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Sample records for polyox fra polyox

  1. Design and Evaluation of Polyox and Pluronic Controlled Gastroretentive Delivery of Troxipide

    PubMed Central

    Jagdale, Swati C.; Kamble, Shraddha B.; Kuchekar, Bhanudas S.; Chabukswar, Aniruddha R.

    2014-01-01

    Objective. Objective of the present work was to develop site-specific gastroretentive drug delivery of Troxipide using polymers Pluronic F127 and Polyox 205 WSR. Troxipide is a novel gastroprotective agent with antiulcer, anti-inflammatory, and mucus secreting properties with elimination half-life of 7.4 hrs. Troxipide inhibits H. pylori-derived urease. It is mainly absorbed from stomach. Methods. 32 factorial design was applied to study the effect of independent variable. Effects of concentration of polymer on dependant variables as swelling index, hardness, and % drug release were studied. Pluronic F127 and Polyox 205 WSR were used as rate controlled polymer. Sodium bicarbonate and citric acid were used as effervescent-generating agent. Results. From the factorial batches, it was observed that formulation F5 (19% Pluronic F127 and 80% Polyox 205 WSR) showed optimum controlled drug release (98.60% ± 1.82) for 10 hrs with ability to float >12 hrs. Optimized formulation characterized by FTIR and DSC studies confirmed no chemical interactions between drug and polymer. Gastroretention for 6 hrs for optimized formulations was confirmed by in vivo X-ray placebo study. Conclusion. Results demonstrated feasibility of Troxipide in the development of gastroretentive site-specific drug delivery. PMID:25505995

  2. An Investigation on the Effect of Polyethylene Oxide Concentration and Particle Size in Modulating Theophylline Release from Tablet Matrices.

    PubMed

    Shojaee, Saeed; Emami, Parastou; Mahmood, Ahmad; Rowaiye, Yemisi; Dukulay, Alusine; Kaialy, Waseem; Cumming, Iain; Nokhodchi, Ali

    2015-12-01

    Polyethylene oxide has been researched extensively as an alternative polymer to hydroxypropyl methylcellulose (HPMC) in controlled drug delivery due to its desirable swelling properties and its availability in a number of different viscosity grades. Previous studies on HPMC have pointed out the importance of particle size on drug release, but as of yet, no studies have investigated the effect of particle size of polyethylene oxide (polyox) on drug release. The present study explored the relationship between polymer level and particle size to sustain the drug release. Tablets produced contained theophylline as their active ingredient and consisted of different polyethylene oxide particle size fractions (20-45, 45-90, 90-180 and 180-425 μm). It was shown that matrices containing smaller particle sizes of polyox produced harder tablets than when larger polyox particles were used. The release studies showed that matrices consisting of large polyox particles showed a faster release rate than matrices made from smaller particles. Molecular weight (MW) of the polymer was a key determining step in attaining sustained release, with the high MW of polyox resulting in a delayed release profile. The results showed that the effect of particle size on drug release was more detrimental when a low concentration of polyox was used. This indicates that care must be taken when low levels of polyox with different particle size fractions are used. More robust formulations could be obtained when the concentration of polyox is high. Differential scanning calorimetry (DSC) traces showed that particle size had no major effect on the thermal behaviour of polyox particles.

  3. An Investigation on the Effect of Polyethylene Oxide Concentration and Particle Size in Modulating Theophylline Release from Tablet Matrices.

    PubMed

    Shojaee, Saeed; Emami, Parastou; Mahmood, Ahmad; Rowaiye, Yemisi; Dukulay, Alusine; Kaialy, Waseem; Cumming, Iain; Nokhodchi, Ali

    2015-12-01

    Polyethylene oxide has been researched extensively as an alternative polymer to hydroxypropyl methylcellulose (HPMC) in controlled drug delivery due to its desirable swelling properties and its availability in a number of different viscosity grades. Previous studies on HPMC have pointed out the importance of particle size on drug release, but as of yet, no studies have investigated the effect of particle size of polyethylene oxide (polyox) on drug release. The present study explored the relationship between polymer level and particle size to sustain the drug release. Tablets produced contained theophylline as their active ingredient and consisted of different polyethylene oxide particle size fractions (20-45, 45-90, 90-180 and 180-425 μm). It was shown that matrices containing smaller particle sizes of polyox produced harder tablets than when larger polyox particles were used. The release studies showed that matrices consisting of large polyox particles showed a faster release rate than matrices made from smaller particles. Molecular weight (MW) of the polymer was a key determining step in attaining sustained release, with the high MW of polyox resulting in a delayed release profile. The results showed that the effect of particle size on drug release was more detrimental when a low concentration of polyox was used. This indicates that care must be taken when low levels of polyox with different particle size fractions are used. More robust formulations could be obtained when the concentration of polyox is high. Differential scanning calorimetry (DSC) traces showed that particle size had no major effect on the thermal behaviour of polyox particles. PMID:25771738

  4. Fra-1 is a key driver of colon cancer metastasis and a Fra-1 classifier predicts disease-free survival

    PubMed Central

    Iskit, Sedef; Schlicker, Andreas; Wessels, Lodewyk; Peeper, Daniel S.

    2015-01-01

    Fra-1 (Fos-related antigen-1) is a member of the AP-1 (activator protein-1) family of transcription factors. We previously showed that Fra-1 is necessary for breast cancer cells to metastasize in vivo, and that a classifier comprising genes that are expressed in a Fra-1-dependent fashion can predict breast cancer outcome. Here, we show that Fra-1 plays an important role also in colon cancer progression. Whereas Fra-1 depletion does not affect 2D proliferation of human colon cancer cells, it impairs growth in soft agar and in suspension. Consistently, subcutaneous tumors formed by Fra-1-depleted colon cancer cells are three times smaller than those produced by control cells. Most remarkably, when injected intravenously, Fra-1 depletion causes a 200-fold reduction in tumor burden. Moreover, a Fra-1 classifier generated by comparing RNA profiles of parental and Fra-1-depleted colon cancer cells can predict the prognosis of colon cancer patients. Functional pathway analysis revealed Wnt as one of the central pathways in the classifier, suggesting a possible mechanism of Fra-1 function in colon cancer metastasis. Our results demonstrate that Fra-1 is an important determinant of the metastatic potential of human colon cancer cells, and that the Fra-1 classifier can be used as a prognostic predictor in colon cancer patients. PMID:26646695

  5. 49 CFR 230.19 - Posting of FRA Form No. 1 and FRA Form No. 3.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... the cab of the steam locomotive before the inspected boiler is put into service. This FRA Form No. 1... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS.... 1. The steam locomotive owner and/or operator shall place a copy of the 31 and 92 service...

  6. 76 FR 41859 - Waiver Petition Docket Numbers FRA-2011-0002, CSX Transportation Railroad, and FRA-2004-17565...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-15

    ..., and FRA-2004-17565, Union Pacific Railroad; Public Hearing On February 23, 2011, the Federal Railroad Administration (FRA) published a notice in the Federal Register (76 FR 10087) announcing the CSX Transportation... Register (75 FR 224) announcing the Union Pacific Railroad's request for an amendment to their...

  7. Simultaneous generation of fra-2 conditional and fra-2 knock-out mice.

    PubMed

    Eferl, Robert; Zenz, Rainer; Theussl, Hans-Christian; Wagner, Erwin F

    2007-07-01

    Loss of function mouse models comprise knock-out mice, where a gene is deleted in the germline, and conditional knock-out mice with somatic deletion of a floxed allele in defined tissues. Both types of mice are used for comprehensive studies of gene functions in vivo. Here, we describe a simple method for simultaneous generation of mice with conditional or knock-out alleles for the transcription factor fra-2 (Fos-related antigen 2) using a single embryonic stem (ES) cell clone. ES cells with a floxed fra-2 allele were transiently transfected with a Cre-recombinase expression plasmid and plated at low density. Most of the resulting ES cell colonies consisted of a mixture of cells that have either retained or lost the conditional allele. We demonstrate that these mixed ES cell clones can be directly used for generation of chimeras that give rise to offspring with conditional or knock-out alleles simultaneously. This strategy shortens the time and reduces the number of germline transmission events to generate genetically modified mice.

  8. 49 CFR Appendix C to Part 230 - FRA Inspection Forms

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false FRA Inspection Forms C Appendix C to Part 230 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Pt. 230, App. C Appendix...

  9. 49 CFR Appendix C to Part 230 - FRA Inspection Forms

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false FRA Inspection Forms C Appendix C to Part 230 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Pt. 230, App. C Appendix...

  10. 49 CFR Appendix C to Part 230 - FRA Inspection Forms

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false FRA Inspection Forms C Appendix C to Part 230 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Pt. 230, App. C Appendix...

  11. Formulation and in vitro evaluation of floating tablets of hydroxypropyl methylcellulose and polyethylene oxide using ranitidine hydrochloride as a model drug

    PubMed Central

    Gharti, KP; Thapa, P; Budhathoki, U; Bhargava, A

    2012-01-01

    The present study was carried out with an objective of preparation and in vitro evaluation of floating tablets of hydroxypropyl methyl cellulose (HPMC) and polyethylene oxide (PEO) using ranitidine hydrochloride as a model drug. The floating tablets were based on effervescent approach using sodium bicarbonate a gas generating agent. The tablets were prepared by dry granulation method. The effect of polymers concentration and viscosity grades of HPMC on drug release profile was evaluated. The effect of sodium bicarbonate and stearic acid on drug release profile and floating properties were also investigated. The result of in vitro dissolution study showed that the drug release profile could be sustained by increasing the concentration of HPMC K15MCR and Polyox WSR303. The formulation containing HPMC K15MCR and Polyox WSR303 at the concentration of 13.88% showed 91.2% drug release at the end of 24 hours. Changing the viscosity grade of HPMC from K15MCR to K100MCR had no significant effect on drug release profile. Sodium bicarbonate and stearic acid in combination showed no significant effect on drug release profile. The formulations containing sodium bicarbonate 20 mg per tablet showed desired buoyancy (floating lag time of about 2 minutes and total floating time of >24 hours). The present study shows that polymers like HPMC K15MCR and Polyox WSR303 in combination with sodium bicarbonate as a gas generating agent can be used to develop sustained release floating tablets of ranitidine hydrochloride. PMID:23493037

  12. Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells.

    PubMed

    Ried, K; Finnis, M; Hobson, L; Mangelsdorf, M; Dayan, S; Nancarrow, J K; Woollatt, E; Kremmidiotis, G; Gardner, A; Venter, D; Baker, E; Richards, R I

    2000-07-01

    Fluorescence in situ hybridization of a tile path of DNA subclones has previously enabled the cyto-genetic definition of the minimal DNA sequence which spans the FRA16D common chromosomal fragile site, located at 16q23.2. Homozygous deletion of the FRA16D locus has been reported in adenocarcinomas of stomach, colon, lung and ovary. We have sequenced the 270 kb containing the FRA16D fragile site and the minimal homozygously deleted region in tumour cells. This sequence enabled localization of some of the tumour cell breakpoints to regions which contain AT-rich secondary structures similar to those associated with the FRA10B and FRA16B rare fragile sites. The FRA16D DNA sequence also led to the identification of an alternatively spliced gene, named FOR (fragile site FRA16D oxidoreductase), exons of which span both the fragile site and the minimal region of homozygous deletion. In addition, the complete DNA sequence of the FRA16D-containing FOR intron reveals no evidence of additional authentic transcripts. Alternatively spliced FOR transcripts (FOR I, FOR II and FOR III) encode proteins which share N-terminal WW domains and differ at their C-terminus, with FOR III having a truncated oxidoreductase domain. FRA16D-associated deletions selectively affect the FOR gene transcripts. Three out of five previously mapped translocation breakpoints in multiple myeloma are also located within the FOR gene. FOR is therefore the principle genetic target for DNA instability at 16q23.2 and perturbation of FOR function is likely to contribute to the biological consequences of DNA instability at FRA16D in cancer cells. PMID:10861292

  13. Presence of hydroxyl in the Fra Mauro region

    NASA Astrophysics Data System (ADS)

    Berezhnoy, Alexey; Wöhler, Christian; Sinitsyn, Mikhail; Grumpe, Arne; Feoktistova, Ekaterina; Shevchenko, Vladislav

    Lunar pyroclastic deposits (LPDs) are known to consist of volcanic material (basalt and glass) ejected by eruptions [1]. In the southern part of the crater Fra Mauro, a localised LPD is associated with Rima Parry V [2]. In [3], a suppressed neutron flux is described for the Fra Mauro region based on measurements of the Lunar Exploration Neutron Detector (LEND) [4], interpreted as an indicator of hydroxyl (OH). In this study we compare these measurements with NIR hyperspectral data acquired by the Moon Mineralogy Mapper (M(3) ) [5] instrument. The suppression factor of the neutron flux is defined according to delta = (N_ref-N_ex)/N_ref [6,7] with N_ex as the average count rate of the omnidirectional sensor (SETN) [8] of LEND for the region under study (here: the Fra Mauro region) and N_ref as the average count rate for a reference area (here: immediately west of Fra Mauro). For Fra Mauro crater, a suppression factor of 2.4% with a standard error of 0.41% was found. The epithermal neutron flux can be assumed to be inversely proportional to the hydrogen content. Hence, the measured positive suppression factor indicates a positive anomaly of the hydrogen content at up to 1 m depth. Under the approximative assumption of a proportional relation between the suppression factor delta and the hydrogen content, the observation in [7] of a suppression factor of 18% in the crater Cabeus associated with a homogeneous hydrogen content of about 500 ppm implies an enrichment in hydrogen by about 70 ppm for the Fra Mauro region. However, these values do not specifically refer to the small Fra Mauro LPD but to a larger area of about 150 km diameter. To identify the LPD-specific suppression factor, it would be necessary to acquire collimated neutron flux measurements. We have complemented the LEND-based measurements by the analysis of spectral reflectance data acquired by the M(3) instrument. The presence of OH in the surface material leads to an absorption band beyond 2700 nm

  14. A metabolic intermediate of the fructose-asparagine utilization pathway inhibits growth of a Salmonella fraB mutant

    PubMed Central

    Sabag-Daigle, Anice; Blunk, Henry M.; Sengupta, Anindita; Wu, Jikang; Bogard, Alexander J.; Ali, Mohamed M.; Stahl, Christopher; Wysocki, Vicki H.; Gopalan, Venkat; Behrman, Edward J.; Ahmer, Brian M. M.

    2016-01-01

    Insertions in the Salmonella enterica fra locus, which encodes the fructose-asparagine (F-Asn) utilization pathway, are highly attenuated in mouse models of inflammation (>1000-fold competitive index). Here, we report that F-Asn is bacteriostatic to a fraB mutant (IC50 19 μM), but not to the wild-type or a fra island deletion mutant. We hypothesized that the presence of FraD kinase and absence of FraB deglycase causes build-up of a toxic metabolite: 6-phosphofructose-aspartate (6-P-F-Asp). We used biochemical assays to assess FraB and FraD activities, and mass spectrometry to confirm that the fraB mutant accumulates 6-P-F-Asp. These results, together with our finding that mutants lacking fraD or the fra island are not attenuated in mice, suggest that the extreme attenuation of a fraB mutant stems from 6-P-F-Asp toxicity. Salmonella FraB is therefore an excellent drug target, a prospect strengthened by the absence of the fra locus in most of the gut microbiota. PMID:27403719

  15. A metabolic intermediate of the fructose-asparagine utilization pathway inhibits growth of a Salmonella fraB mutant.

    PubMed

    Sabag-Daigle, Anice; Blunk, Henry M; Sengupta, Anindita; Wu, Jikang; Bogard, Alexander J; Ali, Mohamed M; Stahl, Christopher; Wysocki, Vicki H; Gopalan, Venkat; Behrman, Edward J; Ahmer, Brian M M

    2016-01-01

    Insertions in the Salmonella enterica fra locus, which encodes the fructose-asparagine (F-Asn) utilization pathway, are highly attenuated in mouse models of inflammation (>1000-fold competitive index). Here, we report that F-Asn is bacteriostatic to a fraB mutant (IC50 19 μM), but not to the wild-type or a fra island deletion mutant. We hypothesized that the presence of FraD kinase and absence of FraB deglycase causes build-up of a toxic metabolite: 6-phosphofructose-aspartate (6-P-F-Asp). We used biochemical assays to assess FraB and FraD activities, and mass spectrometry to confirm that the fraB mutant accumulates 6-P-F-Asp. These results, together with our finding that mutants lacking fraD or the fra island are not attenuated in mice, suggest that the extreme attenuation of a fraB mutant stems from 6-P-F-Asp toxicity. Salmonella FraB is therefore an excellent drug target, a prospect strengthened by the absence of the fra locus in most of the gut microbiota. PMID:27403719

  16. 49 CFR 219.206 - FRA access to breath test results.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false FRA access to breath test results. 219.206 Section 219.206 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD... § 219.206 FRA access to breath test results. Documentation of breath test results must be made...

  17. 49 CFR 219.206 - FRA access to breath test results.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false FRA access to breath test results. 219.206 Section 219.206 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD... § 219.206 FRA access to breath test results. Documentation of breath test results must be made...

  18. 49 CFR 219.206 - FRA access to breath test results.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false FRA access to breath test results. 219.206 Section 219.206 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD... § 219.206 FRA access to breath test results. Documentation of breath test results must be made...

  19. Apollo 14 - Nature and origin of rock types in soil from the Fra Mauro formation.

    NASA Technical Reports Server (NTRS)

    Aitken, F. K.; Anderson, D. H.; Bass, M. N.; Brown, R. W.; Butler, P., Jr.; Heiken, G.; Jakes, P.; Reid, A. M.; Ridley, W. I.; Takeda, H.

    1971-01-01

    Compositions of glasses in the Apollo 14 soil correspond to four types of Fra Mauro basalts, to mare basalts and soils, and, in minor amounts, to gabbroic anorthosite and potash granite. The Fra Mauro basalts can be related by simple low pressure crystal-liquid fractionation that implies a parent composition like that of Apollo 14 sample 14310.

  20. 49 CFR 219.206 - FRA access to breath test results.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false FRA access to breath test results. 219.206 Section 219.206 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD... § 219.206 FRA access to breath test results. Documentation of breath test results must be made...

  1. 49 CFR 219.206 - FRA access to breath test results.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false FRA access to breath test results. 219.206 Section 219.206 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD... § 219.206 FRA access to breath test results. Documentation of breath test results must be made...

  2. 49 CFR Appendix C to Part 209 - FRA's Policy Statement Concerning Small Entities

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) explains FRA's communication and enforcement policies concerning small entities subject to the federal... hazardous materials shippers meeting the economic criteria established for Class III railroads in 49 CFR... enforcement actions against small businesses. Small Entity Communication Policy It is FRA's policy that...

  3. 49 CFR Appendix C to Part 209 - FRA's Policy Statement Concerning Small Entities

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) explains FRA's communication and enforcement policies concerning small entities subject to the federal... hazardous materials shippers meeting the economic criteria established for Class III railroads in 49 CFR... enforcement actions against small businesses. Small Entity Communication Policy It is FRA's policy that...

  4. 49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false FRA Freight Car Standards Defect Code C Appendix C... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Pt. 215, App. C Appendix C to Part 215—FRA Freight Car Standards Defect Code The following defect code has been established for...

  5. Requirement of Fra proteins for communication channels between cells in the filamentous nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120.

    PubMed

    Omairi-Nasser, Amin; Mariscal, Vicente; Austin, Jotham R; Haselkorn, Robert

    2015-08-11

    The filamentous nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120 differentiates specialized cells, heterocysts, that fix atmospheric nitrogen and transfer the fixed nitrogen to adjacent vegetative cells. Reciprocally, vegetative cells transfer fixed carbon to heterocysts. Several routes have been described for metabolite exchange within the filament, one of which involves communicating channels that penetrate the septum between adjacent cells. Several fra gene mutants were isolated 25 y ago on the basis of their phenotypes: inability to fix nitrogen and fragmentation of filaments upon transfer from N+ to N- media. Cryopreservation combined with electron tomography were used to investigate the role of three fra gene products in channel formation. FraC and FraG are clearly involved in channel formation, whereas FraD has a minor part. Additionally, FraG was located close to the cytoplasmic membrane and in the heterocyst neck, using immunogold labeling with antibody raised to the N-terminal domain of the FraG protein.

  6. FRA1 promotes squamous cell carcinoma growth and metastasis through distinct AKT and c-Jun dependent mechanisms.

    PubMed

    Zhang, Xiaoling; Wu, Joseph; Luo, Suju; Lechler, Terry; Zhang, Jennifer Y

    2016-06-01

    FRA1 (Fos-like antigen 1) is highly expressed in many epithelial cancers including squamous cell carcinoma of the skin (cSCC) and head and neck (HNSCC). However, the functional importance and the mechanisms mediating FRA1 function in these cancers are not fully understood. Here, we demonstrate that FRA1 gene silencing in HNSCC and cSCC cells resulted in two consequences - impaired cell proliferation and migration. FRA1 regulation of cell growth was distinct from that of c-Jun, a prominent Jun group AP-1 factor. While c-Jun was required for the expression of the G1/S phase cell cycle promoter CDK4, FRA1 was essential for AKT activation and AKT-dependent expression of CyclinB1, a molecule required for G2-M progression. Exogenous expression of a constitutively active form of AKT rescued cancer cell growth defect caused by FRA1-loss. Additionally, FRA1 knockdown markedly slowed cell adhesion and migration, and conversely expression of an active FRA1 mutant (FRA1DD) expedited these processes in a JNK/c-Jun-dependent manner. Through protein and ChIP-PCR analyses, we identified KIND1, a cytoskeletal regulator of the cell adhesion molecule β1-integrin, as a novel FRA1 transcriptional target. Restoring KIND1 expression rescued migratory defects induced by FRA1 loss. In agreement with these in vitro data, HNSCC cells with FRA1 loss displayed markedly reduced rates of subcutaneous tumor growth and pulmonary metastasis. Together, these results indicate that FRA1 promotes cancer growth through AKT, and enhances cancer cell migration through JNK/c-Jun, pinpointing FRA1 as a key integrator of JNK and AKT signaling pathways and a potential therapeutic target for cSCC and HNSCC.

  7. FRA1 promotes squamous cell carcinoma growth and metastasis through distinct AKT and c-Jun dependent mechanisms

    PubMed Central

    Zhang, Xiaoling; Wu, Joseph; Luo, Suju; Lechler, Terry; Zhang, Jennifer Y.

    2016-01-01

    FRA1 (Fos-like antigen 1) is highly expressed in many epithelial cancers including squamous cell carcinoma of the skin (cSCC) and head and neck (HNSCC). However, the functional importance and the mechanisms mediating FRA1 function in these cancers are not fully understood. Here, we demonstrate that FRA1 gene silencing in HNSCC and cSCC cells resulted in two consequences – impaired cell proliferation and migration. FRA1 regulation of cell growth was distinct from that of c-Jun, a prominent Jun group AP-1 factor. While c-Jun was required for the expression of the G1/S phase cell cycle promoter CDK4, FRA1 was essential for AKT activation and AKT-dependent expression of CyclinB1, a molecule required for G2-M progression. Exogenous expression of a constitutively active form of AKT rescued cancer cell growth defect caused by FRA1-loss. Additionally, FRA1 knockdown markedly slowed cell adhesion and migration, and conversely expression of an active FRA1 mutant (FRA1DD) expedited these processes in a JNK/c-Jun-dependent manner. Through protein and ChIP-PCR analyses, we identified KIND1, a cytoskeletal regulator of the cell adhesion molecule β1-integrin, as a novel FRA1 transcriptional target. Restoring KIND1 expression rescued migratory defects induced by FRA1 loss. In agreement with these in vitro data, HNSCC cells with FRA1 loss displayed markedly reduced rates of subcutaneous tumor growth and pulmonary metastasis. Together, these results indicate that FRA1 promotes cancer growth through AKT, and enhances cancer cell migration through JNK/c-Jun, pinpointing FRA1 as a key integrator of JNK and AKT signaling pathways and a potential therapeutic target for cSCC and HNSCC. PMID:27144339

  8. NrrA directly regulates expression of the fraF gene and antisense RNAs for fraE in the heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120.

    PubMed

    Ehira, Shigeki; Ohmori, Masayuki

    2014-05-01

    The heterocystous cyanobacterium Anabaena sp. strain PCC 7120 grows as linear multicellular filaments that can contain hundreds of cells. Heterocysts, which are specialized cells for nitrogen fixation, are regularly intercalated among photosynthetic vegetative cells, and these cells are metabolically dependent on each other. Thus, multicellularity is essential for diazotrophic growth of heterocystous cyanobacteria. In Anabaena sp. strain PCC 7120, the fraF gene, which is required to limit filament length, is induced by nitrogen deprivation. The fraF transcripts extend to the fraE gene, which lies on the opposite DNA strand and could possess dual functionality, mRNAs for fraF and antisense RNAs for fraE. In the present study, we found that NrrA, a nitrogen-regulated response regulator, directly regulated expression of fraF. Induction of fraF by nitrogen deprivation was abolished by the nrrA disruption. NrrA specifically bound to the promoter region of fraF, and recognized an inverted repeat sequence. Thus, it is concluded that NrrA controls expression of mRNAs for fraF and antisense RNAs for fraE in response to nitrogen deprivation.

  9. NrrA directly regulates expression of the fraF gene and antisense RNAs for fraE in the heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120.

    PubMed

    Ehira, Shigeki; Ohmori, Masayuki

    2014-05-01

    The heterocystous cyanobacterium Anabaena sp. strain PCC 7120 grows as linear multicellular filaments that can contain hundreds of cells. Heterocysts, which are specialized cells for nitrogen fixation, are regularly intercalated among photosynthetic vegetative cells, and these cells are metabolically dependent on each other. Thus, multicellularity is essential for diazotrophic growth of heterocystous cyanobacteria. In Anabaena sp. strain PCC 7120, the fraF gene, which is required to limit filament length, is induced by nitrogen deprivation. The fraF transcripts extend to the fraE gene, which lies on the opposite DNA strand and could possess dual functionality, mRNAs for fraF and antisense RNAs for fraE. In the present study, we found that NrrA, a nitrogen-regulated response regulator, directly regulated expression of fraF. Induction of fraF by nitrogen deprivation was abolished by the nrrA disruption. NrrA specifically bound to the promoter region of fraF, and recognized an inverted repeat sequence. Thus, it is concluded that NrrA controls expression of mRNAs for fraF and antisense RNAs for fraE in response to nitrogen deprivation. PMID:24554757

  10. Histidine 103 in Fra2 Is an Iron-Sulfur Cluster Ligand in the [2Fe-2S] Fra2-Grx3 Complex and Is Required for in Vivo Iron Signaling in Yeast*

    PubMed Central

    Li, Haoran; Mapolelo, Daphne T.; Dingra, Nin N.; Keller, Greg; Riggs-Gelasco, Pamela J.; Winge, Dennis R.; Johnson, Michael K.; Outten, Caryn E.

    2011-01-01

    The BolA homologue Fra2 and the cytosolic monothiol glutaredoxins Grx3 and Grx4 together play a key role in regulating iron homeostasis in Saccharomyces cerevisiae. Genetic studies indicate that Grx3/4 and Fra2 regulate activity of the iron-responsive transcription factors Aft1 and Aft2 in response to mitochondrial Fe-S cluster biosynthesis. We have previously shown that Fra2 and Grx3/4 form a [2Fe-2S]2+-bridged heterodimeric complex with iron ligands provided by the active site cysteine of Grx3/4, glutathione, and a histidine residue. To further characterize this unusual Fe-S-binding complex, site-directed mutagenesis was used to identify specific residues in Fra2 that influence Fe-S cluster binding and regulation of Aft1 activity in vivo. Here, we present spectroscopic evidence that His-103 in Fra2 is an Fe-S cluster ligand in the Fra2-Grx3 complex. Replacement of this residue does not abolish Fe-S cluster binding, but it does lead to a change in cluster coordination and destabilization of the [2Fe-2S] cluster. In vivo genetic studies further confirm that Fra2 His-103 is critical for control of Aft1 activity in response to the cellular iron status. Using CD spectroscopy, we find that ∼1 mol eq of apo-Fra2 binds tightly to the [2Fe-2S] Grx3 homodimer to form the [2Fe-2S] Fra2-Grx3 heterodimer, suggesting a mechanism for formation of the [2Fe-2S] Fra2-Grx3 heterodimer in vivo. Taken together, these results demonstrate that the histidine coordination and stability of the [2Fe-2S] cluster in the Fra2-Grx3 complex are essential for iron regulation in yeast. PMID:20978135

  11. The F8H Glycosyltransferase is a Functional Paralog of FRA8 Involved in Glucuronoxylan Biosynthesis in Arabidopsis

    EPA Science Inventory

    The FRAGILE FIBER8 gene was previously shown to be required for the biosynthesis of the reducing end tetrasaccharide sequence of glucuronoxylan (GX) in Arabidopsis thaliana. Here, we demonstrate that F8H, a close homolog of FRA8, is a functional ortholog of FRA8 involved in GX bi...

  12. 49 CFR 228.407 - Analysis of work schedules; submissions; FRA review and approval of submissions; fatigue...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... in paragraph (g) of this section do not have to be analyzed. A level of fatigue at which safety may... model that is already accepted by FRA. FRA has approved the Fatigue Avoidance Scheduling ToolTM (FAST... during review and approval of items required by this section. (g) Schedules not requiring analysis....

  13. 49 CFR 228.407 - Analysis of work schedules; submissions; FRA review and approval of submissions; fatigue...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... in paragraph (g) of this section do not have to be analyzed. A level of fatigue at which safety may... model that is already accepted by FRA. FRA has approved the Fatigue Avoidance Scheduling ToolTM (FAST... during review and approval of items required by this section. (g) Schedules not requiring analysis....

  14. Visualization of Fra-1/AP-1 activation during LPS-induced inflammatory lung injury using fluorescence optical imaging

    PubMed Central

    Rajasekaran, Subbiah; Tamatam, Chandramohan R.; Potteti, Haranatha R.; Raman, Venu; Lee, Jae-Woo; Matthay, Michael A.; Mehta, Dolly; Reddy, Sekhar P.

    2015-01-01

    Inappropriate lung inflammatory response following oxidant and toxicant exposure can lead to abnormal repair and disease pathogenesis, including fibrosis. Thus early detection of molecular and cellular processes and mediators promoting lung inflammation is necessary to develop better strategies for therapeutic intervention and disease management. Previously, we have shown that transcription factor Fra-1/AP-1 plays key roles in lung inflammatory response, as Fra-1-null mice are less susceptible than wild-type mice to LPS-induced lung injury and mortality. Herein, we developed a transgenic reporter mouse model expressing tdTomato under the control of FRA-1 (human) promoter (referred to as FRA-1TdTg mice) to monitor its activation during inflammatory lung injury using fluorescence protein-based optical imaging and molecular analysis in vivo and ex vivo. A higher red fluorescent signal was observed in the lungs of LPS-treated FRA-1TdTg mice compared with vehicle controls, and Western blot and qRT-PCR analyses revealed a significant correlation with the FRA-1-tdTomato reporter expression. Immunocolocalization demonstrated expression of FRA-1-tdTomato largely in lung alveolar macrophages and to some extent in epithelial cells. Moreover, we validated these results with a second reporter mouse model that expressed green fluorescent protein upon activation of endogenous Fra-1 promoter. Additionally, we demonstrated increased expression of FRA-1 in alveolar macrophages in human lung instilled with Escherichia coli ex vivo. Collectively, our data obtained from two independent reporter mouse models and from human samples underscore the significance of Fra-1 activation in alveolar macrophages during inflammatory lung injury and may aid in developing strategies to target this transcription factor in lung injury and repair. PMID:26071555

  15. DEP-induced fra-1 expression correlates with a distinct activation of AP-1-dependent gene transcription in the lung.

    PubMed

    Zhang, Qin; Kleeberger, Steven R; Reddy, Sekhar P

    2004-02-01

    Recent studies indicate a potential role for Fra-1, a heterodimeric partner of activator protein (AP)-1, in toxicant-induced epithelial injury, repair, and cellular transformation. Here we have investigated the effects of diesel exhaust particles (DEP) on fra-1 expression in C10 cells, a murine lung epithelial cell line. DEP markedly upregulated fra-1, but not fra-2, expression. The increase in fra-1 mRNA expression correlated well with its protein- and DNA-binding activity. DNA-binding assays also revealed a predominant presence of Jun-B and Jun-D in the AP-1 complex. Interestingly, DEP did not alter Jun-B and Jun-D protein levels. Transcriptional analysis revealed that fra-1 induction is regulated in part at the transcriptional level. The -379 to +32 bp 5'-flanking region mediated this induction. Furthermore, inhibitors of ERK1/2, JNK1, and p38 mitogen-activated protein kinases (MAPKs) significantly suppressed DEP-stimulated fra-1 transcription, suggesting their involvement in the induction process. Consistent with this finding, DEP stimulated phosphorylation of ERK1/2, JNK1, and p38 MAPKs with a distinct activation pattern. Overexpression of Fra-1 downregulated c-Jun and Nrf2 enhanced AP-1- and ARE-mediated reporter gene expression, respectively. In contrast, Fra-1 had the opposite effect on matrix metalloproteinase (MMP)-9 promoter activity. In particular, it bound to the functional AP-1 site of the MMP-9 promoter after DEP stimulation. Consistent with this result, DEP also markedly upregulated MMP-9 promoter activity. Collectively, these findings suggest that fra-1 induction by DEP may play a role in selectively regulating gene expression involved in alveolar epithelial cell injury and repair. PMID:14565943

  16. 49 CFR 240.103 - Approval of design of individual railroad programs by FRA.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Approval of design of individual railroad programs... (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION QUALIFICATION AND CERTIFICATION OF... individual railroad programs by FRA. (a) Each railroad shall submit its written certification program and...

  17. 49 CFR 240.103 - Approval of design of individual railroad programs by FRA.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Approval of design of individual railroad programs... (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION QUALIFICATION AND CERTIFICATION OF... individual railroad programs by FRA. (a) Each railroad shall submit its written certification program and...

  18. 49 CFR 240.103 - Approval of design of individual railroad programs by FRA.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Approval of design of individual railroad programs... (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION QUALIFICATION AND CERTIFICATION OF... individual railroad programs by FRA. (a) Each railroad shall submit its written certification program and...

  19. 49 CFR 240.103 - Approval of design of individual railroad programs by FRA.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Approval of design of individual railroad programs... (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION QUALIFICATION AND CERTIFICATION OF... individual railroad programs by FRA. (a) Each railroad shall submit its written certification program and...

  20. 49 CFR Appendix C to Part 229 - FRA Locomotive Standards-Code of Defects

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... FR 21121, Mar. 31, 1980, as part of the original document, is not carried in the CFR. ... 49 Transportation 4 2010-10-01 2010-10-01 false FRA Locomotive Standards-Code of Defects C Appendix C to Part 229 Transportation Other Regulations Relating to Transportation (Continued)...

  1. 49 CFR Appendix C to Part 229 - FRA Locomotive Standards-Code of Defects

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... FR 21121, Mar. 31, 1980, as part of the original document, is not carried in the CFR. ... 49 Transportation 4 2013-10-01 2013-10-01 false FRA Locomotive Standards-Code of Defects C Appendix C to Part 229 Transportation Other Regulations Relating to Transportation (Continued)...

  2. 49 CFR Appendix C to Part 229 - FRA Locomotive Standards-Code of Defects

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... FR 21121, Mar. 31, 1980, as part of the original document, is not carried in the CFR. ... 49 Transportation 4 2014-10-01 2014-10-01 false FRA Locomotive Standards-Code of Defects C Appendix C to Part 229 Transportation Other Regulations Relating to Transportation (Continued)...

  3. 49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... of the code is to establish a uniform language among FRA, States, and the railroad industry that will... Freight Car Truck. Car Bodies 215.121Defective Car Body. Draft System 215.123Defective Couplers. 215.... 215.121Defective car body. (A) Improper clearance—less than 21/2″ from top of rail. (B) Center sill...

  4. 49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... of the code is to establish a uniform language among FRA, States, and the railroad industry that will... Freight Car Truck. Car Bodies 215.121Defective Car Body. Draft System 215.123Defective Couplers. 215.... 215.121Defective car body. (A) Improper clearance—less than 21/2″ from top of rail. (B) Center sill...

  5. 49 CFR Appendix C to Part 209 - FRA's Policy Statement Concerning Small Entities

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... SBREFA: The severity of the safety or health risk presented; the existence of alternative methods of... hazardous materials shippers meeting the economic criteria established for Class III railroads in 49 CFR... of civil penalties and resolution of those assessments. Pursuant to FRA's statutory authority, and...

  6. 75 FR 34213 - Solicitation of Applications and Notice of Funding Availability for the FRA Railroad System...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-16

    ... 13, 2010 (75 FR 27112), the FRA sought applications from interested and responsible parties for two grants: to conduct a Locomotive Biofuel Study, and to conduct a Study of the Use of Bio-based... consult the notice published on May 13, 2010 in the Federal Register (75 FR 27112) for additional...

  7. Uniparental disomy (UPD) for fra(X) in a 47,XXY male

    SciTech Connect

    Torfs, C.P.; Christianson, R.E.; Amos, J.A.; Huang, X.L.; Kang, X.Z.

    1994-09-01

    We report a 4-year-old hyperactive, mentally retarded male with 47,XXY and UPD for fra(X). Speech and motor delay were first noted at age 15 months. He has no dysmorphic features, normal ears, hyperextensible joints, small testes, and no history of seizures. His mother has prominent lowest ears, a long midface, anteverted nostrils, hyperextensible joints, malocclusion, and had learning problems in school. Routine chromosome analysis revealed the proband to be 47,XXY. Parental chromosomes were normal in number. The proband was fra(X) positive [30/160 cells, 18%]. No cells had two expressed fra(X)s; however, this may be a function of the low level of expression and the number of cells scored. Maternal cells were also fra(X) positive [19/205, 9.2%]. Southern analysis demonstrated the mother to be heterozygous for a methylated, full mutation (>220 repeats); her normal FMR-1 gene was disproportionately unmethylated. The proband had two fully expanded and methylated FMR-1 genes, one the same size as the maternal gene and the other >620 repeats. RFLP analysis revealed a maternal meiotic II error, the result of which was UPD of the X chromosome.

