related deaths in the United States, and is projected to be second by 2025. It has the worst survival rate among all major cancers. Two pressing needs for extending life expectancy of affected individuals are the development of new approaches to identify improved therapeutics, addressed herein, and the identification of early markers. PDA advances through a complex series of intercellular and physiological interactions that drive cancer progression in response to organ stress, organ failure, malnutrition, and infiltrating immune and stromal cells. Candidate drugs identified in organ culture or cell-based screens must be validated in preclinical models such as KIC (p48Cre;LSL-KrasG12D;Cdkn2af/f) mice, a genetically engineered model of PDA in which large aggressive tumors develop by 4 weeks of age. We report a rapid, systematic and robust in vivo screen for effective drug combinations to treat Kras-dependent PDA. Kras mutations occur early in tumor progression in over 90% of human PDA cases. Protein kinase and G-protein coupled receptor (GPCR) signaling activates Kras. Regulators of G-protein signaling (RGS) proteins are coincidence detectors that can be induced by multiple inputs to feedback-regulate GPCR signaling. We crossed Rgs16::GFP bacterial artificial chromosome (BAC) transgenic mice with KIC mice and show that the Rgs16::GFP transgene is a KrasG12D-dependent marker of all stages of PDA, and increases proportionally to tumor burden in KIC mice. RNA sequencing (RNA-Seq) analysis of cultured primary PDA cells reveals characteristics of embryonic progenitors of pancreatic ducts and endocrine cells, and extraordinarily high expression of the receptor tyrosine kinase Axl, an emerging cancer drug target. In proof-of-principle drug screens, we find that weanling KIC mice with PDA treated for 2 weeks with gemcitabine (with or without Abraxane) plus inhibitors of Axl signaling

  5. Movable anode x-ray source with enhanced anode cooling

    DOEpatents

    Bird, Charles R.; Rockett, Paul D.

    1987-01-01

    An x-ray source having a cathode and a disc-shaped anode with a peripheral surface at constant radius from the anode axis opposed to the cathode. The anode has stub axle sections rotatably carried in heat conducting bearing plates which are mounted by thermoelectric coolers to bellows which normally bias the bearing plates to a retracted position spaced from opposing anode side faces. The bellows cooperate with the x-ray source mounting structure for forming closed passages for heat transport fluid. Flow of such fluid under pressure expands the bellows and brings the bearing plates into heat conducting contact with the anode side faces. A worm gear is mounted on a shaft and engages serrations in the anode periphery for rotating the anode when flow of coolant is terminated between x-ray emission events.

  6. Movable anode x-ray source with enhanced anode cooling

    DOEpatents

    Bird, C.R.; Rockett, P.D.

    1987-08-04

    An x-ray source is disclosed having a cathode and a disc-shaped anode with a peripheral surface at constant radius from the anode axis opposed to the cathode. The anode has stub axle sections rotatably carried in heat conducting bearing plates which are mounted by thermoelectric coolers to bellows which normally bias the bearing plates to a retracted position spaced from opposing anode side faces. The bellows cooperate with the x-ray source mounting structure for forming closed passages for heat transport fluid. Flow of such fluid under pressure expands the bellows and brings the bearing plates into heat conducting contact with the anode side faces. A worm gear is mounted on a shaft and engages serrations in the anode periphery for rotating the anode when flow of coolant is terminated between x-ray emission events. 5 figs.

  7. Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics.

    PubMed

    Savidis, George; McDougall, William M; Meraner, Paul; Perreira, Jill M; Portmann, Jocelyn M; Trincucci, Gaia; John, Sinu P; Aker, Aaron M; Renzette, Nicholas; Robbins, Douglas R; Guo, Zhiru; Green, Sharone; Kowalik, Timothy F; Brass, Abraham L

    2016-06-28

    The flaviviruses dengue virus (DENV) and Zika virus (ZIKV) are severe health threats with rapidly expanding ranges. To identify the host cell dependencies of DENV and ZIKV, we completed orthologous functional genomic screens using RNAi and CRISPR/Cas9 approaches. The screens recovered the ZIKV entry factor AXL as well as multiple host factors involved in endocytosis (RAB5C and RABGEF), heparin sulfation (NDST1 and EXT1), and transmembrane protein processing and maturation, including the endoplasmic reticulum membrane complex (EMC). We find that both flaviviruses require the EMC for their early stages of infection. Together, these studies generate a high-confidence, systems-wide view of human-flavivirus interactions and provide insights into the role of the EMC in flavivirus replication. PMID:27342126

  8. The molecular necklace: a rotaxane containing many threaded α-cyclodextrins

    NASA Astrophysics Data System (ADS)

