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Sample records for axles

  1. Giving AXL the axe: targeting AXL in human malignancy

    PubMed Central

    Gay, Carl M; Balaji, Kavitha; Byers, Lauren Averett

    2017-01-01

    The receptor tyrosine kinase AXL, activated by a complex interaction between its ligand growth arrest-specific protein 6 and phosphatidylserine, regulates various vital cellular processes, including proliferation, survival, motility, and immunologic response. Although not implicated as an oncogenic driver itself, AXL, a member of the TYRO3, AXL, and MERTK family of receptor tyrosine kinases, is overexpressed in several haematologic and solid malignancies, including acute myeloid leukaemia, non-small cell lung cancer, gastric and colorectal adenocarcinomas, and breast and prostate cancers. In the context of malignancy, evidence suggests that AXL overexpression drives wide-ranging processes, including epithelial to mesenchymal transition, tumour angiogenesis, resistance to chemotherapeutic and targeted agents, and decreased antitumor immune response. As a result, AXL is an attractive candidate not only as a prognostic biomarker in malignancy but also as a target for anticancer therapies. Several AXL inhibitors are currently in preclinical and clinical development. This article reviews the structure, regulation, and function of AXL; the role of AXL in the tumour microenvironment; the development of AXL as a therapeutic target; and areas of ongoing and future investigation. PMID:28072762

  2. Two speed axle assembly

    SciTech Connect

    Heine, C.F.; Krisher, J.A.; Pifer, R.L.

    1988-10-04

    This patent describes a two speed axle assembly comprising an input sun gear, an output sun gear, a plant carrier mounted for rotation about the input and output sun gears, at least one compound planetary gear rotatably mounted on the planet carrier and drivingly connected to the input sun gear and the output sun gear, first clutch means for selectively locking the planet carrier relative to the input sun gear for rotation therewith including means normally loading the first clutch means whereby the planet carrier rotates the input sun gear, second clutch means for alternatively locking the planet carrier against rotation whereby the compound planet gear rotates on the planet carrier in response to rotation of the input sun gear, and inflatable bladder means adapted when selectively inflated to load the second clutch means and simultaneously unload the normally loaded first clutch means whereby the planet carrier is unlocked relative to the input sun gear and locked against rotation, including means selectively supplying hydraulic fluid under pressure to the bladder means, means supplying hydraulic fluid comprising accumulator means, pump means remote from the axle assembly for pressurizing the hydraulic fluid and maintaining a supply of the fluid under at least a minimum pressure in the accumulator means, and valve means for selectively admitting the pressurized fluid from the accumulator means to the bladder means to inflate the bladder means and relieving the pressure to deflate the bladder means.

  3. 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.

  4. Laboratory Based Axle Lubricant Efficiency Evaluation

    DTIC Science & Technology

    2014-07-01

    SUBJECT TERMS Axle lubricant efficiency; FMTV, SCPL, Gear Oil, Engine Oil, HMMWV, Stationary Axle Test, SAE J2360 16. SECURITY...Seconds ASTM American Society for Testing and Materials CAT Caterpillar cSt CentiStoke FMTV Family of Medium Tactical Vehicles GO Gear Oil GVW...engine, transmission, and axle gear lubricants as used in the Family of Medium Tactical Vehicles (FMTV) [3]. Fuel consumption changes were determined

  5. 49 CFR 215.105 - Defective axle.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... conjunction with a plain bearing, has an end collar that is broken or cracked; (d) A journal on the car shows evidence of overheating, as evidenced by a pronounced blue black discoloration; or (e) The surface of the plain bearing journal on the axle, or the fillet on the axle, has— (1) A ridge; (2) A depression; (3)...

  6. 49 CFR 215.105 - Defective axle.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... conjunction with a plain bearing, has an end collar that is broken or cracked; (d) A journal on the car shows evidence of overheating, as evidenced by a pronounced blue black discoloration; or (e) The surface of the plain bearing journal on the axle, or the fillet on the axle, has— (1) A ridge; (2) A depression; (3)...

  7. 49 CFR 215.105 - Defective axle.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... conjunction with a plain bearing, has an end collar that is broken or cracked; (d) A journal on the car shows evidence of overheating, as evidenced by a pronounced blue black discoloration; or (e) The surface of the plain bearing journal on the axle, or the fillet on the axle, has— (1) A ridge; (2) A depression; (3)...

  8. 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)...

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

    DOE PAGES

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

    2014-09-21

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

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

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

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

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

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

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

  12. 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.

  13. The Receptor Tyrosine Kinase AXL in Cancer Progression

    PubMed Central

    Rankin, Erinn B.; Giaccia, Amato J.

    2016-01-01

    The AXL receptor tyrosine kinase (AXL) has emerged as a promising therapeutic target for cancer therapy. Recent studies have revealed a central role of AXL signaling in tumor proliferation, survival, stem cell phenotype, metastasis, and resistance to cancer therapy. Moreover, AXL is expressed within cellular components of the tumor microenvironment where AXL signaling contributes to the immunosuppressive and protumorigenic phenotypes. A variety of AXL inhibitors have been developed and are efficacious in preclinical studies. These agents offer new opportunities for therapeutic intervention in the prevention and treatment of advanced disease. Here we review the literature that has illuminated the cellular and molecular mechanisms by which AXL signaling promotes tumor progression and we will discuss the therapeutic potential of AXL inhibition for cancer therapy. PMID:27834845

  14. 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

  15. 49 CFR 215.105 - Defective axle.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Defective axle. 215.105 Section 215.105 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Suspension...

  16. 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

  17. Hypoxia stabilizes GAS6/AXl signaling in metastatic prostate cancer

    PubMed Central

    Mishra, Anjali; Wang, Jingcheng; Shiozawa, Yusuke; McGee, Samantha; Kim, Jinkoo; Jung, Younghun; Joseph, Jeena; Berry, Janice E.; Havens, Aaron; Pienta, Kenneth J.; Taichman, Russell S.

    2012-01-01

    The receptor tyrosine kinase Axl is over-expressed in a variety of cancers and is known to play a role in proliferation and invasion. Previous data from our lab indicates that Axl and its ligand GAS6 may play a role in establishing metastatic dormancy in the bone marrow microenvironment. In the current study, we found that Axl is highly expressed in metastatic prostate cancer (PCa) cell lines PC3 and DU145 and has negligible levels of expression in a non-metastatic cancer cell line LNCaP. Knockdown of Axl in PC3 and DU145 cells resulted in decreased expression of several mesenchymal markers including Snail, Slug, and N-cadherin, and enhanced expression of the epithelial marker E-cadherin, suggesting that Axl is involved in the epithelial to mesenchymal transition in PCa cells. The Axl-knockdown PC3 and DU145 cells also displayed decreased in vitro migration and invasion. Interestingly, when PC3 and DU145 cells were treated with GAS6, Axl protein levels were down-regulated. Moreover, CoCl2, a hypoxia mimicking agent, prevented GAS6 mediated down-regulation of Axl in these cell lines. Immunochemical staining of human PCa tissue microarrays demonstrated that Axl, GAS6 and Hif1-α (indicator of hypoxia) were all co-expressed in PCa and in bone metastases, compared to normal tissues. Together, our studies indicate that Axl plays a crucial role in PCa metastasis, and that GAS6 regulates the expression of Axl. Importantly, in a hypoxic tumor microenvironment Axl expression maintained leading to enhanced signaling. PMID:22516347

  18. Single-axle, double-axis solar tracker

    NASA Technical Reports Server (NTRS)

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

    1979-01-01

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

  19. 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

  20. 49 CFR 230.98 - Driving, trailing, and engine truck axles.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Locomotives and Tenders Running Gear § 230.98 Driving, trailing, and engine truck axles. (a) Condemning...; (2) Cut journals that cannot be made to run cool without turning; (3) Transverse seams in iron or steel axles; (4) Seams in axles causing journals to run hot; (5) Axles that are unsafe on account...

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

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Locomotives and Tenders Running Gear § 230.98 Driving, trailing, and engine truck axles. (a) Condemning...; (2) Cut journals that cannot be made to run cool without turning; (3) Transverse seams in iron or steel axles; (4) Seams in axles causing journals to run hot; (5) Axles that are unsafe on account...

  2. The AXL Receptor is a Sensor of Ligand Spatial Heterogeneity

    PubMed Central

    Meyer, Aaron S.; Zweemer, Annelien J.M.; Lauffenburger, Douglas A.

    2015-01-01

    The AXL receptor is a TAM (Tyro3, AXL, MerTK) receptor tyrosine kinase (RTK) important in physiological inflammatory processes such as blood clotting, viral infection, and innate immune-mediated cell clearance. Overexpression of the receptor in a number of solid tumors is increasingly appreciated as a key drug resistance and tumor dissemination mechanism. Although the ligand-receptor (Gas6-AXL) complex structure is known, literature reports on ligand-mediated signaling have provided conflicting conclusions regarding the influence of other factors such as phosphatidylserine binding, and a detailed, mechanistic picture of AXL activation has not emerged. Integrating quantitative experiments with mathematical modeling, we show here that AXL operates to sense local spatial heterogeneity in ligand concentration, a feature consistent with its physiological role in inflammatory cell responses. This effect arises as a result of an intricate reaction-diffusion interaction. Our results demonstrate that AXL functions distinctly from other RTK families, a vital insight for envisioned design of AXL-targeted therapeutic intervention. PMID:26236777

  3. Inertial Stabilization Of Periscopic Sights Band Driven Three Axle Gimbal

    NASA Astrophysics Data System (ADS)

    Ellison, Bruce; Richi, James

    1983-10-01

    There are many applications for the use of optical instruments in vehicles, especially in the military. It is required that these instruments function while the vehicle is on the move, in rough terrain. Angular distrubances of the line-of-sight pointing vector can render these instruments useless as observation or pointing devices, due to image blurring. Instruments that must retain resolution in this environment are usually stabilized by means of gimbals. If the entire instrument (such as a large television camera) is to be stabilized, the problem becomes one of a simple stable platform, or, a single axle gimbal. If, however, the instrument is hard mounted to the vehicle and the image is instead to be stabilized by means of a compensating optical component, such as a periscope head mirror, the problem is a little more complex. In a periscopic sight the head mirror must be driven at half-speed to the line-of-sight disturbance to compensate for the angle doubling effect of the mirror. That is, in order to stabilize the line-of-sight, the mirror cannot be inertiallv stable, but must be coupled to a stable mass at a ratio of 1:2. In many applications it is necessary to transmit the elevation angle of the line-of-sight to a fire control system, or, to direct the lines-of-sight of other platforms. In order to do this, transducers are mounted on the "drive axle", (gyros, synchros, tachometers, potentiometers, motors), which detect and trasmit the angular position and rate of the elevation line-of-sight. This drive axle becomes the stable element and is coupled to the mirror axle, at a 2:1 ratio, by means of gears or metallic belts or bands. This is a double axle gimbal system. When subjected to a rotational disturbance such as boat or vehicle motion the inertias of the drive and mirror axles react with one-another to cause a displacement of the line-of-sight pointing vector. This disturbance is a dynamic coupling of inertias. It exists even in the absence of friction

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  5. 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.

  6. The Application of Phased Array Ultrasonic Techniques for Inspection of Railway Axles from Their End Face

    NASA Astrophysics Data System (ADS)

    Liaptsis, D.; Cooper, I.; Boyle, K.; Nicholson, P. I.

    2011-06-01

    As part of the development of a non destructive testing (NDT) system combining complementary inspection techniques, an inspection system based on phased array ultrasonic testing (PAUT) for detection of transverse cracking in solid railway axles is being developed. This paper presents the initial study, which includes the PAUT experimental setup and the initial results obtained after testing the system on railway axle blocks. The inspection of solid axles from their axle end face is investigated.

  7. Mechanisms of AXL overexpression and function in Imatinib-resistant chronic myeloid leukemia cells

    PubMed Central

    Dufies, Maeva; Jacquel, Arnaud; Belhacene, Nathalie; Robert, Guillaume; Cluzeau, Thomas; Luciano, Fréderic; Cassuto, Jill Patrice; Raynaud, Sophie; Auberger, Patrick

    2011-01-01

    AXL is a receptor tyrosine kinase of the TAM family, the function of which is poorly understood. We previously identified AXL overexpression in Imatinib (IM)-resistant CML cell lines and patients. The present study was conducted to investigate the role of AXL and the mechanisms underlying AXL overexpression in Tyrosine Kinase Inhibitor (TKI)-resistant CML cells. We present evidence that high AXL expression level is a feature of TKI-resistant CML cells and knockdown of AXL sensitized TKI-resistant cells to IM. In addition, expression of wild-type AXL but not a dominant negative form of AXL confers IM-sensitive CML cells the capacity to resist IM effect. AXL overexpression required PKCα and β and constitutive activation of ERK1/2. Accordingly, GF109203X a PKC inhibitor, U0126 a MEK1 inhibitor and PKCα/β knockdown restore sensitivity to IM while PKCα or PKCβ overexpression in CML cells promotes protection against IM-induced cell death. Finally, using luciferase promoter activity assays we established that AXL is regulated transcriptionally through the AP1 transcription factor. Our findings reveal an unexpected role of AXL in resistance to TKI in CML cells, identify the molecular mechanisms involved in its overexpression and support the notion that AXL is a new marker of resistance to TKI in CML. PMID:22141136

  8. 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

  9. 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

  10. Reprogramming the immunological microenvironment through radiation and targeting Axl

    PubMed Central

    Aguilera, Todd A.; Rafat, Marjan; Castellini, Laura; Shehade, Hussein; Kariolis, Mihalis S.; Hui, Angela Bik-Yu; Stehr, Henning; von Eyben, Rie; Jiang, Dadi; Ellies, Lesley G.; Koong, Albert C.; Diehn, Maximilian; Rankin, Erinn B.; Graves, Edward E.; Giaccia, Amato J.

    2016-01-01

    Increasing evidence suggests that ionizing radiation therapy (RT) in combination with checkpoint immunotherapy is highly effective in treating a subset of cancers. To better understand the limited responses to this combination we analysed the genetic, microenvironmental, and immune factors in tumours derived from a transgenic breast cancer model. We identified two tumours with similar growth characteristics but different RT responses primarily due to an antitumour immune response. The combination of RT and checkpoint immunotherapy resulted in cures in the responsive but not the unresponsive tumours. Profiling the tumours revealed that the Axl receptor tyrosine kinase is overexpressed in the unresponsive tumours, and Axl knockout resulted in slower growth and increased radiosensitivity. These changes were associated with a CD8+ T-cell response, which was improved in combination with checkpoint immunotherapy. These results suggest a novel role for Axl in suppressing antigen presentation through MHCI, and enhancing cytokine release, which promotes a suppressive myeloid microenvironment. PMID:28008921

  11. Eddy current system for inspection of train hollow axles

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

    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.

  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 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

  14. 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

  15. 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.

  16. AXL modulates extracellular matrix protein expression and is essential for invasion and metastasis in endometrial cancer

    PubMed Central

    Meller, Eric; Desai, Riva A.; Arif, Batool; Rankin, Erinn B.; Bligard, Katherine H.; Meyerson, Cherise; Hagemann, Ian S.; Massad, Maria; Thaker, Premal H.; Hagemann, Andrea R.; McCourt, Carolyn K.; Powell, Matt A.; Mutch, David G.; Fuh, Katherine C.

    2016-01-01

    The receptor tyrosine kinase AXL promotes migration, invasion, and metastasis. Here, we evaluated the role of AXL in endometrial cancer. High immunohistochemical expression of AXL was found in 76% (63/83) of advanced-stage, and 77% (82/107) of high-grade specimens and correlated with worse survival in uterine serous cancer patients. In vitro, genetic silencing of AXL inhibited migration and invasion but had no effect on proliferation of ARK1 endometrial cancer cells. AXL-deficient cells showed significantly decreased expression of phospho-AKT as well as uPA, MMP-1, MMP-2, MMP-3, and MMP-9. In a xenograft model of human uterine serous carcinoma with AXL-deficient ARK1 cells, there was significantly less tumor burden than xenografts with control ARK1 cells. Together, these findings underscore the therapeutic potentials of AXL as a candidate target for treatment of metastatic endometrial cancer. PMID:27764792

  17. 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

  18. 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...

  19. 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.

  20. Soluble Axl is generated by ADAM10-dependent cleavage and associates with Gas6 in mouse serum.

    PubMed

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

    2005-11-01

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

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

    PubMed Central

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

    2005-01-01

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

  2. 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.

  3. Implication of the Receptor Tyrosine Kinase AXL in Head and Neck Cancer Progression

    PubMed Central

    von Mässenhausen, Anne; Brägelmann, Johannes; Billig, Hannah; Thewes, Britta; Queisser, Angela; Vogel, Wenzel; Kristiansen, Glen; Schröck, Andreas; Bootz, Friedrich; Brossart, Peter; Kirfel, Jutta; Perner, Sven

    2016-01-01

    Head and neck squamous cell carcinoma (HNSCC) remains a clinical challenge and identification of novel therapeutic targets is necessary. The receptor tyrosine kinase AXL has been implicated in several tumor entities and a selective AXL small molecule inhibitor (BGB324) is currently being tested in clinical trials for patients suffering from non-small cell lung cancer or acute myeloid leukemia. Our study investigates AXL expression during HNSCC progression and its use as a potential therapeutic target in HNSCC. AXL protein expression was determined in a HNSCC cohort (n = 364) using immunohistochemical staining. For functional validation, AXL was either overexpressed or inhibited with BGB324 in HNSCC cell lines to assess proliferation, migration and invasion. We found AXL protein expression increasing during tumor progression with highest expression levels in recurrent tumors. In HNSCC cell lines in vitro, AXL overexpression increased migration as well as invasion. Both properties could be reduced through treatment with BGB324. In contrast, proliferation was neither affected by AXL overexpression nor by inhibition with BGB324. Our patient-derived data and in vitro results show that, in HNSCC, AXL is important for the progression to more advanced tumor stages. Moreover, they suggest that AXL could be a target for precision medicine approaches in this dismal tumor entity. PMID:28025482

  4. 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.

  5. Preclinical validation of AXL receptor as a target for antibody-based pancreatic cancer immunotherapy

    PubMed Central

    Leconet, Wilhem; Larbouret, Christel; Chardès, Thierry; Thomas, Gaëlle; Neiveyans, Madeline; Busson, Muriel; Jarlier, Marta; Radosevic-Robin, Nina; Pugnière, Martine; Bernex, Florence; Penault-Llorca, Frédérique; Pasquet, Jean-Max; Pèlegrin, André; Robert, Bruno

    2014-01-01

    AXL receptor tyrosine kinases is implicated in proliferation and invasion of many cancers, particularly in pancreatic ductal adenocarcinoma (PDAC), for which new therapeutic options are urgently required. We investigated whether inhibition of AXL activity by specific monoclonal antibodies (mAbs) is efficient in limiting proliferation and migration of pancreatic cancer cells. Expression of AXL was evaluated by immunohistochemistry in 42 PDAC. The AXL role in oncogenesis was studied using the short hairpin RNA approach in a pancreatic carcinoma cell line. We further generated anti-human AXL mAbs and evaluated their inhibitory effects and the AXL downstream signaling pathways first in vitro, in a panel of pancreatic cancer cell lines and then in vivo, using subcutaneous or orthotopic pancreatic tumor xenografts. AXL receptor was found expressed in 76% (32/42) of PDAC and was predominantly present in invasive cells. The AXL-knockdown Panc-1 cells decreased in vitro cell migration, survival and proliferation, and reduced in vivo tumor growth. Two selected anti-AXL mAbs (D9 and E8), which inhibited phosphorylation of AXL and of its downstream target AKT without affecting GAS6 binding, induced down-expression of AXL by internalization, leading to an inhibition of proliferation and migration in the four pancreatic cancer cell lines studied. In vivo, treatment by anti-AXL mAbs significantly reduced growth of both subcutaneous and orthotopic pancreatic tumor xenografts independently of their KRAS mutation status. Our in vitro and preclinical in vivo data demonstrate that anti-human AXL mAbs could represent a new approach to the pancreatic cancer immunotherapy. PMID:24240689

  6. Coexpression of receptor tyrosine kinase AXL and EGFR in human primary lung adenocarcinomas.

    PubMed

    Wu, Zhenzhou; Bai, Fan; Fan, Liyun; Pang, Wenshuai; Han, Ruiyu; Wang, Juan; Liu, Yueping; Yan, Xia; Duan, Huijun; Xing, Lingxiao

    2015-12-01

    AXL has been identified as a tyrosine kinase switch that causes resistance to inhibitors targeting epidermal growth factor receptor (EGFR) signaling in non-small cell lung cancer (NSCLC). However, the relationship between 2 receptor tyrosine kinases, AXL and EGFR, and the relevance of AXL expression with EGFR mutation status in treatment-naive human NSCLCs remain uncertain. In this study, we evaluated the coexpression pattern of AXL, EGFR, and pEGFR(1068) in 109 lung adenocarcinoma patients with or without an EGFR mutation. There were 68 (62.4%) patients with tumors harboring EGFR mutations such as 19 del and/or L858R; 2 patients were T790M positive. The expression of AXL, EGFR, and pEGFR(1068) was detected in 60 (55%), 68 (62.4%), and 57 (52.3%) of 109 patients, respectively. The positive rates of EGFR and pEGFR(1068) were associated with the L858R mutation alone or with the 19 del and L858R mutation status. Further analysis indicated that the percentage of AXL(+)/EGFR(+)/pEGFR(1068) coexpression in 68 EGFR-activating mutations patients was significantly higher than that in 39 EGFR wild-type patients (30.9% versus 10.3%, P=.015). Furthermore, in the subgroup of AXL(+) patients (35 mutation(+) and 23 wild-type patients), the coexpression rates of AXL(+)/pEGFR(1068+) and AXL(+)/EGFR(+)/pEGFR(1068+) in patients with EGFR mutations were significantly higher compared with those in wild-type patients (both P<.05). Our study emphasized that the AXL and EGFR receptor tyrosine kinases were coexpressed in a subgroup of treatment-naive lung adenocarcinomas with or without EGFR mutations. Anti-AXL therapeutics delivered up front in combination with an EGFR inhibitor might prevent or delay resistance in patients with AXL-positive, EGFR-mutant, or wild-type NSCLC.

  7. Soluble AXL: a possible circulating biomarker for neurofibromatosis type 1 related tumor burden.

    PubMed

    Johansson, Gunnar; Peng, Po-Chun; Huang, Po-Yuan; Chien, Hsiung-Fei; Hua, Kuo-Tai; Kuo, Min-Liang; Chen, Chin-Tin; Lee, Ming-Jen

    2014-01-01

    Neurofibromatosis type 1 (NF1) is the most common tumor predisposition disorder affecting 1/3500 worldwide. Patients are at risk of developing benign (neurofibromas) and malignant peripheral nerve sheath tumors (MPNST). The AXL receptor tyrosine kinase has been implicated in several kinds of cancers, but so far no studies have investigated the role of AXL in NF1 related tumorigenesis. Recently, the soluble fraction from the extracellular domain of AXL (sAXL) has been found in human plasma, and its level was correlated to poor prognosis in patients with renal cancer. Compared to normal human Schwann cells, a significantly high expression level of AXL was found in three of the four MPNST cell lines and two of the three primary MPNST tissues. Similarly, the level of sAXL in conditioned media corresponded to the protein and mRNA levels of AXL in the MPNST cell lines. Furthermore, in two different human MPNST xenograft models, the human sAXL could be detected in the mouse plasma. Its level was proportionate to the size of the xenograft tumors, while no human sAXL was detect prior to the formation of the tumors. Treatment with a newly developed photodynamic therapy, prevented further tumor growth and resulted in drastically reduced the levels of sAXL compared to that of the control group. Finally, the level of sAXL was significantly increased in patients with plexiform tumors compared to patients with only dermal neurofibromas, further supporting the role of sAXL as a marker for NF1 related tumor burden.

  8. Rotation of artificial rotor axles in rotary molecular motors.

    PubMed

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

    2016-10-04

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

  9. Rotation of artificial rotor axles in rotary molecular motors

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2005-12-21

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

  11. 49 CFR 230.100 - Defects in tender truck axles and journals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Steam Locomotives and Tenders Running Gear § 230.100 Defects in tender truck axles and journals....

  12. Axl receptor tyrosine kinase is a novel target of apigenin for the inhibition of cell proliferation.

    PubMed

    Kim, Kyung-Chan; Choi, Eun-Ha; Lee, Chuhee

    2014-08-01

    The Axl receptor tyrosine kinase (RTK), along with Tyro 3 and Mer, belongs to the TAM subfamily that promotes survival, stimulates proliferation and/or inhibits apoptosis. In various types of human cancer, including breast, lung and prostate cancer, Axl expression is increased and correlates with an advanced clinical stage. In this study, we examined whether apigenin has an effect on Axl expression, which in turn can affect cell proliferation. The treatment of the non‑small cell lung cancer (NSCLC) cells, A549 and H460, with apigenin decreased Axl mRNA and protein expression in a dose‑dependent manner. Axl promoter activity was also inhibited by apigenin, indicating that apigenin suppressed Axl expression at the transcriptional level. Upon treatment with apigenin, the viability of both the A549 and H460 cells was gradually decreased and the anti-proliferative effects were further confirmed by the dose‑dependent decrease in the clonogenic ability of the apigenin‑treated cells. Subsequently, we found that the viability and clonogenic ability of the cells treated with apigenin was less or more affected by transfection of the cells with a Axl-expressing plasmid or Axl targeting siRNA, compared to transfection with the empty vector or control siRNA, respectively. In addition, apigenin increased the expression of p21, a cyclin-dependent kinase inhibitor, but reduced the expression of X-linked inhibitor of apoptosis protein (XIAP). These cell cycle arrest and pro-apoptotic effects of apigenin were also attenuated or augmented by the up- or downregulation of Axl expression, respectively, which suggests that Axl is a novel target of apigenin through which it exerts its inhibitory effects on cell proliferation. Taken together, our data indicate that apigenin downregulates Axl expression, which subsequently results in the inhibition of NSCLC cell proliferation through the increase and decrease of p21 and XIAP expression, respectively.

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-06

    ..., 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...

  14. 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)...

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

    PubMed Central

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

    2005-01-01

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

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

    PubMed Central

    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.

    2014-01-01

    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

  18. Expression of Axl and its prognostic significance in human breast cancer

    PubMed Central

    Jin, Gaoyuan; Wang, Zhenzhen; Wang, Jianguang; Zhang, Like; Chen, Yanbin; Yuan, Pengfei; Liu, Dechun

    2017-01-01

    Breast cancer is the most common malignant cancer and second leading cause of cancer-related death among women, and its prevalence continues to increase. Axl overexpression has been identified in the many types of human cancer, and it has been demonstrated to participate in signaling pathways related to carcinogenesis and cancer development. In the present study, Axl expression was examined by performing immunohistochemical staining in 60 breast cancer tumors and 40 benign breast lesions (25 mammary dysplasia and 15 breast fibroadenoma). In total, 34 (56.67%) cancer tissues and 13 (32.5%) benign breast lesions were classified as exhibiting high levels of Axl expression, indicating a significant association between malignancy and high Axl expression. High Axl expression was also associated with estrogen receptor (ER) positivity (P=0.028), progesterone receptor (PR) positivity (P=0.007), and poor tumor differentiation (P=0.033). No significant associations were observed between Axl expression and age, tumor size, lymph node metastasis, tumor node metastasis staging, human epidermal growth factor receptor 2 and Ki67 antigen. The Kaplan-Meier survival analysis and Cox proportional hazard model both demonstrated that there was no statistical difference between Axl expression and breast cancer prognosis. However, it remains unclear whether the expression of Axl is correlated with the prognosis of luminal type breast cancer patients. PMID:28356938

  19. 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)...

  20. 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)...

  1. 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)...

  2. 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)...

  3. 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)...

  4. Role of AXL expression in non-small cell lung cancer

    PubMed Central

    Qu, Xiaohan; Liu, Jinlu; Zhong, Xinwen; Li, Xi; Zhang, Qigang

    2016-01-01

    The present study aimed to investigate the expression profile of AXL in non-small cell lung cancer (NSCLC) and its clinical significance. The current study included 257 NSCLC patients, tyrosine-protein kinase receptor UFO (AXL) expression in paired lung cancer and adjacent normal lung tissues of NSCLC patients were compared by immunohistochemistry, western blot analysis and quantitative polymerase chain reaction (qPCR). These methods were used to detect the expression of the AXL gene and protein in fresh tissues from 35 patients. Small interfering RNA (siRNA) was transfected into the H1299 lung cancer cell line to knock down AXL expression; the effects of AXL-siRNA on cell proliferation and migration were examined by MTT and Transwell migration assay, respectively. It was found that AXL staining density in lung cancer tissues was significantly increased compared with adjacent normal lung tissues (55.25 vs. 26.85%; P<0.01); and the expression level of AXL in NSCLC patients was significantly associated with the degree of tumor differentiation (P<0.01) and the clinical stage of disease (P<0.01). Western blotting and qPCR showed that AXL expression was significantly higher in cancer tissues compared with that in adjacent lung tissue (P<0.05). Additionally, the current study also showed that AXL-siRNA inhibited H1299 cell proliferation and migration in vitro. The present study demonstrates the association between increased expression of AXL in NSCLC and the low differentiation phenotype, and its effects on cell proliferation and migration, suggesting its potential clinical values for the prognosis of NSCLC. PMID:28105215

  5. Role of AXL expression in non-small cell lung cancer.

    PubMed

    Qu, Xiaohan; Liu, Jinlu; Zhong, Xinwen; Li, Xi; Zhang, Qigang

    2016-12-01

    The present study aimed to investigate the expression profile of AXL in non-small cell lung cancer (NSCLC) and its clinical significance. The current study included 257 NSCLC patients, tyrosine-protein kinase receptor UFO (AXL) expression in paired lung cancer and adjacent normal lung tissues of NSCLC patients were compared by immunohistochemistry, western blot analysis and quantitative polymerase chain reaction (qPCR). These methods were used to detect the expression of the AXL gene and protein in fresh tissues from 35 patients. Small interfering RNA (siRNA) was transfected into the H1299 lung cancer cell line to knock down AXL expression; the effects of AXL-siRNA on cell proliferation and migration were examined by MTT and Transwell migration assay, respectively. It was found that AXL staining density in lung cancer tissues was significantly increased compared with adjacent normal lung tissues (55.25 vs. 26.85%; P<0.01); and the expression level of AXL in NSCLC patients was significantly associated with the degree of tumor differentiation (P<0.01) and the clinical stage of disease (P<0.01). Western blotting and qPCR showed that AXL expression was significantly higher in cancer tissues compared with that in adjacent lung tissue (P<0.05). Additionally, the current study also showed that AXL-siRNA inhibited H1299 cell proliferation and migration in vitro. The present study demonstrates the association between increased expression of AXL in NSCLC and the low differentiation phenotype, and its effects on cell proliferation and migration, suggesting its potential clinical values for the prognosis of NSCLC.