  8. 49 CFR 240.103 - Approval of design of individual railroad programs by FRA.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Approval of design of individual railroad programs... (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION QUALIFICATION AND CERTIFICATION OF... individual railroad programs by FRA. (a) Each railroad shall submit its written certification program and...

  9. FRA2A Is a CGG Repeat Expansion Associated with Silencing of AFF3

    PubMed Central

    Metsu, Sofie; Rooms, Liesbeth; Rainger, Jacqueline; Taylor, Martin S.; Bengani, Hemant; Wilson, David I.; Chilamakuri, Chandra Sekhar Reddy; Morrison, Harris; Vandeweyer, Geert; Reyniers, Edwin; Douglas, Evelyn; Thompson, Geoffrey; Haan, Eric; Gecz, Jozef; FitzPatrick, David R.; Kooy, R. Frank

    2014-01-01

    Folate-sensitive fragile sites (FSFS) are a rare cytogenetically visible subset of dynamic mutations. Of the eight molecularly characterized FSFS, four are associated with intellectual disability (ID). Cytogenetic expression results from CGG tri-nucleotide-repeat expansion mutation associated with local CpG hypermethylation and transcriptional silencing. The best studied is the FRAXA site in the FMR1 gene, where large expansions cause fragile X syndrome, the most common inherited ID syndrome. Here we studied three families with FRA2A expression at 2q11 associated with a wide spectrum of neurodevelopmental phenotypes. We identified a polymorphic CGG repeat in a conserved, brain-active alternative promoter of the AFF3 gene, an autosomal homolog of the X-linked AFF2/FMR2 gene: Expansion of the AFF2 CGG repeat causes FRAXE ID. We found that FRA2A-expressing individuals have mosaic expansions of the AFF3 CGG repeat in the range of several hundred repeat units. Moreover, bisulfite sequencing and pyrosequencing both suggest AFF3 promoter hypermethylation. cSNP-analysis demonstrates monoallelic expression of the AFF3 gene in FRA2A carriers thus predicting that FRA2A expression results in functional haploinsufficiency for AFF3 at least in a subset of tissues. By whole-mount in situ hybridization the mouse AFF3 ortholog shows strong regional expression in the developing brain, somites and limb buds in 9.5–12.5dpc mouse embryos. Our data suggest that there may be an association between FRA2A and a delay in the acquisition of motor and language skills in the families studied here. However, additional cases are required to firmly establish a causal relationship. PMID:24763282

  10. Blood flow velocity measurements in rat mesentery arterioles in health and under hypertensive conditions

    NASA Astrophysics Data System (ADS)

    Polyakova, Marina S.; Sokolova, Irina A.; Priezzhev, Alexander V.; Proskurin, Sergei G.; Savchenko, Natalia B.; Shakhnazarov, Alexander A.

    1994-07-01

    Laser Doppler measurements of blood flow velocities in the vessels of rat mesentery have been performed to study the effect of the drag-reducing agent polyethylene oxide Polyox WSR-301 on microcirculation. These agents are capable of increasing the cardiac output and decreasing the arterial pressure. Measurements performed on spontaneously hypertensive rats anesthetized by Nembutal showed that the mean blood velocities in all groups of studied vessels are higher (by nearly two to three times) as compared to those in controls. Most likely these results reflect the effects of hypertensive raising pressure drop and the `rarefaction' phenomenon.

  11. Requirement of Fra proteins for communication channels between cells in the filamentous nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120

    PubMed Central

    Omairi-Nasser, Amin; Mariscal, Vicente; Austin, Jotham R.; Haselkorn, Robert

    2015-01-01

    The filamentous nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120 differentiates specialized cells, heterocysts, that fix atmospheric nitrogen and transfer the fixed nitrogen to adjacent vegetative cells. Reciprocally, vegetative cells transfer fixed carbon to heterocysts. Several routes have been described for metabolite exchange within the filament, one of which involves communicating channels that penetrate the septum between adjacent cells. Several fra gene mutants were isolated 25 y ago on the basis of their phenotypes: inability to fix nitrogen and fragmentation of filaments upon transfer from N+ to N− media. Cryopreservation combined with electron tomography were used to investigate the role of three fra gene products in channel formation. FraC and FraG are clearly involved in channel formation, whereas FraD has a minor part. Additionally, FraG was located close to the cytoplasmic membrane and in the heterocyst neck, using immunogold labeling with antibody raised to the N-terminal domain of the FraG protein. PMID:26216997

  12. Requirement of Fra proteins for communication channels between cells in the filamentous nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120.

    PubMed

    Omairi-Nasser, Amin; Mariscal, Vicente; Austin, Jotham R; Haselkorn, Robert

    2015-08-11

    The filamentous nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120 differentiates specialized cells, heterocysts, that fix atmospheric nitrogen and transfer the fixed nitrogen to adjacent vegetative cells. Reciprocally, vegetative cells transfer fixed carbon to heterocysts. Several routes have been described for metabolite exchange within the filament, one of which involves communicating channels that penetrate the septum between adjacent cells. Several fra gene mutants were isolated 25 y ago on the basis of their phenotypes: inability to fix nitrogen and fragmentation of filaments upon transfer from N+ to N- media. Cryopreservation combined with electron tomography were used to investigate the role of three fra gene products in channel formation. FraC and FraG are clearly involved in channel formation, whereas FraD has a minor part. Additionally, FraG was located close to the cytoplasmic membrane and in the heterocyst neck, using immunogold labeling with antibody raised to the N-terminal domain of the FraG protein. PMID:26216997

  13. Fra-1 is upregulated in gastric cancer tissues and affects the PI3K/Akt and p53 signaling pathway in gastric cancer.

    PubMed

    He, Junyu; Zhu, Guangchao; Gao, Lu; Chen, Pan; Long, Yuehua; Liao, Shan; Yi, Hong; Yi, Wei; Pei, Zhen; Wu, Minghua; Li, Xiaoling; Xiang, Juanjuan; Peng, Shuping; Ma, Jian; Zhou, Ming; Xiong, Wei; Zeng, Zhaoyang; Xiang, Bo; Tang, Ke; Cao, Li; Li, Guiyuan; Zhou, Yanhong

    2015-11-01

    Gastric cancer is an aggressive disease that continues to have a daunting impact on global health. Fra-1 (FOSL1) plays important roles in oncogenesis in various malignancies. We investigated the expression of Fra-1 in gastric cancer (GC) tissues by qPCR, immunohistochemistry (IHC) and western blot technologies. The results showed that Fra-1 was overexpressed in gastric cancer tissues compared with the adjacent non‑cancerous tissues. To explore the possible mechanism of Fra-1 in GC, we elucidated the effect of Fra-1 in the apoptosis and cell cycle of gastric cancer cells, AGS, and found that a considerable decrease in apoptotic cells and increase of S phase rate were observed for AGS cells with Fra-1 overexpession. We identified and confirmed that Fra-1 affected the expression level of CTTN and EZR in vitro through LC-MS/MS analyses and western blot technology. Furthermore, we found that Fra-1 was correlated with dysregulation PI3K/Akt and p53 signaling pathway in gastric cancer tissues in vitro. Moreover, we found that Fra-1 overexpression affected the expression of PI3K, Akt, MDM2 and p53 in vivo. In summary, our results suggest that Fra-1 is upregulated in gastric cancer tissues and plays its function by affecting the PI3K/Akt and p53 signaling pathway in gastric cancer.

  14. Fra-1/AP-1 induces EMT in mammary epithelial cells by modulating Zeb1/2 and TGFβ expression

    PubMed Central

    Bakiri, L; Macho-Maschler, S; Custic, I; Niemiec, J; Guío-Carrión, A; Hasenfuss, S C; Eger, A; Müller, M; Beug, H; Wagner, E F

    2015-01-01

    Epithelial-to-mesenchymal transition (EMT) is essential for embryonic morphogenesis and wound healing and critical for tumour cell invasion and dissemination. The AP-1 transcription factor Fra-1 has been implicated in tumorigenesis and in tumour-associated EMT in human breast cancer. We observed a significant inverse correlation between Fra-1 mRNA expression and distant-metastasis-free survival in a large cohort of breast cancer patients derived from multiple array data sets. This unique correlation among Fos genes prompted us to assess the evolutionary conservation between Fra-1 functions in EMT of human and mouse cells. Ectopic expression of Fra-1 in fully polarized, non-tumourigenic, mouse mammary epithelial EpH4 cells induced a mesenchymal phenotype, characterized by a loss of epithelial and gain of mesenchymal markers. Proliferation, motility and invasiveness were also increased in the resulting EpFra1 cells, and the cells were tumourigenic and efficiently colonized the lung upon transplantation. Molecular analyses revealed increased expression of Tgfβ1 and the EMT-inducing transcription factors Zeb1, Zeb2 and Slug. Mechanistically, Fra-1 binds to the tgfb1 and zeb2 promoters and to an evolutionarily conserved region in the first intron of zeb1. Furthermore, increased activity of a zeb2 promoter reporter was detected in EpFra1 cells and shown to depend on AP-1-binding sites. Inhibiting TGFβ signalling in EpFra1 cells moderately increased the expression of epithelial markers, whereas silencing of zeb1 or zeb2 restored the epithelial phenotype and decreased migration in vitro and tumorigenesis in vivo. Thus Fra-1 induces changes in the expression of genes encoding EMT-related transcription factors leading to the acquisition of mesenchymal, invasive and tumorigenic capacities by epithelial cells. This study defines a novel function of Fra-1/AP-1 in modulating tgfb1, zeb1 and zeb2 expression through direct binding to genomic regulatory regions, which establishes

  15. Investigating the cubosomal ability for transnasal brain targeting: In vitro optimization, ex vivo permeation and in vivo biodistribution.

    PubMed

    Abdelrahman, Fatma Elzahraa; Elsayed, Ibrahim; Gad, Mary Kamal; Badr, Ahmed; Mohamed, Magdi Ibrahim

    2015-07-25

    The aim of this study was to enhance the risperidone delivery to the brain through the transnasal route via optimization of cubosomal gel. Cubosomes were prepared using glycerol mono-oleate (GMO), Pluronic F127 (PF127) and Tween 80 (T80). The prepared formulae were characterized by testing their particle size, polydispersity index, zeta potential, entrapment efficiency, in vitro drug release and transmission electron microscopy. Central composite design was planned for the formulae optimization and the selected formula (containing PF127 with concentration 15 mg/g GMO and T80 with concentration of 20mg/L) was re-prepared in presence of gelling polymer (gellan gum or polyox). The optimal cubosomal gel (containing 0.4% w/v polyox) had been subjected to ex-vivo permeation, histopathological evaluation and in vivo biodistribution studies. It showed significantly higher transnasal permeation and better distribution to the brain, when compared to the used control (drug solution and/or suspension). Finally, the cubosomal gel could be considered as a promising carrier for brain targeting of CNS acting drugs through the transnasal route.

  16. Hot-melts in buccoadhesive patches: an approach for bioavailability enhancement of highly-metabolized drugs with short elimination half-life.

    PubMed

    El Mahrouk, Galal M; ElGazayerly, Omaima N; Aboelwafa, Ahmed A; Taha, Maie S

    2014-11-01

    The present study deals with the inclusion or incorporation of hot-melts into buccoadhesive patches. Our aim is to develop a patient-friendly dosage form that is capable of extending release of short elimination half-life drugs so to decrease dosing frequency and to increase the bioavailability of highly-metabolized drugs with the ultimate aim of dose reduction. Tizanidine hydrochloride (TIZ) was used as a model drug.TIZ was incorporated into Compritol-based hot-melts, and then further formulated into buccal patches prepared using HPMC, PVA and Polyox. A Central Composite Face-centered Design was employed to statistically optimize the formulation variables; HPMC solution/PVA solution weight ratio, Compritol/TIZ ratio in the hot-melts and percentage Polyox. The optimized formula suggested by the software was successful in controlling drug release, where 85% of TIZ was released after 4 h and the patch showed acceptable mucoadhesion properties. Pharmacokinetic parameters of TIZ from the optimized formula were compared to those of the immediate release tablet, Sirdalud®, as reference in human volunteers using a randomized crossover design. Significant increase was observed for Cmax, Tmax, AUC(0-12) and AUC(0-1). The increase in relative bioavailability of TIZ from the optimized formula was 2.57 folds.

  17. Apollo 14 mineral ages and the thermal history of the Fra Mauro formation.

    NASA Technical Reports Server (NTRS)

    Compston, W.; Vernon, M. J.; Berry, H.; Rudowski, R.; Gray, C. M.; Ware, N.; Chappell, B. W.; Kaye, M.

    1972-01-01

    The thermal inertia of the Fra Mauro formation limits its rate of cooling. The calculations of Jaeger (1961) for the cooling of an extrusive sheet are used to estimate the time required for a central temperature drop of 10%. This time is found to be about 45 years. For a 90% temperature drop, the time is about 200 years. Analytical methods used in the investigations are discussed together with the diffusion of Rb and Sr within lunar basalt. Isochron diagrams for various minerals are presented.

  18. Fra Angelico's painting technique revealed by terahertz time-domain imaging (THz-TDI)

    NASA Astrophysics Data System (ADS)

    Koch Dandolo, Corinna Ludovica; Picollo, Marcello; Cucci, Costanza; Jepsen, Peter Uhd

    2016-10-01

    We have investigated with terahertz time-domain imaging (THz-TDI) the well-known Lamentation over the dead Christ panel painting (San Marco Museum, Florence) painted by Fra Giovanni Angelico within 1436 and 1441. The investigation provided a better understanding of the construction and gilding technique used by the eminent artist, as well as the plastering technique used during the nineteenth-century restoration intervention. The evidence obtained from THz-TDI scans was correlated with the available documentation on the preservation history of the art piece. Erosion and damages documented for the wooden support, especially in the lower margin, found confirmation in the THz-TD images.

  19. Expression of AP-1 family transcription factors in the amygdala during conditioned taste aversion learning: role for Fra-2

    PubMed Central

    Kwon, Bumsup; Goltz, Marion; Houpt, Thomas A.

    2009-01-01

    Conditioned taste aversion (CTA) learning occurs after the pairing of a novel taste with a toxin (e.g. sucrose with LiCl). The immediate-early gene c-Fos is necessary for CTA learning, but c-Fos alone cannot be sufficient for consolidation. The expression of other AP-1 proteins from the Fos- and Jun-families may also be required shortly after conditioning for CTA consolidation. To screen for the expression of AP-1 transcription factors within small subregions, RT-PCR analysis was used after laser capture microdissection of the amygdala. Rats were infused intraorally with 5% sucrose (6ml/6min) or injected with LiCl (12ml/kg, 0.15M, i.p.) or given sucrose paired with LiCl (sucrose/LiCl), or not treated; 1 h later their brains were dissected. The lateral (LA), basolateral (BLA), and central (CeA) subnuclei of the amgydala of single 5 μm sections from individual rats were dissected using the Arcturus PixCell II system. Semi-quantitative RT-PCR showed the consistent presence of c-Fos, Fra-2, c-Jun, and JunD in the amygdala. In situ hybridization confirmed that c-Fos and Fra-2 mRNA expression was increased in the CeA after LiCl and sucrose/LiCl treatment. Immunohistochemistry for Fra-2 revealed high baseline levels of Fra-2 protein in the BLA and CeA, but also an increase in Fra-2 in the BLA and CeA after LiCl and sucrose/LiCl treatment. The similarity of response in LiCl and sucrose/LiCl treated groups might reflect activation by LiCl in both groups. To control for the effects of LiCl, rats were tested in a learned safety experiment. Fra-2 and c-Fos were examined in response to sucrose/LiCl in rats with prior familiarity with sucrose compared to rats without prior exposure to sucrose. The familiar (pre-exposure) group showed a significantly decreased number of Fra-2-positive cells compared with the novel group in the BLA, but not in the CeA. Because pre-exposure to sucrose attenuates CTA learning, a decreased cellular response in pre-exposed rats suggests a specific

  20. Fra a 1.02 Is the Most Potent Isoform of the Bet v 1-like Allergen in Strawberry Fruit.

    PubMed

    Franz-Oberdorf, Katrin; Eberlein, Bernadette; Edelmann, Kathrin; Hücherig, Stephanie; Besbes, Fatma; Darsow, Ulf; Ring, Johannes; Schwab, Wilfried

    2016-05-11

    The strawberry fruit proteins Fra a 1.01E-1.08 are homologues of the major birch pollen allergen Bet v 1. Three of the proteins are known to have essential biological functions in pigment formation during fruit ripening and seem to be responsible for allergic reactions to strawberry fruit. We evaluated the cross-reactive allergenic potential of these putative strawberry allergens in patients allergic to birch pollen. Activation of basophils of eight atopic patients was studied using different concentrations of Fra a 1 isoforms. Bet v 1a was used as control and as atopic patient selection criterion. Although Fra a 1.01E-1.08 have amino acid sequence identities of 74.5-97.5% with Fra a 1.02, the basophil activation mediated by the eight Fra a 1 proteins differed substantially. Fra a 1.03 and Fra a 1.02 showed the highest activation of basophils, 73 and 66% of total basophils, respectively. On the basis of the high relative expression of the gene Fra a 1.02 in ripe strawberry fruits of allergenic varieties, Fra a 1.02 was identified as the main strawberry allergen of the Bet v 1 superfamily. Knowledge of the allergenic potential of Fra a 1.02/1.03 will help to improve food safety and can serve as a valuable marker for the development of red-fruited hypoallergenic strawberry cultivars. PMID:27086707

  1. Characterization of FRA7B, a human common fragile site mapped at the 7p chromosome terminal region.

    PubMed

    Bosco, Nazario; Pelliccia, Franca; Rocchi, Angela

    2010-10-01

    Common fragile sites (CFS) are specific regions of the mammalian chromosomes that are particularly prone to gaps and breaks. They are a cause of genome instability, and the location of many CFS correlates with breakpoints of aberrations recurrent in some cancers. The molecular characterization of some CFS has not clarified the causes of their fragility. In this work, by using fluorescence in situ hybridization analysis with BAC and PAC clones, we determined the DNA sequence of the CFS FRA7B. The FRA7B sequence was then analyzed to identify coding sequences and some structural features possibly involved in fragility. FRA7B spans about 12.2 megabases, and is therefore one of the largest CFS analyzed. It maps at the 7p21.3-22.3 chromosome bands, therefore at the interface of G- and R-band regions that are probably difficult to replicate. A 90-kilobase long sequence that presents very high flexibility values was identified at the very beginning of the more fragile CFS region. Three large genes (THSD7A, SDK1, and MAD1L1) and two miRNA genes (MIRN589 and MIRN339) map in the fragile region. The chromosome band 7p22 is a recurrent breakpoint in chromosome abnormalities in different types of neoplasm. FRA7B is the first characterized CFS located in a chromosome terminal region.

  2. 49 CFR 228.407 - Analysis of work schedules; submissions; FRA review and approval of submissions; fatigue...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... review and approval of submissions; fatigue mitigation plans. 228.407 Section 228.407 Transportation... schedules; submissions; FRA review and approval of submissions; fatigue mitigation plans. (a) Analysis of... by action in compliance with the railroad's fatigue mitigation plan that has been approved by...

  3. Fracture network evaluation program (FraNEP): A software for analyzing 2D fracture trace-line maps

    NASA Astrophysics Data System (ADS)

    Zeeb, Conny; Gomez-Rivas, Enrique; Bons, Paul D.; Virgo, Simon; Blum, Philipp

    2013-10-01

    Fractures, such as joints, faults and veins, strongly influence the transport of fluids through rocks by either enhancing or inhibiting flow. Techniques used for the automatic detection of lineaments from satellite images and aerial photographs, LIDAR technologies and borehole televiewers significantly enhanced data acquisition. The analysis of such data is often performed manually or with different analysis software. Here we present a novel program for the analysis of 2D fracture networks called FraNEP (Fracture Network Evaluation Program). The program was developed using Visual Basic for Applications in Microsoft Excel™ and combines features from different existing software and characterization techniques. The main novelty of FraNEP is the possibility to analyse trace-line maps of fracture networks applying the (1) scanline sampling, (2) window sampling or (3) circular scanline and window method, without the need of switching programs. Additionally, binning problems are avoided by using cumulative distributions, rather than probability density functions. FraNEP is a time-efficient tool for the characterisation of fracture network parameters, such as density, intensity and mean length. Furthermore, fracture strikes can be visualized using rose diagrams and a fitting routine evaluates the distribution of fracture lengths. As an example of its application, we use FraNEP to analyse a case study of lineament data from a satellite image of the Oman Mountains.

  4. Sedimentology of clastic rocks from the Fra Mauro region of the moon.

    NASA Technical Reports Server (NTRS)

    Lindsay, J. F.

    1972-01-01

    A thin-section examination of sixteen clastic rock samples returned by the Apollo 14 mission from the Fra Mauro region of the moon suggests the presence of at least two distinctly different lithologies. Five of the samples (group I) are characterized by an abundant glassy matrix and glass particles and lesser amounts of plagioclase and pyroxene grains, and lithic clasts. The other eleven samples (group II) are relatively fine grained, very poorly sorted, and consist largely of pyroxene, plagioclase, and lithic clasts set in an abundant mineralic matrix. Group I and II lithologies were probably both deposited from impact generated base surges. The differences between them stem not as much from the basic sedimentary processes as from the differences in the magnitude of the events generating the base surges and the resultant difference in available detrital materials.

  5. Rb-Sr ages of igneous rocks from the Apollo 14 mission and the age of the Fra Mauro formation.

    NASA Technical Reports Server (NTRS)

    Papanastassiou, D. A.; Wasserburg, G. J.

    1971-01-01

    Internal Rb-Sr isochrons were determined on four basaltic rocks and on a basaltic clast from a breccia from the Fra Mauro landing site. An internal isochron was determined for rock 12004 and yielded a value in agreement with previous results for basaltic rocks from the Apollo 12 site. The crystallization ages for Apollo 14 basalts are only 0.2 to 0.3 AE older than were found for mare basalts from the Sea of Tranquility. Assuming these leucocratic igneous rocks to be representative of the Fra Mauro site, it follows that there were major igneous processes active in these regions, and presumably throughout the highlands, at times only slightly preceding the periods at which the maria were last flooded.

  6. The Fra-1–miR-134–SDS22 feedback loop amplifies ERK/JNK signaling and reduces chemosensitivity in ovarian cancer cells

    PubMed Central

    Wu, Jianmin; Sun, Yimin; Zhang, Pei-Ying; Qian, Mengyao; Zhang, Hengchao; Chen, Xiao; Ma, Di; Xu, Yunsheng; Chen, Xiaoming; Tang, Kai-Fu

    2016-01-01

    The Fra-1 transcription factor is frequently upregulated in multiple types of tumors. Here we found that Fra-1 promotes miR-134 expression. miR-134 activates JNK and ERK by targeting SDS22, which in turn induces Fra-1 expression and leads to miR-134 upregulation. In addition, miR-134 augmented H2AX S139 phosphorylation by activating JNK and promoted non-homologous end joining (NHEJ)-mediated DNA repair. Therefore, ectopic miR-134 expression reduced chemosensitivity in ovarian cancer cells. Furthermore, miR-134 promotes cell proliferation, migration and invasion of ovarian cancer cells, and enhances tumor growth in vivo. Of particular significance, both Fra-1 and miR-134 are upregulated in ovarian cancer tissues, and Fra-1 and miR-134 expression is positively correlated. High levels of miR-134 expression were associated with a reduced median survival of ovarian cancer patients. Our study revealed that a Fra-1-miR-134 axis drives a positive feedback loop that amplifies ERK/JNK signaling and reduces chemosensitivity in ovarian cancer cells. PMID:27685628

  7. UCSD/FRA non-contact ultrasonic guided-wave system for rail inspection: an update

    NASA Astrophysics Data System (ADS)

    Coccia, Stefano; Phillips, Robert; Nucera, Claudio; Bartoli, Ivan; Salamone, Salvatore; Lanza di Scalea, Francesco; Fateh, Mahmood; Carr, Gary

    2011-04-01

    The University of California at San Diego (UCSD), under a Federal Railroad Administration (FRA) Office of Research and Development (R&D) grant, is developing a system for high-speed and non-contact rail defect detection. A prototype has been designed and field tested with the support of Volpe National Transportation Systems Center and ENSCO, Inc. The goal of this project is to develop a rail defect detection system that provides (a) better defect detection reliability (including internal transverse head defects under shelling and vertical split head defects), and (b) higher inspection speed than achievable by current rail inspection systems. This effort is also in direct response to Safety Recommendations issued by the National Transportation Safety Board (NTSB) following the disastrous train derailments at Superior, WI in 1992 and Oneida, NY in 2007 among others. The UCSD prototype uses non-contact ultrasonic probing of the rail head (laser and air-coupled), ultrasonic guided waves, and a proprietary real-time statistical analysis algorithm that maximizes the sensitivity to defects while minimizing false positives. The current design allows potential inspection speeds up to 40 mph, although all field tests have been conducted up to 15 mph so far. This paper summarizes (a) the latest technology development test conducted at the rail defect farm of Herzog, Inc. in St Joseph, MO in June 2010, and (b) the completion of the new Rail Defect Farm facility at the UCSD Camp Elliott Field Station with partial in-kind donations from the Burlington Northern Santa Fe (BNSF) Railway.

  8. Neoplastic transformation of rat thyroid cells requires the junB and fra-1 gene induction which is dependent on the HMGI-C gene product.

    PubMed Central

    Vallone, D; Battista, S; Pierantoni, G M; Fedele, M; Casalino, L; Santoro, M; Viglietto, G; Fusco, A; Verde, P

    1997-01-01

    The expression of the high mobility group I (HMGI)-C chromatin component was shown previously to be essential for the establishment of the neoplastic phenotype in retrovirally transformed thyroid cell lines. To identify possible targets of the HMGI-C gene product, we have analyzed the AP-1 complex in normal, fully transformed and antisense HMGI-C-expressing rat thyroid cells. We show that neoplastic transformation is associated with a drastic increase in AP-1 activity, which reflects multiple compositional changes. The strongest effect is represented by the dramatic junB and fra-1 gene induction, which is prevented in cell lines expressing the antisense HMGI-C. These results indicate that the HMGI-C gene product is essential for the junB and fra-1 transcriptional induction associated with neoplastic transformation. The inhibition of Fra-1 protein synthesis by stable transfection with a fra-1 antisense RNA vector significantly reduces the malignant phenotype of the transformed thyroid cells, indicating a pivotal role for the fra-1 gene product in the process of cellular transformation. PMID:9311991

  9. Mice with a fra-1 knock-in into the c-fos locus show impaired spatial but regular contextual learning and normal LTP.

    PubMed

    Gass, Peter; Fleischmann, Alexander; Hvalby, Oivind; Jensen, Vidar; Zacher, Christiane; Strekalova, Tatyana; Kvello, Ane; Wagner, Erwin F; Sprengel, Rolf

    2004-11-01

    The immediate early gene c-fos is part of the AP-1 transcription factor complex, which is involved in molecular mechanisms underlying learning and memory. Mice that lack c-Fos in the brain show impairments in spatial reference and contextual learning, and also exhibit a reduced long-term potentiation of synaptic transmission (LTP) at CA3-to-CA1 synapses. In the present study, we investigated mice in which c-fos was deleted and replaced by fra-1 (c-fos(fra-1) mice) to determine whether other members of the c-fos gene family can substitute for the functions of the c-fos gene. In c-fos(fra-1) mice, both CA3-to-CA1 LTP and contextual learning in a Pavlovian fear conditioning task were similar to wild-type littermates, indicating that Fra-1 expression restored the impairments caused by brain-specific c-Fos depletion. However, c-Fos-mediated learning deficits in a reference memory task of the Morris watermaze were also present in c-fos(fra-1) mice. These findings suggest that different c-Fos target genes are involved in LTP, contextual learning, and spatial reference memory formation.

  10. Reverse mapping of the gene encoding the human fos-related antigen-1 (fra-1) within chromosome band 11q13

    SciTech Connect

    Sinke, R.J. ); Tanigami, A.; Nakamura, Y.; Kessel, A.G. van )

    1993-10-01

    For the identification of sequence-tagged sites within cosmid clones derived from the q13 region of human chromosome 11, the authors subcloned a number of single copy BamHI fragments in a pT7T3 19U vector. Surprisingly, within one of these subclones, they encountered a stretch of DNA that matches perfectly with 5' end of the known cDNA sequence for the human fos-related antigen. This match comes to an abrupt end at nucleotide 328, which coincides with a perfect splice donor site. At position 231 an ATG codon (translation initiation) was found. From these data they conclude that position 328 marks the boundary of the first exon of the fra-1 gene. Homology of this same region with the rat fra-1 cDNA sequence is [+-]70%. This human fra-1 genomic fragment is contained within cosmid clone cCL11-254 (D11S460), which was previously mapped to region V of a long-range contig map of 11q13. The localization of fra-1 on chromosome 11 was cross-checked and confirmed by hybridizing the fra-1 containing fragment to a panel of somatic cell hybrids, including one line that contains chromosome 11 as its only human constituent. In addition to a cross-hybridizing rodent fragment, a single human-specific band was revealed in all the chromosome 11-containing hybrids. This subchromosomal localization of fra-1 to 11q13 adds yet another proto-oncogene to this restricted genomic region, which appears to be involved in a number of neoplastic disorders, e.g., multiple endocrine neoplasia type 1, breast cancer, squamous cell tumors of head and neck, esophageal carcinoma, hepatocellular carcinoma, melanoma, bladder carcinoma, extragonadal germ cell tumors, and some hematopoietic malignancies. 7 refs., 1 fig.

  11. WWOX, the chromosomal fragile site FRA16D spanning gene: Its role in metabolism and contribution to cancer

    PubMed Central

    Choo, Amanda; Lee, Cheng Shoou; Dayan, Sonia; O’Keefe, Louise

    2015-01-01

    The WWOX gene spans the common chromosomal fragile site FRA16D that is located within a massive (780 kb) intron. The WWOX gene is very long, at 1.1 Mb, which may contribute to the very low abundance of the full-length 1.4 kb mRNA. Alternative splicing also accounts for a variety of aberrant transcripts, most of which are devoid of C-terminal sequences required for WWOX to act as an oxidoreductase. The mouse WWOX gene also spans a chromosomal fragile site implying some sort of functional relationship that confers a selective advantage. The encoded protein domains of WWOX are conserved through evolution (between humans and Drosophila melanogaster) and include WW domains, an NAD -binding site, short-chain dehydrogenase/reductase enzyme and nuclear compartmentalization signals. This homology has enabled functional analyses in D. melanogaster that demonstrate roles for WWOX in reactive oxygen species regulation and metabolism. Indeed the human WWOX gene is also responsive to altered metabolism. Cancer cells typically exhibit altered metabolism (Warburg effect). Many cancers exhibit FRA16D DNA instability that results in aberrant WWOX expression and is associated with poor prognosis for these cancers. It is therefore thought that aberrant WWOX expression contributes to the altered metabolism in cancer. In addition, others have found that a specific (low-expression) allele of WWOX genotype contributes to cancer predisposition. PMID:25595186

  12. SOX4 is a direct target gene of FRA-2 and induces expression of HDAC8 in adult T-cell leukemia/lymphoma.

    PubMed

    Higuchi, Tomonori; Nakayama, Takashi; Arao, Tokuzo; Nishio, Kazuto; Yoshie, Osamu

    2013-05-01

    Previously, we have shown that an AP-1 family member, FRA-2, is constitutively expressed in adult T-cell leukemia/lymphoma (ATL) and, together with JUND, upregulates CCR4 and promotes ATL cell growth. Among the identified potential target genes of FRA-2/JUND was SOX4. Here, we examine the expression and function of SOX4 in ATL. SOX4 was indeed consistently expressed in primary ATL cells. FRA-2/JUND efficiently activated the SOX4 promoter via an AP-1 site. Knockdown of SOX4 expression by small interfering RNA (siRNA) strongly suppressed cell growth of ATL cell lines. Microarray analyses revealed that SOX4 knockdown reduced the expression of genes such as germinal center kinase related (GCKR), NAK-associated protein 1 (NAP1), and histone deacetylase 8 (HDAC8). We confirmed consistent expression of GCKR, NAP1, and HDAC8 in primary ATL cells. We also showed direct activation of the HDAC8 promoter by SOX4. Furthermore, siRNA knockdown of GCKR, NAP1, and HDAC8 each significantly suppressed cell growth of ATL cell lines. Taken together, we have revealed an important oncogenic cascade involving FRA-2/JUND and SOX4 in ATL, which leads to the expression of genes such as GCKR, NAP1, and HDAC8. PMID:23482931

  13. 49 CFR Appendix F to Part 236 - Minimum Requirements of FRA Directed Independent Third-Party Assessment of PTC System Safety...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Third-Party Assessment of PTC System Safety Verification and Validation F Appendix F to Part 236..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Pt. 236, App. F Appendix F to Part 236—Minimum Requirements of FRA Directed Independent Third-Party Assessment of PTC...

  14. 49 CFR Appendix F to Part 236 - Minimum Requirements of FRA Directed Independent Third-Party Assessment of PTC System Safety...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Third-Party Assessment of PTC System Safety Verification and Validation F Appendix F to Part 236..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Pt. 236, App. F Appendix F to Part 236—Minimum Requirements of FRA Directed Independent Third-Party Assessment of PTC...

  15. 49 CFR Appendix F to Part 236 - Minimum Requirements of FRA Directed Independent Third-Party Assessment of PTC System Safety...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Third-Party Assessment of PTC System Safety Verification and Validation F Appendix F to Part 236..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Pt. 236, App. F Appendix F to Part 236—Minimum Requirements of FRA Directed Independent Third-Party Assessment of PTC...

  16. Selective participation of c-Jun with Fra-2/c-Fos promotes aggressive tumor phenotypes and poor prognosis in tongue cancer

    PubMed Central

    Gupta, Shilpi; Kumar, Prabhat; Kaur, Harsimrut; Sharma, Nishi; Saluja, Daman; Bharti, Alok C.; Das, Bhudev C.

    2015-01-01

    Tongue squamous cell carcinoma (TSCC) is most aggressive head and neck cancer often associated with HR-HPV infection. The role of AP-1 which is an essential regulator of HPV oncogene expression and tumorigenesis is not reported in tongue cancer. One hundred tongue tissue biopsies comprising precancer, cancer and adjacent controls including two tongue cancer cell lines were employed to study the role of HPV infection and AP-1 family proteins. An exclusive prevalence (28%) of HR-HPV type 16 was observed mainly in well differentiated tongue carcinomas (78.5%). A higher expression and DNA binding activity of AP-1 was observed in tongue tumors and cancer cell lines with c-Fos and Fra-2 as the major binding partners forming the functional AP-1 complex but c-Jun participated only in HPV negative and poorly differentiated carcinoma. Knocking down of Fra-2 responsible for aggressive tongue tumorigenesis led to significant reduction in c-Fos, c-Jun, MMP-9 and HPVE6/E7 expression but Fra-1 and p53 were upregulated. The binding and expression of c-Fos/Fra-2 increased as a function of severity of tongue lesions, yet selective participation of c-Jun appears to promote poor differentiation and aggressive tumorigenesis only in HPV negative cases while HPV infection leads to well differentiation and better prognosis preferably in nonsmokers. PMID:26581505

  17. An AT-rich sequence in human common fragile site FRA16D causes fork stalling and chromosome breakage in S. cerevisiae.

    PubMed

    Zhang, Haihua; Freudenreich, Catherine H

    2007-08-01

    Common fragile sites are regions of human chromosomes prone to breakage. Fragile site FRA16D spans the WWOX/FOR tumor suppressor gene and has been linked to cancer-causing deletions and translocations. Using a genetic assay in yeast, we found that a short AT-rich region (Flex1) within FRA16D increases chromosome fragility, whereas three other sequences within FRA16D do not. To our knowledge, this is the first identification of a sequence element within a common fragile site that increases chromosome fragility. The fragility of Flex1 was exacerbated by the absence of Rad52 or the presence of hydroxyurea. Flex1 contains a polymorphic AT repeat predicted to form a DNA structure, and two-dimensional gel analysis showed accumulation of stalled replication forks at the Flex1 sequence that was dependent on AT length. Our data suggest that the FRA16D Flex1 sequence causes increased chromosome breakage by forming secondary structures that stall replication fork progression.

  18. 49 CFR Appendix F to Part 236 - Minimum Requirements of FRA Directed Independent Third-Party Assessment of PTC System Safety...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Third-Party Assessment of PTC System Safety Verification and Validation F Appendix F to Part 236..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Pt. 236, App. F Appendix F to Part 236—Minimum Requirements of FRA Directed Independent Third-Party Assessment of PTC...

  19. In quest of lunar regolith breccias of exotic provenance - A uniquely anorthositic sample from the Fra Mauro (Apollo 14) highlands

    NASA Astrophysics Data System (ADS)

    Jerde, E. A.; Morris, R. V.; Warren, P. H.

    1990-04-01

    Bulk compositions of 21 Apollo regolith breccias were determined using an INAA procedure modified from that of Kallemeyn et al. (1989). With one major exception, namely, the 14076,1 sample, the regolith breccias analyzed were found to be not significantly different from the surfaces from which they were collected. In contrast, the 14076,1 sample from the Fra Mauro (Apollo 14) region is a highly anorthositic regolith breccia from a site where anorthosites are extremely scarce. The sample's composition resembles soils from the Descartes (Apollo 16) highlands. However, the low statistical probability for long-distance horizontal transport by impact cratering, together with the relatively high contents of imcompatible elements in 14076,1 suggest that this regolith breccia originated within a few hundred kilometers of the Apollo 14 site. Its compositional resemblance to ferroan anorthosite strengthens the hypothesis that ferroan anorthosite originated as the flotation crust of a global magmasphere.

  20. In quest of lunar regolith breccias of exotic provenance - A uniquely anorthositic sample from the Fra Mauro (Apollo 14) highlands

    NASA Technical Reports Server (NTRS)

    Jerde, Eric A.; Warren, Paul H.; Morris, Richard V.