    Harada, Akira; Li, Jun; Kamachi, Mikiharu

    1992-03-01

    THE importance of non-covalent interactions in biological systems motivates much of the current interest in supramolecular assemblies1. A classic example of a supermolecule is provided by the rotaxanes2-5, in which a molecular 'rotor' is threaded by a linear 'axle'. Previous examples have included cyclic crown ethers threaded by polymers6, paraquat-hydroquinone complexes7 and cyclodextrin complexes8,9. We found recently that α-cyclodextrin will form high yields of a crystalline complex with polyethylene glycol (PEG), and suggested that the PEG penetrates the 'beaker-like' tunnel of the cyclodextrin10,11. We report here the preparation of a compound in which several cyclodextrins are threaded on a single PEG chain and are trapped by capping the chain with bulky end groups. This brings a step closer the 'molecular abacus' proposed by Stoddart and coworkers7. We call this supramolecular assembly a 'molecular necklace'.

  9. Identification of GPR65, a novel regulator of matrix metalloproteinases using high through-put screening.

    PubMed

    Xu, Hongbo; Chen, Xiaohong; Huang, Junwei; Deng, Weiwei; Zhong, Qi; Yue, Changli; Wang, Pingzhang; Huang, Zhigang

    2013-06-21

    Matrix metalloproteinases (MMPs) are over-expressed in nearly all cancers. To study novel regulatory factors of MMP expression in head and neck cancer (HNC), we screened a total of 636 candidate genes encoding putative human transmembrane proteins using MMP promoter reporter in a dual luciferase assay system. Three genes GPR65, AXL and TNFRSF10B dramatically activated the induction of MMP3 expression. The induction of MMP expression by GPR65 was further confirmed in A549 and/or FaDu cells. GPR65 mediated MMP induction under acidic conditions. The AP-1 binding site in MMP3 promoter was crucial for MMP3 induction. Moreover, the A549 cells infected by recombinant adenovirus of GPR65 showed accelerated cell invasion. In conclusion, we validate that GPR65 is vital regulatory genes upstream of MMP3, and define a novel mechanism of MMP3 regulation by proton-sensing G-protein-coupled receptors. PMID:23707809

  10. Hybrid Electric Transit Bus

    NASA Technical Reports Server (NTRS)

    Viterna, Larry A.

    1997-01-01

    A government, industry, and university cooperative is developing an advanced hybrid electric city transit bus. Goals of this effort include doubling the fuel economy compared to current buses and reducing emissions to one-tenth of current EPA standards. Unique aspects of the vehicle's power system include the use of ultra-capacitors as an energy storage system, and a planned natural gas fueled turbogenerator developed from a small jet engine. Power from both the generator and energy storage system is provided to a variable speed electric motor attached to the rear axle. At over 15000 kg gross weight, this is the largest vehicle of its kind ever built using ultra-capacitor energy storage. This paper describes the overall power system architecture, the evolution of the control strategy, and its performance over industry standard drive cycles.

  11. Energy harvester for rotating environments using offset pendulum and nonlinear dynamics

    NASA Astrophysics Data System (ADS)

    Roundy, Shad; Tola, Jeffry

    2014-10-01

    We present an energy harvester for environments that rotate through the Earth’s gravitational field. Example applications include shafts connected to motors, axles, propellers, fans, and wheels or tires. Our approach uses the unique dynamics of an offset pendulum along with a nonlinear bistable restoring spring to improve the operational bandwidth of the system. Depending on the speed of the rotating environment, the system can act as a bistable oscillator, monostable stiffening oscillator, or linear oscillator. We apply our approach to a tire pressure monitoring system mounted on a car rim. Simulation and experimental test results show that the prototype generator is capable of directly powering an RF transmission every 60 s or less over a speed range of 10 to 155 kph.

  12. Designs and analyses of flywheel energy storage systems using high- Tc superconductor bearings

    NASA Astrophysics Data System (ADS)

    Sung, T. H.; Han, S. C.; Han, Y. H.; Lee, J. S.; Jeong, N. H.; Hwang, S. D.; Choi, S. K.

    2002-06-01

    A horizontal axle-type flywheel energy storage system was manufactured using high- Tc superconductor bearings. The system running in a vacuum chamber mainly consists of a composite flywheel rotor, superconductor bearings, a motor/generator and its controller. The present system was designed to have an energy storage capacity of 440 W h at its operating speed of 40,000 rpm, which is way above two rigid body mode critical speeds. Rotordynamic analysis was performed on this system. Another flywheel system with vertical axis was conceptualized, which uses a hybrid superconductor bearing set to carry the wheel part load. The models for permanent magnet parts of the bearing set were designed using numerical magnetostatic analysis tool. The vertical magnetic force characteristics of the bearing set were experimentally measured. These results were discussed in regard of application to the flywheel system with a passive hybrid superconductor bearing set.