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

    PubMed

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

    2016-12-06

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

  7. Deficiency of AXL in Bone Marrow-Derived Cells Does Not Affect Advanced Atherosclerotic Lesion Progression.

    PubMed

    Subramanian, Manikandan; Proto, Jonathan D; Matsushima, Glenn K; Tabas, Ira

    2016-12-13

    AXL, a member of the TAM (Tyro3, Axl, MerTK) family of receptors, plays important roles in cell survival, clearance of dead cells (efferocytosis), and suppression of inflammation, which are processes that critically influence atherosclerosis progression. Whereas MerTK deficiency promotes defective efferocytosis, inflammation, and plaque necrosis in advanced murine atherosclerosis, the role of Axl in advanced atherosclerosis progression is not known. Towards this end, bone marrow cells from Axl(-/-) or wild-type mice were transplanted into lethally irradiated Ldlr(-/-) mice. These chimeric mice were then fed the Western-type diet (WD) for 17 weeks. We demonstrate that lesional macrophages in WT mice express Axl but that Axl deficiency in bone marrow-derived cells does not affect lesion size, cellularity, necrosis, or inflammatory parameters in advanced atherosclerotic plaques. Moreover, apoptosis of lesional cells was unaffected, and we found no evidence of defective lesional efferocytosis. In contrast to previously reported findings with MerTK deficiency, hematopoietic cell-Axl deficiency in WD-fed Ldlr(-/-) mice does not affect the progression of advanced atherosclerosis or lesional processes associated with TAM receptor signaling. These findings suggest a heretofore unappreciated TAM receptor hierarchy in advanced atherosclerosis.

  8. Feedback regulation of IFN-α/β signaling by Axl receptor tyrosine kinase modulates HBV immunity.

    PubMed

    Huang, Miao-Tzu; Liu, Wei-Liang; Lu, Chun-Wei; Huang, Jian-Jhih; Chuang, Hsiao-Li; Huang, Yen-Te; Horng, Jau-Haw; Liu, Peng; Han, Dai-Shu; Chiang, Bor-Luen; Shih, Chiaho; Chen, Pei-Jer; Chen, Ding-Shinn

    2015-06-01

    Hepatitis B virus (HBV) is known to cause age-dependent infection outcomes wherein most infections during young age result in chronicity. The mechanism underlying the differential outcome remains elusive. By using hydrodynamic injection of the replication-competent pAAV-HBV, we established a mouse model in which HBV persistence was generated in 4-5 w/o C57BL/6 young mice, but not in adult mice over 10 w/o. HBV-tolerant young mice expressed higher interferon (IFN)-α/β levels in hepatocytes and intrahepatic plasmacytoid DCs (pDCs) than adult mice after pAAV-HBV injection. Excessive IFN-α/β expression in young mice was associated with induction of the Axl regulatory pathway and expansion of intrahepatic Treg cells. In line with these findings, augmented IFN-β expression increased Axl expression in the liver and HBV persistence in adult mice, whereas IFN-α/β signaling blockage decreased Axl expression and HBV persistence in young mice. Accordingly, Axl overexpression decreased HBV clearance of adult mice whereas Axl silencing enhanced HBV clearance of young mice. In vitro, IFN-β priming of pDCs and Axl-overexpressing macrophages enhanced Treg-cell differentiation. These findings suggest that age-dependent HBV chronicity is attributed to IFN-β-Axl immune regulation, which is selectively induced in young mice by excessive IFN-α/β production at early stage of HBV infection.

  9. Split axle drive mechanism for part-time four-wheel drive vehicle

    SciTech Connect

    Onodera, T.

    1986-12-02

    A split axle drive mechanism is described for a part-time four-wheel drive vehicle equipped with a transfer device adapted to change the operating mode of the vehicle drive system to a two wheel drive mode and a four wheel drive mode, comprising: a differential housing; a differential case rotatably mounted within the housing. The differential case is provided thereon with a ring gear for rotation about a first axis and provided therein with pinion gears for rotation about a second axis perpendicular to the first axis and a pair of side gear for rotation about the first axis and in meshing engagement with each of the pinion gears; a first axle shaft disposed along the first axis and connected to one of the side gears for rotation therewith; a second axle shaft disposed along the first axis and axially slidably connected to the other side gear for rotation therewith; a first output member disposed along the first axis to be connected to the first axle shaft and having an outer end adapted for attachment to one split axle part for driving one of a pair of vehicle road wheels; and a second output member disposed along the first axis to be connected to the second axle shaft and having an outer end adapted for attachment to the other split axle part for driving the other road wheel.

  10. Numerical study for a new methodology of flaws detection in train axles.

    PubMed

    Mineo, C; Cerniglia, D; Pantano, A

    2014-03-01

    Train loads and travel speeds have increased over time, requiring more efficient non-destructive inspection methods. Railway axles are critical elements; despite being designed to last more than 20 years several cases of premature failure have been recorded. Train axles are inspected regularly, but the limits associated to the traditional inspection technologies create a growing interest towards new solutions. Here a novel non-destructive inspection method of in-service axles based on non-contact data collection is presented. The propagation of surface waves, generated by a thermo-elastic laser source, is investigated using a finite element method based on dynamic explicit integration. Coupled thermo-mechanical simulations allow visualization of the ultrasonic field guiding the definition of the optimal NDT setup. The geometry of the axle and of the elements mounted on it is accurately reproduced; moreover the press fit effect caused by the wheel and the bearing rings is implemented. The current NDT techniques for railway axles require removing wheels and other components from the axle. The presented scheme uses non-contact ultrasonic generation and detection allowing non-contact in-service inspection of railway axles at trackside station. The numerical results are promising and encourage us to test the new approach experimentally.

  11. 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

  12. Gas6/Axl pathway is activated in chronic liver disease and its targeting reduces fibrosis via hepatic stellate cell inactivation

    PubMed Central

    Bárcena, Cristina; Stefanovic, Milica; Tutusaus, Anna; Joannas, Leonel; Menéndez, Anghara; García-Ruiz, Carmen; Sancho-Bru, Pau; Marí, Montserrat; Caballeria, Joan; Rothlin, Carla V.; Fernández-Checa, José C.; de Frutos, Pablo García; Morales, Albert

    2015-01-01

    Background & Aims Liver fibrosis, an important health concern associated to chronic liver injury that provides a permissive environment for cancer development, is characterized by accumulation of extracellular matrix components mainly derived from activated hepatic stellate cells (HSCs). Axl, a receptor tyrosine kinase, and its ligand Gas6 are involved in cell differentiation, immune response and carcinogenesis. Methods HSCs were obtained from wild type and Axl−/− mice, treated with recombinant Gas6 protein (rGas6), Axl siRNAs or the Axl inhibitor BGB324, and analyzed by western blot and real-time PCR. Experimental fibrosis was studied in CCl4-treated wild type and Axl−/− mice, and in combination with Axl inhibitor. Gas6 and Axl serum levels were measured in alcoholic liver disease (ALD) and hepatitis C virus (HCV) patients. Results In primary mouse HSCs, Gas6 and Axl levels paralleled HSC activation. rGas6 phosphorylated Axl and AKT prior to HSC phenotypic changes, while Axl siRNA silencing reduced HSC activation. Moreover, BGB324 blocked Axl/AKT phosphorylation and diminished HSC activation. In addition, Axl KO mice displayed decreased HSC activation in vitro and liver fibrogenesis after chronic damage by CCl4 administration. Similarly, BGB324 reduced collagen deposition and CCl4-induced liver fibrosis in mice. Importantly, Gas6 and Axl serum levels increased in ALD and HCV patients, inversely correlating with liver functionality. Conclusions: The Gas6/Axl axis is required for full HSC activation. Gas6 and Axl serum levels increase in parallel to chronic liver disease progression. Axl targeting may be a therapeutic strategy for liver fibrosis management. PMID:25908269

  13. Regulated intramembrane proteolysis of the AXL receptor kinase generates an intracellular domain that localizes in the nucleus of cancer cells

    PubMed Central

    Lu, Yinzhong; Wan, Jun; Yang, Zhifeng; Lei, Xiling; Niu, Qi; Jiang, Lanxin; Passtoors, Willemijn M.; Zang, Aiping; Fraering, Patrick C.; Wu, Fang

    2017-01-01

    Deregulation of the TAM (TYRO3, AXL, and MERTK) family of receptor tyrosine kinases (RTKs) has recently been demonstrated to predominately promote survival and chemoresistance of cancer cells. Intramembrane proteolysis mediated by presenilin/γ-secretase is known to regulate the homeostasis of some RTKs. In the present study, we demonstrate that AXL, but not TYRO3 or MERTK, is efficiently and sequentially cleaved by α- and γ-secretases in various types of cancer cell lines. Proteolytic processing of AXL redirected signaling toward a secretase-mediated pathway, away from the classic, well-known, ligand-dependent canonical RTK signaling pathway. The AXL intracellular domain cleavage product, but not full-length AXL, was further shown to translocate into the nucleus via a nuclear localization sequence that harbored a basic HRRKK motif. Of interest, we found that the γ-secretase–uncleavable AXL mutant caused an elevated chemoresistance in non–small-cell lung cancer cells. Altogether, our findings suggest that AXL can undergo sequential processing mediated by various proteases kept in a homeostatic balance. This newly discovered post-translational processing of AXL may provide an explanation for the diverse functions of AXL, especially in the context of drug resistance in cancer cells.—Lu, Y., Wan, J., Yang, Z., Lei, X., Niu, Q., Jiang, L., Passtoors, W. M., Zang, A., Fraering, P. C., Wu, F. Regulated intramembrane proteolysis of the AXL receptor kinase generates an intracellular domain that localizes in the nucleus of cancer cells. PMID:28034848

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

    PubMed Central

    Wong, Li-Fan; Lee, Jang-Ming

    2016-01-01

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

  15. 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.

  16. Non-intrusive schemes for speed and axle identification in bridge-weigh-in-motion systems

    NASA Astrophysics Data System (ADS)

    Kalhori, Hamed; Makki Alamdari, Mehrisadat; Zhu, Xinqun; Samali, Bijan; Mustapha, Samir

    2017-02-01

    Bridge weigh-in-motion (BWIM) is an approach through which the axle and gross weight of trucks travelling at normal highway speed are identified using the response of an instrumented bridge. The vehicle speed, the number of axles, and the axle spacing are crucial parameters, and are required to be determined in the majority of BWIM algorithms. Nothing-on-the-road (NOR) strategy suggests using the strain signals measured at some particular positions underneath the deck or girders of a bridge to obtain this information. The objective of this research is to present a concise overview of the challenges of the current non-intrusive schemes for speed and axle determination through bending-strain and shear-strain based approaches. The problem associated with the global bending-strain responses measured at quarter points of span is discussed and a new sensor arrangement is proposed as an alternative. As for measurement of local responses rather than the global responses, the advantage of shear strains over bending strains is presented. However, it is illustrated that shear strains at quarter points of span can only provide accurate speed estimation but fail to detect the correct number of axles. As a remedy, it is demonstrated that, even for closely-spaced axles, the shear strain at the beginning of the bridge is capable of reliably identifying the number of axles. In order to provide a fully automated speed and axle identification system, appropriate signal processing including low-pass filtering and wavelet transforms are applied to the raw time signals. As case studies, the results of experimental testing in laboratory and on a real bridge are presented.

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

    NASA Astrophysics Data System (ADS)

    Wu, Jungang; Zhang, Siqin; Yang, Qinglong

    2013-03-01

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

  18. AXL.Net: Web-Enabled Case Method Instruction for Accelerating Tacit Knowledge Acquisition in Leaders

    DTIC Science & Technology

    2006-11-01

    King, Salvo Lavis , Scott Rocher USC Institute for Creative Technologies ABSTRACT AXL.Net is a prototype web-based immersive technology...needed to be invented for augmenting existing techniques or creating wholly new ones. Finally, theories about the acquisition of tacit knowledge... attention to the issues that they did not select. AXL.Net provides different points of view through a virtual (though currently non-animated

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

    PubMed

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

    2015-01-01

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

  20. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

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

  2. Deficiency of AXL in Bone Marrow-Derived Cells Does Not Affect Advanced Atherosclerotic Lesion Progression

    PubMed Central

    Subramanian, Manikandan; Proto, Jonathan D.; Matsushima, Glenn K.; Tabas, Ira

    2016-01-01

    AXL, a member of the TAM (Tyro3, Axl, MerTK) family of receptors, plays important roles in cell survival, clearance of dead cells (efferocytosis), and suppression of inflammation, which are processes that critically influence atherosclerosis progression. Whereas MerTK deficiency promotes defective efferocytosis, inflammation, and plaque necrosis in advanced murine atherosclerosis, the role of Axl in advanced atherosclerosis progression is not known. Towards this end, bone marrow cells from Axl−/− or wild-type mice were transplanted into lethally irradiated Ldlr−/− mice. These chimeric mice were then fed the Western-type diet (WD) for 17 weeks. We demonstrate that lesional macrophages in WT mice express Axl but that Axl deficiency in bone marrow-derived cells does not affect lesion size, cellularity, necrosis, or inflammatory parameters in advanced atherosclerotic plaques. Moreover, apoptosis of lesional cells was unaffected, and we found no evidence of defective lesional efferocytosis. In contrast to previously reported findings with MerTK deficiency, hematopoietic cell-Axl deficiency in WD-fed Ldlr−/− mice does not affect the progression of advanced atherosclerosis or lesional processes associated with TAM receptor signaling. These findings suggest a heretofore unappreciated TAM receptor hierarchy in advanced atherosclerosis. PMID:27958361

  3. 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.

  4. 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’.

  5. Identification of Axl as a downstream effector of TGF-β1 during Langerhans cell differentiation and epidermal homeostasis

    PubMed Central

    Bauer, Thomas; Zagórska, Anna; Jurkin, Jennifer; Yasmin, Nighat; Köffel, René; Richter, Susanne; Gesslbauer, Bernhard; Lemke, Greg

    2012-01-01

    Transforming growth factor-β1 (TGF-β1) is a fundamental regulator of immune cell development and function. In this study, we investigated the effects of TGF-β1 on the differentiation of human Langerhans cells (LCs) and identified Axl as a key TGF-β1 effector. Axl belongs to the TAM (Tyro3, Axl, and Mer) receptor tyrosine kinase family, whose members function as inhibitors of innate inflammatory responses in dendritic cells and are essential to the prevention of lupus-like autoimmunity. We found that Axl expression is induced by TGF-β1 during LC differentiation and that LC precursors acquire Axl early during differentiation. We also describe prominent steady-state expression as well as inflammation-induced activation of Axl in human epidermal keratinocytes and LCs. TGF-β1–induced Axl enhances apoptotic cell (AC) uptake and blocks proinflammatory cytokine production. The antiinflammatory role of Axl in the skin is reflected in a marked impairment of the LC network preceding spontaneous skin inflammation in mutant mice that lack all three TAM receptors. Our findings highlight the importance of constitutive Axl expression to tolerogenic barrier immunity in the epidermis and define a mechanism by which TGF-β1 enables silent homeostatic clearing of ACs to maintain long-term self-tolerance. PMID:23071254

  6. Dynamic axle and wheel loads identification: laboratory studies

    NASA Astrophysics Data System (ADS)

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

    2003-12-01

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

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

    PubMed Central

    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

    2016-01-01

    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

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

    PubMed Central

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

    2015-01-01

    Increased expression of the Microphthalmia-associated transcription factor (MITF) contributes to melanoma progression and resistance to BRAF pathway inhibition. Here we show that the lack of MITF is associated with more severe resistance to a range of inhibitors, while its presence is required for robust drug responses. Both in primary and acquired resistance, MITF levels inversely correlate with the expression of several activated receptor tyrosine kinases, most frequently AXL. The MITF-low/AXL-high/drug-resistance phenotype is common among mutant BRAF and NRAS melanoma cell lines. The dichotomous behaviour of MITF in drug response is corroborated in vemurafenib-resistant biopsies, including MITF-high and -low clones in a relapsed patient. Furthermore, drug cocktails containing AXL inhibitor enhance melanoma cell elimination by BRAF or ERK inhibition. Our results demonstrate that a low MITF/AXL ratio predicts early resistance to multiple targeted drugs, and warrant clinical validation of AXL inhibitors to combat resistance of BRAF and NRAS mutant MITF-low melanomas. PMID:25502142

  9. AXL-dependent infection of human fetal endothelial cells distinguishes Zika virus from other pathogenic flaviviruses

    PubMed Central

    Richard, Audrey Stéphanie; Shim, Byoung-Shik; Kwon, Young-Chan; Zhang, Rong; Otsuka, Yuka; Schmitt, Kimberly; Berri, Fatma; Diamond, Michael S.; Choe, Hyeryun

    2017-01-01

    Although a causal relationship between Zika virus (ZIKV) and microcephaly has been established, it remains unclear why ZIKV, but not other pathogenic flaviviruses, causes congenital defects. Here we show that when viruses are produced in mammalian cells, ZIKV, but not the closely related dengue virus (DENV) or West Nile virus (WNV), can efficiently infect key placental barrier cells that directly contact the fetal bloodstream. We show that AXL, a receptor tyrosine kinase, is the primary ZIKV entry cofactor on human umbilical vein endothelial cells (HUVECs), and that ZIKV uses AXL with much greater efficiency than does DENV or WNV. Consistent with this observation, only ZIKV, but not WNV or DENV, bound the AXL ligand Gas6. In comparison, when DENV and WNV were produced in insect cells, they also infected HUVECs in an AXL-dependent manner. Our data suggest that ZIKV, when produced from mammalian cells, infects fetal endothelial cells much more efficiently than other pathogenic flaviviruses because it binds Gas6 more avidly, which in turn facilitates its interaction with AXL. PMID:28167751

  10. AXL-dependent infection of human fetal endothelial cells distinguishes Zika virus from other pathogenic flaviviruses.

    PubMed

    Richard, Audrey Stéphanie; Shim, Byoung-Shik; Kwon, Young-Chan; Zhang, Rong; Otsuka, Yuka; Schmitt, Kimberly; Berri, Fatma; Diamond, Michael S; Choe, Hyeryun

    2017-02-21

    Although a causal relationship between Zika virus (ZIKV) and microcephaly has been established, it remains unclear why ZIKV, but not other pathogenic flaviviruses, causes congenital defects. Here we show that when viruses are produced in mammalian cells, ZIKV, but not the closely related dengue virus (DENV) or West Nile virus (WNV), can efficiently infect key placental barrier cells that directly contact the fetal bloodstream. We show that AXL, a receptor tyrosine kinase, is the primary ZIKV entry cofactor on human umbilical vein endothelial cells (HUVECs), and that ZIKV uses AXL with much greater efficiency than does DENV or WNV. Consistent with this observation, only ZIKV, but not WNV or DENV, bound the AXL ligand Gas6. In comparison, when DENV and WNV were produced in insect cells, they also infected HUVECs in an AXL-dependent manner. Our data suggest that ZIKV, when produced from mammalian cells, infects fetal endothelial cells much more efficiently than other pathogenic flaviviruses because it binds Gas6 more avidly, which in turn facilitates its interaction with AXL.

  11. Axl promotes the proliferation, invasion and migration of Wilms’ tumor and can be used as a prognostic factor

    PubMed Central

    Zhu, Shibo; Liu, Guochang; Fu, Wen; Hu, Jinhua; Fu, Kai; Jia, Wei

    2017-01-01

    Purpose Overexpression of Axl has been reported in many tumors, where it promotes tumorigenesis and progression, as well as correlates with the prognosis of different malignancies. However, Axl expression and its function have rarely been reported in Wilms’ tumor (WT). This study aimed to reveal the clinical significance of Axl expression in patients with WT and determine its mechanisms. Materials and methods We analyzed the expression of Axl and its correlations with various clinicopathological features in 72 WT tissues and 72 adjacent non-cancerous tissues by immunohistochemistry. Cox proportional hazards regression models were used to investigate the correlations between Axl expression and the prognosis of WT patients. Fresh frozen samples from 20 WT patients were examined using Western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). In WT cell line, after Axl knockdown by sh-Axl and growth arrest-specific 6 (Gas6) stimulation, the cell proliferation, migration and invasion abilities were detected by methyl-thiazolyl-tetrazolium (MTT), clone-forming, wound-healing and transwell assays. Meanwhile, the tumor-forming ability was tested on nude mice xenograft models. Finally, the expression of several proteins in signal pathways was quantified by WB assays. Results Compared with the adjacent non-cancerous tissues, the expression of Axl was significantly higher in WT tissues (P<0.05). High expression of Axl was associated with tumor recurrence or lung metastasis of WT patients and was a prognostic factor for WT patients (P<0.05). In vitro assays, the proliferation, migration and invasion of WT cells decreased with Axl knockdown and significantly increased with Axl activation by Gas6 (P<0.05). In vivo assays, the ability of tumorigenicity in WT cells reduced dramatically after Axl knockout (P<0.05). Moreover, PI3K–Akt pathway proteins decreased with Axl knockdown. Conclusion Our results suggest that Axl is highly expressed in WT and

  12. 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

    2016-05-04

    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.

  13. Axl signaling induces development of natural killer cells in vitro and in vivo.

    PubMed

    Kim, Eun-Mi; Lee, Eun-Hee; Lee, Hwa-Yeon; Choi, Ha-Rim; Ji, Kon-Young; Kim, Su-Man; Kim, Kwang Dong; Kang, Hyung-Sik

    2017-03-01

    Natural killer (NK) cells have been well known to play a critical role in innate immunity, but they are also capable of regulating adaptive immunity through the induction of T cell-mediated memory response and B cell-mediated autoimmune response. NK cells are differentiated from hematopoietic stem cells (HSCs) in the bone marrow (BM), and a series of surface molecules are expressed on NK cells in a differentiation stage-specific manner. Axl receptor tyrosine kinase is originally identified as homeostatic regulators for antigen-presenting cells, and its ligand, growth-arrest-specific gene 6 (Gas6), has been reported to promote cell survival, proliferation, and migration, but their regulatory role in the development and effector function of NK cells is not yet fully understood. In this study, to investigate whether Axl is required for the regulation of NK cell development, the expression of mature NK (mNK) cell-specific receptors and NK cell-associated genes was analyzed in the differentiated HSCs-derived NK cells in vitro and the NK cells harvested from Axl(-/-) mice. We found that agonistic anti-Axl antibody or recombinant Gas6 specifically upregulated the expression of mNK cell-specific receptors, such as LY49A, Ly49G2, Ly49C/F/I, NKG2A/C/E (1.5- to 3.5-fold increase), and NK cell-associated genes, such as IL-2Rβ (2.3- or 2.4-fold increase), Perforin (4.1- or 2.1-fold increase), IL-15Rα (2.14- or 2.04-fold increase), and IFN-γ (3.3- or 2.8-fold increase) compared to each isotype control, whereas it was abrogated by treatment of Axl-Ig. Anti-Axl antibody or rGas6 also induced a 2.5- or 1.9-fold increase in the proliferation of developing NK cells compared to each control, respectively. mNK cell populations expressing mNK cell-specific receptors were reduced about twofold in NK cells differentiated from HSCs of Axl(-/-) mice compared with those of wild-type mice. Furthermore, the triggering of Axl signaling by agonistic anti-Axl antibody promoted the

  14. Axl is required for TGF-β2-induced dormancy of prostate cancer cells in the bone marrow

    PubMed Central

    Yumoto, Kenji; Eber, Matthew R.; Wang, Jingcheng; Cackowski, Frank C.; Decker, Ann M.; Lee, Eunsohl; Nobre, Ana Rita; Aguirre-Ghiso, Julio A.; Jung, Younghun; Taichman, Russell S.

    2016-01-01

    Disseminated prostate cancer (PCa) cells in the marrow survive for years without evidence of proliferation, while maintaining the capacity to develop into metastatic lesions. These dormant disseminated tumor cells (DTCs) may reside in close proximity to osteoblasts, while expressing high levels of Axl, one of the tyrosine kinase receptors for growth arrest specific 6 (Gas6). Yet how Axl regulates DTC proliferation in marrow remains undefined. Here, we explored the impact of the loss of Axl in PCa cells (PC3 and DU145) on the induction of their dormancy when they are co-cultured with a pre-osteoblastic cell line, MC3T3-E1. MC3T3-E1 cells dramatically decrease the proliferation of PCa cells, however this suppressive effect of osteoblasts is significantly reduced by the reduction of Axl expression in PCa cells. Interestingly, expression of both TGF-β and its receptors were regulated by Axl expression in PCa cells, while specific blockade of TGF-β signaling limited the ability of the osteoblasts to induce dormancy of PCa cells. Finally, we found that both Gas6 and Axl are required for TGF-β2-mediated cell growth suppression. Taken together, these data suggest that a loop between the Gas6/Axl axis and TGF-β2 signaling plays a significant role in the induction of PCa cell dormancy. PMID:27819283

  15. 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

  16. Influence of axle-wheel interface on ultrasonic testing of fatigue cracks in wheelset.

    PubMed

    Makino, Kazunari; Biwa, Shiro

    2013-01-01

    For the ultrasonic testing at the wheel seat of railway axles, quantitative investigation of the reflection and transmission phenomena at the axle-wheel interface is important. This paper describes the influence of the axle-wheel interface on the ultrasonic testing of a fatigue crack in a wheelset by applying the spring interface model. The normal and tangential stiffnesses were identified experimentally for an as-manufactured wheelset at the normal incidence, and the reflection coefficient for the shear-wave oblique incidence was calculated. A parametric study was performed to clarify the influence of these interfacial stiffnesses on the incident-angle dependence of the reflection coefficient. The calculated reflection coefficient at the incident angle of 45° qualitatively explained the relative echo-height decrease due to the presence of a wheel observed experimentally for a wheelset in fatigue loading by rotating bending. The quantitative difference between the experimental and calculated results was considered to be due to the reduction of the effective interference of shrink fit by the wear at the axle-wheel interface during the fatigue loading as well as by the applied bending moment. For the estimated relative echo-height decrease to agree with the experimental results, the interfacial stiffnesses were found to be smaller than the values identified for the as-manufactured wheelset by a factor of 0.5-0.7.

  17. 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…

  18. Development of an Army Stationary Axle Efficiency Test Stand - Interim Report TFLRF No. 471

    DTIC Science & Technology

    2015-09-01

    chemically charged filters  Excellent heat transfer for high-temperature applications, such as engines with EGR and SCR systems  Outstanding...and outstanding heat transfer, while nitrite-free coolants use organic acid inhibitors to provide guaranteed protection for all cooling system ...UNCLASSIFIED UNCLASSIFIED DEVELOPMENT OF AN ARMY STATIONARY AXLE EFFICIENCY TEST STAND INTERIM REPORT TFLRF No. 471 by Adam C

  19. 75 FR 76036 - American Axle & Manufacturing Detroit Manufacturing Complex Holbrook Avenue and Saint Aubin...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-07

    ... Avenue and Saint Aubin Including On-Site Leased Workers From Paint Tech International Detroit, MI... from Paint Tech International were employed on-site at the Detroit, Michigan location of American Axle..., the Department is amending this certification to include workers leased from Paint Tech...

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

    PubMed

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

    2016-12-01

    Severe hepatic inflammation is a common cause of acute or chronic liver disease. Macrophages are one of the key mediators which regulate the progress of hepatic inflammation. Increasing evidence shows that the TAM (TYRO3, AXL and MERTK) family of RTKs (receptor tyrosine kinases), which is expressed in macrophages, alleviates inflammatory responses through a negative feedback loop. However, the functional contribution of each TAM family member to the progression of hepatic inflammation remains elusive. In this study, we explore the role of individual TAM family proteins during autophagy induction and evaluate their contribution to hepatic inflammation. Among the TAM family of RTKs, AXL (AXL receptor tyrosine kinase) only induces autophagy in macrophages after interaction with its ligand, GAS6 (growth arrest specific 6). Based on our results, autophosphorylation of 2 tyrosine residues (Tyr815 and Tyr860) in the cytoplasmic domain of AXL in mice is required for autophagy induction and AXL-mediated autophagy induction is dependent on MAPK (mitogen-activated protein kinase)14 activity. Furthermore, induction of AXL-mediated autophagy prevents CASP1 (caspase 1)-dependent IL1B (interleukin 1, β) and IL18 (interleukin 18) maturation by inhibiting NLRP3 (NLR family, pyrin domain containing 3) inflammasome activation. In agreement with these observations, axl(-/-) mice show more severe symptoms than do wild-type (Axl(+/+)) mice following acute hepatic injury induced by administration of lipopolysaccharide (LPS) or carbon tetrachloride (CCl4). Hence, GAS6-AXL signaling-mediated autophagy induction in murine macrophages ameliorates hepatic inflammatory responses by inhibiting NLRP3 inflammasome activation.

  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

    ... production of automotive axles a substantial portion of which are shipped to an affiliated plant where they are used in the assembly of automotive vehicles. New information shows that workers leased...

