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Sample records for axles

  1. Axle Shaft Optical Inspection System

    NASA Astrophysics Data System (ADS)

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

    1980-11-01

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

  2. Drive axle for electric vehicle

    SciTech Connect

    Travis, J.M.

    1981-06-02

    An electric powered vehicle drive axle is disclosed. The axle of the present invention comprises a ring gear; a first pinion gear for rotating the ring gear; a differential carried by the ring gear; a pair of axle shafts driven by the differential for rotatably driving a pair of drive wheels; the device supported and enclosed by a housing. A second pinion gear is employed which rotatably engages the ring gear. A first electric motor rotatably connected to the first pinion gear is connected to a power source for rotatably driving the vehicle. A second electric motor/generator is connected to the second pinion gear and electrically connected to the power source. The second electric motor/generator selectively powers the differential or derives power from the differential to recharge the power source as dictated by the power needs of the electric vehicle. A plurality of bevel gears are deployed along the length of the axles. Each bevel gear is rotatably connected to a pair of opposed bevel gears, each opposed bevel gear is rotatably connected to an electric motor/generator. By selectively and electrically causing the plurality of motors/generators to either power the axle or be powered by the axle optimum efficiency and recharging of the battery over a range of vehicle operating conditions is obtained.

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

    DOE PAGES

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

    2014-09-21

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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 49 CFR 230.98 - Driving, trailing, and engine truck axles.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...; (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 of... journal diameter, except as provided in paragraph (a)(7) of this section; (7) Any driving axles other...

  10. 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

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

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

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

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

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

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

  13. Axl-Targeted Cancer Imaging with Humanized Antibody h173

    PubMed Central

    Li, Dan; Liu, Shuanglong; Liu, Ren; Park, Ryan; Yu, Haiyang; Krasnoperov, Valery; Gill, Parkash S.; Li, Zibo; Shan, Hong; Conti, Peter S.

    2014-01-01

    Purpose The tyrosine kinase receptor Axl is overexpressed in various types of cancer and correlated with cancer malignancy. Selective Axl blockade reduces tumor growth and metastasis. The purpose of this study was to examine whether the humanized anti-Axl antibody humanized 173 (h173) labeled with near-infrared fluorescence (NIRF) dye Cy5.5 could be applied as a molecular imaging probe for NIRF imaging of Axl expression in tumor models. Procedures NIRF dye Cy5.5 was conjugated to h173 or human normal immunoglobulin G (hIgG) control through amino groups. The resulting probes were evaluated in both A549 (Axl positive) and NCI-H249 (Axl negative) lung cancer xenografts through in vivo NIRF imaging. Ex vivo imaging and probe distribution assay were also carried out to confirm the in vivo imaging results. Results After conjugation, binding activity of h173-Cy5.5 was determined to be 97.75 %± 2.09 % of the unmodified h173. In vitro fluorescence-activated cell sorting (FACS) and fluorescence microscopy analysis validated the specific binding of h173 toward Axl-positive A549 cells. h173-Cy5.5 was then applied to image Axl expression in vivo. In A549 (Axl positive) cancer xenografts, the tumor uptake of h173-Cy5.5 was significantly higher than that of the hIgG-Cy5.5 control (P<0.05) at late time points (1, 2, 3, 4, and 7 days). On the contrary, in NCI-H249 (Axl negative) cancer xenografts, the tumor uptake of both hIgG-Cy5.5 and h173-Cy5.5 was low and showed no significant difference (P>0.05) at all time points examined. Ex vivo imaging and immunofluorescence staining analysis further validated the in vivo imaging results. Conclusions Collectively, all in vitro, in vivo, and ex vivo data suggested that h173-Cy5.5 could serve as a valid probe for Axl-targeted cancer imaging, which could therefore aid in tumor diagnosis, prognosis, and treatment monitoring. PMID:24424460

  14. 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.

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

    PubMed Central

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

    2016-01-01

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

  16. Axl 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

  17. 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... Locomotives and Tenders Running Gear § 230.98 Driving, trailing, and engine truck axles. (a) Condemning defects. Driving, trailing, and engine truck axles with any of the following defects shall be removed...

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

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  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... Locomotives and Tenders Running Gear § 230.98 Driving, trailing, and engine truck axles. (a) Condemning defects. Driving, trailing, and engine truck axles with any of the following defects shall be removed...

  20. 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... Locomotives and Tenders Running Gear § 230.98 Driving, trailing, and engine truck axles. (a) Condemning defects. Driving, trailing, and engine truck axles with any of the following defects shall be removed...

  1. 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.

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

    ERIC Educational Resources Information Center

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

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

  3. 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...

  4. 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.

  5. 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

  6. Sunitinib activates Axl signaling in renal cell cancer.

    PubMed

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

    2016-06-15

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

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

    SciTech Connect

    Xu, Fei; Li, Hongling; Sun, Yong

    2014-11-28

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

  8. Axl modulates immune activation of smooth muscle cells in vein graft remodeling.

    PubMed

    Batchu, Sri N; Xia, Jixiang; Ko, Kyung Ae; Doyley, Marvin M; Abe, Jun-Ichi; Morrell, Craig N; Korshunov, Vyacheslav A

    2015-09-15

    The pathophysiological mechanisms of the immune activation of smooth muscle cells are not well understood. Increased expression of Axl, a receptor tyrosine kinase, was recently found in arteries from patients after coronary bypass grafts. In the present study, we hypothesized that Axl-dependent immune activation of smooth muscle cells regulates vein graft remodeling. We observed a twofold decrease in intimal thickening after vascular and systemic depletion of Axl in vein grafts. Local depletion of Axl had the greatest effect on immune activation, whereas systemic deletion of Axl reduced intima due to an increase in apoptosis in vein grafts. Primary smooth muscle cells isolated from Axl knockout mice had reduced proinflammatory responses by prevention of the STAT1 pathway. The absence of Axl increased suppressor of cytokine signaling (SOCS)1 expression in smooth muscle cells, a major inhibitory protein for STAT1. Ultrasound imaging suggested that vascular depletion of Axl reduced vein graft stiffness. Axl expression determined the STAT1-SOCS1 balance in vein graft intima and progression of the remodeling. The results of this investigation demonstrate that Axl promotes STAT1 signaling via inhibition of SOCS1 in activated smooth muscle cells in vein graft remodeling.

  9. 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.

  10. 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

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

    PubMed Central

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

    2016-01-01

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

  12. A traffic accident caused by fatigue failure of axle.

    PubMed

    Park, Chan-Seong; Lee, Sang-Hoon; Lee, Kyu-Jung

    2007-09-01

    An investigation of a traffic accident involving a tractor-trailer and a passenger car that were traveling at high speed is presented. The cause was the fracture of a trailer axle. The investigation showed that the fracture was because of the fatigue failure. In addition, cracks were found in the remaining three trailer wheels. Hardness measurements showed that, because of inadequate heat treatment of the metal, they were prone to failure.

  13. Effect of axle misalignments on rolling resistance and wheel wear

    SciTech Connect

    Leary, J.F.; Wilson, N.G.

    1985-01-01

    High energy costs impacting the railroad industry and the use of rail lubrication to lower energy consumption have led to investigation of axle misalignment as a cause of train resistance and wear. This paper brings together the results of field and laboratory misalignment tests designed to measure the effects of axle misalignment on roller resistance and wheel wear of standard trucks run on curved and tangent track. These tests employed the Transportation Test Center's Roll Dynamics Unit for the lab tests, an instrumented coupler for field testing, and a modified version of the AAR Curving Model to validate the RDU results and correlate them to field data. All testing was conducted at the Transportation Test Center near Pueblo, Colorado, under the sponsorship of the Association of American Railroads (RDU Test) and the Federal Railroad Administration (Track Test). During testing, deliberate misalignments were introduced in test wheelsets, and measurements were taken in field and laboratory settings. The train resistance and wheel wear data correlated well with the curving model, showing that reasonably accurate results are achievable by modeling within a common range of known conditions. The undesirable effects of axle misalignment on train resistance and wear were confirmed.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2009-01-01

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

  16. Warfarin blocks Gas6-mediated Axl activation required for pancreatic cancer epithelial plasticity and metastasis

    PubMed Central

    Kirane, Amanda; Ludwig, Kathleen F.; Sorrelle, Noah; Haaland, Gry; Sandal, Tone; Ranaweera, Renate; Toombs, Jason E.; Wang, Miao; Dineen, Sean P.; Micklem, David; Dellinger, Michael T.; Lorens, James B.; Brekken, Rolf A.

    2015-01-01

    Repurposing ‘old’ drugs can facilitate rapid clinical translation but necessitates novel mechanistic insight. Warfarin, a vitamin K “antagonist” used clinically for the prevention of thrombosis for over 50 years, has been shown to have anti-cancer effects. We hypothesized that the molecular mechanism underlying its anti-tumor activity is unrelated to its effect on coagulation, but is due to inhibition of the Axl receptor tyrosine kinase on tumor cells. Activation of Axl by its ligand Gas6, a vitamin K-dependent protein, is inhibited at doses of warfarin that do not affect coagulation. Here we show that inhibiting Gas6-dependent Axl activation with low dose warfarin or with other tumor-specific Axl targeting agents, blocks the progression and spread of pancreatic cancer. Warfarin also inhibited Axl-dependent tumor cell migration, invasiveness and proliferation while increasing apoptosis and sensitivity to chemotherapy. We conclude that Gas6-induced Axl signaling is a critical driver of pancreatic cancer progression and its inhibition with low dose warfarin or other Axl targeting agents may improve outcome in patients with Axl-expressing tumors. PMID:26206560

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

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Defects in tender truck axles and journals. 230... Steam Locomotives and Tenders Running Gear § 230.100 Defects in tender truck axles and journals. (a... wheel seats that is more than 1/8 of an inch in depth. (b) Tender truck journal condemning...

  18. 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)...

  19. 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)...

  20. 49 CFR 230.100 - Defects in tender truck axles and journals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  1. 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)...

  2. A Versatile Axle for the Construction of Disassemblage Rotaxanes.

    PubMed

    Powers, Lucas A; Smithrud, David B

    2016-01-01

    Rotaxanes are unique mechanical devices that hold great promise as sensors. We report on two new rotaxanes that contain an acid or base sensitive trigger and readily disassemble in a wide range of environments. Disassemblage was observed under TLC and ¹H-NMR analysis. The axle is highly charged, which enhances solubility in aqueous environments, and can be readily derivatized with sensor components. The trigger was swapped in a one-pot method, which is promising for the rapid production of a series of sensors. PMID:27517897

  3. Multicenter analysis of soluble Axl reveals diagnostic value for very early stage hepatocellular carcinoma.

    PubMed

    Reichl, Patrick; Fang, Meng; Starlinger, Patrick; Staufer, Katharina; Nenutil, Rudolf; Muller, Petr; Greplova, Kristina; Valik, Dalibor; Dooley, Steven; Brostjan, Christine; Gruenberger, Thomas; Shen, Jiayun; Man, Kwan; Trauner, Michael; Yu, Jun; Gao, Chun Fang; Mikulits, Wolfgang

    2015-07-15

    If diagnosed at early stages, patients with hepatocellular carcinoma (HCC) can receive curative therapies, whereas therapeutic options at later stages are very limited. Here, we addressed the potential of soluble Axl (sAxl) as a biomarker of early HCC by analyzing levels of sAxl in 311 HCC and 237 control serum samples from centers in Europe and China. Serum concentrations of sAxl were significantly increased in HCC (18.575 ng/mL) as compared to healthy (13.388 ng/mL) or cirrhotic (12.169 ng/mL) controls. Receiver operating characteristic curve analysis of sAxl in very early stage HCC patients (BCLC 0) showed an area under the curve (AUC) of 0.848, with a sensitivity of 76.9% and a specificity of 69.2%. α-Fetoprotein (AFP)-negative HCC patients displayed an AUC of 0.803, with sensitivity and specificity of 73% and 70.8%. Combination of sAxl and AFP improved diagnostic accuracy to 0.936 in very early HCC patients and to 0.937 in all HCC. Differential diagnosis of very early HCC versus liver cirrhosis showed a combined performance for sAxl and AFP of 0.901 with a sensitivity of 88.5% and a specificity of 76.7%. Furthermore, sAxl levels failed to be elevated in primary ovarian, colorectal and breast carcinomas as well as in secondary hepatic malignancies derived from colon. In summary, sAxl outperforms AFP in detecting very early HCC as compared to healthy or cirrhotic controls and shows high diagnostic accuracy for AFP-negative patients. sAxl is specific for HCC and suggested as a biomarker for routine clinical use.

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

    PubMed Central

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

    2016-01-01

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

  5. Gas6/Axl pathway promotes tumor invasion through the transcriptional activation of Slug in hepatocellular carcinoma.

    PubMed

    Lee, Hsin-Jung; Jeng, Yung-Ming; Chen, Yu-Ling; Chung, Ling; Yuan, Ray-Hwang

    2014-04-01

    Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide. Other than the sorafenib treatment, no effective systemic therapy has been available thus far. Most targets in molecularly targeted therapy for cancer are receptor tyrosine kinases (RTKs). Therefore, identifying activated RTKs in HCC is critical for developing new molecularly targeted therapies. Using a phospho-RTK array, we found that Axl is one of the most frequently activated RTKs in liver cancer cell lines. The knockdown of Axl by RNA interference significantly reduced cell migration and invasion in the HCC cell lines HA22T and Mahlavu. Stimulation of HCC cell lines by Axl ligand growth arrest-specific 6 (Gas6) enhanced cell migration and invasion. The Gas6/Axl pathway enhanced the expression of the epithelial-mesenchymal transition-inducing transcription factor Slug, which is essential for the invasion-promoting activity of Axl. Treating HCC cells with the Axl inhibitor bosutinib suppressed Slug expression and decreased the invasiveness of HCC cell lines. These findings indicate that Gas6/Axl regulates tumor invasion through the transcriptional activation of Slug.

  6. Active suspension for a two-axle railway vehicle

    NASA Astrophysics Data System (ADS)

    Pacchioni, Alessandro; Goodall, Roger M.; Bruni, Stefano

    2010-12-01

    The aim of this paper is to investigate how the ride quality of a two-axle railway vehicle with single-stage suspension might be improved by the use of active control, compensating for the lack of the double suspension stage, and thereby taking full advantage of vehicle lightweight construction. The basic requirement is to improve the ride quality on random track unevenness while keeping suspension deflection within acceptable levels when the vehicle negotiates deterministic track features such as a gradient. Two active suspension configurations are considered - skyhook damping and linear quadratic Gaussian (LQG) optimal control. Finally, actuator dynamics are included in the analysis, to assess the impact on the overall success of an active suspension implementation. The paper shows that both skyhook and LQG control strategies offer significant improvements in ride quality and also that careful design of the actuators and their force control loops is essential.

  7. Axl tyrosine kinase protects against tubulo-interstitial apoptosis and progression of renal failure in a murine model of chronic kidney disease and hyperphosphataemia.

    PubMed

    Hyde, Gareth D; Taylor, Rebecca F; Ashton, Nick; Borland, Samantha J; Wu, Hon Sing Geoffrey; Gilmore, Andrew P; Canfield, Ann E

    2014-01-01

    Chronic kidney disease (CKD) is defined as the progressive loss of renal function often involving glomerular, tubulo-interstitial and vascular pathology. CKD is associated with vascular calcification; the extent of which predicts morbidity and mortality. However, the molecular regulation of these events and the progression of chronic kidney disease are not fully elucidated. To investigate the function of Axl receptor tyrosine kinase in CKD we performed a sub-total nephrectomy and fed high phosphate (1%) diet to Axl+/+ and Axl-/- mice. Plasma Gas6 (Axl' ligand), renal Axl expression and downstream Akt signalling were all significantly up-regulated in Axl+/+ mice following renal mass reduction and high phosphate diet, compared to age-matched controls. Axl-/- mice had significantly enhanced uraemia, reduced bodyweight and significantly reduced survival following sub-total nephrectomy and high phosphate diet compared to Axl+/+ mice; only 45% of Axl-/- mice survived to 14 weeks post-surgery compared to 87% of Axl+/+ mice. Histological analysis of kidney remnants revealed no effect of loss of Axl on glomerular hypertrophy, calcification or renal sclerosis but identified significantly increased tubulo-interstitial apoptosis in Axl-/- mice. Vascular calcification was not induced in Axl+/+ or Axl-/- mice in the time frame we were able to examine. In conclusion, we identify the up-regulation of Gas6/Axl signalling as a protective mechanism which reduces tubulo-interstitial apoptosis and slows progression to end-stage renal failure in the murine nephrectomy and high phosphate diet model of CKD.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

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

    PubMed Central

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

    2014-01-01

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

  13. 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’.

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

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2014-12-15

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

  16. 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

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2016-05-01

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

  20. Inhibition of Mer and Axl receptor tyrosine kinases leads to increased apoptosis and improved chemosensitivity in human neuroblastoma.

    PubMed

    Li, Yixin; Wang, Xiqian; Bi, Shaojie; Zhao, Kun; Yu, Chao

    2015-02-13

    Ectopic expression of Mer and Axl receptor tyrosine kinases (RTKs) are frequently found in various cancers as known to promote oncogenesis by activating antiapoptotic signaling pathways. However, the roles of these receptors in neuroblastoma remain unclear. We found Mer and Axl was co-expressed in neuroblastoma patient samples and cell lines. Ligand-dependent Mer or Axl activation led to an increase in phosphorylated ERK1/2, AKT and FAK indicating roles for these RTKs in multiple oncogenic processes. Furthermore, Mer and Axl knockdown led to apoptosis and inhibition of migration as well as a significant increase in chemosensitivity in response to cisplatin and vincristine treatment. Taken together, our results demonstrated that inhibition of Mer and Axl improved apoptotic response and chemosensitivity in neuroblastoma, providing new insights into development of novel therapeutic strategies by targeting these oncogenes.

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

    PubMed

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

    2016-07-28

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

  2. Coordinated expression of tyro3, axl, and mer receptors in macrophage ontogeny

    PubMed Central

    Malawista, Anna; Wang, Xiaomei; Trentalange, Mark; Allore, Heather G.; Montgomery, Ruth R.

    2016-01-01

    The TAM receptors (Tyro3, Axl, and Mer) are a family of homologous receptor-tyrosine kinases that inhibit Toll-like receptor signaling to regulate downstream pathways and restore homeostasis. TAM triple mutant mice (Tyro3−/−, Axl−/−, Mer−/−) have elevated levels of pro-inflammatory cytokines and are prone to developing lymphoproliferative disorders and autoimmunity. Understanding differential expression of TAM receptors among human subjects is critical to harnessing this pathway for therapeutic interventions. We have quantified changes in TAM expression during the ontogeny of human macrophages using paired samples of monocytes and macrophages to take advantage of characteristic expression within an individual. No significant differences in levels of Tyro3 were found between monocytes and macrophages (flow cytometry: p=0.652, immunoblot: p=0.231, qPCR: p=0.389). Protein levels of Axl were reduced (flow cytometry: p=0.049, immunoblot: p<0.001) when monocytes matured to macrophages. No significant differences in the levels of Axl mRNA transcripts were found (qPCR: p=0.082), however, Tyro3 and Axl were proportionate. The most striking difference was upregulation of expression of Mer with both protein and mRNA being significantly increased when monocytes developed into macrophages (flow cytometry: p<0.001, immunoblot: p<0.001, qPCR: p=0.004). A fuller characterization of TAM receptor expression in macrophage ontogeny informs our understanding of their function and potential therapeutic interventions.