    1990-01-01

    Bulk compositions of 21 Apollo regolith breccias were determined using an INAA procedure modified from that of Kallemeyn et al. (1989). With one major exception, namely, the 14076,1 sample, the regolith breccias analyzed were found to be not significantly different from the surfaces from which they were collected. In contrast, the 14076,1 sample from the Fra Mauro (Apollo 14) region is a highly anorthositic regolith breccia from a site where anorthosites are extremely scarce. The sample's composition resembles soils from the Descartes (Apollo 16) highlands. However, the low statistical probability for long-distance horizontal transport by impact cratering, together with the relatively high contents of imcompatible elements in 14076,1 suggest that this regolith breccia originated within a few hundred kilometers of the Apollo 14 site. Its compositional resemblance to ferroan anorthosite strengthens the hypothesis that ferroan anorthosite originated as the flotation crust of a global magmasphere.

  1. HDAC inhibitors suppress c-Jun/Fra-1-mediated proliferation through transcriptionally downregulating MKK7 and Raf1 in neuroblastoma cells

    PubMed Central

    Tang, Xiaomei; Xia, Yong; He, Guozhen; Min, Zhiqun; Li, Chun; Xiong, Shiqiu; Shi, Zhi; Lu, Yongjian; Yuan, Zhongmin

    2016-01-01

    Activator protein 1 (AP-1) is a transcriptional factor composed of the dimeric members of bZIP proteins, which are frequently deregulated in human cancer cells. In this study, we aimed to identify an oncogenic AP-1 dimer critical for the proliferation of neuroblastoma cells and to investigate whether histone deacetylase inhibitors (HDACIs), a new generation of anticancer agents, could target the AP-1 dimer. We report here that HDACIs including trichostatin A, suberoylanilidehydroxamic acid, valproic acid and M344 can transcriptionally suppress both c-Jun and Fra-1, preceding their inhibition of cell growth. c-Jun preferentially interacting with Fra-1 as a heterodimer is responsible for AP-1 activity and critical for cell growth. Mechanistically, HDACIs suppress Fra-1 expression through transcriptionally downregulating Raf1 and subsequently decreasing MEK1/2-ERK1/2 activity. Unexpectedly, HDACI treatment caused MKK7 downregulation at both the protein and mRNA levels. Deletion analysis of the 5′-flanking sequence of the MKK7 gene revealed that a major element responsible for the downregulation by HDACI is located at −149 to −3 relative to the transcriptional start site. Knockdown of MKK7 but not MKK4 remarkably decreased JNK/c-Jun activity and proliferation, whereas ectopic MKK7-JNK1 reversed HDACI-induced c-Jun suppression. Furthermore, suppression of both MKK-7/c-Jun and Raf-1/Fra-1 activities was involved in the tumor growth inhibitory effects induced by SAHA in SH-SY5Y xenograft mice. Collectively, these findings demonstrated that c-Jun/Fra-1 dimer is critical for neuroblastoma cell growth and that HDACIs act as effective suppressors of the two oncogenes through transcriptionally downregulating MKK7 and Raf1. PMID:26734995

  2. Cloning and sequencing of the Bet v 1-homologous allergen Fra a 1 in strawberry (Fragaria ananassa) shows the presence of an intron and little variability in amino acid sequence.

    PubMed

    Musidlowska-Persson, Anna; Alm, Rikard; Emanuelsson, Cecilia

    2007-02-01

    The Fra a 1 allergen in strawberry (Fragaria ananassa) is homologous to the major birch pollen allergen Bet v 1, which has numerous isoforms differing in terms of amino acid sequence and immunological impact. To map the extent of sequence differences in the Fra a 1 allergen, PCR cloning and sequencing was applied. Several genomic sequences of Fra a 1, with a length of either 584, 591 or 594 nucleotides, were obtained from three different strawberry varieties. All contained one intron, with the length of either 101 or 110 nucleotides. By sequencing 30 different clones, eight different DNA sequences were obtained, giving in total five potential Fra a 1 protein isoforms, with high sequence similarity (>97% sequence identity) and only seven positions of amino acid variability, which were largely confirmed by mass spectrometry of expressed proteins. We conclude that the sequence variability in the strawberry allergen Fra a 1 is small, within and between strawberry varieties, and that multiple spots, previously detected in 2DE, are presumably due to differences in post-translational modification rather than differences in amino acid sequence. The most abundant Fra a 1 isoform sequence, recombinantly expressed in Escherichia coli after removal of the intron, was recognized by IgE from strawberry allergic patients. It cross-reacted with antibodies to Bet v 1 and the homologous apple allergen Mal d 1 (61 and 78% sequence identity, respectively), and will be used in further analyses of variation in Fra a 1-expression.

  3. Ubiquitin-independent- versus ubiquitin-dependent proteasomal degradation of the c-Fos and Fra-1 transcription factors: is there a unique answer?

    PubMed

    Basbous, Jihane; Jariel-Encontre, Isabelle; Gomard, Tiphanie; Bossis, Guillaume; Piechaczyk, Marc

    2008-02-01

    The Fos family of transcription factors comprises c-Fos, Fra-1, Fra-2 and FosB, which are all intrinsically unstable proteins. Fos proteins heterodimerize with a variety of other transcription factors to control genes encoding key cell regulators. Their best known partners are the Jun family proteins (c-Jun, JunB, and JunD). At the cellular level, Fos-involving dimers control proliferation, differentiation, apoptosis and responses to environmental cues. At the organism level, they play paramount parts in organogenesis, immune responses and cognitive functions, among others. fos family genes are subjected to exquisite, complex and intermingled transcriptional and post-transcriptional regulations, which are necessary to avoid pathological effects. In particular, the Fos proteins undergo to numerous post-translational modifications, such as phosphorylations and sumoylation, regulating their transcriptional activity, their subcellular localization and their turnover. The mechanisms whereby c-Fos and Fra-1 are degraded have been studied in detail. Contrasting with the classical scenario, according to which most unstable key cell regulators are hydrolyzed by the proteasome after conjugation of polyubiquitin chains, the bulk of c-Fos and Fra-1 can be hydrolyzed independently of any prior ubiquitylation in different situations. c-Fos and Fra-1 share a common destabilizing domain whose primary sequence is conserved in Fra-2 and FosB, suggesting that similar breakdown mechanisms might be at play in the latter two proteins. However, a database search indicates that this domain is not found in any other protein, suggesting that the mechanisms underlying Fos protein destruction may be specific to this family. Interestingly, under particular conditions, a fraction of cytoplasmic c-Fos is ubiquitylated, leading to faster turnover. This poses the question of the multiplicity of degradation pathways that can target the same substrate depending on its activation state, its protein

  4. Contribution of REM sleep to Fos and FRA expression in the vestibular nuclei of rat leading to vestibular adaptation during the STS-90 Neurolab Mission.

    PubMed

    Pompeiano, O

    2007-01-01

    1. Electrophysical studies performed in ground-based experiments have shown that VN neurons respond to labyrinthine signals following stimulation of macular gravity receptors. Additional evidence indicates that VN neurons may also respond to extralabyrinthine signals of pontine origin, which occur during the PGO waves typical of REM sleep (Bizzi et al., 1964a, b; cf. also Pompeiano, 1967, 1970, 1974 for ref.). 2. In a previous study (Pompeiano et al., 2002) changes in Fos and FRA expression were used to identify the short-term (Fos) and the long-term (FRA) molecular changes which affect the VN neurons at different time points of the space flight. In particular, while Fos protein persists in the brain tissue only for a few hours (6-8 hrs) after its induction, FRA proteins, which can also be induced in the same experimental conditions, persist in the brain tissue for longer periods of time (i.e. from 12/24 hrs to days). 3. In order to relate the changes in gene expression which occurred in the VN during the space flight either to gravity changes or to REM sleep, we investigated in a recent study (Centini et al, 2006) the changes in Fos and FRA expression which occurred in different phases of the sleep-waking cycle, thus being indicative of the animal state. We could then compare the results obtained during the space lab Mission with those previously observed either in ground-based experiments during the physiological state of waking and slow-wave (SWS) or during neurochemically induced episodes of PS, as obtained after microinjection of appropriate agents in dorsal pontine structures of rats. 4. Our findings indicated that a waking state possibly associated with episodes of SWS, occurred at FD2 and FD14, i.e. at launch and after exposure of the animal to microgravity. It appeared also that at the reentry (R + 1) rather than at launch (FD2), an increase in Fos and FRA expression affected the noradrenergic LC neurons, as well as several related structures. These

  5. Reducing inpatient falls in a 100% single room elderly care environment: evaluation of the impact of a systematic nurse training programme on falls risk assessment (FRA)

    PubMed Central

    Singh, Inderpal; Okeke, Justin

    2016-01-01

    Inpatient falls (IF) are the most commonly reported safety incidents. The high rate of inpatient falls was reported in a newly built hospital, within Aneurin Bevan University Health Board, Wales (UK). The aim of the project is to reduce the incidence of IF and associated adverse clinical outcomes in a hospital with 100% single rooms. The key mechanism for improvement was education and training of nursing staff around falls risk factors. A Plan-Do-Study-Act methodology was used and a geriatrician-led, systematic nurse training programme on the understanding and correct use of existing multifactorial falls risk assessment (FRA) tool was implemented in April 2013. Pre-training baseline data revealed inadequate falls assessment and low completion rates of the FRA tool. Subsequent, post-training data showed improvement in compliance with all aspects of FRA. Concurrent with nurse training, the actual falls incidence/1000 patient-bed-days fell significantly from the baseline of 18.19±3.46 (Nov 2011-March 2013) to 13.36±2.89 (p<0.001) over next 12 months (April 2013-March 2014) and remained low (mean falls 12.81±2.85) until November 2015. Improved clinical outcomes have been observed in terms of a reduction of length of stay and new care home placements, making total annualised savings of £642,055. PMID:27559476

  6. Genomic rearrangements at the FRA2H common fragile site frequently involve non-homologous recombination events across LTR and L1(LINE) repeats.

    PubMed

    Brueckner, Lena M; Sagulenko, Evgeny; Hess, Elisa M; Zheglo, Diana; Blumrich, Anne; Schwab, Manfred; Savelyeva, Larissa

    2012-08-01

    Common fragile sites (cFSs) are non-random chromosomal regions that are prone to breakage under conditions of replication stress. DNA damage and chromosomal alterations at cFSs appear to be critical events in the development of various human diseases, especially carcinogenesis. Despite the growing interest in understanding the nature of cFS instability, only a few cFSs have been molecularly characterised. In this study, we fine-mapped the location of FRA2H using six-colour fluorescence in situ hybridisation and showed that it is one of the most active cFSs in the human genome. FRA2H encompasses approximately 530 kb of a gene-poor region containing a novel large intergenic non-coding RNA gene (AC097500.2). Using custom-designed array comparative genomic hybridisation, we detected gross and submicroscopic chromosomal rearrangements involving FRA2H in a panel of 54 neuroblastoma, colon and breast cancer cell lines. The genomic alterations frequently involved different classes of long terminal repeats and long interspersed nuclear elements. An analysis of breakpoint junction sequence motifs predominantly revealed signatures of microhomology-mediated non-homologous recombination events. Our data provide insight into the molecular structure of cFSs and sequence motifs affected by their activation in cancer. Identifying cFS sequences will accelerate the search for DNA biomarkers and targets for individualised therapies.

  7. Reducing inpatient falls in a 100% single room elderly care environment: evaluation of the impact of a systematic nurse training programme on falls risk assessment (FRA).

    PubMed

    Singh, Inderpal; Okeke, Justin

    2016-01-01

    Inpatient falls (IF) are the most commonly reported safety incidents. The high rate of inpatient falls was reported in a newly built hospital, within Aneurin Bevan University Health Board, Wales (UK). The aim of the project is to reduce the incidence of IF and associated adverse clinical outcomes in a hospital with 100% single rooms. The key mechanism for improvement was education and training of nursing staff around falls risk factors. A Plan-Do-Study-Act methodology was used and a geriatrician-led, systematic nurse training programme on the understanding and correct use of existing multifactorial falls risk assessment (FRA) tool was implemented in April 2013. Pre-training baseline data revealed inadequate falls assessment and low completion rates of the FRA tool. Subsequent, post-training data showed improvement in compliance with all aspects of FRA. Concurrent with nurse training, the actual falls incidence/1000 patient-bed-days fell significantly from the baseline of 18.19±3.46 (Nov 2011-March 2013) to 13.36±2.89 (p<0.001) over next 12 months (April 2013-March 2014) and remained low (mean falls 12.81±2.85) until November 2015. Improved clinical outcomes have been observed in terms of a reduction of length of stay and new care home placements, making total annualised savings of £642,055. PMID:27559476

  8. Sources of clasts in terrestrial impact melts - Clues to the origin of LKFM. [Low-K Fra Mauro

    NASA Technical Reports Server (NTRS)

    Mccormick, K. A.; Taylor, G. J.; Keil, K.; Spudis, P. D.; Grieve, R. A. F.

    1989-01-01

    Low-K Fra Mauro (LKFM) 'basalt', which is found exclusively as an impact melt rock, cannot be modeled geochemically from its clast population or from any combination of known pristine lunar rock types. To clarify clast/melt relationships, a study was made of impact melt rocks from Mistastin Lake crater, Labrador, where there are only three target rocks: anorthosite, quartz monzonite, and granodiorite. Feldspar compositions in these rocks define distinct fields on the An-Ab-Or ternary diagram, making it possible to identify the source of each feldspar clast. Clasts in the Mistastin impact melts do not reflect the abundance of target rocks melted during the impact. The abundance of anorthosite in the clast population varies from 34 to 100 percent compared to a relatively constant value of 65 percent calculated to be in the melt matrix. Therefore the clasts appear to be derived predominantly from material relatively far removed from the zone of impact melting. Melt-matrix composition is dictated strictly by the composition of the target materials within a small radius around and below the point of impact. This suggests that the LKFM composition was derived from a lower crustal source.

  9. Scribble Modulates the MAPK/Fra1 Pathway to Disrupt Luminal and Ductal Integrity and Suppress Tumour Formation in the Mammary Gland

    PubMed Central

    Godde, Nathan J.; Sheridan, Julie M.; Smith, Lorey K.; Pearson, Helen B.; Britt, Kara L.; Galea, Ryan C.; Yates, Laura L.; Visvader, Jane E.; Humbert, Patrick O.

    2014-01-01

    Polarity coordinates cell movement, differentiation, proliferation and apoptosis to build and maintain complex epithelial tissues such as the mammary gland. Loss of polarity and the deregulation of these processes are critical events in malignant progression but precisely how and at which stage polarity loss impacts on mammary development and tumourigenesis is unclear. Scrib is a core polarity regulator and tumour suppressor gene however to date our understanding of Scrib function in the mammary gland has been limited to cell culture and transplantation studies of cell lines. Utilizing a conditional mouse model of Scrib loss we report for the first time that Scrib is essential for mammary duct morphogenesis, mammary progenitor cell fate and maintenance, and we demonstrate a critical and specific role for Scribble in the control of the early steps of breast cancer progression. In particular, Scrib-deficiency significantly induced Fra1 expression and basal progenitor clonogenicity, which resulted in fully penetrant ductal hyperplasia characterized by high cell turnover, MAPK hyperactivity, frank polarity loss with mixing of apical and basolateral membrane constituents and expansion of atypical luminal cells. We also show for the first time a role for Scribble in mammalian spindle orientation with the onset of mammary hyperplasia being associated with aberrant luminal cell spindle orientation and a failure to apoptose during the final stage of duct tubulogenesis. Restoring MAPK/Fra1 to baseline levels prevented Scrib-hyperplasia, whereas persistent Scrib deficiency induced alveolar hyperplasia and increased the incidence, onset and grade of mammary tumours. These findings, based on a definitive genetic mouse model provide fundamental insights into mammary duct maturation and homeostasis and reveal that Scrib loss activates a MAPK/Fra1 pathway that alters mammary progenitor activity to drive premalignancy and accelerate tumour progression. PMID:24852022

  10. Mechanisms of acute uremic encephalopathy: early activation of Fos and Fra-2 gene products in different nuclei/areas of the rat brain.

    PubMed

    Heidland, August; Sebekova, Katarina; Klassen, André; Palkovits, Miklós

    2010-09-01

    High levels of various uremic toxins such as guanidino compounds and advanced glycation endproducts, as well as an excess of parathyroid hormones, are involved in the pathogenesis of acute uremic encephalopathy. Moreover, distant effects of the damaged kidney with enhanced production of inflammatory mediators are implicated. Data on the pump activity of an abnormal Na-K-ATPase and inhibition of the organic anion transporter system in the brain have been published previously. Recently, the effect of an experimentally induced acute renal failure (ARF) on the neuronal cell activation of Fos and Fra-2 in the rat brain was investigated by immunohistochemistry. ARF was induced by using the following 3 rat models: bilateral nephrectomy, bilateral ureter ligation, and uranyl acetate injection with corresponding controls. The Fos and the Fra-2 immunoreactive neurons of the brain were determined in a total of 120 brain areas over a period of 3 days post bilateral nephrectomy and bilateral ureter ligation and 12 days after uranyl acetate. An activation response was observed in 73 of 120 areas of the brain. The responses were classified into 4 groups: (1) biogenic amines (noradrenaline, adrenaline, histamine, and 5-hydroxytryptamine), (2) stress-sensitive forebrain areas, (3) neuronal cell groups involved in the regulation of water and electrolyte homeostasis, and (4) central autonomic cell groups. In the uranyl acetate-induced ARF, activation of Fos and Fra-2 immunoreactivity took place at the earliest time-point (3 hours) which persisted even after improvement of ARF. This suggests the involvement of the toxic effects of uranium as a result of its accumulation in the brain.

  11. A scientific approach to the characterization of the painting materials of Fra Mattia della Robbia polychrome terracotta altarpiece

    NASA Astrophysics Data System (ADS)

    Amadori, M. L.; Barcelli, S.; Casoli, A.; Mazzeo, R.; Prati, S.

    2013-12-01

    During the last restoration (2008-2011) of the polychrome terracotta altarpiece called Coronation of Virgin between Saints Rocco, Sebastian, Peter martyr and Antonio abbot, located in the collegiate church of S. Maria Assunta in Montecassiano (Macerata, Italy), scientific investigations were carried out to acquire detailed information about the painting technique. The identification of materials allowed a correct restoration. The altarpiece is almost entirely realized by Marco della Robbia (Fra Mattia), dates back to the first half of the XVI century and represents an interesting example of painted terracotta produced by using two different techniques: glazed polychrome terracotta and the "cold painting" technique. The characterization of the samples' material constituents was obtained by analysing the cross-sections and the fragments by different techniques (optical, SEM-EDS and ATR-FTIR microscopy as well as GC-MS), as the real nature of a component is often difficult to assess with one single technique. The optical microscope examination of paint cross-sections shows the presence of many layers, indicating the complexity of the paint stratigraphic morphologies. The original polychromy of della Robbia's masterpiece is constituted of cinnabar, red lake, red lead, orpiment, red ochre, lead white, lead tin yellow, green earth and raw umber. Two different types of gilding technique have been distinguished. The first one presents a glue mordant, and the second one shows an oil mordant composed by a mixture of red lead, red ochre, cinnabar and orpiment. The GC-MS analysis allowed the characterisation of linseed oil and a mixture of animal glue and egg as binding media stratigraphically located by the use of ATR-FTIR mapping microscopy. The analytical results of the painted terracotta integrated investigations show that original technique adopted is characterised by the application of pigments in an oil-binding medium directly applied on the substrates, probably treated

  12. Forest cover maps of China in 2010 from multiple approaches and data sources: PALSAR, Landsat, MODIS, FRA, and NFI

    NASA Astrophysics Data System (ADS)

    Qin, Yuanwei; Xiao, Xiangming; Dong, Jinwei; Zhang, Geli; Shimada, Masanobu; Liu, Jiyuan; Li, Chungan; Kou, Weili; Moore, Berrien

    2015-11-01

    Forests and their changes are important to the regional and global carbon cycle, biodiversity and ecosystem services. Some uncertainty about forest cover area in China calls for an accurate and updated forest cover map. In this study, we combined ALOS PALSAR orthorectified 50-m mosaic images (FBD mode with HH and HV polarization) and MODIS time series data in 2010 to map forests in China. We used MODIS-based NDVI dataset (MOD13Q1, 250-m spatial resolution) to generate a map of annual maximum NDVI and used it to mask out built-up lands, barren lands, and sparsely vegetated lands. We developed a decision tree classification algorithm to identify forest and non-forest land cover, based on the signature analysis of PALSAR backscatter coefficient data. The PALSAR-based algorithm was then applied to produce a forest cover map in China in 2010. The resulting forest/non-forest classification map has an overall accuracy of 96.2% and a Kappa Coefficient of 0.91. The resultant 50-m PALSAR-based forest cover map was compared to five forest cover databases. The total forest area (2.02 × 106 km2) in China from the PALSAR-based forest map is close to the forest area estimates from China National Forestry Inventory (1.95 × 106 km2), JAXA (2.00 × 106 km2), and FAO FRA (2.07 × 106 km2). There are good linear relationships between the PALSAR-based forest map and the forest maps from the JAXA, MCD12Q1, and NLCD-China datasets at the province and county scales. All the forest maps have similar spatial distributions of forest/non-forest at pixel scale. Our PALSAR-based forest map recognizes well the agro-forests in China. The results of this study demonstrate the potential of integrating PALSAR and MODIS images to map forests in large areas. The resultant map of forest cover in China in 2010 can be used for many studies such as forest carbon cycle and ecological restoration.

  13. Retinoblastoma Protein and MyoD Function Together to Effect the Repression of Fra-1 and in Turn Cyclin D1 during Terminal Cell Cycle Arrest Associated with Myogenesis*

    PubMed Central

    Rajabi, Hasan N.; Takahashi, Chiaki; Ewen, Mark E.

    2014-01-01

    The acquisition of skeletal muscle-specific function and terminal cell cycle arrest represent two important features of the myogenic differentiation program. These cellular processes are distinct and can be separated genetically. The lineage-specific transcription factor MyoD and the retinoblastoma protein pRb participate in both of these cellular events. Whether and how MyoD and pRb work together to effect terminal cell cycle arrest is uncertain. To address this question, we focused on cyclin D1, whose stable repression is required for terminal cell cycle arrest and execution of myogenesis. MyoD and pRb are both required for the repression of cyclin D1; their actions, however, were found not to be direct. Rather, they operate to regulate the immediate early gene Fra-1, a critical player in mitogen-dependent induction of cyclin D1. Two conserved MyoD-binding sites were identified in an intronic enhancer of Fra-1 and shown to be required for the stable repression of Fra-1 and, in turn, cyclin D1. Localization of MyoD alone to the intronic enhancer of Fra-1 in the absence of pRb was not sufficient to elicit a block to Fra-1 induction; pRb was also recruited to the intronic enhancer in a MyoD-dependent manner. These observations suggest that MyoD and pRb work together cooperatively at the level of the intronic enhancer of Fra-1 during terminal cell cycle arrest. This work reveals a previously unappreciated link between a lineage-specific transcription factor, a tumor suppressor, and a proto-oncogene in the control of an important facet of myogenic differentiation. PMID:25006242

  14. A CGG-repeat expansion mutation in ZNF713 causes FRA7A: association with autistic spectrum disorder in two families.

    PubMed

    Metsu, Sofie; Rainger, Jacqueline K; Debacker, Kim; Bernhard, Birgitta; Rooms, Liesbeth; Grafodatskaya, Daria; Weksberg, Rosanna; Fombonne, Eric; Taylor, Martin S; Scherer, Stephen W; Kooy, R Frank; FitzPatrick, David R

    2014-11-01

    We report de novo occurrence of the 7p11.2 folate-sensitive fragile site FRA7A in a male with an autistic spectrum disorder (ASD) due to a CGG-repeat expansion mutation (∼450 repeats) in a 5' intron of ZNF713. This expanded allele showed hypermethylation of the adjacent CpG island with reduced ZNF713 expression observed in a proband-derived lymphoblastoid cell line (LCL). His unaffected mother carried an unmethylated premutation (85 repeats). This CGG-repeat showed length polymorphism in control samples (five to 22 repeats). In a second unrelated family, three siblings with ASD and their unaffected father were found to carry FRA7A premutations, which were partially or mosaically methylated. In one of the affected siblings, mitotic instability of the premutation was observed. ZNF713 expression in LCLs in this family was increased in three of these four premutation carriers. A firm link cannot yet be established between ASD and the repeat expansion mutation but plausible pathogenic mechanisms are discussed.

  15. Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase1 gene.

    PubMed

    Venugopal, R; Jaiswal, A K

    1996-12-10

    Twenty-four base pairs of the human antioxidant response element (hARE) are required for high basal transcription of the NAD(P)H:quinone oxidoreductase1 (NQO1) gene and its induction in response to xenobiotics and antioxidants. hARE is a unique cis-element that contains one perfect and one imperfect AP1 element arranged as inverse repeats separated by 3 bp, followed by a "GC" box. We report here that Jun, Fos, Fra, and Nrf nuclear transcription factors bind to the hARE. Overexpression of cDNA derived combinations of the nuclear proteins Jun and Fos or Jun and Fra1 repressed hARE-mediated chloramphenicol acetyltransferase (CAT) gene expression in transfected human hepatoblastoma (Hep-G2) cells. Further experiments suggested that this repression was due to overexpression of c-Fos and Fra1, but not due to Jun proteins. The Jun (c-Jun, Jun-B, and Jun-D) proteins in all the possible combinations were more or less ineffective in repression or upregulation of hARE-mediated gene expression. Interestingly, overexpression of Nrf1 and Nrf2 individually in Hep-G2 and monkey kidney (COS1) cells significantly increased CAT gene expression from reporter plasmid hARE-thymidine kinase-CAT in transfected cells that were inducible by beta-naphthoflavone and teri-butyl hydroquinone. These results indicated that hARE-mediated expression of the NQO1 gene and its induction by xenobiotics and antioxidants are mediated by Nrf1 and Nrf2. The hARE-mediated basal expression, however, is repressed by overexpression of c-Fos and Fra1. PMID:8962164

  16. The Natural Selection of the Chemical Elements (by R. J. P. Williams and J. J. R. Fraústo da Silva)

    NASA Astrophysics Data System (ADS)

    Kauffman, George B.

    1998-12-01

    Clarendon: New York, 1996. xxvi + 646 pp. Figs., tables. 20.5 x 25.6 cm. ISBN 0-19-855843-0. $80.00. R. J. P. Williams, Royal Society Research Professor Emeritus at Wadham College, Oxford University, and J. J. R. Fraústo da Silva, Professor of Analytical Chemistry at the Instituto Superior Técnico, Universidade Técnica de Lisboa, have collaborated on two previous volumes: New Trends in Bio-inorganic Chemistry (1978) and The Biological Chemistry of the Elements (3rd printing, 1994). Their latest collaborative effort is a book whose ambitious objective is "to show the relationship of every kind of material around us, living and nonliving, to the properties of the chemical elements of the periodic table." The "natural selection" of the chemical elements results from a number of factors, all of which are described in detail. Among these are chemical affinity related to the electronic configuration of their atoms, thermodynamic and kinetic stability, and "functional value to an organisation such as a living system". The physicist's approach to material through phase structure and the phase rule is stressed rather than the chemist's approach through bonding theories. The entire book possesses a strong environmental and interdisciplinary emphasis.

  17. Effect of estrogen and tamoxifen on the expression pattern of AP-1 factors in MCF-7 cells: role of c-Jun, c-Fos, and Fra-1 in cell cycle regulation.

    PubMed

    Babu, R L; Naveen Kumar, M; Patil, Rajeshwari H; Devaraju, K S; Ramesh, Govindarajan T; Sharma, S Chidananda

    2013-08-01

    The activated transcription factor ERα plays an important role in the breast development and progression of cancer. In a non-classical pathway ER interacts with other transcription factors AP-1, NFkB, SP1, etc. AP-1 transcription factors control rapid responses of mammalian cells to stimuli that impact proliferation, differentiation, and transformation. AP-1 factors are leucine zipper proteins belonging to members of the Jun family (c-Jun, JunB, and JunD) and Fos family (c-Fos, FosB, Fra-1, and Fra-2) proteins. Although AP-1 factors are well characterized, not much is known about the expression pattern of the AP-1 factors in breast cancer cells. Hence to determine which AP-1 factors are expressed and regulated by estrogen, we used human breast cancer MCF-7 cells as in vitro model system. The MCF-7 cells were treated with or without estradiol-17β (E2) or antiestrogen tamoxifen (TMX) and the cell proliferation and viability was assessed by MTT assay. The expression of different AP-1 factors was analyzed by semi-quantitative RT-PCR. The cells treated with E2 found to increase the cell proliferation by more than 35 % and TMX an antiestrogen decreased by 29 % compared to control. The E2 found to induce the expression of c-Jun, Fra-1, and c-Fos, while TMX decreased the expression. In addition TMX also decreased the mRNA levels of Jun-D and Fra-2. These results suggest that the AP-1 factors c-Jun, c-Fos, and Fra-1 may be involved in the proliferation and transformation of MCF-7 cells. E2 also found to induce cyclin D1 and cyclin E1 mRNA transcripts of cell cycle regulators while TMX significantly decreased compared to control. Further E2 induced the anti-apoptotic Bcl-2 and TMX decreased mRNA transcripts. The data presented here support the E2-ERα-mediated MCF-7 cell proliferation and confirms the role of AP-1 factors in cell cycle regulation. PMID:23625206

  18. Swimming speed of an oscillating sheet in Newtonian and viscoelastic fluids

    NASA Astrophysics Data System (ADS)

    Dasgupta, Moumita; Berhanu, Michael; Kudrolli, Arshad; Liu, Bin; Breuer, Kenneth; Powers, Thomas

    2011-11-01

    We discuss a mechanical experimental model of a flexible sheet swimming with a prescribed wave pattern through a fluid. We are motivated by a need for a fundamental understanding of microorganism locomotion through non-Newtonian fluids. To simplify the problem, we suspend a tall flexible cylindrical sheet concentric within a cylindrical tank filled with the fluid. Torque free boundary conditions are imposed by supporting the flexible sheet and the tank with friction-free ball-bearings. A traveling wave is imposed on the sheet with a pair of rollers in the azimuthal direction. We first show that the swimming speed is linear with respect to the phase velocity of the traveling wave for a viscous Newtonian fluid. Then we show that the system is essentially two dimensional as the results do not depend on the height of fluid in the tank. We measure swimming speed in Polyox-water mixtures and Sodium CMC solutions as a function of wave speed. We again demonstrate linear response in the swimming speeds, which also decrease in these viscoelastic fluids relative to the Newtonian case as wave speed increases. Decrease in swimming speed is observed with increase in viscoelasticity of the fluids. We then discuss the dependence of swimming speed on the Deborah number of the fluids.

  19. Swimming speed of an oscillating sheet in Newtonian and viscoelastic fluids

    NASA Astrophysics Data System (ADS)

    Dasgupta, Moumita; Berhanu, Michael; Kudrolli, Arshad; Fu, Henry; Breuer, Kenneth; Powers, Thomas

    2011-03-01

    We discuss a mechanical experimental model of a flexible sheet swimming with a prescribed wave pattern - a Taylor swimmer - through a fluid. Our study is motivated by a need for a fundamental understanding of microorganism locomotion through non-Newtonian fluids. In order to simplify the problem, we suspend a tall flexible cylindrical sheet concentric within a cylindrical tank filled with the fluid. Torque free boundary conditions are imposed by supporting the flexible sheet and the tank with friction-free ball-bearings. A traveling wave is imposed on the sheet with a pair of rollers in the azimuthal direction. We first demonstrate a linear response in the swimming velocity of the sheet with respect to its phase velocity in a viscous Newtonian fluid. Further, we show that the analytical system is essentially two dimensional by varying the height of fluid in the tank. We then discuss measurements of swimming speed in Polyox-water mixtures as a function of wave speed. We demonstrate that the swimming speed in this viscoelastic fluid decrease relative to the Newtonian case as wave speed is increased. We will further discuss the dependence of swimming speed on Deborah number and other characteristics of the fluid.

  20. Development of gastroretentive drug delivery system for cefuroxime axetil: in vitro and in vivo evaluation in human volunteers.

    PubMed

    Bomma, Ramesh; Veerabrahma, Kishan

    2013-01-01

    The objective of this investigation was to develop the cefuroxime axetil sustained-release floating tablets to prolong the gastric residence time and compare their pharmacokinetic behavior with marketed conventional tablets (Zocef). The floating tablets were developed using polymers like HPMC K4M and HPMC K100M alone, and polymer combination of HPMC K4M and Polyox WSR 303 by effervescent technique. Tablets were prepared by slugging method and evaluated for their physical characteristics, in vitro drug release, and buoyancy lag time. The best formulation (F10) was selected based on in vitro characteristics and used in vivo radiographic and bioavailability studies in healthy human volunteers. All the formulations could sustain drug release for 12 h. The dissolution profiles were subjected to various kinetic release models and it was found that the mechanism of drug release followed Peppas model. The in vivo radiographic studies revealed that the tablets remained in stomach for 225 ± 30 min. Based on in vivo performance, the developed floating tablets showed superior bioavailability than Zocef tablet. Based on in vivo performance significant difference was observed between Cmax, tmax, t1/2, AUC0-∞, and mean residence time of test and reference (p<0.05). The increase in relative bioavailability of test was 1.61 fold when compared to reference.

  1. Multifunctional medicated lyophilised wafer dressing for effective chronic wound healing.

    PubMed

    Pawar, Harshavardhan V; Boateng, Joshua S; Ayensu, Isaac; Tetteh, John

    2014-06-01

    Wafers combining weight ratios of Polyox with carrageenan (75/25) or sodium alginate (50/50) containing streptomycin and diclofenac were prepared to improve chronic wound healing. Gels were freeze-dried using a lyophilisation cycle incorporating an annealing step. Wafers were characterised for morphology, mechanical and in vitro functional (swelling, adhesion, drug release in the presence of simulated wound fluid) characteristics. Both blank (BLK) and drug-loaded (DL) wafers were soft, flexible, elegant in appearance and non-brittle in nature. Annealing helped to improve porous nature of wafers but was affected by the addition of drugs. Mechanical characterisation demonstrated that the wafers were strong enough to withstand normal stresses but also flexible to prevent damage to newly formed skin tissue. Differences in swelling, adhesion and drug release characteristics could be attributed to differences in pore size and sodium sulphate formed because of the salt forms of the two drugs. BLK wafers showed relatively higher swelling and adhesion than DL wafers with the latter showing controlled release of streptomycin and diclofenac. The optimised dressing has the potential to reduce bacterial infection and can also help to reduce swelling and pain associated with injury due to the anti-inflammatory action of diclofenac and help to achieve more rapid wound healing.

  2. Suppression of Tip Vortex Cavitation by Water and Polymer Injection

    NASA Astrophysics Data System (ADS)

    Chang, Natasha; Yakushiji, Ryo; Ceccio, Steven

    2008-11-01

    Tip vortex cavitation (TVC) is typically the first form of cavitation observed in propellers; therefore a delay of its inception is desirable. In this study, TVC inception was delayed via mass injection from the tip of a modified NACA-66 elliptic plan-form hydrofoil. The injected mass used were water and Polyox WSR 301 solutions with concentrations from 10 to 500 ppm. The free-stream nuclei content was measured using a Cavitation Susceptibility Meter, and the TVC inception event rate was quantified with a light scattering system. The vortical flow field in the region of inception was characterized using Stereo Particle Imaging and Velocimetry (SPIV), with measurements taken from 0.25 to 1 chord length at various concentrations and injection rates. It was observed that TVC inception was delayed with injection by a δσ of 0.03 to 1.8 from a baseline of σ = 3.5. Injection with higher polymer concentrations and higher volume flux led to larger delays. A saturation effect for the TVC suppression was observed for both the polymer concentration (125ppm) and volume flux rate (Qj/Qc = 0.48). These effects are related to the SPIV flow field.

  3. Design and Development of Polyethylene Oxide Based Matrix Tablets for Verapamil Hydrochloride

    PubMed Central

    Vidyadhara, S.; Sasidhar, R. L. C.; Nagaraju, R.

    2013-01-01

    In the present investigation an attempt has been made to increase therapeutic efficacy, reduced frequency of administration and improved patient compliance by developing controlled release matrix tablets of verapamil hydrochloride. Verapamil hydrochloride was formulated as oral controlled release matrix tablets by using the polyethylene oxides (Polyox WSR 303). The aim of this study was to investigate the influence of polymer level and type of fillers namely lactose (soluble filler), swellable filler (starch 1500), microcrystalline cellulose and dibasic calcium phosphate (insoluble fillers) on the release rate and mechanism of release for verapamil hydrochloride from matrix tablets prepared by direct compression process. Higher polymeric content in the matrix decreased the release rate of drug. On the other hand, replacement of lactose with anhydrous dibasic calcium phosphate and microcrystalline cellulose has significantly retarded the release rate of verapamil hydrochloride. Biopharmaceutical evaluation of satisfactory formulations were also carried out on New Zealand rabbits and parameters such as maximum plasma concentration, time to reach peak plasma concentration, area under the plasma concentration time curve(0-t) and area under first moment curve(0-t) were determined. In vivo pharmacokinetic study proves that the verapamil hydrochloride from matrix tablets showed prolonged release and were be able to sustain the therapeutic effect up to 24 h. PMID:24019567

  4. Investigation of Drug Release from PEO Tablet Matrices in the Presence of Vitamin E as Antioxidant.

    PubMed

    Shojaee, Saeed; Nokhodchi, Ali; Cumming, Iain; Alhalaweh, Amjad; Kaialy, Waseem

    2015-01-01

    The objective of this study was to investigate the influence of drug type on the release of drug from PEO matrix tablets accompanied with the impact of vitamin E succinate as antioxidant. The result showed that the presence of vitamin E promoted a stable release rate of soluble drug propranolol HCl from aged PEO matrix tablets, which was similar to fresh sample, regardless of molecular weight (MW) of PEO. However, the influence of the presence of vitamin E on the release rate of partially soluble drug, theophylline, was dependent on the MW of PEO; i.e., fast and unstable drug release was obtained in the case of low MW PEO 750 whereas stable drug release was obtained in the case of high MW PEO 303. The release of low water-soluble drug zonisamide was stable regardless of both the presence of vitamin E and the MW of PEO. The presence of vitamin E slightly slowed the release of zonisamide from aged PEO 303 matrices but not PEO 750 matrices. Therefore, in order to achieve a suitable controlled release profile from PEO matrices, not only the presence of vitamin E but also the solubility of the drug and the MW of polyox should be considered.