  2. n-Butylidenephthalide Regulated Tumor Stem Cell Genes EZH2/AXL and Reduced Its Migration and Invasion in Glioblastoma

    PubMed Central

    Yen, Ssu-Yin; Chuang, Hong-Meng; Huang, Mao-Hsuan; Lin, Shinn-Zong; Chiou, Tzyy-Wen; Harn, Horng-Jyh

    2017-01-01

    Glioblastoma (GBM) is one of the most common and aggressive types of brain tumor. Due to its highly recurrent rate and poor prognosis, the overall survival time with this type of tumor is only 20–21 months. Recent knowledge suggests that its recurrence is in part due to the presence of cancer stem cells (CSCs), which display radioresistant, chemoresistant, self-renewal and tumorigenic potential. Enhancers of Zeste 2 (EZH2) and AXL receptor tyrosine kinase (AXL) are both highly expressed in GBM. Additionally, they are an essential regulator involved in CSCs maintenance, migration, invasion, epithelial-to-mesenchymal transition (EMT), stemness, metastasis and patient survival. In this study, we used a small molecule, n-butylidenephthalide (BP), to assess the anti-GBM stem-like cells potential, and then tried to find out the associated genes involved with regulation in migration and invasion. We demonstrated that BP reduced the expression of AXL and stemness related genes in a dose-dependent manner. The migratory and invasive capabilities of GBM stem-like cells could be reduced by AXL/EZH2. Finally, in the overexpression of AXL, EZH2 and Sox2 by transfection in GBM stem-like cells, we found that AXL/EZH2/TGF-β1, but not Sox2, might be a key regulator in tumor invasion, migration and EMT. These results might help in the development of a new anticancer compound and can be a target for treating GBM. PMID:28208648

  3. n-Butylidenephthalide Regulated Tumor Stem Cell Genes EZH2/AXL and Reduced Its Migration and Invasion in Glioblastoma.

    PubMed

    Yen, Ssu-Yin; Chuang, Hong-Meng; Huang, Mao-Hsuan; Lin, Shinn-Zong; Chiou, Tzyy-Wen; Harn, Horng-Jyh

    2017-02-10

    Glioblastoma (GBM) is one of the most common and aggressive types of brain tumor. Due to its highly recurrent rate and poor prognosis, the overall survival time with this type of tumor is only 20-21 months. Recent knowledge suggests that its recurrence is in part due to the presence of cancer stem cells (CSCs), which display radioresistant, chemoresistant, self-renewal and tumorigenic potential. Enhancers of Zeste 2 (EZH2) and AXL receptor tyrosine kinase (AXL) are both highly expressed in GBM. Additionally, they are an essential regulator involved in CSCs maintenance, migration, invasion, epithelial-to-mesenchymal transition (EMT), stemness, metastasis and patient survival. In this study, we used a small molecule, n-butylidenephthalide (BP), to assess the anti-GBM stem-like cells potential, and then tried to find out the associated genes involved with regulation in migration and invasion. We demonstrated that BP reduced the expression of AXL and stemness related genes in a dose-dependent manner. The migratory and invasive capabilities of GBM stem-like cells could be reduced by AXL/EZH2. Finally, in the overexpression of AXL, EZH2 and Sox2 by transfection in GBM stem-like cells, we found that AXL/EZH2/TGF-ꞵ1, but not Sox2, might be a key regulator in tumor invasion, migration and EMT. These results might help in the development of a new anticancer compound and can be a target for treating GBM.

  4. 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

  5. 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

  6. Mer or Axl receptor tyrosine kinase inhibition promotes apoptosis, blocks growth and enhances chemosensitivity of human non-small cell lung cancer.

    PubMed

    Linger, R M A; Cohen, R A; Cummings, C T; Sather, S; Migdall-Wilson, J; Middleton, D H G; Lu, X; Barón, A E; Franklin, W A; Merrick, D T; Jedlicka, P; DeRyckere, D; Heasley, L E; Graham, D K

    2013-07-18

    Non-small cell lung cancer (NSCLC) is a prevalent and devastating disease that claims more lives than breast, prostate, colon and pancreatic cancers combined. Current research suggests that standard chemotherapy regimens have been optimized to maximal efficiency. Promising new treatment strategies involve novel agents targeting molecular aberrations present in subsets of NSCLC. We evaluated 88 human NSCLC tumors of diverse histology and identified Mer and Axl as receptor tyrosine kinases (RTKs) overexpressed in 69% and 93%, respectively, of tumors relative to surrounding normal lung tissue. Mer and Axl were also frequently overexpressed and activated in NSCLC cell lines. Ligand-dependent Mer or Axl activation stimulated MAPK, AKT and FAK signaling pathways indicating roles for these RTKs in multiple oncogenic processes. In addition, we identified a novel pro-survival pathway-involving AKT, CREB, Bcl-xL, survivin, and Bcl-2-downstream of Mer, which is differentially modulated by Axl signaling. We demonstrated that short hairpin RNA (shRNA) knockdown of Mer or Axl significantly reduced NSCLC colony formation and growth of subcutaneous xenografts in nude mice. Mer or Axl knockdown also improved in vitro NSCLC sensitivity to chemotherapeutic agents by promoting apoptosis. When comparing the effects of Mer and Axl knockdown, Mer inhibition exhibited more complete blockade of tumor growth while Axl knockdown more robustly improved chemosensitivity. These results indicate that Mer and Axl have complementary and overlapping roles in NSCLC and suggest that treatment strategies targeting both RTKs may be more effective than singly-targeted agents. Our findings validate Mer and Axl as potential therapeutic targets in NSCLC and provide justification for development of novel therapeutic compounds that selectively inhibit Mer and/or Axl.

  7. 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

  8. 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.

  9. Kinome-wide shRNA screen identifies the receptor tyrosine kinase AXL as a key regulator for mesenchymal glioblastoma stem-like cells.

    PubMed

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

    2015-05-12

    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.

  10. The TRAIL Receptor Agonist Drozitumab Targets Basal B Triple Negative Breast Cancer Cells that Express Vimentin and Axl

    PubMed Central

    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

    Purpose Previously, we found that GST-tagged tumor necrosis factor-related apoptosis inducing ligand (TRAIL) 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. Methods 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. Results and Conclusions 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

  11. Axl-EGFR receptor tyrosine kinase hetero-interaction provides EGFR with access to pro-invasive signalling in cancer cells

    PubMed Central

    Vouri, M; Croucher, D R; Kennedy, S P; An, Q; Pilkington, G J; Hafizi, S

    2016-01-01

    Acquired resistance to conventional and targeted therapies is becoming a major hindrance in cancer management. It is increasingly clear that cancer cells are able to evolve and rewire canonical signalling pathways to their advantage, thus evading cell death and promoting cell invasion. The Axl receptor tyrosine kinase (RTK) has been shown to modulate acquired resistance to EGFR-targeted therapies in both breast and lung cancers. Glioblastoma multiforme (GBM) is a highly infiltrative and invasive form of brain tumour with little response to therapy. Both Axl and EGFR have been identified as major players in gliomagenesis and invasiveness. However, the mechanisms underlying a potential signalling crosstalk between EGFR and Axl RTKs are unknown. The purpose of this study was to investigate this novel and unconventional interaction among RTKs of different families in human GBM cells. With the use of western blotting, in vitro kinase activity, co-immunoprecipitation and bimolecular fluorescence complementation assays, we show that EGF stimulates activation of Axl kinase and that there is a hetero-interaction between the two RTKs. Through small interfering RNA knockdown and quantitative PCR screening, we identified distinct gene expression patterns in GBM cells that were specifically regulated by signalling from EGFR-EGFR, Axl–Axl and EGFR-Axl RTK parings. These included genes that promote invasion, which were activated only via the EGFR-Axl axis (MMP9), while EGFR-EGFR distinctly regulated the cell cycle and Axl–Axl regulated invasion. Our findings provide critical insights into the role of EGFR-Axl hetero-dimerisation in cancer cells and reveal regulation of cell invasion via Axl as a novel function of EGFR signalling. PMID:27775700

  12. Halotriazolium axle functionalised [2]rotaxanes for anion recognition: investigating the effects of halogen-bond donor and preorganisation.

    PubMed

    Mercurio, James M; Knighton, Richard C; Cookson, James; Beer, Paul D

    2014-09-08

    The anion-templated synthesis of three novel halogen-bonding 5-halo-1,2,3-triazolium axle containing [2]rotaxanes is described, and the effects of altering the nature of the halogen-bond donor atom together with the degree of inter-component preorganisation on the anion-recognition properties of the interlocked host investigated. The ability of the bromotriazolium motif to direct the halide-anion-templated assembly of interpenetrated [2]pseudorotaxanes was studied initially; bromide was found to be the most effective template. As a consequence, bromide anion templation was used to synthesise the first bromotriazolium axle containing [2]rotaxane, the anion-binding properties of which, determined by (1) H NMR spectroscopic titration experiments, revealed enhanced bromide and iodide recognition relative to a hydrogen-bonding protic triazolium rotaxane analogue. Two halogen-bonding [2]rotaxanes with bromo- and iodotriazolium motifs integrated into shortened axles designed to increase inter-component preorganisation were also synthesised. Anion (1) H NMR spectroscopic titration experiments demonstrated that these rotaxanes were able to bind halide anions even more strongly, with the iodotriazolium axle integrated rotaxane capable of recognising halides in aqueous solvent media. Importantly, these observations suggest that a halogen-bonding interlocked host binding domain, in combination with increased inter-component preorganisation, are requisite design features for a potent anion receptor.

  13. 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

  14. Phyllodes tumor of the breast: role of Axl and ST6GalNAcII in the development of mammary phyllodes tumors.

    PubMed

    Ren, Dongliang; Li, Yanyan; Gong, Yanxin; Xu, Jingchao; Miao, Xiaolong; Li, Xiangnan; Liu, Chen; Jia, Li; Zhao, Yongfu

    2014-10-01

    Phyllodes tumor exhibits an aggressive growth. The expression of many biological markers has been explored to discriminate between different grades of phyllodes tumor and to predict their behavior. The purpose of this study was to evaluate the implications of Axl and ST6GalNAcII in phyllodes tumors. Real-time PCR, Western blot, and immunohistochemical were used to analyze differential expression of ST6GalNAcII and Axl in phyllodes tumor (PT) cell lines and tissue specimens. RNAi assay, ECM invasion assay, and tumorigenicity assay were used to analyze the altered expression of ST6GalNAcII gene effects on the expression of Axl and invasive ability of phyllodes tumor cells in vitro and in vivo. Compared to benign tumors, borderline and malignant ones showed a remarkable increase in mRNA levels of Axl and ST6GalNAcII gene, and it was higher in malignant tumor cells than in borderline tumor cells. When ST6GalNAcII was silenced, compared to the control, the expression level of Axl was significantly reduced in malignant tumor cell transfectants and knockdown of ST6GalNAcII gene significantly inhibited invasive activity in malignant tumor cells. The high expression of ST6GalNAcII and Axl was significantly correlated with tumor grade and distance metastasis by immunohistochemical analysis. Axl and ST6GalNAcII expression increases with increasing tumor grade in mammary phyllodes tumors. ST6GalNAc II might be participated in the glycosylation of Axl, and this Axl glycosylation may mediate the tumorigenicity, invasion, and distant metastasis of PT cells.

  15. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  17. Effects of extracellular acid stimulation on rat vascular smooth muscle cell in Gas6/Axl or PI3K/Akt signaling pathway.

    PubMed

    Cui, Liwen; Bai, Yaling; Zhang, Junxia; Zhang, Shenglei; Xu, Jinsheng

    Recent studies have indicated that extracellular acid stimulation inhibited the calcification of vascular smooth muscle cells (VSMCs). Cell apoptosis played an important role in the occurrence and development of vascular calcification. We further explored the effects of Gas6/Axl or PI3K/Akt signaling pathway on the inhibition of rat VSMCs calcification in response to extracellular acid stimulation. Our study demonstrated that a high concentration of phosphorus induced apoptosis and calcification of VSMCs, decreased expression of Axl, and reduced phosphorylation of Akt. Stimulation of extracellular acid counteracted the effects as above by increasing the expression of Axl and Akt phosphorylation and decreasing the expression of activated Caspase3, which thereby decreased cell apoptosis and calcification. Moreover, the effects can be attenuated by PI3K inhibitor. Our study proved that extracellular acid stimulation played a vital role in the inhibition of rat VSMCs calcification and apoptosis in Gas6/Axl or PI3K/Akt signaling pathway.

  18. 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

  19. 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

  20. Suppression of the metastatic spread of breast cancer by DN10764 (AZD7762)-mediated inhibition of AXL signaling

    PubMed Central

    Kim, Dayea; Son, Jung Beom; Ko, Eunhwa; Cho, Joong-Heui; Kim, Nam-Doo; Nan, Hong-Yan; Kim, Choong-Yong; Yoon, Sukkyoon; Lee, Sun-Hwa; Choi, Hwan Geun

    2016-01-01

    Breast cancer is the most common malignant disease occurring in women and represents a substantial proportion of the global cancer burden. In these patients, metastasis but not the primary tumor is the main cause of breast cancer-related deaths. Here, we report the novel finding that DN10764 (AZD7762, a selective inhibitor of checkpoint kinases 1 and 2) can suppress breast cancer metastasis. In breast cancer cells, DN10764 inhibited cell proliferation and GAS6-mediated AXL signaling, consequently resulting in suppressed migration and invasion. In addition, DN10764 induced caspase 3/7-mediated apoptosis in breast cancer cells and inhibited tube formation of human umbilical vein endothelial cells. Finally, DN10764 significantly suppressed the tumor growth and metastasis of breast cancer cells in in vivo metastasis models. Taken together, these data suggest that therapeutic strategies targeting AXL in combination with systemic therapies could improve responses to anti-cancer therapies and reduce breast cancer recurrence and metastases. PMID:27829217

  1. The comparative analysis of different computations methods of strength of materials by the example of calculations of the axle beam

    NASA Astrophysics Data System (ADS)

    Evtushenko, S. I.; Petrov, I. A.; Shutova, M. N.; Alekseeva, A. S.

    2017-02-01

    The paper presents data of calculation the main characteristics of resilience by different ways. The basic data for the article were the calculation of the guiding axle beam of the vehicle. The calculation was performed by the analytic method and it was necessary to re-check strength of materials by any other method for reliability of the carried-out work. The finite element method was chosen as the competing option.

  2. 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.

  3. AP-2α regulates migration of GN-11 neurons via a specific genetic programme involving the Axl receptor tyrosine kinase

    PubMed Central

    Orso, Francesca; Jäger, Richard; Calogero, Raffaele Adolfo; Schorle, Hubert; Sismondi, Piero; De Bortoli, Michele; Taverna, Daniela

    2009-01-01

    Background Neuronal migration is a crucial process that allows neurons to reach their correct target location to allow the nervous system to function properly. AP-2α is a transcription factor essential for neural crest cell migration and its mutation results in apoptosis within this cell population, as demonstrated by genetic models. Results We down-modulated AP-2α expression in GN-11 neurons by RNA interference and observe reduced neuron migration following the activation of a specific genetic programme including the Adhesion Related Kinase (Axl) gene. We prove that Axl is able to coordinate migration per se and by ChIP and promoter analysis we observe that its transcription is directly driven by AP-2α via the binding to one or more functional AP-2α binding sites present in its regulatory region. Analysis of migration in AP-2α null mouse embryo fibroblasts also reveals an essential role for AP-2α in cell movement via the activation of a distinct genetic programme. Conclusion We show that AP-2α plays an essential role in cell movement via the activation of cell-specific genetic programmes. Moreover, we demonstrate that the AP-2α regulated gene Axl is an essential player in GN-11 neuron migration. PMID:19463168

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. Analysis and optimization of an innovative fatigue tests profile for three axle semi-trailers

    NASA Astrophysics Data System (ADS)

    Malon, H.; Tello, L.; Martin, C.

    2011-10-01

    Nowadays, a fundamental aspect in the design of any type of vehicle, in particular of semi-trailers, is the development and testing of prototypes that confirm the correct performance of the vehicles before their launch into the market. At present, fatigue tests exist for different structural components from large machines to small components in vehicles, but up to now, there is no knowledge about fatigue tests of complete vehicles of large dimensions, with the exception of the fatigue tests of semi-trailers that are carried out by the company LECITRAILER S.A., under the supervision of the Transportation Engineering Area of the University of Zaragoza, in particular the research group VEHIVIAL. The aim of this paper is to decribe the process developed for the analysis and optimization of an initial profile of fatigue testing for semitrailer. The result of this optimization process is an innovative profile of fatigue testing for three axle semi-trailers developed by the University of Zaragoza in collaboration with the company LECITRAILER S.A., which is applied to the process of optimization of all the prototypes made by the company.

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

    PubMed Central

    Burnos, Piotr; Gajda, Janusz

    2016-01-01

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

  10. Wheel/rail contact geometry assessment to limit rolling contact fatigue initiation at high axle loads

    NASA Astrophysics Data System (ADS)

    Fröhling, Robert; Spangenberg, Ulrich; Hettasch, Georg

    2012-01-01

    Rolling contact fatigue on any railway system has a significant impact on the safety and efficiency of the operation. This is especially true for heavy haul railways where higher axle loads and demands for higher throughput have, over the years, challenged the limits within the wheel/rail interface. The objective of this paper is to present a methodology to manage this stress state using a detailed wheel/rail contact stress analysis. Based on the results of recent wheel profile and rail profile surveys, a kinematic wheel/rail contact analysis is performed to identify and eliminate profiles that cause high stresses. The results show that the current hollow wear criterion is effective, but that an alternative or additional criterion based on the gauge side false flange gradient or the calculated peak contact stress values can further reduce the stress state. Within the wheel and rail profile combinations investigated, the contact stresses were largely independent of the transverse profile of the high rail.

  11. S49076 is a novel kinase inhibitor of MET, AXL, and FGFR with strong preclinical activity alone and in association with bevacizumab.

    PubMed

    Burbridge, Mike F; Bossard, Céline J; Saunier, Carine; Fejes, Imre; Bruno, Alain; Léonce, Stéphane; Ferry, Gilles; Da Violante, Georges; Bouzom, François; Cattan, Valérie; Jacquet-Bescond, Anne; Comoglio, Paolo M; Lockhart, Brian P; Boutin, Jean A; Cordi, Alex; Ortuno, Jean-Claude; Pierré, Alain; Hickman, John A; Cruzalegui, Francisco H; Depil, Stéphane

    2013-09-01

    Aberrant activity of the receptor tyrosine kinases MET, AXL, and FGFR1/2/3 has been associated with tumor progression in a wide variety of human malignancies, notably in instances of primary or acquired resistance to existing or emerging anticancer therapies. This study describes the preclinical characterization of S49076, a novel, potent inhibitor of MET, AXL/MER, and FGFR1/2/3. S49076 potently blocked cellular phosphorylation of MET, AXL, and FGFRs and inhibited downstream signaling in vitro and in vivo. In cell models, S49076 inhibited the proliferation of MET- and FGFR2-dependent gastric cancer cells, blocked MET-driven migration of lung carcinoma cells, and inhibited colony formation of hepatocarcinoma cells expressing FGFR1/2 and AXL. In tumor xenograft models, a good pharmacokinetic/pharmacodynamic relationship for MET and FGFR2 inhibition following oral administration of S49076 was established and correlated well with impact on tumor growth. MET, AXL, and the FGFRs have all been implicated in resistance to VEGF/VEGFR inhibitors such as bevacizumab. Accordingly, combination of S49076 with bevacizumab in colon carcinoma xenograft models led to near total inhibition of tumor growth. Moreover, S49076 alone caused tumor growth arrest in bevacizumab-resistant tumors. On the basis of these preclinical studies showing a favorable and novel pharmacologic profile of S49076, a phase I study is currently underway in patients with advanced solid tumors. Mol Cancer Ther; 12(9); 1749-62. ©2013 AACR.

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

    PubMed Central

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

    2015-01-01

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

  13. 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.

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

    PubMed

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

    1996-05-01

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

  15. 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

  16. Vehicle design influences whole body vibration exposures: effect of the location of the front axle relative to the cab.

    PubMed

    Blood, Ryan P; Rynell, Patrik W; Johnson, Peter W

    2011-06-01

    Using a repeated measure design, this study compared differences in whole body vibration (WBV) exposures among 13 drivers who drove a truck with the cab over the front axle (cab-over design) and a truck with the cab situated behind the front axle (non-cab-over design). The drivers drove both trucks over a standardized route that comprised three distinct segments: a freeway segment, a city street segment with stop-and-go driving (traffic lights), and a city street segment without traffic lights. A portable WBV data acquisition system collected tri-axial time-weighted and raw WBV data per ISO 2631-1 and 2631-5 standards. Simultaneous global positioning system (GPS) data were also collected to compare vehicle speeds. The GPS data indicated that there were no speed differences between the two vehicles. However, average and impulsive z-axis vibration levels were significantly higher for the cab-over design than for the non-cab-over design. In addition, significant WBV exposure differences between road types were found, with the freeway segments having the lowest exposures and the city street segments without traffic lights having the highest exposures. Vehicle type and the associated WBV exposures should be considered when purchasing vehicles to be used by full-time professional vehicle operators.

  17. Substituent effects on axle binding in amide pseudorotaxanes: comparison of NMR titration and ITC data with DFT calculations.

    PubMed

    Kaufmann, Lena; Dzyuba, Egor V; Malberg, Friedrich; Löw, Nora L; Groschke, Matthias; Brusilowskij, Boris; Huuskonen, Juhani; Rissanen, Kari; Kirchner, Barbara; Schalley, Christoph A

    2012-08-14

    The binding behaviour of differently substituted diamide axle molecules to Hunter/Vögtle tetralactam macrocycles was studied with a combination of NMR titration, isothermal titration calorimetry (ITC) experiments and calculations employing density functional theory (DFT), along with dispersion-corrected exchange-correlation functionals. Guests with alkyl or alkenyl chains attached to the diamide carbonyl groups have a significantly higher binding affinity to the macrocycle than guests with benzoyl amides and their substituted analogues. While the binding of the benzoyl and alkenyl substituted axles is enthalpically driven, the alkyl-substituted guest binds mainly because of a positive binding entropy. The electronic effects of para-substituents at the benzoyl moieties have an influence on the binding affinities. Electron donating substituents increase, while electron-withdrawing substituents decrease the binding energies. The binding affinities obtained from both NMR titration and ITC experiments correlate well with each other. The substituent effects observed in the experimental data are reflected in adiabatic interaction energies calculated with density functional methods. The calculated structures also agree well with pseudorotaxane crystal structures.

  18. 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).

  19. How can rotaxanes be modified by varying functional groups at the axle?--a combined theoretical and experimental analysis of thermochemistry and electronic effects.

    PubMed

    Spickermann, Christian; Felder, Thorsten; Schalley, Christoph A; Kirchner, Barbara

    2008-01-01

    We present theoretically as well as experimentally determined thermochemical data of the non-covalent interactions in different axle-substituted pseudorotaxanes. The overall interaction energy lies in the region of 35 kJ mol(-1), independent of the substitution pattern at the axle. Because rearrangement energies of 7 and 3 kJ mol(-1) are required for wheel and axle, respectively, the sum of the net interactions of individual non-covalent bonds must exceed 10 kJ mol(-1) to achieve a successful host-guest interaction. The geometrical analysis shows three hydrogen bonds, and the close inspection of the individual dipole moments as well as the individual hydrogen bonds reveals trends according to the different functional groups at the axle. The individual trends for the different hydrogen bonds almost lead to a cancellation of the substitution effects. From solvent-effect considerations it can be predicted that the pseudorotaxane is stable in CHCl(3) and CH(2)Cl(2), whereas it would dethread in water. Comparing experimentally and theoretically calculated Gibbs free enthalpies, we find reasonable agreement if an exchange reaction of one solvent molecule instead of the direct formation reaction is considered.

  20. O-Glycosylation of Axl2/Bud10p by Pmt4p Is Required for Its Stability, Localization, and Function in Daughter Cells

    PubMed Central

    Sanders, Sylvia L.; Gentzsch, Martina; Tanner, Widmar; Herskowitz, Ira

    1999-01-01

    Cells of the yeast Saccharomyces cerevisiae choose bud sites in a manner that is dependent upon cell type: a and α cells select axial sites; a/α cells utilize bipolar sites. Mutants specifically defective in axial budding were isolated from an α strain using pseudohyphal growth as an assay. We found that a and α mutants defective in the previously identified PMT4 gene exhibit unipolar, rather than axial budding: mother cells choose axial bud sites, but daughter cells do not. PMT4 encodes a protein mannosyl transferase (pmt) required for O-linked glycosylation of some secretory and cell surface proteins (Immervoll, T., M. Gentzsch, and W. Tanner. 1995. Yeast. 11:1345–1351). We demonstrate that Axl2/Bud10p, which is required for the axial budding pattern, is an O-linked glycoprotein and is incompletely glycosylated, unstable, and mislocalized in cells lacking PMT4. Overexpression of AXL2 can partially restore proper bud-site selection to pmt4 mutants. These data indicate that Axl2/Bud10p is glycosylated by Pmt4p and that O-linked glycosylation increases Axl2/ Bud10p activity in daughter cells, apparently by enhancing its stability and promoting its localization to the plasma membrane. PMID:10366591

  1. 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),…

  2. Growth Arrest-Specific 6 Enhances the Suppressive Function of CD4+CD25+ Regulatory T Cells Mainly through Axl Receptor

    PubMed Central

    Zhao, Guang-ju; Zheng, Jia-yi; Bian, Jia-lan; Chen, Long-wang; Dong, Ning; Yu, Yan; Hong, Guang-liang; Chandoo, Arvine

    2017-01-01

    Background. Growth arrest-specific (Gas) 6 is one of the endogenous ligands of TAM receptors (Tyro3, Axl, and Mertk), and its role as an immune modulator has been recently emphasized. Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are essential for the active suppression of autoimmunity. The present study was designed to investigate whether Tregs express TAM receptors and the potential role of Gas6-TAM signal in regulating the suppressive function of Tregs. Methods. The protein and mRNA levels of TAM receptors were determined by using Western blot, immunofluorescence, flow cytometry, and RT-PCR. Then, TAM receptors were silenced using targeted siRNA or blocked with specific antibody. The suppressive function of Tregs was assessed by using a CFSE-based T cell proliferation assay. Flow cytometry was used to determine the expression of Foxp3 and CTLA4 whereas cytokines secretion levels were measured by ELISA assay. Results. Tregs express both Axl and Mertk receptors. Gas6 increases the suppressive function of Tregs in vitro and in mice. Both Foxp3 and CTLA-4 expression on Tregs are enhanced after Gas6 stimulation. Gas6 enhances the suppressive activity of Tregs mainly through Axl receptor. Conclusion. Gas6 has a direct effect on the functions of CD4+CD25+Tregs mainly through its interaction with Axl receptor. PMID:28270700

  3. Influence of process parameters on the microstructural evolution of a rear axle tube during cross wedge rolling

    NASA Astrophysics Data System (ADS)

    Ma, Jia-wei; Yang, Cui-ping; Zheng, Zhen-hua; Zhang, Kang-sheng; Ma, Wen-yu

    2016-11-01

    In the shaping process of cross wedge rolling (CWR), metal undergoes a complex microstructural evolution, which affects the quality and mechanical properties of the product. Through secondary development of the DEFORM-3D software, we developed a rigid plastic finite element model for a CWR-processed rear axle tube, coupled with thermomechanical and microstructural aspects of workpieces. Using the developed model, we investigated the microstructural evolution of the CWR process. Also, the influence of numerous parameters, including the initial temperature of workpieces, the roll speed, the forming angle, and the spreading angle, on the grain size and the grain-size uniformity of the rolled workpieces was analyzed. The numerical simulation was verified through rolling and metallographic experiments. Good agreement was obtained between the calculated and experimental results, which demonstrated the reliability of the model constructed in this work.

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

  5. Influence on operator's health of hand-transmitted vibrations from handles of a single-axle tractor.

    PubMed

    Goglia, Vlado; Gospodaric, Zlatko; Filipovic, Dubravko; Djukic, Igor

    2006-01-01

    The operators of the single-axle tractors are especially exposed to hand-arm transmitted vibrations. These vibrations can cause the complex of vascular, neurological and musculoskeletal disorders, collectively named hand-arm vibration syndrome. Among these, the most common disorder is vibration-induced white finger (Raynaud's phenomenon). The vibration levels were measured in three tractor's working conditions, namely idling, transportation and soil tillage. The vibration level on the handles was measured and analysed and the frequency spectra for the chosen working conditions were obtained. The frequency-weighted acceleration, given in m/s2, was calculated and the obtained values are graphically presented. The measured vibration levels are then discussed with regard to the operator's daily exposure limits recommended by the ISO 5349. The vibration levels were much higher in the x and y directions than the z-direction in all working conditions. The vibration total values in idling, transportation and soil tillage were 3.37, 8.37 and 9.62 m/s2, respectively. Results showed that the 10% of workers are exposed to a risk of vibration-induced white finger disorder of the hands after relatively short periods (3-4 years), if the tractor is used 8 hour per day in soil tillage and transportation at full load. Considering the criteria of the ISO 5349, the daily working time with the single-axle tractor should be limited in order to protect the operator and work schedules should be arranged to include vibration-free periods.

  6. A phase I pilot study of the insulin-like growth factor 1 receptor pathway modulator AXL1717 in combination with gemcitabine HCl and carboplatin in previously untreated, locally advanced, or metastatic non-small cell lung cancer.

    PubMed

    Holgersson, Georg; Bergström, Stefan; Harmenberg, Johan; Ringbom, Magnus; Klockare, Maria; Jerling, Markus; Ekman, Simon; Lundström, Kristina Lamberg; Koyi, Hirsh; Brandén, Eva; Larsson, Olle; Bergqvist, Michael

    2015-04-01

    AXL1717 is an orally bioavailable IGF-1R pathway modulator that has been shown to have anti-tumoral effects. The objectives of the present study were to define maximum tolerated dose and the recommended phase II dose (RPTD) of AXL1717 in combination with gemcitabine HCl and carboplatin in non-small cell lung cancer (NSCLC). Patients with previously untreated, locally advanced, or metastatic NSCLC (squamous cell cancer or adenocarcinoma) in good performance status and with preserved major organ functions were enrolled in the study. The study was an open-label phase I study with planned cohorts of three patients per dose level of AXL1717 (215, 290, and 390 mg BID). In total, 12 patients were enrolled in the study, and of these, two were prematurely excluded. AXL1717 was administered at one dose level, 215 mg BID. A total number of 81 unique adverse events were reported. Bone marrow toxicity was reported in 10 out of 12 patients, and this organ class showed the largest number of related events. AXL1717 in combination with gemcitabine HCl and carboplatin is a possible treatment approach in previously untreated, locally advanced, or metastatic non-small cell lung cancer. However, due to the bone marrow toxicity profile shown in the present study, further dose increases of AXL1717 above 215 mg BID will probably not be feasible. Therefore, 215 mg BID constitutes maximum tolerated dose and RPTD.