  3. Axl is essential for VEGF-A-dependent activation of PI3K/Akt

    PubMed Central

    Ruan, Guo-Xiang; Kazlauskas, Andrius

    2012-01-01

    Herein, we report that vascular endothelial growth factor A (VEGF-A) engages the PI3K/Akt pathway by a previously unknown mechanism that involves three tyrosine kinases. Upon VEGF-A-dependent activation of VEGF receptor-2 (VEGFR-2), and subsequent TSAd-mediated activation of Src family kinases (SFKs), SFKs engage the receptor tyrosine kinase Axl via its juxtamembrane domain to trigger ligand-independent autophosphorylation at a pair of YXXM motifs that promotes association with PI3K and activation of Akt. Other VEGF-A-mediated signalling pathways are independent of Axl. Interfering with Axl expression or function impairs VEGF-A- but not bFGF-dependent migration of endothelial cells. Similarly, Axl null mice respond poorly to VEGF-A-induced vascular permeability or angiogenesis, whereas other agonists induce a normal response. These results elucidate the mechanism by which VEGF-A activates PI3K/Akt, and identify previously unappreciated potential therapeutic targets of VEGF-A-driven processes. PMID:22327215

  4. 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…

  5. 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

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

    PubMed

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

    2014-08-29

    Withaferin A, a withanolide derived from the medicinal plant Withania somnifera, has been reported to exhibit anti-tumorigenic activity against various cancer cells. In this study, we show that withaferin A inhibits the constitutive and recombinant human growth-arrest-specific protein 6 (rhGas6)-induced phosphorylation of Axl and STAT3. In addition, withaferin A also induces the down-regulation of Axl protein expression in a lysosome-dependent manner and inhibits rhGas6-induced wound healing and cell migration. Furthermore, the overexpression of Axl attenuates withaferin A-induced apoptosis. Taken together, the data from the present study indicate that the withaferin A-mediated down-regulation of the Gas6/Axl signaling pathway mediates the inhibition of cell migration and the induction of apoptosis. PMID:25117439

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

    PubMed

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

    2015-09-01

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

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

    PubMed

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

    2016-05-01

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

  9. Influence of the transmission configuration of a multiple axle vehicle on the obstacle surmounting capacity

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

    Conventional wheeled vehicles have serious mobility limitations in rough terrain while walking vehicles have inherent drawbacks such as a high number of DOF and actuators, control complexity and low-energy efficiency. Vehicles that passively adapt the position of multiple wheels to maintain contact with the ground can be a good compromise between both conventional wheeled and walking vehicles. One way to increase the number of wheels in contact with the ground is using bogies. However, the kinematics of a multiple axle vehicle moving on irregular terrain is quite complex since every wheel can require different angular speed to avoid slippage. The present work aims to quantify the obstacle surmounting capacity of a four axle, double-bogie vehicle depending on the transmission configuration, since it can provoke the slippage of some of its wheels. Some results are presented corresponding to the vehicle moving on a straight upward slope of different angles and facing variable obstacles in any of its axles. It can be observed that as more restricted the transmission is, more wheels are forced to slip and less traction the vehicle has, and, as a consequence, less obstacle surmounting capacity.

  10. 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

  11. 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

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

    PubMed

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

    2016-06-17

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

  13. AUY922 Effectively Overcomes MET- and AXL-Mediated Resistance to EGFR-TKI in Lung Cancer Cells

    PubMed Central

    Choi, Yun Jung; Kim, Seon Ye; So, Kwang Sup; Baek, In-Jeoung; Kim, Woo Sung; Choi, Se Hoon; Lee, Jae Cheol; Bivona, Trever G.; Rho, Jin Kyung; Choi, Chang-Min

    2015-01-01

    The activation of bypass signals, such as MET and AXL, has been identified as a possible mechanism of EGFR-TKI resistance. Because various oncoproteins depend on HSP90 for maturation and stability, we investigated the effects of AUY922, a newly developed non-geldanamycin class HSP90 inhibitor, in lung cancer cells with MET- and AXL-mediated resistance. We established resistant cell lines with HCC827 cells harboring an exon 19-deletion mutation in of the EGFR gene via long-term exposure to increasing concentrations of gefitinib and erlotinib (HCC827/GR and HCC827/ER, respectively). HCC827/GR resistance was mediated by MET activation, whereas AXL activation caused resistance in HCC827/ER cells. AUY922 treatment effectively suppressed proliferation and induced cell death in both resistant cell lines. Accordingly, the downregulation of EGFR, MET, and AXL led to decreased Akt activation. The inhibitory effects of AUY922 on each receptor were confirmed in gene-transfected LK2 cells. AUY922 also effectively controlled tumor growth in xenograft mouse models containing HCC827/GR and HCC827/ER cells. In addition, AUY922 reduced invasion and migration by both types of resistant cells. Our study findings thus show that AUY922 is a promising therapeutic option for MET- and AXL-mediated resistance to EGFR-TKI in lung cancer. PMID:25780909

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

    PubMed

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

    2013-11-01

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

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

    PubMed

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

    2015-12-01

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

  16. Gas6 receptors Axl, Sky and Mer enhance platelet activation and regulate thrombotic responses.

    PubMed

    Gould, W R; Baxi, S M; Schroeder, R; Peng, Y W; Leadley, R J; Peterson, J T; Perrin, L A

    2005-04-01

    Gas6 (encoded by growth arrest-specific gene 6) is a vitamin-K dependent protein highly homologous to coagulation protein S that is secreted from platelet alpha-granules and has recently been demonstrated to participate in platelet thrombus formation. The current study evaluated the contribution of each of the three known Gas6 receptors (Axl, Sky and Mer) in human and mouse platelet function. Flow cytometry analyses confirmed that all three receptors are present on both human and mouse platelets. Pre-incubation of human platelets with either an anti-Gas6 antibody or blocking antibodies to Sky or Mer inhibited platelet aggregation and degranulation responses to both ADP and the PAR-1 activating peptide, SFLLRN, by more than 80%. In contrast, a stimulatory anti-Axl antibody increased activation responses to these agonists, suggesting a potentiating role for Gas6 in platelet activation. Moreover, in a mouse model of thrombosis, administration of Gas6 or Sky blocking antibodies resulted in a decrease in thrombus weight similar to clopidogrel but, unlike clopidogrel, produced no increase in template bleeding. Thus, Gas6 enhances platelet degranulation and aggregation responses through its known receptors, promoting platelet activation and mediating thrombus formation such that its inhibition prevents thrombosis without increasing bleeding. PMID:15733062

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

    PubMed

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

    2016-07-01

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

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

    NASA Astrophysics Data System (ADS)

    Carboni, Michele; Cantini, Stefano

    2016-02-01

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

  19. 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

    2014-09-01

    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.

  20. 75 FR 52981 - Chrysler, LLC, Detroit Axle Plant, Including On-Site Leased Workers from Caravan Knight...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-30

    ... was published in the Federal Register on February 2, 2009 (74 FR 5870). The notice was amended on... notice was published in the Federal Register on March 12, 2010 (75 FR 111914). At the request of a... Employment and Training Administration Chrysler, LLC, Detroit Axle Plant, Including On-Site Leased...

  1. 75 FR 11914 - Chrysler, LLC, Detroit Axle Plant, Including On-Site Leased Workers From Caravan Knight...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-12

    ... the Federal Register on February 2, 2009 (74 FR 5870). At the request of the State agency, the... Employment and Training Administration Chrysler, LLC, Detroit Axle Plant, Including On-Site Leased Workers From Caravan Knight Facilities Management LLC; Detroit, MI; Amended Certification Regarding...

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-08-01

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

  4. 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.

  5. 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

  6. Vision system using linear CCD cameras in fluorescent magnetic particle inspection of axles of railway wheelsets

    NASA Astrophysics Data System (ADS)

    Hao, Hongwei; Li, Luming; Deng, Yuanhui

    2005-05-01

    Automatic magnetic particle inspection based vision system using CCD camera is a new development of magnetic particle inspection. A vision system using linear CCD cameras in semiautomatic fluorescent magnetic particle inspection of axles of railway wheelsets is presented in this paper. The system includes four linear CCD cameras, a PCI data acquisition & logic control card, and an industrial computer. The unique characteristic of striation induced by UV light flicker in scanning image acquired by linear CCD camera are investigated, and some digital image processing methods for images of magnetic particle indications are designed to identify the cracks, including image pre-processing using wavelet, edge detection based connected region using Candy operator and double thresholds. The experimental results show that the system can detect the article cracks effectively, and may improve inspection quality highly and increase productivity practically.

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

    PubMed

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

    2008-02-15

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

  8. Optic-electronic sensor for measuring the deformations of the axle at the radio-telescope

    NASA Astrophysics Data System (ADS)

    Konyakhin, Igor; Turgalieva, Tatyana V.; Li, Renpu

    2014-05-01

    The improved autocollimation sensors for measuring angular deformations of the large constructions as elevation axle and the azimuth columns of the radio telescopes are analyzed. Two new types of the reflector for autocollimation sensors are researched. The first type of the reflector is the composition of the anamorphic prism and ordinary cube-corner retroreflector. This reflector generates the narrow beam, as result the work distance and the range of measurement of the sensor increases. The second type of the reflectors is the tetrahedral reflector with flat reflecting sides and invariant axis. For this reflector the small value of the conversion coefficient is the realization of the measurements on the large work distances. The technical characteristics of the experimental setups of new reflectors are presented. The features of the anamorphic prism and tetrahedral reflector as the reflectors for autocollimation angular sensors are discussed.

  9. 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.

  10. 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

  11. Design, synthesis, and validation of Axl-targeted monoclonal antibody probe for microPET imaging in human lung cancer xenograft.

    PubMed

    Liu, Shuanglong; Li, Dan; Guo, Jiacong; Canale, Nicolette; Li, Xiuqing; Liu, Ren; Krasnoperov, Valery; Gill, Parkash S; Conti, Peter S; Shan, Hong; Li, Zibo

    2014-11-01

    Accumulating experimental evidence indicates that overexpression of the oncogenic receptor tyrosine kinase, Axl, plays a key role in the tumorigenesis and metastasis of various types of cancer. The objective of this study is to design a novel imaging probe based on the monoclonal antibody, h173, for microPET imaging of Axl expression in human lung cancer. A bifunctional chelator, DOTA, was conjugated to h173, followed by radiolabeling with (64)Cu. The binding of DOTA-h173 to the Axl receptor was first evaluated by a cell uptake assay and flow cytometry analysis using human lung cancer cell lines. The probe (64)Cu-DOTA-h173 was further evaluated by microPET imaging, and ex vivo histology studies in the Axl-positive A549 tumors. In vitro cellular study showed that Axl probe, (64)Cu-DOTA-h173, was highly immuno-reactive with A549 cells. Western blot analysis confirmed that Axl is highly expressed in the A549 cell line. For microPET imaging, the A549 xenografts demonstrated a significantly higher (64)Cu-DOTA-h173 uptake compared to the NCI-H249 xenograft (a negative control model). Furthermore, (64)Cu-DOTA-h173 uptake in A549 is significantly higher than that of (64)Cu-DOTA-hIgG. Immuno-fluorescence staining was consistent with the in vivo micro-PET imaging results. In conclusion, (64)Cu-DOTA-h173 could be potentially used as a probe for noninvasive imaging of Axl expression, which could collect important information regarding tumor response to Axl-targeted therapeutic interventions.

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

    PubMed

    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

    2016-04-28

    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

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

    NASA Astrophysics Data System (ADS)

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

    2013-01-01

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

  14. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2011-07-01

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

  16. 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.

  17. 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

  18. Yes-associated protein 1 (YAP1) promotes human gallbladder tumor growth via activation of the AXL/MAPK pathway.

    PubMed

    Li, Maolan; Lu, Jianhua; Zhang, Fei; Li, Huaifeng; Zhang, Bingtai; Wu, Xiangsong; Tan, Zhujun; Zhang, Lin; Gao, Guofeng; Mu, Jiasheng; Shu, Yijun; Bao, Runfa; Ding, Qichen; Wu, Wenguang; Dong, Ping; Gu, Jun; Liu, Yingbin

    2014-12-28

    The transcriptional coactivator Yes-associated protein 1 (YAP1), a key regulator of cell proliferation and organ size in vertebrates, has been implicated in various malignancies. However, little is known about the expression and biological function of YAP1 in human gallbladder cancer (GBC). In this study we examined the clinical significance and biological functions of YAP1 in GBC and found that nuclear YAP1 and its target gene AXL were overexpressed in GBC tissues. We also observed a significant correlation between high YAP1 and AXL expression levels and worse prognosis. The depletion of YAP1 using lentivirus shRNAs significantly inhibited cell proliferation by inducing cell cycle arrest in S phase in concordance with the decrease of CDK2, CDC25A, and cyclin A, and resulted in increased cell apoptosis and invasive repression in GBC cell lines in vitro. Furthermore, knockdown of YAP1 also inhibited tumor growth in vivo. Additionally, we demonstrated that the activation of the AXL/MAPK pathway was involved in the oncogenic functions of YAP1 in GBC. These results demonstrated that YAP1 is a putative oncogene and represents a prognostic marker and potentially a novel therapeutic target for GBC.

  19. 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

  20. 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.

  1. Analysis of the nonlinear dynamics of a 2-axle freight wagon in curves

    NASA Astrophysics Data System (ADS)

    Di Gialleonardo, Egidio; Bruni, Stefano; True, Hans

    2014-01-01

    This paper deals with the study of the nonlinear dynamic behaviour of 2-axle freight wagons in curves, considering the case of one single wagon (neglecting inter-car coupling forces) and of multiple wagons interacting through the buffers and the couplers. A multi-body model of a single wagon and of a three-car assembly is introduced, paying particular attention to the nonlinear and nonsmooth modelling of the suspensions and of the inter-car coupling elements. Using this model, a numerical analysis of the steady-state solution reached after the negotiation of curve transition is presented and bifurcations are identified for some particular values of the curve radius. For the single car case, it is shown that depending on the curve radius and the vehicle speed the carbody may experience severe periodic oscillations at speeds lying in the operating range of the vehicle. For the car-assembly case, it is shown that the coupling forces exchanged by the wagons significantly affect their dynamics in a curve, reducing the amplitude of vibration.

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

    PubMed Central

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

    2015-01-01

    Purpose B-cell chronic lymphocytic leukemia (CLL) is an incurable disease despite aggressive therapeutic approaches. We previously found that Axl receptor tyrosine kinase (RTK) plays a critical role in CLL B-cell survival. Here, we explored the possibility of using a high-affinity Axl inhibitor as a single agent or in combination with Bruton’s tyrosine kinase (BTK) inhibitors for future clinical trial to treat CLL patients. Experimental Design Expression/activation status of other members of the TAM (Tyro3, Axl, MER) family of RTKs in CLL B-cells was evaluated. Cells were treated with a high-affinity orally bioavailable Axl inhibitor TP-0903 with or without presence of CLL bone marrow stromal cells (BMSCs). Inhibitory effects of TP-0903 on Axl signaling pathway was also evaluated in CLL B-cells. Finally, cells were exposed to TP-0903 in combination with BTK inhibitors to determine any synergistic/additive effects of the combination. Results CLL B-cells overexpress Tyro3, but not MER. Of interest, Tyro3 remains as constitutively phosphorylated and form a complex with Axl in CLL B-cells. TP-0903 induces massive apoptosis in CLL B-cells with LD50 values of nanomolar ranges. Importantly, CLL BMSCs could not protect the leukemic B-cells from TP-0903 induced apoptosis. A marked reduction of the anti-apoptotic proteins Mcl-1, Bcl-2, XIAP and upregulation of the pro-apoptotic protein BIM in CLL B-cells were detected as a result of Axl inhibition. Finally, combination of TP-0903 with BTK inhibitors augments CLL B-cell apoptosis. Conclusion Administration of TP-0903 either as a single agent or in combination with BTK inhibitors may be effective in treating CLL patients. PMID:25673699

  3. Strong Expression of Hypoxia-Inducible Factor-1α (HIF-1α) Is Associated with Axl Expression and Features of Aggressive Tumors in African Breast Cancer

    PubMed Central

    Nalwoga, Hawa; Ahmed, Lavina; Arnes, Jarle B.; Wabinga, Henry; Akslen, Lars A.

    2016-01-01

    Purpose Inhibition of hypoxia-inducible factor (HIF) and Axl receptor tyrosine kinase is being evaluated for targeted therapy in solid tumors. Both HIF-1α and Axl influence tumor growth and metastatic potential, and they have been linked to treatment failure in many cancers. However, there is a lack of reports on HIF-1α expression in African breast cancer, which has a poor prognosis, and novel treatment targets must therefore be established. Here, we aimed to evaluate HIF-1α in relation to Axl expression, angiogenesis markers, and other tumor characteristics in a series of African breast cancer. Methods Using immunohistochemistry, we examined 261 invasive breast cancers on tissue microarrays for HIF-1α and Axl as well as several other markers, and a subset of 185 cases had information on VEGF (vascular endothelial growth factor) expression, microvessel density (MVD), proliferating microvessel density (pMVD) and vascular proliferation index (VPI) for important comparisons. Results Strong HIF-1α expression was associated with increased Axl (p = 0.007), VEGF (p<0.0005), and p53 (p = 0.032) expression, as well as high tumor cell proliferation by Ki-67 (p = 0.006), and high tumor grade (p = 0.003). Tumors with strong HIF-1α expression had significantly higher MVD (p = 0.019) and higher pMVD (p = 0.027) than tumors with weak expression. Conclusions High HIF-1α expression is significantly associated with Axl and VEGF expression, and with markers of poor prognosis in this series of breast cancer, suggesting HIF-1α and Axl as potential therapeutic targets in African breast cancer. PMID:26760782

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

    PubMed Central

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

    2015-01-01

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

  5. 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.

  6. 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.