  13. Method of fabricating a multilayer insulation blanket

    DOEpatents

    Gonczy, John D.; Niemann, Ralph C.; Boroski, William N.

    1993-01-01

    An improved multilayer insulation blanket for insulating cryogenic structures operating at very low temperatures is disclosed. An apparatus and method for fabricating the improved blanket are also disclosed. In the improved blanket, each successive layer of insulating material is greater in length and width than the preceding layer so as to accommodate thermal contraction of the layers closest to the cryogenic structure. The fabricating apparatus has a rotatable cylindrical mandrel having an outer surface of fixed radius that is substantially arcuate, preferably convex, in cross-section. The method of fabricating the improved blanket comprises (a) winding a continuous sheet of thermally reflective material around the circumference of the mandrel to form multiple layers, (b) binding the layers along two lines substantially parallel to the edges of the circumference of the mandrel, (c) cutting the layers along a line parallel to the axle of the mandrel, and (d) removing the bound layers from the mandrel.

  14. Multilayer insulation blanket, fabricating apparatus and method

    DOEpatents

    Gonczy, John D.; Niemann, Ralph C.; Boroski, William N.

    1992-01-01

    An improved multilayer insulation blanket for insulating cryogenic structures operating at very low temperatures is disclosed. An apparatus and method for fabricating the improved blanket are also disclosed. In the improved blanket, each successive layer of insulating material is greater in length and width than the preceding layer so as to accommodate thermal contraction of the layers closest to the cryogenic structure. The fabricating apparatus has a rotatable cylindrical mandrel having an outer surface of fixed radius that is substantially arcuate, preferably convex, in cross-section. The method of fabricating the improved blanket comprises (a) winding a continuous sheet of thermally reflective material around the circumference of the mandrel to form multiple layers, (b) binding the layers along two lines substantially parallel to the edges of the circumference of the mandrel, (c) cutting the layers along a line parallel to the axle of the mandrel, and (d) removing the bound layers from the mandrel.

  15. Method of fabricating a multilayer insulation blanket

    DOEpatents

    Gonczy, J.D.; Niemann, R.C.; Boroski, W.N.

    1993-07-06

    An improved multilayer insulation blanket for insulating cryogenic structures operating at very low temperatures is disclosed. An apparatus and method for fabricating the improved blanket are also disclosed. In the improved blanket, each successive layer of insulating material is greater in length and width than the preceding layer so as to accommodate thermal contraction of the layers closest to the cryogenic structure. The fabricating apparatus has a rotatable cylindrical mandrel having an outer surface of fixed radius that is substantially arcuate, preferably convex, in cross-section. The method of fabricating the improved blanket comprises (a) winding a continuous sheet of thermally reflective material around the circumference of the mandrel to form multiple layers, (b) binding the layers along two lines substantially parallel to the edges of the circumference of the mandrel, (c) cutting the layers along a line parallel to the axle of the mandrel, and (d) removing the bound layers from the mandrel.

  16. Multilayer insulation blanket, fabricating apparatus and method

    DOEpatents

    Gonczy, J.D.; Niemann, R.C.; Boroski, W.N.

    1992-09-01

    An improved multilayer insulation blanket for insulating cryogenic structures operating at very low temperatures is disclosed. An apparatus and method for fabricating the improved blanket are also disclosed. In the improved blanket, each successive layer of insulating material is greater in length and width than the preceding layer so as to accommodate thermal contraction of the layers closest to the cryogenic structure. The fabricating apparatus has a rotatable cylindrical mandrel having an outer surface of fixed radius that is substantially arcuate, preferably convex, in cross-section. The method of fabricating the improved blanket comprises (a) winding a continuous sheet of thermally reflective material around the circumference of the mandrel to form multiple layers, (b) binding the layers along two lines substantially parallel to the edges of the circumference of the mandrel, (c) cutting the layers along a line parallel to the axle of the mandrel, and (d) removing the bound layers from the mandrel. 7 figs.

  17. Real-time monitoring of railway traffic using fiber Bragg gratings

    NASA Astrophysics Data System (ADS)

    Filograno, M. L.; Rodriguez-Barrios, A.; Corredera, P.; Martin-Lopez, S.; Rodriguez-Plaza, M.; Andres-Alguacil, A.; Gonzalez-Herraez, M.