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

    PubMed

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

    1999-01-01

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

  8. Expression level of CRKL and AXL combined with exon 19 deletion in EGFR and ALK status confer differential prognosis of lung adenocarcinoma subtypes

    PubMed Central

    Cai, Yi-Ran; Dong, Yu-Jie; Wu, Hong-Bo; Yu, Da-Ping; Zhou, Li-Juan; Su, Dan; Zhang, Li; Chen, Xue-Jing

    2016-01-01

    Non-small cell lung cancer (NSCLC) is a lethal cancer-related disease in population. Adenocarcinoma (AC) is subclassified into several subtypes based on the new classification by the International Association for the Study of Lung Cancer, American Thoracic Society and European Respiratory Society in 2011. Correlation between original expression of Crk-like (CRKL) and anaplastic lymphoma receptor tyrosine kinase in diverse histological components of AC and epidermal growth factor receptor (EGFR) or ALK status was evaluated by immunohistochemistry and sequencing in present study. A total of 106 cases, including 83 patients (78.3%) with mixed-type ACs, were assessed in the present study using eligible follow-up data. The ACs consisted of 32 acinar, 12 papillary, 5 mucinous, 11 micropapillary and 46 solid-predominant ACs. In total, 69.8% samples were composed of 2 or 3 histological components, with different expression levels of CRKL and AXL. ACs with EGFR mutation had a higher level of AXL expression compared with ACs without mutation (P=0.019). Multivariate survival analysis showed that AC subtypes and EGFR mutation subtypes were significantly associated with the progression-free survival (PFS) time. Acinar AC was the subtype with the most notable PFS time (30.6 months), which was significantly different from the PFS time of papillary, mucinous, micropapillary and solid-predominant ACs (hazard ratio, 0.4; 95% CI, 0.21–0.75; P=0.005). Among the ACs with exon 19 mutation, the median PFS time (28.8 months) of patients with a lower level of AXL protein expression was increased compared with the PFS time of patients with the L858R mutation and wild-type EGFR (9.1 months and 11 months, respectively; P=0.03), whereas no significant difference in ACs with an increased level of AXL expression. However, AC patients with higher level of CRKL expression had better PFS (28.8 months) than patients with the L858R mutation and wild-type EGFR (9.1 months and 11.3 months

  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.

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2014-09-15

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

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

    PubMed

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

    1997-06-05

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

  13. 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.

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

    SciTech Connect

    Qu, Jun; Zhou, Yan; Luo, Huimin; Toops, Todd J.; Brookshear, Daniel W.; Stump, Benjamin C.; Viola, Michael B.; Zreik, Khaled; Ahmed, Tasfia

    2017-01-01

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

  15. Axle Lubricant Efficiency

    DTIC Science & Technology

    2014-05-09

    have identical fluids CAN Controller Area Network CAT Caterpillar C.I. Confidence Interval cSt CentiStoke CTIS Central Tire Inflation System ECM...Information Caterpillar Inc. C7 ACERT – 330 hp @ 2400 RPM, 860 ft-lbs @ 1440 RPM, Meets 2006 EPA Emissions Standards under National Security

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

    NASA Astrophysics Data System (ADS)

    Lv, Chen; Zhang, Junzhi; Li, Yutong

    2014-11-01

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

  17. Characterization of Gas6, a member of the superfamily of G domain-containing proteins, as a ligand for Rse and Axl.

    PubMed

    Mark, M R; Chen, J; Hammonds, R G; Sadick, M; Godowsk, P J

    1996-04-19

    Rse, Ax1, and c-Mer comprise a family of cell adhesion molecule-related tyrosine kinase receptors. Human Gas6 was recently shown to act as a ligand for both human Rse (Godowski et al., 1995) and human Ax1 (Varnum et al., 1995). Gas6 contains an NH2-terminal Gla domain followed by four epidermal growth factor-like repeats and tandem globular (G) domains. The G domains are related to those found in sex hormone-binding globulin and to those utilized by laminin and agrin for binding to the dystroglycan complex. A series of Gas6 variants were tested for their ability to bind to Rse and Ax1. The Gla domain and epidermal growth factor-like repeats were not required for receptor binding, as deletion variants of Gas6 which lacked these domains bound to the extracellular domains of both Rse and Axl. A deletion variant of Gas6 containing just the G domain region was shown to activate Rse phosphorylation. These results provide evidence that G domains can act as signaling molecules by activating transmembrane receptor tyrosine kinases. Furthermore, they provide a structural link between the activation of cell adhesion related receptors and the control of cell growth and differentiation by the G domain-containing superfamily of proteins.

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

    PubMed

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

    1994-04-08

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

  19. Transfer case for multiple drive axle vehicle

    SciTech Connect

    Batchelor, R.B.

    1987-07-07

    This patent describes a transfer case for a vehicle drive train having a transmission comprising: a housing; input means for receiving the torque output from the vehicle transmission; a first output shaft and first means for rotatably supporting the first output shaft in the housing; a second output shaft and second means for rotatably supporting the second output shaft in the housing; and means for selectively driving the first and second output shafts in response to actuation of the input means. The means for selectively driving comprises a planetary gear set having an annulus, a first set of first planet gears a second set of second planet gears, engaged with one of the first planet gear. A sun gear engages with the second planet gears, third means for rotatably mounting the sun gear in the housing and a planet carrier having means for rotatably supporting the first and second planet gears and co-axially secured to the first output shaft for rotation. A clutch means for selectively engages the sun gear with the planet carrier and the second output shaft, and the input means comprises means for rotatably driving the annulus.

  20. 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.

  1. Army Excellence in Leadership (AXL): Educating Army Leaders with the Tripwire Film

    DTIC Science & Technology

    2007-03-01

    reading intentions, building trust, converting opinions, and managing perceptions, all tasks that demand an exceptional ability to understand people, their...between two team members, one individual and the entire team, several team members, and between different teams ( Schermerhorn , Hunt, & Osborn, 2000...the team, but interferes with the person’s ability to perform ( Schermerhorn et al.). There are also task conflicts, which involve disputes over how a

  2. Plugging a Bipyridinium Axle into Multichromophoric Calix[6]arene Wheels Bearing Naphthyl Units at Different Rims

    PubMed Central

    Orlandini, Guido; Ragazzon, Giulio; Zanichelli, Valeria; Degli Esposti, Lorenzo; Baroncini, Massimo; Silvi, Serena; Venturi, Margherita; Arduini, Arturo

    2017-01-01

    Abstract Tris‐(N‐phenylureido)‐calix[6]arene derivatives are heteroditopic non‐symmetric molecular hosts that can form pseudorotaxane complexes with 4,4′‐bipyridinium‐type guests. Owing to the unique structural features and recognition properties of the calix[6]arene wheel, these systems are of interest for the design and synthesis of novel molecular devices and machines. We envisaged that the incorporation of photoactive units in the calixarene skeleton could lead to the development of systems the working modes of which can be governed and monitored by means of light‐activated processes. Here, we report on the synthesis, structural characterization, and spectroscopic, photophysical, and electrochemical investigation of two calix[6]arene wheels decorated with three naphthyl groups anchored to either the upper or lower rim of the phenylureido calixarene platform. We found that the naphthyl units interact mutually and with the calixarene skeleton in a different fashion in the two compounds, which thus exhibit a markedly distinct photophysical behavior. For both hosts, the inclusion of a 4,4′‐bipyridinium guest activates energy‐ and/or electron‐transfer processes that lead to non‐trivial luminescence changes. PMID:28168152

  3. 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)…

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

    DTIC Science & Technology

    2007-01-01

    Commander-Excellence in Leadership (TLAC-XL). These individuals include Andrew Gordon, Salvo Lavis , Sudeep Gandhe, David Traum, Stewart King, Reid Swanson...the current operating environment places many demands on junior leaders, the United States Army has devoted substantial attention to the challenge of...information each system can process individually, cognitive load as a whole can be reduced by presenting information in multiple modalities so that

  5. 23 CFR 658.13 - Length.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... axle(s)), including “low boys,” or less than 75 feet on stinger-steered automobile transporters... traditional boat transporters (fifth wheel located on tractor frame over rear axle(s), including “low...

  6. 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.

  7. 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…

  8. 16 CFR 1512.12 - Requirements for wheel hubs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... tightened to the manufacturer's specifications. (1) Rear wheels. There shall be no relative motion between the axle and the frame when a force of 1,780 N (400 lbf) is applied symmetrically to the axle for...

  9. 16 CFR 1512.12 - Requirements for wheel hubs.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... tightened to the manufacturer's specifications. (1) Rear wheels. There shall be no relative motion between the axle and the frame when a force of 1,780 N (400 lbf) is applied symmetrically to the axle for...

  10. 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... requirements of this chapter, and the Act, unless, at a minimum, the trailer running gear assembly...

  11. 36 CFR 7.71 - Delaware Water Gap National Recreation Area.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... at such facility; (iii) On a first come-first served basis, up to 125 northbound and up to 125...-axle vehicle $13 (vi) Five or more-axle vehicle $18 The fees charged are for one trip, one way....

  12. 36 CFR 7.71 - Delaware Water Gap National Recreation Area.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... at such facility; (iii) On a first come-first served basis, up to 125 northbound and up to 125...-axle vehicle $13 (vi) Five or more-axle vehicle $18 The fees charged are for one trip, one way....

  13. 49 CFR 568.4 - Requirements for incomplete vehicle manufacturers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... single value, with the label indicating to which axles the ratings apply. Examples of combined ratings... exceed any of the gross axle weight ratings, if the center of gravity at GVWR is not higher than...

  14. 49 CFR 568.4 - Requirements for incomplete vehicle manufacturers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... single value, with the label indicating to which axles the ratings apply. Examples of combined ratings... exceed any of the gross axle weight ratings, if the center of gravity at GVWR is not higher than...

  15. 49 CFR 568.4 - Requirements for incomplete vehicle manufacturers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... single value, with the label indicating to which axles the ratings apply. Examples of combined ratings... exceed any of the gross axle weight ratings, if the center of gravity at GVWR is not higher than...

  16. 49 CFR 568.4 - Requirements for incomplete vehicle manufacturers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... single value, with the label indicating to which axles the ratings apply. Examples of combined ratings... exceed any of the gross axle weight ratings, if the center of gravity at GVWR is not higher than...

  17. 49 CFR 568.4 - Requirements for incomplete vehicle manufacturers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... single value, with the label indicating to which axles the ratings apply. Examples of combined ratings... exceed any of the gross axle weight ratings, if the center of gravity at GVWR is not higher than...

  18. 49 CFR Appendix A to Part 593 - List of Vehicles Determined to be Eligible for Importation

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Westfalia 14ft Double Axle Cargo trailer 1994 & 1997 56 Yamaha (MC) Drag Star 1100 1999-2007 497 Yamaha (MC... Freightliner FTLD112064SD 1991-1996 178 Gemala Saranaupaya 1600 Double Axle trailer 2001 58 GMC Suburban 1992... ft double axle trailer 1999-2000 38 Heku 750 KG boat trailer 2005 33 Hobby Exclusive 650 KMFE...

  19. 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

  20. FLOYDS Classification of MASTER OT J161308.18+260953.3 as a Type II Supernova and ASASSN-17cq/AT 2017axl as a Type Ia Supernova Near Peak

    NASA Astrophysics Data System (ADS)

    Hosseinzadeh, G.; Arcavi, I.; Howell, D. A.; McCully, C.; Valenti, S.

    2017-02-01

    We obtained a spectrum of MASTER OT J161308.18+260953.3 (ATel #10099) on 2017 February 21.5 UT with the robotic FLOYDS instrument mounted on the Las Cumbres Observatory (LCO) 2-meter telescope on Haleakala, Hawai'i.

  1. Field study on moving force identification

    NASA Astrophysics Data System (ADS)

    Chan, Hung-tin Tommy; Yung, Tak H.; Law, S. S.

    2001-08-01

    A field measurement to validate a moving force identification method was carried out on an existing prestressed concrete highway bridge with a span length of 28 m. The test bridge is located at Ma Tau Wai, Kowloon, Hong Kong. A heavy 2-axle truck with known axle loads was used as a control vehicle. Besides the control vehicle, axle load data of in-service vehicles were also collected. The bridge responses acquired for the identification were indirectly measured using strain gauges. Results show that dynamic axle loads induced from both control and in-service vehicles can be identified indicating the method is valid for identification of moving forces.

  2. 49 CFR 393.207 - Suspension systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  3. 78 FR 23105 - Airworthiness Directives; Airbus Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-18

    ... machined with a radius as small as 0.4 millimeters. This AD requires replacing the wheel axle of the MLG... have been machined with a radius as small as 0.4 mm. This condition, if not corrected, has a... prompted by a report that revealed the wheel axles were machined with a radius as small as 0.4...

  4. 77 FR 51729 - Airworthiness Directives; Airbus Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-27

    ... wheel axles of the main landing gear (MLG) were machined with a radius as small as 0.4 millimeters. This... machined with a radius as small as 0.4 mm. This condition, if not corrected, has a detrimental effect on... prompted by a report that revealed the wheel axles were machined with a radius as small as 0.4...

  5. 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.

  6. 49 CFR 393.207 - Suspension systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Suspension systems. 393.207 Section 393.207... NECESSARY FOR SAFE OPERATION Frames, Cab and Body Components, Wheels, Steering, and Suspension Systems § 393.207 Suspension systems. (a) Axles. No axle positioning part shall be cracked, broken, loose or...

  7. 23 CFR 658.17 - Weight.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... the bridge formula. (c) The maximum gross weight upon any one axle, including any one axle of a group... following formula, referred to as the Bridge Gross Weight Formula: EC14OC91.012 except that two consecutive... formulas on January 4, 1975. Grandfathered weight limits are vested on the date specified by Congress...

  8. 23 CFR 658.17 - Weight.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... the bridge formula. (c) The maximum gross weight upon any one axle, including any one axle of a group... following formula, referred to as the Bridge Gross Weight Formula: EC14OC91.012 except that two consecutive... formulas on January 4, 1975. Grandfathered weight limits are vested on the date specified by Congress...

  9. 23 CFR 658.17 - Weight.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... the bridge formula. (c) The maximum gross weight upon any one axle, including any one axle of a group... following formula, referred to as the Bridge Gross Weight Formula: EC14OC91.012 except that two consecutive... formulas on January 4, 1975. Grandfathered weight limits are vested on the date specified by Congress...

  10. 76 FR 27865 - Airworthiness Directives; Cessna Aircraft Company Models 150, 152, 170, 172, 175, 177, 180, 182...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-13

    ... seat rail holes; seat pin engagement; seat rollers, washers, and axle bolts or bushings; wall thickness... seat rail and seat rail holes; seat pin engagement; seat rollers, washers, and axle bolts or bushings... for inspecting seat track hole wear and for inspecting proper seat lock pin engagement depth....

  11. 75 FR 68543 - Airworthiness Directives; Cessna Aircraft Company Models 150, 152, 170, 172, 175, 177, 180, 182...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-08

    ... rail holes; seat pin engagement; seat rollers, washers, and axle bolts or bushings; wall thickness of...; seat pin engagement; seat rollers, washers, and axle bolts or bushings; wall thickness of roller... engagement of the seat locking pins. Before further flight, after any inspection where dirt or debris...

  12. 49 CFR 571.301 - Standard No. 301; Fuel system integrity.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... nonsteerable front axle and fixed rear axle attached directly to the frame rails with no spring or other type... through S6.4. Each of these types of vehicles that is manufactured to use alcohol fuels shall also meet... solvent, having the physical and chemical properties of type 1 solvent, Table I of ASTM...

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

    ERIC Educational Resources Information Center

    Entrikin, Jerry; Griffiths, David

    1983-01-01

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

  14. 49 CFR 393.42 - Brakes required on all wheels.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... driveaway-towaway operation (including the last truck of triple saddle-mount combinations (see § 393.71(a)(3)) are not required to have operative brakes provided the combination of vehicles meets the requirements... the axle weight of the towed vehicle does not exceed 40 percent of the sum of the axle weights of...

  15. A novel application of E1A in combination therapy with EGFR-TKI treatment in breast cancer

    PubMed Central

    Su, Chih-Ming; Chang, Ting-Yu; Hsu, Hui-Ping; Lai, Hui-Huang; Li, Jie-Ning; Lyu, Yu-Jhen; Kuo, Kuang-Tai; Huang, Ming-Te; Su, Jen-Liang; Chen, Pai-Sheng

    2016-01-01

    Epidermal growth factor receptor (EGFR) is commonly overexpressed in breast cancer and is associated with poor clinical outcomes; however, an increasing number of patients have shown a poor effective response to EGFR tyrosine kinase inhibitors (EGFR-TKI). Here, we found that AXL expression was positively correlated with poor progression in breast cancer patients. Suppression of AXL by an anti-tumor protein, E1A, enhanced EGFR-TKI (gefitinib, erlotinib and lapatinib) sensitization, resulting in significant inhibition of tumor growth in breast cancer cells. Additionally, AXL overexpression dramatically impaired E1A-mediated EGFR-TKI sensitization. These findings show that downregulation of AXL expression by E1A contributes to sensitization to EGFR-TKI in breast cancer, suggesting that combinatorial therapy of AXL inhibitors or E1A gene therapy with EGFR-TKI may be a potential therapeutic strategy for treatment of breast cancer patients. PMID:27590506

  16. 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.

  17. 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.

  18. 40 CFR 205.51 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... contains the operator/passenger compartment is directly above the engine and front axle and the entire cab... or cause the reduction of noise emitted from a vehicle. (19) Noise emission test means a...

  19. 40 CFR 205.51 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... contains the operator/passenger compartment is directly above the engine and front axle and the entire cab... or cause the reduction of noise emitted from a vehicle. (19) Noise emission test means a...

  20. Steel - Structural, reinforcing; Pressure vessel, railway

    SciTech Connect

    Not Available

    1986-01-01

    This book contains specifications for structural steel used in various constructions; concrete reinforcement; plate and forgings for boilers and pressure vesseles; rails, axles, wheels and other accessories for railway service.

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  2. 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...

  3. 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...

  4. 14 CFR 25.509 - Towing loads.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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...

  5. 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...

  6. 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...

  7. 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.

  8. 77 FR 60285 - Airworthiness Directives; The Boeing Company Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-03

    ... (pivot joint), which could result in fracture of the MLG pivot joint components and consequent collapse... axle and shock strut inner cylinder lugs (pivot joint), which could result in fracture of the MLG...

  9. 40 CFR 86.602-98 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... subclassification of an engine-system combination on the basis of engine code, inertia weight class, transmission type and gear ratios, axle ratio, and other parameters which may be designated by the...

  10. A Methodology for Quantitative Comparison of Experimental to Predicted Chemical Deposition Data

    DTIC Science & Technology

    1990-07-01

    INTRODUCTION ..................................................................................... 1 II. BACKGROUN D...Ed Kerhn ANL\\SY-J (J Bloomquist) Dr Ni Charrn ANC -S’i -GD (R Mezan) 1801 N Beauregard Street ANIXS’ (Chandler) Alexandria. %A 22311 AXL\\SY (Chris

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

    SciTech Connect

    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.

  12. 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.

  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 238.419 - Truck-to-car-body and truck component attachment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... on the truck, along with the resulting vertical reaction to this load. (b) Each component of a truck (which include axles, wheels, bearings, the truck-mounted brake system, suspension system components,...

  15. 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)

  16. 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)

  17. 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)

  18. 76 FR 68306 - Airworthiness Directives; Bombardier, Inc. Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ... 49263-3, we want to avoid the possibility of an operator overlooking the intent of this final rule... to include new Note 2 to inform operators that MLG piston axles having P/N 49203-3 or 49203-5 that... cases of failure of the MLG [main landing gear] piston axle, P/N 49203-3 or 49203-5, resulting...

  19. Support structure of differential gear unit

    SciTech Connect

    Yasui, Y.; Suganuma, T.

    1989-04-18

    A support structure is described of a differential gear unit assembled in a trans-axle casing having a pair of axially spaced carrier portions and an open end closed by a removable cover member secured thereto, an outer case of the gear unit having a pair of side journals rotatable supported by a pair of tapered roller bearings which are removably coupled within respective cylindrical bores in the carrier portions of the trans-axle casing.

  20. Soviet Union, Military Affairs.

    DTIC Science & Technology

    1987-07-08

    hydraulic brake linkage is connected separately to the actuating brakes of the front and rear axles . In case of hermetic-seal failure in one of the...safety. Designers had this in mind when they used polypropylene to fabricate the steering wheel and used a joint to connect the steering wheel shaft...good lubrication of the bearing needles. The casing lever of the front- axle rotary cam has been reinforced. The well-known, multi-purpose GAZ-66

  1. Survey of Advanced Propulsion Systems for Surface Vehicles

    DTIC Science & Technology

    1975-01-01

    When wheels are used for off-road conditions, their reduced tractive ability makes all- axle drive a practical necessity. Figures 3.4, 3.5, and...is a constant goal of inventors . One approach is to articulate the vehicle so as to optimize wheel contact area (e.g., the XM 808). Another is...conclusion from this discussion is that high-mobility vehicle demands in thrusters are apparently being met by track and all- axle driven wheels

  2. Apparatus and Method for Generating Electric Energy in a Fluid Environment

    DTIC Science & Technology

    2005-03-14

    IONISTATEIENT A Filing Date 14 March 2005 Approved for Public Release Distribution Unlimited Inventor Donald H. Steinbrecher If you have any questions...member, a gear system disposed 6 in the housing, and an axle interconnects each of the crank 7 members and the gear system. An electrical generator is...fixed to an axle extending into the housing 25 and connected to the gear system, and an electrical generator is 3 1 disposed in the housing and driven

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

    PubMed

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

    2017-02-01

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

  4. Dual trailing arm vehicle suspension system

    SciTech Connect

    Weitzenhof, D.A.; Sayre, C.F.

    1986-11-18

    This patent describes a vehicle suspension system adapted to be interposed between a vehicle frame and at least two wheels arranged one in advance of the other on a side of the vehicle frame; the suspension system including: (a) at least two axles on a side of the vehicle frame for independently rotatably mounting each of the wheels; (b) at least two trailing arms, each of the arms being attached at one end to a respective axle and extending forwardly from the axle wherein the number of the trailing arms does not exceed the number of axles; (c) at least two pivot means mounted on the vehicle frame and connected to the other end of the trailing arms for pivotally mounting the vehicle frame wherein the number of the pivot means, does not exceed the number of axles; (d) lever means attached to and extending outwardly from each of the pivot means for pivotal movement with the pivot means means in relationship to movement of the trailing arms, with the length of the lever means being independent of the spacing between the axles; and (e) elastomer spring means extending between and pivotally mounted on the lever means for absorbing and balancing the forces exerted on the wheels particularly during braking and when encountering variations in the road surface.

  5. 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

  6. 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.

  7. A double-stranded DNA rotaxane.

    PubMed

    Ackermann, Damian; Schmidt, Thorsten L; Hannam, Jeffrey S; Purohit, Chandra S; Heckel, Alexander; Famulok, Michael

    2010-06-01

    Mechanically interlocked molecules such as rotaxanes and catenanes have potential as components of molecular machinery. Rotaxanes consist of a dumb-bell-shaped molecule encircled by a macrocycle that can move unhindered along the axle, trapped by bulky stoppers. Previously, rotaxanes have been made from a variety of molecules, but not from DNA. Here, we report the design, assembly and characterization of rotaxanes in which both the dumb-bell-shaped molecule and the macrocycle are made of double-stranded DNA, and in which the axle of the dumb-bell is threaded through the macrocycle by base pairing. The assembly involves the formation of pseudorotaxanes, in which the macrocycle and the axle are locked together by hybridization. Ligation of stopper modules to the axle leads to the characteristic dumb-bell topology. When an oligonucleotide is added to release the macrocycle from the axle, the pseudorotaxanes are either converted to mechanically stable rotaxanes, or they disassemble by means of a slippage mechanism to yield a dumb-bell and a free macrocycle. Our DNA rotaxanes allow the fields of mechanically interlocked molecules and DNA nanotechnology to be combined, thus opening new possibilities for research into molecular machines and synthetic biology.

  8. A double-stranded DNA rotaxane

    NASA Astrophysics Data System (ADS)

    Ackermann, Damian; Schmidt, Thorsten L.; Hannam, Jeffrey S.; Purohit, Chandra S.; Heckel, Alexander; Famulok, Michael

    2010-06-01

    Mechanically interlocked molecules such as rotaxanes and catenanes have potential as components of molecular machinery. Rotaxanes consist of a dumb-bell-shaped molecule encircled by a macrocycle that can move unhindered along the axle, trapped by bulky stoppers. Previously, rotaxanes have been made from a variety of molecules, but not from DNA. Here, we report the design, assembly and characterization of rotaxanes in which both the dumb-bell-shaped molecule and the macrocycle are made of double-stranded DNA, and in which the axle of the dumb-bell is threaded through the macrocycle by base pairing. The assembly involves the formation of pseudorotaxanes, in which the macrocycle and the axle are locked together by hybridization. Ligation of stopper modules to the axle leads to the characteristic dumb-bell topology. When an oligonucleotide is added to release the macrocycle from the axle, the pseudorotaxanes are either converted to mechanically stable rotaxanes, or they disassemble by means of a slippage mechanism to yield a dumb-bell and a free macrocycle. Our DNA rotaxanes allow the fields of mechanically interlocked molecules and DNA nanotechnology to be combined, thus opening new possibilities for research into molecular machines and synthetic biology.

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

    PubMed Central

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

    2017-01-01

    TAM receptors (Tyro-3, Axl, and Mertk) are a family of three homologous type I receptor tyrosine kinases that are implicated in several human malignancies. Overexpression of TAMs and their major ligand Growth arrest-specific factor 6 (Gas6) is associated with more aggressive staging of cancers, poorer predicted patient survival, acquired drug resistance and metastasis. Here we describe small molecule inhibitors (RU-301 and RU-302) that target the extracellular domain of Axl at the interface of the Ig-1 ectodomain of Axl and the Lg-1 of Gas6. These inhibitors effectively block Gas6-inducible Axl receptor activation with low micromolar IC50s in cell-based reporter assays, inhibit Gas6-inducible motility in Axl-expressing cell lines, and suppress H1299 lung cancer tumor growth in a mouse xenograft NOD-SCIDγ model. Furthermore, using homology models and biochemical verifications, we show that RU301 and 302 also inhibit Gas6 inducible activation of Mertk and Tyro3 suggesting they can act as pan-TAM inhibitors that block the interface between the TAM Ig1 ectodomain and the Gas6 Lg domain. Together, these observations establish that small molecules that bind to the interface between TAM Ig1 domain and Gas6 Lg1 domain can inhibit TAM activation, and support the further development of small molecule Gas6-TAM interaction inhibitors as a novel class of cancer therapeutics. PMID:28272423

  10. Amuvatinib has cytotoxic effects against NRAS-mutant melanoma but not BRAF-mutant melanoma.

    PubMed

    Fedorenko, Inna V; Fang, Bin; Koomen, John M; Gibney, Geoffrey T; Smalley, Keiran S M

    2014-10-01

    Effective targeted therapy strategies are still lacking for the 15-20% of melanoma patients whose melanomas are driven by oncogenic NRAS. Here, we report on the NRAS-specific behavior of amuvatinib, a kinase inhibitor with activity against c-KIT, Axl, PDGFRα, and Rad51. An analysis of BRAF-mutant and NRAS-mutant melanoma cell lines showed the NRAS-mutant cohort to be enriched for targets of amuvatinib, including Axl, c-KIT, and the Axl ligand Gas6. Increasing concentrations of amuvatinib selectively inhibited the growth of NRAS-mutant, but not BRAF-mutant melanoma cell lines, an effect associated with induction of S-phase and G2/M-phase cell cycle arrest and induction of apoptosis. Mechanistically, amuvatinib was noted to either inhibit Axl, AKT, and MAPK signaling or Axl and AKT signaling and to induce a DNA damage response. In three-dimensional cell culture experiments, amuvatinib was cytotoxic against NRAS-mutant melanoma cell lines. Thus, we show for the first time that amuvatinib has proapoptotic activity against melanoma cell lines, with selectivity observed for those harboring oncogenic NRAS.

  11. A self-threaded "molecular 8".

    PubMed

    Reuter, C; Wienand, W; Schmuck, C; Vögtle, F

    2001-04-17

    A new type of [1]rotaxanes containing two aliphatic bridges between axle and wheel is obtained in 39% yield in a one-step synthesis starting from a [2]rotaxane which contained one sulfonamide group each in both the wheel and the axle. Temperature controlled chemoselective substitution reactions first at these sulfonamide nitrogens and then subsequently at the various other carboxamide nitrogens in the wheel and axle give rise to the formation of an isomeric mixture of three double-bridged [1]rotaxanes which could be separated by HPLC. Structure determination of the main product 3a was possible by NMR experiments supported by molecular modeling calculations. Using different reaction conditions, a double-substituted but not yet bridged [2]rotaxane 4 could be isolated as an intermediate giving further evidence for the assigned structure of 3a and the way of its formation. The shape of this double-bridged [1]rotaxane 3a reminds of a self-intertwining chiral "molecular 8", in which any possible racemization due to deslipping is hindered by the two stoppers originating from the former rotaxane axle. Hence, to the best of our knowledge this is the first example of a molecule in which both concepts, cycloenantiomerism and helical chirality, are realised in one structure. Enantiomer separation of the main product was possible by further HPLC using chiral stationary phases. The Cotton effects of the circular dichrograms are different to those of the already synthesized [1]rotaxanes bearing just one aliphatic bridge between axle and wheel.

