Science.gov

Sample records for genstande fra forskningscenter

  1. Elevated Fra-1 expression causes severe lipodystrophy.

    PubMed

    Luther, Julia; Driessler, Frank; Megges, Matthias; Hess, Andreas; Herbort, Bettina; Mandic, Vice; Zaiss, Mario M; Reichardt, Anne; Zech, Christine; Tuckermann, Jan P; Calkhoven, Cornelis F; Wagner, Erwin F; Schett, Georg; David, Jean-Pierre

    2011-05-01

    A shift from osteoblastogenesis to adipogenesis is one of the underlying mechanisms of decreased bone mass and increased fat during aging. We now uncover a new role for the transcription factor Fra-1 in suppressing adipogenesis. Indeed, Fra1 (Fosl1) transgenic (Fra1tg) mice, which developed progressive osteosclerosis as a result of accelerated osteoblast differentiation, also developed a severe general lipodystrophy. The residual fat of these mice appeared immature and expressed lower levels of adipogenic markers, including the fatty acid transporter Cd36 and the CCAAT/enhancer binding protein Cebpa. Consequently accumulation of triglycerides and free fatty acids were detected in the serum of fasting Fra1tg mice. Fra-1 acts cell autonomously because the adipogenic differentiation of Fra1 transgenic primary osteoblasts was drastically reduced, and overexpression of Fra-1 in an adipogenic cell line blocked their differentiation into adipocytes. Strikingly, Cebpa was downregulated in the Fra-1-overexpressing cells and Fra-1 could bind to the Cebpa promoter and directly suppress its activity. Thus, our data add to the known common systemic control of fat and bone mass, a new cell-autonomous level of control of cell fate decision by which the osteogenic transcription factor Fra-1 opposes adipocyte differentiation by inhibiting C/EBPα. PMID:21486951

  2. 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

  3. Experimental Investigation on FRA Diagnosis of Transformer Faults

    NASA Astrophysics Data System (ADS)

    Sano, Takahiro; Miyagi, Katsunori

    The need for economical, reliable and effective delivery of electric power leads to the search for new, efficient and effective methods for diagnosing the high voltage equipments in the industries all over the world. As the average usage period of transformers increases, the necessity to know the internal condition of transformers is increasing. It is therefore critically important to establish monitoring and diagnostic techniques that can perform transformer condition assessment. Frequency response analysis, generally known as FRA, is one of the technologies to diagnose transformers. Using case studies, this paper presents the effectiveness of FRA as measurements for detecting transformer faults. This paper introduces the fact that FRA waveforms have useful information about diagnosis of fault on winding shield and core earths, and that the condition outside transformers can affect frequency response characteristics. The FRA measurement results are further investigated through a simulation study using a computer model.

  4. 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...

  5. 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...

  6. 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...

  7. 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

    ... Register (75 FR 224) announcing the Union Pacific Railroad's request for an amendment to their existing... Administration (FRA) published a notice in the Federal Register (76 FR 10087) announcing the CSX Transportation... submitted on behalf of an association, business, labor union, etc.). You may review DOT's complete...

  8. 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

    ... Headquarters is: 300 West Adams Street, Rm 310, Chicago, Illinois 60606. The fax number is 312-886-9634. The E...-3804. The E-mail address of the Regional Administrator for Region 5 is: John.Megary@fra.dot.gov....

  9. 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

    ... Headquarters is: 300 West Adams Street, Rm 310, Chicago, Illinois 60606. The fax number is 312-886-9634. The E...-3804. The E-mail address of the Regional Administrator for Region 5 is: John.Megary@fra.dot.gov....

  10. 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

    ... Headquarters is: 300 West Adams Street, Rm 310, Chicago, Illinois 60606. The fax number is 312-886-9634. The E...-3804. The E-mail address of the Regional Administrator for Region 5 is: John.Megary@fra.dot.gov....

  11. 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

    ... Headquarters is: 300 West Adams Street, Rm 310, Chicago, Illinois 60606. The fax number is 312-886-9634. The E...-3804. The E-mail address of the Regional Administrator for Region 5 is: John.Megary@fra.dot.gov....

  12. 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

    ... Headquarters is: 300 West Adams Street, Rm 310, Chicago, Illinois 60606. The fax number is 312-886-9634. The E...-3804. The E-mail address of the Regional Administrator for Region 5 is: John.Megary@fra.dot.gov....