    2010-09-01

    In this work we present field tests concerning the application of Fiber Bragg Grating (FBG) sensors for the monitoring of railway traffic. The test campaigns are performed on the Spanish high speed line Madrid-Barcelona, with different types of trains (S-102 TALGO-BOMBARDIER, S-103 SIEMENS-VELARO and S-120 CAF). We located the FBG sensors in the rail track at 70 km from Madrid in the country side, where the trains primarily are tested during commercial operation with maximum speeds between 250-300 km/h. The FBG sensor interrogation system used allows the simultaneous monitoring of four FBG sensors at 8000 samples/s. The different position of the FBG sensors in relation with the rail can be used with different purposes such as train identification, axle counting, speed and acceleration detection, wheel imperfections monitoring and dynamic load calculation.

  18. TAM receptor deficiency affects adult hippocampal neurogenesis

    PubMed Central

    Ji, Rui; Meng, Lingbin; Li, Qiutang; Lu, Qingxian

    2014-01-01

    The Tyro3, Axl and Mertk (TAM) subfamily of receptor protein tyrosine kinases functions in cell growth, differentiation, survival, and most recently found, in the regulation of immune responses and phagocytosis. All three receptors and their ligands, Gas6 (growth arrest-specific gene 6) and protein S, are expressed in the central nervous system (CNS). TAM receptors play pivotal roles in adult hippocampal neurogenesis. Loss of these receptors causes a comprised neurogenesis in the dentate gyrus of adult hippocampus. TAM receptors have a negative regulatory effect on microglia and peripheral antigen-presenting cells, and play a critical role in preventing overproduction of pro-inflammatory cytokines detrimental to the proliferation, differentiation, and survival of adult neuronal stem cells (NSCs). Besides, these receptors also play an intrinsic trophic function in supporting NSC survival, proliferation, and differentiation into immature neurons. All these events collectively ensure a sustained neurogenesis in adult hippocampus. PMID:25487541

  19. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq

    PubMed Central

    Tirosh, Itay; Izar, Benjamin; Prakadan, Sanjay M.; Wadsworth, Marc H.; Treacy, Daniel; Trombetta, John J.; Rotem, Asaf; Rodman, Christopher; Lian, Christine; Murphy, George; Fallahi-Sichani, Mohammad; Dutton-Regester, Ken; Lin, Jia-Ren; Cohen, Ofir; Shah, Parin; Lu, Diana; Genshaft, Alex S.; Hughes, Travis K.; Ziegler, Carly G. K.; Kazer, Samuel W.; Gaillard, Aleth; Kolb, Kellie E.; Villani, Alexandra-Chloé; Johannessen, Cory M.; Andreev, Aleksandr Y.; Van Allen, Eliezer M.; Bertagnolli, Monica; Sorger, Peter K.; Sullivan, Ryan J.; Flaherty, Keith T.; Frederick, Dennie T.; Jané-Valbuena, Judit; Yoon, Charles H.; Rozenblatt-Rosen, Orit; Shalek, Alex K.; Regev, Aviv; Garraway, Levi A.

    2016-01-01

    To explore the distinct genotypic and phenotypic states of melanoma tumors we applied single-cell RNA-seq to 4,645 single cells isolated from 19 patients, profiling malignant, immune, stromal and endothelial cells. Malignant cells within the same tumor displayed transcriptional heterogeneity associated with the cell cycle, spatial context, and a drug resistance program. In particular, all tumors harbored malignant cells from two distinct transcriptional cell states, such that “MITF-high” tumors also contained “AXL-high” tumor cells. Single-cell analyses suggested distinct tumor micro-environmental patterns, including cell-to-cell interactions. Analysis of tumor-infiltrating T cells revealed exhaustion programs, their connection to T cell activation and to clonal expansion, and their variability across patients. Overall, we begin to unravel the cellular ecosystem of tumors and how single cell genomics offers insights with implications for both targeted and immune therapies. PMID:27124452

  20. Time-frequency analysis of railway bridge response in forced vibration

    NASA Astrophysics Data System (ADS)

    Cantero, Daniel; Ülker-Kaustell, Mahir; Karoumi, Raid

    2016-08-01

    This paper suggests the use of the Continuous Wavelet Transform in combination with the Modified Littlewood-Paley basis to analyse bridge responses exited by traversing trains. The analysis provides an energy distribution map in the time-frequency domain that offers a better resolution compared to previous published studies. This is demonstrated with recorded responses of the Skidträsk Bridge, a 36 m long composite bridge located in Sweden. It is shown to be particularly useful to understand the evolution of the energy content during a vehicle crossing event. With this information it is possible to distinguish the effect of several of the governing factors involved in the dynamic response including vehicle's speed and axle configuration as well as non-linear behaviour of the structure.