  12. 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.

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

    PubMed

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

    2014-02-12

    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.

  14. 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.

  15. Identification of cell surface molecules involved in dystroglycan-independent Lassa virus cell entry.

    PubMed

    Shimojima, Masayuki; Ströher, Ute; Ebihara, Hideki; Feldmann, Heinz; Kawaoka, Yoshihiro

    2012-02-01

    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.

  16. 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

  17. 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

  18. Time-resolved fluorescence resonance energy transfer as a versatile tool in the development of homogeneous cellular kinase assays.

    PubMed

    Saville, Lisa; Spais, Chrysanthe; Mason, Jennifer L; Albom, Mark S; Murthy, Seetha; Meyer, Sheryl L; Ator, Mark A; Angeles, Thelma S; Husten, Jean

    2012-12-01

    Homogeneous cellular assays can streamline product detection in the drug discovery process. One commercially available assay employing time-resolved fluorescence resonance energy transfer (TR-FRET) that detects phosphorylated products was used to evaluate inhibitors of the receptor tyrosine kinase AXL in a cell line expressing an AXL-green fluorescent protein fusion protein. This TR-FRET assay was modified to evaluate the phosphorylation state of the AXL family member MER in a cell line expressing MER with a V5 tag by adding a fluorescein-labeled anti-V5 antibody. This homogeneous cellular assay was further modified to evaluate the nonreceptor tyrosine kinase focal adhesion kinase (FAK) in cell lines that expressed an untagged kinase by the inclusion of a commercially available anti-FAK antibody conjugated with an acceptor dye. The methods described here can be further adapted for TR-FRET detection of other cellular kinase activities.

  19. 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.

  20. 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.

  1. Unified Behavior Framework in an Embedded Robot Controller

    DTIC Science & Technology

    2009-03-01

    wheel -legs mounted on three axles . Shown in Figure 2.3, each wheel -leg consists of three spoke “legs” set 120 degrees apart. Each wheel -leg is set 60...leg length by flexing the axle pairs into phase to maximize the torque on the climbing wheel -legs. The arrangement and phase offsets of the three pairs...Mini-WHEGSTM is a small robot that utilize wheel - legs to emulate cockroach walking patterns. Wheel -legs combine wheels and legs for high mobility

  2. USSR Report, Military Affairs, No. 1781.

    DTIC Science & Technology

    2007-11-02

    mechanisms. Both guns are secured to the cradle. The top carriage, platform with . wheel and axle assembly and elevating, traversing and equilibrator...towed at a maximum permissible speed of 70 km/h. Since the mount’s wheel and axle assembly has been equipped with torsion spring suspension, it can...Development, USSR Ministry of Defense: "The Innovators’ Weighty Contribution"] tTextJ On 25 May the 6th Congress of the All-Onion Society of Inventors

  3. Traction Boot for Tires

    DTIC Science & Technology

    1992-04-08

    34AD-D0 15 390 IN THE UNITED STATES PATENT AND TRADEMARK OFFICE Patent Application NAME Or INVENTOR : Joseph G. Warner DLECTI TITLE Of INVENTION...this nature include tiro chains or a loop of track connecting fore and aft wh#ls of a tandem axle assembly. There are disadvqstages with these known...vehicles with tandeo axles . o ed imfd pubr𔃾fl1a 99214-255191 92 9 14 085 SUNMARX My invention ii a boot or temporary recap for a tire that can be

  4. Powered Wheels in the Turned Mode Operating on Yielding Soils

    DTIC Science & Technology

    1976-09-01

    after Schuring , 1966) ... ........ 6 2.2. Conditions of a Wheel on Yielding Soil ..... ........... 7 2.3. Development of Trail Moment SF.C from An...forces and moments applied to the axle and at the interface area. Figure 2.1 (after Schuring , 1966) illustrates the possible combination of torque and...Horizontal Axle Pull P of a Free-Bodied Wheel (after Schuring , 1966). il ll l !ili l I m I U I 1 I II li i~ l6I TORQUE M o PULL P NEGA TI VE SLIP POS1TI

  5. 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.

  6. Better Seals for Vacuum Bags

    NASA Technical Reports Server (NTRS)

    Penn, B.; Clemons, J. M.

    1983-01-01

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

  7. 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,…

  8. Artificial Intelligence Applications for Nuclear Survivability Validation

    DTIC Science & Technology

    1992-11-01

    Speech recognition USAF: Flight simulator support General Devices: Engine Problem Diagnosis Eaton: Multi-axle truck brake control BC Hydro : Power...ENGRG ATTN: SLCHD-TL- WRF ATTN: LTC P J ENGSTROM ATTN: SLCHD-TN DEPUTY UNDER SECRETARY OF DEFENSE ATTN: SLC’S-;M-TL RESEARCH & ADVANCED TECHNOLOGY

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  10. 49 CFR 229.73 - Wheel sets.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Wheel sets. 229.73 Section 229.73 Transportation... TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Safety Requirements Suspension System § 229.73 Wheel sets. (a) The variation in the circumference of wheels on the same axle may not exceed 1/4 inch (two tape...

  11. 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...

  12. 40 CFR 1037.501 - General testing and modeling provisions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 162 inches high (measured from the ground with the trailer level). (ii) It has a king pin located with... inches in thickness. (iv) It includes dual 22.5 inch wheels, standard mudflaps, and standard landing gear... includes dual 24.5 inch wheels. (3) The standard trailer for low-roof tractors is an unloaded two-axle...

  13. 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 style, car line, combined fuel economy, engine code, equivalent test weight, gross vehicle weight, inertia weight, transmission class, and vehicle configuration are used as defined in subpart A of 40...

  14. 49 CFR 537.4 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... weight is used as defined in subpart A of 40 CFR part 86. (2) The terms axle ratio, base level, body style, car line, combined fuel economy, engine code, equivalent test weight, gross vehicle weight, inertia weight, transmission class, and vehicle configuration are used as defined in subpart A of 40...

  15. 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 style, car line, combined fuel economy, engine code, equivalent test weight, gross vehicle weight, inertia weight, transmission class, and vehicle configuration are used as defined in subpart A of 40...

  16. 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,…

  17. 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…

  18. 40 CFR 86.096-8 - Emission standards for 1996 and later model year light-duty vehicles.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., high-altitude axle ratio (rear-wheel drive vehicles) or a unique, high-altitude drivetrain (front-wheel... provisions of subpart Q of this part. (k) Cold Temperature Carbon Monoxide (CO) Standards—Light-Duty Vehicles... cold temperature CO standard of 10.0 grams per mile for an intermediate useful life of 50,000 miles,...

  19. 40 CFR 86.096-8 - Emission standards for 1996 and later model year light-duty vehicles.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., high-altitude axle ratio (rear-wheel drive vehicles) or a unique, high-altitude drivetrain (front-wheel... provisions of subpart Q of this part. (k) Cold Temperature Carbon Monoxide (CO) Standards—Light-Duty Vehicles... cold temperature CO standard of 10.0 grams per mile for an intermediate useful life of 50,000 miles,...

  20. 40 CFR 86.096-8 - Emission standards for 1996 and later model year light-duty vehicles.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., high-altitude axle ratio (rear-wheel drive vehicles) or a unique, high-altitude drivetrain (front-wheel... provisions of subpart Q of this part. (k) Cold Temperature Carbon Monoxide (CO) Standards—Light-Duty Vehicles... cold temperature CO standard of 10.0 grams per mile for an intermediate useful life of 50,000 miles,...

  1. 40 CFR 86.084-2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... automobile is standing and a line tangent to the front tire static loaded radius arc and touching the underside of the automobile forward of the front tire. Axle clearance means the vertical distance from the..., that can be formed by two lines tangent to the front and rear static loaded radii arcs and...

  2. 40 CFR 86.084-2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... automobile is standing and a line tangent to the front tire static loaded radius arc and touching the underside of the automobile forward of the front tire. Axle clearance means the vertical distance from the..., that can be formed by two lines tangent to the front and rear static loaded radii arcs and...

  3. 40 CFR 1066.210 - Dynamometers.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  4. Every Day a New 3D Printing Material

    ERIC Educational Resources Information Center

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

    2017-01-01

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

  5. 75 FR 73132 - Sypris Technologies, Sypris Solutions Division, Kenton, OH; Notice of Revised Determination on...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-29

    ... administrative reconsideration filed by the United Steel Workers, Local 1-109, on behalf of workers and former... contribute importantly to worker separations at the subject firm and no shift in production to a foreign... related to the production of trailer axle beams, meet the worker group certification criteria...

  6. 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…

  7. 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...

  8. 40 CFR 86.097-9 - Emission standards for 1997 and later model year light-duty trucks.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...'s graph. For each transmission/axle ratio combination, only the lowest N/V value shall be used in... lie to the upper right of the line as displayed on the graphs. (C) The exemption line is then defined... simultaneously fall to the lower left of the exemption line as drawn on the graph. (ii) Its design...

  9. 40 CFR 86.096-8 - Emission standards for 1996 and later model year light-duty vehicles.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... points on the manufacturer's graph. For each transmission/axle ratio combination, only the lowest N/V... either fall on the line or lie to the upper right of the line as displayed on the graphs. (C) The... and D/W which simultaneously fall to the lower left of the exemption line as drawn on the graph....

  10. Nuclear receptors license phagocytosis by trem2+ myeloid cells in mouse models of Alzheimer's disease.

    PubMed

    Savage, Julie C; Jay, Taylor; Goduni, Elanda; Quigley, Caitlin; Mariani, Monica M; Malm, Tarja; Ransohoff, Richard M; Lamb, Bruce T; Landreth, Gary E

    2015-04-22

    Alzheimer's disease (AD) is characterized by a robust inflammatory response elicited by the accumulation and subsequent deposition of amyloid (Aβ) within the brain. The brain's immune cells migrate to and invest their processes within Aβ plaques but are unable to efficiently phagocytose and clear plaques from the brain. Previous studies have shown that treatment of myeloid cells with nuclear receptor agonists increases expression of phagocytosis-related genes. In this study, we elucidate a novel mechanism by which nuclear receptors act to enhance phagocytosis in the AD brain. Treatment of murine models of AD with agonists of the nuclear receptors PPARγ, PPARδ, LXR, and RXR stimulated microglial phagocytosis in vitro and rapidly induced the expression of the phagocytic receptors Axl and MerTK. In murine models of AD, we found that plaque-associated macrophages expressed Axl and MerTK and treatment of the cells with an RXR agonist further induced their expression, coincident with the rapid reduction in plaque burden. Further characterization of MerTK(+)/Axl(+) macrophages revealed that they also expressed the phagocytic receptor TREM2 and high levels of CD45, consistent with a peripheral origin of these cells. Importantly, in an ex vivo slice assay, nuclear receptor agonist treatment reversed the AD-related suppression of phagocytosis through a MerTK-dependent mechanism. Thus, nuclear receptor agonists increase MerTK and Axl expression on plaque-associated immune cells, consequently licensing their phagocytic activity and promoting plaque clearance.

  11. 49 CFR Appendix A to Part 593 - List of Vehicles Determined To Be Eligible for Importation

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) VRSCA 2003 394 Harley Davidson (MC) VRSCA 2004 422 Hatty 45 ft double axle trailer 1999-2000 38 Heku 750... Double 1991 529 Rolls Royce Bentley 1989 340 Rolls Royce Bentley Brooklands 1993 186 Rolls Royce Bentley... C70 2000 434 Volvo S70 1998-2000 335 Yamaha (MC) Drag Star 1100 1999-2007 497 Yamaha (MC) FJ1200 (4...

  12. Neutral [2]rotaxane host systems that recognise halide anions in aqueous solvent mixtures.

    PubMed

    Mercurio, James M; Tyrrell, Fergus; Cookson, James; Beer, Paul D

    2013-11-28

    Four pyridine N-oxide axle containing [2]rotaxanes have been synthesised via an anion templated threading-followed-by-stoppering strategy and shown to be the first examples of neutral interlocked host systems capable of recognising halide anions in aqueous solvent mixtures.

  13. 40 CFR 86.094-14 - Small-volume manufacturers certification procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... numerical axle ratio offered in the engine family, and the maximum fuel flow calibration. (2) Heavy-duty... the order listed, highest fuel flow at the speed of maximum rated torque, the engine with the most advanced spark timing, no EGR or lowest EGR flow, and no air pump or lowest actual flow air pump. (3)...

  14. 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,…

  15. Talking Technology: Language and Literacy in the Primary School Examined through Children's Encounters with Mechanisms.

    ERIC Educational Resources Information Center

    Parkinson, Eric

    1999-01-01

    Technical terminology such as shaft and axle has a range of meanings in instructional support materials. Studies of children show that they use their own terms to describe unfamiliar components. Although appropriate vocabulary is desirable in technology education, teachers should find ways to incorporate children's own vocabulary to help them…

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

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

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

  17. Combat Engineers of World War II: Lessons on training and Mobilization

    DTIC Science & Technology

    2014-06-13

    pushed into mine fields and detonated to clear a path wide enough for a tank.65 Another improvement, the “ scorpion ,” was created from lengths of chain...attached to a revolving axle suspended well in front of a tank. As the tank moved forward, the chain flailed the ground. The scorpion was countered

  18. 76 FR 23286 - New Pneumatic Off-the-Road Tires From the People's Republic of China: Final Results of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-26

    ...,\\4\\ log-skidders,\\5\\ agricultural implements, highway-towed implements, agricultural logging, and... trucks, straddle carriers,\\10\\ graders,\\11\\ mobile cranes,\\12\\ compactors; and (3) industrial vehicles... fields. \\4\\ Industrial tractors are dual-axle vehicles that typically are designed to pull...

  19. 78 FR 69320 - Airworthiness Directives; DORNIER LUFTFAHRT GmbH Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-19

    ... main landing gear axle failure caused by initial fatigue cracking and small pre-damage by corrosion. We... caused by initial fatigue cracking and detection of small pre-damage by corrosion. We are issuing this AD... investigation indicated that improper restoration of corrosion protection was the likely cause of the...

  20. 14 CFR 23.509 - Towing loads.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    .... 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. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 49 CFR 665.5 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... vehicles manufactured on a third-party chassis, a change in frame structure, material or configuration, or a change in chassis suspension type. Major change in components means: (1) For those vehicles that... vehicles whose chassis structure has been modified to include: a tandem or tag axle; a drop or...

  6. 49 CFR 665.5 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... vehicles manufactured on a third-party chassis, a change in frame structure, material or configuration, or a change in chassis suspension type. Major change in components means: (1) For those vehicles that... vehicles whose chassis structure has been modified to include: a tandem or tag axle; a drop or...

  7. 75 FR 59060 - Airworthiness Directives; Turboméca S.A. ARRIEL 2B Turboshaft Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-27

    ...-mechanical unit (HMU) acceleration controller axle except on engines that incorporate modification TU 132... modification TU 149. This AD results from reports of engines with modification TU 132 incorporated experiencing... TU 62A, unless the engine incorporates modification TU 132. That AD was the result of several...

  8. 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…

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

    NASA Astrophysics Data System (ADS)

    Nodine, Robert N.; Scudiere, Matthew B.; Jordan, John 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 accuracy range of plus or minus 3.0% to plus or 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 functions with any linear weight sensor and a set of four axle switches per sensor.

  10. 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…

  11. 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…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  13. Dynamic Loads Affecting Artillery Launcher Crew

    DTIC Science & Technology

    2004-10-01

    limiters) front and rear wheel axles, the cabin, driving block, the launcher (or an open load-carrying body) as well as flexible- suppressing tyre ...Driver’s seat suspension change included the replacement of mechanical suspension with the pneumatic one, which can be characterized by a lower

  14. 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.

  15. 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...

  16. A Saturation Balancing Control Method for Enhancing Dynamic Vehicle Stability (PREPRINT)

    DTIC Science & Technology

    2011-03-01

    is re-interpreted for an independent axle drive or torque-vectoring application. A torque biasing PI control can be defined from the balance of the... PI control that uses yaw rate error feedback: desired  Yaw Rate Gain Linear reference Dry Road Wet Road   L VK xusy desired

  17. Gear box assembly

    SciTech Connect

    Harrod, L.R.; Siebern, M.R.

    1989-04-25

    This patent describes a gearbox assembly for a vehicle which includes a driven axle shaft extending transversely of the vehicle having wheels secured thereto: a drive gear concentric with the axle shaft nonrotatably connected to the shaft, the drive gear having an integral hub on each of opposite sides thereof, a pinion gear shiftably mounted above the drive gear having one position engaging the drive gear and shiftable laterally to disengage from the drive gear, a shift lever mounted in a position projecting upwardly from the pinion gear actuatable to shift the pinion gear, an electric motor with output shaft mounted with the output shaft paralleling the axle shaft and having a driving gear mounted thereon, a multiple gear gear train mounted so as to establish a driving connection between the driving gear and the pinion gear, and a transmission housing enclosing the driving gar, gear train, pinion gear and drive gear, the housing including sleeve portions rotatably receiving the hubs of the drive gear and thus rotatably mounting the drive gear and the axle shaft connected to the drive gear.

  18. 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…

  19. 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)

  20. 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…

  1. 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…

  2. 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…

  3. 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,…

  4. 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

  5. 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..., axles and attaching parts, wheels and rims, and steering systems. (2) Pushout windows, emergency doors... indicating their date and nature; and (4) A record of tests conducted on pushout windows, emergency...

  6. 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..., axles and attaching parts, wheels and rims, and steering systems. (2) Pushout windows, emergency doors... indicating their date and nature; and (4) A record of tests conducted on pushout windows, emergency...

  7. 40 CFR 1036.140 - Primary intended service class.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... POLLUTION CONTROLS CONTROL OF EMISSIONS FROM NEW AND IN-USE HEAVY-DUTY HIGHWAY ENGINES Emission Standards... axles, city tractors, and a variety of special purpose vehicles such as small dump trucks, and refuse trucks. Typical applications would include commercial short haul and intra-city delivery and...

  8. 40 CFR 1036.140 - Primary intended service class.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... POLLUTION CONTROLS CONTROL OF EMISSIONS FROM NEW AND IN-USE HEAVY-DUTY HIGHWAY ENGINES Emission Standards... axles, city tractors, and a variety of special purpose vehicles such as small dump trucks, and refuse trucks. Typical applications would include commercial short haul and intra-city delivery and...

  9. 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…

  10. 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

  11. Molecular dynamics study of 2rotaxanes: influence of solvation and cation on co-conformation.

    PubMed

    Fradera, Xavier; Márquez, Manuel; Smith, Bradley D; Orozco, Modesto; Luque, F Javier

    2003-06-13

    The conformational preference of a [2]rotaxane system has been examined by molecular dynamics simulations. The rotaxane wheel consists of two bridged binding components: a cis-dibenzo-18-crown-6 ether and a 1,3-phenyldicarboxamide, and the penetrating axle consists of a central isophthaloyl unit with phenyltrityl capping groups. The influence of solvation on the co-conformation of the [2]rotaxane was evaluated by comparing the conformational flexibility in two solvents: chloroform and dimethyl sulfoxide. Attention was also paid to the effect of cation binding on the dynamical properties of the [2]rotaxane. The conformational stability of the [2]rotaxane was calculated using a MM/PB-SA strategy, and the occurrence of specific motions was examined by essential dynamics analysis. The changes in the co-conformational properties in the two solvents and upon cation binding are discussed in light of the available NMR data. The results indicate that in chloroform solution the [2]rotaxane system exists as a mixture of co-conformational states including some that have hydrogen bonds between axle C=O and wheel NH groups. Analysis of the simulations allow us to hypothesize that the [2]rotaxane's circumrotation motion can occur as the result of a dynamic process that combines a preliminary axle sliding step that breaks these hydrogen bonds and a conformational change in the ester group more distant from the wheel. In contrast, no hydrogen-bonded co-conformation was found in dimethyl sulfoxide, which appears to be due to the preferential formation of hydrogen bonds between the wheel NH groups with solvent molecules. Moreover, the axle experiences notable changes in anisotropic shielding, which would explain why the NMR signals are broadened in this solvent. Insertion of a sodium cation into the crown ether reduces co-conformational flexibility due to an interaction of the axle with the cation. Overall, the results reveal how both solvent and ionic atmosphere can influence the co

  12. 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.

  13. Side gear mounting for differential assembly

    SciTech Connect

    Pederson, H.

    1989-02-21

    A differential gear assembly is described of the type which includes a differential gear housing having means for receiving a pair of axle ends together with a pair of substantially axially aligned side gears coupled to the pair of axle ends for rotation therewith, the side gears having helix angles inclined in the same direction with respect to the axes of rotation thereof, characterized in that the gear assembly includes means for preventing axial thrust forces developed by one of the side gears from loading the other of the side gears. The preventing means includes means for separating the side gears such that there is no direct or indirect engagement between confronting end faces of the side gears when thrust forces of one of the side gears are directed toward the other of the side gears; and the means for axially separating the side gears includes a pair of overlapping elements associated with one of the side gears of the gear housing.

  14. Battery powererd electric motor vehicle

    SciTech Connect

    Muhlbacker, K.

    1984-02-28

    A battery powered vehicle is provided with a vehicle frame and an electric motor whose main shaft is connected to a differential gear by means of a gear train with a variable transmission ratio, the motor shaft and all gear shafts being parallel to the axle of the driving wheels. In order to achieve a compact design and to avoid power-consuming drive elements the electric motor and the variable transmission gear as well as a potential reducing gear mounted between the latter and the differential gear, are positioned on a subframe which is connected to the housing of the driving wheel axle on the one side whereas the other side carrying the electric motor is attached to the vehicle frame by means of a cardanic suspension.

  15. 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.

  16. 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.

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

    NASA Astrophysics Data System (ADS)

    Martell, Eric C.; Martell, Verda Beth

    2013-02-01

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

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

    PubMed

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

    2016-09-05

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

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

    PubMed Central

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

    2016-01-01

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

  20. A pH-sensitive peptide-containing lasso molecular switch.

    PubMed

    Clavel, Caroline; Fournel-Marotte, Karine; Coutrot, Frédéric

    2013-09-17

    The synthesis of a peptide-containing lasso molecular switch by a self-entanglement strategy is described. The interlocked rotaxane molecular machine consists of a benzometaphenylene[25]crown-8 (BMP25C8) macrocycle surrounding a molecular axle. This molecular axle contains a tripeptidic sequence and two molecular stations: a N-benzyltriazolium and a pH-sensitive anilinium station. The tripeptide is located between the macrocycle and the triazolium station, so that its conformation can be tailored depending on the shuttling of the macrocycle from one station to the other. At acidic pH, the macrocycle resides around the anilinium moiety, whereas it shuttles around the triazolium station after deprotonation. This molecular machinery thus forces the lasso to adopt a tightened or a loosened conformation.

  1. Triply Threaded [4]Rotaxanes.

    PubMed

    Danon, Jonathan J; Leigh, David A; McGonigal, Paul R; Ward, John W; Wu, Jhenyi

    2016-09-28

    [4]Rotaxanes featuring three axles threaded through a single ring have been prepared through active metal template synthesis. Nickel-catalyzed sp(3)-sp(3) homocouplings of alkyl bromide "half-threads" through 37- and 38-membered 2,2':6',2″-terpyridyl macrocycles generate triply threaded [4]rotaxanes in up to 11% yield. An analogous 39-membered macrocycle produced no rotaxane products under similar conditions. The constitutions of the [4]rotaxanes were determined by NMR spectroscopy and mass spectrometry. Doubly threaded [3]rotaxanes were also obtained from the reactions but no [2]rotaxanes were isolated, suggesting that upon demetalation the axle of a singly threaded rotaxane can slip through a macrocycle that is sufficiently large to accommodate three threads.

  2. Anion recognition and cation-induced molecular motion in a heteroditopic [2]rotaxane.

    PubMed

    Leontiev, Alexandre V; Jemmett, Charlotte A; Beer, Paul D

    2011-01-17

    A heteroditopic [2]rotaxane consisting of a calix[4]diquinone-isophthalamide macrocycle and 3,5-bis-amide pyridinium axle components with the capability of switching between two positional isomers in response to barium cation recognition is synthesised. The anion binding properties of the rotaxane's interlocked cavity together with Na(+) , K(+) , NH(4) (+) and Ba(2+) cation recognition capabilities are elucidated by (1) H NMR and UV-visible spectroscopic titration experiments. Upon binding of Ba(2+) , molecular displacement of the axle's positively charged pyridinium group from the rotaxane's macrocyclic cavity occurs, whereas the monovalent cations Na(+) , K(+) and NH(4) (+) are bound without causing significant co-conformational change. The barium cation induced shuttling motion can be reversed on addition of tetrabutylammonium sulfate.

  3. 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.

  4. Screening bioactives reveals nanchangmycin as a broad spectrum antiviral active against Zika virus

    PubMed Central

    Rausch, Keiko; Hackett, Brent; Weinbren, Nathan; Reeder, Sophia; Sadovsky, Yoel; Hunter, Christopher; Schultz, David C.; Coyne, Carolyn; Cherry, Sara

    2017-01-01

    Zika virus is an emerging arthropod-borne flavivirus for which there are no vaccines or specific therapeutics. We screened a library of 2000 ‘bioactive’ compounds for their ability to block Zika virus infection in three distinct cell-types with two different strains of Zika virus. Using a microscopy-based assay, we validated 38 drugs that inhibited Zika virus infection, including FDA approved nucleoside analogs. Cells expressing high levels of the attachment factor AXL can be protected from infection with receptor tyrosine kinase inhibitors, while placental-derived cells that lack AXL expression are insensitive to this inhibition. Importantly, we identified nanchangmycin as a potent inhibitor of Zika virus entry across all cell types tested including physiologically relevant primary cells. Nanchanmycin was also active against other medically relevant viruses including West Nile, dengue, and chikungunya virus that use a similar route of entry. This study provides a resource of small molecules to study Zika virus pathogenesis. PMID:28099856

  5. 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.

  6. 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.

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

    PubMed Central

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

    2005-01-01

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

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

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

    PubMed

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

    2014-10-10

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

  14. 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.

  15. Vehicle systems: coupled and interactive dynamics analysis

    NASA Astrophysics Data System (ADS)

    Vantsevich, Vladimir V.

    2014-11-01

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

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

    PubMed

    Gong, Zheng; Sun, Junhua; Zhang, Guangjun

    2016-04-20

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

  17. 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

  18. Improved Engine Performance and Efficiency Utilizing a Superturbocharger

    DTIC Science & Technology

    2012-08-01

    losses, expected system life, overall size and packaging. The planetary designs are chosen from available gear and traction drive designs, or a...exhaust heat recovery to improve fuel productivity. The device consists of a high speed planetary step down mounted on the same shared axle between...the turbine and compressor. The high speed planetary provides the speed reduction necessary to reach CVT operating speeds. The CVT allows for bi

  19. Automobile transmission with output shaft parallel to crank shaft and parking gear fixed to the output shaft

    SciTech Connect

    Kubo, S.; Kuramochi, K.; Kyushima, T.

    1987-06-30

    A driving device is described for an automobile having axles, driving wheels supported by the axles and an engine located proximate the driving wheels, having a crankshaft disposed substantially parallel to the axles supporting the driving wheels, the device comprising: a fluid-type torque converter having coaxial input and output members and disposed on one axial side of the engine connected to and coaxial with the crankshaft; an auxiliary speed change gear assembly having coaxial input and output members and disposed on one axial side of the torque converter remote from the engine with the input member connected to and coaxial of the torque converter; the output member of the auxiliary speed change gear assembly is provided in the shape of a gear; a transmission shaft disposed substantially parallel to the auxiliary speed change gear assembly; a driven gear having a disc portion and toothed peripheral portion; a drive gear drivingly connected to the other end of the transmission shaft closer to the torque converter than the one end of the transmission shaft; a final reduction gear disposed between the driving wheels to be in meshing engagement with the drive gear to transmit power to the axles; a parking gear comprising an annular gear element fixed by bolts proximate the toothed peripheral portion to the axial side surface from which the transmission shaft extends toward the other end. The parking gear is supported by the disc portion for rotation with the driven gear; and means for selectively engaging the parking gear to prevent rotation of shaft when automobile is in parking condition.