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

    NASA Astrophysics Data System (ADS)

    Nastasoiu, Mircea; Ispas, Nicolae

    2014-06-01

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

  8. Peroxisome proliferator-activated receptor-γ agonist troglitazone suppresses transforming growth factor-β1 signalling through miR-92b upregulation-inhibited Axl expression in human keloid fibroblasts in vitro

    PubMed Central

    Zhu, Hua-Yu; Bai, Wen-Dong; Li, Jun; Tao, Ke; Wang, Hong-Tao; Yang, Xue-Kang; Liu, Jia-Qi; Wang, Yun-Chuan; He, Ting; Xie, Song-Tao; Hu, Da-Hai

    2016-01-01

    Keloid, a skin benign tumor, is characterized by overgrowth of fibroblasts and the excessive deposition of extracellular matrix in wounded skin. Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist was recently evaluated to inhibit fibrosis. This study explored the underlying mechanisms. Fibroblasts isolated from 25 keloid patients (KFs) and fibroblasts isolated from healthy controls (NSFBs) were also subjected to treatment with PPAR-γ agonist troglitazone and antagonist GW9662 or for transfection with miR-92 mimics or inhibitor, Axl siRNA, and miR-92b or Axl promoter constructs, as well as being subjected to qRT-PCR, ELISA, Western blot, protein array, luciferase, and ChIP assays. The data demonstrated that TGF-β1 and Axl proteins were significantly elevated in samples from keloid patients, while troglitazone treatment significantly reduced levels of TGF-β1 and Axl mRNA and proteins in KFs. Moreover, knockdown of Axl expression reduced expression of TGF-β1 and its pathway genes (such as α-SMA and Snail). PPAR-γ regulation of Axl expression was through transcriptional activation of miR-92b. miR-92b expression downregulated Axl expression at both mRNA and protein levels, whereas GW9662 completely reversed the inhibitory effects of miR-92b mimics on Axl expression. Gene ontology analysis of miR-92b targeting genes showed that TGF-β and Axl were both potential targets of miR-92b, as confirmed by luciferase assay. These findings demonstrated that PPAR-γ-induced miR-92b expression inhibited Axl expression and in turn reduced expression of TGF-β1 and the downstream genes in KFs, suggesting that targeting of this novel gene pathway may be useful for therapeutic control of fibrosis or keloid.

  9. Peroxisome proliferator-activated receptor-γ agonist troglitazone suppresses transforming growth factor-β1 signalling through miR-92b upregulation-inhibited Axl expression in human keloid fibroblasts in vitro.

    PubMed

    Zhu, Hua-Yu; Bai, Wen-Dong; Li, Jun; Tao, Ke; Wang, Hong-Tao; Yang, Xue-Kang; Liu, Jia-Qi; Wang, Yun-Chuan; He, Ting; Xie, Song-Tao; Hu, Da-Hai

    2016-01-01

    Keloid, a skin benign tumor, is characterized by overgrowth of fibroblasts and the excessive deposition of extracellular matrix in wounded skin. Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist was recently evaluated to inhibit fibrosis. This study explored the underlying mechanisms. Fibroblasts isolated from 25 keloid patients (KFs) and fibroblasts isolated from healthy controls (NSFBs) were also subjected to treatment with PPAR-γ agonist troglitazone and antagonist GW9662 or for transfection with miR-92 mimics or inhibitor, Axl siRNA, and miR-92b or Axl promoter constructs, as well as being subjected to qRT-PCR, ELISA, Western blot, protein array, luciferase, and ChIP assays. The data demonstrated that TGF-β1 and Axl proteins were significantly elevated in samples from keloid patients, while troglitazone treatment significantly reduced levels of TGF-β1 and Axl mRNA and proteins in KFs. Moreover, knockdown of Axl expression reduced expression of TGF-β1 and its pathway genes (such as α-SMA and Snail). PPAR-γ regulation of Axl expression was through transcriptional activation of miR-92b. miR-92b expression downregulated Axl expression at both mRNA and protein levels, whereas GW9662 completely reversed the inhibitory effects of miR-92b mimics on Axl expression. Gene ontology analysis of miR-92b targeting genes showed that TGF-β and Axl were both potential targets of miR-92b, as confirmed by luciferase assay. These findings demonstrated that PPAR-γ-induced miR-92b expression inhibited Axl expression and in turn reduced expression of TGF-β1 and the downstream genes in KFs, suggesting that targeting of this novel gene pathway may be useful for therapeutic control of fibrosis or keloid. PMID:27648136

  10. Peroxisome proliferator-activated receptor-γ agonist troglitazone suppresses transforming growth factor-β1 signalling through miR-92b upregulation-inhibited Axl expression in human keloid fibroblasts in vitro

    PubMed Central

    Zhu, Hua-Yu; Bai, Wen-Dong; Li, Jun; Tao, Ke; Wang, Hong-Tao; Yang, Xue-Kang; Liu, Jia-Qi; Wang, Yun-Chuan; He, Ting; Xie, Song-Tao; Hu, Da-Hai

    2016-01-01

    Keloid, a skin benign tumor, is characterized by overgrowth of fibroblasts and the excessive deposition of extracellular matrix in wounded skin. Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist was recently evaluated to inhibit fibrosis. This study explored the underlying mechanisms. Fibroblasts isolated from 25 keloid patients (KFs) and fibroblasts isolated from healthy controls (NSFBs) were also subjected to treatment with PPAR-γ agonist troglitazone and antagonist GW9662 or for transfection with miR-92 mimics or inhibitor, Axl siRNA, and miR-92b or Axl promoter constructs, as well as being subjected to qRT-PCR, ELISA, Western blot, protein array, luciferase, and ChIP assays. The data demonstrated that TGF-β1 and Axl proteins were significantly elevated in samples from keloid patients, while troglitazone treatment significantly reduced levels of TGF-β1 and Axl mRNA and proteins in KFs. Moreover, knockdown of Axl expression reduced expression of TGF-β1 and its pathway genes (such as α-SMA and Snail). PPAR-γ regulation of Axl expression was through transcriptional activation of miR-92b. miR-92b expression downregulated Axl expression at both mRNA and protein levels, whereas GW9662 completely reversed the inhibitory effects of miR-92b mimics on Axl expression. Gene ontology analysis of miR-92b targeting genes showed that TGF-β and Axl were both potential targets of miR-92b, as confirmed by luciferase assay. These findings demonstrated that PPAR-γ-induced miR-92b expression inhibited Axl expression and in turn reduced expression of TGF-β1 and the downstream genes in KFs, suggesting that targeting of this novel gene pathway may be useful for therapeutic control of fibrosis or keloid. PMID:27648136

  11. 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.

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

    PubMed Central

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

    2014-01-01

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

  13. 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),…

  14. Multipurpose optic-electronic autocollimators for measuring deformations of the axle with a millimeter wave range radiotelescope

    NASA Astrophysics Data System (ADS)

    Konyakhin, Igor; Molev, Fedor; Konyakhin, Alexey; Li, Renpu

    2015-02-01

    The improved autocollimators for measuring angular deformations of the large constructions as support tube of mirror and elevation axle of the radio telescopes are analyzed. Two new types of the reflector for autocollimator are researched. The first type of the reflectors is the tetrahedral reflector with flat reflecting sides and invariant axis. The autocollimator with tetrahedral reflector is used for the measuring 3-D deformations as roll, pitch and yaw angular deviations. The second type of the reflector is the composition of the anamorphic wedge system and ordinary cube-corner retroreflector. This reflector generates the narrow beam, as result the work distance and the range of measurement of the roll angle increase. Technical characteristics of the experimental setups of new reflectors are presented. Features of the tetrahedral reflector and anamorphic system as the reflectors for multipurpose autocollimator are discussed.

  15. 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.

  16. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  18. 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.

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

    PubMed

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

    2016-06-21

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

  20. 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.

  1. 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.

  2. 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

    1997-06-01

    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.

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

    PubMed Central

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

    2016-01-01

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

  4. 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.

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

    NASA Astrophysics Data System (ADS)

    Katzsch, Felix; Gruber, Tobias; Weber, Edwin

    2016-06-01

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

  6. Sertoli cell-initiated testicular innate immune response through toll-like receptor-3 activation is negatively regulated by Tyro3, Axl, and mer receptors.

    PubMed

    Sun, Bing; Qi, Nan; Shang, Tao; Wu, Hui; Deng, Tingting; Han, Daishu

    2010-06-01

    Several Toll-like receptors (TLRs) are expressed in Sertoli cells and can trigger testicular innate responses after activation by ligands. TLR signaling pathway must be tightly controlled because unrestrained TLR activation generates a chronic inflammatory milieu that often leads to pathogenesis of the host. However, the regulation of TLR signaling in Sertoli cells remains to be clarified. Here we demonstrate that Tyro3 subfamily of receptor tyrosine kinases, Tyro3, Axl, and Mer (TAM), negatively regulate TLR3 signaling in Sertoli cells. Sertoli cells from TAM triple mutant (TAM(-/-)) mice exhibit an excessive activation of TLR3 in response to its ligand polyinosinic-polycytidylic acid, resulting in the up-regulation of inflammatory cytokines including IL-1beta, IL-6, TNFalpha, and type I interferons (alpha and beta). Growth arrest-specific gene 6 (Gas6), a common ligand of TAM receptors, inhibits the TLR3-driven expression of cytokines in Sertoli cells. This TAM-mediated inhibition of TLR3 signaling in Sertoli cells is transduced through the up-regulation of TLR signaling suppressors suppressor of cytokine signaling-1/3 by Gas6. Moreover, we provide evidence that TAM inhibition of inflammatory cytokine production by Sertoli cells may have physiological significance in vivo. These results illuminate a negative regulatory mechanism of TLR3 signaling in Sertoli cells, which may participate in controlling the testicular innate immune responses to pathogens.

  7. 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

    1994-04-01

    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.

  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 evidence of overheating, as evidenced by a pronounced blue black discoloration; or (e) The surface of...

  9. 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...

  10. 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...

  11. 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...

  12. 49 CFR 215.105 - Defective axle.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

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

    SciTech Connect

    RICH, J.W.

    2002-06-04

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

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

    PubMed

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

    2014-01-01

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

  15. 75 FR 76036 - American Axle & Manufacturing Detroit Manufacturing Complex Holbrook Avenue and Saint Aubin...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-07

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

  16. 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.

  17. 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

    ... essential to prevent the trailer from off tracking into other lanes or vehicles or off the highway entirely.... 383.3(a)). Current Regulatory Guidance Question 14 to Sec. 390.5 (62 FR 16370, 16407, April 4, 1997... changed by operation of the trailer controls when the CMV is not moving. In the ``locked'' position,...

  18. 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…

  19. Refining the parameters of Archard's wear model for calculating wear of wheels applied for 25 t per axle freight wagons on Russian railways

    NASA Astrophysics Data System (ADS)

    Saidova, Alina; Orlova, Anna

    2014-05-01

    The aim of the research is for a reasonable choice of wear coefficients for severe and mild phases in Archard's abrasive wear theory and friction coefficients for wheel flange and tread that correspond to conditions of Russian track for wheel profile wear modelling using dynamic models of wagons. This paper considers the gondola wagon on bogies model 18-9855 that are of the three-piece Barber S-2-R design. The wagon running test results on Experimental Loop Track in Scherbinka, the results of hardness measurements of wheel flange/tread and of wheel profile wear modelling are presented in this paper. In conclusion, a comparison of wheels wear of two freight wagons' bogies (with friction and elastic-friction links of wheel sets with side frames) on the basis of specified wear model was carried out.

  20. 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

  1. 75 FR 15620 - Federal Motor Vehicle Safety Standards; Air Brake Systems

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-30

    ... regulatory text using the term ``rear axles,'' certain three-axle tractors with one driven rear axle and one.... SUPPLEMENTARY INFORMATION: On July 27, 2009, NHSTA published a final rule \\1\\ in the Federal Register (74 FR... November 13, 2009, NHTSA published in the Federal Register (74 FR 58562) a final rule; partial response...

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

    PubMed

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

    2015-10-28

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

  3. Suspension for automotive vehicles

    SciTech Connect

    Pierce, W.C.

    1986-10-07

    This patent describes a vehicle suspension system for mounting ground-engaging wheels to a vehicle frame. The suspension system comprises at least two substantially rigid arms secured to opposite sides of the frame through substantially aligned pivot mounts; at least one wheel-carrying axle between the arms; and a bracket means securing the at least one axle to each of the arms. The improvements described here is in each of the bracket means comprising: an axle plate means rigidly secured to the axle and having an elongated planar complementary surface at least partially wrapping around the axle; two spaced connecting plates secured transversely to the axle plate means and to one of the arms; and a bracing means comprising at least one curved gusset plate rigidly and angularly secured to and between the axle plate means and one of the connecting plates.

  4. Specialized induction machines for deep surface and surface hardening

    SciTech Connect

    Andryushchenko, V.T.

    1988-01-01

    Designs of specialized hardening equipment for electrothermal hardening of parts using induction heating are described. These designs include induction machines for deep surface hardening of truck axle shafts, the outer and inner rings of railroad car axle roller bearings, camshafts, axle parts, and the side members of truck frames. This study and others help develop and transmit the technology for producing and introducing specialized induction machines which are effective in heat treatment of heavily loaded machine parts and consume less amounts of metal.

  5. 40 CFR 86.085-37 - Production vehicles and engines.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., inertia weight, and transmission class. (3) Vehicle configuration means a unique combination of basic engine, engine code, inertia weight, transmission configuration, and axle ratio within a base...

  6. 49 CFR 537.7 - Pre-model year and mid-model year reports.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... with the equation provided in 49 CFR 533 Figure 4. (4) State the projected final required fuel economy... accordance with 49 CFR 531.5(c) and 49 CFR 533.5 and based upon the projected sales figures provided under... CFR 523.2, (B) Beginning model year 2013, front axle, rear axle and average track width as defined...

  7. 49 CFR 537.7 - Pre-model year and mid-model year reports.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... with the equation provided in 49 CFR 533 Figure 4. (4) State the projected final required fuel economy... accordance with 49 CFR 531.5(c) and 49 CFR 533.5 and based upon the projected sales figures provided under... CFR 523.2, (B) Beginning model year 2013, front axle, rear axle and average track width as defined...

  8. 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.

  9. 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)

  10. 77 FR 71714 - Final Rule

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-04

    ... manufacture, its gross vehicle weight rating or GVWR, the gross axle weight rating or GAWR of each axle, the..., trailer, low-speed vehicle), and the vehicle's Vehicle Identification Number or ``VIN.'' The certification... specifically state that manufacturers of trailers, buses, motorcycles, and low-speed vehicles (those......

  11. 49 CFR 229.63 - Lateral motion.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  12. 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

    ... Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Will not have a significant... 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...

  13. 49 CFR 571.7 - Applicability.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

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

    Code of Federal Regulations, 2014 CFR

    2014-01-01

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

  15. 14 CFR 27.497 - Ground loading conditions: landing gear with tail wheels.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

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

  16. 14 CFR 29.497 - Ground loading conditions: landing gear with tail wheels.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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

  17. 14 CFR 27.497 - Ground loading conditions: landing gear with tail wheels.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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

  18. 14 CFR 29.497 - Ground loading conditions: landing gear with tail wheels.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

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

  19. 14 CFR 29.497 - Ground loading conditions: landing gear with tail wheels.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

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

  20. 49 CFR 393.47 - Brake actuators, slack adjusters, linings/pads and drums/rotors.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... physical characteristics must provide for safe and reliable stopping of the commercial motor vehicle. (b) Brake chambers. The service brake chambers and spring brake chambers on each end of an axle must be the same size. (c) Slack adjusters. The effective length of the slack adjuster on each end of an axle...

  1. 49 CFR 393.47 - Brake actuators, slack adjusters, linings/pads and drums/rotors.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... physical characteristics must provide for safe and reliable stopping of the commercial motor vehicle. (b) Brake chambers. The service brake chambers and spring brake chambers on each end of an axle must be the same size. (c) Slack adjusters. The effective length of the slack adjuster on each end of an axle...

  2. 49 CFR 393.47 - Brake actuators, slack adjusters, linings/pads and drums/rotors.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... physical characteristics must provide for safe and reliable stopping of the commercial motor vehicle. (b) Brake chambers. The service brake chambers and spring brake chambers on each end of an axle must be the same size. (c) Slack adjusters. The effective length of the slack adjuster on each end of an axle...

  3. 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...) Listing of the vehicle types as defined in 49 CFR 571.3 (e.g., truck, MPV, bus, trailer) into which the... exceed any of the gross axle weight ratings, if the center of gravity at GVWR is not higher than...

  4. 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...) Listing of the vehicle types as defined in 49 CFR 571.3 (e.g., truck, MPV, bus, trailer) into which the... exceed any of the gross axle weight ratings, if the center of gravity at GVWR is not higher than...

  5. 49 CFR Appendix C to Part 238 - Suspension System Safety Performance Standards

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... follows: (1) The maximum single wheel lateral to vertical force (L/V) ratio shall not exceed Nadal's limit... axle lateral force shall not exceed 0.5 times the static vertical axle load. (3) The vertical wheel/rail force shall not be less than or equal to 10 percent of the static vertical wheel load. (4) The...

  6. 49 CFR 393.42 - Brakes required on all wheels.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... semitrailer or pole trailer (laden or unladen) with a gross weight of 1,361 kg (3,000 pounds) or less which is subject to this part is not required to be equipped with brakes if the axle weight of the towed vehicle does not exceed 40 percent of the sum of the axle weights of the towing vehicle. (4) Any full...

  7. 49 CFR 393.42 - Brakes required on all wheels.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... a gross weight of 1,361 kg (3,000 pounds) or less which is subject to this part is not required to be equipped with brakes if the axle weight of the towed vehicle does not exceed 40 percent of the sum of the axle weights of the towing vehicle. (4) Any full trailer or four-wheel pole trailer (laden...

  8. 49 CFR 393.42 - Brakes required on all wheels.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... of § 393.52. (3) Any semitrailer or pole trailer (laden or unladen) with a gross weight of 1,361 kg... the axle weight of the towed vehicle does not exceed 40 percent of the sum of the axle weights of the towing vehicle. (4) Any full trailer or four-wheel pole trailer (laden or unladen) with a gross weight...

  9. 77 FR 75825 - Airworthiness Directives; Airbus Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-26

    ... products. That NPRM was published in the Federal Register on September 12, 2012 (77 FR 56172). That NPRM... high tensile standing stress, resulting from dry fit axle assembly method. Improvement has been introduced subsequently with a grease fit axle assembly method. Fatigue and damage tolerance analyses...

  10. 77 FR 56172 - Airworthiness Directives; Airbus Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-12

    ... high tensile standing stress, resulting from dry fit axle assembly method. Improvement has been introduced subsequently with a grease fit axle assembly method. Fatigue and damage tolerance analyses were performed, whose results demonstrated that the current life limit of certain MLG bogie beams with dry...

  11. 40 CFR 86.602-84 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  12. 40 CFR 86.602-84 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  13. 77 FR 25647 - Airworthiness Directives; The Boeing Company Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-01

    ... pitching motion during normal airplane operations. Heat damage or cracking in the MLG center axle and shock... Model 777 airplanes. This proposed AD was prompted by heat damage and cracks at the pivot joint location... cracking in the MLG center axle and shock strut inner cylinder lugs (pivot joint), which could result...

  14. 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...

  15. 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...

  16. 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...

  17. 23 CFR 658.17 - Weight.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1977-01-01

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

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

    PubMed

    Sevick, Edith M; Williams, David R M

    2013-01-01

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

  20. 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.

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

    DOEpatents

    Hoff, Brian

    2008-08-05

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

  2. 16 CFR 20.0 - Scope and purpose of the guides.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... used parts designed for use in automobiles, trucks, motorcycles, tractors, or similar self-propelled..., fan clutches, fuel injectors, fuel pumps, front wheel drive axles, generators, master cylinders, oil... Labeling Guides, 16 CFR part 228.)...

  3. 16 CFR 20.0 - Scope and purpose of the guides.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... used parts designed for use in automobiles, trucks, motorcycles, tractors, or similar self-propelled..., fan clutches, fuel injectors, fuel pumps, front wheel drive axles, generators, master cylinders, oil... Labeling Guides, 16 CFR part 228.)...