  5. Design and development of polyethylene oxide based matrix tablets for verapamil hydrochloride.

    PubMed

    Vidyadhara, S; Sasidhar, R L C; Nagaraju, R

    2013-03-01

    In the present investigation an attempt has been made to increase therapeutic efficacy, reduced frequency of administration and improved patient compliance by developing controlled release matrix tablets of verapamil hydrochloride. Verapamil hydrochloride was formulated as oral controlled release matrix tablets by using the polyethylene oxides (Polyox WSR 303). The aim of this study was to investigate the influence of polymer level and type of fillers namely lactose (soluble filler), swellable filler (starch 1500), microcrystalline cellulose and dibasic calcium phosphate (insoluble fillers) on the release rate and mechanism of release for verapamil hydrochloride from matrix tablets prepared by direct compression process. Higher polymeric content in the matrix decreased the release rate of drug. On the other hand, replacement of lactose with anhydrous dibasic calcium phosphate and microcrystalline cellulose has significantly retarded the release rate of verapamil hydrochloride. Biopharmaceutical evaluation of satisfactory formulations were also carried out on New Zealand rabbits and parameters such as maximum plasma concentration, time to reach peak plasma concentration, area under the plasma concentration time curve(0-t) and area under first moment curve(0-t) were determined. In vivo pharmacokinetic study proves that the verapamil hydrochloride from matrix tablets showed prolonged release and were be able to sustain the therapeutic effect up to 24 h. PMID:24019567

  6. Development of gastroretentive drug delivery system for cefuroxime axetil: in vitro and in vivo evaluation in human volunteers.

    PubMed

    Bomma, Ramesh; Veerabrahma, Kishan

    2013-01-01

    The objective of this investigation was to develop the cefuroxime axetil sustained-release floating tablets to prolong the gastric residence time and compare their pharmacokinetic behavior with marketed conventional tablets (Zocef). The floating tablets were developed using polymers like HPMC K4M and HPMC K100M alone, and polymer combination of HPMC K4M and Polyox WSR 303 by effervescent technique. Tablets were prepared by slugging method and evaluated for their physical characteristics, in vitro drug release, and buoyancy lag time. The best formulation (F10) was selected based on in vitro characteristics and used in vivo radiographic and bioavailability studies in healthy human volunteers. All the formulations could sustain drug release for 12 h. The dissolution profiles were subjected to various kinetic release models and it was found that the mechanism of drug release followed Peppas model. The in vivo radiographic studies revealed that the tablets remained in stomach for 225 ± 30 min. Based on in vivo performance, the developed floating tablets showed superior bioavailability than Zocef tablet. Based on in vivo performance significant difference was observed between Cmax, tmax, t1/2, AUC0-∞, and mean residence time of test and reference (p<0.05). The increase in relative bioavailability of test was 1.61 fold when compared to reference. PMID:22348334

  7. A novel bi-layer ascending release osmotic pump tablet: in vitro investigation and in vivo investigation in pharmacokinetic study and IVIVC evaluation.

    PubMed

    Xu, Heming; Li, Zhao; Pan, Hao; Zhang, Zhihong; Liu, Dandan; Tian, Baocheng; Ma, Shilin; Song, Shilong; Pan, Weisan

    2013-12-15

    This study was aimed to develop an ascending release push-pull osmotic pump (APOP) system with a novel mechanism and an easy manufacture process. Theoretical analysis showed that the key to obtain the non-zero order drug release was to break the balance between the drug suspension release rate in the drug layer and the swelling rate of the core, and an ascending drug release rate was achieved when the former was slower than the latter. A polymer (Polyox WSR N-12K) was introduced as a suspension agent in drug layer to slow down the hydration rate of drug layer. Influence of the composition of drug layer (PEO category, total amount, drug loading and fraction of NaCl), push layer (NaCl amount), and also the level of coating weight gain on the drug release profiles was investigated. Observation of hydration state was estimated by taking photos, and also was confirmed by the theories. Paliperidone was delivered successfully by APOP at an ascending release rate up to 20 h in vitro. The in vivo plasma concentration of paliperidone in beagle dogs increased gradually up to 19 h. The APOP with an easy manufacture process was a promising strategy to deliver drug at an ascending rate.

  8. Variations in the FRA10AC1 Fragile Site and 15q21 Are Associated with Cerebrospinal Fluid Aβ1-42 Level

    PubMed Central

    Li, Qingqin S.; Parrado, Antonio R.; Samtani, Mahesh N.; Narayan, Vaibhav A.

    2015-01-01

    Proteolytic fragments of amyloid and post-translational modification of tau species in Cerebrospinal fluid (CSF) as well as cerebral amyloid deposition are important biomarkers for Alzheimer’s Disease. We conducted genome-wide association study to identify genetic factors influencing CSF biomarker level, cerebral amyloid deposition, and disease progression. The genome-wide association study was performed via a meta-analysis of two non-overlapping discovery sample sets to identify genetic variants other than APOE ε4 predictive of the CSF biomarker level (Aβ1–42, t-Tau, p-Tau181P, t-Tau:Aβ1–42 ratio, and p-Tau181P:Aβ1–42 ratio) in patients enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. Loci passing a genome-wide significance threshold of P < 5 x 10−8 were followed-up for replication in an independent sample set. We also performed joint meta-analysis of both discovery sample sets together with the replication sample set. In the discovery phase, we identified variants in FRA10AC1 associated with CSF Aβ1–42 level passing the genome-wide significance threshold (directly genotyped SNV rs10509663 PFE = 1.1 x 10−9, imputed SNV rs116953792 PFE = 3.5 x 10−10), rs116953792 (Pone-sided = 0.04) achieved replication. This association became stronger in the joint meta-analysis (directly genotyped SNV rs10509663 PFE = 1.7 x 10−9, imputed SNV rs116953792 PFE = 7.6 x 10−11). Additionally, we identified locus 15q21 (imputed SNV rs1503351 PFE = 4.0 x 10−8) associated with CSF Aβ1–42 level. No other variants passed the genome-wide significance threshold for other CSF biomarkers in either the discovery sample sets or joint analysis. Gene set enrichment analyses suggested that targeted genes mediated by miR-33, miR-146, and miR-193 were enriched in various GWAS analyses. This finding is particularly important because CSF biomarkers confer disease susceptibility and may be predictive of the likelihood of disease progression in

  9. Two different approaches for the prediction of in vivo plasma concentration-time profile from in vitro release data of once daily formulations of diltiazem hydrochloride.

    PubMed

    Bendas, Ehab R

    2009-09-01

    The aim of this study was to employ two different mathematical approaches: first, a convolution approach using computer software; second, a mathematical calculation exploiting Wagner-Nelson calculation to predict in vivo plasma concentration-time profile from the in vitro release study for the once daily formulations of a model drug diltiazem hydrochloride. The once daily extended release tablets (120 mg) were prepared by the wet granulation technique. Ethanol or ethanolic solutions of ethylcellulose (N22), were used as granulating agents along with hydrophilic matrix polymers like hydroxypropyl methylcellulose (HPMC) (K 15M). The granules showed satisfactory flow properties, compressibility, moisture content and drug content. All the tablet formulations showed acceptable properties and complied with pharmacopeial limits. The in vitro drug release study revealed that formula F7-T which contains drug: HPMC ratio 1:1 and 20 mg of ethylcellulose was able to sustain the drug release for 24 h and satisfied the USP dissolution limits. Fitting the in vitro drug release data to Korsmeyer-Peppas equation indicated that the mechanism of drug release could be zero-order. The capsule formulation F14-C which consists of drug: HPMC ratio 1:2, 12 mg of ethylcellulose and 20 mg of polyox 100 showed in vitro drug release similar to the tablet F7-T using the similarity factor (f 2). The mechanism of drug release could be coupled diffusion, and polymer matrix relaxation. The percent dissolved data from the two formulations were used as input function to predict the in vivo plasma data by the two approaches (Convolution by Kinetica software and Wagner-Nelson calculation). The two methods were validated by prediction of plasma data from in vitro release data of FDA approved 300 mg extended release capsule. Prediction errors were estimated for Cmax and area under the curve (AUC) to determine the validity of the methods. The percent prediction error for each parameter is not exceeding 15

  10. The group-based social skills training SOSTA-FRA in children and adolescents with high functioning autism spectrum disorder - study protocol of the randomised, multi-centre controlled SOSTA - net trial

    PubMed Central

    2013-01-01

    Background Group-based social skills training (SST) has repeatedly been recommended as treatment of choice in high-functioning autism spectrum disorder (HFASD). To date, no sufficiently powered randomised controlled trial has been performed to establish efficacy and safety of SST in children and adolescents with HFASD. In this randomised, multi-centre, controlled trial with 220 children and adolescents with HFASD it is hypothesized, that add-on group-based SST using the 12 weeks manualised SOSTA–FRA program will result in improved social responsiveness (measured by the parent rated social responsiveness scale, SRS) compared to treatment as usual (TAU). It is further expected, that parent and self reported anxiety and depressive symptoms will decline and pro-social behaviour will increase in the treatment group. A neurophysiological study in the Frankfurt HFASD subgroup will be performed pre- and post treatment to assess changes in neural function induced by SST versus TAU. Methods/design The SOSTA – net trial is designed as a prospective, randomised, multi-centre, controlled trial with two parallel groups. The primary outcome is change in SRS score directly after the intervention and at 3 months follow-up. Several secondary outcome measures are also obtained. The target sample consists of 220 individuals with ASD, included at the six study centres. Discussion This study is currently one of the largest trials on SST in children and adolescents with HFASD worldwide. Compared to recent randomised controlled studies, our study shows several advantages with regard to in- and exclusion criteria, study methods, and the therapeutic approach chosen, which can be easily implemented in non-university-based clinical settings. Trial registration ISRCTN94863788 – SOSTA – net: Group-based social skills training in children and adolescents with high functioning autism spectrum disorder. PMID:23289935

  11. Apollo 14: Science at Fra Mauro.

    ERIC Educational Resources Information Center

    National Aeronautics and Space Administration, Washington, DC.

    The many scientific activities and experiments performed during the Apollo 14 Mission are presented in a descriptive, non-technical format. Content relates to experiments on the lunar surface and to those performed while traveling in space, and provides a great deal of information about the flight. Many photographs from the journey, a map of the…

  12. Fra leggi fisiche ed equazioni matematiche

    NASA Astrophysics Data System (ADS)

    Castaldi, Francesco

    2006-04-01

    The author deals with the common names usually given to mathematical expressions. Newton's law of universal gravitation was never expressed by Newton in the complete form presented below as equation number 1. A different case is represented by Kepler's equation indicated here as equation number 4. That formula contains the definition of a uniform angular motion for the mean anomaly, which Kepler constantly refused and substituted with an area measure for this anomaly. The author would like to suggest two names to be remembered for these mathematical expressions: Henry Cavendish, for the first, and Leonard Euler, for the second.

  13. Preparation, optimisation and characterisation of novel wound healing film dressings loaded with streptomycin and diclofenac.

    PubMed

    Pawar, H V; Tetteh, J; Boateng, J S

    2013-02-01

    Streptomycin (STP) and diclofenac (DLF) loaded film dressings were prepared by blending Polyox(®) (POL) with four hydrophilic polymers [hydroxypropylmethylcellulose (HPMC), carrageenan (CAR), sodium alginate (SA) or chitosan (CS)] using glycerol (GLY) as plasticiser. The films were characterised by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy, texture analysis (tensile and swelling characteristics) and in vitro dissolution profiles using Franz diffusion cell. SEM showed homogeneous morphology for both blank (BLK) and drug loaded (DL) films. Films prepared by blending of POL with the other polymers showed a reduction in the crystallisation of POL in descending order of SA>CS>HPMC>CAR respectively. DSC and XRD showed no crystalline peaks of STP and DLF suggesting molecular dispersion of both drugs as well as possible drug interaction with negatively charged sulphate ions present in CAR. The DL films did not show any IR bands of both drugs, confirming the DSC and XRD results. POL-CAR-BLK films showed higher tensile strength (12.32±1.40 MPa) than the POL-CAR-DL films (9.52±1.12 MPa). DL films plasticised with 25%w/w GLY revealed soft and tough (tensile strength 1.02±0.28 MPa, % elongation 1031.33±16.23) formulations. The swelling capacities of POL-CAR-BLK and POL-CAR-DL films were (733.17±25.78%) and (646.39±40.39%), increasing to (1072.71±80.30%) and (1051±86.68%) for POL-CAR-BLK-25% GLY and POL-CAR-DL-25% GLY respectively. POL-CAR-DL films showed significantly (n=3, p<0.0318) lower cumulative release of STP and DLF (52.11±1.34, 55.26±2.25) compared to POL-CAR-DL-25% GLY films (60.07±1.56, 63.39±1.92) respectively.

  14. Vínculos sobre um modelo de quartessência de Chaplygin usando observações do satélite chandra da fração de massa de gás em aglomerados de galáxias

    NASA Astrophysics Data System (ADS)

    de Souza, R. S.

    2003-08-01

    Observações de Supernovas do tipo Ia mostram que a expansão do Universo está acelerando. Segundo as equações de Einstein uma componente com pressão negativa (energia escura) é necessária para explicar a aceleração cósmica. Além da energia escura é usualmente admitido que no Universo há também uma matéria exótica com pressão zero, que é chamada de matéria escura. Essa componente possui um papel fundamental na formação de estruturas no Universo. Recentemente tem se explorado a possibilidade de que matéria e energia escura poderiam ser unificadas através de uma única componente, que tem sido denominada de quartessência. Um exemplo de fluido com essas características é o Gás de Chaplygin Generalizado, que possui uma equação de estado da forma p = -A/ra. Inicialmente consideramos o caso especial a = 1 (gás de Chaplygin) e vinculamos parâmetros do modelo utilizando observações em raios-X do satélite Chandra da fração de massa de gás em aglomerados de galáxias. Uma comparação dos vínculos obtidos com esse teste com outros testes, tais como supernovas e idade do Universo, mostra que esse teste é bastante restritivo. Exibiremos ainda resultados para o caso em que a curvatura é nula e o parâmetro a está compreendido no intervalo -1 < a 1.

  15. Ancient crustal components in the Fra Mauro breccias

    NASA Technical Reports Server (NTRS)

    Shervais, J. W.; Taylor, L. A.; Laul, J. C.

    1983-01-01

    Texturally pristine clasts preserve primary petrographic relationships and mineral compositions, yielding insights into igneous processes of the early lunar crust that cannot be gained from highly shocked and brecciated 'chemically pristine' samples. The use of texture as a prime criterion allows for expansion of the data base derived solely from chemical criteria, and provides complementary data. Texturally pristine clasts from the Apollo 14 site studied here include anorthosite, troctolites, gabbronorites, and basalts. Alkali anorthosites are plagioclase orthocumulates and may form by flotation in Mg-suite plutons. Ferroan anorthosite was cataclastically deformed and metamorphosed to granulite facies. Troctolites include both 01 + Plg and 01 + En + Plg cumulates. Major and trace element analyses of two troctolites reveal 'eastern' geochemical affinities that contrast other 'western' troctolites. Gabbronorites are Pig + Plg + or - Sp cumulates whose parent magmas may range from high-Al to intermediate-Ti mare basalt. At least three varieties of mare basalt are found at Apollo 14: high-Al, low-Ti; low-Al, intermediate-Ti; and low-Al, Ti VHK basalt. VHK (Very High Potassium) basalt is a new variety indigenous to Apollo 14.

  16. Ancient crustal components in the Fra Mauro breccias

    NASA Astrophysics Data System (ADS)

    Shervais, J. W.; Taylor, L. A.; Laul, J. C.

    1983-11-01

    Texturally pristine clasts preserve primary petrographic relationships and mineral compositions, yielding insights into igneous processes of the early lunar crust that cannot be gained from highly shocked and brecciated 'chemically pristine' samples. The use of texture as a prime criterion allows for expansion of the data base derived solely from chemical criteria, and provides complementary data. Texturally pristine clasts from the Apollo 14 site studied here include anorthosite, troctolites, gabbronorites, and basalts. Alkali anorthosites are plagioclase orthocumulates and may form by flotation in Mg-suite plutons. Ferroan anorthosite was cataclastically deformed and metamorphosed to granulite facies. Troctolites include both 01 + Plg and 01 + En + Plg cumulates. Major and trace element analyses of two troctolites reveal 'eastern' geochemical affinities that contrast other 'western' troctolites. Gabbronorites are Pig + Plg + or - Sp cumulates whose parent magmas may range from high-Al to intermediate-Ti mare basalt. At least three varieties of mare basalt are found at Apollo 14: high-Al, low-Ti; low-Al, intermediate-Ti; and low-Al, Ti VHK basalt. VHK (Very High Potassium) basalt is a new variety indigenous to Apollo 14.

  17. 49 CFR Appendix C to Part 241 - Geographical Boundaries of FRA's Regions and Addresses of FRA's Regional Headquarters

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... consists of Minnesota, Wisconsin, Michigan, Illinois, and Indiana. The mailing address of the Regional Headquarters is: 300 West Adams Street, Rm 310, Chicago, Illinois 60606. The fax number is 312-886-9634. The E... mailing address of the Regional Headquarters is: Murdock Executive Plaza, 703 Broadway, Suite...

  18. 49 CFR Appendix C to Part 241 - Geographical Boundaries of FRA's Regions and Addresses of FRA's Regional Headquarters

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... consists of Minnesota, Wisconsin, Michigan, Illinois, and Indiana. The mailing address of the Regional Headquarters is: 300 West Adams Street, Rm 310, Chicago, Illinois 60606. The fax number is 312-886-9634. The E... mailing address of the Regional Headquarters is: Murdock Executive Plaza, 703 Broadway, Suite...

  19. 49 CFR Appendix C to Part 241 - Geographical Boundaries of FRA's Regions and Addresses of FRA's Regional Headquarters

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... consists of Minnesota, Wisconsin, Michigan, Illinois, and Indiana. The mailing address of the Regional Headquarters is: 300 West Adams Street, Rm 310, Chicago, Illinois 60606. The fax number is 312-886-9634. The E... mailing address of the Regional Headquarters is: Murdock Executive Plaza, 703 Broadway, Suite...

  20. 49 CFR Appendix C to Part 241 - Geographical Boundaries of FRA's Regions and Addresses of FRA's Regional Headquarters

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... consists of Minnesota, Wisconsin, Michigan, Illinois, and Indiana. The mailing address of the Regional Headquarters is: 300 West Adams Street, Rm 310, Chicago, Illinois 60606. The fax number is 312-886-9634. The E... mailing address of the Regional Headquarters is: Murdock Executive Plaza, 703 Broadway, Suite...

  1. 49 CFR Appendix C to Part 241 - Geographical Boundaries of FRA's Regions and Addresses of FRA's Regional Headquarters

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... consists of Minnesota, Wisconsin, Michigan, Illinois, and Indiana. The mailing address of the Regional Headquarters is: 300 West Adams Street, Rm 310, Chicago, Illinois 60606. The fax number is 312-886-9634. The E... mailing address of the Regional Headquarters is: Murdock Executive Plaza, 703 Broadway, Suite...

  2. 49 CFR 242.103 - Approval of design of individual railroad programs by FRA.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Approval of design of individual railroad programs... (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION QUALIFICATION AND CERTIFICATION OF CONDUCTORS Program and Eligibility Requirements § 242.103 Approval of design of individual railroad...

  3. 49 CFR 242.103 - Approval of design of individual railroad programs by FRA.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Approval of design of individual railroad programs... (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION QUALIFICATION AND CERTIFICATION OF CONDUCTORS Program and Eligibility Requirements § 242.103 Approval of design of individual railroad...

  4. 49 CFR 242.103 - Approval of design of individual railroad programs by FRA.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Approval of design of individual railroad programs... (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION QUALIFICATION AND CERTIFICATION OF CONDUCTORS Program and Eligibility Requirements § 242.103 Approval of design of individual railroad...

  5. "Speech Act" Fra Teoria e Prassi Didattica. (The Speech Act between Theory and Pedagogical Practice).

    ERIC Educational Resources Information Center

    Minardi, Giovanni

    1982-01-01

    The author traces the development of speech act theory from Wittgenstein and Austin through Searle to Grice and shows how their work led to the notional functional approach to language teaching, which is based on the learner and his/her communicative needs. (CFM)

  6. 75 FR 27112 - Solicitation of Applications and Notice of Funding Availability for the FRA Railroad System...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-13

    ... chemical properties of biofuel, is eligible to apply. Eligible participants must show their ability to..., equipment and/or procurement fees, engineering fees, testing facilities fees, actual testing fees,...

  7. 75 FR 59322 - Notice of Availability of Answers to Frequently Asked Questions Regarding Buy America & FRA's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-27

    ..., 2000 (65 FR 19477), or visit http://www.regulations.gov . FOR FURTHER INFORMATION CONTACT: For... Passenger Rail (HSIPR) Interim Guidance (74 FR 29900 (June 23, 2009)) and as further detailed in a second set of HSIPR interim program guidance governing the distribution of fiscal year 2010 funding (75...

  8. 75 FR 8785 - Agency Request for Emergency Processing of Collection of Information Associated With FRA's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-25

    .... Robert Brogan (tel. (202) 493-6292) or Ms. Kimberly Toone (tel. (202) 493-6132). These numbers are not toll-free. A copy of this ICR may also be obtained electronically by contacting Mr. Brogan at...

  9. Geomorphology of crater and basin deposits - Emplacement of the Fra Mauro formation

    NASA Technical Reports Server (NTRS)

    Morrison, R. H.; Oberbeck, V. R.

    1975-01-01

    Characteristics of continuous deposits near lunar craters larger than about 1 km wide are considered, and it is concluded that (1) concentric dunes, radial ridges, and braided lineations result from deposition of the collision products of ejecta from adjacent pairs of similarly oriented secondary-crater chains and are, therefore, concentrations of secondary-crater ejecta; (2) intracrater ridges are produced within preexisting craters surrounding a fresh primary crater by ricocheting and focusing of secondary-crater ejecta from the preexisting craters' walls; and (3) secondary cratering has produced many of the structures of the continuous deposits of relatively small lunar craters and is the dominant process for emplacement of most of the radial facies of the continuous deposits of large lunar craters and basins. The percentages of Imbrium ejecta in deposits and the nature of Imbrium sculpturing are investigated.

  10. Exposure ages and neutron capture record in lunar samples from Fra Mauro.

    NASA Technical Reports Server (NTRS)

    Lugmair, G. W.; Marti, K.

    1972-01-01

    Cosmic-ray exposure ages of Apollo 14 rocks and rock fragments obtained by the Kr81-Kr83 method range from 27 to 700 m.y. Rock 14321, collected near the Cone crater rim, is one of the many approximately 27 m.y. old ejecta which were reported at the Third Lunar Science Conference. All the other rocks have considerably higher exposure ages. Isotopic anomalies from neutron capture in gadolinium, bromine, and barium are used to obtain information on the lunar neutron spectrum at various depths below the lunar surface. The flux ratio of resonance and slow (less than 0.3 eV) neutrons is found to be nearly constant in the topmost approximately 100 g/sq cm.

  11. 49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... facilitate communication, recordkeeping, and statistical analyses. The code may not be substituted for the... of plain bearing journal or fillet has (1) ridge, (2) depression, (3) circumferential score,...

  12. On Pu-244 in lunar rocks from Fra Mauro and implications regarding their origin.

    NASA Technical Reports Server (NTRS)

    Marti, K.; Lightner, B. D.; Lugmair, G. W.

    1973-01-01

    The evidence for in situ produced fission xenon from Pu-244 in rock 14321 is presented. The inferred abundance ratio Pu-244/U-238 is found to be consistent with values observed in a meteorite. Data from a stepwise release of the xenon permits a characterization of the trapped component, which can be shown to be distinct from solar xenon. We discuss the evidence for the presence of fission gases and of uncorrelated radiogenic argon in this and in other Apollo 14 rocks and some implications regarding their origin.

  13. 49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... designation in effect; (2) The basis for this designation. 215.013Failure to perform pre-departure inspection... is 9/16″ or less; (D) Wheel cracked or broken in: (1) rim, (2) flange, (3) plate or (4) hub area. (E) Wheel chip or gouge in flange: (1) 11/2″ length and 1/2″ in width or more; (2) 15/8″ length and 5/8″...

  14. 49 CFR Appendix C to Part 209 - FRA's Policy Statement Concerning Small Entities

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... continue to evolve to meet the needs of the railroad industry. For purposes of this policy statement, the... hazardous materials shippers meeting the economic criteria established for Class III railroads in 49 CFR... understands that small entities in the railroad industry have significantly different characteristics...

  15. 49 CFR Appendix C to Part 209 - FRA's Policy Statement Concerning Small Entities

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... continue to evolve to meet the needs of the railroad industry. For purposes of this policy statement, the... hazardous materials shippers meeting the economic criteria established for Class III railroads in 49 CFR... understands that small entities in the railroad industry have significantly different characteristics...

  16. 49 CFR 228.407 - Analysis of work schedules; submissions; FRA review and approval of submissions; fatigue...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... a scientifically valid, biomathematical model of human performance and fatigue that has been... railroad subject to this subpart wishes to use a model of human performance and fatigue, not previously..., biomathematical models of human performance and fatigue for the purpose of making the analysis required...

  17. 49 CFR Appendix B to Part 221 - Approved Rear End Marking Devices

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... for or by manufacturers 1. Manufacturer: Star Headlight & Lantern Co., 168 West Main Street, Honeoye Falls, NY 14472. FRA identification Nos. FRA-PLE-STAR-845-F (flasher) and FRA-PLE-STAR-845-C (steady... devices. FRA identification Nos. FRA-DRGW-YANK-300 (portable strobe), FRA-WP-YANK-301R (flashing),...

  18. 76 FR 50359 - Hours of Service of Railroad Employees; Substantive Regulations for Train Employees Providing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-12

    ... comments in response to FRA's March 22, 2011 proposed rule in this rulemaking (76 FR 16200), FRA issues... Public Law 110-432, Div. A, and FRA Interim Statement of Agency Policy and Interpretation at 74 FR...

  19. 49 CFR Appendix B to Part 221 - Approved Rear End Marking Devices

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... for or by manufacturers 1. Manufacturer: Star Headlight & Lantern Co., 168 West Main Street, Honeoye Falls, NY 14472. FRA identification Nos. FRA-PLE-STAR-845-F (flasher) and FRA-PLE-STAR-845-C...

  20. 49 CFR Appendix B to Part 221 - Approved Rear End Marking Devices

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... for or by manufacturers 1. Manufacturer: Star Headlight & Lantern Co., 168 West Main Street, Honeoye Falls, NY 14472. FRA identification Nos. FRA-PLE-STAR-845-F (flasher) and FRA-PLE-STAR-845-C...

  1. 49 CFR Appendix B to Part 221 - Approved Rear End Marking Devices

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... for or by manufacturers 1. Manufacturer: Star Headlight & Lantern Co., 168 West Main Street, Honeoye Falls, NY 14472. FRA identification Nos. FRA-PLE-STAR-845-F (flasher) and FRA-PLE-STAR-845-C...

  2. 49 CFR Appendix B to Part 221 - Approved Rear End Marking Devices

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... for or by manufacturers 1. Manufacturer: Star Headlight & Lantern Co., 168 West Main Street, Honeoye Falls, NY 14472. FRA identification Nos. FRA-PLE-STAR-845-F (flasher) and FRA-PLE-STAR-845-C...

  3. Petrogenesis of the western highlands of the moon - Evidence from a diverse group of whitlockite-rich rocks from the Fra Mauro formation

    NASA Technical Reports Server (NTRS)

    Snyder, Gregory A.; Taylor, Lawrence A.; Liu, Yun-Gang; Schmitt, Roman A.

    1992-01-01

    A group of KREEPy basalts has been discovered in Apollo 14 soils. These samples exhibit similarities to both HA and VHK basalts, albeit with much higher REE abundances, and contain up to 2 vol pct whitlockite and can be explained by assimilation of a K-, REE- and P-rich fluids by an original HA or VHK basalt. This KREEP component could have been produced late in the evolution of the lunar magma ocean and is similar in composition to QMD at Apollo 14. Two rocks have trace element compositions that are representative of actual KREEP. One of the samples appears to be petrographically pristine and could represent an actual KREEP basalt rock. Five subophitic high-Al basalts represent sampling of either a slowly cooled impact melt sheet or, more likely, the same basalt flow. Two 'quasi-pristine' highland rocks confirm the postulate of a connection between KREEP and the alkali suite. A newly discovered alkali anorthosite is a plagioclase cumulate with about 15 percent trapped KREEPy liquid.

  4. La ténorraphie percutanée dans les ruptures fraîches du tendon calcanéen: à propos de 67 cas

    PubMed Central

    Bessam, Aman; Hassani, Zouhir Ameziane; Kharmaz, Mohamed; Steinmetz, Alain

    2014-01-01

    La rupture du tendon calcanéen est une des lésions les plus fréquentes en pathologie du sport, les deux options thérapeutiques classiques sont le traitement orthopédique et la chirurgie à ciel ouvert. Dans le but de minimiser ces complications, des techniques mini-invasives de ténorraphie percutanée ont été proposées dont les résultats sont encourageants. Il s'agit d'une étude rétrospective d'une série de cas de rupture sous cutanée du tendon d'Achille s’étalant de Avril 2005 au Juin 2012 concernant 67 patients; 11 femmes et 56 hommes avec un âge moyen de 41 ans. La cause principale était un accident de sport dans 45 cas. Le diagnostic était évident à l'examen chez tous les patients. Dans deux cas il s'agissait d'une rerupture survenant à 1 et 5 ans d'un traitement orthopédique. Dans un cas il s'agissait d'une rerupture survenant après une ténorraphie percutanée. Dans deux cas il s'agissait d'une rupture sur tendinopathie chronique. Tous les patients avaient bénéficié d'une radio de la cheville qui avait montré une horizontalisation du calcanéum chez 5 patients et surtout elle n'avait pas montré de fracture associée, alors que 15 patients avaient bénéficié d'une échographie qui a confirmé le diagnostic. Tous les patients avaient été opérés dans un délai de moins de 48 heures Une ténorraphie percutanée a été pratiqué chez tous les patients. Le recul moyen est de 43 mois, trois patients ont été perdus de vue Nous avons noté une reprise des activités professionnelle effective en moyen 90 jours après l'intervention et celle des activités sportive à 6 mois en moyenne L’état cutané local a été jugée bon dans 63 cas. Par ailleurs les complications ont été marquées par un seul cas d'infection ayant nécessité une reprise chirurgical a été noté mise à plat, trois cas de rerupture repris par suture à ciel ouvert, un cas d'algodystrophie et un cas de tendinopathie Il n'y a eu aucune complication thromboembolique ni neurologique. Il n'existe pas de réel consensus concernant la prise en charge des ruptures du tendon calcanéen. Ainsi, La ténorraphie percutanée du tendon calcanéen est une méthode simple rapide et efficace, elle allie les avantages de la chirurgie à ciel ouvert en termes de pourcentage de rerupture et les avantages du traitement fonctionnel en rapport avec un faible risque infectieux. PMID:25332749

  5. Copy number and haplotype variation at the VRN-A1 and central FR-A2 loci are associated with frost tolerance in hexaploid wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Frost tolerance is a key trait to ensure winter wheat survival. Natural variation for this trait is mainly associated with allelic differences at the VERNALIZATION 1 (VRN1) and FROST RESISTANCE 2 (FR2) loci. VRN1 regulates the transition between vegetative and reproductive stages and FR2, a locus in...

  6. 78 FR 78275 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2014

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-26

    .... SUMMARY: According to data from FRA's Management Information System, the rail industry's random drug... determination is effective December 26, 2013. FOR FURTHER INFORMATION CONTACT: Jerry Powers, FRA Drug...

  7. 75 FR 36551 - State Highway-Rail Grade Crossing Action Plans

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-28

    ... accordance with its ``Procedures for Considering Environmental Impacts'' (FRA's Procedures) (64 FR 28545, May..., 2009 (74 FR 45336). FRA received one adverse comment regarding the direct final rule. Pursuant to 49... events must be reported to FRA pursuant to 49 CFR 225.19. From this database, FRA identified the...

  8. 49 CFR 225.21 - Forms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... miles, yard switching train miles, and other train miles run during the month. (c) Form FRA 6180.55a... Office of Safety, FRA, 400 Seventh Street, SW., Washington, DC 20590. (a) Form FRA F 6180.54—Rail Equipment Accident/Incident Report. Form FRA F 6180.54 shall be used to report each reportable...

  9. Cluster of genes that encode positive and negative elements influencing filament length in a heterocyst-forming cyanobacterium.

    PubMed

    Merino-Puerto, Victoria; Herrero, Antonia; Flores, Enrique

    2013-09-01

    The filamentous, heterocyst-forming cyanobacteria perform oxygenic photosynthesis in vegetative cells and nitrogen fixation in heterocysts, and their filaments can be hundreds of cells long. In the model heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120, the genes in the fraC-fraD-fraE operon are required for filament integrity mainly under conditions of nitrogen deprivation. The fraC operon transcript partially overlaps gene all2395, which lies in the opposite DNA strand and ends 1 bp beyond fraE. Gene all2395 produces transcripts of 1.35 kb (major transcript) and 2.2 kb (minor transcript) that overlap fraE and whose expression is dependent on the N-control transcription factor NtcA. Insertion of a gene cassette containing transcriptional terminators between fraE and all2395 prevented production of the antisense RNAs and resulted in an increased length of the cyanobacterial filaments. Deletion of all2395 resulted in a larger increase of filament length and in impaired growth, mainly under N2-fixing conditions and specifically on solid medium. We denote all2395 the fraF gene, which encodes a protein restricting filament length. A FraF-green fluorescent protein (GFP) fusion protein accumulated significantly in heterocysts. Similar to some heterocyst differentiation-related proteins such as HglK, HetL, and PatL, FraF is a pentapeptide repeat protein. We conclude that the fraC-fraD-fraE←fraF gene cluster (where the arrow indicates a change in orientation), in which cis antisense RNAs are produced, regulates morphology by encoding proteins that influence positively (FraC, FraD, FraE) or negatively (FraF) the length of the filament mainly under conditions of nitrogen deprivation. This gene cluster is often conserved in heterocyst-forming cyanobacteria. PMID:23813733

  10. Cluster of Genes That Encode Positive and Negative Elements Influencing Filament Length in a Heterocyst-Forming Cyanobacterium

    PubMed Central

    Merino-Puerto, Victoria; Herrero, Antonia

    2013-01-01

    The filamentous, heterocyst-forming cyanobacteria perform oxygenic photosynthesis in vegetative cells and nitrogen fixation in heterocysts, and their filaments can be hundreds of cells long. In the model heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120, the genes in the fraC-fraD-fraE operon are required for filament integrity mainly under conditions of nitrogen deprivation. The fraC operon transcript partially overlaps gene all2395, which lies in the opposite DNA strand and ends 1 bp beyond fraE. Gene all2395 produces transcripts of 1.35 kb (major transcript) and 2.2 kb (minor transcript) that overlap fraE and whose expression is dependent on the N-control transcription factor NtcA. Insertion of a gene cassette containing transcriptional terminators between fraE and all2395 prevented production of the antisense RNAs and resulted in an increased length of the cyanobacterial filaments. Deletion of all2395 resulted in a larger increase of filament length and in impaired growth, mainly under N2-fixing conditions and specifically on solid medium. We denote all2395 the fraF gene, which encodes a protein restricting filament length. A FraF-green fluorescent protein (GFP) fusion protein accumulated significantly in heterocysts. Similar to some heterocyst differentiation-related proteins such as HglK, HetL, and PatL, FraF is a pentapeptide repeat protein. We conclude that the fraC-fraD-fraE←fraF gene cluster (where the arrow indicates a change in orientation), in which cis antisense RNAs are produced, regulates morphology by encoding proteins that influence positively (FraC, FraD, FraE) or negatively (FraF) the length of the filament mainly under conditions of nitrogen deprivation. This gene cluster is often conserved in heterocyst-forming cyanobacteria. PMID:23813733

  11. 78 FR 76191 - Operational Tests and Inspections for Compliance With Maximum Authorized Train Speeds and Other...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-16

    ... Train Speeds and Other Speed Restrictions AGENCY: Federal Railroad Administration (FRA), Department of... maximum authorized train speeds and other speed restrictions. SUMMARY: FRA is issuing Safety Advisory 2013... and applicable railroad operating rules regarding maximum authorized train speed limits and...

  12. Serum folate receptor alpha as a biomarker for ovarian cancer: Implications for diagnosis, prognosis and predicting its local tumor expression.

    PubMed

    Kurosaki, Akira; Hasegawa, Kosei; Kato, Tomomi; Abe, Kenji; Hanaoka, Tatsuya; Miyara, Akiko; O'Shannessy, Daniel J; Somers, Elizabeth B; Yasuda, Masanori; Sekino, Tetsuo; Fujiwara, Keiichi

    2016-04-15

    Folate receptor alpha (FRA) is a GPI-anchored glycoprotein and encoded by the FOLR1 gene. High expression of FRA is observed in specific malignant tumors of epithelial origin, including ovarian cancer, but exhibits very limited normal tissue expression, making it as an attractive target for the ovarian cancer therapy. FRA is known to shed from the cell surface into the circulation which allows for its measurement in the serum of patients. Recently, methods to detect the soluble form of FRA have been developed and serum FRA (sFRA) is considered a highly promising biomarker for ovarian cancer. We prospectively investigated the levels of sFRA in patients clinically suspected of having malignant ovarian tumors. A total of 231 patients were enrolled in this study and analyzed for sFRA as well as tumor expression of FRA by immunohistochemistry. High sFRA was predominantly observed in epithelial ovarian cancer patients, but not in patients with benign or borderline gynecological disease or metastatic ovarian tumors from advanced colorectal cancers. Levels of sFRA were highly correlated to clinical stage, tumor grade and histological type and demonstrated superior accuracy for the detection of ovarian cancer than did serum CA125. High sFRA was significantly associated with shorter progression-free survival in both early and advanced ovarian cancer patients. Finally, tumor FRA expression status was strongly correlated with sFRA levels. Taken together, these data suggest that sFRA might be a useful noninvasive serum biomarkers for future clinical trials assessing FRA-targeted therapy.