  20. Simultaneous Magnetometer and EM61 MK2 Vehicle-Towed Array for Wide Area Assessment

    DTIC Science & Technology

    2008-09-01

    years old whereas other portions were only designed to survive a single 2002 APG fielding, the system is best operated by its inventors . Through...check, cleaning air filters, and greasing the axles of the tow platform. Major unforeseen problems included persistent jamming of our GPS base-to-radio...coils are deployed on their native wheels ). Although the system is capable of using EM61 upper coils and employing the “D” setting on the electronics

  1. USSR Report Machine Tools and Metalworking Equipment

    DTIC Science & Technology

    2007-11-02

    presses. Unique presses for sheet-metal stamping and synthesis of super-hard materials were created and wheels for railway rolling stock were...manufactured using Soviet-made high-output unique machinery for screw rolling and helical rolling of round periodical sections, wheels , spheres and other...parts. Two plants produced wagon axles by rolling them in- stead of forging them with hydraulic presses and reduced metal content by about 80 kg

  2. ’MLRS’: A Rocket System for the Marine Corps

    DTIC Science & Technology

    1990-03-29

    In 1846, an English inventor , William Hale, entered rocket history by improving the designing of the Congreve rocket. Rockets known for their erratic...or "curved vanes", were used in conjunction with "tangential holes at the periphery of the base" (developed by an American inventor named Court) to...twelve launchers each, which were mounted over the rear axle and fired electrically from the cab. These were the 4.5-inch rockets (MB) used in the T45

  3. Company Command: The Bottom Line

    DTIC Science & Technology

    1990-11-20

    steering Jeep No. 583-6 around a corner, the right front wheel falls off. The vehicle over- turns. The driver suffers two broken legs and a dislocated...the accident was a missing cotter pin in the front wheel ; the pin was removed when the bearings were repacked, but was never replaced. NOW WHAT...around the axle " over the accident it- self, rather than analyzing possible causes for it. Study your accident reports. You may discover a trend you can

  4. The Technological Fix: Weapons and the Cost of War.

    DTIC Science & Technology

    1995-06-06

    millennium B.C. was replaced by the horse. Second, a light chariot evolved boasting standard features that transcended regional variations−two spoked wheels , a...central, curved draft pole harnessing two to four horses, a fixed axle set beneath the rear of the rider’s box, and a railing to support the driver...fix by an enterprising American painter, inventor , and opportunist named Robert Fulton.36 Penetrating the reigning paradigm of naval warfare, Fulton

  5. JPRS Report, Soviet Union Economic Affairs

    DTIC Science & Technology

    1988-11-01

    automatic engagement of the front axle drive). The introduction of new components and sets of hearts in order to raise the technical level and increase...route specialists, yard masters, car inspectors, innovators, and inventors ... They speak of difficulties, state problems which in their opinion demand...of the teams, partic- ularly the young locomotive engineers, have been lax. The accidents which have taken place attest to this. A wheel pair on a

  6. JPRS Report, Soviet Union, EKO: Economics & Organization of Industrial Production, No. 11, November 1987.

    DTIC Science & Technology

    1988-03-22

    pride. And then—this success in the past, what kind was it? Did it turn the wheel of industry like the elimination of unemployment, the defeat of...for example, it could consist of a direct current microengine and an axle meter of rotations which is applied in any threshing machine or...efficiency experts and the inventors , and so forth. As concerns the complexity of the account- ing, it is not great and it can even be simplified by the

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

    DTIC Science & Technology

    2010-02-01

    measures pavement friction using the braked -wheel, fixed-slip principle. Two wheels support the Grip Tester on a drive axle, while a measuring wheel with...force and vertical load force. A transmission system routinely brakes the measuring wheel, causing it to slip. This action provides the responses that...completed, the area subjected to shot blasting is further cleaned with a magnetic sweeper. Figure 16 shows the pavement surface condition with and with

  8. Handling Qualities Evaluation of the RAAF Museum Fokker Triplane

    DTIC Science & Technology

    1993-06-01

    surface of the axle fairing. 140 mm aft (14 degrees) Pneumatic tyres (with a correct inflation of * 35 psi) are provided. Automotive drum 100 mm laterally...filler caps secure. 10. Tyre condition, inflation and BEFORE ENGINE START wear. Check underneath the brake units for hydraulic fluid 1. Strap-in...although smooth grass runways are aircraft should be landed on the mainwheels, satisfactory (and preferable for tyre wear keeping the tail in the air

  9. The Shock and Vibration Digest. Volume 12, Number 2,

    DTIC Science & Technology

    1980-02-01

    plans as well as with standard stationary frame pneumatic instru- mentation. 80-217 80-215 Reliability of Steam Turbine Rotors: Summary Re- Study in a...of the carbody is determined using inelastic time- history analysis. Practical and wheel-axle sets. Dynamic interaction equations for the methods of...derived from this study provides a basis for under- forms of the response time history and the synthesized input standing the fundamental principles of

  10. SAE J1321 Testing Using M1083A1 FMTVS

    DTIC Science & Technology

    2010-03-01

    Lubrican ts Research Facility (TFLRF) located at Southwest Research I nstitute (SwRI), San Antonio, Texas, perf ormed this work durin g the per iod ...In contrast , the candidate axle oil sh owed a negative im pact on fuel effi ciency between the tested candidate and baseline fluids. A large number...losses and less heat produced in the bulk fluid from this m anner. However, this is coun tered by an in crease in hea t production at the sliding

  11. Flight Test Evaluation of Airborne Tire Pressure Indicating Systems.

    DTIC Science & Technology

    1979-09-01

    reasons they were not selected follows: Aoproaeh/Concent 1. Differential Valve - Discrete (Concept I, Part I Report) Differential valve opens when...system sensors are closed loop servo inclinometers, mounted on the bogie beam for main gear and inside the axle for the nose gear. 5. Go-No-Go Discrete...is an indication of a lack of symmetry between wheels of the same category. The differential level is set at 35 psi. If the particular tire is 35 psi

  12. Deployable Command and Control System for Over the Horizon Small Boat Operations

    DTIC Science & Technology

    2006-09-01

    contact with ESRI support facilities. b. After the DNC is copied to the local machine, you can proceed to add it to the geodatabase . This is...accomplished, ArcIMS Designer can be used to build the web site which uses the service to deliver the .axl files ( ESRI , Getting Started 38 with ArcIMS...is a prototype system designed to facilitate Command and Control during over the horizon small boat operations. It is designed to allow small boats

  13. Fuel consumption of freight trains hauled by diesel electric locomotives

    SciTech Connect

    Radford, R.W.

    1983-05-01

    The cost of railway diesel fuel has become an increasingly high proportion of railway operating expenses. The paper analyzes the generation and utilization of rail horsepower in freight train operations. The effects on fuel consumption of variations in several parameters including train consist, car weight, gradient, average speed, meet strategy, throttle control, locomotive axle arrangement, and train marshalling are examined. Estimates are made of the value, in terms of fuel cost, of weight reduction of freight cars and of selective train marshalling.

  14. 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.

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

    PubMed

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

    2007-04-01

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

  16. Improving the Value Engineering Change Proposal Process within the U.S. Army Corps of Engineers

    DTIC Science & Technology

    1993-08-01

    his staff engineers, Lawrence Miles, to investigate the feasibility of substituting one product for another in order to increase efficiency. Miles...TO UEV!tL ARW TEM 2 rT AXL 447 -- X50~S 3. D=Iz the next few mzithe, our , qmrters will pibiisi guLc~m iff lesscwo Leavied to further ct d=eStenUmu

  17. 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.

  18. 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

  19. The Coast Artillery Journal. Volume 72, Number 5, May 1930

    DTIC Science & Technology

    1930-05-01

    wheels penetrate into the soft ground. By using dual pneumatic tires on all axles the ground pressures under the front tires for a six-inch penetration...ground pressure , which is about the same as the ground pressure for the Ford cross-country car, insures cross-country mobility. MECHANIZED MACHINE GUNS...this purpose, a twenty-gallon aluminum water tank is placed under the firing platform in a position to counter-balance the weight of the director

  20. Targeting Tumor Oct4 to Deplete Prostate Tumor- and Metastasis-Initiating Cells

    DTIC Science & Technology

    2015-10-01

    NOTCH1, NOTCH2 WNT Signaling DKK1 , EPCAM, FZD7, WNT1 PI3K/AKT/mTOR signaling ABCG2, GSK3B S / κ S g g IKBKB, JAK2, NFKB1 Therapeutic...Targets ABCG2, ATM, AXL, CHEK1, DDR1, DKK1 , EPCAM, FZD7, GSK3B, ID1, IKBKB, JAK2, KLF17, NFKB1, PTCH1, SMO, STAT3, TGFBR1, WEE1 19 (A

  1. Identification and regulation of receptor tyrosine kinases Rse and Mer and their ligand Gas6 in testicular somatic cells.

    PubMed

    Chan, M C; Mather, J P; McCray, G; Lee, W M

    2000-01-01

    Receptor tyrosine kinases act to convey extracellular signals to intracellular signaling pathways and ultimately control cell proliferation and differentiation. Rse, Axl, and Mer belong to a newly identified family of cell adhesion molecule-related receptor tyrosine kinase. They bind the vitamin K-dependent protein growth arrest-specific gene 6 (Gas6), which is also structurally related to the anticoagulation factor Protein S. The aim of this study is to investigate the possible role of Rse/Axl/Mer tyrosine kinase receptors and their ligand in regulating testicular functions. Gene expression of Rse, Axl, Mer, and Gas6 in the testis was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot analysis. The results indicated that receptors Rse and Mer and the ligand Gas6 were expressed in the rat endothelial cell line (TR1), mouse Leydig cell line (TM3), rat peritubular myoid cell line (TRM), mouse Sertoli cell line (TM4), and primary rat Sertoli cells. Axl was not expressed in the testicular somatic cells by RT-PCR or Northern blot analysis. The highest level of expression of Gas6 messenger RNA (mRNA) was observed in the Sertoli cells, and its expression was responsive to the addition of forskolin in vitro. The effects of serum, insulin, and transferrin on Gas6 expression by TM4 cells were examined. It was shown that they all exhibited an up-regulating effect on Gas6 expression. The forskolin-stimulated Gas6 expression was accompanied by an increase in tyrosine phosphorylation of the Rse receptor in vitro, suggesting that Gas6 may exhibit an autocrine effect in the Sertoli cells through multiple tyrosine kinase receptors. Our studies so far have demonstrated that tyrosine kinase receptors Rse and Mer and their ligand Gas6 are widely expressed in the testicular somatic cell lines and may play a marked role in promoting testicular cell survival.

  2. Asset Management and Facility Equipment Maintenance Nexus: Maintenance Effectiveness

    DTIC Science & Technology

    2013-09-01

    WEEKS B2AS-MA 3 MONTHS ERDC/CERL TR-13-15 192 100 LUBRICATE AXLE COUPLERS 110 CLEAN ENGINE COOLING FINS 72 BSL-2355 6 MONTH JOH N DEERE GATOR...1469 MONTHLY GRINDER/ BUFFER MAINT. & INSP. B2AS-MA 1 MONTHS Next 7/9/12 Next Job BSL-13791 Use Target Start: y BSL-13791 MONTHLY GRINDER/ BUFFER MAl NT

  3. Proceedings of the European Conference (4th), Held in Wageningen, The Netherlands on March 21-23, 1989. Volume 2

    DTIC Science & Technology

    1989-03-01

    business . So we pursue and hope for mutual knowledge exchange, and general progress for our joint discipline of terra-mechanics. As conference theme we... business is synonymous to transport business . For productivity reasons, heavy farm trailers have been introduced. High wheel and axle loads cause a...this business with pleasure during your stay in our country. References Eimer, M and Dreses, V, 1985. Wirtschaftliche Auslastung verschiedener

  4. 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.

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

    DTIC Science & Technology

    2008-03-01

    Institute for the Behavioral and Socia Sc’ ,ices (ARI), including Dr. Michelle Sams and Dr. Zita Simutis, and especially its Fort Leave’ "orth Research...through a process of analysis and reflection of those experiences. Specifically, AXL provides an online, media -rich environment for delivering case...points of view (Kutner, Greenburg, & Baer, 2005). Thus, case study materials that are presented through media other than the written form can create an

  6. The theoretical analysis of an instrument for linear and angular displacements of the steered wheel measuring

    NASA Astrophysics Data System (ADS)

    Wach, K.

    2016-09-01

    In the paper the theoretical analysis of the measuring instrument for determination of translation and rotation of the stub axle with the steered wheel against car body was presented. The instrument is made of nine links with elongation sensors embedded in it. One of several possible structures of instrument of this kind was presented. Basing on solution of the geometrical constraints system of equations of the device, the numerical analysis of the measurement accuracy was conducted.

  7. 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…

  8. 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.

  9. Potential of spark ignition engine, 1979 summary source document. Final report

    SciTech Connect

    Trella, T.; Zub, R.; Colello, R.

    1980-03-01

    This report provides an assessment of the potential for spark ignition engines passenger cars and light trucks. The assessment includes: tradeoffs between fuel economy and emissions; improvements in spark ignition engine efficiency; improvements in engine parasitics; improvements due to transmissions; effect of aerodynamic drag and tire rolling resistance on fuel economy; effect on performance and fuel economy of weight and axle ratio; lubricant improvements; impact of fuels; and noise considerations.

  10. Study of Early Elevated Gas6 Plasma Level as a Predictor of Mortality in a Prospective Cohort of Patients with Sepsis

    PubMed Central

    Calzavarini, Sara; Burnier, Laurent; Kosinski, Christophe; Ballabeni, Pierluigi; Roger, Thierry; Calandra, Thierry; Duchosal, Michel A.; Liaudet, Lucas

    2016-01-01

    Background Growth arrest-specific gene 6 (Gas6), a vitamin K-dependent protein interacting with anionic phospholipids and TAM tyrosine kinase receptors, is elevated in plasma of septic patients. Previous studies did not find different levels between survivors and non-survivors at admission because either they included a low number of patients (<50) or a low number of non-survivors (5%). Objectives To determine, in a larger cohort of septic patients comprising an expected number of non-survivors, the performance of the plasma level of Gas6 and its soluble receptor Axl (sAxl) within 24 hours of admission to predict in-ICU mortality. Patients Septic adults with or without shock. Methods Gas6 and sAxl were prospectively measured by ELISA at day 0, 3, 7, and then weekly until discharge or death. Results We evaluated 129 septic patients, including 82 with and 47 without shock, with in-ICU mortality rate of 19.4% and in-hospital mortality rate of 26%. Gas6 level was higher in non-survivors than in survivors (238 vs. 167%, P = 0.003); this difference remained constant during the ICU stay. The area under the ROC curve for Gas6 (0.695 [95% CI: 0.58–0.81]) was higher than for sAxl, procalcitonin, CRP, IL-1beta, IL-6 and-alpha, and slightly higher than for IL-8, IL-10, SOFA and APACHEII scores in predicting in-ICU mortality. Considering 249% as a cut-off value, Gas6 measurement had a negative predictive value for mortality of 87%. Conclusion It seems that Gas6 plasma level within 24 hours of ICU admission may predicts in-ICU mortality in patients with sepsis. If our result are confirmed in external validation, Gas6 plasma level measurement could contribute to the identification of patients who may benefit most from more aggressive management. PMID:27788141

  11. 49 CFR 393.47 - Brake actuators, slack adjusters, linings/pads and drums/rotors.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... steering axle of a truck, truck-tractor or bus shall not be less than 4.8 mm (3/16 inch) at the shoe center for a shoe with a continuous strip of lining; less than 6.4 mm (1/4 inch) at the shoe center for a shoe with two pads; or worn to the wear indicator if the lining is so marked, for air drum brakes....

  12. 49 CFR 393.47 - Brake actuators, slack adjusters, linings/pads and drums/rotors.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... steering axle of a truck, truck-tractor or bus shall not be less than 4.8 mm (3/16 inch) at the shoe center for a shoe with a continuous strip of lining; less than 6.4 mm (1/4 inch) at the shoe center for a shoe with two pads; or worn to the wear indicator if the lining is so marked, for air drum brakes....

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

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... steering axle of a truck, truck-tractor or bus shall not be less than 4.8 mm (3/16 inch) at the shoe center for a shoe with a continuous strip of lining; less than 6.4 mm (1/4 inch) at the shoe center for a shoe with two pads; or worn to the wear indicator if the lining is so marked, for air drum brakes....

  14. 49 CFR 393.47 - Brake actuators, slack adjusters, linings/pads and drums/rotors.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... steering axle of a truck, truck-tractor or bus shall not be less than 4.8 mm (3/16 inch) at the shoe center for a shoe with a continuous strip of lining; less than 6.4 mm (1/4 inch) at the shoe center for a shoe with two pads; or worn to the wear indicator if the lining is so marked, for air drum brakes....

  15. 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.

  16. Evaluation of Anterior Chamber Volume in Cataract Patients with Swept-Source Optical Coherence Tomography

    PubMed Central

    He, Wenwen; Zhu, Xiangjia; Wolff, Don; Sun, Xinghuai

    2016-01-01

    Purpose. To evaluate the anterior chamber volume in cataract patients with Swept-Source Optical Coherence Tomography (SS-OCT) and its influencing factors. Methods. Anterior chamber volume of 92 cataract patients was evaluated with SS-OCT in this cross-sectional study. Univariate analyses and multiple linear regression were used to investigate gender, age, operated eye, posterior vitreous detachment, lens opacity grading, and axial length (AXL) related variables capable of influencing the ACV. Results. The average ACV was 139.80 ± 38.21 mm3 (range 59.41 to 254.09 mm3). The average ACV was significantly larger in male patients than in female patients (P = 0.001). ACV was negatively correlated with age and LOCS III cortical (C) grading of the lens (Pearson's correlation analysis, r = −0.443, P < 0.001, and Spearman's correlation analysis, ρ = −0.450, P < 0.001). ACV was also increased with AXL (Pearson's correlation analysis, r = 0.552, P < 0.001). Multiple linear regression showed that, with all of the covariates entered into the model, gender (P = 0.002), age (P = 0.015), LOCS III C grade (P = 0.043), and AXL (P = 0.001) were still associated with ACV (F = 10.252  P < 0.001  R2 = 0.498). Conclusion. With SS-OCT, we found that, in healthy cataract patients, ACV varied significantly among different subjects. Influencing factors that contribute to reduced ACV were female gender, increased age, LOCS III C grade, and shorter AXL. PMID:27688910

  17. Evaluation of Anterior Chamber Volume in Cataract Patients with Swept-Source Optical Coherence Tomography.

    PubMed

    He, Wenwen; Zhu, Xiangjia; Wolff, Don; Zhao, Zhennan; Sun, Xinghuai; Lu, Yi

    2016-01-01

    Purpose. To evaluate the anterior chamber volume in cataract patients with Swept-Source Optical Coherence Tomography (SS-OCT) and its influencing factors. Methods. Anterior chamber volume of 92 cataract patients was evaluated with SS-OCT in this cross-sectional study. Univariate analyses and multiple linear regression were used to investigate gender, age, operated eye, posterior vitreous detachment, lens opacity grading, and axial length (AXL) related variables capable of influencing the ACV. Results. The average ACV was 139.80 ± 38.21 mm(3) (range 59.41 to 254.09 mm(3)). The average ACV was significantly larger in male patients than in female patients (P = 0.001). ACV was negatively correlated with age and LOCS III cortical (C) grading of the lens (Pearson's correlation analysis, r = -0.443, P < 0.001, and Spearman's correlation analysis, ρ = -0.450, P < 0.001). ACV was also increased with AXL (Pearson's correlation analysis, r = 0.552, P < 0.001). Multiple linear regression showed that, with all of the covariates entered into the model, gender (P = 0.002), age (P = 0.015), LOCS III C grade (P = 0.043), and AXL (P = 0.001) were still associated with ACV (F = 10.252  P < 0.001  R (2) = 0.498). Conclusion. With SS-OCT, we found that, in healthy cataract patients, ACV varied significantly among different subjects. Influencing factors that contribute to reduced ACV were female gender, increased age, LOCS III C grade, and shorter AXL.

  18. Evaluation of the Impact of Towing DC-9 Transport Airplanes at Boston-Logan Airport.

    DTIC Science & Technology

    1980-05-01

    47 6. BOLT-SHOULDER-DRAG BRACE. .. ..... ..... ...... 47 7. HOUSING . .. ... ..... .... ..... ......... 52 8. PISTON-AXLE...DC-9 SERIES 30 PART NO. 3920626 BOLT, SHOULDER-DRAG BRACE . . . 53 31 DC-9 SERIES 50 PART NO. 3920626 BOLT, SHOULDER-DRAG BRACE . . . 54 32 HOUSING ...55 33 DC-9 SERIES 10 PART NO. 5927071 AND PART NO. 5928678, HOUSING . . 57 33 DC-9 SERIES 30 PART NO. 5927079

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Aptamer-miRNA-212 Conjugate Sensitizes NSCLC Cells to TRAIL

    PubMed Central

    Iaboni, Margherita; Russo, Valentina; Fontanella, Raffaela; Roscigno, Giuseppina; Fiore, Danilo; Donnarumma, Elvira; Esposito, Carla Lucia; Quintavalle, Cristina; Giangrande, Paloma H; de Franciscis, Vittorio; Condorelli, Gerolama

    2016-01-01

    TNF-related apoptosis-inducing ligand (TRAIL) is a promising antitumor agent for its remarkable ability to selectively induce apoptosis in cancer cells, without affecting the viability of healthy bystander cells. The TRAIL tumor suppressor pathway is deregulated in many human malignancies including lung cancer. In human non-small cell lung cancer (NSCLC) cells, sensitization to TRAIL therapy can be restored by increasing the expression levels of the tumor suppressor microRNA-212 (miR-212) leading to inhibition of the anti-apoptotic protein PED/PEA-15 implicated in treatment resistance. In this study, we exploited a previously described RNA aptamer inhibitor of the tyrosine kinase receptor Axl (GL21.T) expressed on lung cancer cells, as a means to deliver miR-212 into human NSCLC cells expressing Axl. We demonstrate efficient delivery of miR-212 following conjugation of the miR to GL21.T (GL21.T-miR212 chimera). We show that the chimera downregulates PED and restores TRAIL-mediate cytotoxicity in cancer cells. Importantly, treatment of Axl+ lung cancer cells with the chimera resulted in (i) an increase in caspase activation and (ii) a reduction of cell viability in combination with TRAIL therapy. In conclusion, we demonstrate that the GL21.T-miR212 chimera can be employed as an adjuvant to TRAIL therapy for the treatment of lung cancer. PMID:27111415

  5. 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.

  6. Moment generation in wheelchair propulsion.

    PubMed

    Guo, Lan-Yuen; Zhao, K D; Su, Fong-Chin; An, Kai-Nan

    2003-01-01

    Wheelchair propulsion is a man machine interaction in which chair design and fit affect the relative positions and orientations of the upper extremity relative to the handrim and wheel axle. To understand these relationships better, experimental data were collected in five hand positions from five subjects exerting maximal effort to propel an instrumented wheelchair with its wheel in a locked position. The results of experiments revealed that the progression moment was greater at both initial and terminal propulsion positions and smaller in the mid-propulsion position. The vertical and horizontal force components were directed radially away from the wheel axle posterior to the dead centre position and radially towards the wheel axle anterior to top dead centre. Subsequently, a subject-specific quasi-static model of the upper extremity which maximized wheel progression moment was developed to augment our understanding of experimental measures. Model-predicted trends in progression moments and hand force direction were similar to experiment. Model predictions revealed that the optimal progression moment generation could potentially be affected by an individual's anthropometric parameters, joint strengths and also the direction of force applied by the hand on the handrim. Through wheelchair fitting and training of wheelchair users, it may be possible to improve propulsion technique.

  7. 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

  8. The Mechanism of Interferon Refractoriness During Hepatitis C Virus Infection and Its Reversal with a Peroxisome Proliferator-Activated Receptor α Agonist.

    PubMed

    Read, Scott A; Tay, Enoch S; Shahidi, Mahsa; McLauchlan, John; George, Jacob; Douglas, Mark W

    2015-06-01

    Patients who respond poorly to therapies for hepatitis C virus (HCV) infection display a characteristic phenotype with high basal hepatic interferon-stimulated gene (ISG) expression, but limited induction following interferon (IFN) treatment. The molecular pathways that mediate this refractory state are not known. We examined whether the AMPK activator metformin, the PPARγ agonist pioglitazone, or the PPARα agonist WY-14643 could potentiate IFN responses, reverse IFN refractoriness, and enhance viral eradication in hepatocytes. WY-14643 demonstrated the strongest antiviral synergy with IFN-α and so was tested in the context of chronic IFN activation. Cells rendered refractory to IFN by IFN-α pretreatment were resensitized by WY-14643, as demonstrated by improved STAT1 phosphorylation, promoter activation, and ISG expression. WY-14643 treatment reduced the expression of key negative regulators of IFN signaling: the AXL receptor tyrosine kinase, suppressor of cytokine signaling (SOCS) 1 and 3, which are upregulated in the IFN-refractory state. AXL is a novel regulator of IFN-α signaling that is induced by HCV infection in vitro and which may drive SOCS3 expression. Our data suggests that PPARα agonists could be a useful adjunct treatment for chronic HCV infection by reducing the expression of AXL/SOCS and increasing the sensitivity to IFN.

  9. The c-MET Network as Novel Prognostic Marker for Predicting Bladder Cancer Patients with an Increased Risk of Developing Aggressive Disease

    PubMed Central

    Jeong, Phildu; Kim, Seon-Kyu; Kim, Seon-Young; Yan, Chunri; Seo, Sung Phil; Lee, Sang Keun; Kim, Jayoung; Kim, Wun-Jae

    2015-01-01

    Previous studies have shown that c-MET is overexpressed in cases of aggressive bladder cancer (BCa). Identification of crosstalk between c-MET and other RTKs such as AXL and PDGFR suggest that c-MET network genes (c-MET-AXL-PDGFR) may be clinically relevant to BCa. Here, we examine whether expression of c-MET network genes can be used to identify BCa patients at increased risk of developing aggressive disease. In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis. In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients. These results suggest that c-MET network gene expression is a novel prognostic marker for predicting which BCa patients have an increased risk of developing aggressive disease. These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients. PMID:26225770

  10. TAM receptors regulate multiple features of microglial physiology

    PubMed Central

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

    2016-01-01

    Microglia are damage sensors for the central nervous system (CNS), and the phagocytes responsible for the routine non-inflammatory clearance of dead brain cells1. Here we show that the TAM receptor tyrosine kinases Mer and Axl2 regulate these microglial functions. We find that mice deficient in microglial Mer and Axl exhibit a marked accumulation of apoptotic cells (ACs) specifically in neurogenic regions of the adult CNS, and that microglial phagocytosis of the ACs generated during adult neurogenesis3,4 is normally driven by both TAM receptor ligands – Gas6 and Protein S5. Live two-photon imaging demonstrates 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 up-regulated in the inflammatory environment that develops in a mouse model of Parkinson’s disease6. Together, these results establish TAM receptors as both controllers of microglial physiology and potential targets for therapeutic intervention in CNS disease. PMID:27049947

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

    PubMed

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

    2015-06-01

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

  12. Cabozantinib in the treatment of advanced renal cell carcinoma: clinical trial evidence and experience

    PubMed Central

    Ruiz-Morales, Jose Manuel; Heng, Daniel Y.C.

    2016-01-01

    The treatment of metastatic renal cell carcinoma (mRCC) is rapidly changing. During first-line treatment with targeted therapy, patients ultimately develop resistance to therapy and the disease progresses. Recently, cabozantinib has demonstrated a better response rate, progression-free survival and overall survival compared with everolimus after failure of prior targeted therapy in patients with advanced or metastatic renal cell carcinoma (RCC). Cabozantinib is a small-molecule tyrosine kinase inhibitor (TKI). It exerts inhibition of MET, vascular endothelial growth factor receptor type 2, AXL, and many other receptor tyrosine kinases that are also implicated in tumor pathobiology, including RET, KIT, and FLT3. MET drives tumor survival, invasion, angiogenesis, and metastasis through several downstream signaling pathways. AXL has recently been described as an essential mediator of cancer metastasis that mediates crosstalk and resistance to TKIs. MET and AXL are thought to be anti-vascular endothelial growth factor receptor (VEGF) resistance pathways and thus cabozantinib represents a logical choice after progression on initial VEGF therapy. Subgroup analyses examining those with good performance status or visceral and bone metastases indicate that the hazard ratios may be better when using cabozantinib versus everolimus. However, there were no clear statistically significant differences between any subgroups. PMID:27904650

  13. Theoretical development of a simplified wheelset model to evaluate collision-induced derailments of rolling stock

    NASA Astrophysics Data System (ADS)

    Koo, Jeong Seo; Choi, Se Young

    2012-06-01

    A theoretical method is proposed to predict and evaluate collision-induced derailments of rolling stock by using a simplified wheelset model and is verified with dynamic simulations. Because the impact forces occurring during collision are transmitted from the car body to the bogies and axles through suspensions, rolling stock leads to derailment as a result of the combination of horizontal and vertical impact forces applied to the axle and a simplified wheelset model enforced at the axle can be used to theoretically formulate derailment behaviors. The derailment type depends on the combination of the horizontal and vertical forces, the flange angle and the friction coefficient. According to collision conditions, wheel-climb, wheel-lift or roll-over derailment can occur between the wheel and the rail. In this theoretical derailment model of a simplified wheelset, the derailment types are classified as Slip-up, Slip/roll-over, Climb-up, Climb/roll-over and pure Roll-over according to the derailment mechanisms between the wheel and the rail and the theoretical conditions needed to generate each derailment mechanism are proposed. The theoretical wheelset model is verified by dynamic simulation and its applicability is demonstrated by comparing the simulation results of the theoretical wheelset model with those of an actual wheelset model. The theoretical derailment wheelset model is in good agreement with the virtual testing model simulation for a collision-induced derailment of rolling stock.

  14. Monitoring self-sorting by electrospray ionization mass spectrometry: formation intermediates and error-correction during the self-assembly of multiply threaded pseudorotaxanes.

    PubMed

    Jiang, Wei; Schäfer, Andreas; Mohr, Parveen Choudhary; Schalley, Christoph A

    2010-02-24

    Three binary pseudorotaxanes, which are based on two different secondary ammonium/crown ether binding motifs, have been studied by (1)H NMR and (1)H,(1)H EXSY NMR experiments with respect to their thermodynamic stabilities and their axle exchange kinetics. The stability ranking does not follow the order of axle exchange rates, and the thermodynamically most stable axle-wheel combinations assemble only slowly. On the basis of these binding motifs, a series of self-sorting systems have been studied ranging from simple four-component mixtures through sequence-specific pseudorotaxanes to multiply threaded complexes. Because of the mismatch of kinetic and thermodynamic order, wrongly assembled structures are unavoidable, which require error-correction steps to yield the final thermodynamically controlled self-sorted products. These error-correction steps can easily be monitored by electrospray mass spectrometry, when a mixed-flow microreactor is coupled to the ion source to cover second time scales. Self-assembly intermediates, wrongly assembled structures, and the final thermodynamic products can be simultaneously identified. The determination of preferred assembly pathways as well as the formation of dead-end structures provides a clear picture of a rich kinetic behavior of the self-sorting systems under study.

  15. The c-MET Network as Novel Prognostic Marker for Predicting Bladder Cancer Patients with an Increased Risk of Developing Aggressive Disease.