  4. 16 CFR 20.0 - Scope and purpose of the guides.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... used parts designed for use in automobiles, trucks, motorcycles, tractors, or similar self-propelled..., fan clutches, fuel injectors, fuel pumps, front wheel drive axles, generators, master cylinders, oil... Labeling Guides, 16 CFR part 228.)...

  5. 49 CFR 396.3 - Inspection, repair, and maintenance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., 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

    ..., 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. 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.

  8. 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.

  9. Weighing system for vehicles with temperature and inclinometer correction

    SciTech Connect

    Bambauer, B.R.; Dunkle, D.H.; Loscutoff, S.

    1986-11-18

    This patent describes for use in conjunction with a vehicle having a frame and a plurality of axles wherein each axle has a pair of springs, an improved weighing system comprising: a pair of enclosed cylinder means mounted on each of the axles adjacent the springs and connected to the frame; each of the enclosed cylinder means comprising two telescoping support tubes which slide vertically with respect to each other as the frame moves vertically with respect to the axles; ultrasonic transducer means mounted inside one end of the enclosed cylinder means; ultrasonic reflector means mounted inside the other end of the enclosed cylinder means; temperature sensing means mounted inside the cylinder means; and circuit means for sequentially sensing the displacement of each of the transducer means relative to its corresponding reflector means, correcting for temperatures sensed in each of enclosed cylinder means, and integrating the displacement signals to correct for any inclined terrain on which the tractor-trailer stands when weighed.

  10. Daisy Chain Rotaxanes Made from Interlocked DNA Nanostructures.

    PubMed

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

    2016-04-25

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

  11. Guide for rotating sucker rods

    SciTech Connect

    Harrel, R.D.

    1986-11-04

    This patent describes an improved guide for use in a string of sucker rods rotated in a tubing string in a borehole, the sucker rods having threaded male ends, the guide comprising: an elongated upright solid cylindrical coupling body of external diameter less than the internal diameter of tubing in which it is to be used; a pair of spaced apart axle holders positioned in three recess; an axle received in each recess in the coupling body, the axis of each axle being parallel and spaced from the body longitudinal axis; a roller rotatably received on each axle, the periphery of each roller extending exteriorly of the external cylindrical surface of the coupling body; and means to retain each of the holders in the coupling body recess.

  12. 16 CFR 20.0 - Scope and purpose of the guides.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... used parts designed for use in automobiles, trucks, motorcycles, tractors, or similar self-propelled..., fan clutches, fuel injectors, fuel pumps, front wheel drive axles, generators, master cylinders, oil... Labeling Guides, 16 CFR part 228.)...

  13. 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.

  14. 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.

  15. 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...

  16. 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...

  17. 14 CFR 25.509 - Towing loads.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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

  18. Daisy Chain Rotaxanes Made from Interlocked DNA Nanostructures

    PubMed Central

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

    2016-01-01

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

  19. Daisy Chain Rotaxanes Made from Interlocked DNA Nanostructures.

    PubMed

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

    2016-04-25

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

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

    NASA Astrophysics Data System (ADS)

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

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

  1. 40 CFR 86.518-78 - Dynamometer calibration.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... then calibrated as required. The dynamometer is driven above the test speed range. The device used to... bearing friction due to the drive axle weight of the vehicle. (b) Calibration shall consist of...

  2. 40 CFR 1037.805 - Symbols, acronyms, and abbreviations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Transportation. EPAEnvironmental Protection Agency. ETWequivalent test weight. FELFamily Emission Limit. ggrams. GAWRgross axle weight rating. GCWRgross combination weight rating. GVWRgross vehicle weight rating... States Code. VSLvehicle speed limiter. WFwork factor....

  3. 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)

  4. 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)

  5. 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)

  6. 78 FR 79391 - Foreign-Trade Zone (FTZ) 22-Chicago, Illinois, Notification of Proposed Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-30

    ... turn retainers; catch springs; flap springs; springs; torque springs; wire racks; bake pans; pizza pans...; latch, pedal, coil and torque springs; wire racks; bake pans; retaining rings; bushing axles; pizza...

  7. 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... steering axle brake lining/pad thickness shall not be less than 3.2 mm (1/8 inch) for air disc brakes, or...

  8. 49 CFR 393.47 - Brake actuators, slack adjusters, linings/pads and drums/rotors.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... steering axle of a truck, truck-tractor or bus shall not be less than 4.8 mm (3/16 inch) at the shoe center....6 mm (1/16 inch) or less for hydraulic disc, drum and electric brakes. (2) Non-steering axle brakes... for drum brakes); or less than 3.2 mm (1/8 inch) for disc brakes. Hydraulic or electric...

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

    PubMed

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

    2016-08-11

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

  10. Mechanosensing Controlled Directly by Tyrosine Kinases.

    PubMed

    Yang, Bo; Lieu, Zi Zhao; Wolfenson, Haguy; Hameed, Feroz M; Bershadsky, Alexander D; Sheetz, Michael P

    2016-09-14

    To understand how cells form tissues, we need to understand how the tyrosine kinases are involved in controlling cell mechanics, whether they act directly as parts of mechanosensing machines or indirectly. Cells test the critical parameter of matrix rigidity by locally contracting ("pinching") matrices and measuring forces, and the depletion of contractile units causes transformation. We report here that knocking down the receptor tyrosine kinases (RTKs), AXL, and ROR2, alters rigidity sensing and increases the magnitude or duration of local contraction events, respectively. Phospho-AXL and ROR2 localize to contraction units and bind major contractile components, tropomyosin 2.1 (AXL), myosin IIA (AXL), and filamin A (ROR2). At a molecular level, phosphorylated AXL localizes to active myosin filaments and phosphorylates tropomyosin at a tyrosine critical for adhesion formation. ROR2 binding of ligand is unnecessary, but binding filamin A helps function. Thus, AXL and ROR2 alter rigidity sensing and consequently morphogenic processes by directly controlling local mechanosensory contractions without ligands. PMID:27559755

  11. Substitution effect and effect of axle’s flexibility at (pseudo-)rotaxanes

    PubMed Central

    Malberg, Friedrich; Brandenburg, Jan Gerit; Reckien, Werner; Hollóczki, Oldamur

    2014-01-01

    Summary This study investigates the effect of substitution with different functional groups and of molecular flexibility by changing within the axle from a single C–C bond to a double C=C bond. Therefore, we present static quantum chemical calculations at the dispersion-corrected density functional level (DFT-D3) for several Leigh-type rotaxanes. The calculated crystal structure is in close agreement with the experimental X-ray data. Compared to a stiffer axle, a more flexible one results in a stronger binding by 1–3 kcal/mol. Alterations of the binding energy in the range of 5 kcal/mol could be achieved by substitution with different functional groups. The hydrogen bond geometry between the isophtalic unit and the carbonyl oxygen atoms of the axle exhibited distances in the range of 2.1 to 2.4 Å for six contact points, which shows that not solely but to a large amount the circumstances in the investigated rotaxanes are governed by hydrogen bonding. Moreover, the complex with the more flexible axle is usually more unsymmetrical than the one with the stiff axle. The opposite is observed for the experimentally investigated axle with the four phenyl stoppers. Furthermore, we considered an implicit continuum solvation model and found that the complex binding is weakened by approximately 10 kcal/mol, and hydrogen bonds are slightly shortened (by up to 0.2 Å). PMID:24991282

  12. Shaft-driven motor vehicle

    SciTech Connect

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

    1987-03-03

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

  13. Circulating levels of soluble MER in lupus reflect M2c activation of monocytes/macrophages, autoantibody specificities and disease activity

    PubMed Central

    2013-01-01

    Introduction Systemic lupus erythematosus (SLE) is characterized by impaired efferocytosis and aberrant activation of innate immunity. We asked if shedding of MER receptor tyrosine kinase (MerTK) and AXL into soluble (s) ectodomains was related to immunological and clinical aspects of SLE. Methods Levels of sMER and sAXL in the plasma of 107 SLE patients and 45 matched controls were measured by ELISA. In 40 consecutive SLE patients, we examined potential correlations between either sMER or sAXL and plasma levels of sCD163, a marker of M2 activation. All three soluble receptors were measured in supernatants of monocytes/macrophages cultured in various immunological conditions. Membrane expression of MerTK, AXL and CD163 was assessed by flow cytometry. Results Both sMER and sAXL were associated with anti-chromatin and anti-phospholipid autoantibodies, and with hematological and renal involvement. However, sMER and sAXL did not significantly correlate with each other; sAXL correlated with growth arrest-specific 6 (Gas6), whereas sMER correlated with reduced free protein S (PROS) levels. Only sMER showed significant associations with lupus-specific anti-dsDNA, anti-Sm, anti-ribonucleoprotein (anti-RNP) and anti-Ro60 autoantibodies. Strong correlations with disease activity indices (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), complement reduction, titer of circulating anti-dsDNA) were found for sMER, not for sAXL. Patients with active SLEDAI, nephritis, anti-dsDNA and anti-Ro60 positivity showed higher levels of sMER compared to controls. Levels of sMER, not sAXL, correlated with sCD163 levels, and these correlated with SLEDAI. Production of sMER and sCD163 occurred under “M2c” polarizing conditions, whereas sAXL was released upon type-I IFN exposure. Conclusions Alterations in homeostasis of anti-inflammatory and efferocytic “M2c” monocytes/macrophages may have a role in immunopathogenesis of SLE. PMID:24325951

  14. [2]Rotaxane with multiple functional groups.

    PubMed

    Saha, Subrata; Santra, Saikat; Akhuli, Bidyut; Ghosh, Pradyut

    2014-11-21

    High-yield syntheses of Cu(II)- and Ni(II)-templated [2]pseudorotaxane precursors (CuPRT and NiPRT, respectively) were achieved by threading bis(azide)bis(amide)-2,2'-bipyridine axle into a bis(amide)tris(amine) macrocycle. Single-crystal X-ray structural analysis of CuPRT revealed complete threading of the axle fragment into the wheel cavity, where strong aromatic π-π stacking interactions between two parallel arene moieties of the wheel and the pyridyl unit of axle are operative in addition to metal ion templation. Attachment of a newly developed bulky stopper molecule with a terminal alkyne to CuPRT via a Cu(I)-catalyzed azide-alkyne cycloaddition reaction failed as a result of dethreading of the azide-terminated axle under the reaction conditions. However, the synthesis of a metal-free [2]rotaxane containing triazole with other functionalities in the axle was achieved in ∼45% yield upon coupling between azide-terminated NiPRT and the alkyne-terminated stopper. The [2]rotaxane was characterized by mass spectrometry, 1D and 2D NMR (COSY, DOSY, and ROESY) experiments. Comparative solution-state NMR studies of the [2]rotaxane in its unprotonated and protonated states were carried out to locate the position of the wheel on the axle of the metal-free [2]rotaxane. Furthermore, a variable-temperature (1)H NMR study in DMSO-d6 of [2]rotaxane supported the kinetic inertness of the interlocked structure, where the newly developed stopper prevents dethreading of the 30-membered wheel from the axle.

  15. 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

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

    PubMed Central

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

    2014-01-01

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

  17. The rectifying device for optical axis of sighting devices

    NASA Astrophysics Data System (ADS)

    Fu, RongGuo; Chang, BenKang; Qian, YunSheng; Zhan, QiHai; Qiu, YaFeng

    2005-02-01

    The combination photo electronic sighting device usually composed of different optical devices, including telescope and low light level night vision device or infrared thermal imaging system. Every optical axle of the optical device of the combination sighting device is needed to be parallel. When a target away enough from the sighting device is observed, if the images of the target locate on the center of the field of the vision of the different optical devices, it shows that the axis are parallel. According to this principle, a rectifying device for optical axis of sighting device is designed. It includes off-axle paraboloid reflector, the target of cross line, light sources, precision modifying devices and other devices. The target of cross line is put on the focus of the off-axle paraboloid reflector, thus it forms a parallel light beam through the off-axle paraboloid reflector, the sighting device is immerged in the parallel light beam. The observing effect is like a target of long distance. The target is connected with a precision modifying device, by moving modifying device, until the image of the target coincide with the center of the field of vision of every optical device, whose degree of deviation of the optical axle can be calculated. The paper gives the structure of the rectifying device and the way of testing. The parameters of the device is given too.

  18. 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.

  19. 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.

  20. Stress distribution under heavy haul transporters

    SciTech Connect

    Davie, J.R.; Senapathy, H.

    1999-11-01

    In a previous cited paper, comparisons were made between the relationship of maximum vertical compressive stress generated with depth by various vehicles, including an automobile, a fully-loaded 18-wheel tractor-trailer combination, a test-loaded 12-axle, 96-wheel heavy transporter trailer, and the transporter prime mover, also test loaded. This paper extends the usefulness of those comparisons by adding a 12-axle, 144-wheel heavy transporter trailer. The transporter is a one-and-one-half-wide hydraulic platform trailer test loaded to 110% of the loading from a Westinghouse steam generator. The total weight on the transporter trailer tires is just over 675 tons. This trailer will be used in an upcoming steam generator replacement project. In addition to examining the distribution of maximum vertical stress with depth, the paper looks at the variation of loading beneath the maximum loaded axle of the transporter at different depths.

  1. 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

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

    PubMed

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

    2016-09-20

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

  3. 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.

  4. Diversification of TAM receptor function

    PubMed Central

    Zagórska, Anna; Través, Paqui G.; Lew, Erin D.; Dransfield, Ian; Lemke, Greg

    2014-01-01

    Apoptotic cell clearance is critical for both tissue homeostasis and the resolution of inflammation. We found that the TAM receptor tyrosine kinases Axl and Mer played distinct roles as phagocytic receptors in these two settings, where they exhibited divergent expression, regulation, and activity. Mer acted as a tolerogenic receptor in resting macrophages and in settings of immune suppression. Conversely, Axl was an inflammatory response receptor whose expression was induced by pro-inflammatory stimuli. Axl and Mer displayed distinct ligand specificities, ligand-receptor complex formation in tissues, and receptor shedding upon activation. These differences notwithstanding, phagocytosis by either protein was strictly dependent on receptor activation that was triggered by bridging TAM receptor–ligand complexes to the ‘eat-me’ signal phosphatidylserine on apoptotic cell surfaces. PMID:25194421

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

    PubMed

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

    2016-09-20

    Zika virus (ZIKV) is an emerging flavivirus that causes congenital abnormalities and Guillain-Barré syndrome. ZIKV infection also results in severe eye disease characterized by optic neuritis, chorioretinal atrophy, and blindness in newborns and conjunctivitis and uveitis in adults. We evaluated ZIKV infection of the eye by using recently developed mouse models of pathogenesis. ZIKV-inoculated mice developed conjunctivitis, panuveitis, and infection of the cornea, iris, optic nerve, and ganglion and bipolar cells in the retina. This phenotype was independent of the entry receptors Axl or Mertk, given that Axl(-/-), Mertk(-/-), and Axl(-/-)Mertk(-/-) double knockout mice sustained levels of infection similar to those of control animals. We also detected abundant viral RNA in tears, suggesting that virus might be secreted from lacrimal glands or shed from the cornea. This model provides a foundation for studying ZIKV-induced ocular disease, defining mechanisms of viral persistence, and developing therapeutic approaches for viral infections of the eye. PMID:27612415

  6. Driving device for a mining machine

    SciTech Connect

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

    1980-11-18

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

  7. 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.

  8. 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.

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

    PubMed

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

    2007-06-01

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

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

    NASA Astrophysics Data System (ADS)

    Lay, Geoff R.

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

  11. Driveline Fundamentals and Lubrication

    NASA Astrophysics Data System (ADS)

    Joseph, I.

    The various gear types and automotive transmissions in drive trains are described. The need for automotive differential axle gears is demonstrated. SAE gear lubricant classifications are related to performance specifications. Automatic transmission fluids, ATFs, are described together with agricultural and off-highway fluids. Generic formulations of driveline fluids are discussed in terms of their tribology and performance and also the contribution of various additive classes to that performance. The main functions of manual gearbox, automatic transmission and axle lubricants are described. General trends and emerging technologies in drive train components are discussed in terms of the requirements placed on the lubricant, evolution in transmission technologies and relative market penetration.

  12. 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.

  13. 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.

  14. 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.

  15. 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,…

  16. 76 FR 68306 - Airworthiness Directives; Bombardier, Inc. Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ..., 2011 (76 FR 4264). That NPRM proposed to correct an unsafe condition for the specified products. The... Axle Part Numbers Comair, Inc. (Comair) requested that we revise paragraph (g) of the NPRM (76 FR 4264...) requested that we revise the NPRM (76 FR 4264, January 25, 2011) to extend the proposed compliance time...

  17. 49 CFR 537.4 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  18. 14 CFR 23.499 - Supplementary conditions for nose wheels.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., the application of 1.33 times the full steering torque combined with a vertical reaction equal to 1.33 times the maximum static reaction on the nose gear must be assumed. However, if a torque limiting device... components at the axle must be— (1) A vertical component of 2.25 times the static load on the wheel; and...

  19. 14 CFR 23.499 - Supplementary conditions for nose wheels.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., the application of 1.33 times the full steering torque combined with a vertical reaction equal to 1.33 times the maximum static reaction on the nose gear must be assumed. However, if a torque limiting device... components at the axle must be— (1) A vertical component of 2.25 times the static load on the wheel; and...

  20. 14 CFR 23.499 - Supplementary conditions for nose wheels.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., the application of 1.33 times the full steering torque combined with a vertical reaction equal to 1.33 times the maximum static reaction on the nose gear must be assumed. However, if a torque limiting device... components at the axle must be— (1) A vertical component of 2.25 times the static load on the wheel; and...

  1. 14 CFR 23.499 - Supplementary conditions for nose wheels.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., the application of 1.33 times the full steering torque combined with a vertical reaction equal to 1.33 times the maximum static reaction on the nose gear must be assumed. However, if a torque limiting device... components at the axle must be— (1) A vertical component of 2.25 times the static load on the wheel; and...

  2. 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…

  3. 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.

  4. 49 CFR 537.4 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

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

    PubMed

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

    2012-08-17

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

  6. 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...

  7. 75 FR 65514 - Sypris Technologies, Sypris Solutions Division, Kenton, OH; Notice of Affirmative Determination...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-25

    ... articles like or directly competitive with trailer axles. The investigation also revealed that the subject... February 18, 2010, and was published in the Federal Register on March 12, 2010 (75 FR 11925). The workers... period, there was no increase in imports of articles like or directly competitive with the trailer...

  8. 49 CFR 229.45 - General condition.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... endanger the safety of the crew, locomotive or train. These conditions include: insecure attachment of components, including third rail shoes or beams, traction motors and motor gear cases, and fuel tanks; fuel... other structural infirmities of components, including quill drives, axles, gears, pinions,...

  9. 49 CFR 229.45 - General condition.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... endanger the safety of the crew, locomotive or train. These conditions include: insecure attachment of components, including third rail shoes or beams, traction motors and motor gear cases, and fuel tanks; fuel... other structural infirmities of components, including quill drives, axles, gears, pinions,...

  10. 49 CFR 229.45 - General condition.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... endanger the safety of the crew, locomotive or train. These conditions include: insecure attachment of components, including third rail shoes or beams, traction motors and motor gear cases, and fuel tanks; fuel... other structural infirmities of components, including quill drives, axles, gears, pinions,...