  13. 78 FR 16051 - Vehicle/Track Interaction Safety Standards; High-Speed and High Cant Deficiency Operations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-13

    ... vehicle/track interaction safety, see 75 FR 25928, FRA issues this final rule amending the Track Safety... granted to FRA comprehensive authority over ``all areas of railroad safety.'' See 36 FR 20336. FRA... 22, 1998, see 63 FR 33992, which, effective September 21, 1998, revised the Track Safety Standards...

  14. 77 FR 546 - Adjustment of Nationwide Significant Risk Threshold

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-05

    ... Locomotive Horns at Highway-Rail Grade Crossings,'' was amended, the NSRT was 17,030 (71 FR 47614, August 17, 2006). In 2007, FRA recalculated the NSRT to be 19,047 (72 FR 14850, March 29, 2007). In 2008, FRA recalculated the NSRT to be 17,610 (73 FR 30661, May 28, 2008). In 2009, FRA recalculated the NSRT to be...

  15. 75 FR 82136 - Adjustment of Nationwide Significant Risk Threshold

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-29

    ... Locomotive Horns at Highway-Rail Grade Crossings,'' was amended, the NSRT was 17,030 (71 FR 47614, August 17, 2006). In 2007, FRA recalculated the NSRT to be 19,047 (72 FR 14850, March 29, 2007). In 2008, FRA recalculated the NSRT to be 17,610 (73 FR 30661, May 28, 2008). In 2009, FRA recalculated the NSRT to be...

  16. Aberrant Neural Function during Emotion Attribution in Female Subjects with Fragile X Syndrome

    ERIC Educational Resources Information Center

    Hagan, Cindy C.; Hoeft, Fumiko; Mackey, Allyson; Mobbs, Dean; Reiss, Allan L.

    2008-01-01

    The neurobiological systems which underlie emotion attribution among female patients with Fragile X (FraX) syndrome are examined. Results show that the emotion circuit which regulates responses to facial stimuli is potentially disrupted among female subjects with FraX syndrome. Anterior cingulate cortex activity in female subjects with FraX…

  17. 75 FR 39325 - Notice of Draft Finding of No Significant Impact for the Washington State Portion of the Pacific...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-08

    ... FONSI are available on FRA's Web site at: http://www.fra.dot.gov/Pages/3006.shtml and WSDOT's Web site... Department of Transportation, State Rail and Marine Office, 310 Maple Park Ave., SE., P.O. Box 47407, Olympia... Railroad Administration (FRA), United States Department of Transportation (DOT). ACTION: Notice...

  18. 78 FR 71785 - Passenger Train Emergency Systems II

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-29

    ... FRA's January 3, 2012, proposed rule on passenger train emergency systems, see 77 FR 153, FRA issues... the Act, FRA published the Passenger Train Emergency Preparedness (PTEP) final rule. See 63 FR 24629...) final rule. See 64 FR 25540. The rule established comprehensive safety standards for railroad...

  19. 78 FR 57450 - State Rail Plan Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-18

    ... requirements for State rail plans. The State Rail Plan Guidance is available on FRA's Web site at http://www.fra.dot.gov/Page/P0511 . DATES: The final State Rail Plan Guidance is effective as of the publication....dot.gov/Page/P0511 . The purpose of FRA's final State Rail Plan Guidance is to describe the...

  20. Frontal association cortex is engaged in stimulus integration during associative learning.

    PubMed

    Nakayama, Daisuke; Baraki, Zohal; Onoue, Kousuke; Ikegaya, Yuji; Matsuki, Norio; Nomura, Hiroshi

    2015-01-01

    The frontal association cortex (FrA) is implicated in higher brain function. Aberrant FrA activity is likely to be involved in dementia pathology. However, the functional circuits both within the FrA and with other regions are unclear. A recent study showed that inactivation of the FrA impairs memory consolidation of an auditory fear conditioning in young mice. In addition, dendritic spine remodeling of FrA neurons is sensitive to paired sensory stimuli that produce associative memory. These findings suggest that the FrA is engaged in neural processes critical to associative learning. Here we characterize stimulus integration in the mouse FrA during associative learning. We experimentally separated contextual fear conditioning into context exposure and shock, and found that memory formation requires protein synthesis associated with both context exposure and shock in the FrA. Both context exposure and shock trigger Arc, an activity-dependent immediate-early gene, expression in the FrA, and a subset of FrA neurons was dually activated by both stimuli. In addition, we found that the FrA receives projections from the perirhinal (PRh) and insular (IC) cortices and basolateral amygdala (BLA), which are implicated in context and shock encoding. PRh and IC neurons projecting to the FrA were activated by context exposure and shock, respectively. Arc expression in the FrA associated with context exposure and shock depended on PRh activity and both IC and BLA activities, respectively. These findings indicate that the FrA is engaged in stimulus integration and contributes to memory formation in associative learning. PMID:25496961

  1. Arabidopsis Fragile Fiber8, Which Encodes a Putative Glucuronyltransferase, Is Essential for Normal Secondary Wall Synthesis

    PubMed Central

    Zhong, Ruiqin; Peña, Maria J.; Zhou, Gong-Ke; Nairn, C. Joseph; Wood-Jones, Alicia; Richardson, Elizabeth A.; Morrison, W. Herbert; Darvill, Alan G.; York, William S.; Ye, Zheng-Hua

    2005-01-01

    Secondary walls in vessels and fibers of dicotyledonous plants are mainly composed of cellulose, xylan, and lignin. Although genes involved in biosynthesis of cellulose and lignin have been intensively studied, little is known about genes participating in xylan synthesis. We found that Arabidopsis thaliana fragile fiber8 (fra8) is defective in xylan synthesis. The fra8 mutation caused a dramatic reduction in fiber wall thickness and a decrease in stem strength. FRA8 was found to encode a member of glycosyltransferase family 47 and exhibits high sequence similarity to tobacco (Nicotiana plumbaginifolia) pectin glucuronyltransferase. FRA8 is expressed specifically in developing vessels and fiber cells, and FRA8 is targeted to Golgi. Comparative analyses of cell wall polysaccharide fractions from fra8 and wild-type stems showed that the xylan and cellulose contents are drastically reduced in fra8, whereas xyloglucan and pectin are elevated. Further structural analysis of cell walls revealed that although wild-type xylans contain both glucuronic acid and 4-O-methylglucuronic acid residues, xylans from fra8 retain only 4-O-methylglucuronic acid, indicating that the fra8 mutation results in a specific defect in the addition of glucuronic acid residues onto xylans. These findings suggest that FRA8 is a glucuronyltransferase involved in the biosynthesis of glucuronoxylan during secondary wall formation. PMID:16272433

  2. Mind the gap: the distributional effects of raising the early eligibility age and full retirement age.

    PubMed

    Olsen, Anya

    2012-01-01

    Policymakers have proposed increases to the early eligibility age (EEA) and/or full retirement age (FRA) to address increasing life expectancy and Social Security solvency issues. This analysis uses the Social Security Administration's Modeling Income in the Near Term, version 6 (MINT6) model to compare three retirement-age increases suggested by the Social Security Advisory Board: increase the gap between the EEA and FRA by raising only the FRA, increase both the EEA and FRA to maintain a 4-year gap between them, and increase both the EEA and FRA to maintain a 5-year gap between them. Although all three options would improve system solvency by similar proportions, their effect on individual beneficiaries in the future would vary. Benefit reductions are greater under the proposals with more months between the EEA and FRA, while the option that maintains a 4-year gap results in benefit increases for some beneficiaries compared with current law. PMID:23397744

  3. 78 FR 70623 - Adjustment of Nationwide Significant Risk Threshold

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-26

    ... calculated to be 17,030 (71 FR 47614, August 17, 2006). In 2007, FRA recalculated the NSRT to be 19,047 (72 FR 14850, March 29, 2007). In 2008, FRA recalculated the NSRT to be 17,610 (73 FR 30661, May 28, 2008). In 2009, FRA recalculated the NSRT to be 18,775 (74 FR 45270, September 1, 2009). In 2010,...

  4. 49 CFR Appendix D to Part 230 - Civil Penalty Schedule

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... the boiler: (1) FRA Form No. 19 not properly filled out 1,000 1,500 (2) FRA Form No. 19 not properly maintained 1,000 1,500 (c) Repairs to stayed portions of the boiler: (1) FRA Form No. 19 not properly filled... document steam locomotive number Change 1,000 1,500 Subpart B—Boilers and Appurtenances 230.22Failure...

  5. 49 CFR Appendix D to Part 230 - Civil Penalty Schedule

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... the boiler: (1) FRA Form No. 19 not properly filled out 1,000 1,500 (2) FRA Form No. 19 not properly maintained 1,000 1,500 (c) Repairs to stayed portions of the boiler: (1) FRA Form No. 19 not properly filled... document steam locomotive number Change 1,000 1,500 Subpart B—Boilers and Appurtenances 230.22Failure...

  6. 49 CFR Appendix D to Part 230 - Civil Penalty Schedule

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... the boiler: (1) FRA Form No. 19 not properly filled out 1,000 1,500 (2) FRA Form No. 19 not properly maintained 1,000 1,500 (c) Repairs to stayed portions of the boiler: (1) FRA Form No. 19 not properly filled... document steam locomotive number Change 1,000 1,500 Subpart B—Boilers and Appurtenances 230.22Failure...

  7. 49 CFR Appendix D to Part 230 - Civil Penalty Schedule

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... the boiler: (1) FRA Form No. 19 not properly filled out 1,000 1,500 (2) FRA Form No. 19 not properly maintained 1,000 1,500 (c) Repairs to stayed portions of the boiler: (1) FRA Form No. 19 not properly filled... document steam locomotive number Change 1,000 1,500 Subpart B—Boilers and Appurtenances 230.22Failure...

  8. 49 CFR Appendix D to Part 230 - Civil Penalty Schedule

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... the boiler: (1) FRA Form No. 19 not properly filled out 1,000 1,500 (2) FRA Form No. 19 not properly maintained 1,000 1,500 (c) Repairs to stayed portions of the boiler: (1) FRA Form No. 19 not properly filled... document steam locomotive number Change 1,000 1,500 Subpart B—Boilers and Appurtenances 230.22Failure...

  9. 77 FR 75896 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-26

    .... According to data from FRA's Management Information System, the rail industry's random drug testing positive... notice of determination is effective December 26, 2012. FOR FURTHER INFORMATION CONTACT: Elizabeth...

  10. 49 CFR 229.211 - Processing of petitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., FRA will consider proper documentation of competent engineering analysis, or practical demonstrations, or both which may include validated computer modeling, structural crush analysis, component...

  11. Netrins and Frazzled/DCC promote the migration and mesenchymal to epithelial transition of Drosophila midgut cells

    PubMed Central

    Pert, Melissa; Gan, Miao; Saint, Robert; Murray, Michael J.

    2015-01-01

    ABSTRACT Mesenchymal-epithelial transitions (METs) are important in both development and the growth of secondary tumours. Although the molecular basis for epithelial polarity is well studied, less is known about the cues that induce MET. Here we show that Netrins, well known as chemotropic guidance factors, provide a basal polarising cue during the Drosophila midgut MET. Both netrinA and netrinB are expressed in the visceral mesoderm, the substrate upon which midgut cells migrate, while their receptor frazzled (fra) is expressed in midgut cells. Netrins are required to polarise Fra to the basal surface, and Netrins and Fra undergo mutually-dependent endocytosis, with Fra subsequently trafficking to late endosomes. Mutations to fra and netrins affect both migration and MET but to different degrees. Loss of fra strongly delays migration, midgut cells fail to extend protrusions, and apico-basal polarisation of proteins and epithelium formation is inhibited. In netrin mutants, the migration phenotype is weaker and cells still extend protrusions. However, apico-basal polarisation of proteins, including Fra, and FActin is greatly disrupted and a monolayer fails to form. Delocalised accumulations of FActin are prevalent in netrin mutants but not fra mutants suggesting delocalised Fra may disrupt the MET. βPS localisation is also affected in netrin mutants in that a basal gradient is reduced while localisation to the midgut/VM interface is increased. Since a similar effect is seen when endocytosis is inhibited, Netrin and Fra may regulate Integrin turnover. The results suggest Netrin-dependent basal polarisation of Fra is critical for the formation of an epithelium. PMID:25617422

  12. Netrins and Frazzled/DCC promote the migration and mesenchymal to epithelial transition of Drosophila midgut cells.

    PubMed

    Pert, Melissa; Gan, Miao; Saint, Robert; Murray, Michael J

    2015-01-23

    Mesenchymal-epithelial transitions (METs) are important in both development and the growth of secondary tumours. Although the molecular basis for epithelial polarity is well studied, less is known about the cues that induce MET. Here we show that Netrins, well known as chemotropic guidance factors, provide a basal polarising cue during the Drosophila midgut MET. Both netrinA and netrinB are expressed in the visceral mesoderm, the substrate upon which midgut cells migrate, while their receptor frazzled (fra) is expressed in midgut cells. Netrins are required to polarise Fra to the basal surface, and Netrins and Fra undergo mutually-dependent endocytosis, with Fra subsequently trafficking to late endosomes. Mutations to fra and netrins affect both migration and MET but to different degrees. Loss of fra strongly delays migration, midgut cells fail to extend protrusions, and apico-basal polarisation of proteins and epithelium formation is inhibited. In netrin mutants, the migration phenotype is weaker and cells still extend protrusions. However, apico-basal polarisation of proteins, including Fra, and FActin is greatly disrupted and a monolayer fails to form. Delocalised accumulations of FActin are prevalent in netrin mutants but not fra mutants suggesting delocalised Fra may disrupt the MET. βPS localisation is also affected in netrin mutants in that a basal gradient is reduced while localisation to the midgut/VM interface is increased. Since a similar effect is seen when endocytosis is inhibited, Netrin and Fra may regulate Integrin turnover. The results suggest Netrin-dependent basal polarisation of Fra is critical for the formation of an epithelium.

  13. Assignment of human KH-box-containing genes by in situ hybridization: HNRNPK maps to 9q21.32-q21.33, PCBP1 to 2p12-p13, and PCBP2 to 12q13.12-q13.13, distal to FRA12A

    SciTech Connect

    Tommerup, N.; Leffers, H.

    1996-03-01

    This report describes the localization of various human KH-box-containing genes using fluorescence in situ hybridization. Accordingly, HNRNPK was mapped to human chromosome 9q21.32-q21.33, PCBP1 was mapped to human chromosome 2p12-p13, and PCBP2 was mapped to human chromosome 12q13.12-q13.13. These proteins affect RNA-binding capability. 13 refs., 1 fig.

  14. 76 FR 30855 - Accident/Incident Reporting Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-27

    ... regulations and to enhance the quality of information available for railroad casualty analysis. See 73 FR... recording standards and guidance. See 75 FR 68862. Following the publication of the final rule, FRA received... related to the railroad's rail transportation business. 68 FR 10108-09, March 3, 2003 (FRA's 2003...

  15. 49 CFR 236.915 - Implementation and operation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... the informational filing for that product. The FRA filing date can be found in FRA's acknowledgment... any time submit an amended PSP according to the procedures outlined in § 236.913. (c) What precautions... depend on normal functioning of such product. (d) What actions must be taken immediately upon failure...

  16. 49 CFR 236.915 - Implementation and operation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... the informational filing for that product. The FRA filing date can be found in FRA's acknowledgment... any time submit an amended PSP according to the procedures outlined in § 236.913. (c) What precautions... depend on normal functioning of such product. (d) What actions must be taken immediately upon failure...

  17. 77 FR 58907 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-24

    ....) SUPPLEMENTARY INFORMATION: The Paperwork Reduction Act of 1995 (PRA), Public Law 104-13, Sec. 2, 109 Stat. 163... safety laws and regulations. Additionally, railroads are required to report to FRA actions taken to remedy certain alleged violations of law. Form Number(s): FRA F...

  18. 78 FR 12826 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-25

    ... General Railroad System by Conventional Railroads and Light Rail Transit Systems, 65 FR 42626 (July 10... the Tracks of the General Railroad System by Light Rail and Conventional Equipment, 65 FR 42529 (July... safety regulations. FRA assigned the petition Docket Number FRA-1999-6254. VTA's 42.2-mile light...

  19. 78 FR 13154 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-26

    ... Conventional Railroads and Light ] Rail Transit Systems, 65 FR 42626 (July 10, 2000).) FRA assigned the petition Docket Number FRA-2002-11809. NCTD operates its SPRINTER light rail transit system (SPRINTER... Railroad System by Light Rail and Conventional Equipment, 65 FR 42529 (July 10, 2000). See also...

  20. 75 FR 65707 - Notice Regarding Consideration and Processing of Applications for Financial Assistance Under the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-26

    ... Federal Register on September 29, 2010 (75 FR 60165) regarding consideration and processing of... published a notice in the Federal Register on September 29, 2010 (75 FR 60165) regarding FRA's consideration...-178 (1998) (TEA-21). FRA is hereby correcting that information, stated in the first column,...

  1. 75 FR 38365 - High-Speed Intercity Passenger Rail (HSIPR) Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-01

    ... making multiple awards from the maximum $245 million available for Individual Projects. As such, FRA... identified through a rational planning process that analyzes the investment needs and service objectives of.... Similarly, FRA may require the return of obligated funds that remain unexpended if the grantee is not...

  2. 49 CFR 268.11 - Project eligibility standards.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION MAGNETIC LEVITATION TRANSPORTATION TECHNOLOGY DEPLOYMENT PROGRAM... metropolitan planning requirements; (vi) Be approved by FRA based on an application submitted by a State or... expected to review proposed work statements with FRA at pre-application meetings or through some...

  3. 49 CFR 268.3 - Different phases of the Maglev Deployment Program.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION MAGNETIC LEVITATION TRANSPORTATION TECHNOLOGY... applications) are for planning purposes only and are subject to change—including possible acceleration of..., applications must be filed with FRA by February 15, 1999. FRA will select one or more projects to...

  4. 49 CFR 268.3 - Different phases of the Maglev Deployment Program.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION MAGNETIC LEVITATION TRANSPORTATION TECHNOLOGY... applications) are for planning purposes only and are subject to change—including possible acceleration of..., applications must be filed with FRA by February 15, 1999. FRA will select one or more projects to...

  5. 78 FR 65422 - Notice of Funding Availability and Solicitation of Applications for Grants Under the Railroad...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-31

    ... Procedures for Considering Environmental Impacts (64 FR 28545) (May 26, 1999) ( http://www.fra.dot.gov/Page... oversized engineering drawings), applicants may submit an original and two (2) copies to FRA at the... status or progress toward completing any environmental documentation or clearance for the...

  6. 78 FR 2713 - Update to NEPA Implementing Procedures

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-14

    ... that some types of waste water treatment systems may be appropriate for exclusion under this CE. Oil... Environmental Impacts (FRA Environmental Procedures), 64 FR 28545 (May 26, 1999), which are available on the... June 13, 2012, FRA published a notice in the Federal Register (77 FR 35471) advising the public of...

  7. 76 FR 18298 - Notice of Availability of a Final Environmental Impact Statement for the DesertXpress High-Speed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-01

    ... Considering Environmental Impacts (64 FR 28545, May 26, 1999). The Bureau of Land Management (BLM), Surface... DesertXpress High-Speed Passenger Train Project AGENCY: Federal Railroad Administration (FRA), United... High-Speed Passenger Train Project (DesertXpress project). FRA is the Lead Agency for the...

  8. 76 FR 66126 - Notice of Public Hearing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-25

    ... Federal Railroad Administration Notice of Public Hearing The Central Oregon and Pacific Railroad (CORP) has petitioned the Federal Railroad Administration (FRA) seeking the approval of the proposed....regulations.gov . FRA has conducted a field investigation in this matter and has issued a public...

  9. 76 FR 71116 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-16

    ... the Transportation Equity Act for the 21st Century of 1998, Public Law 105-178 (1998) (TEA 21), and..., FRA published a final rule (FR) with procedures and requirements to cover applications of financial... Act by section 7203 of TEA 21. On September 29, 2010, FRA published a Notice Regarding...

  10. 78 FR 48218 - Emergency Order Establishing Additional Requirements for Attendance and Securement of Certain...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-07

    ... Terminal The Federal Railroad Administration (FRA) of the United States Department of Transportation (DOT... terminal are properly secured against unintended movement. FRA re-examined its regulations governing the... mainline track or mainline siding outside of a yard or terminal to ensure ] the safe transportation by...

  11. 49 CFR 216.11 - Special notice for repairs-railroad freight car.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Special notice for repairs-railroad freight car...—railroad freight car. (a) When an FRA Motive Power and Equipment Inspector or a State Equipment Inspector determines that a railroad freight car is not in conformity with the requirements of the FRA Freight...

  12. 49 CFR 216.11 - Special notice for repairs-railroad freight car.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Special notice for repairs-railroad freight car...—railroad freight car. (a) When an FRA Motive Power and Equipment Inspector or a State Equipment Inspector determines that a railroad freight car is not in conformity with the requirements of the FRA Freight...

  13. 49 CFR 216.11 - Special notice for repairs-railroad freight car.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Special notice for repairs-railroad freight car...—railroad freight car. (a) When an FRA Motive Power and Equipment Inspector or a State Equipment Inspector determines that a railroad freight car is not in conformity with the requirements of the FRA Freight...

  14. 78 FR 5161 - National Highway-Rail Crossing Inventory Reporting Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-24

    ... to present oral statements and to proffer information and views related to FRA's proposal at the... contact information. FRA reserves the right to limit the duration of presentations, if necessary, to... hearing and to provide interested parties the opportunity to submit comments in response to views...

  15. 75 FR 79308 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2011

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    .... SUMMARY: Using data from Management Information System annual reports, FRA has determined that the 2009... taken from FRA's Management Information System. Based on this data, the Administrator publishes a... effective December 20, 2010. FOR FURTHER INFORMATION CONTACT: Lamar Allen, Alcohol and Drug Program...

  16. 75 FR 76345 - Risk Reduction Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-08

    ... Secretary has since delegated those responsibilities to the FRA Administrator. See 49 CFR 1.49(oo); 74 FR... disorders. Effects on employee fatigue of an employee's short-term or sustained response to emergency.... Overall, a risk reduction approach could help railroads, FRA, and labor organizations learn how...

  17. 77 FR 75045 - Locomotive Safety Standards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-19

    ... proceeding on January 12, 2011. See 76 FR 2199. The specific regulatory language recommended by the RSAC was... comments FRA issued a final rule on April 9, 2012. See 77 FR 21312. In accordance with the provisions of... what was been learned from FRA's retrospective review of the regulation. E.O. 13563 requires...

  18. 78 FR 57447 - Environmental Impact Statement for the ACEforward

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-18

    ... TRANSPORTATION Federal Railroad Administration Environmental Impact Statement for the ACEforward Program From Merced, Modesto and Stockton to San Jose, California AGENCY: Federal Railroad Administration (FRA) U.S... service to Modesto and Merced, California. FRA has responsibility for overseeing the safety of...

  19. 77 FR 20691 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-05

    ... September 26, 2011, Iowa Interstate Railroad, Ltd. (IAIS) has petitioned the Federal Railroad Administration... contained at 49 CFR part 230. FRA assigned the petition Docket Number FRA-2011-0078. IAIS seeks relief from... annual inspection. IAIS will perform all other inspections as required by 49 CFR 230.16,...

  20. 76 FR 34801 - Petition for Modification of Single Car Air Brake Test Procedures

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-14

    ... Federal Railroad Administration Petition for Modification of Single Car Air Brake Test Procedures In... (PATH) has requested the Federal Railroad Administration (FRA) grant a modification of the single car... FRA-2010-0174. PATH operates a fleet of 25 flat cars in consist with revenue cars utilized...

  1. 77 FR 4271 - Special Permit Marking Removal

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    ... Register notice providing such approval for certain tank cars. 76 FR 4250. In that notice, FRA stated that... From Tank Cars Each rail tank car subject to FRA's January 25, 2011, Federal Register notice (76 FR... that had an established safety record. 75 FR 27205. The final rule amended the HMR to allow, upon...

  2. 49 CFR 216.11 - Special notice for repairs-railroad freight car.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Special notice for repairs-railroad freight car...—railroad freight car. (a) When an FRA Motive Power and Equipment Inspector or a State Equipment Inspector determines that a railroad freight car is not in conformity with the requirements of the FRA Freight...

  3. 76 FR 8397 - Environmental Impact Statement for the Chicago, IL to St. Louis, MO High Speed Rail Program Corridor

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-14

    ... through the following Web site: http://www.idothsr.org . SUPPLEMENTARY INFORMATION: FRA, in cooperation... Impacts (64 FR 28545; May 26, 1999). The FRA and IDOT will ] use a tiered process, as provided for in 40.../highway traffic conflicts. There are six projects specifically identified by CREATE (P1, P2, P3, EW2,...

  4. 49 CFR 1106.4 - The Safety Integration Plan process.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ongoing environmental review process under 49 CFR part 1105. The procedures governing the process shall be as follows: (1) In accordance with 49 CFR 244.17, FRA will provide its findings and conclusions on... at 49 CFR part 244, or other FRA guidelines or requirements regarding the contents of a SIP, with...

  5. 49 CFR 1106.4 - The Safety Integration Plan process.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ongoing environmental review process under 49 CFR part 1105. The procedures governing the process shall be as follows: (1) In accordance with 49 CFR 244.17, FRA will provide its findings and conclusions on... at 49 CFR part 244, or other FRA guidelines or requirements regarding the contents of a SIP, with...

  6. 78 FR 77601 - Adjustment of Monetary Threshold for Reporting Rail Equipment Accidents/Incidents for Calendar...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-24

    ... 61 FR 60632 (Nov. 29, 1996). In 2005, FRA again amended its method for calculating the reporting... Surface Transportation Board for the BLS data that was no longer collected (70 FR 75414 (Dec. 20, 2005... threshold was revised. 77 FR 71354 (November 30, 2012). Consequently, FRA has recalculated the threshold,...

  7. 76 FR 72850 - Adjustment of Monetary Threshold for Reporting Rail Equipment Accidents/Incidents for Calendar...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ... reporting threshold was revised. 75 FR 75911 (December 7, 2010). Consequently, FRA has recalculated the... published December 20, 2005, 70 FR 75414. FRA has found that both the current cost data inserted into this... addition to DOT policies and procedures (44 FR 11034 (Feb. 26, 1979)). Regulatory Flexibility Act...

  8. 77 FR 71354 - Adjustment of Monetary Threshold for Reporting Rail Equipment Accidents/Incidents for Calendar...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-30

    ... reporting threshold was revised. 76 FR 72850 (November 28, 2011). Consequently, FRA has recalculated the... final rule published December 20, 2005, 70 FR 75414. FRA has found that both the current cost data... 12866 and 13563 in addition to DOT policies and procedures (44 FR 11034 (Feb. 26, 1979))....

  9. 49 CFR Appendix A to Part 222 - Approved Supplementary Safety Measures

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... of the crossing. VPD should be installed on one or both sides of the crossing and/or in the surface.... FRA's web-based Quiet Zone Calculator may be used to complete this calculation.) 2. Adjust the risk... qualifying, pre-existing SSM. (See appendix D. FRA's web-based Quiet Zone Calculator may be used to...

  10. 49 CFR Appendix A to Part 222 - Approved Supplementary Safety Measures

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... of the crossing. VPD should be installed on one or both sides of the crossing and/or in the surface.... FRA's web-based Quiet Zone Calculator may be used to complete this calculation.) 2. Adjust the risk... qualifying, pre-existing SSM. (See appendix D. FRA's web-based Quiet Zone Calculator may be used to...

  11. 75 FR 26839 - Metrics and Standards for Intercity Passenger Rail Service under Section 207 of the Passenger...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-12

    ... Standards for Intercity Passenger Rail Service,'' on the FRA's Web site. Simultaneously, the FRA published a notice in the Federal Register (74 FR 10983) requesting comments on the Proposed Metrics and Standards from the Surface Transportation Board, rail carriers over whose rail lines Amtrak trains...

  12. 77 FR 24415 - Inflation Adjustment of the Aggravated Maximum Civil Monetary Penalty for a Violation of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-24

    ... $650, the ordinary maximum of $25,000, and the aggravated maximum CMP of $100,000). See 73 FR 79698...-adjusted $550. 69 FR 30591 (May 28, 2004) and 69 FR 62817 (Oct. 28, 2004). (In 2004, FRA had determined, by... should be increased to $650. 73 FR 79698 (Dec. 30, 2008). In 2009, FRA also published a...

  13. 49 CFR 241.7 - Waivers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Canada or Mexico pursuant to regulations contained in 49 CFR part 241, revised as of October 1, 2002, may... CFR part 241, revised as of October 1, 2002. FRA will notify the railroad if FRA determines that the... regulations contained in 49 CFR part 241, revised as of October 1, 2002, the route miles shall be the...

  14. 49 CFR 241.7 - Waivers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Canada or Mexico pursuant to regulations contained in 49 CFR part 241, revised as of October 1, 2002, may... CFR part 241, revised as of October 1, 2002. FRA will notify the railroad if FRA determines that the... regulations contained in 49 CFR part 241, revised as of October 1, 2002, the route miles shall be the...

  15. 49 CFR 241.7 - Waivers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Canada or Mexico pursuant to regulations contained in 49 CFR part 241, revised as of October 1, 2002, may... CFR part 241, revised as of October 1, 2002. FRA will notify the railroad if FRA determines that the... regulations contained in 49 CFR part 241, revised as of October 1, 2002, the route miles shall be the...

  16. 49 CFR 241.7 - Waivers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Canada or Mexico pursuant to regulations contained in 49 CFR part 241, revised as of October 1, 2002, may... CFR part 241, revised as of October 1, 2002. FRA will notify the railroad if FRA determines that the... regulations contained in 49 CFR part 241, revised as of October 1, 2002, the route miles shall be the...

  17. 49 CFR 241.7 - Waivers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Canada or Mexico pursuant to regulations contained in 49 CFR part 241, revised as of October 1, 2002, may... CFR part 241, revised as of October 1, 2002. FRA will notify the railroad if FRA determines that the... regulations contained in 49 CFR part 241, revised as of October 1, 2002, the route miles shall be the...

  18. 77 FR 65935 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-31

    ... safety regulations contained in 49 CFR part 230--Steam Locomotive Inspection and Maintenance Standards. FRA assigned the petition Docket Number FRA- 2012-0076. Steam Locomotive Number 2719 is a former Soo...&TPF restored Steam Locomotive Number 2719 and completed the current 1,472-service-day inspection...

  19. 49 CFR Appendix C to Part 219 - Post-Accident Testing Specimen Collection

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...-Accident Testing Blood/Urine Custody and Control Form (49 CFR part 219) (Form FRA F 6180.74 (revised.... Collection of blood and urine specimens is required to be conducted at an independent medical facility... and transfer of blood and urine specimens for three surviving employees can be found in the FRA...

  20. 49 CFR Appendix C to Part 219 - Post-Accident Testing Specimen Collection

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...-Accident Testing Blood/Urine Custody and Control Form (49 CFR part 219) (Form FRA F 6180.74 (revised.... Collection of blood and urine specimens is required to be conducted at an independent medical facility... and transfer of blood and urine specimens for three surviving employees can be found in the FRA...

  1. 49 CFR Appendix C to Part 219 - Post-Accident Testing Specimen Collection

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...-Accident Testing Blood/Urine Custody and Control Form (49 CFR part 219) (Form FRA F 6180.74 (revised.... Collection of blood and urine specimens is required to be conducted at an independent medical facility... and transfer of blood and urine specimens for three surviving employees can be found in the FRA...

  2. 49 CFR Appendix C to Part 219 - Post-Accident Testing Specimen Collection

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...-Accident Testing Blood/Urine Custody and Control Form (49 CFR part 219) (Form FRA F 6180.74 (revised.... Collection of blood and urine specimens is required to be conducted at an independent medical facility... and transfer of blood and urine specimens for three surviving employees can be found in the FRA...

  3. 49 CFR Appendix C to Part 219 - Post-Accident Testing Specimen Collection

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...-Accident Testing Blood/Urine Custody and Control Form (49 CFR part 219) (Form FRA F 6180.74 (revised.... Collection of blood and urine specimens is required to be conducted at an independent medical facility... and transfer of blood and urine specimens for three surviving employees can be found in the FRA...

  4. The Fragile Fiber1 Kinesin Contributes to Cortical Microtubule-Mediated Trafficking of Cell Wall Components1[OPEN

    PubMed Central

    Zhu, Chuanmei; Ganguly, Anindya; Baskin, Tobias I.; McClosky, Daniel D.; Anderson, Charles T.; Foster, Cliff; Meunier, Kristoffer A.; Okamoto, Ruth; Berg, Howard

    2015-01-01

    The cell wall consists of cellulose microfibrils embedded within a matrix of hemicellulose and pectin. Cellulose microfibrils are synthesized at the plasma membrane, whereas matrix polysaccharides are synthesized in the Golgi apparatus and secreted. The trafficking of vesicles containing cell wall components is thought to depend on actin-myosin. Here, we implicate microtubules in this process through studies of the kinesin-4 family member, Fragile Fiber1 (FRA1). In an fra1-5 knockout mutant, the expansion rate of the inflorescence stem is halved compared with the wild type along with the thickness of both primary and secondary cell walls. Nevertheless, cell walls in fra1-5 have an essentially unaltered composition and ultrastructure. A functional triple green fluorescent protein-tagged FRA1 fusion protein moves processively along cortical microtubules, and its abundance and motile density correlate with growth rate. Motility of FRA1 and cellulose synthase complexes is independent, indicating that FRA1 is not directly involved in cellulose biosynthesis; however, the secretion rate of fucose-alkyne-labeled pectin is greatly decreased in fra1-5, and the mutant has Golgi bodies with fewer cisternae and enlarged vesicles. Based on our results, we propose that FRA1 contributes to cell wall production by transporting Golgi-derived vesicles along cortical microtubules for secretion. PMID:25646318

  5. 76 FR 78731 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-19

    ... February 10, 2011, Drake Switching Company, LLC (DSC) has petitioned the Federal Railroad Administration... contained at 49 CFR part 223. FRA assigned the petition Docket Number FRA-2011-0015. DSC seeks a waiver of... (Car Number SWX735), which is used as a locomotive. DSC states that this shuttlewagon is equipped...

  6. 76 FR 55819 - Track Safety Standards; Concrete Crossties

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ... concrete crossties. See 76 FR 18,073. FRA received two petitions for reconsideration in response to the... 403(d), of the Rail Safety Improvement Act of 2008 (Pub. L. 110-432, Division A) (RSIA). See 75 FR 52..., FRA delayed the effective date of the final rule until October 1, 2011. See 76 FR 34,890 (June...

  7. 77 FR 75697 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-21

    ... cracked window--there has been no accident or injury attributed to window glazing of these cars came under... Cars and Cabooses). FRA assigned the petition Docket Number FRA-2012-0077. ORHS has petitioned for a permanent waiver of compliance for three passenger cars, numbered RPCX 101 (named ``William B Baer''),...

  8. 76 FR 71433 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ...In accordance with the Paperwork Reduction Act of 1995 and its implementing regulations, the Federal Railroad Administration (FRA) hereby announces that it is seeking reinstatement of previously approved information collection activities. Before submitting these information collection requirements for clearance by the Office of Management and Budget (OMB), FRA is soliciting public comment on......

  9. 49 CFR 216.11 - Special notice for repairs-railroad freight car.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Special notice for repairs-railroad freight car...—railroad freight car. (a) When an FRA Motive Power and Equipment Inspector or a State Equipment Inspector determines that a railroad freight car is not in conformity with the requirements of the FRA Freight...

  10. 75 FR 75911 - Adjustment of Monetary Threshold for Reporting Rail Equipment Accidents/Incidents for Calendar...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-07

    ... reporting threshold was revised. 74 FR 65458 (December 10, 2009). Consequently, FRA has recalculated the... final rule published December 20, 2005, 70 FR 75414. FRA has found that both the current cost data... both Executive Order 12866 and DOT policies and procedures (44 FR 11034 (Feb. 26, 1979))....

  11. 49 CFR Appendix D to Part 236 - Independent Review of Verification and Validation

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... D Appendix D to Part 236 Transportation Other Regulations Relating to Transportation (Continued..., AND APPLIANCES Pt. 236, App. D Appendix D to Part 236—Independent Review of Verification and..., in FRA's judgment, for FRA to monitor the assessment. (d) The reviewer shall evaluate the...

  12. 49 CFR Appendix D to Part 236 - Independent Review of Verification and Validation

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... D Appendix D to Part 236 Transportation Other Regulations Relating to Transportation (Continued..., AND APPLIANCES Pt. 236, App. D Appendix D to Part 236—Independent Review of Verification and..., in FRA's judgment, for FRA to monitor the assessment. (d) The reviewer shall evaluate the...

  13. 75 FR 74131 - Notice of Finding of No Significant Impact for the Washington State Portion of the Pacific...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... passenger rail service by reducing travel times, achieving greater schedule reliability, and creating... schedule reliability, and reduced travel times. The FRA intends to provide funding under the HSIPR Program... Procedures for Considering Environmental Impacts (FRA Environmental Procedures) (64 FR 28545 (May 26,...

  14. 49 CFR 230.60 - Time of washing.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Boilers and Appurtenances Washing Boilers § 230.60 Time of washing. (a) Frequency of washing. All boilers shall thoroughly be washed... inspection. The date of the boiler wash shall be noted on the FRA Form No. 1 or FRA Form No. 3. (See...

  15. 49 CFR 230.60 - Time of washing.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Boilers and Appurtenances Washing Boilers § 230.60 Time of washing. (a) Frequency of washing. All boilers shall thoroughly be washed... inspection. The date of the boiler wash shall be noted on the FRA Form No. 1 or FRA Form No. 3. (See...

  16. 49 CFR 230.60 - Time of washing.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Boilers and Appurtenances Washing Boilers § 230.60 Time of washing. (a) Frequency of washing. All boilers shall thoroughly be washed... inspection. The date of the boiler wash shall be noted on the FRA Form No. 1 or FRA Form No. 3. (See...