    PubMed

    Kim, Young-Won; Yun, Seok Joong; Jeong, Phildu; Kim, Seon-Kyu; Kim, Seon-Young; Yan, Chunri; Seo, Sung Phil; Lee, Sang Keun; Kim, Jayoung; Kim, Wun-Jae

    2015-01-01

    Previous studies have shown that c-MET is overexpressed in cases of aggressive bladder cancer (BCa). Identification of crosstalk between c-MET and other RTKs such as AXL and PDGFR suggest that c-MET network genes (c-MET-AXL-PDGFR) may be clinically relevant to BCa. Here, we examine whether expression of c-MET network genes can be used to identify BCa patients at increased risk of developing aggressive disease. In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis. In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients. These results suggest that c-MET network gene expression is a novel prognostic marker for predicting which BCa patients have an increased risk of developing aggressive disease. These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients.

  16. 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.

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

    PubMed

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

    2013-01-01

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

  18. Bucket chain excavator

    SciTech Connect

    Bryan, J.F. Jr.

    1993-07-20

    A machine is described for excavating, elevating and loading material comprising: a main frame having forward and rearward ends; undercarriage means having forward and rearward movement capability for supporting said main frame; a transverse axle rigidly located with respect to said main frame at the forward end thereof; rotating means mounted on said axle so as to extend cantilever wider than any other part of said machine for excavating and for discharging excavated material rearward at an elevated position; chain drive means mounted inwardly on said axle for driving said rotating means and for digging and elevating a portion of the width of a path so that said rotating means and said chain drive means together dig a path wider than any other part of said machine; conveyor means located behind said rotating means for receiving and taking away all material excavated by said chain drive means and said rotating means and conveying said material rearwardly to a material delivery position; and adjustment means for raising and lowering said rotating means relative to said undercarriage.

  19. 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

  20. 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

  1. Lubrication device in transmission unit for automotive vehicles

    SciTech Connect

    Fukuchi, H.; Inui, H.; Iwata, H.

    1986-05-06

    This patent describes a transmission unit for automotive vehicles, which consists of: a casing arranged to store an amount of lubricating oil in a bottom portion thereof and having a pair of carrier portions at the opposite sides thereof; a differential gear unit arranged within the casing and having a pair of side-journals rotatably supported by a pair of axially spaced side-bearings carried on the respective carrier portions of the casing; a ring gear integral with the differential gear unit and in mesh with an output gear on an output shaft of the transmission unit to drive the differential gear unit; a pair of wheel axles extending outwardly through the respective side-journals from the differential gear unit and surrounded by a pair of annular seal members carried on the respective carrier portions; a pair of annular shim plates interposed between each of the carrier portions and each of the side-bearings to position the respective side-journals in place; and passage means for leading lubricating oil picked up by the ring gear into a pair of annular side-spaces formed around each of the wheel axles between the respective side-bearings and the respective seal members; wherein each of the annular shim plates is formed the inner peripheral portion thereof with circumferentially spaced radial projections and recesses which are arranged in such a manner that a portion of the lubricating oil flowing along each outside peripheral portion of the annular shim plate is guided radially inwardly by the radial projections of the respective shim plates to flow onto each of the wheel axles for lubrication of the side-journals.

  2. 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.

  3. None of the rotor residues of F1-ATPase are essential for torque generation.

    PubMed

    Chiwata, Ryohei; Kohori, Ayako; Kawakami, Tomonari; Shiroguchi, Katsuyuki; Furuike, Shou; Adachi, Kengo; Sutoh, Kazuo; Yoshida, Masasuke; Kinosita, Kazuhiko

    2014-05-20

    F1-ATPase is a powerful rotary molecular motor that can rotate an object several hundred times as large as the motor itself against the viscous friction of water. Forced reverse rotation has been shown to lead to ATP synthesis, implying that the mechanical work against the motor's high torque can be converted into the chemical energy of ATP. The minimal composition of the motor protein is α3β3γ subunits, where the central rotor subunit γ turns inside a stator cylinder made of alternately arranged α3β3 subunits using the energy derived from ATP hydrolysis. The rotor consists of an axle, a coiled coil of the amino- and carboxyl-terminal α-helices of γ, which deeply penetrates the stator cylinder, and a globular protrusion that juts out from the stator. Previous work has shown that, for a thermophilic F1, significant portions of the axle can be truncated and the motor still rotates a submicron sized bead duplex, indicating generation of up to half the wild-type (WT) torque. Here, we inquire if any specific interactions between the stator and the rest of the rotor are needed for the generation of a sizable torque. We truncated the protruding portion of the rotor and replaced part of the remaining axle residues such that every residue of the rotor has been deleted or replaced in this or previous truncation mutants. This protrusionless construct showed an unloaded rotary speed about a quarter of the WT, and generated one-third to one-half of the WT torque. No residue-specific interactions are needed for this much performance. F1 is so designed that the basic rotor-stator interactions for torque generation and control of catalysis rely solely upon the shape and size of the rotor at very low resolution. Additional tailored interactions augment the torque to allow ATP synthesis under physiological conditions.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. None of the Rotor Residues of F1-ATPase Are Essential for Torque Generation

    PubMed Central

    Chiwata, Ryohei; Kohori, Ayako; Kawakami, Tomonari; Shiroguchi, Katsuyuki; Furuike, Shou; Adachi, Kengo; Sutoh, Kazuo; Yoshida, Masasuke; Kinosita, Kazuhiko

    2014-01-01

    F1-ATPase is a powerful rotary molecular motor that can rotate an object several hundred times as large as the motor itself against the viscous friction of water. Forced reverse rotation has been shown to lead to ATP synthesis, implying that the mechanical work against the motor’s high torque can be converted into the chemical energy of ATP. The minimal composition of the motor protein is α3β3γ subunits, where the central rotor subunit γ turns inside a stator cylinder made of alternately arranged α3β3 subunits using the energy derived from ATP hydrolysis. The rotor consists of an axle, a coiled coil of the amino- and carboxyl-terminal α-helices of γ, which deeply penetrates the stator cylinder, and a globular protrusion that juts out from the stator. Previous work has shown that, for a thermophilic F1, significant portions of the axle can be truncated and the motor still rotates a submicron sized bead duplex, indicating generation of up to half the wild-type (WT) torque. Here, we inquire if any specific interactions between the stator and the rest of the rotor are needed for the generation of a sizable torque. We truncated the protruding portion of the rotor and replaced part of the remaining axle residues such that every residue of the rotor has been deleted or replaced in this or previous truncation mutants. This protrusionless construct showed an unloaded rotary speed about a quarter of the WT, and generated one-third to one-half of the WT torque. No residue-specific interactions are needed for this much performance. F1 is so designed that the basic rotor-stator interactions for torque generation and control of catalysis rely solely upon the shape and size of the rotor at very low resolution. Additional tailored interactions augment the torque to allow ATP synthesis under physiological conditions. PMID:24853745

  9. 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.

  10. 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

  11. On-Line Condition Monitoring of a Power Transmission Unit of a Rail Vehicle

    NASA Astrophysics Data System (ADS)

    Deuszkiewicz, P.; Radkowski, S.

    2003-11-01

    The paper addresses the issue of selection of diagnostic parameters and methods of an object's condition classification. The research was conducted for a power transmission unit of a commuter train. We analysed the vibration of the axle box as measured on the track for systems before and after an overhaul. In the final part of the paper, we proposed an algorithm that can be used to identify the technical condition of a machine while using neural networks and we also described the operation of an on-line diagnostic system.

  12. Chinese-English Rocketry Dictionary. Volume 2

    DTIC Science & Technology

    1978-02-01

    jignd tagnatiton 16 jingzuhiou~%q ~static tytrcs17 Jinzbeg ~dead weighit 18 NOngfhA dead axle 19 jingzhuiqtv Op f)one or silence; CanIe Of’ 210 nulls...shiliang LI f3] Ph Poynting vector 03 Po polonium 04 PoC promethlum 05 pojiang •f forced landing 06 Poertie xiaoying Il • f3 Peltier effect 07...4 1 N1het-inisulation mate-rial ol. ! ao of saibestos fiber, h-ininn yo’lfqi 41 gi -di arbetos paint ilijjiiiazibori ¾ asbestos plat :ansbestos board

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Ras-Directed N-Glycoproteins are Novel Early Biomarkers for Tumorigenesis and Malignant Transformation, and Therapeutic Targets of Neurofibromatosis Type I

    DTIC Science & Technology

    2012-09-01

    phosphorylation of AXL, EGFR, and c-MET and impaired receptor-mediated MEK- ERK1/2 and PI3K-AKT signaling in a dose -dependent manner, and inhibited the...glycosylation of cell surface proteins, known as the ‘Warren phenomenon’[21]. The appropriate and accurate modification of sugar or glycan to proteins...Fig 2A MPNST cells were treated with Tunicamycin or 2-DG at various dose . Cell viability (%) was determined by MTS assay, data represent 72 hours

  18. 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.

  19. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

    Biomolecular motors convert energy into directed motion and operate away from thermal equilibrium. The development of dynamic chemical systems that exploit dissipative (non-equilibrium) processes is a challenge in supramolecular chemistry and a premise for the realization of artificial nanoscale motors. Here, we report the relative unidirectional transit of a non-symmetric molecular axle through a macrocycle powered solely by light. The molecular machine rectifies Brownian fluctuations by energy and information ratchet mechanisms and can repeat its working cycle under photostationary conditions. The system epitomizes the conceptual and practical elements forming the basis of autonomous light-powered directed motion with a minimalist molecular design.

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

    PubMed

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

    2017-02-01

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

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

    PubMed Central

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

    2017-01-01

    Abstract Detailed characterizations of ocular biometrics and parameters of aqueous humor dynamics are lacking in primary angle closure suspect (PACS) patients. This study aims to characterize these parameters and compare them with age-matched healthy volunteers. Elderly healthy volunteers (60.6 ± 7.2 years of age, mean ± SD, n = 28) and PACS patients (64.1 ± 11.6 years, n = 30) completed the study. Parameters investigated were axial length (AXL), anterior chamber depth (ACD), anterior chamber volume (ACV), central cornea thickness (CCT), intraocular pressure (IOP), aqueous flow (Fa), outflow facility (C), episcleral venous pressure (EVP), and uveoscleral outflow (Fu). Comparisons and correlations were made between and within groups. In healthy volunteers, ocular biometric parameters, IOP, and EVP correlated very well between the 2 eyes of each individual, but Fa, C, and Fu were not significantly correlated. Biometric parameters of the PACS group significantly (P < 0.001) differed from those of the healthy controls: AXL (23.31 ± 1.03 mm [PACS] vs 22.39 ± 1.04 mm [Control]; mean ± SD), ACD (2.44 ± 0.33 mm [PACS] vs 1.86 ± 0.25 mm [Control]), ACV (136.0 ± 36.1 μL [PACS] vs 81.4 ± 21.8 μL [Control]), CCT (526.9 ± 37.0 μm [PACS] vs 556.1 ± 28.4 μm [Control]). There was no significant change in IOP, Fa, C, EVP, or Fu between Control and PACS. Furthermore, IOP showed no significant correlations with AXL, ACD, ACV, CCT, or C in both groups. The PACS eyes had a shorter AXL, a shallower ACD, and a smaller ACV, but a thicker CCT. Despite these morphological changes, the PACS eyes did not have any significant changes in IOP, and aqueous humor dynamics parameters. This is consistent with the findings that IOP did not show significant correlations with biometrics, or C. PMID:28207520

  3. 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.

  4. 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

  5. Development of IR Transmitting Chalcogenide Windows

    DTIC Science & Technology

    1975-02-01

    obtained from the transmission T, the sample thirknessx, and the reflectivity R by the equation r-O-.R)2exp (-a*)/(1 -/?2exp(-2ax)l. (1) which is valid...for normal incidence of the light beam on the sample surface in reg- ions in which aX * 1, where X is wavelength. The reflectivity R used in eq. (1...cm-1 and 785 cm-1 whose relative u’rensities varied with the glass preparation was first noted by Vasko et al. (11 ]. On the basis of the spectr ? of

  6. [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.

  7. Neutral redox-active hydrogen- and halogen-bonding [2]rotaxanes for the electrochemical sensing of chloride.

    PubMed

    Lim, Jason Y C; Cunningham, Matthew J; Davis, Jason J; Beer, Paul D

    2014-12-14

    The first examples of redox-active ferrocene-functionalised neutral [2]rotaxanes have been synthesised via chloride anion templation. (1)H NMR spectroscopic titrations reveal that these [2]rotaxane host systems recognize chloride selectively over other halides and oxoanions in highly-competitive aqueous media. By replacing the hydrogen bonding prototriazole units of the rotaxane axle component with iodotriazole halogen bond-donor groups, the degree of chloride selectivity of the [2]rotaxanes is modulated. Electrochemical voltammetric experiments demonstrate that the rotaxanes can sense chloride via cathodic perturbations of the respective rotaxanes' ferrocene-ferrocenium redox-couple upon anion addition.

  8. [The Black Forest arched clock in the x-ray picture].

    PubMed

    Beck, A

    1988-05-01

    The typical painted wooden Black Forest clock of the late eighteenth and early nineteenth century was the original famous Black Forest clock. The clocks changed from a useful article to an object in great demand by collectors; however, among them there are many fakes. Because of the use of colors containing lead and zinc at that time, the paint on these clocks can be evaluated radiologically and restaurations made later or even fakes can be detected easily. Important information can even be obtained about the wood used: its condition, the wooden axles, and abrasion of the gears.

  9. Photovoltaic panel clamp

    SciTech Connect

    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.

  10. Photovoltaic panel clamp

    SciTech Connect

    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.

  11. Design of a Prototype Autonomous Amphibious WHEGS(Trademark) Robot for Surf-Zone Operations

    DTIC Science & Technology

    2005-06-01

    slip differential . Figure 4 shows how a single axle responds to an obstacle. Figure 4. Compliance in WhegsTM design [From Ref. [3] During normal... equator ) is equal to 2000 yards, we can arrive at a more specific formula for range: 2000*cos( )long cR lat= (2) 8 2 2( ) (2000...d c long d cRange yds lat lat R long long= − + − (3) In the above equations , Rlong is the range in yards per minute of longitude, latc

  12. Photoresponsive Supramolecular Complexes as Efficient DNA Regulator

    PubMed Central

    Cheng, Hong-Bo; Zhang, Ying-Ming; Xu, Chao; Liu, Yu

    2014-01-01

    Two supramolecular complexes of trans-1⊂CB[8] and trans-2⊂CB[8] were successfully achieved by the controlled selective complexation process of cucurbit[8]uril (CB[8]) with hetero-guest pair containing azobenzene and bispyridinium moieties in aqueous solution, exhibiting the reversibly light-driven movements of CB[8] upon the photocontrollable isomerization of azophenyl axle components. Significantly, the obtained bistable supramolecular complexes and their corresponding [2]pseudorotaxanes could act as a promising concentrator and cleavage agent to regulate the binding behaviors with DNA molecules. PMID:24572680

  13. 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.

  14. 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.

  15. Employment of the 307th Medical Battalion (Airborne) in Operations Desert Shield and Desert Storm: A Personal Experience Monograph

    DTIC Science & Technology

    1992-05-08

    limited in duration and scope, we didn’t deploy our heavier equipment; X-Ray, Dental , canvas tentage, cots, autoclaves, and miscellaneous support...Oxygen/Fluids Requirements MAJ Clark 16. Medical Supply Stockage 1LT Branch 17. Dental Configuration MAJ Madison 18. Personnel Decontamination SSG...APPARATUS GAS W/ 02 1 0 A6Z252 ANESTESIA SET FIELD: IN CHEST. .. A72260 ANTENNA RC-29- A0712b AXLE CABLE REEL: RL-27 1 0 A79381 ANTENNA GROUP, OE-254 2 1

  16. Effect of thermal noise on noncontact rack and pinion device.

    PubMed

    Nasiri, Mojtaba; Miri, MirFaez

    2012-04-01

    We study a nanoscale system composed of one corrugated plate (rack) and one corrugated cylinder (pinion) coupled via the lateral Casimir force. We assume that the rack moves uniformly. The axle of the pinion experiences frictional torque and random torque due to a surrounding fluid. We show that even in the presence of thermal noise, the device can work against external loads: The pinion rotates with a nonzero average velocity. The device operation becomes less influenced by the noise as the gap between rack and pinion decreases.

  17. Fractography of induction-hardened steel fractured in fatigue and overload

    SciTech Connect

    Santos, C.G.; Laird, C.

    1997-07-01

    The fracture surfaces of induction-hardened steel specimens obtained from an auto axle were characterized, macroscopically and microscopically, after being fractured in fatigue and monotonic overload. Specimens were tested in cyclic three-point bending under load control, and the S-N curve was established for specimens that had been notched by spark machining to facilitate fractography. Scanning electron microscopy of the fractured surfaces obtained for lives spanning the range 17,000 to 418,000 cycles revealed diverse fracture morphologies, including intergranular fracture and transgranular fatigue fracture. The results are being offered to assist in the analysis of complex field failures in strongly hardened steel.

  18. 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.

  19. ASASSN-17cq and ASASSN-17cs: Discovery of Two Probable Supernovae

    NASA Astrophysics Data System (ADS)

    Brimacombe, J.; Cacella, P.; Kiyota, S.; Brown, J. S.; Stanek, K. Z.; Holoien, T. W.-S.; Kochanek, C. S.; Shields, J.; Thompson, T. A.; Shappee, B. J.; Prieto, J. L.; Bersier, D.; Dong, Subo; Bose, S.; Chen, Ping; Fernandez, J. M.; Post, R. S.

    2017-02-01

    During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN, Shappee et al. 2014), using data from the quadruple 14-cm "Cassius" telescope in Cerro Tololo, Chile, we discovered two new transient sources, most likely supernovae, in an uncatalogued galaxy and ESO 015-G 010. ASASSN-17cq (AT 2017axl) was discovered in images obtained on UT 2017-02-18.22 at V 16.9 mag. We do not detect (V > 17.4) the object in images taken on UT 2017-02-17.22 and before.

  20. Nondestructive Vibratory Testing and Evaluation Procedure for Military Roads and Streets.

    DTIC Science & Technology

    1984-07-01

    number ( CDTN ), the pavement is structurally adequate. The CDTN is determined from traffic data as described in paragraphs 51 and 52 and is the...equivalent number of 18,000-lb single-axle load passes using a pavement each day. If the ADTN is less than the CDTN the section is structurally inadequate and...with the Current Daily Traffic Number ( CDTN ). The NODET load-deflection data obtained at 20-Hz frequency and the 5,000- and 7,000-lb force levels pro

  1. Conformational isomers of linear rotaxanes

    NASA Astrophysics Data System (ADS)

    Sevick, Edith M.; Williams, David R. M.

    2014-09-01

    We examine a simple model of rotaxane structure, with 3 asymmetric rings interacting via repulsive power-law forces. This interlocked molecule exhibits conformational isomerisation which is different from that of molecules whose connectedness is through covalent bonds. The rings are free to translate along and rotate around the axle, and hence weak interaction forces between the rings can lead to distinct rotamer states. We use energy minimisation to determine these states exactly, and show that there can be transitions from asymmetric to symmetric states by varying the bond lengths. We also use classical statistical mechanics to show the effect of thermal noise.

  2. A Microcomputer Based Aircraft Flight Control System.

    DTIC Science & Technology

    1980-04-01

    GRANT NUMSEiI(se) AFOSR-78-3633 VIKRAM RAJ SAKSENA N00014-79-C-0424 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGAM ELEMENT PROJECT. TASK AREA...being highly nonlinear , rthe direct application of these techniques is computationally involved. No closed form solution is available for such problems...2.7) yields the fifth-order nonlinear system below l -4 11- [7 PX2S(Co +C axl +C fu2)-Wcos (x3-x1)] M 1 2 2 CdfU1) 2 M[-W sin (x3 x Px2S(Cdo+Cdc (Co

  3. 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

  4. 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.

  5. Power transfer device for four-wheel drive

    SciTech Connect

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

    1989-02-07

    A power transfer device is described for four-wheel drive in combination with a power transmission, comprising: a first differential of the bevel gear type arranged to split the two driving torque from the power transmission into two torque delivery paths respectively for front-wheel drive and rear-wheel drive; a second differential of the bevel gear type arranged coaxially with the first differential at one side thereof to transfer the split driving torque from a first side gear of the first differential to one of front and rear-wheel axles; an output gear arranged coaxially with the first differential at the other side thereof to transfer the split driving torque from a second side gear of the first differential to the other of the rear and front-wheel axles; and a limited-slip differential assembled within a mounting case for the output gear to effect limited slip torque proportional to the difference in rotational speed between the side gears.

  6. The dynamic study of locomotives under saturated adhesion

    NASA Astrophysics Data System (ADS)

    Yuan, Yao; Hong-jun, Zhang; Ye-ming, Li; Shi-hui, Luo

    2011-08-01

    In order to study the dynamic behaviours of locomotives under saturated adhesion, the stability and characteristics of stick-slip vibration are analysed using the concepts of mean and dynamic slip rates. The longitudinal vibration phenomenon of the wheelset when stick-slip occurs is put forward and its formation mechanism is made clear innovatively. The stick-slip vibration is a dynamic process between the stick and the slip states. The decreasing of mean and dynamic slip rates is conducive to its stability, which depends on the W/R adhesion damping. The torsion vibration of the driving system and the longitudinal vibration of the wheelset are coupled through the longitudinal tangential force when the wheelset alternates between the stick and the slip states. The longitudinal oscillation frequencies of the wheelset are integral multiples of the natural frequency of torsion vibration of the driving system. A train dynamic model integrated with an electromechanical and a control system is established to simulate the stick-slip vibration phenomenon under saturated adhesion to verify the theoretical analysis. The results show that increases of the longitudinal axle guidance stiffness and the motor suspension stiffness are beneficial to the stick-slip vibration stability and the locomotive's traction ability. The optimised matching of the longitudinal axle guidance stiffness and the motor suspension stiffness are helpful to avoid longitudinal resonance when the stick-slip vibration occurs.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Versatile synthesis of end-reactive polyrotaxanes applicable to fabrication of supramolecular biomaterials.

    PubMed

    Tamura, Atsushi; Tonegawa, Asato; Arisaka, Yoshinori; Yui, Nobuhiko

    2016-01-01

    Cyclodextrin (CD)-threaded polyrotaxanes (PRXs) with reactive functional groups at the terminals of the axle polymers are attractive candidates for the design of supramolecular materials. Herein, we describe a novel and simple synthetic method for end-reactive PRXs using bis(2-amino-3-phenylpropyl) poly(ethylene glycol) (PEG-Ph-NH2) as an axle polymer and commercially available 4-substituted benzoic acids as capping reagents. The terminal 2-amino-3-phenylpropyl groups of PEG-Ph-NH2 block the dethreading of the α-CDs after capping with 4-substituted benzoic acids. By this method, two series of azide group-terminated polyrotaxanes (benzylazide: PRX-Bn-N3, phenylazide: PRX-Ph-N3,) were synthesized for functionalization via click reactions. The PRX-Bn-N3 and PRX-Ph-N3 reacted quickly and efficiently with p-(tert-butyl)phenylacetylene via copper-catalyzed click reactions. Additionally, the terminal azide groups of the PRX-Bn-N3 could be modified with dibenzylcyclooctyne (DBCO)-conjugated fluorescent molecules via a copper-free click reaction; this fluorescently labeled PRX was utilized for intracellular fluorescence imaging. The method of synthesizing end-reactive PRXs described herein is simple and versatile for the design of diverse functional PRXs and can be applied to the fabrication of PRX-based supramolecular biomaterials.

  13. Expression of growth arrest-specific gene 6 and its receptors in dysfunctional human renal allografts.

    PubMed

    Yin, Jian L; Hambly, Brett D; Bao, Shi S; Painter, Dorothy; Bishop, G Alex; Eris, Josette M

    2003-09-01

    Growth arrest-specific gene 6 (Gas6) and its receptors Rse, Axl and Mer have recently been found to be involved in a rat model of chronic allograft nephropathy (CAN). Thus, in this study we investigated the function of Gas6 and its receptors in human renal allograft dysfunction. Expression of Gas6 and its receptors was detected by immunohistochemical staining. Gas6 and its receptors were widely expressed in glomeruli, tubules and vessels of renal allografts. Gas6 expression was detected in normal-functioning allografts and was increased in acute rejection ( P<0.05), acute tubular necrosis ( P<0.05) and CAN ( P<0.01). Gas6 receptors were not upregulated in any of the allograft groups, except for the Axl receptor, which increased only in acute tubular necrosis ( P<0.01). Gas6 expression was also found to correspond with the expression of alpha-smooth muscle actin, a general marker of CAN ( r(2)=0.21, P<0.01). These findings suggest that Gas6, acting as a growth factor, is increased in the process of kidney allograft dysfunction and in CAN.

  14. Laboratory experiment for the study of friction forces using rotating apparatus

    NASA Astrophysics Data System (ADS)

    Kladivová, Mária; Kovaľaková, Mária; Gibová, Zuzana; Fričová, Oľga; Hutníková, Mária; Kecer, Ján

    2016-11-01

    The standard experimental set-up enabling observation of rotational motion of a bar around its centre of mass, which is set into motion due to the external torque generated by the small weight, was extended with an optical gate and position sensor and connected to a computer with software, which made it possible to display measured values of bar half-rotations during accelerated and decelerated motion as well as to process the data immediately. The detailed analysis of experimental data obtained for decelerated rotational motion due to frictional torque only (without small weight) showed that, besides the constant term due to dry friction at an axle, the expression for friction forces in the system has to include terms depending on the first and/or second power of angular speed, which is evidence that viscous forces influence the motion of a bar. The frictional torque due to viscous forces can be evaluated as the difference between the effective frictional torque acting on the system and the frictional torque due to dry friction at an axle. The data obtained in the experiment in which the bar performed damped oscillatory motion provided the values of effective frictional torque and the moment of inertia of rotating bodies. The frictional torque due to dry friction can be obtained as a minimum torque (calculated using minimum mass of weight) needed to start rotational motion. The last two proposed experiments can be included in undergraduate laboratory practicals.

  15. Fisetin, a dietary phytochemical, overcomes Erlotinib-resistance of lung adenocarcinoma cells through inhibition of MAPK and AKT pathways.

    PubMed

    Zhang, Liang; Huang, Yi; Zhuo, Wenlei; Zhu, Yi; Zhu, Bo; Chen, Zhengtang

    2016-01-01

    Erlotinib (Tarceva) is a selective epidermal growth factor receptor tyrosine kinase inhibitor for treatment of non-small cell lung cancer (NSCLC). However, its efficacy is usually reduced by the occurrence of drug resistance. Our recent study showed that a flavonoid found in many plants, Fisetin, might have a potential to reverse the acquired Cisplatin-resistance of lung adenocarcinoma. In the present study, we aimed to test whether Fisetin could have the ability to reverse Erlotinib-resistance of lung cancer cells. Erlotinib-resistant lung adenocarcinoma cells, HCC827-ER, were cultured from the cell line HCC827, and the effects of Fisetin and Erlotinib on the cell viability and apoptosis were evaluated. The possible signaling pathways in this process were also detected. As expected, the results showed that Fisetin effectively increased sensitivity of Erlotinib-resistant lung cancer cells to Erlotinib, possibly by inhibiting aberrant activation of MAPK and AKT signaling pathways resulted from AXL suppression. In conclusion, Fisetin was a potential agent for reversing acquired Erlotinib-resistance of lung adenocarcinoma. Inactivation of AXL, MAPK and AKT pathways might play a partial role in this process.

  16. 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.

  17. Switching Torque Converter: Concept and Preliminary Implementation

    NASA Astrophysics Data System (ADS)

    Hirota, Koichi; Ikei, Yasushi

    It is preferable to refrain from switching the torque in mechanical systems because the abrupt change tends to cause vibration and noise. However, such vibration can be beneficial if it is used to store mechanical energy. Moreover, torque switching operations at higher frequencies are becoming possible because of the recent advances in clutch devices. This paper describes a novel torque conversion mechanism based on torque switching operations. The fundamental principle of the mechanism is the reciprocal translation between the work to and from axles and the rotational energy of a flywheel. Clutches are used to intermittently connect or disconnect the axles with the flywheel; the output torque is controlled by changing the time ratio of the connection. By performing switching operations at a higher frequency, almost continuous torque conversion can be realized. A prototype was created using electrorheological fluid clutches, and it showed the potential for torque conversion. The performance of the prototype was also analyzed by numerical simulation; this showed that the prototype worked in accordance with the principle. Moreover, the potential capability of the principle was investigated using a numerical model and the results suggest that by improving the mechanical design, a considerable improvement in performance is possible.

  18. 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

    2015-08-05

    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.

  19. The experimental validation of a numerical model for the prediction of the vibrations in the free field produced by road traffic

    NASA Astrophysics Data System (ADS)

    Lombaert, G.; Degrande, G.

    2003-04-01

    The objective of the present paper is the experimental validation of a numerical model for the prediction of traffic-induced vibrations. The vibrations in the free field, generated by the passage of a vehicle on an uneven road, are predicted in two stages. First, the equations of motion of the vehicle are solved to determine the dynamic axle loads. Next, these axle loads are applied to the road and the free field vibrations are computed. An elaborate measurement campaign has been set up to validate this model. The response of a Volvo FL6 truck and the response in the free field have been measured simultaneously during the passage of the truck over an artificial road unevenness. The parameters related to the vehicle, the road and the soil have been determined experimentally. A comparison of the predicted and the measured response demonstrates the predictive qualities of the numerical model. Furthermore, the results provide a clear insight in the influence of the vehicle speed on the vehicle's and the free field response.