  11. 49 CFR 229.45 - General condition.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... endanger the safety of the crew, locomotive or train. These conditions include: insecure attachment of components, including third rail shoes or beams, traction motors and motor gear cases, and fuel tanks; fuel... other structural infirmities of components, including quill drives, axles, gears, pinions,...

  12. 49 CFR 229.45 - General condition.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... endanger the safety of the crew, locomotive or train. These conditions include: insecure attachment of components, including third rail shoes or beams, traction motors and motor gear cases, and fuel tanks; fuel... other structural infirmities of components, including quill drives, axles, gears, pinions,...

  13. 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.

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-27

    ...) metering valve body. We are issuing this AD to prevent loss of control of engine fuel flow in manual... stuck controller axles in the metering valve body. We are issuing this AD to prevent loss of control of engine fuel flow in manual control mode or mixed control mode, which can lead to engine overspeed, and...

  16. Vibration reduction on automotive shafts using piezoceramics

    NASA Astrophysics Data System (ADS)

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

    2003-08-01

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

  17. 49 CFR 571.121 - Standard No. 121; Air brake systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... is not less than 95 percent of its GVWR; and (g) Any load divider dolly. S4. Definitions... fifth wheel and to load this cargo only by means of the towed vehicle. Common diaphragm means a single.... Load divider dolly means a trailer composed of a trailer chassis and one or more axles, with no...

  18. 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...

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

    ERIC Educational Resources Information Center

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

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

  20. 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

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

    ERIC Educational Resources Information Center

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

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

  2. Thermodynamic Analysis of Allosteric and Chelate Cooperativity in Di- and Trivalent Ammonium/Crown-Ether Pseudorotaxanes.

    PubMed

    Nowosinski, Karol; von Krbek, Larissa K S; Traulsen, Nora L; Schalley, Christoph A

    2015-10-16

    A detailed thermodynamic analysis of the axle-wheel binding in di- and trivalent secondary ammonium/[24]crown-8 pseudorotaxanes is presented. Isothermal titration calorimetry (ITC) data and double mutant cycle analyses reveal an interesting interplay of positive as well as negative allosteric and positive chelate cooperativity thus providing profound insight into the effects governing multivalent binding in these pseudorotaxanes.

  3. 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…

  4. Axillary lymphoscintigraphy in the management of patients with breast cancer: A study of 341 patients

    SciTech Connect

    McLean, R.G.; Ege, G.N.

    1985-05-01

    Axillary lymphoscintigraph (AxLS) has been proposed preoperatively to diagnose breast cancer and postoperatively to predict recurrence; its role in routine management of carcinoma of the breast has not yet been determined. In a population with predominantly Stage I or II disease AxLS was performed in 140 patients who underwent surgery without axillary dissection (GpI), and in 201 whose surgery included axillary dissection (GpII), 49 of whom were studied prior to surgery; 84% of all patients were studied within 2 months of operation. Bilateral interdigital injections of Tc-99mSb/sub 2/S/sub 3/ (20MBq) were given and anterior images obtained 2 hours later. Internal mammary lymphoscintigraphy (IMLS) was performed concurrently. Scans were classed as normal (NOR) or abnormal (ABN) by adapting criteria used in interpretation of IMLS. For analysis of prognostic value, only patients with a minimum follow-up of 2 years were assessed. In patients scanned prior to surgery, AxLS sensitivity and specificity in predicting nodal involvement were 74% and 77% respectively. Clinical correlation suggests that features in the AxLS can be recognized which may be predictive of disease outcome despite the lack of direct correlation between the image and histopathological findings.

  5. 40 CFR 86.084-2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... automobile is standing and a line tangent to the front tire static loaded radius arc and touching the... level surface on which an automobile is standing to the lowest point on the axle differential of the... at a point on the underside of the automobile. Curb-idle means: (1) For manual transmission...

  6. 40 CFR 86.1218-85 - Dynamometer calibration.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... The measured absorbed road power includes the dynamometer friction as well as the power absorbed by... variations in roll bearing friction due to the drive axle weight of the vehicle. In the case of dynamometers... single inertia mass, engage the inertial flywheel or other inertial simulation system for the most...

  7. 40 CFR 86.118-78 - Dynamometer calibration.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... friction as well as the power absorbed by the power absorption unit. The dynamometer is driven above the... dynamometer. This method neglects the variations in roll bearing friction due to the drive axle weight of the... inertial simulation system for the most common vehicle mass category for which the dynamometer is used....

  8. 40 CFR 86.118-78 - Dynamometer calibration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... friction as well as the power absorbed by the power absorption unit. The dynamometer is driven above the... dynamometer. This method neglects the variations in roll bearing friction due to the drive axle weight of the... inertial simulation system for the most common vehicle mass category for which the dynamometer is used....

  9. 40 CFR 86.1218-85 - Dynamometer calibration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... The measured absorbed road power includes the dynamometer friction as well as the power absorbed by... variations in roll bearing friction due to the drive axle weight of the vehicle. In the case of dynamometers... single inertia mass, engage the inertial flywheel or other inertial simulation system for the most...

  10. 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...

  11. 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...

  12. 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...

  13. 49 CFR 571.110 - Tire selection and rims and motor home/recreation vehicle trailer load carrying capacity...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  14. 49 CFR 571.110 - Tire selection and rims and motor home/recreation vehicle trailer load carrying capacity...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  15. 49 CFR 571.110 - Tire selection and rims and motor home/recreation vehicle trailer load carrying capacity...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... GAWR of the axle system as specified on the vehicle's certification label required by 49 CFR part 567... the vehicle next to the driver's seating position. This information shall be in the English language... certification label required by § 567.4 or § 567.5 of this chapter. This information shall be in the...

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

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... GAWR of the axle system as specified on the vehicle's certification label required by 49 CFR part 567... the vehicle next to the driver's seating position. This information shall be in the English language... certification label required by § 567.4 or § 567.5 of this chapter. This information shall be in the...

  17. 49 CFR 571.110 - Tire selection and rims and motor home/recreation vehicle trailer load carrying capacity...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... GAWR of the axle system as specified on the vehicle's certification label required by 49 CFR part 567... the vehicle next to the driver's seating position. This information shall be in the English language... certification label required by § 567.4 or § 567.5 of this chapter. This information shall be in the...

  18. 49 CFR 661.11 - Rolling stock procurements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... under the procedures set forth in 19 CFR 10.11 through 10.24, the subcomponent retains its domestic... States and it does not receive tariff exemption under the procedures set forth in 19 CFR 10.11 through 10... Devices; (21) Car Axle Counters; (22) Communication Based Train Control (CBTC). (u)...

  19. 49 CFR 537.4 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  20. 49 CFR 537.4 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  1. 49 CFR 537.4 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  2. 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.

  3. 49 CFR 571.135 - Standard No. 135; Light vehicle brake systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... utilize electrical energy to actuate the foundation brakes. Functional failure means a failure of a... temperature or IBT means the average temperature of the service brakes on the hottest axle of the vehicle 0.32.... Maximum speed of a vehicle or VMax means the highest speed attainable by accelerating at a maximum...

  4. 49 CFR 571.105 - Standard No. 105; Hydraulic and electric brake systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... brake actuating forces in response to signals from one or more sensed wheels. Initial brake temperature means the average temperature of the service brakes on the hottest axle of the vehicle 0.2 mi before any... instrumentation). Maximum drive-through speed means the highest possible constant speed at which the vehicle...

  5. 78 FR 27951 - Foreign-Trade Zone (FTZ) 75-Phoenix, Arizona; Notification of Proposed Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-13

    ...(b), FTZ activity would be limited to the specific foreign-status materials and components and...; hydraulic actuators; air- turbine starters; wheel turbines; air-turbine pump systems; duct temperature...-data transducers; axles with wheel and brake assemblies; aeronautical instruments; duct...

  6. 40 CFR 205.54-1 - Low speed sound emission test procedures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... wind speed accurate within ±10 percent. (5) A thermometer for measurement of ambient temperature... material such as gravel. EC01FE92.052 (13) Vehicles with diesel engines shall be tested using Number 1D or... only for those vehicles equipped with an engine brake. (i) Select the highest rear axle...

  7. 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…

  8. 49 CFR 230.112 - Wheels and tires.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 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 axles. Prick punching or shimming the wheel fit will not be permitted. The diameter of wheels on...

  9. 49 CFR 230.112 - Wheels and tires.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Wheels and tires. 230.112 Section 230.112... Tenders Wheels and Tires § 230.112 Wheels and tires. (a) Mounting. Wheels shall be securely mounted on axles. Prick punching or shimming the wheel fit will not be permitted. The diameter of wheels on...

  10. 49 CFR 570.60 - Steering system.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... steering axle wheels in the straight ahead position, turn the steering wheel in one direction until there is a perceptible movement of the wheel. If a point on the steering wheel rim moves more than the value shown in Table 1 before perceptible return movement of the wheel under observation, there...

  11. 49 CFR 570.60 - Steering system.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... steering axle wheels in the straight ahead position, turn the steering wheel in one direction until there is a perceptible movement of the wheel. If a point on the steering wheel rim moves more than the value shown in Table 1 before perceptible return movement of the wheel under observation, there...

  12. 49 CFR 230.112 - Wheels and tires.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Wheels and tires. 230.112 Section 230.112... Tenders Wheels and Tires § 230.112 Wheels and tires. (a) Mounting. Wheels shall be securely mounted on axles. Prick punching or shimming the wheel fit will not be permitted. The diameter of wheels on...

  13. 49 CFR 229.73 - Wheel sets.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 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...

  14. 49 CFR 229.73 - Wheel sets.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 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...

  15. 49 CFR 570.60 - Steering system.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... steering axle wheels in the straight ahead position, turn the steering wheel in one direction until there is a perceptible movement of the wheel. If a point on the steering wheel rim moves more than the value shown in Table 1 before perceptible return movement of the wheel under observation, there...

  16. 49 CFR 229.115 - Slip/slide alarms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... sliding wheels on powered axles under power. When two or more locomotives are coupled in multiple or remote control, the wheel slip/slide alarm of each locomotive shall be shown in the cab of the... road service, or continue in road service following a daily inspection, unless the wheel...

  17. 49 CFR 229.115 - Slip/slide alarms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... sliding wheels on powered axles under power. When two or more locomotives are coupled in multiple or remote control, the wheel slip/slide alarm of each locomotive shall be shown in the cab of the... road service, or continue in road service following a daily inspection, unless the wheel...

  18. 49 CFR 229.73 - Wheel sets.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 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...

  19. 49 CFR 230.112 - Wheels and tires.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Wheels and tires. 230.112 Section 230.112... Tenders Wheels and Tires § 230.112 Wheels and tires. (a) Mounting. Wheels shall be securely mounted on axles. Prick punching or shimming the wheel fit will not be permitted. The diameter of wheels on...

  20. 6. VIEW OF BORING MILL. Chuck action of locomotive wheel ...

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

    6. VIEW OF BORING MILL. Chuck action of locomotive wheel Wheel weight 1200 pounds, 3'-0' diameter. Table 53' in diameter Wheel is 48'. Largest hole that can be bored is 9-1/2' plus (GE axle is 10'). - Juniata Shops, Erecting Shop & Machine Shop, East of Fourth Avenue, between Fourth & Fifth Streets, Altoona, Blair County, PA

  1. 49 CFR 229.73 - Wheel sets.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 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...

  2. 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...

  3. 49 CFR 229.115 - Slip/slide alarms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... sliding wheels on powered axles under power. When two or more locomotives are coupled in multiple or remote control, the wheel slip/slide alarm of each locomotive shall be shown in the cab of the... road service, or continue in road service following a daily inspection, unless the wheel...

  4. [Experience of obesity's treatment by an interdisciplinary team].

    PubMed

    Vindevogel, M; Farber, B; Gourmet, L M; Verbanck, P; Kutnowski, M; Minner, P

    2006-09-01

    Owing to the multifactorial origin of obesity, we have created an interdisciplinary team devoted to a limited-in-time treatment, following three axles : nutritional education, body self-perception and emotions expression. The philosophy of this approach and some results are presented.

  5. 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…

  6. 16 CFR 1512.9 - Requirements for protective guards.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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

  7. 49 CFR 230.112 - Wheels and tires.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... wheels mounted on the same axle shall not vary more than 1/4 inch. (d) Tire thickness. Wheels may not have tires with a minimum thickness less than that indicated in the table in this paragraph (d). When retaining rings are used, measurements of tires to be taken from the outside circumference of the ring,...

  8. 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.

  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. 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,…

  11. 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,…

  12. Pseudorotaxanes with self-sorted sequence and stereochemical orientation.

    PubMed

    Talotta, Carmen; Gaeta, Carmine; Qi, Zhenhui; Schalley, Christoph A; Neri, Placido

    2013-07-15

    Partner preferences in pseudorotaxane formation were exploited to establish an integrative self-sorting system able to discriminate simultaneously at the sequence and stereochemical level (see picture). It was found that calix[6]arenes were threaded selectively with a preferred orientation onto bisammonium axles, even when the structural differences between the possible building blocks were small and located remote from the binding sites.

  13. 78 FR 43965 - American Honda Motor Co., Inc., Receipt of Petition for Decision of Inconsequential Noncompliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-22

    ... Federal Register published on April 11, 2000, (65 FR 19477-78). The petition, supporting materials, and.... The maximum load capacity for each of the P225/45ZR 18 95Y tires for this vehicle is 575 kilograms (1... Gross Axle Weight Ratings (GAWR) for a 2011 or 2012 Acura TSX is 546.6 kilograms (1,207.2 lbs) for...

  14. 76 FR 9717 - Parts and Accessories Necessary for Safe Operation; Saddle-Mount Braking Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-22

    ... address, an e-mail address, or a phone number in the body of your document so that FMCSA can contact you... complete Privacy Act Statement in the Federal Register notice published on April 11, 2000 (65 FR 19476). II... after March 1, 1998.\\5\\ (70 FR 48008, Aug. 15, 2005). The axle weight of an unladen dolly is so low...

  15. 49 CFR 393.48 - Brakes to be operative.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (regardless of whether or not an antilock system failure has occurred on any axle). The device must not be operable by the driver except upon application of the control that activates the braking system. The device... with air brakes) or 85 percent of the maximum system pressure (for vehicles which are not equipped...

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-03

    ... airworthiness directive (AD) for certain of The Boeing Company Model 777 airplanes. This AD was prompted by heat... issuing this AD to detect and correct cracking in the MLG center axle and shock strut inner cylinder lugs... Register on May 1, 2012 (77 FR 25647). That NPRM proposed to require repetitive lubrication of the...

  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. 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…

  19. 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…

  20. 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…

  1. 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…

  2. 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)

  3. 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…

  4. 49 CFR 567.5 - Requirements for manufacturers of vehicles manufactured in two or more stages.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... appropriate value in kilograms and (pounds) for each axle, identified in order from front to rear (e.g., front... type classification of the vehicle as defined in 49 CFR 571.3 (e.g., truck, MPV, bus, trailer). (e... specified in 49 CFR 567.4(c) are not practicable, the label may be provided as part of the IVD package...

  5. Cam drive internal combustion engine

    SciTech Connect

    Vadnjal, I.

    1993-06-01

    A cam drive internal combustion engine is described, comprising, a cylindrical crank case housing, and an axle co-axially directed through the crank case housing, and a cam ring fixedly mounted to the axle medially of the axle in an orthogonal relationship relative thereto, and a predetermined number of first cylinder bores positioned in an equally spaced annular array on a first side of the cam ring, and second cylinder bores positioned on a second side of the cam ring within the crank case housing, with said second cylinder bores defining a number equal to the predetermined number, wherein each cylinder bore of said first set of cylinders bores is co axially aligned with one of said cylinder bores of said second set of cylinder bores, and the first set of cylinder bores each include a first piston reciprocatably mounted there within, and the second set of cylinder bores include a second piston reciprocatably mounted there within, and the first set of pistons each include a first piston rod, and the second set of pistons each include a second piston rod, wherein the first piston rods and second piston rod are arranged parallel relative to the axle, and the first piston rods include rollers mounted thereon, and the second piston rods include second rollers mounted thereon, the cam ring including a first cam surface rotatably mounting the first rollers, and the cam ring further including a second cam surface mounting the second cam rollers rotatably thereon.

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Vehicles, Tires, Tubes, Tread Rubber, and Taxable Fuel Automotive and Related Items § 48.4061(a)-1... be subject to the tax on automotive parts or accessories imposed by section 4061(b). Therefore, the... chassis frame, the axle capacity and placement, and the spring, brake, rim, and tire capacities....

  7. 49 CFR 570.9 - Tires.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... OF TRANSPORTATION VEHICLE IN USE INSPECTION STANDARDS Vehicles With GVWR of 10,000 Pounds or Less... vehicles other than passenger cars, it may be necessary to measure tread depth with a tread gauge. (b) Type. Vehicle shall be equipped with tires on the same axle that are matched in tire size...

  8. 49 CFR 570.9 - Tires.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OF TRANSPORTATION VEHICLE IN USE INSPECTION STANDARDS Vehicles With GVWR of 10,000 Pounds or Less... vehicles other than passenger cars, it may be necessary to measure tread depth with a tread gauge. (b) Type. Vehicle shall be equipped with tires on the same axle that are matched in tire size...

  9. 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

  10. Sucker rod guide

    SciTech Connect

    White, R.C.

    1988-10-25

    This patent describes an improved guide for use in a string of sucker rods for reciprocation in a tubing string in a borehole, the sucker rods having threaded male ends, the guide comprising: an elongated upright cylindrical member of external diameter less than the internal diameter of tubing in which it is to be used, the member having sucker rod receiving female threaded openings at the upper and lower ends, the threaded openings being coaxial of the member cylindrical axis whereby the member may be positioned in a string of sucker rods, and including a plurality of spaced-apart parallel sided slots within the member, each slot being of semi-circular configuration and of depth greater than the radius and less than the diameter of the cylindrical member, the sidewalls of each slot being parallel to and equally spaced from a plane of the member cylindrical axis; the member having an axle bore therein for each of the slots, the axle bores being parallel and spaced apart from each other, a plane of the axis of each bore being perpendicular the member cylindrical axis and the axis of each bore being displaced away from the member cylindrical axis; an axle received in each axle bore; and a wheel received on each axle the diameter of each wheel being approximately the diameter of the cylindrical member, the periphery of each wheel extending beyond the member cylindrical wall whereby the wheels are positioned to engage and roll on the internal cylindrical surface of tubing, the planes of adjacent slots in the member being rotationally displaced from each other, a portion of each wheel extending beyond the cylindrical surface of the member, the opposed portion of each wheel being within the confines of the member cylindrical surface whereby each wheel can contact a tubing wall at only one point on its cylindrical surface.

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

    PubMed

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

    2016-06-20

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

  12. 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.

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

    PubMed

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

    2016-09-01

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

  14. Solar concentrator

    SciTech Connect

    Smyth, J.S.

    1982-06-08

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

  15. Acoustofluidic actuation of in situ fabricated microrotors.

    PubMed

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

    2016-09-21

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

  16. 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.

  17. 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.

  18. 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.