  17. 49 CFR 230.60 - Time of washing.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Boilers and Appurtenances Washing Boilers § 230.60 Time of washing. (a) Frequency of washing. All boilers shall thoroughly be washed... inspection. The date of the boiler wash shall be noted on the FRA Form No. 1 or FRA Form No. 3. (See...

  18. 49 CFR 230.60 - Time of washing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Boilers and Appurtenances Washing Boilers § 230.60 Time of washing. (a) Frequency of washing. All boilers shall thoroughly be washed... inspection. The date of the boiler wash shall be noted on the FRA Form No. 1 or FRA Form No. 3. (See...

  19. 76 FR 55335 - Alternate Passenger Rail Service Pilot Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    ... procedures. See 44 FR 11034; February 26, 1979. FRA ] has prepared and placed in the docket a regulatory...,000 or less. See 68 FR 24891 (May 9, 2003) (codified at Appendix C to 49 CFR part 209). The $20... Impacts'' (FRA's Procedures) (64 FR 28545, May 26, 1999) as required by the National Environmental...

  20. 76 FR 77716 - Alternate Passenger Rail Service Pilot Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-14

    ... proposed rulemaking (NPRM) published on September 7, 2011 (76 FR 55335), FRA proposed an alternate... 44 FR 11034; February 26, 1979. FRA has prepared and placed in the docket a regulatory impact... jurisdictions that serve populations of 50,000 or less. See 68 FR 24891 (May 9, 2003) (codified at Appendix C...

  1. 49 CFR 1106.4 - The Safety Integration Plan process.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... at 49 CFR part 244, or other FRA guidelines or requirements regarding the contents of a SIP, with SEA... ongoing environmental review process under 49 CFR part 1105. The procedures governing the process shall be as follows: (1) In accordance with 49 CFR 244.17, FRA will provide its findings and conclusions...

  2. 75 FR 3784 - Safety Advisory 2009-03

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-22

    ... Federal Railroad Administration Safety Advisory 2009-03 AGENCY: Federal Railroad Administration (FRA...-Rail Grade Crossings with Vertical Profile Conditions. SUMMARY: FRA is issuing Safety Advisory 2009-03... Highway and Transportation Officials' Policy on Geometric Design of Highways and Streets (``AASHTO...

  3. Common fragile sites are conserved features of human and mouse chromosomes and relate to large active genes

    PubMed Central

    Helmrich, Anne; Stout-Weider, Karen; Hermann, Klaus; Schrock, Evelin; Heiden, Thomas

    2006-01-01

    Common fragile sites (CFSs) are seen as chromosomal gaps and breaks brought about by inhibition of replication, and it is thought that they cluster with tumor breakpoints. This study presents a comprehensive analysis using conventional and molecular cytogenetic mapping of CFSs and their expression frequencies in two mouse strains, BALB/c and C57BL/6, and in human probands. Here we show that induced mouse CFSs relate to sites of spontaneous gaps and breaks and that CFS expression levels in chromosome bands are conserved between the two mouse strains and between syntenic mouse and human DNA segments. Furthermore, four additional mouse CFSs were found to be homologous to human CFSs on the molecular cytogenetic level (Fra2D-FRA2G, Fra4C2-FRA9E, Fra6A3.1-FRA7G, and Fra6B1-FRA7H), increasing the number of such CFSs already described in the literature to eight. Contrary to previous reports, DNA helix flexibility is not increased in the 15 human and eight mouse CFSs molecularly defined so far, compared to large nonfragile control regions. Our findings suggest that the mechanisms that provoke instability at CFSs are evolutionarily conserved. The role that large transcriptionally active genes may play in CFS expression is discussed. PMID:16954539

  4. Gene, brain, and behavior relationships in fragile X syndrome: evidence from neuroimaging studies.

    PubMed

    Lightbody, Amy A; Reiss, Allan L

    2009-01-01

    Fragile X syndrome (FraX) remains the most common inherited cause of intellectual disability and provides a valuable model for studying gene-brain-behavior relationships. Over the past 15 years, structural and functional magnetic resonance imaging studies have emerged with the goal of better understanding the neural pathways contributing to the cognitive and behavioral outcomes seen in individuals with FraX. Specifically, structural MRI studies have established and begun to refine the specific topography of neuroanatomical variation associated with FraX. In addition, functional neuroimaging studies have begun to elucidate the neural underpinnings of many of the unique characteristics of FraX including difficulties with eye gaze, executive functioning, and behavioral inhibition. This review highlights studies with a focus on the relevant gene-brain-behavior connections observed in FraX. The relationship of brain regions and activation patterns to FMRP are discussed as well as the clinical cognitive and behavioral correlates of these neuroimaging findings.

  5. On the History and Origin of LKFM

    NASA Astrophysics Data System (ADS)

    Korotev, Randy L.

    1998-01-01

    Fra Mauro is the name of a geologic formation surrounding the Imbrium Basin of the Moon as well as the name of the region of the Apollo 14 lunar landing site. The formation was named for a 16th century Italian geographer and cartographer. In its original invocation in 1971 by the Apollo Soil Survey (ASS), Fra Mauro basalt was not a crystalline basalt, but the designation of a "compositional group" of impact glasses found in the Apollo 14 soil that were basaltic in composition. The ASS noted the similarity between the Fra Mauro basalt glass composition and sample 14310, an unbrecciated, crystalline Apollo 14 rock that would now be designated an impact melt rock. In 1972 the term Fra Mauro basalt was first applied to a rock, sample 14310, although in related papers, Fra Mauro basaltic glass was equated with KREEP. In 1973 the ASS noted that a wide range of K concentrations occurred among glasses of Fra Mauro basaltic composition in the Apollo 15 regolith. The terms high-K, moderate-K and low-K Fra Mauro first occurred in that context, but always as an adjective. Lock Fra Mauro glasses were those with 0.12 +/- 0.07% K2O, compared with 0.47 +/- 0.17% and 1.1 +/- 0.4% for moderate and high-K Fra Mauro glasses and 0.6% for Apollo 15 KREEP basalt. An important evolutionary step in the concept of low Fra Mauro basalt occurred in 1973 when the composition was first used as a component in a mass-balance (mixing) model for Apollo 16 soils [8,9] and later average highlands crust, despite that the term had not yet been applied to an actual rock sample. The first use of the acronym LKFM occurred in a 1973 paper describing glass compositions in Apollo 16 soil.

  6. Fos family members: regulation, structure and role in oncogenic transformation.

    PubMed

    Tulchinsky, E

    2000-07-01

    The members of the Fos protein family might be subdivided in two groups, according to their ability to transform rodent fibroblasts, transforming (c-Fos and FosB) and non-transforming (Fra-1 and Fra-2) proteins. Members of these groups are differently activated in response to external stimuli and possess different structural features. Importantly, whilst c-Fos and FosB contain multiple transactivation modules in their N- and C-terminal parts, transactivation domains are absent in the non-transforming Fos proteins. As a result, Fra-1 and Fra-2 though efficiently form dimers with the Jun proteins, are weak transcriptional activators and inhibit the c-Fos-dependent activation in transient transfection assay. The numerous experiments performed with the different Fos mutant proteins with impaired transforming ability, as well as with chimeric proteins revealed the importance of the transactivation function for transformation. Fra-1 and Fra-2 proteins albeit ineffectively triggering oncogenic transformation, are abundant in ras- and src-transformed murine and chicken fibroblasts, in neoplastic thyroid cells and in highly malignant mouse adenocarcinoma cells, which underwent mesenchymal transition. The abundance of the non-transforming Fos proteins in these systems might be mediated by a positive AP-l-dependent feedback mechanism, as well as by wnt signals. Furthermore, the manipulation of the Fra-1 expression level in thyroid and mammary tumor cells modulated the transcription of several tumor progression markers and affected cell morphology and invasiveness. These recent data demonstrate a novel function of non-transforming Fos proteins in the maintenance and progression of the transformed state. Interestingly, this function is independent of the documented invalidity of the Fra-1 and Fra-2 proteins as transcriptional activators in rodent fibroblasts.

  7. 12 CFR 308.3 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Insurance Corporation acting pursuant to authority delegated by the Board of Directors as provided in 12 CFR...) of the HOLA (12 U.S.C. 1467(a)); (4) Any organization operating under section 25 of the FRA (12...

  8. 12 CFR 308.3 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Insurance Corporation acting pursuant to authority delegated by the Board of Directors as provided in 12 CFR...) of the HOLA (12 U.S.C. 1467(a)); (4) Any organization operating under section 25 of the FRA (12...

  9. 12 CFR 308.3 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Insurance Corporation acting pursuant to authority delegated by the Board of Directors as provided in 12 CFR...) of the HOLA (12 U.S.C. 1467(a)); (4) Any organization operating under section 25 of the FRA (12...

  10. 49 CFR 228.205 - Access to electronic records.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...; SLEEPING QUARTERS Electronic Recordkeeping § 228.205 Access to electronic records. (a) FRA inspectors and State inspectors participating under 49 CFR Part 212 must have access to hours of service...

  11. 49 CFR 228.19 - Monthly reports of excess service.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... electronic record; and (iii) Allows FRA inspectors and State inspectors participating under 49 CFR part 212...; SLEEPING QUARTERS Records and Reporting § 228.19 Monthly reports of excess service. (a) In general....

  12. 49 CFR 228.19 - Monthly reports of excess service.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... electronic record; and (iii) Allows FRA inspectors and State inspectors participating under 49 CFR part 212...; SLEEPING QUARTERS Records and Reporting § 228.19 Monthly reports of excess service. (a) In general....

  13. 49 CFR 228.19 - Monthly reports of excess service.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... electronic record; and (iii) Allows FRA inspectors and State inspectors participating under 49 CFR part 212...; SLEEPING QUARTERS Records and Reporting § 228.19 Monthly reports of excess service. (a) In general....

  14. 49 CFR 228.205 - Access to electronic records.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...; SLEEPING QUARTERS Electronic Recordkeeping § 228.205 Access to electronic records. (a) FRA inspectors and State inspectors participating under 49 CFR Part 212 must have access to hours of service...

  15. 49 CFR 228.205 - Access to electronic records.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...; SLEEPING QUARTERS Electronic Recordkeeping § 228.205 Access to electronic records. (a) FRA inspectors and State inspectors participating under 49 CFR Part 212 must have access to hours of service...

  16. 77 FR 74737 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-17

    ... October 26, 2012, the Port Manatee Railroad (PMRR) has petitioned the Federal Railroad Administration (FRA... performed within the confines of Port Manatee, which consists of slow speed yard tracks. Additionally,...

  17. 49 CFR 239.7 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... rail modes of transportation means other railroads, trolleys, light rail, heavy transit, and other vehicles operating on rails or electromagnetic guideways which are expressly identified in a railroad's... emergency situation. FRA means the Federal Railroad Administration. Joint operations means rail...

  18. Fuzzy Risk Analyzer

    1994-03-04

    FRA is a general purpose code for risk analysis using fuzzy, not numeric, attributes. It allows the user to evaluate the risk associated with a composite system on the basis of the risk estimates of the individual components.

  19. Network II Database

    1994-11-07

    The Oak Ridge National Laboratory (ORNL) Rail and Barge Network II Database is a representation of the rail and barge system of the United States. The network is derived from the Federal Rail Administration (FRA) rail database.

  20. Application of Taguchi's method to optimize fiber Raman amplifier

    NASA Astrophysics Data System (ADS)

    Zaman, Mohammad Asif

    2016-04-01

    Taguchi's method is introduced to perform multiobjective optimization of fiber Raman amplifier (FRA). The optimization requirements are to maximize gain and keep gain ripple minimum over the operating bandwidth of a wavelength division multiplexed (WDM) communication link. Mathematical formulations of FRA and corresponding numerical solution techniques are discussed. A general description of Taguchi's method and how it can be integrated with the FRA optimization problem are presented. The proposed method is used to optimize two different configurations of FRA. The performance of Taguchi's method is compared with genetic algorithm and particle swarm optimization in terms of output performance and convergence rate. Taguchi's method is found to produce good results with fast convergence rate, which makes it well suited for the nonlinear optimization problems.

  1. 49 CFR 260.35 - Environmental assessment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Transportation Act (49 U.S.C. 303(c)), the National Historic Preservation Act (16 U.S.C. 470(f)), the Coastal... Council on Environmental Quality (“CEQ Regulation”) (40 CFR Part 1500) will govern the FRA's...

  2. 49 CFR 260.35 - Environmental assessment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Transportation Act (49 U.S.C. 303(c)), the National Historic Preservation Act (16 U.S.C. 470(f)), the Coastal... Council on Environmental Quality (“CEQ Regulation”) (40 CFR Part 1500) will govern the FRA's...

  3. 49 CFR 219.205 - Specimen collection and handling.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Post-Accident Toxicological Testing..., marked, preserved, handled, and made available to FRA consistent with the requirements of this...

  4. 49 CFR 219.205 - Specimen collection and handling.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Post-Accident Toxicological Testing..., marked, preserved, handled, and made available to FRA consistent with the requirements of this...

  5. 77 FR 15450 - Tier 1 Environmental Impact Statement for the Chicago, Illinois, to Omaha, Nebraska, Regional...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-15

    ... FRA's Procedures for Considering Environmental Impacts (64 FR 28454) (Environmental Procedures), in... improve passenger ride quality and comfort Promoting environmental benefits: reduced air pollutant emissions, improved land use options, and fewer adverse impacts to surrounding habitat and water...

  6. 77 FR 19413 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-30

    ... than 8 hours, as clarified in 71 FR 47626, to a period of no more than 6 months. ] UP also requests FRA... horn blasts and the resulting impact on the surrounding community and personnel is reduced),...

  7. Susceptibility of ornamental pepper banker plant candidates to common greenhouse pests

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Susceptibility of four potential ornamental pepper banker plant candidates [Black Pearl (BP), Explosive Ember (EE), Masquerade (MA), Red Missile (RM), and a commercial pepper cultivar Blitz (BL)] were evaluated against three common greenhouse pests - Bemisia tabaci, Polyphagotarsonemus latus and Fra...

  8. 75 FR 20420 - Privacy Act of 1974: System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-19

    ... close call events to prevent serious accidents in the rail industry. A close call or near miss is an... damage to equipment above FRA's reportable threshold level. Employees can report about a near miss...

  9. 78 FR 28012 - Tier One Environmental Impact Statement for the Rochester, Minnesota to Twin Cities, Minnesota...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-13

    ... FRA's Procedures for Considering Environmental Impacts (64 FR 28546) (Environmental Procedures), in... potentially affected by the proposed action. Developing evaluation criteria to identify route alternatives... reasonable route alternatives that satisfy the purpose and need for the proposed action. Developing the...

  10. 76 FR 414 - Tier 1 Environmental Impact Statement for the Los Angeles to San Luis Obispo (LOSSAN North) Rail...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-04

    ...), Division 13, Public Resources Code; and FRA's Procedures for Considering Environmental Impacts (64 FR 28545... Lowry Davis Center, Lu Gilbert Room, 1232 De La Vina St., Santa Barbara, CA, 93101. San Luis...

  11. Acute Toxicological Responses of Fischer Rats to Naturally Occurring Asbestos from theUnited States and Canada

    EPA Science Inventory

    This study was designed to provide understanding of the toxicity of naturally occurring asbestos (NOA) including Libby amphibole (LA), Sumas Mountain chrysotile (SM), EI Dorado Hills tremolite (ED) and Ontario actinolite/ferroactinolite cleavage fragments (ON). Ratrespirable fra...

  12. 75 FR 76778 - Environmental Impact Statement for the Milwaukee, WI (Milwaukee Intermodal Station) to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-09

    ... Federal Railroad Administration Environmental Impact Statement for the Milwaukee, WI (Milwaukee Intermodal... Railroad Administration, Department of Transportation. ACTION: Notice of intent to prepare an Environmental... Vaughn, Office of Railroad Policy and Development, Federal Railroad Administration (FRA), 1200 New...

  13. Hourly Illumination of Shackleton Crater

    NASA Video Gallery

    Illumination of Shackleton crater, a 21-km-diameter (12.5 mile-diameter) structure situated adjacent to the Moon’s south pole. The resolution is 30 meters (approximately 100 feet) per pixel. Fra...

  14. 49 CFR 211.45 - Petitions for emergency waiver of safety rules.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... hearing pursuant to the provisions contained in 49 CFR part 211; or (3) Determine that a public hearing is... document submitted to the docket in 2009 will be identified as FRA-2009-XXX-1.) Thus, each...

  15. 49 CFR 211.45 - Petitions for emergency waiver of safety rules.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... hearing pursuant to the provisions contained in 49 CFR part 211; or (3) Determine that a public hearing is... document submitted to the docket in 2009 will be identified as FRA-2009-XXX-1.) Thus, each...

  16. The Fos family of transcription factors and their role in tumourigenesis.

    PubMed

    Milde-Langosch, Karin

    2005-11-01

    Members of the Fos family (c-Fos, FosB and its smaller splice variants, Fra-1 and Fra-2) dimerise with Jun proteins to form the AP-1 transcription factor complex. Based on the rapidly growing amount of data from experimental studies, animal models and investigations on clinical tumour samples, this review summarises the current knowledge about the role of these proteins in carcinogenesis. In addition to c-Fos, which has oncogenic activity and is frequently overexpressed in tumour cells, Fra-1 seems to play a role in the progression of many carcinomas. The results obtained from various studies show different implications for these transcription factors according to tumour type, i.e., Fra-1 overexpression enhances the motility and invasion of breast and colorectal cancer cells, but inhibits the tumourigenicity of cervical carcinoma cell lines. Knowledge about regulation of invasion and metastasis in different malignant tumours in vivo might open promising perspectives to targeted therapeutic approaches.

  17. 49 CFR 238.223 - Locomotive fuel tanks.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... an industry standard providing at least an equivalent level of safety if approved by FRA under § 238..., at a minimum, be equivalent to a 5/16-inch thick steel plate with a yield strength of 25,000...

  18. 75 FR 22674 - Moynihan Station Development Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-29

    ... Quality NEPA implementing regulations, 40 CFR parts 1500-1508, and the FRA NEPA procedures, 64 FR 28545... transportation facility, to be called the Daniel Patrick Moynihan Station (Moynihan Station). Moynihan...

  19. Lunar laser ranging data deposited in the National Space Science Data Center: Filtered observations for January - June 1971 and unfiltered photon detections for July - December 1971

    NASA Technical Reports Server (NTRS)

    Mulholland, J. D.; Shelus, P. J.

    1973-01-01

    The filtered data are discussed which were obtained during laser ranging operations with Apollo reflectors placed on the moon at Tranquility Base, Fra Mauro, and Hadley. Unfiltered photon detections are described.

  20. 78 FR 62002 - Railroad Safety Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-10

    ... 11, 1996 (61 FR 9740), for additional information about the RSAC. Issued in Washington, DC, on... Federal Railroad Administration Railroad Safety Advisory Committee; Notice of Meeting AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Announcement of Railroad...

  1. 78 FR 49321 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-13

    ... response to section ] 307(b) of the Rail Safety Improvement Act of 2008, signed into law by President George W. Bush on October 16, 2008, which requires Federal Railroad Administration (FRA) to ``provide...

  2. 78 FR 42998 - Hazardous Materials: Improving the Safety of Railroad Transportation of Hazardous Materials

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-18

    ... TRANSPORTATION Federal Railroad Administration Hazardous Materials: Improving the Safety of Railroad Transportation of Hazardous Materials AGENCY: Pipeline and Hazardous Materials, Safety Administration (PHMSA... participate in a public meeting addressing the transportation of hazardous materials by rail. FRA and......

  3. 77 FR 40144 - Adoption of the Environmental Impact Statement (EIS) and Participation in the Section 106...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-06

    ..., 64 FR 28545, May 26, 1999. First, FRA's review concluded that the action encompassed by the MTA RRIF... action. Issued in Washington, DC, on July 2, 2012. Paul Nissenbaum, Associate Administrator, Office...

  4. 75 FR 67451 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-02

    ... relief. Austin & Texas Central Railroad (Waiver Petition Docket Number FRA-2010-0149) The Austin & Texas...) 54.5 at Milby in Austin, Texas, and MP 115.0 at Burnet, Texas. Since before 1992, there have been...

  5. 76 FR 24561 - Railroad Safety Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-02

    ... advisory committee that develops railroad safety regulations through a consensus process. The RSAC meeting... Federal Railroad Administration Railroad Safety Advisory Committee; Notice of Meeting AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Announcement of Railroad...

  6. 77 FR 77183 - Railroad Safety Advisory Committee; Notice of Meeting Postponement

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-31

    ... consensus process (77 FR 73734). This meeting has been postponed until further notice and will be... Federal Railroad Administration Railroad Safety Advisory Committee; Notice of Meeting Postponement AGENCY... Safety Advisory Committee (RSAC) Meeting Postponement. SUMMARY: FRA recently announced the...

  7. 77 FR 73734 - Railroad Safety Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-11

    ... Advisory Committee that develops railroad safety regulations through a consensus process. The RSAC meeting... Federal Railroad Administration Railroad Safety Advisory Committee; Notice of Meeting AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Announcement of Railroad...

  8. 77 FR 52393 - Railroad Safety Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-29

    ... Advisory Committee that develops railroad safety regulations through a consensus process. The RSAC meeting... Federal Railroad Administration Railroad Safety Advisory Committee; Notice of Meeting AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Announcement of Railroad...

  9. 75 FR 3959 - Railroad Safety Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-25

    ... TRANSPORTATION Federal Railroad Administration Railroad Safety Advisory Committee; Notice of Meeting AGENCY... Railroad Safety Advisory Committee (RSAC) Meeting. SUMMARY: FRA announces the forty-first meeting of the RSAC, a Federal advisory committee that develops railroad safety regulations through a...

  10. 75 FR 44046 - Railroad Safety Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-27

    ... advisory committee that develops railroad safety regulations through a consensus process. The RSAC meeting... Federal Railroad Administration Railroad Safety Advisory Committee; Notice of Meeting AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Announcement of Railroad...

  11. 77 FR 28421 - Railroad Safety Advisory Committee; Charter Renewal

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-14

    ... Federal Railroad Administration Railroad Safety Advisory Committee; Charter Renewal AGENCY: Federal... of the Railroad Safety Advisory Committee (RSAC). SUMMARY: FRA announces the charter renewal of the RSAC, a Federal Advisory Committee that develops railroad safety regulations through a...

  12. 78 FR 26423 - Railroad Safety Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-06

    ... Advisory Committee that develops railroad safety regulations through a consensus process. The RSAC meeting... Federal Railroad Administration Railroad Safety Advisory Committee; Notice of Meeting AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Announcement of Railroad...

  13. 75 FR 27053 - Railroad Safety Advisory Committee; Charter Renewal

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-13

    ... Federal Railroad Administration Railroad Safety Advisory Committee; Charter Renewal AGENCY: Federal... of the Railroad Safety Advisory Committee (RSAC). SUMMARY: FRA announces the charter renewal of the RSAC, a Federal Advisory Committee that develops railroad safety regulations through a...

  14. 76 FR 50323 - Notice of Availability of a Draft Environmental Impact Report/Environmental Impact Statement for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-12

    ..., Environment and Systems Planning Division, Office of Railroad Policy and Development, Federal Railroad... Federal Railroad Administration Notice of Availability of a Draft Environmental Impact Report...: Federal Railroad Administration (FRA), United States Department of Transportation (DOT). ACTION:...

  15. 76 FR 55729 - Notice of the Extension of the Comment Period for the Draft Environmental Impact Report...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-08

    ..., Environment and Systems Planning Division, Office of Railroad Policy and Development, Federal Railroad... Federal Railroad Administration Notice of the Extension of the Comment Period for the Draft Environmental... Section AGENCY: Federal Railroad Administration (FRA), United States Department of Transportation...

  16. 77 FR 61472 - Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-09

    ... CONTACT: Ms. Janet Wylie, Office of Planning and Administration, RPD-3, Federal Railroad Administration... Federal Railroad Administration Agency Information Collection Activities; Comment Request AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Notice and request for...

  17. 76 FR 50324 - Notice of Availability of a Draft Environmental Impact Report/Environmental Impact Statement for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-12

    ... Valenstein, Chief, Environment and Systems Planning Division, Office of Railroad Policy and Development... Federal Railroad Administration Notice of Availability of a Draft Environmental Impact Report...: Federal Railroad Administration (FRA), United States Department of Transportation (DOT). ACTION:...

  18. 76 FR 53998 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-30

    ... automatic signals at Big Manatee Drawbridge in Bradenton, Florida, at Milepost AZA 915.8, in the... proceedings by submitting written views, data, or comments. FRA does not anticipate scheduling a...

  19. 77 FR 43646 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-25

    ... February 28, 2012, Canadian Pacific Railway (CP) has petitioned the Federal Railroad Administration (FRA... in order to shield the reporting employee(s) and the railroad from punitive sanctions that...

  20. 75 FR 26838 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-12

    ... Act Statement in the Federal Register published on April 11, 2000 (65 FR 19477) or at http://www.dot... below. Docket Number FRA-2010-0023 Applicant: Union Pacific Railroad Company, Mr. William E. Van...

  1. 75 FR 31834 - Adoption of Environmental Impact Statement; Availability of an Environmental Reevaluation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-04

    ... Impacts (64 FR 28545, May 26, 1999) require the reevaluation of a Final EIS if major steps toward... Federal Railroad Administration Adoption of Environmental Impact Statement; Availability of an Environmental Reevaluation AGENCY: Federal Railroad Administration (FRA), Department of Transportation...

  2. 78 FR 77553 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-23

    ... role these sectors of transportation play in the overall national economy, FRA is requesting OMB to.... Respondent Universe: 49. Total Annual Responses: 6. Average Time per Response: 84. Total Annual Burden...

  3. 78 FR 76190 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-16

    ... pathways and the important role these sectors of transportation play in the overall national economy, FRA...-out Procedures. Respondent Universe: 49. Total Annual Responses: 6. Average time per response:...

  4. 75 FR 9018 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-26

    ... April 11, 2000 (65 FR 19477) or at http://www.dot.gov/privacy.html . Issued in Washington, DC, on... relief. Genesis Worldwide Logistics The Genesis Worldwide Logistics (GWWL) has petitioned FRA for...

  5. 49 CFR 244.1 - Scope, application, and purpose.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... approval by the Surface Transportation Board. See 49 CFR part 1106. ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS ON SAFETY INTEGRATION PLANS GOVERNING RAILROAD... part prescribes requirements for filing and implementing a Safety Integration Plan with FRA whenever...

  6. 49 CFR 244.1 - Scope, application, and purpose.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... approval by the Surface Transportation Board. See 49 CFR part 1106. ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS ON SAFETY INTEGRATION PLANS GOVERNING RAILROAD... part prescribes requirements for filing and implementing a Safety Integration Plan with FRA whenever...

  7. 49 CFR 244.1 - Scope, application, and purpose.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... approval by the Surface Transportation Board. See 49 CFR part 1106. ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS ON SAFETY INTEGRATION PLANS GOVERNING RAILROAD... part prescribes requirements for filing and implementing a Safety Integration Plan with FRA whenever...

  8. 49 CFR 244.1 - Scope, application, and purpose.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... approval by the Surface Transportation Board. See 49 CFR part 1106. ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS ON SAFETY INTEGRATION PLANS GOVERNING RAILROAD... part prescribes requirements for filing and implementing a Safety Integration Plan with FRA whenever...

  9. 49 CFR 244.1 - Scope, application, and purpose.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... approval by the Surface Transportation Board. See 49 CFR part 1106. ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS ON SAFETY INTEGRATION PLANS GOVERNING RAILROAD... part prescribes requirements for filing and implementing a Safety Integration Plan with FRA whenever...

  10. 12 CFR 308.3 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Insurance Corporation acting pursuant to authority delegated by the Board of Directors as provided in 12 CFR...) of the HOLA (12 U.S.C. 1467(a)); (4) Any organization operating under section 25 of the FRA (12...

  11. 12 CFR 308.3 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Insurance Corporation acting pursuant to authority delegated by the Board of Directors as provided in 12 CFR...) of the HOLA (12 U.S.C. 1467(a)); (4) Any organization operating under section 25 of the FRA (12...

  12. 78 FR 25347 - Petition for Amending Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-30

    ... published on April 11, 2000 (65 FR 19477). Issued in Washington, DC, on April 24, 2013. Robert C. Lauby... Number FRA-2012-0054. On January 15, 2013, FRA granted Amtrak a waiver of compliance from 49 CFR 242.403(b), (c)(1)-(3), (d), (e)(1)-(4), (e)(6)-(11), and (f)(1)-(2). The relief granted to Amtrak...

  13. Expression of Fos-related antigens in the nucleus accumbens and associated regions following exposure to a cocaine-paired environment.

    PubMed

    Franklin, T R; Druhan, J P

    2000-06-01

    This study examined whether conditioned hyperactivity measured in a cocaine-paired environment was associated with increased expression of Fos-related antigens (FRA) within the nucleus accumbens (NAc) and associated forebrain regions of rats. Three groups of rats were given repeated injections of either cocaine in the test environment and saline in the colony room (group Paired), saline in the test environment and cocaine in the colony room (group Unpaired), or saline in both environments (group Control). All rats were subsequently given a drug-free test for conditioned hyperactivity in the test environment, and their brains were removed so that FRA immunohistochemistry could be conducted. Rats in the Paired group showed conditioned hyperactivity during the conditioning test, and this behavioural response was associated with increased FRA expression within the caudal NAc, the medial prefrontal cortex and the lateral septum relative to the Unpaired and Control groups. Paired rats also showed increased FRA expression within the orbital prefrontal cortex, the claustrum, the caudal amygdala (basolateral and central regions), the paraventricular thalamic nucleus, the subiculum of the hippocampus, and the lateral habenula relative to the Control group. However, the FRA levels in these latter sites were not significantly increased relative to those of Unpaired rats, indicating that genomic responses in these regions were not entirely context dependent. The correspondence between conditioned hyperactivity and enhanced FRA expression within the caudal NAc, the medial prefrontal cortex and lateral septum suggests that these regions may participate in the expression of conditioned responses to cocaine-related stimuli.

  14. The marine triterpene glycoside frondoside A exhibits activity in vitro and in vivo in prostate cancer.

    PubMed

    Dyshlovoy, Sergey A; Menchinskaya, Ekaterina S; Venz, Simone; Rast, Stefanie; Amann, Kerstin; Hauschild, Jessica; Otte, Katharina; Kalinin, Vladimir I; Silchenko, Alexandra S; Avilov, Sergey A; Alsdorf, Winfried; Madanchi, Ramin; Bokemeyer, Carsten; Schumacher, Udo; Walther, Reinhard; Aminin, Dmitry L; Fedorov, Sergey N; Shubina, Larisa K; Stonik, Valentin A; Balabanov, Stefan; Honecker, Friedemann; von Amsberg, Gunhild

    2016-05-15

    Despite recent advances in the treatment of metastatic castration-resistant prostate cancer (CRPC), outcome of patients remains poor due to the development of drug resistance. Thus, new drugs are urgently needed. We investigated efficacy, toxicity and mechanism of action of marine triterpene glycoside frondoside A (FrA) using CRPC cell lines in vitro and in vivo. FrA revealed high efficacy in human prostate cancer cells, while non-malignant cells were less sensitive. Remarkably, proliferation and colony formation of cells resistant to enzalutamide and abiraterone (due to the androgen receptor splice variant AR-V7) were also significantly inhibited by FrA. The marine compound caused cell type specific cell cycle arrest and induction of caspase-dependent or -independent apoptosis. Up-regulation or induction of several pro-apoptotic proteins (Bax, Bad, PTEN), cleavage of PARP and caspase-3 and down-regulation of anti-apoptotic proteins (survivin and Bcl-2) were detected in treated cells. Global proteome analysis revealed regulation of proteins involved in formation of metastases, tumor cell invasion, and apoptosis, like keratin 81, CrkII, IL-1β and cathepsin B. Inhibition of pro-survival autophagy was observed following FrA exposure. In vivo, FrA inhibited tumor growth of PC-3 and DU145 cells with a notable reduction of lung metastasis, as well as circulating tumor cells in the peripheral blood. Increased lymphocyte counts of treated animals might indicate an immune modulating effect of FrA. In conclusion, our results suggest that FrA is a promising new drug for the treatment of mCRPC. Induction of apoptosis, inhibition of pro-survival autophagy, and immune modulatory effects are suspected modes of actions.

  15. Flamingo, a seven-pass transmembrane cadherin, cooperates with Netrin/Frazzled in Drosophila midline guidance.

    PubMed

    Organisti, Cristina; Hein, Irina; Grunwald Kadow, Ilona C; Suzuki, Takashi

    2015-01-01

    During central nervous system development, several guidance cues and receptors, as well as cell adhesion molecules, are required for guiding axons across the midline and along the anterior-posterior axis. In Drosophila, commissural axons sense the midline attractants Netrin A and B (Net) through Frazzled (Fra) receptors. Despite their importance, lack of Net or fra affects only some commissures, suggesting that additional molecules can fulfill this function. Recently, planar cell polarity (PCP) proteins have been implicated in midline axon guidance in both vertebrate and invertebrate systems. Here, we report that the atypical cadherin and PCP molecule Flamingo/Starry night (Fmi/Stan) acts jointly with Net/Fra signaling during midline development. Additional removal of fmi strongly increases the guidance defects in Net/fra mutants. Rescue and domain deletion experiments suggest that Fmi signaling facilitates commissural pathfinding potentially by mediating axonal fasciculation in a partly homophilic manner. Altogether, our results indicate that contact-mediated cell adhesion via Fmi acts in addition to the Net/Fra guidance system during axon pathfinding across the midline, underlining the importance of PCP molecules during vertebrates and invertebrates midline development.

  16. Effect of serotonin on the expression of antigens and DNA levels in Yersinia pestis cells with different plasmid content

    NASA Astrophysics Data System (ADS)

    Klueva, Svetlana N.; Korsukov, Vladimir N.; Schukovskaya, Tatyana N.; Kravtsov, Alexander L.

    2004-08-01

    Using flow cytometry (FCM) the influence of exogenous serotonin on culture growth, DNA content and fluorescence intensity of cells binding FITC-labelled plague polyclonal immunoglobulins was studied in Yersinia pestis EV (pFra+, pCad+, pPst+), Yersinia pestis KM218 (pFra-, pCad-, pPst-), Yersinia pestis KM 216 (pFra-, pCad-, pPst+). The results have been obtained by FCM showed serotonin accelerated Yersinia pestis EV (pFra+, pCad+, pPst+), Yersinia pestis KM218 (pFra-, pCad-, pPst-) culture growth during cultivation in Hottinger broth pH 7.2 at 28°C at concentration of 10-5 M. The presence of 10-5 M serotonin in nutrient broth could modulate DNA content in 37°C growing population of plague microbe independently of their plasmid content. Serotonin have been an impact on the distribution pattern of the cells according to their phenotypical characteristics, which was reflected in the levels of population heterogeneity in the intensity of specific immunofluorescence determined by FMC.

  17. Bidirectional Transformation of a Metamorphic Protein between the Water-Soluble and Transmembrane Native States.

    PubMed

    Tanaka, Koji; Caaveiro, Jose M M; Tsumoto, Kouhei

    2015-11-24

    The bidirectional transformation of a protein between its native water-soluble and integral transmembrane conformations is demonstrated for FraC, a hemolytic protein of the family of pore-forming toxins. In the presence of biological membranes, the water-soluble conformation of FraC undergoes a remarkable structural reorganization generating cytolytic transmembrane nanopores conducive to cell death. So far, the reverse transformation from the native transmembrane conformation to the native water-soluble conformation has not been reported. We describe the use of detergents with different physicochemical properties to achieve the spontaneous conversion of transmembrane pores of FraC back into the initial water-soluble state. Thermodynamic and kinetic stability data suggest that specific detergents cause an asymmetric change in the energy landscape of the protein, allowing the bidirectional transformation of a membrane protein.

  18. Fructose-asparagine is a primary nutrient during growth of Salmonella in the inflamed intestine.

    PubMed

    Ali, Mohamed M; Newsom, David L; González, Juan F; Sabag-Daigle, Anice; Stahl, Christopher; Steidley, Brandi; Dubena, Judith; Dyszel, Jessica L; Smith, Jenee N; Dieye, Yakhya; Arsenescu, Razvan; Boyaka, Prosper N; Krakowka, Steven; Romeo, Tony; Behrman, Edward J; White, Peter; Ahmer, Brian M M

    2014-06-01

    Salmonella enterica serovar Typhimurium (Salmonella) is one of the most significant food-borne pathogens affecting both humans and agriculture. We have determined that Salmonella encodes an uptake and utilization pathway specific for a novel nutrient, fructose-asparagine (F-Asn), which is essential for Salmonella fitness in the inflamed intestine (modeled using germ-free, streptomycin-treated, ex-germ-free with human microbiota, and IL10-/- mice). The locus encoding F-Asn utilization, fra, provides an advantage only if Salmonella can initiate inflammation and use tetrathionate as a terminal electron acceptor for anaerobic respiration (the fra phenotype is lost in Salmonella SPI1- SPI2- or ttrA mutants, respectively). The severe fitness defect of a Salmonella fra mutant suggests that F-Asn is the primary nutrient utilized by Salmonella in the inflamed intestine and that this system provides a valuable target for novel therapies.

  19. Safety recommendations and responses availability. [Tank car safety

    SciTech Connect

    Not Available

    1980-08-28

    Documents available from the US National Transportation Safety Board (NTSB) include a response by the US Federal Railroad Administration (FRA) to NTSB's report, ''The Accident Performance of Tank Car Safeguards''. FRA has agreed to extend the requirements for top-and-bottom shelf couplers to all tank cars used to transport hazardous materials, and those for head shields and thermal protection to new and rebuilt specification DOT 105 tank cars; to examine the protection afforded to ''nonpressure'' tank cars used to transport specialty products and Class A poisons; to study the ways in which to minimize the damage to the top fittings and bottom outlet valves following train accidents and incorporate these with new car construction; to collect data on tank car derailment behavior to identify breach mechanisms (FRA work in progress); and to conduct studies to evaluate the safe positions in freight trains for placarded hazardous materials rail cars.