  20. 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

  1. 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

  2. TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation.

    PubMed

    Ji, Rui; Tian, Shifu; Lu, Helen J; Lu, Qingjun; Zheng, Yan; Wang, Xiaomin; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

    2013-12-15

    TAM tyrosine kinases play multiple functional roles, including regulation of the target genes important in homeostatic regulation of cytokine receptors or TLR-mediated signal transduction pathways. In this study, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impairs hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAPK and NF-κB activation and elevated production of proinflammatory cytokines that are detrimental to neuron stem cell proliferation and neuronal differentiation. Injection of LPS causes even more severe inhibition of BrdU incorporation in the Tyro3(-/-)Axl(-/-)Mertk(-/-) triple-knockout (TKO) brains, consistent with the LPS-elicited enhanced expression of proinflammatory mediators, for example, IL-1β, IL-6, TNF-α, and inducible NO synthase, and this effect is antagonized by coinjection of the anti-inflammatory drug indomethacin in wild-type but not TKO brains. Conditioned medium from TKO microglia cultures inhibits neuron stem cell proliferation and neuronal differentiation. IL-6 knockout in Axl(-/-)Mertk(-/-) double-knockout mice overcomes the inflammatory inhibition of neurogenesis, suggesting that IL-6 is a major downstream neurotoxic mediator under homeostatic regulation by TAM receptors in microglia. Additionally, autonomous trophic function of the TAM receptors on the proliferating neuronal progenitors may also promote progenitor differentiation into immature neurons.

  3. 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.

  4. Patterning of Fibroblast and Matrix Anisotropy within 3D Confinement is Driven by the Cytoskeleton.

    PubMed

    Serbo, Janna V; Kuo, Scot; Lewis, Shawna; Lehmann, Matthew; Li, Jiuru; Gracias, David H; Romer, Lewis H

    2016-01-07

    Effects of 3D confinement on cellular growth and matrix assembly are important in tissue engineering, developmental biology, and regenerative medicine. Polydimethylsiloxane wells with varying anisotropy are microfabicated using soft-lithography. Microcontact printing of bovine serum albumin is used to block cell adhesion to surfaces between wells. The orientations of fibroblast stress fibers, microtubules, and fibronectin fibrils are examined 1 day after cell seeding using laser scanning confocal microscopy, and anisotropy is quantified using a custom autocorrelation analysis. Actin, microtubules, and fibronectin exhibit higher anisotropy coefficients for cells grown in rectangular wells with aspect ratios of 1:4 and 1:8, as compared to those in wells with lower aspect ratios or in square wells. The effects of disabling individual cytoskeletal components on fibroblast responses to anisotropy are then tested by applying actin or microtubule polymerization inhibitors, Rho kinase inhibitor, or by siRNA-mediated knockdown of AXL or cofilin-1. Latrunculin A decreases cytoskeletal and matrix anisotropy, nocodazole ablates both, and Y27632 mutes cellular polarity while decreasing matrix anisotropy. AXL siRNA knockdown has little effect, as does siRNA knockdown of cofilin-1. These data identify several specific cytoskeletal strategies as targets for the manipulation of anisotropy in 3D tissue constructs.

  5. Assignment of the human GAS6 gene to chromosome 13q34 by fluorescene in situ hybridization

    SciTech Connect

    Saccone, S.; Della Valle, G.; Marcandalli, P.; Gostissa, M.; Schneider, C.

    1995-11-01

    GAS6 was originally isolated as a set of growth-arrest-specific (gas) genes whose expression is increased at growth arrest and becomes negatively regulated after synchronous cell cycle induction in murine NIH3T3 cells. Sequence of the human full-length cDNA homologue revealed that the protein encoded belongs to the class of vitamin K-dependent proteins, more specifically related to protein S, a negative coregulator in the blood coagulation cascade (43% aa identity). The regions with the highest degree of similarity between Gas6 and the related protein S comprise the Gla domain ({gamma} carboxylated glutamic acid-rich region) and the four EFG-like domains. In between these two regions, protein S presents a linking segment with a thrombin-sensitive site, which has been lost by Gas6. Recently, it has been demonstrated that Gas6 is the ligand of the tyrosine kinase receptor Axl. Axl is the first described member of a receptor tyrosine kinase family comprising various members that have in common the presence of tandem repeats of immunoglobulin-like and fibronectin type III domains in the extracellular portion of the receptor. In this report we describe the chromosomal localization of GAS6 using fluorescence in situ hybridization on metaphase chromosomes. 10 refs., 1 fig.

  6. 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

  7. Genetic Analysis of Default Mating Behavior in Saccharomyces Cerevisiae

    PubMed Central

    Dorer, R.; Boone, C.; Kimbrough, T.; Kim, J.; Hartwell, L. H.

    1997-01-01

    Haploid Saccharomyces cerevisiae cells find each other during conjugation by orienting their growth toward each other along pheromone gradients (chemotropism). However, when their receptors are saturated for pheromone binding, yeast cells must select a mate by executing a default pathway in which they choose a mating partner at random. We previously demonstrated that this default pathway requires the SPA2 gene. In this report we show that the default mating pathway also requires the AXL1, FUS1, FUS2, FUS3, PEA2, RVS161, and BNI1 genes. These genes, including SPA2, are also important for efficient cell fusion during chemotropic mating. Cells containing null mutations in these genes display defects in cell fusion that subtly affect mating efficiency. In addition, we found that the defect in default mating caused by mutations in SPA2 is partially suppressed by multiple copies of two genes, FUS2 and MFA2. These findings uncover a molecular relationship between default mating and cell fusion. Moreover, because axl1 mutants secrete reduced levels of a-factor and are defective at both cell fusion and default mating, these results reveal an important role for a-factor in cell fusion and default mating. We suggest that default mating places a more stringent requirement on some aspects of cell fusion than does chemotropic mating. PMID:9135999

  8. 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.

  9. Re-evaluation of the AASHTO-flexible pavement design equation with neural network modeling.

    PubMed

    Tiğdemir, Mesut

    2014-01-01

    Here we establish that equivalent single-axle loads values can be estimated using artificial neural networks without the complex design equality of American Association of State Highway and Transportation Officials (AASHTO). More importantly, we find that the neural network model gives the coefficients to be able to obtain the actual load values using the AASHTO design values. Thus, those design traffic values that might result in deterioration can be better calculated using the neural networks model than with the AASHTO design equation. The artificial neural network method is used for this purpose. The existing AASHTO flexible pavement design equation does not currently predict the pavement performance of the strategic highway research program (Long Term Pavement Performance studies) test sections very accurately, and typically over-estimates the number of equivalent single axle loads needed to cause a measured loss of the present serviceability index. Here we aimed to demonstrate that the proposed neural network model can more accurately represent the loads values data, compared against the performance of the AASHTO formula. It is concluded that the neural network may be an appropriate tool for the development of databased-nonparametric models of pavement performance.

  10. 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.

  11. Reduced Proteolytic Shedding of Receptor Tyrosine Kinases is a Post-Translational Mechanism of Kinase Inhibitor Resistance

    PubMed Central

    Miller, Miles A.; Oudin, Madeleine J.; Sullivan, Ryan J.; Wang, Stephanie J.; Meyer, Aaron S.; Im, Hyungsoon; Frederick, Dennie T.; Tadros, Jenny; Griffith, Linda G.; Lee, Hakho; Weissleder, Ralph; Flaherty, Keith T.; Gertler, Frank B.; Lauffenburger, Douglas A.

    2016-01-01

    Kinase inhibitor resistance often involves upregulation of poorly understood “bypass” signaling pathways. Here, we show that extracellular proteomic adaptation is one path to bypass signaling and drug resistance. Proteolytic shedding of surface receptors, which can provide negative feedback on signaling activity, is blocked by kinase inhibitor treatment and enhances bypass signaling. In particular, MEK inhibition broadly decreases shedding of multiple receptor tyrosine kinases (RTKs) including HER4, MET, and most prominently AXL, an ADAM10 and ADAM17 substrate, thus increasing surface RTK levels and mitogenic signaling. Progression-free survival of melanoma patients treated with clinical BRAF/MEK inhibitors inversely correlates with RTK shedding reduction following treatment, as measured non-invasively in blood plasma. Disrupting protease inhibition by neutralizing TIMP1 improves MAPK inhibitor efficacy, and combined MAPK/AXL inhibition synergistically reduces tumor growth and metastasis in xenograft models. Altogether, extracellular proteomic rewiring through reduced RTK shedding represents a surprising mechanism for bypass signaling in cancer drug resistance. PMID:26984351

  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.

  13. 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.

  14. A single synthetic small molecule that generates force against a load

    NASA Astrophysics Data System (ADS)

    Lussis, Perrine; Svaldo-Lanero, Tiziana; Bertocco, Andrea; Fustin, Charles-André; Leigh, David A.; Duwez, Anne-Sophie

    2011-09-01

    Some biomolecules are able to generate directional forces by rectifying random thermal motions. This allows these molecular machines to perform mechanical tasks such as intracellular cargo transport or muscle contraction in plants and animals. Although some artificial molecular machines have been synthesized and used collectively to perform mechanical tasks, so far there have been no direct measurements of mechanical processes at the single-molecule level. Here we report measurements of the mechanical work performed by a synthetic molecule less than 5 nm long. We show that biased Brownian motion of the sub-molecular components in a hydrogen-bonded [2]rotaxane--a molecular ring threaded onto a molecular axle--can be harnessed to generate significant directional forces. We used the cantilever of an atomic force microscope to apply a mechanical load to the ring during single-molecule pulling-relaxing cycles. The ring was pulled along the axle, away from the thermodynamically favoured binding site, and was then found to travel back to this site against an external load of 30 pN. Using fluctuation theorems, we were able to relate measurements of the work done at the level of individual rotaxane molecules to the free-energy change as previously determined from ensemble measurements. The results show that individual rotaxanes can generate directional forces of similar magnitude to those generated by natural molecular machines.

  15. Fisetin, a dietary phytochemical, overcomes Erlotinib-resistance of lung adenocarcinoma cells through inhibition of MAPK and AKT pathways

    PubMed Central

    Zhang, Liang; Huang, Yi; Zhuo, Wenlei; Zhu, Yi; Zhu, Bo; Chen, Zhengtang

    2016-01-01

    Erlotinib (Tarceva) is a selective epidermal growth factor receptor tyrosine kinase inhibitor for treatment of non-small cell lung cancer (NSCLC). However, its efficacy is usually reduced by the occurrence of drug resistance. Our recent study showed that a flavonoid found in many plants, Fisetin, might have a potential to reverse the acquired Cisplatin-resistance of lung adenocarcinoma. In the present study, we aimed to test whether Fisetin could have the ability to reverse Erlotinib-resistance of lung cancer cells. Erlotinib-resistant lung adenocarcinoma cells, HCC827-ER, were cultured from the cell line HCC827, and the effects of Fisetin and Erlotinib on the cell viability and apoptosis were evaluated. The possible signaling pathways in this process were also detected. As expected, the results showed that Fisetin effectively increased sensitivity of Erlotinib-resistant lung cancer cells to Erlotinib, possibly by inhibiting aberrant activation of MAPK and AKT signaling pathways resulted from AXL suppression. In conclusion, Fisetin was a potential agent for reversing acquired Erlotinib-resistance of lung adenocarcinoma. Inactivation of AXL, MAPK and AKT pathways might play a partial role in this process. PMID:27904686

  16. The Roles of Bud-Site-Selection Proteins during Haploid Invasive Growth in Yeast

    PubMed Central

    Cullen, Paul J.; Sprague, George F.

    2002-01-01

    In haploid strains of Saccharomyces cerevisiae, glucose depletion causes invasive growth, a foraging response that requires a change in budding pattern from axial to unipolar-distal. To begin to address how glucose influences budding pattern in the haploid cell, we examined the roles of bud-site-selection proteins in invasive growth. We found that proteins required for bipolar budding in diploid cells were required for haploid invasive growth. In particular, the Bud8p protein, which marks and directs bud emergence to the distal pole of diploid cells, was localized to the distal pole of haploid cells. In response to glucose limitation, Bud8p was required for the localization of the incipient bud site marker Bud2p to the distal pole. Three of the four known proteins required for axial budding, Bud3p, Bud4p, and Axl2p, were expressed and localized appropriately in glucose-limiting conditions. However, a fourth axial budding determinant, Axl1p, was absent in filamentous cells, and its abundance was controlled by glucose availability and the protein kinase Snf1p. In the bud8 mutant in glucose-limiting conditions, apical growth and bud site selection were uncoupled processes. Finally, we report that diploid cells starved for glucose also initiate the filamentous growth response. PMID:12221111

  17. Development of an Evaluation System for Vertical Vibration of Railway Vehicles with Field-Portable Actuators (1st Report, Data Processing Method to Estimate Running-Vehicle Vibration from Stationary Vibration Test)

    NASA Astrophysics Data System (ADS)

    Tomioka, Takahiro; Takigami, Tadao

    The authors are developing a vibration evaluation system, which consists of field-portable exciters (actuators) and data processing software, to estimate vertical vibration and ride quality of railway vehicles. One of the main characteristics of the system is that the acceleration power spectral density (PSD) at arbitrary point on the carbody in running condition is synthesized numerically from measured data obtained when each axle box or each wheelset is excited individually using limited number of actuators. This paper focuses upon the data processing method for the vibration evaluation system. A series of excitation tests for a commuter vehicle is carried out to confirm the basic concept to estimate the PSD by using the rolling stock testing plant at Railway Technical Research Institute. Some excitation methodologies and data processing formulae are compared among each other. It is clearly shown that the estimated PSDs well agree with actual PSD. It is found out that the estimation gives high accurate results when only excited axle box acceleration are used in estimation analysis.

  18. The transcription factor RUNX2 regulates receptor tyrosine kinase expression in melanoma

    PubMed Central

    Boregowda, Rajeev K.; Medina, Daniel J.; Markert, Elke; Bryan, Michael A.; Chen, Wenjin; Chen, Suzie; Rabkin, Anna; Vido, Michael J.; Gunderson, Samuel I.; Chekmareva, Marina; Foran, David J.; Lasfar, Ahmed; Goydos, James S.; Cohen-Solal, Karine A.

    2016-01-01

    Receptor tyrosine kinases-based autocrine loops largely contribute to activate the MAPK and PI3K/AKT pathways in melanoma. However, the molecular mechanisms involved in generating these autocrine loops are still largely unknown. In the present study, we examine the role of the transcription factor RUNX2 in the regulation of receptor tyrosine kinase (RTK) expression in melanoma. We have demonstrated that RUNX2-deficient melanoma cells display a significant decrease in three receptor tyrosine kinases, EGFR, IGF-1R and PDGFRβ. In addition, we found co-expression of RUNX2 and another RTK, AXL, in both melanoma cells and melanoma patient samples. We observed a decrease in phosphoAKT2 (S474) and phosphoAKT (T308) levels when RUNX2 knock down resulted in significant RTK down regulation. Finally, we showed a dramatic up regulation of RUNX2 expression with concomitant up-regulation of EGFR, IGF-1R and AXL in melanoma cells resistant to the BRAF V600E inhibitor PLX4720. Taken together, our results strongly suggest that RUNX2 might be a key player in RTK-based autocrine loops and a mediator of resistance to BRAF V600E inhibitors involving RTK up regulation in melanoma. PMID:27102439

  19. 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.

  20. Versatile synthesis of end-reactive polyrotaxanes applicable to fabrication of supramolecular biomaterials

    PubMed Central

    Tamura, Atsushi; Tonegawa, Asato; Arisaka, Yoshinori

    2016-01-01

    Cyclodextrin (CD)-threaded polyrotaxanes (PRXs) with reactive functional groups at the terminals of the axle polymers are attractive candidates for the design of supramolecular materials. Herein, we describe a novel and simple synthetic method for end-reactive PRXs using bis(2-amino-3-phenylpropyl) poly(ethylene glycol) (PEG-Ph-NH2) as an axle polymer and commercially available 4-substituted benzoic acids as capping reagents. The terminal 2-amino-3-phenylpropyl groups of PEG-Ph-NH2 block the dethreading of the α-CDs after capping with 4-substituted benzoic acids. By this method, two series of azide group-terminated polyrotaxanes (benzylazide: PRX-Bn-N3, phenylazide: PRX-Ph-N3,) were synthesized for functionalization via click reactions. The PRX-Bn-N3 and PRX-Ph-N3 reacted quickly and efficiently with p-(tert-butyl)phenylacetylene via copper-catalyzed click reactions. Additionally, the terminal azide groups of the PRX-Bn-N3 could be modified with dibenzylcyclooctyne (DBCO)-conjugated fluorescent molecules via a copper-free click reaction; this fluorescently labeled PRX was utilized for intracellular fluorescence imaging. The method of synthesizing end-reactive PRXs described herein is simple and versatile for the design of diverse functional PRXs and can be applied to the fabrication of PRX-based supramolecular biomaterials. PMID:28144361

  1. An implantable seal-less centrifugal pump with integrated double-disk motor.

    PubMed

    Schima, H; Schmallegger, H; Huber, L; Birgmann, I; Reindl, C; Schmidt, C; Roschal, K; Wieselthaler, G; Trubel, W; Losert, U

    1995-07-01

    Thrombus formation and sealing problems at the shaft as well as the compact and efficient design of the driving unit have been major difficulties in the construction of a long-term implantable centrifugal pump. To eliminate the problems of the seal, motor size, and efficiency, two major steps were taken by modifying the Vienna implantable centrifugal pump. First, a special driving unit was developed, in which the permanent magnets of the motor themselves are used for coupling the force into the rotor. Second, the rotor shaft in the pumping chamber was eliminated by adopting a concept recently presented by Ohara. The rotor is supported by 3 pins, which run on a carbon disk, whose concave shape leads to stabilization. The device has the following specifications: size: 65 mm (diameter) by 35 mm (height), 101 cm3; priming volume 30 cm3, 240 g; and a 6-pole brushless double disk DC motor. The required input power of the described prototype is 15 W at 150 mm Hg, 5 L/min (overall eta = 11%), and has an in vitro index of hemolysis (IH) of 0.0046 g/100 L. The test for in vitro thrombus growth exhibited far less thrombus formation in the new design than in designs with axles. In conclusion, the design of a special driving unit and the elimination of the axle led to the construction of a small pump with very low blood traumatization.

  2. 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.

  3. 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.

  4. Toward a four-toothed molecular bevel gear with C2-symmetrical rotors.

    PubMed

    Kao, Chen-Yi; Hsu, Ya-Ting; Lu, Hsiu-Feng; Chao, Ito; Huang, Shou-Ling; Lin, Ying-Chih; Sun, Wei-Ting; Yang, Jye-Shane

    2011-07-15

    The design, synthesis, conformational analysis, and variable-temperature NMR studies of pentiptycene-based molecular gears Pp(2)X, where Pp is the unlabeled (in 1H) or methoxy groups-labeled (in 1OM) pentiptycene rotor and X is the phenylene stator containing ortho-bridged ethynylene axles, are reported. The approach of using shape-persistent rotors of four teeth but C(2) symmetry for constructing four-toothed molecular gears is unprecedented. In addition, the first example of enantioresolution of chiral pentiptycene scaffolds is demonstrated. Density functional theory (DFT) and AM1 calculations on these Pp(2)X systems suggest two possible correlated torsional motions, geared rocking and four-toothed geared rotations, which compete with the uncorrelated gear slippage. The DFT-derived torsional barriers in 1H for rocking, four-toothed rotation, and gear slippage are approximately 2.9, 5.5, and 4.7 kcal mol(-1), respectively. The low energy barriers for these torsional motions result from the low energy cost of bending the ethynylene axles. Comparison of the NMR spectra of 1OM in a mixture of stereoisomers (1OM-mix) and in an enantiopure form (1OM-op) confirms a fast gear slippage in these Pp(2)X systems. The effect of the methoxy labels on rotational potential energy surface and inter-rotor dynamics is also discussed.

  5. 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.

  6. 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

  7. Correlations of the instantaneous carrying force and pressure distribution in the case of the narrow sliding radial bearing under hard shocks

    NASA Astrophysics Data System (ADS)

    Alexandrescu, I. M.; Coteţiu, R.; Darabă, D.

    2017-02-01

    We present the determining relationship of carriage in non-dimensional form for narrow radial bearings subjected to shocks and vibrations, as well as the determining relationships of the lubricant minimum thickness in relation to the dynamic loading. Due to the very short time of loading radial bearings subjected to shocks and vibrations, of about 0.5-1 ms, we consider only the approaching motion between spindle/axle and bushing on the direction of the centre line, without the rotation of the spindle/axle (the case of the non-rotating bearing), so that the effect of the lubricant expulsion be prevalent in the achieving of the self-carrying film. The paper is focused on determining relationship of carriage in dimensional form for narrow radial bearings exposed to shocks and vibrations, as well as the determining relationships of the pressure distribution from the film to be lubricated in various places of the bearing’s body. It is showed the details during the measuring accomplishments and the experimental results are registered in a record of obtained results. This paper was accepted for publication in Proceedings after double peer reviewing process but was not presented at the Conference ROTRIB’16

  8. Wireless sensor node for detection of freight train derailment

    NASA Astrophysics Data System (ADS)

    Costa, Andrea; Milani, Damiano; Resta, Ferruccio; Tomasini, Gisella

    2016-04-01

    The target of the research activity presented in this paper is to design, to realize and to test an autonomous sensor node able to measure the accelerations in correspondence of the axle box of a freight train. The final goal of the sensor is to identify the derailment conditions by observing the variations in the spectra of the box accelerations, around the frequencies associated to the wheel revolution and its multiples. The sensor node embeds an accelerometer, a microprocessor, a transmission system, a piezoelectric bimorph energy harvester and an integrated circuit for managing the power distribution to each component of the node. In particular, a mechanical filter to be applied to the node was specifically designed to increment the energy recovered by the harvester and to filter out the high frequency components of the axle-box acceleration, allowing the use of a more sensitive accelerometer. The harvesting system was setup by means of laboratory tests carried out with an electromechanical shaker and the sensor node was finally tested through field tests on freight trains.

  9. 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.

  10. Demonstration of a heavy-duty vehicle chassis screening test for compliance testing heavy-duty engines. Final report

    SciTech Connect

    Clark, N.N.; McKain, D.L.; Hoppie, J.A.; Lyons, D.W.; Gautam, M.

    1998-07-01

    Emissions testing of new heavy-duty engines is performed to ensure compliance with governmental emissions standards. This testing involves operating the engine through the heavy-duty diesel transient Federal Test Procedure (FTP). While in-use engine emissions testing would be beneficial in aiding regions to meet standards dictated by the Clean Air Act, the process of removing the engine from the vehicle, fitting it to an engine dynamometer, testing, and refitting the engine in the chassis, combined with costs associated with removing the vehicle from service, is prohibitively expensive. A procedure for screening engine emissions testing with the engine in the vehicle using a chassis dynamometer was developed to mimic the FTP. Data from two engines and vehicles (a 195 hp Navistar T 444E in a single axle straight truck and a 370 hp Cummins N-14 in a tandem drive axle tractor) is presented as well as correlation between engine and chassis emissions tests. Also included was data gathered to gauge the effects of engine tampering and malfunctioning on emissions levels. It was concluded that engine and chassis emissions levels were well correlated with respect to oxides of nitrogen, but less well so with respect to particulate matter.

  11. A novel approach identifies new differentially methylated regions (DMRs) associated with imprinted genes

    PubMed Central

    Choufani, Sanaa; Shapiro, Jonathan S.; Susiarjo, Martha; Butcher, Darci T.; Grafodatskaya, Daria; Lou, Youliang; Ferreira, Jose C.; Pinto, Dalila; Scherer, Stephen W.; Shaffer, Lisa G.; Coullin, Philippe; Caniggia, Isabella; Beyene, Joseph; Slim, Rima; Bartolomei, Marisa S.; Weksberg, Rosanna

    2011-01-01

    Imprinted genes are critical for normal human growth and neurodevelopment. They are characterized by differentially methylated regions (DMRs) of DNA that confer parent of origin-specific transcription. We developed a new strategy to identify imprinted gene-associated DMRs. Using genome-wide methylation profiling of sodium bisulfite modified DNA from normal human tissues of biparental origin, candidate DMRs were identified by selecting CpGs with methylation levels consistent with putative allelic differential methylation. In parallel, the methylation profiles of tissues of uniparental origin, i.e., paternally-derived androgenetic complete hydatidiform moles (AnCHMs), and maternally-derived mature cystic ovarian teratoma (MCT), were examined and then used to identify CpGs with parent of origin-specific DNA methylation. With this approach, we found known DMRs associated with imprinted genomic regions as well as new DMRs for known imprinted genes, NAP1L5 and ZNF597, and novel candidate imprinted genes. The paternally methylated DMR for one candidate, AXL, a receptor tyrosine kinase, was also validated in experiments with mouse embryos that demonstrated Axl was expressed preferentially from the maternal allele in a DNA methylation-dependent manner. PMID:21324877

  12. 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.

  13. 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.

  14. Design and optimization of a flexible arrayed eddy current sensor

    NASA Astrophysics Data System (ADS)

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

    2017-04-01

    The inspection of the hollow axle inner surfaces is a key process to guarantee the safety of high-speed trains. A novel flexible arrayed eddy current sensor was developed to improve the reliability of the non-destructive testing of the hollow axle inner surfaces, whose main innovative aspect was the new design of excitation/sensing traces to achieve a differential and arrayed configuration. Only two independent excitation traces were used in the sensor to induce eddy currents, which can be detected by 16 differential sensing elements. The lift-off effects and the influence of the excitation frequency and geometrical parameters of the proposed sensor was investigated and presented in this paper. Finite element models were built to analyze the effects of each parameter on the sensor response amplitude. Experimental validations were conducted using a representative set of sensors. Results from experiments and simulations were consistent with each other, which showed that the sensor design can substantially suppress the lift-off effects and modifications of the studied parameters can substantially improve the sensor performance.

  15. 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

  16. 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

  17. 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

  18. Multipoint targeting of the PI3K/mTOR pathway in mesothelioma

    PubMed Central

    Zhou, S; Liu, L; Li, H; Eilers, G; Kuang, Y; Shi, S; Yan, Z; Li, X; Corson, J M; Meng, F; Zhou, H; Sheng, Q; Fletcher, J A; Ou, W-B

    2014-01-01

    Background: Mesothelioma is a notoriously chemotherapy-resistant neoplasm, as is evident in the dismal overall survival for patients with those of asbestos-associated disease. We previously demonstrated co-activation of multiple receptor tyrosine kinases (RTKs), including epidermal growth factor receptor (EGFR), MET, and AXL in mesothelioma cell lines, suggesting that these kinases could serve as novel therapeutic targets. Although clinical trials have not shown activity for EGFR inhibitors in mesothelioma, concurrent inhibition of various activated RTKs has pro-apoptotic and anti-proliferative effects in mesothelioma cell lines. Thus, we hypothesised that a coordinated network of multi-RTK activation contributes to mesothelioma tumorigenesis. Methods: Activation of PI3K/AKT/mTOR, Raf/MAPK, and co-activation of RTKs were evaluated in mesotheliomas. Effects of RTK and downstream inhibitors/shRNAs were assessed by measuring mesothelioma cell viability/growth, apoptosis, activation of signalling intermediates, expression of cell-cycle checkpoints, and cell-cycle alterations. Results: We demonstrate activation of the PI3K/AKT/p70S6K and RAF/MEK/MAPK pathways in mesothelioma, but not in non-neoplastic mesothelial cells. The AKT activation, but not MAPK activation, was dependent on coordinated activation of RTKs EGFR, MET, and AXL. In addition, PI3K/AKT/mTOR pathway inhibition recapitulated the anti-proliferative effects of concurrent inhibition of EGFR, MET, and AXL. Dual targeting of PI3K/mTOR by BEZ235 or a combination of RAD001 and AKT knockdown had a greater effect on mesothelioma proliferation and viability than inhibition of individual activated RTKs or downstream signalling intermediates. Inhibition of PI3K/AKT was also associated with MDM2-p53 cell-cycle regulation. Conclusions: These findings show that PI3K/AKT/mTOR is a crucial survival pathway downstream of multiple activated RTKs in mesothelioma, underscoring that PI3K/mTOR is a compelling target for

  19. Efficiency Improvement through Reduction in Friction and Wear in Powertrain Systems

    SciTech Connect

    Michael Killian

    2009-09-30

    The objective of this project is to improve the efficiency of truck drivelines through reduction of friction and parasitic losses in transmission and drive axles. Known efficiencies for these products exceeded 97 percent, so the task was not trivial. The project relied on a working relationship between modeling and hardware testing. Modeling was to shorten the development cycle by guiding the selection of materials, processes and strategies. Bench top and fixture tests were to validate the models. Modeling was performed at a world class, high academic level, but in the end, modeling did not impact the hardware development as much as intended. Insights leading to the most significant accomplishments came from bench top and fixture tests and full scale dynamometer tests. A key development in the project was the formulation of the implementation strategy. Five technical elements with potential to minimize friction and parasitic losses were identified. These elements included churning, lubrication, surface roughness, coatings and textures. An interesting fact is that both Caterpillar and Eaton independently converged on the same set of technical elements in formulating their implementation strategies. Exploiting technical elements of the implementation strategy had a positive impact on transmission and drive axle efficiencies. During one dynamometer test of an Eaton Best Tech 1 transmission, all three gear ranges tested: Under drive, direct drive and over drive, showed efficiencies greater than 99 percent. Technology boosts to efficiency for transmissions reached 1 percent, while efficiency improvements to drive axle pushed 2 percent. These advancements seem small, but the accomplishment is large considering that these products normally run at greater than 97 percent efficiency. Barriers and risks to implementing these technology elements are clear. Schemes using a low fill sump and spray tubes endanger the gears and bearings by lubricant starvation. Gear coatings have

  20. Ampoule sealing apparatus and process

    NASA Technical Reports Server (NTRS)

    Debnam, Jr., William J. (Inventor); Clark, Ivan O. (Inventor)

    1988-01-01

    An apparatus 10 for effecting sealing of a fused quartz ampoule 24 while maintaining a vacuum on the ampoule via system 12 is disclosed. A plug 28 of fused quartz is lowered into the vertically disposed ampoule 24 (while maintaining the vacuum thereon) and heat sealed therein to prevent any vapor escape from, or contamination of, the contained semiconductor growth charge 29 during subsequent semiconductor crystal growth processes. A rotary vacuum feed-through mechanism 16 selectively rotates axle 34 and spool 32 to unwind wire 30 for lowering of plug 28 into the reduced diameter portion 24b of ampoule 24. Ampoule 24 is hermatically connected to vacuum housing 18 by quick release flange 20 wherein O-ring 22 retains ampoule 24.