  19. 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

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

    PubMed

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

    2016-09-01

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

  1. Photocontrolled On-Surface Pseudorotaxane Formation with Well-Ordered Macrocycle Multilayers.

    PubMed

    Schwarz, Felix B; Heinrich, Thomas; Kaufmann, J Ole; Lippitz, Andreas; Puttreddy, Rakesh; Rissanen, Kari; Unger, Wolfgang E S; Schalley, Christoph A

    2016-09-26

    The photoinduced pseudorotaxane formation between a photoresponsive axle and a tetralactam macrocycle was investigated in solution and on glass surfaces with immobilized multilayers of macrocycles. In the course of this reaction, a novel photoswitchable binding station with azobenzene as the photoswitchable unit and diketopiperazine as the binding station was synthesized and studied by NMR and UV/Vis spectroscopy. Glass surfaces have been functionalized with pyridine-terminated SAMs and subsequently with multilayers of macrocycles through layer-by-layer self assembly. A preferred orientation of the macrocycles could be confirmed by NEXAFS spectroscopy. The photocontrolled deposition of the axle into the surface-bound macrocycle-multilayers was monitored by UV/Vis spectroscopy and led to an increase of the molecular order, as indicated by more substantial linear dichroism effects in angle-resolved NEXAFS spectra. PMID:27539781

  2. Laithwaite's Heavy Spinning Disk Demonstration

    NASA Astrophysics Data System (ADS)

    Cross, Rod

    2014-09-01

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

  3. Fast tracking using edge histograms

    NASA Astrophysics Data System (ADS)

    Rokita, Przemyslaw

    1997-04-01

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

  4. 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.

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

    NASA Astrophysics Data System (ADS)

    Klomp, Matthijs; Gao, Yunlong; Bruzelius, Fredrik

    2014-05-01

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

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

    PubMed

    Gong, Zheng; Sun, Junhua; Zhang, Guangjun

    2016-01-01

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

  7. 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.

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

    SciTech Connect

    Beshears, David L; Scudiere, Matthew B; White, Clifford P

    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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. Apparatus for raising or tilting a micromechanical structure

    SciTech Connect

    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.

  16. Dual Involvement of Growth Arrest-Specific Gene 6 in the Early Phase of Human IgA Nephropathy

    PubMed Central

    Kake, Takei; Fukushima, Naoshi; Matsuura, Motokazu; Shibata, Eriko; Yamada, Satoshi; Yoshikawa, Kazuhiro; Kanayama, Hiro-omi; Fukawa, Tomoya; Yamaguchi, Kunihisa; Izaki, Hirofumi; Mima, Akira; Abe, Naoko; Araoka, Toshikazu; Murakami, Taichi; Kishi, Fumi; Kishi, Seiji; Tominaga, Tatsuya; Moriya, Tatsumi; Abe, Hideharu; Doi, Toshio

    2013-01-01

    Background Gas6 is a growth factor that causes proliferation of mesangial cells in the development of glomerulonephritis. Gas6 can bind to three kinds of receptors; Axl, Dtk, and Mer. However, their expression and functions are not entirely clear in the different glomerular cell types. Meanwhile, representative cell cycle regulatory protein p27 has been reported to be expressed in podocytes in normal glomeruli with decreased expression in proliferating glomeruli, which inversely correlated with mesangial proliferation in human IgA nephropathy (IgAN). Methods The aim of this study is to clarify Gas6 involvement in the progression of IgAN. Expression of Gas6/Axl/Dtk was examined in 31 biopsy proven IgAN cases. We compared the expression levels with histological severity or clinical data. Moreover, we investigated the expression of Gas6 and its receptors in cultured podocytes. Results In 28 of 31 cases, Gas6 was upregulated mainly in podocytes. In the other 3 cases, Gas6 expression was induced in endothelial and mesangial cells, which was similar to animal nephritis models. Among 28 podocyte type cases, the expression level of Gas6 correlated with the mesangial hypercellularity score of IgAN Oxford classification and urine protein excretion. It also inversely correlated with p27 expression in glomeruli. As for the receptors, Axl was mainly expressed in endothelial and mesangial cells, while Dtk was expressed in podocytes. In vitro, Dtk was expressed in cultured murine podocytes, and the expression of p27 was decreased by Gas6 stimulation. Conclusions Gas6 was uniquely upregulated in either endothelial/mesangial cells or podocytes in IgAN. The expression pattern can be used as a marker to classify IgAN. Gas6 has a possibility to be involved in not only mesangial proliferation via Axl, but also podocyte injury via Dtk in IgAN. PMID:23826128

  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. 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. PMID:27688910

  19. A chromophoric switch based on pseudorotaxanes

    NASA Astrophysics Data System (ADS)

    Liu, Yu; Li, Chun-Ju; Zhang, Heng-Yi; Wang, Li-Hua; Luo, Qian; Wang, Ge

    2007-02-01

    In a three-component system containing dibenzo-24-crown-8 (1), diamino-dibenzo-24-crown-8 (2), and 1,2-bis(4,4'-dipyridyl)ethane (32+), axle 32+ can shuttle between wheels 1 and 2 by acid-base control, accompanying color changes from yellow to red. This system could not only be taken as a chromophoric supramolecular switch, but also exhibit a function as INHIBIT logic gate.

  20. A chromophoric switch based on pseudorotaxanes.

    PubMed

    Liu, Yu; Li, Chun-Ju; Zhang, Heng-Yi; Wang, Li-Hua; Luo, Qian; Wang, Ge

    2007-02-14

    In a three-component system containing dibenzo-24-crown-8 (1), diamino-dibenzo-24-crown-8 (2), and 1,2-bis(4,4(')-dipyridyl)ethane (3(2+)), axle 3(2+) can shuttle between wheels 1 and 2 by acid-base control, accompanying color changes from yellow to red. This system could not only be taken as a chromophoric supramolecular switch, but also exhibit a function as INHIBIT logic gate.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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…

  7. 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.

  8. 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.

  9. 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.

  10. 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.

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

    PubMed

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

    2014-06-01

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

  12. Active roll control for rollover prevention of heavy articulated vehicles with multiple-rollover-index minimisation

    NASA Astrophysics Data System (ADS)

    Huang, Hsun-Hsuan; Yedavalli, Rama K.; Guenther, Dennis A.

    2012-03-01

    This paper presents the application of a nominal control design algorithm for rollover prevention of heavy articulated vehicles with active anti-roll-bar control. This proposed methodology is based on an extension of linear quadratic regulator control for 'state derivative-induced (control coupled) output regulation' problems. For heavy articulated vehicles with multiple axles, a performance index with multiple rollover indices is proposed. The proposed methodology allows us to compare the usefulness of various control configurations (i.e. actuators at different axles of the vehicle) based on the interaction of this control configuration with vehicle dynamics. Application of this methodology to a specific heavy articulated vehicle with a tractor semi-trailer shows that a single active anti-roll-bar system at the trailer unit gives better performance than multiple-axle actuators at tractor and trailer together with the single lane change manoeuvre as the external disturbance. Thus, the proposed methodology of this paper not only highlights the importance of the interactions between control and vehicle dynamics in rollover prevention problems but, in fact, proposes a novel technique to exploit the benefits of these interactions judiciously.

  13. 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.

  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. PMID:26236772

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

    DOEpatents

    Woolley, Robert D.

    1998-01-01

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

  16. 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.

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

    PubMed

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

    2016-06-16

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

  18. 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. PMID:24699971

  19. 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

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

    PubMed

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

    2011-08-25

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

  1. 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

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

    PubMed

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

    2016-06-16

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

  3. 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.

  4. Vehicle with magnetic engine

    SciTech Connect

    Wortham, C.

    1993-06-15

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

  5. TAM receptors regulate multiple features of microglial physiology.

    PubMed

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

    2016-04-14

    Microglia are damage sensors for the central nervous system (CNS), and the phagocytes responsible for routine non-inflammatory clearance of dead brain cells. Here we show that the TAM receptor tyrosine kinases Mer and Axl regulate these microglial functions. We find that adult mice deficient in microglial Mer and Axl exhibit a marked accumulation of apoptotic cells specifically in neurogenic regions of the CNS, and that microglial phagocytosis of the apoptotic cells generated during adult neurogenesis is normally driven by both TAM receptor ligands Gas6 and protein S. Using live two-photon imaging, we demonstrate that the microglial response to brain damage is also TAM-regulated, as TAM-deficient microglia display reduced process motility and delayed convergence to sites of injury. Finally, we show that microglial expression of Axl is prominently upregulated in the inflammatory environment that develops in a mouse model of Parkinson's disease. Together, these results establish TAM receptors as both controllers of microglial physiology and potential targets for therapeutic intervention in CNS disease. PMID:27049947

  6. 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.

  7. Variations of archived static-weight data and WIM

    SciTech Connect

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

    1998-12-01

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

  8. 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

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

    PubMed Central

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

    2015-01-01

    Objective: Growth arrest-specific 6 (Gas6) is a newly discovered vitamin K-dependent protein, which is a ligand for TAM receptors [Tyro3 (Sky), Axl, and Mer] from the tyrosine kinase family. Gas6 knockout mice were resistant to venous and arterial thrombosis. There are contradictory reports on the presence of Gas6 and its receptors in mouse platelets. The objective of this study was to investigate whether Gas6 and its receptors were present in mouse platelets or not. Materials and Methods: Specific pathogen-free BALB/c male and female mice of 8-10 weeks old and 25-30 g in weight were anesthetized under light ether anesthesia and blood samples were taken from their hearts. RNAs were isolated from isolated platelets, and then mRNAs encoding Gas6 and TAM receptors were detected by reverse transcription-polymerase chain reaction (RT-PCR). Protein concentrations of Gas6 and TAM receptors in platelets were measured by ELISA, but not those of Mer, because of the absence of any commercial ELISA kit for mouse specimens. Results: RT-PCR results indicated the presence of mRNAs encoding Gas6 and Mer in mouse platelets. However, although RT-PCR reactions were performed at various temperatures and cycles, we could not detect the presence of mRNAs encoding Axl and Tyro3 (Sky). Receptor protein levels of Axl and Tyro3 were below the detection limits of the ELISA method. Conclusion: We found the presence of mRNAs encoding Gas6 and the receptor Mer in mouse platelets, but not Axl and Tyro3. Gas6, Axl, and Tyro3 protein levels were below the detection limits of the ELISA. The presence of mRNA is not obvious evidence of protein expression in platelets that have no nucleus or DNA. Further studies are required to clarify the presence of Gas6/TAM receptors in platelets using real-time PCR and more sensitive immunological methods, and future studies on mechanisms will indicate whether the Gas6/TAM pathway is a strategy for treatment of disorders. PMID:25805676

  10. 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

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

    PubMed Central

    Zhao, Rui; Li, Yan; Dai, Wen

    2016-01-01

    Epidemiological studies have shown a high prevalence of low serum testosterone levels in men with cardiovascular disease. Moreover, the tyrosine kinase receptor Axl, the ligand of which is growth arrest-specific protein 6 (GAS6), is expressed in the vasculature, and serum GAS6 levels are associated with endothelial dysfunction and cardiovascular events. Testosterone regulates GAS6 gene transcription directly, which inhibits calcification of vascular smooth muscle cells and provides a mechanistic insight into the cardioprotective action of androgens. This study was designed to determine the correlation between serum GAS6 and testosterone levels in male patients with coronary heart disease (CHD). We recruited 225 patients with CHD and 102 apparently healthy controls. Serum concentrations of GAS6 and soluble Axl were quantified by an enzyme-linked immunosorbent assay. Levels of high-sensitivity C-reactive protein, testosterone, estradiol, and other routine biochemical markers were also measured. Testosterone decreased from 432.69 ± 14.40 to 300.76 ± 6.23 ng dl−1 (P < 0.001) and GAS6 decreased from 16.20 ± 0.31 to 12.51 ± 0.19 ng ml−1 (P < 0.001) in patients with CHD, compared with control subjects. Multiple linear regression analysis showed that serum testosterone and GAS6 levels were positively associated in male patients with CHD. Alterations in GAS6 levels may influence the development of CHD. Downregulation of GAS6/Axl signaling in the presence of low sex hormone levels during disease progression is a potential mechanism by which GAS6 affects CHD. This study provides novel results regarding the influence of sex hormones on serum GAS6 levels in patients with CHD. PMID:26924277

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Beyond Scheme F

    SciTech Connect

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

    1996-07-01

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

  18. 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.

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

    PubMed

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

    2004-10-15

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  2. BLAISDELL SLOW SAND FILTER WASHING MACHINE. VIEW LOOKING SOUTH. THE ...

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

    BLAISDELL SLOW SAND FILTER WASHING MACHINE. VIEW LOOKING SOUTH. THE SUCTION (INTAKE) HOSE IS SEEN AT THE LEFT RESTING ON THE FILTER BED SURFACE; THE DISCHARGE HOSE IS AT THE RIGHT, RUNNING FROM THE BOTTOM OF THE CENTRAL VERTICAL AXLE TO THE CENTRIFUGAL PUMP. FROM THE PUMP WATER IS DISCHARGED THROUGH THE HORIZONTAL PIPE LOCATED UNDER THE EDGE OF PLATFORM DECK INTO THE WASTE-WATER TROUGH (NOT SEEN IN THIS VIEW). - Yuma Main Street Water Treatment Plant, Blaisdell Slow Sand Filter Washing Machine, Jones Street at foot of Main Street, Yuma, Yuma County, AZ

  3. Kinematic and dynamic analysis of a heavy truck with individual front suspension

    NASA Astrophysics Data System (ADS)

    Yarmohamadi, Hoda; Berbyuk, Viktor

    2013-06-01

    The main focus of this work is on the characteristics of a commercial vehicle with individual front suspension (IFS). Both kinematic and dynamic properties of the vehicle are investigated through simulations and analytical expressions. Moreover, employing the model of the tractor semitrailer combination, the study presents the results of comparison between the trucks with IFS and rigid front axle with respect to comfort and handling. This is done by analysing the responses of the vehicles to different road and steering inputs. The obtained results show enhanced comfort and steering feeling for the truck with IFS.

  4. Device to relieve sucker rod torque below ground level in a petroleum well

    SciTech Connect

    Dysarz, E.D.

    1987-12-22

    An apparatus is described for use in a sucker rod string having a polished rod for relieving torque below the polished rod and inside of a well while the sucker rod string is moving up and down inside of the well, comprising: a body, the body that is suitably fastened to the lower end of the polished rod; at least one set of rollers that are suitably mounted within the body by axles, the rollers with a diameter greater than the width of the body; a lower swivel, and a guide. The guide is a tube that is square in section and is set vertically within the well.

  5. 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.

  6. 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.

  7. Photovoltaic panel clamp

    DOEpatents

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

    2012-06-05

    A photovoltaic panel clamp includes an upper and lower section. The interface between the assembled clamp halves and the module edge is filled by a flexible gasket material, such as EPDM rubber. The gasket preferably has small, finger like protrusions that allow for easy insertion onto the module edge while being reversed makes it more difficult to remove them from the module once installed. The clamp includes mounting posts or an integral axle to engage a bracket. The clamp also may include a locking tongue to secure the clamp to a bracket.

  8. Reliability-based robust design optimization of vehicle components, Part I: Theory

    NASA Astrophysics Data System (ADS)

    Zhang, Yimin

    2015-06-01

    The reliability-based design optimization, the reliability sensitivity analysis and robust design method are employed to present a practical and effective approach for reliability-based robust design optimization of vehicle components. A procedure for reliability-based robust design optimization of vehicle components is proposed. Application of the method is illustrated by reliability-based robust design optimization of axle and spring. Numerical results have shown that the proposed method can be trusted to perform reliability-based robust design optimization of vehicle components.

  9. A theory of wheelchair wheelie performance.

    PubMed

    Kauzlarich, J J; Thacker, J G

    1987-01-01

    The results of this analytical study of wheelchair wheelie performance can be summarized into two wheelchair design equations, or rules of thumb, as developed in the paper. The equation containing the significant parameters involved in popping a wheelie for curb climbing is: fh = 0.8 mg theta c.g. [A] where fh is handrim force, m is the mass of the wheelchair + user less rear wheels, g is acceleration of gravity (9.807 m/s2), and theta c.g. is "c.g. angle," i.e., the angle between the vertical through the rear axle and a line connecting the rear axle and the system center-of-gravity. Equation [A] shows that reducing the mass and/or the c.g. angle will make it easier to pop a wheelie. The c.g. angle is reduced by moving the rear axle position forward on the wheelchair. Wheelie balance is the other aspect of performance considered; where the user balances the wheelchair on the rear wheels for going down curbs or just for fun. The ease with which a system can be controlled (balanced) is related to the static stability of the system. The static stability is defined as: omega 2 = mgl/J [B] where J is the mass moment of inertia at the center of gravity of the system about the direction perpendicular to the sideframe. For better wheelchair control during wheelchair balance the static stability should be reduced. Measurements of the value for the polar mass moment of inertia for a typical wheelchair + user of m = 90 kg was found to be J = 8.7 kg-m2. In order to decrease the value of the static stability, Equation [B], one can increase J or decrease m and/or l, where l is the distance from the rear axle to the c.g. of the system. It is also shown that balancing a rod in the palm of the hand (inverted pendulum) is a mathematical problem similar to the wheelie balance problem, and a rod of length 1.56 meters is similar to a wheelchair + user system mass of 90 kg. However, balancing a rod is done primarily by using visual perception, whereas wheelie balance involves human

  10. Synthesis of fluorescent dye-tagged nanomachines for single-molecule fluorescence spectroscopy.

    PubMed

    Vives, Guillaume; Guerrero, Jason M; Godoy, Jazmin; Khatua, Saumyakanti; Wang, Yu-Pu; Kiappes, J L; Link, Stephan; Tour, James M

    2010-10-01

    In an effort to elucidate the mechanism of movement of nanovehicles on nonconducting surfaces, the synthesis and optical properties of five fluorescently tagged nanocars are reported. The nanocars were specifically designed for studies by single-molecule fluorescence spectroscopy and bear a tetramethylrhodamine isothiocyanate fluorescent tag for excitation at 532 nm. The molecules were designed such that the arrangement of their molecular axles and p-carborane wheels relative to the chassis would be conducive to the control of directionality in the motion of these nanovehicles.

  11. 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.

  12. Structural analysis in real time using continuous monitoring

    NASA Astrophysics Data System (ADS)

    Braunstein, Juergen; Viano, Charles; Hodac, Bernard

    2005-05-01

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

  13. 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. 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.

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

    SciTech Connect

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

    2012-01-01

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

  16. 49 CFR Appendix B to Part 215 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... length; or 5/8″ or more in width 5,000 7,500 (f) Slid flat or shelled spot(s): (1)(i) One spot more than 21/2″, but less than 3″, in length 2,500 5,000 (ii) One spot 3″ or more in length 5,000 7,500 (2)(i... than 41/2″ 2,500 5,000 (2) 41/2″ or more 5,000 7,500 (i) Welded 5,000 7,500 215.105Defective axle:...

  17. 49 CFR Appendix B to Part 215 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... length; or 5/8″ or more in width 5,000 7,500 (f) Slid flat or shelled spot(s): (1)(i) One spot more than 21/2″, but less than 3″, in length 2,500 5,000 (ii) One spot 3″ or more in length 5,000 7,500 (2)(i... than 41/2″ 2,500 5,000 (2) 41/2″ or more 5,000 7,500 (i) Welded 5,000 7,500 215.105Defective axle:...