  20. Fructose-Asparagine Is a Primary Nutrient during Growth of Salmonella in the Inflamed Intestine

    PubMed Central

    Ali, Mohamed M.; Newsom, David L.; González, Juan F.; Sabag-Daigle, Anice; Stahl, Christopher; Steidley, Brandi; Dubena, Judith; Dyszel, Jessica L.; Smith, Jenee N.; Dieye, Yakhya; Arsenescu, Razvan; Boyaka, Prosper N.; Krakowka, Steven; Romeo, Tony; Behrman, Edward J.; White, Peter; Ahmer, Brian M. M.

    2014-01-01

    Salmonella enterica serovar Typhimurium (Salmonella) is one of the most significant food-borne pathogens affecting both humans and agriculture. We have determined that Salmonella encodes an uptake and utilization pathway specific for a novel nutrient, fructose-asparagine (F-Asn), which is essential for Salmonella fitness in the inflamed intestine (modeled using germ-free, streptomycin-treated, ex-germ-free with human microbiota, and IL10−/− mice). The locus encoding F-Asn utilization, fra, provides an advantage only if Salmonella can initiate inflammation and use tetrathionate as a terminal electron acceptor for anaerobic respiration (the fra phenotype is lost in Salmonella SPI1− SPI2− or ttrA mutants, respectively). The severe fitness defect of a Salmonella fra mutant suggests that F-Asn is the primary nutrient utilized by Salmonella in the inflamed intestine and that this system provides a valuable target for novel therapies. PMID:24967579

  1. Variation at the fragile X locus does not influence susceptibility to bipolar disorder

    SciTech Connect

    Craddock, N.; Daniels, J.; McGuffin, P.

    1994-06-15

    Over the last 20 years several pedigrees have been reported which are suggestive of linkage between susceptibility to bipolar disorder and markers on chromosome Xq28. Other workers have failed to replicate these reports and the methodology of the positive reports has been criticized. Recently there have been several reports of an association between fragile X (FRA(X)) and affective disorder within families and in unrelated individuals compared with controls. Such reports could be consistent with the Xq28 marker reports because FRA(X) maps to Xq27.3. We report a study at the FRA(X) CGG repeat locus in 79 unrelated Caucasian bipolar probands without fragile X syndrome and 77 unrelated controls. We found no evidence that variation at this locus confers susceptibility to bipolar disorder. 28 refs., 1 fig.

  2. Falls risk assessment begins with hello: lessons learned from the use of one home health agency's fall risk tool.

    PubMed

    Flemming, Patricia J; Ramsay, Katherine

    2012-10-01

    Identifying older adults at risk for falls is a challenge all home healthcare agencies (HHAs) face. The process of assessing for falls risk begins with the initial home visit. One HHA affiliated with an academic medical center describes its experience in development and use of a Falls Risk Assessment (FRA) tool over a 10-year period. The FRA tool has been modified since initial development to clarify elements of the tool based on research and to reflect changes in the Outcome and Assessment Information Set (OASIS) document. The primary purpose of this article is to share a validated falls risk assessment tool to facilitate identification of fall-related risk factors in the homebound population. A secondary purpose is to share lessons learned by the HHA during the 10 years using the FRA.

  3. When the past is lost: focal retrograde amnesia. Focus on the "functional" form.

    PubMed

    Stracciari, Andrea; Fonti, Cristina; Guarino, Maria

    2008-01-01

    We report the clinical findings and neuropsychological profiles of a sample of patients exhibiting a focal retrograde amnesia (FRA) seen consecutively during the period 1992-2007. The cohort comprised 13 patients, five males, with a mean age of 30 years (range 16-49). They were given a neurologic examination, psychiatric interview and formal neuropsychological examination (all but one) during the amnesic phase, underwent neuroimaging, and were followed up for six months to ten years. All presented with an acute amnesia characterized by an impaired recollection of memories predating the acute event, with spared or minimally and transiently affected anterograde memory, thus consistent with FRA. The events triggering FRA varied widely: mild to severe head injury, road accident without head injury, seizure, dissociative fugue, BDZ overdose, posttraumatic headache, syncope, migraine attack, acute distress. The neuropsychological hallmark of FRA was a selective or prominent impairment of autobiographical memory. The defect was often so severe as to cover most or all of the patients' lives and, in some cases, to erase the knowledge of their own identity. Conventional neuroimaging (brain CT and MRI) was unimpressive. Cerebral SPECT/PET disclosed unilateral frontal hypoperfusion in three (two left). All but one patient fully recovered, time of recovery ranging from three days to six months. FRA is a condition reflecting a block of memory function triggered by heterogeneous events, including both physical and psychic insults. Analogies shared with the more frequently encountered and better known condition of transient global amnesia suggests common pathogenetic mechanisms. A tentative nosographic classification of FRA is finally offered. PMID:19641249

  4. Regulation of Heart Rate in Drosophila via Fragile X Mental Retardation Protein

    PubMed Central

    Novak, Stefanie Mares; Joardar, Archi; Gregorio, Carol C.; Zarnescu, Daniela C.

    2015-01-01

    RNA binding proteins play a pivotal role in post-transcriptional gene expression regulation, however little is understood about their role in cardiac function. The Fragile X (FraX) family of RNA binding proteins is most commonly studied in the context of neurological disorders, as mutations in Fragile X Mental Retardation 1 (FMR1) are the leading cause of inherited mental retardation. More recently, alterations in the levels of Fragile X Related 1 protein, FXR1, the predominant FraX member expressed in vertebrate striated muscle, have been linked to structural and functional defects in mice and zebrafish models. FraX proteins are established regulators of translation and are known to regulate specific targets in different tissues. To decipher the direct role of FraX proteins in the heart in vivo, we turned to Drosophila, which harbors a sole, functionally conserved and ubiquitously expressed FraX protein, dFmr1. Using classical loss of function alleles as well as muscle specific RNAi knockdown, we show that Drosophila FMRP, dFmr1, is required for proper heart rate during development. Functional analyses in the context of cardiac-specific dFmr1 knockdown by RNAi demonstrate that dFmr1 is required cell autonomously in cardiac cells for regulating heart rate. Interestingly, these functional defects are not accompanied by any obvious structural abnormalities, suggesting that dFmr1 may regulate a different repertoire of targets in Drosophila than in vertebrates. Taken together, our findings support the hypothesis that dFmr1 protein is essential for proper cardiac function and establish the fly as a new model for studying the role(s) of FraX proteins in the heart. PMID:26571124

  5. Intercellular Diffusion of a Fluorescent Sucrose Analog via the Septal Junctions in a Filamentous Cyanobacterium

    PubMed Central

    Nürnberg, Dennis J.; Mariscal, Vicente; Bornikoel, Jan; Nieves-Morión, Mercedes; Krauß, Norbert; Herrero, Antonia

    2015-01-01

    ABSTRACT Many filamentous cyanobacteria produce specialized nitrogen-fixing cells called heterocysts, which are located at semiregular intervals along the filament with about 10 to 20 photosynthetic vegetative cells in between. Nitrogen fixation in these complex multicellular bacteria depends on metabolite exchange between the two cell types, with the heterocysts supplying combined-nitrogen compounds but dependent on the vegetative cells for photosynthetically produced carbon compounds. Here, we used a fluorescent tracer to probe intercellular metabolite exchange in the filamentous heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120. We show that esculin, a fluorescent sucrose analog, is incorporated by a sucrose import system into the cytoplasm of Anabaena cells. The cytoplasmic esculin is rapidly and reversibly exchanged across vegetative-vegetative and vegetative-heterocyst cell junctions. Our measurements reveal the kinetics of esculin exchange and also show that intercellular metabolic communication is lost in a significant fraction of older heterocysts. SepJ, FraC, and FraD are proteins located at the intercellular septa and are suggested to form structures analogous to gap junctions. We show that a ΔsepJ ΔfraC ΔfraD triple mutant shows an altered septum structure with thinner septa but a denser peptidoglycan layer. Intercellular diffusion of esculin and fluorescein derivatives is impaired in this mutant, which also shows a greatly reduced frequency of nanopores in the intercellular septal cross walls. These findings suggest that FraC, FraD, and SepJ are important for the formation of junctional structures that constitute the major pathway for feeding heterocysts with sucrose. PMID:25784700

  6. APOLLO 14: Docking trouble (pt 1/2)

    NASA Technical Reports Server (NTRS)

    1974-01-01

    APOLLO 14: The crew are having problems docking the command module to the lunar module: the locking mechanism will not engage. From the film documentary 'APOLLO 14: 'Mission to Fra Mauro'', part of a documentary series on the APOLLO missions made in the early '70's and narrated by Burgess Meredith. APOLO 14: Third manned lunar landing with Alan B. Shepard, Jr.,Stuart A. Roosa, and Edgar D. Mitchell. Landed in the Fra Mauro area on Ferurary 5, 1971; performed EVA, deployed lunar experiments, returned lunar samples. Mission Duration 216 hrs 1 min 58 sec

  7. APOLLO 14: Lift off from lunar surface

    NASA Technical Reports Server (NTRS)

    1974-01-01

    APOLLO 14: The lunar module 'Falcon' lifts off from the lunar surface From the film documentary 'APOLLO 14: 'Mission to Fra Mauro'', part of a documentary series on the APOLLO missions made in the early '70's and narrated by Burgess Meredith. APOLO 14: Third manned lunar landing with Alan B. Shepard, Jr.,Stuart A. Roosa, and Edgar D. Mitchell. Landed in the Fra Mauro area on Ferurary 5, 1971; performed EVA, deployed lunar experiments, returned lunar samples. Mission Duration 216 hrs 1 min 58 sec

  8. APOLLO 14: Docking trouble (pt 2/2)

    NASA Technical Reports Server (NTRS)

    1974-01-01

    APOLLO 14: At last the crew is able to mate the command and lunar modules. But the hitch has raised some serious issues.. From the film documentary 'APOLLO 14: 'Mission to Fra Mauro'', part of a documentary series on the APOLLO missions made in the early '70's and narrated by Burgess Meredith. APOLO 14: Third manned lunar landing with Alan B. Shepard, Jr.,Stuart A. Roosa, and Edgar D. Mitchell. Landed in the Fra Mauro area on Ferurary 5, 1971; performed EVA, deployed lunar experiments, returned lunar samples. Mission Duration 216 hrs 1 min 58 sec

  9. Major element chemistry of glasses in Apollo 14 soil 14156.

    NASA Technical Reports Server (NTRS)

    Reid, A. M.; Ridley, W. I.; Harmon, R. S.; Jakes, P.

    1973-01-01

    Glasses in a soil sample (14156) from the middle layer of the trench at the Fra Mauro landing site show a wide range of compositions clustered around certain preferred compositions. Ninety per cent of the glasses are of two major types - Fra Mauro basalt (63%) with high K and 17 wt % Al2O3 and Highland basalt or anorthositic gabbro (27%) with low K and 25 to 26 wt % Al2O3. The glass population is almost identical with that of the comprehensive soil 14259.

  10. The amnestic syndrome: applying the Rorschach Inkblot method for differential diagnosis.

    PubMed

    Tibon Czopp, Shira; Zeligman, Ruth; Kedem, Sagit; Hadar, Uri

    2014-01-01

    Dissociative processes were investigated in a man diagnosed with focal retrograde amnesia (FRA) following a traumatic head injury without any anterograde memory deficit. Findings were derived from the Rorschach Inkblot method, which was administered together with other performance-based tests and a self-report inventory for evaluating dissociative proneness in personality functioning. A substantial set of behavioral and test response variables indicated dissociation proneness and the activation of dissociative mechanisms. This conception was supported a few months following the evaluation when the patient reported a total spontaneous recovery of the memory deficit. The interplay between neurological and functional factors in FRA is discussed with a view for creating an integrated model.

  11. 75 FR 32236 - Information Collection Requirement; Notice and Request for Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-07

    ... soliciting comments on the following collection of information was published on March 31, 2010 (75 FR 16228... Register soliciting comment on this ICR that the agency was seeking OMB approval. 75 FR 16228. FRA... day notice is published. 44 U.S.C. 3507(b)-(c); 5 CFR 1320.12(d); see also 60 FR 44978, 44983, Aug....

  12. 49 CFR Appendix B to Part 229 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... violation where circumstances warrant. See 49 CFR part 209, appendix A. Failure to observe any condition for... SAs: (a) Failure to notify FRA 1,000 2,000 (b) Failure to report 1,000 2,000 (c) Failure to...

  13. 49 CFR Appendix B to Part 229 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... violation where circumstances warrant. See 49 CFR part 209, appendix A. Failure to observe any condition for... SAs: (a) Failure to notify FRA 1,000 2,000 (b) Failure to report 1,000 2,000 (c) Failure to...

  14. 49 CFR Appendix B to Part 229 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... violation where circumstances warrant. See 49 CFR part 209, appendix A. Failure to observe any condition for... SAs: (a) Failure to notify FRA 1,000 2,000 (b) Failure to report 1,000 2,000 (c) Failure to...

  15. 49 CFR 225.41 - Suicide data.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Suicide data. 225.41 Section 225.41 Transportation... TRANSPORTATION RAILROAD ACCIDENTS/INCIDENTS: REPORTS CLASSIFICATION, AND INVESTIGATIONS § 225.41 Suicide data. FRA does not include suicide data (as defined in § 225.5) in its periodic summaries of data on...

  16. 49 CFR 225.41 - Suicide data.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Suicide data. 225.41 Section 225.41 Transportation... TRANSPORTATION RAILROAD ACCIDENTS/INCIDENTS: REPORTS CLASSIFICATION, AND INVESTIGATIONS § 225.41 Suicide data. FRA does not include suicide data (as defined in § 225.5) in its periodic summaries of data on...

  17. 49 CFR 225.41 - Suicide data.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Suicide data. 225.41 Section 225.41 Transportation... TRANSPORTATION RAILROAD ACCIDENTS/INCIDENTS: REPORTS CLASSIFICATION, AND INVESTIGATIONS § 225.41 Suicide data. FRA does not include suicide data (as defined in § 225.5) in its periodic summaries of data on...

  18. 49 CFR 225.41 - Suicide data.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Suicide data. 225.41 Section 225.41 Transportation... TRANSPORTATION RAILROAD ACCIDENTS/INCIDENTS: REPORTS CLASSIFICATION, AND INVESTIGATIONS § 225.41 Suicide data. FRA does not include suicide data (as defined in § 225.5) in its periodic summaries of data on...

  19. 75 FR 61386 - Emergency Escape Breathing Apparatus Standards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... also means the user must be cleanly shaven or otherwise free of excessive facial hair. The enforcement... this section of the RSIA to the Administrator of FRA. 74 FR 26981, 26982, June 5, 2009, 49 CFR 1.49(oo.... See 73 FR 75207, December 10, 2008, re Docket No. HHS-OS-2009-0025 at http://www.regulations.gov ....

  20. 49 CFR Appendix A to Part 237 - Supplemental Statement of Agency Policy on the Safety of Railroad Bridges

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... FRA in 2000 as Appendix C of the Federal Track Safety Standards, 49 CFR Part 213. With the promulgation of 49 CFR Part 237, Bridge Safety Standards, many of the non-regulatory provisions in that Policy... principles and the law of physics. Track owners should use those principles to assess the integrity...

  1. 76 FR 63582 - Reporting Requirements for Positive Train Control Expenses and Investments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-13

    ... implementation. Positive Train Control Systems, 76 FR 52,918 (Aug. 24, 2011). \\6\\ See UP's Pet. 2; A Primer for... Control Systems, 75 FR 2,598, 2,684 (Jan. 15, 2010). That estimate may decrease, as FRA has proposed an... Surface Transportation Board 49 CFR Part 1241 Reporting Requirements for Positive Train Control...

  2. 76 FR 23714 - Railroad Safety Appliance Standards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-28

    ... Process. See 66 FR 4104, 4198 (January 17, 2001). To FRA's knowledge this requirement has not presented... Transport Canada participate as a non-voting members), as well as ergonomics experts. The Task Force was... participate in the Task Force as a non-voting member, provided that an ergonomics expert,...

  3. 49 CFR Appendix A to Part 214 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... citations will cite the CFR section and the penalty code, if any. FRA reserves the right, should litigation... 49 Transportation 4 2012-10-01 2012-10-01 false Schedule of Civil Penalties 1 A Appendix A to Part...—Schedule of Civil Penalties 1 Section Violation Willful Subpart B—Bridge Worker Safety Standards...

  4. 78 FR 69745 - Safety and Security Plans for Class 3 Hazardous Materials Transported by Rail

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-20

    ... rail transportation of Class 3 hazardous materials, including FRA's Emergency Order No. 28 (78 FR 48218 (EO 28)); the agencies' Joint Safety Advisory published on August 7, 2013 (78 FR 48224) (First Joint... of hazardous materials by rail (78 FR 42998); the referral of safety issues related to EO 28 and...

  5. 49 CFR Appendix A to Part 214 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... to assess a penalty of up to $105,000 for any violation where circumstances warrant. See 49 CFR part... numbers from 49 CFR part 214. If more than one item is listed as a type of violation of a given section... citations will cite the CFR section and the penalty code, if any. FRA reserves the right, should...

  6. 49 CFR 236.588 - Periodic test.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Periodic test. 236.588 Section 236.588... shall be made at least once every 92 days, and on multiple-unit cars as specified by the carrier, subject to approval by the FRA. [49 FR 3387, Jan. 26, 1984]...

  7. 49 CFR 268.21 - Down-selection of one or more Maglev projects for further study and selection of one project for...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Down-selection of one or more Maglev projects for... Procedures For Financial Assistance § 268.21 Down-selection of one or more Maglev projects for further study... completion of Phase III of the Maglev Deployment Program, FRA will down-select one or more projects...

  8. 49 CFR 268.21 - Down-selection of one or more Maglev projects for further study and selection of one project for...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Down-selection of one or more Maglev projects for... Procedures For Financial Assistance § 268.21 Down-selection of one or more Maglev projects for further study... completion of Phase III of the Maglev Deployment Program, FRA will down-select one or more projects...

  9. 49 CFR 268.21 - Down-selection of one or more Maglev projects for further study and selection of one project for...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Down-selection of one or more Maglev projects for... Procedures For Financial Assistance § 268.21 Down-selection of one or more Maglev projects for further study... completion of Phase III of the Maglev Deployment Program, FRA will down-select one or more projects...

  10. 75 FR 67451 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-02

    ... address the problems that may be revealed. The aggregate data may prove useful in FRA's decisionmaking... discovered by Amtrak, for example, through subsequent retrospective analysis of locomotive event recorder data, etc. In order to encourage employee reporting of close calls, the IMOU contains provisions...

  11. Genome-wide profiling of AP-1-regulated transcription provides insights into the invasiveness of triple-negative breast cancer.

    PubMed

    Zhao, Chunyan; Qiao, Yichun; Jonsson, Philip; Wang, Jian; Xu, Li; Rouhi, Pegah; Sinha, Indranil; Cao, Yihai; Williams, Cecilia; Dahlman-Wright, Karin

    2014-07-15

    Triple-negative breast cancer (TNBC) is an aggressive clinical subtype accounting for up to 20% of all breast cancers, but its malignant determinants remain largely undefined. Here, we show that in TNBC the overexpression of Fra-1, a component of the transcription factor AP-1, offers prognostic potential. Fra-1 depletion or its heterodimeric partner c-Jun inhibits the proliferative and invasive phenotypes of TNBC cells in vitro. Similarly, RNAi-mediated attenuation of Fra-1 or c-Jun reduced cellular invasion in vivo in a zebrafish tumor xenograft model. Exploring the AP-1 cistrome and the AP-1-regulated transcriptome, we obtained insights into the transcriptional regulatory networks of AP-1 in TNBC cells. Among the direct targets identified for Fra-1/c-Jun involved in proliferation, adhesion, and cell-cell contact, we found that AP-1 repressed the expression of E-cadherin by transcriptional upregulation of ZEB2 to stimulate cell invasion. Overall, this work illuminates the pathways through which TNBC cells acquire invasive and proliferative properties.

  12. 76 FR 18294 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-01

    ... upon request. Through these rules, FRA learns the condition of operating rules and practices with.../Designated 644 railroads...... 9 lists 1 hour 9 Existing On-Track Roadway Maintenance Machines Conforming... minutes 83 Displayed on Each New Roadway stencils. Maintenance Machine (RMM)....

  13. 77 FR 35106 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-12

    ... are not toll-free.) SUPPLEMENTARY INFORMATION: The Paperwork Reduction Act of 1995 (PRA), Public Law... 6180.4(a)-(q). Affected Public: Businesses. Respondent Universe: 130 Federal and State Inspectors... universe responses per response burden hours (forms) (minutes) (hours) New Form FRA F 6180.4EZ 130...

  14. 78 FR 38878 - Critical Incident Stress Plans

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-28

    ... report prepared by FRA grantee, Dr. Richard Gist, in support of Grant FR-RRD-0024-11- 01, titled... involved in a critical incident, often outside the control of the railroad employees, which can lead to... of duty upon request, often involving contact with occupational medicine or EAP...

  15. Knowledge and information management for integrated water resource management

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Watershed information systems that integrate data and analytical tools are critical enabling technologies to support Integrated Water Resource Management (IWRM) by converting data into information, and information into knowledge. Many factors bring people to the table to participate in an IWRM fra...

  16. Watershed Central: An Integrated Watershed Assessment and Management Website (MO presentation)

    EPA Science Inventory

    The U.S. EPA’s Office of Water (OW), Office of Research and Development (ORD), and Office of Environmental Information (OEI) have teamed together with other Federal Agencies, state and local agencies, tribal agencies, and non-government organizations, to develop an integrated fra...

  17. 78 FR 1933 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-09

    ... glass replacement continues to be an extremely high cost for an excursion operation and would jeopardize... replacing noncompliant window glass with Part 223-compliant glazing. Since the last waiver request was granted by FRA, FGLK replaced 22 pieces of noncompliant glass in 2009 at a cost of nearly $9,000. A...

  18. 49 CFR 225.23 - Joint operations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Joint operations. 225.23 Section 225.23....23 Joint operations. (a) Any reportable death, injury, or illness of an employee arising from an accident/incident involving joint operations must be reported on Form FRA F 6180.55a by the...

  19. 49 CFR 225.23 - Joint operations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Joint operations. 225.23 Section 225.23....23 Joint operations. (a) Any reportable death, injury, or illness of an employee arising from an accident/incident involving joint operations must be reported on Form FRA F 6180.55a by the...

  20. 49 CFR 225.23 - Joint operations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Joint operations. 225.23 Section 225.23....23 Joint operations. (a) Any reportable death, injury, or illness of an employee arising from an accident/incident involving joint operations must be reported on Form FRA F 6180.55a by the...

  1. 49 CFR 225.23 - Joint operations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Joint operations. 225.23 Section 225.23....23 Joint operations. (a) Any reportable death, injury, or illness of an employee arising from an accident/incident involving joint operations must be reported on Form FRA F 6180.55a by the...

  2. 49 CFR 225.23 - Joint operations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Joint operations. 225.23 Section 225.23....23 Joint operations. (a) Any reportable death, injury, or illness of an employee arising from an accident/incident involving joint operations must be reported on Form FRA F 6180.55a by the...

  3. 77 FR 3556 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-24

    ... 17, 2011 (76 FR 71433). DATES: Comments must be submitted on or before February 23, 2012. FOR FURTHER... seeking OMB approval. 76 FR 71433. FRA received no comments in response to this notice. Before OMB decides...(d); see also 60 FR 44978, 44983, Aug. 29, 1995. OMB believes that the 30 day notice informs...

  4. 75 FR 16552 - High-Speed Intercity Passenger Rail (HSIPR) Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-01

    ... 23, 2009 interim program guidance (74 FR 29900), and details the application requirements and... predetermined minimum or maximum dollar thresholds for awards, FRA anticipates making one or more awards for the... through a rational planning process (ideally a High-Speed Intercity Passenger Rail Service...

  5. O3, CO2 and chemical fractionation in ponderosa pine saplings

    EPA Science Inventory

    Environmental factors can affect plant tissue quality which is important for quality of organic matter inputs into soil food webs and decomposition of soil organic matter. Thus the effects of increases in CO2 and O3 and their interactions were determined for various chemical fra...

  6. 76 FR 49975 - Inspection of Towing Vessels

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-11

    ... notice regarding our public dockets in the January 17, 2008 issue of the Federal Register (73 FR 3316). D... Administration FR Federal Register FRA Federal Railroad Administration GAO Government Accountability Office gpm... public meetings titled ``Inspection of Towing Vessels'' in the Federal Register (69 FR 78471). The...

  7. 77 FR 48591 - State Rail Plan Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-14

    ... complete Privacy Act Statement in the Federal Register published on April 11, 2000 (65 FR 19477), or visit... Federal Railroad Administration State Rail Plan Guidance AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Request for Public Comment on Proposed State Rail Plan...

  8. 49 CFR Appendix B to Part 223 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., 21304, and 49 CFR part 209, appendix A. If more than one item is listed as a type of violation of a... convenience, penalty citations will cite the CFR section and the penalty code, if any. FRA reserves the right, should litigation become necessary, to substitute in its complaint the CFR citation in place of...

  9. 78 FR 18285 - Direct Final Rulemaking Procedures

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-26

    ... Transportation's (DOT) complete Privacy Act Statement in the Federal Register published on April 11, 2000 (65 FR... would be useful to its rulemaking activities. \\1\\ 69 FR 4455. \\2\\ See 70 FR 67318 (FTA), 72 FR 10086 (FRA), and 75 FR 29915 (FMCSA). Notice and comment rulemaking procedures are not required under...

  10. 77 FR 15108 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-14

    ... FRA (12 U.S.C. 611- 631); and Regulation K (12 CFR 211.8(c)-211.10(a)). Since the Federal Reserve does... must be submitted on or before May 14, 2012. ADDRESSES: You may submit comments, identified by FR 2064...: Recordkeeping Requirements Associated with Changes in Foreign Investments (Made Pursuant to Regulation...

  11. 78 FR 13747 - Safety Advisory 2013-01; Passing Stop Signals Protecting Movable Bridges

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-28

    ... Federal Railroad Administration Safety Advisory 2013-01; Passing Stop Signals Protecting Movable Bridges... movable bridge. FRA is issuing this notice in response to a recent train accident involving a derailment... movable bridges to determine if effective span locking is being provided; (2) review current...

  12. 77 FR 74737 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-17

    ... the U.S. Department of Transportation's (DOT) Docket Operations Facility, 1200 New Jersey Avenue SE., W12-140, Washington, DC 20590. The Docket Operations Facility is open from 9 a.m. to 5 p.m., Monday... proceedings by submitting written views, data, or comments. FRA does not anticipate scheduling a...

  13. 78 FR 59754 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-27

    .... Department of Transportation's (DOT) Docket Operations Facility, 1200 New Jersey Avenue SE., W12-140, Washington, DC 20590. The Docket Operations Facility is open from 9 a.m. to 5 p.m., Monday through Friday... written views, data, or comments. FRA does not anticipate scheduling a public hearing in connection...

  14. 76 FR 73770 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ...'s (DOT) Docket Operations Facility, 1200 New Jersey Ave., SE., W12-140, Washington, DC 20590. The Docket Operations Facility is open from 9 a.m. to 5 p.m., Monday through Friday, except Federal Holidays... comments. FRA does not anticipate scheduling a public hearing in connection with these proceedings...

  15. 75 FR 29805 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ... change is to improve efficiency of train operation. Interested parties are invited to participate in these proceedings by submitting written views, data, or comments. FRA does not anticipate scheduling a... Operations Facility, U.S. Department of Transportation, 1200 New Jersey Avenue, SE., W12-140, Washington,...

  16. 78 FR 59756 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-27

    ... the U.S. Department of Transportation's Docket Operations Facility, 1200 New Jersey Avenue SE., W12-140, Washington, DC 20590. The Docket Operations Facility is open from 9 a.m. to 5 p.m., Monday... proceedings by submitting written views, data, or comments. FRA does not anticipate scheduling a...

  17. 75 FR 34204 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-16

    ... relief. Santa Cruz, Big Trees & Pacific Railway Company The Santa Cruz, Big Trees & Pacific Railway... written views, data, or comments. FRA does not anticipate scheduling a public hearing in connection with... complete Privacy Act Statement in the Federal Register published on April 11, 2000 (65 FR 19477) or at...

  18. 75 FR 15484 - Railroad Safety Technology Program Grant Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-29

    ... Federal Railroad Administration Railroad Safety Technology Program Grant Program AGENCY: Federal Railroad... Applications. SUMMARY: The Rail Safety Technology Program is a newly authorized program under the Rail Safety... ), or Mr. David Blackmore, FRA, Program Manager- Advanced Technologies (Phone: (312) 835-3903,...

  19. 78 FR 13747 - Railroad Safety: Advisory Notice Related to Railroad Accidents in Vicinity of Underground Pipelines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-28

    ... CONTACT: Karl Alexy, Staff Director, Hazardous Materials Division, Office of Railroad Safety, FRA, 1200 New Jersey Avenue SE., Washington, DC 20590; telephone: (202) 493-6245; or Karl.Alexy@dot.gov ; or... Materials Safety Administration (PHMSA) issued an advisory bulletin in the Federal Register (77 FR...

  20. An “ADME Module” in the Adverse Outcome Pathway Knowledgebase

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework has generated intense interest for its utility to organize knowledge on the toxicity mechanisms, starting from a molecular initiating event (MIE) to an adverse outcome across various levels of biological organization. While the AOP fra...

  1. 78 FR 49323 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-13

    ... ICR for which the agency was seeking OMB approval. 78 FR 29203. FRA received no comments in response....S.C. 3507 (b)-(c); 5 CFR 1320.12(d); see also 60 FR 44978, 44983, Aug. 29, 1995. OMB believes that... adequate time to digest public comments before it renders a decision. 60 FR 44983, Aug. 29, 1995....

  2. Cytological and molecular characterization of three gametoclones of citrus clementina

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Three gametoclonal plants of Citrus clementina Hort. ex Tan., cv. Nules, designated ESP, FRA, and ITA (derived from three labs in Spain, France, and Italy, respectively), were selected for cytological and molecular characterization in order to elucidate genomic rearrangements provoked by haploidizat...

  3. 75 FR 44051 - Resolicitation of Applications for the Railroad Safety Technology Program Grant Program (RS-TEC...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-27

    ... Grant Program (RS-TEC-10-001) AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Notice of Funds Availability, Resolicitation of Applications (RS-TEC-10-001... Railroad Safety Technology Grant Program ] (Funding Opportunity RS-TEC-10-001), the Federal...

  4. 76 FR 65777 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-24

    ... soliciting comments on the following collection of information was published on August 12, 2011 (76 FR 50320... approval. 76 FR 50320. FRA received no comments in response to this notice. Before OMB decides whether to... also 60 FR 44978, 44983, Aug. 29, 1995. OMB believes that the 30 day notice informs the...

  5. Third Lunar Science Conference.

    NASA Technical Reports Server (NTRS)

    Burlingame, A.; Burnett, D.; Doe, B.; Gault, D.; Haskin, L.; Schnoes, H.; Heymann, D.; Melson, W.; Papike, J.; Tilling, R.

    1972-01-01

    Discussion of the nature and properties of lunar rock as deduced from the examination of Apollo lunar rock samples. The topics include the lunar crust, the Fra Mauro formation, the interior of the moon, lunar chronology, surface processes, and earth-moon environment.

  6. 49 CFR 219.800 - Annual reports.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) form and instructions as required by 49 CFR part 40 (at § 40.25 and appendix H to part 40). You may..., see: http://www.fra.dot.gov/Content3.asp?P=504. (c) Each railroad shall ensure the accuracy...

  7. 49 CFR 219.800 - Annual reports.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) form and instructions as required by 49 CFR part 40 (at § 40.25 and appendix H to part 40). You may..., see: http://www.fra.dot.gov/Content3.asp?P=504. (c) Each railroad shall ensure the accuracy...

  8. 49 CFR 219.800 - Annual reports.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) form and instructions as required by 49 CFR part 40 (at § 40.25 and appendix H to part 40). You may..., see: http://www.fra.dot.gov/Content3.asp?P=504. (c) Each railroad shall ensure the accuracy...

  9. 75 FR 49551 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Federal Railroad Administration Petition for Waiver of Compliance Pursuant to title 49 Code of Federal Regulations (CFR) part 235 and 49 U.S.C. 20502(a), the following railroad has petitioned the Federal Railroad Administration (FRA)...

  10. 76 FR 72496 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-23

    ... 8, 2011 (76 FR 55726). DATES: Comments must be submitted on or before December 23, 2011. FOR FURTHER... seeking OMB approval. 76 FR 55726. FRA received no comments in response to this notice. Before OMB decides...(d); see also 60 FR 44978, 44983, Aug. 29, 1995. OMB believes that the 30 day notice informs...

  11. 78 FR 21705 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-11

    ... February 21, 2013, the Old Augusta Railroad (OAR) has petitioned the Federal Railroad Administration (FRA... this type of schedule for 18 years without any safety problems, and that it was awarded the American Short Line and Regional Railroad Association Jake Award each year during those 18 years. A copy of...

  12. Automated riverine landscape characterization: GIS-based tools for watershed-scale research, assessment, and management

    EPA Science Inventory

    River systems consist of hydrogeomorphic patches (HPs) that emerge at multiple spatiotemporal scales. Functional process zones (FPZs) are HPs that exist at the river valley scae and are important strata for fraing whole-watershed research questions and management plans. Hierarchi...

  13. 49 CFR Appendix A to Part 237 - Supplemental Statement of Agency Policy on the Safety of Railroad Bridges

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... FRA in 2000 as Appendix C of the Federal Track Safety Standards, 49 CFR Part 213. With the promulgation of 49 CFR Part 237, Bridge Safety Standards, many of the non-regulatory provisions in that Policy... bridge to safely support its traffic can be determined only by intelligent application of...

  14. 76 FR 34138 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-10

    ...' responsibilities, as well as employees' rights and responsibilities thereto; well-defined procedures for..., 2011 (76 FR 18294). DATES: Comments must be submitted on or before July 11, 2011. FOR FURTHER... agency is seeking OMB approval. 76 FR 18294. FRA received no comments in response to this notice....

  15. 75 FR 38343 - High-Speed Intercity Passenger Rail (HSIPR) Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-01

    ... acquisition or construction (including designing, engineering, location surveying, mapping, environmental... Engineering/NEPA for Individual Projects with a 20 percent non-Federal match. The notice of funding... environmental review process; (2) FRA's use of a Letter of Intent (LOI) to contingently commit funds to...

  16. 77 FR 70876 - Revised Guidance for Requesting One-Time Movement Approvals (OTMA)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-27

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Federal Railroad Administration Revised Guidance for Requesting One-Time Movement Approvals (OTMA) AGENCY.... SUMMARY: FRA is notifying the public of the availability of revised guidance for requesting...

  17. 75 FR 25927 - Vehicle/Track Interaction Safety Standards; High-Speed and High Cant Deficiency Operations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-10

    ... areas of railroad safety.'' See 36 FR 20336. FRA envisioned the new Standards to be an evolving set of... 63 FR 33992, which, effective September 21, 1998, revised the Track Safety Standards in their... standards for railroad passenger equipment. See 61 FR 30672. The ANPRM provided background information...

  18. 78 FR 56995 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-16

    ... employees. 10 letters......... 2 hours 20 225.13--Late Reports--RR 763 railroads...... 25 late reports.... 1 hour 25 Discovery of Improperly Omitted Report of Accident/Incident. --RR Late/Amended Report of 763... Employee Hours and Casualties, By State--Form FRA F 6180.56. 225.21/25--Railroad Employee 763...

  19. 78 FR 70398 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-25

    ... following collections of information was published on September 16, 2013 (78 FR 56995). DATES: Comments must.... SE., Mail Stop 25, Washington, DC 20590 (telephone: (202) 493-6292), or Ms. Kimberly Toone, Office of... the agency was seeking OMB approval. 78 FR 56995. FRA received no comments in response to...

  20. 49 CFR 238.421 - Glazing.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... penetration or spall. An impact angle that is perpendicular (90 degrees) to the window's surface shall be... “FRA TYPE IHP” to indicate that the material has successfully passed the testing requirements specified... less severe than horizontal to the vehicle, with no penetration or spall. An impact angle that...

  1. 49 CFR 238.421 - Glazing.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... penetration or spall. An impact angle that is perpendicular (90 degrees) to the window's surface shall be... “FRA TYPE IHP” to indicate that the material has successfully passed the testing requirements specified... less severe than horizontal to the vehicle, with no penetration or spall. An impact angle that...

  2. 49 CFR 238.421 - Glazing.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... penetration or spall. An impact angle that is perpendicular (90 degrees) to the window's surface shall be... “FRA TYPE IHP” to indicate that the material has successfully passed the testing requirements specified... less severe than horizontal to the vehicle, with no penetration or spall. An impact angle that...

  3. 49 CFR 238.421 - Glazing.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... penetration or spall. An impact angle that is perpendicular (90 degrees) to the window's surface shall be... “FRA TYPE IHP” to indicate that the material has successfully passed the testing requirements specified... less severe than horizontal to the vehicle, with no penetration or spall. An impact angle that...

  4. 49 CFR 238.421 - Glazing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... penetration or spall. An impact angle that is perpendicular (90 degrees) to the window's surface shall be... “FRA TYPE IHP” to indicate that the material has successfully passed the testing requirements specified... less severe than horizontal to the vehicle, with no penetration or spall. An impact angle that...

  5. 49 CFR 260.35 - Environmental assessment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Council on Environmental Quality (“CEQ Regulation”) (40 CFR Part 1500) will govern the FRA's compliance... 49 Transportation 4 2012-10-01 2012-10-01 false Environmental assessment. 260.35 Section 260.35... REHABILITATION AND IMPROVEMENT FINANCING PROGRAM Applications for Financial Assistance § 260.35...

  6. 78 FR 14152 - Notice of Intent To Grant Buy America Waiver to Illinois Department of Transportation To Use...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-04

    ... Federal Register published on April 11, 2000 (65 FR 19477), or visit http://www.regulations.gov . FOR...: (1) An ethernet cable; (2) an omni directional antenna; and (3) a router/server combination. FRA..., antennae, displays, and sensors, which are assembled into each end product, are components and must...

  7. 78 FR 18668 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-27

    ... or alcohol use. FRFB train and dispatching service employees testing positive for unauthorized use of... Budget (OMB), FRA is soliciting public comment on specific aspects of the activities identified below... prohibition against the abuse of alcohol and controlled substances. Because of the increase in...