  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. 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.

  20. 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.

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

    NASA Astrophysics Data System (ADS)

    Zhang, Yimin

    2015-06-01

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

  2. Anion Sensing by Solution- and Surface-Assembled Osmium(II) Bipyridyl Rotaxanes

    PubMed Central

    Lehr, Joshua; Lang, Thomas; Blackburn, Octavia A; Barendt, Timothy A; Faulkner, Stephen; Davis, Jason J; Beer, Paul D

    2013-01-01

    We report the preparation of [2]rotaxanes containing an electrochemically and optically active osmium(II) bipyridyl macrocyclic component mechanically bonded with cationic pyridinium axles. Such interlocked host systems are demonstrated to recognise and sense anionic guest species as shown by 1H NMR, luminescence and electrochemical studies. The rotaxanes can be surface assembled on to gold electrodes through anion templation under click copper(I)-catalysed Huisgen cycloaddition conditions to form rotaxane molecular films, which, after template removal, respond electrochemically and selectively to chloride. PMID:24127251

  3. 26. SOUTH TO CIRCA 1865 METALTURNING LATHE (POSSIBLY MADE BY ...

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

    26. SOUTH TO CIRCA 1865 METAL-TURNING LATHE (POSSIBLY MADE BY AMES MFG. CO., CHICOPEE, MASS.) WITH PARTS/TOOL BINS ALONG EAST INTERIOR WALL OF FACTORY. BENEATH THE LATHE ON THE FLOOR IS A STACK OF AUTOMOBILE AXLES AS 'RAW MATERIAL' FOR FABRICATING REPAIR PARTS FOR PUMPS AND WATER SUPPLY EQUIPMENT. ON THE POST BEHIND THE MACHINE IS ONE OF THE HISTORIC ELECTRICAL FUSE/SWITCH BOXES FOR THE FACTORY. - Kregel Windmill Company Factory, 1416 Central Avenue, Nebraska City, Otoe County, NE

  4. Low-Noise Spiral Bevel Gears

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

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

  5. A synthetic approach to a molecular crank mechanism: toward intramolecular motion transformation between rotation and translation.

    PubMed

    Okuno, Erika; Hiraoka, Shuichi; Shionoya, Mitsuhiko

    2010-05-01

    A molecular crank mechanism that enables transformation between rotational and translational motions was designed and synthesized. This molecule consists of a molecular ball bearing as the rotational part in which two disk-shaped rotors can rotate relative to each other through ligand exchange and flipping motion, and a [2]rotaxane as a translational part in which an axle molecule can move back-and-forth through the cavity of a crown ether-based macrocycle. (1)H NMR analysis revealed that these two motions influence each other.

  6. Potential advantages of CUDC-101, a multitargeted HDAC, EGFR, and HER2 inhibitor, in treating drug resistance and preventing cancer cell migration and invasion.

    PubMed

    Wang, Jing; Pursell, Natalie W; Samson, Maria Elena S; Atoyan, Ruzanna; Ma, Anna W; Selmi, Abdelkader; Xu, Wanlu; Cai, Xiong; Voi, Maurizio; Savagner, Pierre; Lai, Cheng-Jung

    2013-06-01

    CUDC-101 is a novel, small-molecule, anticancer agent targeting histone deacetylase (HDAC), EGF receptor (EGFR), and HER2. It is currently in phase I clinical development in patients with solid tumors. Previously, we reported that CUDC-101 has potent antiproliferative and proapoptotic activity in cultured tumor cells and in vivo xenograft models. We now show that cancer cells that have acquired resistance to single-target EGFR inhibitors through upregulation of AXL or loss of E-cadherin remain sensitive to CUDC-101, which inhibits MET- and AXL-mediated signaling, restores E-cadherin expression, and reduces cell migration. CUDC-101 also efficiently inhibited the proliferation of MET-overexpressing non-small cell lung cancer and gastric cancer cell lines and inhibited the migration and invasion of invasive tumor cells. Taken together, these results suggest that coupling HDAC and HER2 inhibitory activities to an EGFR inhibitor may potentially be effective in overcoming drug resistance and preventing cancer cell migration.

  7. 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.

  8. Characterization of the cytotoxic activity of [2]rotaxane (TRO-A0001), a novel supramolecular compound, in cancer cells.

    PubMed

    Fujita, Yoshihiko; Kimura, Masahiko; Sato, Hiroki; Takata, Toshikazu; Ono, Nobufumi; Nishio, Kazuto

    2016-06-01

    Rotaxanes comprise a class of interlocked molecules containing a wheel threaded onto an axle with blocking groups on the ends to keep the wheel from sliding off. Here, we show that [2][bis(2-(3,5-dimethylphenylcarbonyloxy)ethyl) ammoniumtrifluoromethanesulfonate]-[dibenzo-24-crown-8] rotaxane (TRO-A0001), a rotaxane compound, exerted a growth inhibitory effect on several human cancer cell lines. An MTT assay revealed an IC50 of 14-830 nM for TRO-A0001 in these cells. Neither the wheel nor the axle part alone inhibited tumor cell growth, suggesting that the complete rotaxane molecule with its unique "intramolecular mobility" is required to inhibit cell growth. Annexin-V/PI staining provided evidence of the induction of apoptosis, which was further confirmed by the observation of poly (ADP-ribose) polymerase cleavage. Furthermore, a cell cycle analysis using flow cytometry showed that TRO-A0001 treatment resulted in G1 arrest in glioblastoma T98G and melanoma G361 cells. An immunoblot analysis revealed that in both cell lines, TRO-A0001 treatment caused the induction of p21/Cip1, thereby down-regulating Cdks 2, 4 and 6 and reducing Cyclins D1 and E. The results presented in this study demonstrate cytotoxicity of the rotaxane compound and its potential as a lead compound for the development of a chemotherapeutic agent against cancer. PMID:27052614

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  10. Analysis of Ebola Virus Entry Into Macrophages.

    PubMed

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

    2015-10-01

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

  11. 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.

  12. Dynamic pavement deflection

    NASA Astrophysics Data System (ADS)

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

    1981-06-01

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

  13. A hub dynamometer for measurement of wheel forces in off-road bicycling.

    PubMed

    De Lorenzo, D S; Hull, M L

    1999-02-01

    A dynamometric hubset that measures the two ground contact force components acting on a bicycle wheel in the plane of the bicycle during off-road riding while either coasting or braking was designed, constructed, and evaluated. To maintain compatibility with standard mountain bike construction, the hubs use commercially available shells with modified, strain gage-equipped axles. The axle strain gages are sensitive to forces acting in the radial and tangential directions, while minimizing sensitivity to transverse forces, steering moments, and variations in the lateral location of the center of pressure. Static calibration and a subsequent accuracy check that computed differences between applied and apparent loads developed during coasting revealed root mean squared errors of 1 percent full-scale or less (full-scale load = 4500 N). The natural frequency of the rear hub with the wheel attached exceeded 350 Hz. These performance capabilities make the dynamometer useful for its intended purpose during coasting. To demonstrate this usefulness, sample ground contact forces are presented for a subject who coasted downhill over rough terrain. The dynamometric hubset can also be used to determine ground contact forces during braking providing that the brake reaction force components are known. However, compliance of the fork can lead to high cross-sensitivity and corresponding large (> 5 percent FS) measurement errors at the front wheel.

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

    NASA Astrophysics Data System (ADS)

    Hac', A.; Youn, I.

    1993-10-01

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

  15. 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.

  16. 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.

  17. 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.

  18. Use of Finite Elements Analysis for a Weigh-in-Motion Sensor Design

    PubMed Central

    Opitz, Rigobert; Goanta, Viorel; Carlescu, Petru; Barsanescu, Paul-Doru; Taranu, Nicolae; Banu, Oana

    2012-01-01

    High speed weigh-in-motion (WIM) sensors are utilized as components of complex traffic monitoring and measurement systems. They should be able to determine the weights on wheels, axles and vehicle gross weights, and to help the classification of vehicles (depending on the number of axles). WIM sensors must meet the following main requirements: good accuracy, high endurance, low price and easy installation in the road structure. It is not advisable to use cheap materials in constructing these devices for lower prices, since the sensors are normally working in harsh environmental conditions such as temperatures between −40 °C and +70 °C, dust, temporary water immersion, shocks and vibrations. Consequently, less expensive manufacturing technologies are recommended. Because the installation cost in the road structure is high and proportional to the WIM sensor cross section (especially with its thickness), the device needs to be made as flat as possible. The WIM sensor model presented and analyzed in this paper uses a spring element equipped with strain gages. Using Finite Element Analysis (FEA), the authors have attempted to obtain a more sensitive, reliable, lower profile and overall cheaper elastic element for a new WIM sensor. PMID:22969332

  19. 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. PMID:25397962

  20. 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.

  1. 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

  2. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

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

  4. 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.

  5. 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.

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

    PubMed Central

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

    2015-01-01

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

  7. 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.

  8. Analysis of Ebola Virus Entry Into Macrophages

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  10. Driver assistance system for passive multi-trailer vehicles with haptic steering limitations on the leading unit.

    PubMed

    Morales, Jesús; Mandow, Anthony; Martínez, Jorge L; Reina, Antonio J; García-Cerezo, Alfonso

    2013-01-01

    Driving vehicles with one or more passive trailers has difficulties in both forward and backward motion due to inter-unit collisions, jackknife, and lack of visibility. Consequently, advanced driver assistance systems (ADAS) for multi-trailer combinations can be beneficial to accident avoidance as well as to driver comfort. The ADAS proposed in this paper aims to prevent unsafe steering commands by means of a haptic handwheel. Furthermore, when driving in reverse, the steering-wheel and pedals can be used as if the vehicle was driven from the back of the last trailer with visual aid from a rear-view camera. This solution, which can be implemented in drive-by-wire vehicles with hitch angle sensors, profits from two methods previously developed by the authors: safe steering by applying a curvature limitation to the leading unit, and a virtual tractor concept for backward motion that includes the complex case of set-point propagation through on-axle hitches. The paper addresses system requirements and provides implementation details to tele-operate two different off- and on-axle combinations of a tracked mobile robot pulling and pushing two dissimilar trailers. PMID:23552102

  11. 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.

  12. Risk appraisal of passing zones on two-lane rural highways and policy applications.

    PubMed

    Mwesige, Godfrey; Farah, Haneen; Koutsopoulos, Haris N

    2016-05-01

    Passing on two-lane rural highways is associated with risks of head-on collision resulting from unsafe completion of passing maneuvers in the opposite traffic lane. In this paper, we explore the use of time-to-collision (TTC) as a surrogate safety measure of the risk associated with passing maneuvers. Logistic regression models to predict the probability to end the passing maneuver with TTC less than 2 or 3s-threshold were developed with the time-gap from initiation of the maneuver to arrival of the opposite vehicle (effective accepted gap), and the passing duration as explanatory variables. The data used for model estimation was collected using stationary tripod-mounted camcorders at 19 passing zones in Uganda. Results showed that passing maneuvers completed with TTC less than 3s are unsafe and often involved sudden speed reduction, flashing headlights, and lateral shift to shoulders. Model sensitivity analysis was conducted for observed passing durations involving passenger cars or short trucks (2-3 axles), and long trucks (4-7 axles) as the passed vehicles for 3s TTC-threshold. Three risk levels were proposed based on the probability to complete passing maneuvers with TTC less than 3s for a range of opposite direction traffic volumes. Applications of the results for safety improvements of two-lane rural highways are also discussed. PMID:26874293

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

    PubMed

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

    2015-12-01

    The TAM receptors Tyro3, Axl and Mertk are receptor tyrosine kinases that dampen host innate immune responses following engagement with their ligands Gas6 and Protein S, which recognize phosphatidylserine on apoptotic cells. In a form of apoptotic mimicry, many enveloped viruses display phosphatidylserine on the outer leaflet of their membranes, enabling TAM receptor activation and downregulation of antiviral responses. Accordingly, we hypothesized that a deficiency of TAM receptors would enhance antiviral responses and protect against viral infection. Unexpectedly, mice lacking Mertk and/or Axl, but not Tyro3, exhibited greater vulnerability to infection with neuroinvasive West Nile and La Crosse encephalitis viruses. This phenotype was associated with increased blood-brain barrier permeability, which enhanced virus entry into and infection of the brain. Activation of Mertk synergized with interferon-β to tighten cell junctions and prevent virus transit across brain microvascular endothelial cells. Because TAM receptors restrict pathogenesis of neuroinvasive viruses, these findings have implications for TAM antagonists that are currently in clinical development. PMID:26523970

  14. 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.

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

    PubMed

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

    2015-12-01

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

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. Detection of rail corrugation based on fiber laser accelerometers

    NASA Astrophysics Data System (ADS)

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

    2013-09-01

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

  2. 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

  3. 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.

  4. Vertical and pitching resonance of train cars moving over a series of simple beams

    NASA Astrophysics Data System (ADS)

    Yang, Y. B.; Yau, J. D.

    2015-02-01

    The resonant response, including both vertical and pitching motions, of an undamped sprung mass unit moving over a series of simple beams is studied by a semi-analytical approach. For a sprung mass that is very small compared with the beam, we first simplify the sprung mass as a constant moving force and obtain the response of the beam in closed form. With this, we then solve for the response of the sprung mass passing over a series of simple beams, and validate the solution by an independent finite element analysis. To evaluate the pitching resonance, we consider the cases of a two-axle model and a coach model traveling over rough rails supported by a series of simple beams. The resonance of a train car is characterized by the fact that its response continues to build up, as it travels over more and more beams. For train cars with long axle intervals, the vertical acceleration induced by pitching resonance dominates the peak response of the train traveling over a series of simple beams. The present semi-analytical study allows us to grasp the key parameters involved in the primary/sub-resonant responses. Other phenomena of resonance are also discussed in the exemplar study.

  5. Evaluation of powertrain solutions for future tactical truck vehicle systems

    NASA Astrophysics Data System (ADS)

    Pisu, Pierluigi; Cantemir, Codrin-Gruie; Dembski, Nicholas; Rizzoni, Giorgio; Serrao, Lorenzo; Josephson, John R.; Russell, James

    2006-05-01

    The article presents the results of a large scale design space exploration for the hybridization of two off-road vehicles, part of the Future Tactical Truck System (FTTS) family: Maneuver Sustainment Vehicle (MSV) and Utility Vehicle (UV). Series hybrid architectures are examined. The objective of the paper is to illustrate a novel design methodology that allows for the choice of the optimal values of several vehicle parameters. The methodology consists in an extensive design space exploration, which involves running a large number of computer simulations with systematically varied vehicle design parameters, where each variant is paced through several different mission profiles, and multiple attributes of performance are measured. The resulting designs are filtered to choose the design tradeoffs that better satisfy the performance and fuel economy requirements. At the end, few promising vehicle configuration designs will be selected that will need additional detailed investigation including neglected metrics like ride and drivability. Several powertrain architectures have been simulated. The design parameters include the number of axles in the vehicle (2 or 3), the number of electric motors per axle (1 or 2), the type of internal combustion engine, the type and quantity of energy storage system devices (batteries, electrochemical capacitors or both together). An energy management control strategy has also been developed to provide efficiency and performance. The control parameters are tunable and have been included into the design space exploration. The results show that the internal combustion engine and the energy storage system devices are extremely important for the vehicle performance.

  6. Static Scale Conversion (SSC)

    2007-01-19

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

  7. Analysis of Ebola Virus Entry Into Macrophages.

    PubMed

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

    2015-10-01

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

  8. Engine classification using vibrations measured by Laser Doppler Vibrometer on different surfaces

    NASA Astrophysics Data System (ADS)

    Wei, J.; Liu, Chi-Him; Zhu, Zhigang; Vongsy, Karmon; Mendoza-Schrock, Olga

    2015-05-01

    In our previous studies, vehicle surfaces' vibrations caused by operating engines measured by Laser Doppler Vibrometer (LDV) have been effectively exploited in order to classify vehicles of different types, e.g., vans, 2-door sedans, 4-door sedans, trucks, and buses, as well as different types of engines, such as Inline-four engines, V-6 engines, 1-axle diesel engines, and 2-axle diesel engines. The results are achieved by employing methods based on an array of machine learning classifiers such as AdaBoost, random forests, neural network, and support vector machines. To achieve effective classification performance, we seek to find a more reliable approach to pick authentic vibrations of vehicle engines from a trustworthy surface. Compared with vibrations directly taken from the uncooperative vehicle surfaces that are rigidly connected to the engines, these vibrations are much weaker in magnitudes. In this work we conducted a systematic study on different types of objects. We tested different types of engines ranging from electric shavers, electric fans, and coffee machines among different surfaces such as a white board, cement wall, and steel case to investigate the characteristics of the LDV signals of these surfaces, in both the time and spectral domains. Preliminary results in engine classification using several machine learning algorithms point to the right direction on the choice of type of object surfaces to be planted for LDV measurements.

  9. Static Scale Conversion (SSC)

    SciTech Connect

    2007-01-19

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

  10. Quantification of uncertainty in the prediction of railway induced ground vibration due to the use of statistical track unevenness data

    NASA Astrophysics Data System (ADS)

    Lombaert, G.; Galvín, P.; François, S.; Degrande, G.

    2014-09-01

    Environmental vibrations due to railway traffic are predominantly due to dynamic axle loads caused by wheel and track unevenness and impact excitation by rail joints and wheel flats. Because of its irregular character, track unevenness is commonly processed statistically and represented by its power spectral density function or its root mean square (RMS) value in one-third octave bands. This statistical description does not uniquely define the track unevenness at a given site, however, and different track unevenness profiles matching the statistical description will lead to different predictions of dynamic axle loads and resulting ground vibration. This paper presents a methodology that allows quantifying the corresponding variability in ground vibration predictions. The procedure is derived assuming the geometry of the track and soil to be homogeneous along the track. The procedure is verified by means of Monte Carlo simulations and its usefulness for assessing the mismatch between predicted and measured ground vibrations is demonstrated in a case study. The results show that the response in time domain and its narrow band spectrum exhibit significant variability which is reduced when the running RMS value or the one-third octave band spectrum of the response is considered.

  11. Prediction of Ground Vibration from Freight Trains

    NASA Astrophysics Data System (ADS)

    Jones, C. J. C.; Block, J. R.

    1996-05-01

    Heavy freight trains emit ground vibration with predominant frequency components in the range 4-30 Hz. If the amplitude is sufficient, this may be felt by lineside residents, giving rise to disturbance and concern over possible damage to their property. In order to establish the influence of parameters of the track and rolling stock and thereby enable the design of a low vibration railway, a theoretical model of both the generation and propagation of vibration is required. The vibration is generated as a combination of the effects of dynamic forces, due to the unevenness of the track, and the effects of the track deformation under successive axle loads. A prediction scheme, which combines these effects, has been produced. A vehicle model is used to predict the dynamic forces at the wheels. This includes the non-linear effects of friction damped suspensions. The loaded track profile is measured by using a track recording coach. The dynamic loading and the effects of the moving axles are combined in a track response model. The predicted track vibration is compared to measurements. The transfer functions from the track to a point in the ground can be calculated by using a coupled track and a three-dimensional layered ground model. The propagation effects of the ground layers are important but the computation of the transfer function from each sleeper, which would be required for a phase coherent summation of the vibration in the ground, would be prohibitive. A compromise summation is used and results are compared with measurements.

  12. 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.

  13. 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.

  14. 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.

  15. Driver assistance system for passive multi-trailer vehicles with haptic steering limitations on the leading unit.

    PubMed

    Morales, Jesús; Mandow, Anthony; Martínez, Jorge L; Reina, Antonio J; García-Cerezo, Alfonso

    2013-01-01

    Driving vehicles with one or more passive trailers has difficulties in both forward and backward motion due to inter-unit collisions, jackknife, and lack of visibility. Consequently, advanced driver assistance systems (ADAS) for multi-trailer combinations can be beneficial to accident avoidance as well as to driver comfort. The ADAS proposed in this paper aims to prevent unsafe steering commands by means of a haptic handwheel. Furthermore, when driving in reverse, the steering-wheel and pedals can be used as if the vehicle was driven from the back of the last trailer with visual aid from a rear-view camera. This solution, which can be implemented in drive-by-wire vehicles with hitch angle sensors, profits from two methods previously developed by the authors: safe steering by applying a curvature limitation to the leading unit, and a virtual tractor concept for backward motion that includes the complex case of set-point propagation through on-axle hitches. The paper addresses system requirements and provides implementation details to tele-operate two different off- and on-axle combinations of a tracked mobile robot pulling and pushing two dissimilar trailers.

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

    2006-05-04

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

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

    2006-05-04

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

  18. 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

  19. 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

  20. Analysis of limit forces on the vehicle wheels using an algorithm of Dynamic Square Method

    NASA Astrophysics Data System (ADS)

    Brukalski, M.

    2016-09-01

    This article presents a method named as Dynamic Square Method (DSM) used for dynamic analysis of a vehicle equipped with a four wheel drive system. This method allows determination of maximum (limit) forces acting on the wheels. Here, the maximum longitudinal forces acting on the wheels are assumed and then used to predict whether they can be achieved by a specific dynamic motion or whether the actual friction forces under a given wheel is large enough to transfer lateral forces. For the analysis of DSM a four wheel vehicle model is used. On the basis of this characteristic it is possible to determine the maximum longitudinal force acting on the wheels of the given axle depending on the lateral acceleration of the vehicle. The results of this analysis may be useful in the development of a control algorithm used for example in active differentials.

  1. Low toxicity β-cyclodextrin-caged 4,4'-bipyridinium-bis(siloxane): synthesis and evaluation.

    PubMed

    Marangoci, Narcisa; Maier, Stelian S; Ardeleanu, Rodinel; Arvinte, Adina; Fifere, Adrian; Petrovici, Anca Roxana; Nicolescu, Alina; Nastasa, Valentin; Mares, Mihai; Pasca, Sorin A; Moraru, Ramona F; Pinteala, Mariana; Chiriac, Anca

    2014-04-21

    The toxicity of viologens can be significantly reduced by including them in tight [2]rotaxane structures alongside β-cyclodextrin, thus turning them into candidates of pharmaceutical interest. Here, we report a synthesis pathway for a benign viologen, by capping a small β-cyclodextrin-caged molecule, the 4,4'-bipyridine, with minimal-length presynthesized axle-stopper segments of the propyl-3-pentamethyldisiloxane type. After 90 min from the oral administration to laboratory mice, the product concentration in the bloodstream reaches a value equivalent to 0.634% of the initial dose of 800 mg·kg(-1). As compared to the nude viologen having the same structure, which proved to be lethal in doses of 40 mg·kg(-1), the product induces reversible morphological changes in the liver, kidney, lung, and cerebellum, up to a dose of 400 mg·kg(-1), with higher dosages giving rise to a chronic slow evolution.

  2. Implantation of an ergonomics administration system in a company: report of an occupational therapist specialist in ergonomics.

    PubMed

    Moraes, Berla; Andrade, Valéria Sousa

    2012-01-01

    This article aims to describe step-by-step the implementation of an ergonomics administration system in a company from March 2009 till March 2011 by an occupational therapist specialist in ergonomics based on the OSHAS 18001 guidelines and the Regulatory Norms 17 manual. The process began with the definition of five requisites with bases on the manual of application of the Regulatory Norms 17: survey; materials individual transportation and discharge; workplace furniture; workplace equipments; work environment and organization of the work to be managed with bases on the OSHAS 18001 guidelines. The following steps were established: sensitization of the company high administration, elaboration and institution of an ergonomics politics, development of ergonomics committees, ergonomics analysis of the work with recommendation of ergonomic improvements, implantation of improvements and evaluation or the results. This research experiment suggests the importance not only of a guiding axle but also of a professional qualification and participation of the company on the implementation of an ergonomics management system.

  3. 3D homogenised strength criterion for masonry: Application to drystone retaining walls

    NASA Astrophysics Data System (ADS)

    Le, Hong Hanh; Garnier, Denis; Colas, Anne-Sophie; Terrade, Benjamin; Morel, Jean-Claude

    2016-10-01

    A 3D strength criterion for masonry is constructed based on yield design theory. Yield design homogenisation provides a rigorous theoretical framework to determine the yield strength properties of a periodic medium, based on the properties of its constituent materials. First, theoretical basis of 2D homogenisation of periodic media, and more particularly its application in the framework of yield design, will be retrieved. Then, 2D principles are extended to exhibit a 3D domain of running-bond masonry. This criterion is finally used to assess the stability of a drystone retaining wall loaded by an axle load, and theoretical results are compared to experimental data. Perspectives on this work are given as a conclusion.

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

    PubMed

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

    2016-06-28

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

  5. Time-frequency analysis of railway bridge response in forced vibration

    NASA Astrophysics Data System (ADS)

    Cantero, Daniel; Ülker-Kaustell, Mahir; Karoumi, Raid

    2016-08-01

    This paper suggests the use of the Continuous Wavelet Transform in combination with the Modified Littlewood-Paley basis to analyse bridge responses exited by traversing trains. The analysis provides an energy distribution map in the time-frequency domain that offers a better resolution compared to previous published studies. This is demonstrated with recorded responses of the Skidträsk Bridge, a 36 m long composite bridge located in Sweden. It is shown to be particularly useful to understand the evolution of the energy content during a vehicle crossing event. With this information it is possible to distinguish the effect of several of the governing factors involved in the dynamic response including vehicle's speed and axle configuration as well as non-linear behaviour of the structure.

  6. Structure of the vacuolar H+-ATPase rotary motor reveals new mechanistic insights.

    PubMed

    Rawson, Shaun; Phillips, Clair; Huss, Markus; Tiburcy, Felix; Wieczorek, Helmut; Trinick, John; Harrison, Michael A; Muench, Stephen P

    2015-03-01

    Vacuolar H(+)-ATPases are multisubunit complexes that operate with rotary mechanics and are essential for membrane proton transport throughout eukaryotes. Here we report a ∼ 1 nm resolution reconstruction of a V-ATPase in a different conformational state from that previously reported for a lower-resolution yeast model. The stator network of the V-ATPase (and by implication that of other rotary ATPases) does not change conformation in different catalytic states, and hence must be relatively rigid. We also demonstrate that a conserved bearing in the catalytic domain is electrostatic, contributing to the extraordinarily high efficiency of rotary ATPases. Analysis of the rotor axle/membrane pump interface suggests how rotary ATPases accommodate different c ring stoichiometries while maintaining high efficiency. The model provides evidence for a half channel in the proton pump, supporting theoretical models of ion translocation. Our refined model therefore provides new insights into the structure and mechanics of the V-ATPases. PMID:25661654

  7. 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

  8. A chemically powered unidirectional rotary molecular motor based on a palladium redox cycle

    NASA Astrophysics Data System (ADS)

    Collins, Beatrice S. L.; Kistemaker, Jos C. M.; Otten, Edwin; Feringa, Ben L.

    2016-09-01

    The conversion of chemical energy to drive directional motion at the molecular level allows biological systems, ranging from subcellular components to whole organisms, to perform a myriad of dynamic functions and respond to changes in the environment. Directional movement has been demonstrated in artificial molecular systems, but the fundamental motif of unidirectional rotary motion along a single-bond rotary axle induced by metal-catalysed transformation of chemical fuels has not been realized, and the challenge is to couple the metal-centred redox processes to stepwise changes in conformation to arrive at a full unidirectional rotary cycle. Here, we present the design of an organopalladium-based motor and the experimental demonstration of a 360° unidirectional rotary cycle using simple chemical fuels. Exploiting fundamental reactivity principles in organometallic chemistry enables control of directional rotation and offers the potential of harnessing the wealth of opportunities offered by transition-metal-based catalytic conversions to drive motion and dynamic functions.

  9. On the optimum ride control of a stochastic model of a tractor-semitrailer vehicle

    NASA Astrophysics Data System (ADS)

    ElMadany, M. M.; Samaha, M. E.

    1992-07-01

    A systematic approach based on stochastic optimal control and estimation theories for the optimal design of active suspension systems for a tractor-semitrailer vehicle is presented. The vehicle-road system dynamics combined with the human perception of random vibrations are cast in the standard linear quadratic Gaussian format. The time delays of the stochastic excitation process of the multi-axled vehicle are represented by a first order Padé approximation. The optimal controller/observer is derived which minimizes the mean-squared values of performance variables reflecting the human comfort, cargo safety, suspension working space, roadholding ability and control forces. The advantages of optimally controlled suspension systems over their passive counterparts are indicated.

  10. Ferroelectric Coordination Polymers Self-Assembled from Mesogenic Zinc(II) Porphyrin and Dipolar Bridging Ligands.

    PubMed

    Hui, Joseph K-H; Kishida, Hiroyuki; Ishiba, Keita; Takemasu, Kenta; Morikawa, Masa-Aki; Kimizuka, Nobuo

    2016-09-26

    A new class of ferroelectric coordination-based polymers has been developed by the self-assembly of lipophilic zinc porphyrin (ZnP) and ditopic bridging ligands. The ligands contain dipolar benzothiadiazole or fluorobenzene units, which are axially coordinated to ZnP with the dipole moments oriented perpendicular to the coordination axes. The coordination-based polymers show ferroelectric characteristics in the liquid crystalline state, as revealed by distinctive hysteresis in the polarization-electric field (P-E) loops and inversion current peaks in current-voltage (I-V) loops. The observed ferroelectric properties are explainable by flip-flop rotation of the dipolar axle ligands induced by the applied electric field, as demonstrated by the positive-up-negative-down (PUND) measurements. The present system provides a new operating principle in supramolecular ferroelectrics.

  11. Automatic guidance control of an articulated all-wheel-steered vehicle

    NASA Astrophysics Data System (ADS)

    Kim, Young Chol; Yun, Kyong-Han; Min, Kyung-Deuk

    2014-04-01

    This paper presents automatic guidance control of a single-articulated all-wheel-steered vehicle being developed by the Korea Railroad Research Institute. The vehicle has an independent drive motor on each wheel except for the front axle. The guidance controller is designed so that the vehicle follows the given reference path within permissible lateral deviations. We use a three-input/three-output linearised model derived from the nonlinear dynamic model of the vehicle. For the purpose of simplifying the controller and making it tunable, we consider a decentralised control configuration. We first design a second-order decoupling compensator for the two-input/two-output system that is strongly coupled and then design a first-order controller for each decoupled feedback loop by using the characteristic ratio assignment method. The simulation results for the nonlinear dynamic model indicate that the proposed control configuration successfully achieves the design objectives.

  12. Vehicle dynamic stability and rollover

    NASA Astrophysics Data System (ADS)

    Allen, R. W.; Szostak, H. T.; Klyde, D. H.; Rosenthal, T. J.; Owens, K. J.

    1992-06-01

    The report considers ground vehicle lateral/directional stability which is of primary concern in traffic safety. Lateral/directional dynamics involve yawing, rolling, and lateral acceleration motions, and stability concerns include spinout and rollover. The report describes accident analysis, vehicle testing, and computer simulation analysis designed to give insight into basic vehicle design variables that contribute to stability problems. The results of vehicle testing and simulation analysis indicate that a vehicle that has both a relatively low ratio of track width to center of gravity height and is equipped with tires which have a relatively high peak coefficient of friction will have a propensity to rollover during steering maneuvers on a flat surface. Vehicle testing and computer simulation analysis also indicate that directional stability is significantly influenced by the relationship between vehicle weight distribution and lateral load transfer distribution that is greater than or equal to the percent weight on the front axle.

  13. Synthesis and Dynamics of Nanosized Phenylene-Ethynylene-Butadiynylene Rotaxanes and the Role of Shape Persistence.

    PubMed

    Schweez, Christopher; Shushkov, Philip; Grimme, Stefan; Höger, Sigurd

    2016-03-01

    Phenylacetylene-based [2]rotaxanes were synthesized by a covalent-template approach by aminolysis of the corresponding prerotaxanes. The wheel and the bulky stoppers are made of phenylene-ethynylene-butadiynylene macrocycles of the same size. The stoppers are large enough to enable the synthesis and purification of the rotaxane. However, the wheel unthreads from the axle at elevated temperatures. The deslipping kinetics and the activation parameters were determined. We described theoretically the unthreading by state-of-the-art DFT-based molecular-mechanics models and a string method for the simulation of rare events. This approach enabled us to characterize in detail the unthreading mechanism, which involves the folding of the stopper during its passage through the wheel opening, a process that defies intuitive geometrical considerations. The conformational and energetic features of the transition allowed us to infer the molecular residues controlling the disassembly timescale.

  14. Dynamic response of elastic layered medium to moving loads

    NASA Astrophysics Data System (ADS)

    Zafir, Zia; Siddharthan, Raj

    A new method of analysis to study the response of horizontally layered elastic medium to moving surface pressure loads under plane strain conditions has been developed. Important factors such as the two dimensional nature of wave propagation, inertia, and damping effects of the medium are accounted for. The proposed method can handle single loads or multiple loads. In the case of fast moving loads, it has been found that the inertia and damping considerations are important. An increase of about 35 percent in the vertical displacement of the surface was noted when the speed of the load was increased from 20 m/s to 100 m/s. For truck loads with tandem axle configuration on flexible pavements, it has been found that the two important strains, E(t) (major principal) at the bottom of the asphalt concrete (AC) layer and E(p) (minor principal) at the top of the subgrade layer are cyclic and not unidirectional as often assumed.

  15. Diagnostic device for monitoring the technical condition of mechanical assemblies

    NASA Technical Reports Server (NTRS)

    Osovskiy, V. I.; Shergin, V. V.; Shumilin, V. I.

    1973-01-01

    An automatic diagnostic device for monitoring the condition of tractor transmission gears is described. The structural noise spectrum of the gearshift box and rear axle of the tractor were analyzed in a digital computer, by an algorithm based on the multiple correlation method. The optimum assembly of operating frequencies, by use of which the errors in measurement were minimized, was selected from the entire frequency spectrum. Selected frequencies are necessary for choosing the measurement range of the diagnostic device. It turned out that, to obtain a relative error of no more than 2%, it was sufficient to use two filters, vibrating only at the frequencies carrying the maximum data of the mechanical parameter being investigated. The measurement system consists of frequency-selection filters, amplifiers and quadratic detectors, at the outlets of which constant voltages are created, which are proportional to the signal level at the frequencies selected.

  16. Voltage Controller

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Power Efficiency Corporation, specifically formed to manufacture and develop products from NASA technology, has a license to a three-phase power factor controller originally developed by Frank Nola, an engineer at Marshall Space Flight Center. Power Efficiency and two major distributors, Performance Control and Edison Power Technologies, use the electronic control boards to assemble three different motor controllers: Power Commander, Performance Controller, and Energy Master. The company Power Factor Controller reduces excessive energy waste in AC induction motors. It is used in industries and applications where motors operate under variable loads, including elevators and escalators, machine tools, intake and exhaust fans, oil wells, conveyors, pumps, die casting, and compressors. Customer lists include companies such as May Department Stores, Caesars Atlantic City, Ford Motors, and American Axle.

  17. Single rotating molecule-machines: nanovehicles and molecular motors.

    PubMed

    Rapenne, Gwénaël; Joachim, Christian

    2014-01-01

    In the last decade many molecular machines with controlled molecular motions have been synthesized. In the present review chapter we will present and discuss our contribution to the field, in particular through some examples of rotating molecular machines that have been designed, synthesized, and studied in our group. After starting by explaining why it is so important to study such machines as single molecules, we will focus on two families of molecular machines, nanovehicles and molecular motors. The first members of the nanovehicle family are molecules with two triptycenes as wheels: the axle and the wheelbarrow. Then come the four-wheel nanocars. Since triptycene wheels are not very mobile on metallic surfaces, alternative wheels with a bowl-shape structure have also been synthesized and studied on surfaces. The molecular motors are built around ruthenium organometallic centers and have a piano-stool geometry with peripheric ferrocenyl groups.

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

    NASA Astrophysics Data System (ADS)

    Roundy, Shad; Tola, Jeffry

    2014-10-01

    We present an energy harvester for environments that rotate through the Earth’s gravitational field. Example applications include shafts connected to motors, axles, propellers, fans, and wheels or tires. Our approach uses the unique dynamics of an offset pendulum along with a nonlinear bistable restoring spring to improve the operational bandwidth of the system. Depending on the speed of the rotating environment, the system can act as a bistable oscillator, monostable stiffening oscillator, or linear oscillator. We apply our approach to a tire pressure monitoring system mounted on a car rim. Simulation and experimental test results show that the prototype generator is capable of directly powering an RF transmission every 60 s or less over a speed range of 10 to 155 kph.

  19. TAM Receptor Signaling in Immune Homeostasis

    PubMed Central

    Rothlin, Carla V.; Carrera-Silva, Eugenio A.; Bosurgi, Lidia; Ghosh, Sourav

    2015-01-01

    The TAM receptor tyrosine kinases (RTKs)—TYRO3, AXL, and MERTK—together with their cognate agonists GAS6 and PROS1 play an essential role in the resolution of inflammation. Deficiencies in TAM signaling have been associated with chronic inflammatory and autoimmune diseases. Three processes regulated by TAM signaling may contribute, either independently or collectively, to immune homeostasis: the negative regulation of the innate immune response, the phagocytosis of apoptotic cells, and the restoration of vascular integrity. Recent studies have also revealed the function of TAMs in infectious diseases and cancer. Here, we review the important milestones in the discovery of these RTKs and their ligands and the studies that underscore the functional importance of this signaling pathway in physiological immune settings and disease. PMID:25594431

  20. A transportable satellite earth station for television outside broadcast contributions

    NASA Astrophysics Data System (ADS)

    Scott, J. M. C.

    1983-07-01

    In connection with the availability of communications satellites in Europe, the feasibility was considered of using satellites as a means of providing television outside broadcast sound and vision contribution circuits. The feasibility of designing a practical transportable satellite ground station was explored. It was finally decided to employ a two-axle trailer towed by a standard radio-link vehicle. The dish antenna is mounted on a turntable on the trailer. Attention is given to details concerning the design features, aspects of acceptance testing, and questions of operational experience. It is hoped to provide with the aid of the terminal circuits which would be impossible in the case of a use of conventional terrestrial links.