  8. 77 FR 33266 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-05

    ... it is a nonprofit independent agency of the State of Utah doing business as the Heber Valley Railroad... request, HVRR understands that a permanent roster of restricted cars shall be maintained for the benefit of the railroad and FRA at all times. A copy of the petition, as well as any written...

  9. 49 CFR 229.211 - Processing of petitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... to the U.S. Department of Transportation Docket Operations (M-30), West Building Ground Floor, Room... requires additional information to appropriately consider the petition, FRA will conduct a hearing on the..., or both which may include validated computer modeling, structural crush analysis, component...

  10. A multiplex PCR assay for determination of mating type in isolates of the honey bee fungal pathogen, Ascosphaera apis.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study we developed a multiplex PCR for identification of mating type idiomorphs in the filamentous fungus, Ascosphaera apis, the causative agent of chalkbrood disease in the honey bee (Apis melliffera). A combination of gene-specific primers was designed to amplify Mat1-1 and Mat1-2 gene fra...

  11. 78 FR 28940 - Environmental Impact Statement for the Atlanta to Charlotte Portion of the Southeast High Speed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-16

    ... Southeast High Speed Rail Corridor AGENCY: Federal Rail Administration (FRA), DOT. ACTION: Notice of Intent... between Atlanta, GA and Charlotte, NC, along the Southeast High-Speed Rail Corridor (SEHSR) as designated by the USDOT. The Study is being advanced consistent with the federal High-Speed Intercity...

  12. 77 FR 69920 - Notice of Availability of a Final Tier 1 Environmental Impact Statement, for the Chicago, IL to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-21

    ... 1500 et seq.), and FRA's Procedures for Considering Environmental Impacts (64 FR 28545; May 26, 1999..., for the Chicago, IL to St. Louis, MO High Speed Rail Corridor Program and Tier 2 Evaluation for the... (Final EIS) has been prepared for the Chicago, Illinois to St. Louis, Missouri High Speed Rail...

  13. 77 FR 43902 - Notice of Availability of a Supplemental Draft Environmental Impact Statement for the California...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-26

    ... NEPA (40 CFR parts 1500 et seq.), and FRA's Procedures for Considering Environmental Impacts (64 FR... Statement for the California High-Speed Train Project Fresno to Bakersfield Section AGENCY: Federal Railroad... Statement (EIS) has been prepared for the Fresno to Bakersfield Section of the California High- Speed...

  14. 75 FR 32240 - Draft Tier II Environmental Impact Statement: Southeast High Speed Rail Corridor-Richmond, VA...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-07

    ... Quality NEPA implementing regulations, 40 CFR parts 1500-1508, and the FRA NEPA guidance, 64 FR 28545 (May... Federal Railroad Administration Draft Tier II Environmental Impact Statement: Southeast High Speed Rail... Draft Environmental Impact Statement and public hearings for the Southeast High Speed Rail, Richmond,...

  15. 78 FR 57449 - Notice Rescinding a Notice of Intent To Prepare a Programmatic Environmental Impact Statement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-18

    ... Environmental Impact Statement: High Speed Rail Corridor Las Vegas, Nevada to Anaheim, California AGENCY... and 2000s, the California- Nevada Super Speed Train Commission (CNSSTC), a public agency chartered... magnetic levitation ] technology high-speed ground transportation system. During the late 1990s, FRA...

  16. 78 FR 32007 - Environmental Impact Statement for Tulsa-Oklahoma City Passenger Rail Corridor, Oklahoma, Lincoln...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-28

    ... implementing NEPA and the FRA's Procedures for Considering Environmental Impacts as set forth in 64 FR 28545...) for the State of Oklahoma High-Speed Rail Initiative: Tulsa--Oklahoma City Passenger Rail Corridor... currently has no passenger rail service. This corridor is part of the South Central High Speed Rail...

  17. 75 FR 54694 - Notice of Availability of a Supplemental Draft Environmental Impact Statement for the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-08

    ... Considering Environmental Impacts (64 FR 28545; May 26, 1999). DesertXpress Enterprises Inc., the Project... Statement for the DesertXpress High-Speed Passenger Rail Project AGENCY: Federal Railroad Administration...- Speed Passenger Train Project (Project). FRA is the lead agency for the environmental review process...

  18. 78 FR 16357 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-14

    ... OMB approval. 77 FR 77181. FRA received no comments in response to this notice. Before OMB decides... also 60 FR 44978, 44983, Aug. 29, 1995. OMB believes that the 30 day notice informs the regulated... renders a decision. 60 FR 44983, Aug. 29, 1995. Therefore, respondents should submit their...

  19. 78 FR 13155 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION... Model SW-1200, Number LKRR 1205, from 49 CFR Section 223.11, Requirements for existing locomotives. FRA... available for review online at www.regulations.gov and in person at the U.S. Department of...

  20. 76 FR 26682 - Study on Protection of Certain Railroad Risk Reduction Data From Discovery or Use in Litigation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-09

    ... documents that are not simply recitations of platitudes or pamphlets suitable for public relations campaigns... Transportation (DOT). ACTION: Notice and request for public comment. SUMMARY: In accordance with section 109 of the Rail Safety Improvement Act of 2008 (RSIA), FRA is soliciting public comment on the issue...

  1. 77 FR 65764 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-30

    ... by age. It is retained primarily for use on excursion trains, historical and public relation events... Code of Federal Regulations (CFR), this document provides the public notice that by a document dated.... FRA does not anticipate scheduling a public hearing in connection with these proceedings since...

  2. 76 FR 67073 - Safety and Health Requirements Related to Camp Cars

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-31

    ... the hours of service laws at 49 U.S.C. 21106). See notice of proposed rulemaking (NPRM), 76 FR 64... facilities, potable water, and other features to protect the health of employees. 49 U.S.C. 21106(a)(1). RSIA... the responsibility to carry out his responsibilities under RSIA to the Administrator of FRA. 74...

  3. 49 CFR Appendix A to Part 237 - Supplemental Statement of Agency Policy on the Safety of Railroad Bridges

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... FRA in 2000 as Appendix C of the Federal Track Safety Standards, 49 CFR Part 213. With the promulgation of 49 CFR Part 237, Bridge Safety Standards, many of the non-regulatory provisions in that Policy... principles and the law of physics. Track owners should use those principles to assess the integrity...

  4. 78 FR 25344 - Petition for a Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-30

    ... Federal Railroad Administration Petition for a Waiver of Compliance In accordance with Part 211 of Title 49 Code of Federal Regulations (CFR), this document provides the public notice that by a document... Administration (FRA) for a waiver of compliance from certain provisions of the Federal railroad...

  5. 49 CFR Table 4 of Subpart B to... - Alternative Schedule for Application of Retroreflective Material to Locomotives per § 224.107(b...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... take such additional action as may be necessary to achieve future compliance. (D) Locomotives to be... Report with FRA no later than January 26, 2006, identifying the cars already so equipped. See appendix B... end of calendar year 2004, and does not share locomotive power with another railroad with 400,000...

  6. 49 CFR Table 4 of Subpart B to... - Alternative Schedule for Application of Retroreflective Material to Locomotives per § 224.107(b...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... take such additional action as may be necessary to achieve future compliance. (D) Locomotives to be... Report with FRA no later than January 26, 2006, identifying the cars already so equipped. See appendix B... end of calendar year 2004, and does not share locomotive power with another railroad with 400,000...

  7. 49 CFR Table 4 of Subpart B to... - Alternative Schedule for Application of Retroreflective Material to Locomotives per § 224.107(b...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... take such additional action as may be necessary to achieve future compliance. (D) Locomotives to be... Report with FRA no later than January 26, 2006, identifying the cars already so equipped. See appendix B... end of calendar year 2004, and does not share locomotive power with another railroad with 400,000...

  8. 75 FR 2466 - State Highway-Rail Grade Crossing Action Plans

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-15

    ...) published on November 13, 2009 (74 FR 58589), FRA proposed a rule to require the ten States with the most... Statement in the Federal Register published on April 11, 2000 (65 FR 19477-78) or you may visit http://www... Federal Railroad Administration 49 CFR Part 234 RIN 2130-AC20 State Highway-Rail Grade Crossing...

  9. 49 CFR 234.7 - Accidents involving grade crossing signal failure.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... be filed with FRA pursuant to § 234.9 of this part (activation failure report) and 49 CFR 225.11... 49 Transportation 4 2013-10-01 2013-10-01 false Accidents involving grade crossing signal failure... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION GRADE CROSSING SAFETY, INCLUDING SIGNAL...

  10. 77 FR 68722 - National Highway-Rail Crossing Inventory Reporting Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-16

    ... Federal Railroad Administration 49 CFR Part 234 RIN 2130-AC26 National Highway-Rail Crossing Inventory..., FRA published a Notice of Proposed Rulemaking (NPRM) on National Highway-Rail Crossing Inventory... U.S. DOT National Highway-Rail Crossing Inventory (Crossing Inventory). This notice announces...

  11. 49 CFR 234.7 - Accidents involving grade crossing signal failure.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... be filed with FRA pursuant to § 234.9 of this part (activation failure report) and 49 CFR 225.11... 49 Transportation 4 2012-10-01 2012-10-01 false Accidents involving grade crossing signal failure... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION GRADE CROSSING SAFETY, INCLUDING SIGNAL...

  12. 49 CFR 236.919 - Operations and Maintenance Manual.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Operations and Maintenance Manual. 236.919 Section... for Processor-Based Signal and Train Control Systems § 236.919 Operations and Maintenance Manual. (a... Maintenance Manual, readily available to persons required to perform such tasks and for inspection by FRA...

  13. 75 FR 32237 - Information Collection Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-07

    ... collections of information was published on April 2, 2010 (75 FR 16896). DATES: Comments must be submitted on... 20590 (telephone: (202) 493-6132). (These telephone numbers are not toll-free.). SUPPLEMENTARY... agency was seeking OMB approval. 75 FR 16896. FRA received no comments after issuing this 60-day...

  14. 76 FR 38452 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-30

    ... soliciting comments on the following collection of information was published on April 20, 2011 (76 FR 22165... approval. 76 FR 22165. FRA received no comments in response to this notice. Before OMB decides whether to... also 60 FR 44978, 44983, Aug. 29, 1995. OMB believes that the 30 day notice informs the...

  15. 77 FR 22843 - Notice of Product Development

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Federal Railroad Administration Notice of Product Development In accordance with Part 211 of Title 49 Code...) have provided the Federal Railroad Administration (FRA) a Notice of Product Development per 49 CFR...

  16. 49 CFR Appendix C to Part 227 - Audiometric Baseline Revision

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... CFR 1910.95(g)(10)(i). D. Initially, the baseline is the latest audiogram obtained before entry into...-correction provisions. FRA's is found in appendix F of part 227 and OSHA's in appendix F of 29 CFR 1910.95... 49 Transportation 4 2014-10-01 2014-10-01 false Audiometric Baseline Revision C Appendix C to...

  17. 49 CFR Appendix C to Part 220 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... warrant. See 49 CFR part 209, appendix A. 2 The penalty schedule uses section numbers from 49 CFR part 220... CFR section and the penalty code, if any. FRA reserves the right, should litigation become necessary, to substitute in its complaint the CFR citation in place of the combined CFR and penalty...

  18. 49 CFR Appendix C to Part 218 - Statement of Agency Enforcement Policy on Tampering

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... similar contexts. (See 49 CFR 107.299, defining “knowingly” under the Hazardous Materials Transportation... operating. Also, unlike the case where willfulness must be shown (see FRA's statement of policy at 49 CFR... Tampering C Appendix C to Part 218 Transportation Other Regulations Relating to Transportation...

  19. 49 CFR Appendix C to Part 227 - Audiometric Baseline Revision

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... CFR 1910.95(g)(10)(i). D. Initially, the baseline is the latest audiogram obtained before entry into...-correction provisions. FRA's is found in appendix F of part 227 and OSHA's in appendix F of 29 CFR 1910.95... 49 Transportation 4 2013-10-01 2013-10-01 false Audiometric Baseline Revision C Appendix C to...

  20. 49 CFR Appendix C to Part 220 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... warrant. See 49 CFR part 209, appendix A. 2 The penalty schedule uses section numbers from 49 CFR part 220... CFR section and the penalty code, if any. FRA reserves the right, should litigation become necessary, to substitute in its complaint the CFR citation in place of the combined CFR and penalty...

  1. 49 CFR Appendix C to Part 218 - Statement of Agency Enforcement Policy on Tampering

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... similar contexts. (See 49 CFR 107.299, defining “knowingly” under the Hazardous Materials Transportation... operating. Also, unlike the case where willfulness must be shown (see FRA's statement of policy at 49 CFR... Tampering C Appendix C to Part 218 Transportation Other Regulations Relating to Transportation...

  2. 77 FR 12407 - Statement of Agency Policy and Interpretation on the Hours of Service Laws as Amended; Response...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-29

    ... policy and interpretation (Interim Interpretations) and its proposed interpretation, 74 FR 30665, FRA... with respect to the hours of service laws as amended by the RSIA (the new hours of service laws). 74 FR..., Limitations on employee sleeping quarters, effective October 16, 2008. See 76 FR 67073 (Oct. 31, 2011). Nor...

  3. 49 CFR 239.101 - Emergency preparedness plan.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Emergency preparedness plan. 239.101 Section 239....101 Emergency preparedness plan. (a) Each railroad to which this part applies shall adopt and comply with a written emergency preparedness plan approved by FRA under the procedures of § 239.201. The...

  4. 77 FR 25228 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-27

    ... waiver from the provisions of 49 CFR 222.9, the definition of a non-traversable curb, so that an existing... that the posted highway speed limit is 45 mph instead of 40 mph, as required in the definition. A copy.... FRA does not anticipate scheduling a public hearing in connection with these proceedings since...

  5. 78 FR 22363 - Environmental Impact Statement for the All Aboard Florida Miami-Orlando Passenger Rail Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-15

    .... 4321 et seq.) (NEPA) and FRA's Procedures for Considering Environmental Impacts (64 FR 28545, May 26... Federal Railroad Administration Environmental Impact Statement for the All Aboard Florida Miami-- Orlando... service proposed by the private company, All Aboard Florida--Operations LLC (AAF), between Miami...

  6. 49 CFR 219.4 - Recognition of a foreign railroad's workplace testing program.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... program promulgated under the laws of its home country as a compatible alternative to the return-to... necessary. (b) Alternative programs. (1) Upon FRA's recognition of a foreign railroad's workplace testing... Building Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590-0001. (iv)...

  7. 49 CFR 219.4 - Recognition of a foreign railroad's workplace testing program.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... program promulgated under the laws of its home country as a compatible alternative to the return-to... necessary. (b) Alternative programs. (1) Upon FRA's recognition of a foreign railroad's workplace testing... Building Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590-0001. (iv)...

  8. 49 CFR 219.4 - Recognition of a foreign railroad's workplace testing program.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... program promulgated under the laws of its home country as a compatible alternative to the return-to... necessary. (b) Alternative programs. (1) Upon FRA's recognition of a foreign railroad's workplace testing... Building Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590-0001. (iv)...

  9. 49 CFR 225.6 - Consolidated reporting.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Consolidated reporting. 225.6 Section 225.6 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Consolidated reporting. A parent corporation may request in writing that FRA treat its commonly...

  10. Functional focal retrograde amnesia: lost access to abstract autobiographical knowledge?

    PubMed

    Stracciari, Andrea; Mattarozzi, Katia; Fonti, Cristina; Guarino, Maria

    2005-10-01

    We describe three patients exhibiting an acute reversible amnesia characterised by an impaired recollection of past events with preserved anterograde memory, thus consistent with a focal retrograde amnesia (FRA). This occurred after variable events: state of fugue, road accident, post-traumatic headache. Retrograde amnesia affected autobiographical memory so severely as to cover all of the patients' lives and to erase knowledge of their own identity. The retrieval of public events was variably affected, ranging from normality to severe impairment. No lesions were found on neuroimaging, and neurophysiological findings were unimpressive. FRA subsided in a few days, leaving a gap for the onset. The hypothesis of a psychogenic amnesia is considered, but overcoming the organic/psychogenic dichotomy the episodes appear as examples of "functional" memory inhibition, potentially triggered by different conditions, including events classifiable as psychic trauma. The clinical and neuropsychological traits of functional FRA are discussed. According to a current theory of autobiographical memory, the memory profile may be explained by a lost access to abstract autobiographical knowledge. Given some analogies with the more common transient global amnesia, a mechanism of spreading depression may also be hypothesised for functional FRA. PMID:16191819

  11. 76 FR 34287 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-13

    ... requirements (ICRs) for clearance by the Office of Management and Budget (OMB), FRA is soliciting public... test records... 90 minutes......... 1,050 229.135--Certified Memory Modules 744 Railroads...... 200 certified 2 hours + 200 hours 600 memory modules. for test design. Lead Locomotives w/Certified...

  12. 77 FR 74738 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-17

    ... May 29, 2012, Peter J. Douglas, on behalf of Union Tank Car Company (UTLX), has petitioned the Federal... FRA-2012-0065. UTLX requests relief for cars where the side horizontal handholds are currently in... each corner of each car. Twelve cars are in the process of being constructed that are affected by...

  13. 49 CFR 219.800 - Annual reports.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... perform a service for the railroad. (b) As a railroad, you must use the Management Information System (MIS) form and instructions as required by 49 CFR part 40 (at § 40.25 and appendix H to part 40). You may... submission to FRA. For information on where to submit MIS forms and for the electronic version of the...

  14. 49 CFR 219.800 - Annual reports.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... perform a service for the railroad. (b) As a railroad, you must use the Management Information System (MIS) form and instructions as required by 49 CFR part 40 (at § 40.25 and appendix H to part 40). You may... submission to FRA. For information on where to submit MIS forms and for the electronic version of the...

  15. 75 FR 1547 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2010

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-12

    ... Transportation (DOT). ACTION: Notice of Determination. SUMMARY: Using data from Management Information System... alcohol program data taken from FRA's Management Information System. Based on this data, the Administrator.... DATES: This notice is effective upon publication. FOR FURTHER INFORMATION CONTACT: Lamar Allen,...

  16. 49 CFR Appendix A to Part 237 - Supplemental Statement of Agency Policy on the Safety of Railroad Bridges

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... FRA in 2000 as Appendix C of the Federal Track Safety Standards, 49 CFR Part 213. With the promulgation of 49 CFR Part 237, Bridge Safety Standards, many of the non-regulatory provisions in that Policy... principles and the law of physics. Track owners should use those principles to assess the integrity...

  17. 77 FR 26703 - Inflation Adjustment of the Aggravated Maximum Civil Monetary Penalty for a Violation of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-07

    ... authority. See 77 FR 24416. In preparing that final ] rule for publication, three errors were made as... 24, 2012. See 77 FR 24416. FRA failed to account for an October 31, 2011 amendment to 49 CFR part 228... removed and reserved Sec. 228.21. See 76 FR 67073, 67087-88. In preparing the April 24, 2012, final...

  18. 75 FR 40026 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-13

    ... crossings in the existing Pre-Rule Quiet Zone extending from Elder Road (MP 429.21) to Russell Avenue (MP... any additional risk to public health or safety. There have been only 2 crossing collisions involving... for oral comment, they should notify FRA, in writing, before the end of the comment period and...

  19. 77 FR 53252 - Tier 1 Environmental Impact Statement for the Chicago, IL, to Detroit-Pontiac, MI, Regional...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-31

    ... for the reasonable build alternatives. Identifying, at a corridor planning level, the infrastructure... Federal Railroad Administration Tier 1 Environmental Impact Statement for the Chicago, IL, to Detroit-Pontiac, MI, Regional Passenger Rail System AGENCY: Federal Railroad Administration (FRA), U.S....

  20. 49 CFR Appendix A to Part 237 - Supplemental Statement of Agency Policy on the Safety of Railroad Bridges

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... FRA in 2000 as Appendix C of the Federal Track Safety Standards, 49 CFR Part 213. With the promulgation of 49 CFR Part 237, Bridge Safety Standards, many of the non-regulatory provisions in that Policy... pier reactions as necessary for a comprehensive evaluation and statement of the capacity of a...

  1. 49 CFR Appendix A to Part 214 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... to assess a penalty of up to $100,000 for any violation where circumstances warrant. See 49 CFR part... section numbers from 49 CFR part 214. If more than one item is listed as a type of violation of a given... citations will cite the CFR section and the penalty code, if any. FRA reserves the right, should...

  2. 75 FR 52490 - Track Safety Standards; Concrete Crossties

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-26

    ... alternative for use in modern track. Test sections on various railroads were set up in the 1970s to evaluate... uneconomical. Modern concrete crossties are designed to accept the stresses imposed by irregular rail head... proposes new methodologies for inspection. \\5\\ See 49 CFR 213.335(d). II. Overview of FRA's Railroad...

  3. Associations between Repetitive Questioning, Resistance to Change, Temper Outbursts and Anxiety in Prader-Willi and Fragile-X Syndromes

    ERIC Educational Resources Information Center

    Woodcock, K.; Oliver, C.; Humphreys, G.

    2009-01-01

    Background: The behavioural phenotypes of Prader-Willi (PWS) and Fragile-X (FraX) syndromes both comprise repetitive behaviours with differences between the profiles. In this study we investigated the context and antecedents to the repetitive behaviours and the association with other behavioural phenotypic characteristics in order to generate…

  4. Global forest cover mapping for the United Nations Food and Agriculture Organization forest resources assessment 2000 program

    USGS Publications Warehouse

    Zhu, Z.; Waller, E.

    2003-01-01

    Many countries periodically produce national reports on the status and changes of forest resources, using statistical surveys and spatial mapping of remotely sensed data. At the global level, the Food and Agriculture Organization (FAO) of the United Nations has conducted a Forest Resources Assessment (FRA) program every 10 yr since 1980, producing statistics and analysis that give a global synopsis of forest resources in the world. For the year 2000 of the FRA program (FRA2000), a global forest cover map was produced to provide spatial context to the extensive survey. The forest cover map, produced at the U.S. Geological Survey (USGS) EROS Data Center (EDC), has five classes: closed forest, open or fragmented forest, other wooded land, other land cover, and water. The first two forested classes at the global scale were delineated using combinations of temporal compositing, modified mixture analysis, geographic stratification, and other classification techniques. The remaining three FAO classes were derived primarily from the USGS global land cover characteristics database (Loveland et al. 1999). Validated on the basis of existing reference data sets, the map is estimated to be 77% accurate for the first four classes (no reference data were available for water), and 86% accurate for the forest and nonforest classification. The final map will be published as an insert to the FAO FRA2000 report.

  5. 77 FR 21311 - Locomotive Safety Standards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-09

    .... Alerters are currently required on passenger locomotives pursuant to Sec. 238.237 (67 FR 19991), and are..., 2007 (72 FR 59216). FRA continued to utilize the RSAC process to address additional locomotive safety... text for these issues with minor clarifying modifications on January 12, 2011. See 76 FR 2199. The...

  6. 76 FR 7627 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-10

    ... electronic controls. Electronic airbrake systems began to be introduced in the early 1990s. Due to the clean... electronic air brake equipment. They have also submitted information from WRE supporting combining EPIC.... Waiver Docket Number FRA-2000-7367 (formerly H-95-3), applies to electronic brake systems manufactured...

  7. 76 FR 4250 - Operating Certain Railroad Tank Cars in Excess of 263,000 Pounds Gross Rail Load; Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-25

    ... hazardous materials such as PIH materials (HM-246; 74 FR 1770 (Jan. 13, 2009) (the ``Tank Car Rule'')), FRA... implement a crashworthiness performance standard as discussed in the Tank Car Rule. See 74 FR at 1771. II... record. 75 FR 27205 (Final Rule). The Final Rule titled, Hazardous Materials: Incorporation of...

  8. 76 FR 67020 - Railroad Safety Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-28

    ... the Electronic Device Distraction, Critical Incident, Track Safety Standards, Dark Territory... to FRA on railroad safety matters. The RSAC is composed of 54 voting representatives from 31 member....gov/ . Please refer to the notice published in the Federal Register on March 11, 1996 (61 FR...

  9. 77 FR 19054 - Railroad Safety Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-29

    ... the Track Safety Standards, Critical Incident, Dark Territory, Fatigue Management, Risk Reduction... recommendations to FRA on railroad safety matters. The RSAC is composed of 54 voting representatives from 31....dot.gov/ . Please refer to the notice published in the Federal Register on March 11, 1996 (61 FR...

  10. 77 FR 36603 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-19

    ... comments on the following collection of information was published on April 4, 2012 (77 FR 20478). DATES... ICRs for which the agency was seeking OMB approval. 77 FR 20478. FRA received no comments in response....S.C. 3507 (b)-(c); 5 CFR 1320.12(d); see also 60 FR 44978, 44983, Aug. 29, 1995. OMB believes...

  11. 75 FR 81710 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-28

    ... comments on the following collections of information was published on October 18, 2010 (75 FR 63889). DATES... comment on ICRs that the agency was seeking OMB approval. 75 FR 63889. FRA received no comments after....S.C. 3507 (b)-(c); 5 CFR 1320.12(d); see also 60 FR 44978, 44983, Aug. 29, 1995. OMB believes...

  12. 77 FR 20478 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-04

    ... Appliances). Section 233.5 provides that each railroad must report to FRA within 24 hours after learning of an accident or incident arising from the failure of a signal appliance, device, method, or ] system... departure test test of cab signal, train stop, or train control devices on locomotives before...

  13. 77 FR 35471 - National Environmental Policy Act Implementation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-13

    ... complete Privacy Act Statement in the Federal Register published on April 11, 2000 (65 FR 19477), or visit... Register on May 26, 1999 (64 FR 28545) and are available on the agency's Web site at http://www.fra.dot.gov..., electric traction equipment and structures, electronics, photonics, and communications systems...

  14. 77 FR 23159 - Locomotive Safety Standards; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-18

    ... rule related to locomotive safety standards. See 77 FR 21312. The final rule established a public... safety standards and comments on such petitions. That final rule mistakenly lists FR-2009- 0095... is FRA-2009-0094. The final rule issued on April 9, 2012, incorrectly identified docket number...

  15. 77 FR 3555 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-24

    ... 17, 2011 (76 FR 71432). DATES: Comments must be submitted on or before February 23, 2012. FOR FURTHER... seeking OMB approval. 76 FR 71432. FRA received no comments in response to this notice. Before OMB decides...(d); see also 60 FR 44978, 44983, Aug. 29, 1995. OMB believes that the 30 day notice informs...

  16. A short-filament mutant of Anabaena sp. strain PCC 7120 that fragments in nitrogen-deficient medium.

    PubMed Central

    Bauer, C C; Buikema, W J; Black, K; Haselkorn, R

    1995-01-01

    Strain 129 is a fragmentation mutant of the filamentous cyanobacterium Anabaena sp. strain PCC 7120. Growing with fixed nitrogen, this mutant forms filaments that are much shorter than wild-type filaments. Following starvation for fixed nitrogen, strain 129 becomes nearly unicellular and forms few heterocysts, although electron microscopy suggests that proheterocysts form while fragmentation occurs. Starvation for sulfate, phosphate, iron, and calcium does not cause this fragmentation. The affected gene in strain 129, fraC, was cloned by complementation and characterized. It encodes a unique 179-amino-acid protein rich in phenylalanine. Insertional inactivation of the chromosomal copy of fraC results in a phenotype identical to that of strain 129, while complementation using a truncated version of FraC results in only partial complementation of the original mutant. Heterocysts could be induced to form in N-replete cultures of strain 129, as in wild-type cells, by supplying extra copies of the hetR gene on a plasmid. Thus, FraC is required for the integrity of cell junctions in general but is apparently not directly involved in normal differentiation and nitrogen fixation. PMID:7883709

  17. 78 FR 75442 - Emergency Order Under 49 U.S.C. 20104 Establishing Requirements for Controlling Passenger Train...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-11

    ... railroad safety regulations and the railroad's own operating rules. These factors lead FRA to the... ] involving a hazard of death, personal injury, or significant harm to the environment. Authority Authority to... significant harm to the environment.'' 49 U.S.C. 20104. These orders may immediately impose ``restrictions...

  18. 75 FR 4703 - Track Safety Standards; Continuous Welded Rail (CWR)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-29

    ..., including common law, regulation, or order. Part 213 establishes Federal standards of care that preempt... (74 FR 42988). FRA published a correcting amendment on October 21, 2009, which added compliance dates... policies and procedures (44 FR 11034, Feb. 26, 1979). The original final rule was determined to be...

  19. 77 FR 14976 - Approval and Promulgation of Implementation Plans; Tennessee; 110(a)(1) and (2) Infrastructure...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-14

    ... NSR Update) recognizing nitrogen oxide (NOx) as an ozone precursor, among other elements. See 70 FR...(a)(2)(C) and (J) for the 1997 8-hour ozone NAAQS by March 1, 2008. See 73 FR 16205. Specifically... May 28, 2009, SIP revision. See 77 FR 6016. The May 28, 2009, submission was one of two required...

  20. 49 CFR 229.209 - Alternative locomotive crashworthiness designs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Alternative locomotive crashworthiness designs... Locomotive Crashworthiness Design Requirements § 229.209 Alternative locomotive crashworthiness designs. (a... locomotive crashworthiness designs which are not consistent with any FRA-approved locomotive...

  1. 76 FR 38455 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-30

    ... dated October 12, 2010, the Sacramento Regional Transit District (SRTD) has petitioned the Federal.... By letters dated October 12, 2010, and February 24, 2011, SRTD has petitioned FRA to extend the terms... that share corridors, including highway-rail grade crossings, with the Union Pacific Railroad....

  2. 75 FR 39617 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-09

    ... requirements for existing cabooses'' because of the high costs of FRA Type I and Type II Glazing, as opposed to the very low incidences of vandalism. MIDH operates its own rail line between Middletown and Hummelstown, Pennsylvania, a distance of approximately 7 miles. The maximum passenger train speed is 15...

  3. Determining the dispersion characteristics of rivers from the frequency response of the system

    NASA Astrophysics Data System (ADS)

    Lambertz, Peter; Palancar, MaríA. C.; Aragón, José M.; Gil, Roberto

    2006-09-01

    A new method of determining the parameters of an aggregated dead zone model (ADZ) to predict longitudinal dispersion in rivers is presented. The method is based on the frequency response analysis (FRA) of observed field tests, which consist of tracer injections (input) and measurement of tracer in downstream sampling points (output) located downstream from the injection point. The ADZ is a combination of plug and completely mixed flow compartments. The ADZ parameters (number of compartments, mean residence time, and delay time) are evaluated by means of Bode plots that give the system order (number of compartments), gain, time constant (mean residence time of each compartment) and delay time. The FRA-ADZ method was checked with tracer data runs in two Spanish rivers, the Tagus and the Ebro rivers. The experimental tracer concentration versus time distributions were compared with the ADZ predicted curves, which were calculated using parameters obtained from the FRA method, and with curves predicted by several classical models. The residence time of several reaches within the two studied rivers was predicted by the FRA-ADZ method with a relative error lower than 10%. The method is generally applicable to ideal and nonideal inputs and is particularly well suited to arbitrary-shaped initial source concentration distributions.

  4. 78 FR 44189 - Petition for Modification of Single Car Air Brake Test Procedures

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ..., 2000 (65 FR 19477). Robert C. Lauby, Deputy Associate Administrator for Regulatory and Legislative... Federal Railroad Administration Petition for Modification of Single Car Air Brake Test Procedures In... the Federal Railroad Administration (FRA) per 49 CFR 232.307 to modify the single car air brake...

  5. 49 CFR 211.45 - Petitions for emergency waiver of safety rules.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... radiological, chemical, explosive, or biological material, or a war-related activity, that poses a risk of..., regional, or national in scope. (b) Emergency Relief Docket. Each calendar year FRA creates an Emergency... 24 hours a day, seven days a week, via the Internet at the docket's Web site at...

  6. 49 CFR 211.45 - Petitions for emergency waiver of safety rules.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... radiological, chemical, explosive, or biological material, or a war-related activity, that poses a risk of..., regional, or national in scope. (b) Emergency Relief Docket. Each calendar year FRA creates an Emergency... 24 hours a day, seven days a week, via the Internet at the docket's Web site at...

  7. 49 CFR 211.45 - Petitions for emergency waiver of safety rules.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... radiological, chemical, explosive, or biological material, or a war-related activity, that poses a risk of..., regional, or national in scope. (b) Emergency Relief Docket. Each calendar year FRA creates an Emergency... 24 hours a day, seven days a week, via the Internet at the docket's Web site at...

  8. 78 FR 58829 - Second Interim Statement of Agency Policy and Interpretation on the Hours of Service Laws as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-24

    ... Amended; Response to Public Comment'' published at 77 FR 12408-31 (February 29, 2012). Freight train... Amended; Proposed Interpretation; Request for Public Comment'' published at 74 FR 30665-77 (June 26, 2009... laws as amended by the RSIA (the new HS laws). 74 FR 30665 (June 26, 2009). Subsequently FRA...

  9. 77 FR 60169 - Safety Advisory 2012-04; Worn Rail Conditions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-02

    ... rail with severe rail head wear and rolling contact fatigue (RCF) conditions. FRA is issuing this... significant vertical head loss (rail head wear) and gage-side-oriented RCF. This notice contains... comply with the requirements of the applicable engineering procedures that address critical rail...

  10. 49 CFR 213.119 - Continuous welded rail (CWR); plan contents.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... arrangement in the CWR plans. (7) Specify the recordkeeping requirements related to joint bars in CWR... paragraphs (h)(1) through (h)(7) of this section, a track owner may seek approval from FRA to use alternate...)(1) through (h)(7) of this section, the Associate Administrator will approve the alternate...

  11. 49 CFR Table 3 of Subpart B to... - Alternative Schedule for Application of Retroreflective Material to Freight Cars per § 224.107(a...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., DEPARTMENT OF TRANSPORTATION REFLECTORIZATION OF RAIL FREIGHT ROLLING STOCK Pt. 224, Subpt. B, Table 3 Table... freight rolling stock owner shall submit to FRA an updated Reflectorization Implementation Compliance... requirements of this section have not been met— (1) The freight rolling stock owner shall be considered...

  12. 76 FR 15362 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-21

    ... soliciting comments on the following collection of information was published on January 13, 2011 (76 FR 2441... approval. 76 FR 2441. FRA received no comments in response to this notice. Before OMB decides whether to... also 60 FR 44978, 44983, Aug. 29, 1995. OMB believes that the 30 day notice informs the...

  13. 49 CFR 223.5 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...”. Emergency window means the segment of a side-facing glazing panel that has been designed to permit rapid and... location or a side facing location shall be considered a front facing location. FRA means the Federal Railroad Administration. Locomotive means a self-propelled unit of equipment designed primarily for...

  14. 76 FR 69801 - Conductor Certification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-09

    ... Federal Register on November 10, 2010. See 75 FR 69166. In the NPRM, FRA solicited public comment on the... (75 FR 69166, 69170 (Nov. 10, 2010)) and in the section-by-section analysis to this final rule: Under....105(c)(1)-(3), a railroad may test and evaluate its designated conductors under subpart B before...

  15. 75 FR 59579 - Restrictions on Railroad Operating Employees' Use of Cellular Telephones and Other Electronic...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-27

    ... electronic devices by railroad operating employees. 75 FR 27672 (May 18, 2010). The NPRM proposed to codify many of the requirements of Emergency Order 26 (Order or EO 26, 73 FR 58702 (Oct. 7, 2008)), but... telephones and other electronic devices while on duty. (73 FR 58702, Oct. 7, 2008). This FRA action was...

  16. 76 FR 2199 - Locomotive Safety Standards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-12

    ... methods: Web Site: Federal eRulemaking Portal, http://www.regulations.gov . Follow the online instructions.... and 5 p.m. Monday through Friday, except Federal holidays. Federal eRulemaking Portal: Go to http... October 19, 2007 (72 FR 59216). FRA continued to utilize the RSAC process to address additional...

  17. The lunar highland melt-rock suite

    NASA Technical Reports Server (NTRS)

    Vaniman, D. T.; Papike, J. J.

    1978-01-01

    Size can be used as a criterion to select 18 large (larger than 1 cm) samples from among 148 melt-rock fragments of all sizes. This selection provides a suite of large samples which represent the important chemical variants among highland melt rocks; each large sample has enough material for a number of sample-destructive studies, as well as for future reference. Cluster analysis of the total data base of 148 highland melt rocks shows six distinct groups: anorthosite, gabbroic anorthosite, anorthositic gabbro ('highland basalt'), low K Fra Mauro, intermediate-K Fra Mauro, and high-K. Large samples are available for four of the melt-rock groups (gabbroic anorthosite, anorthositic gabbro, low-K Fra Mauro, and intermediate-K Fra Mauro). This sample selection reveals two subgroups of anorthositic gabbro (one anorthite-poor with negative Eu anomaly and one anorthite-rich without Eu anomaly). There is a sharp distinction between those Apollo 16 melt rocks and glasses which have both been classified as 'gabbroic anorthosite'.

  18. 76 FR 41555 - Tupelo, Mississippi Railroad Relocation Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-14

    ... Environmental Quality NEPA implementing regulations, 40 CFR Parts 1500-1508, and the FRA NEPA procedures, 64 FR... Federal Railroad Administration Tupelo, Mississippi Railroad Relocation Project AGENCY: Federal Railroad... Environmental Impact Statement and public hearing for the Tupelo, Mississippi Railroad Relocation...

  19. 75 FR 61552 - Federal Railroad Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... Federal Railroad Administration Notice of Informational Filing In accordance with Section 236.913 of Title 49 of the Code of Federal Regulations (CFR), notice is hereby given that the Federal Railroad Administration (FRA) has received an informational filing from the Northeast Illinois Regional Commuter...

  20. 78 FR 16414 - Systems for Telephonic Notification of Unsafe Conditions at Highway-Rail and Pathway Grade Crossings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-15

    ...) or ENS programs. On March 4, 2011, FRA issued a notice of proposed rulemaking (NPRM) (76 FR 11992... conditions at crossings. See 76 FR 11992. A public hearing on the proposal was held on September 29, ] 2011. 76 FR 55622(Sept. 8, 2011). On June 12, 2012, following consideration of written comments received...