  13. 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

  14. Transmission of the fra(X) haplotype from three nonpenetrant brothers to their affected grandsons.

    PubMed

    Kirkilionis, A J; Chudley, A E; Greenberg, C R; Yan, D L; McGillivray, B; Hamerton, J L

    1992-06-01

    We report on a family showing transmission of the fra(X) gene by 3 nonpenetrant, fra(X) negative, normally intelligent, full and half-brothers to their affected grandsons. The mothers of the affected boys are obligate carriers, fra(X) negative, and of normal intelligence. This family illustrates the "Sherman Paradox" and is compatible with the predictions of the Laird X-inactivation imprinting model. In addition, molecular and/or cytogenetic studies have enabled at-risk relatives to learn more about their carrier fra(X) status and have allowed for more accurate genetic counselling. PMID:1605253

  15. 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

  16. 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

  17. 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

  18. 49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false FRA Freight Car Standards Defect Code C Appendix C to Part 215 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Pt. 215, App. C Appendix C to Part 215—FRA Freight Car...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. News and views on EMT Fra-1 controls EMT in mammary epithelial cells

    PubMed Central

    Bakiri, Latifa; Wagner, Erwin F.

    2016-01-01

    Epithelial-to-mesenchymal transition (EMT), a process critical for breast cancer cell dissemination, engages the Fos-related antigen 1 (Fra-1) transcription factor. Molecular and cellular analyses revealed an evolutionary conservation of Fra-1 functions in EMT of mouse and human mammary cells, establishing a solid basis for preclinical studies in genetically engineered mouse models.

  5. 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.

  6. 49 CFR Appendix C to Part 209 - FRA's Policy Statement Concerning Small Entities

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) 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...

  7. 49 CFR Appendix C to Part 209 - FRA's Policy Statement Concerning Small Entities

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false FRA's Policy Statement Concerning Small Entities C Appendix C to Part 209 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY ENFORCEMENT PROCEDURES Pt. 209, App. C Appendix C to Part 209—FRA's...

  8. 49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false FRA Administrator's determination of random drug... (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random...

  9. Fra-2/AP-1 controls bone formation by regulating osteoblast differentiation and collagen production.

    PubMed

    Bozec, Aline; Bakiri, Latifa; Jimenez, Maria; Schinke, Thorsten; Amling, Michael; Wagner, Erwin F

    2010-09-20

    The activator protein-1 (AP-1) transcription factor complex, in particular the Fos proteins, is an important regulator of bone homeostasis. Fra-2 (Fosl2), a Fos-related protein of the AP-1 family, is expressed in bone cells, and newborn mice lacking Fra-2 exhibit defects in chondrocytes and osteoclasts. Here we show that Fra-2-deficient osteoblasts display a differentiation defect both in vivo and in vitro. Moreover, Fra-2-overexpressing mice are osteosclerotic because of increased differentiation of osteoblasts, which appears to be cell autonomous. Importantly, the osteoblast-specific osteocalcin (Oc) gene and collagen1α2 (col1α2) are transcriptional targets of Fra-2 in both murine and human bone cells. In addition, Fra-2, Oc, and col1 are expressed in stromal cells of human chondroblastic and osteoblastic osteosarcomas (Os's) as well as during osteoblast differentiation of human Os cell lines. These findings reveal a novel function of Fra-2/AP-1 as a positive regulator of bone and matrix formation in mice and humans. PMID:20837772

  10. 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

    ... ICR, with applicable supporting documentation, may be obtained by calling FRA's Clearance Officers, Mr... toll-free. A copy of this ICR may also be obtained electronically by contacting Mr. Brogan at...

  11. 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

  12. FRaC: a feature-modeling approach for semi-supervised and unsupervised anomaly detection

    PubMed Central

    Brodley, Carla; Slonim, Donna

    2011-01-01

    Anomaly detection involves identifying rare data instances (anomalies) that come from a different class or distribution than the majority (which are simply called “normal” instances). Given a training set of only normal data, the semi-supervised anomaly detection task is to identify anomalies in the future. Good solutions to this task have applications in fraud and intrusion detection. The unsupervised anomaly detection task is different: Given unlabeled, mostly-normal data, identify the anomalies among them. Many real-world machine learning tasks, including many fraud and intrusion detection tasks, are unsupervised because it is impractical (or impossible) to verify all of the training data. We recently presented FRaC, a new approach for semi-supervised anomaly detection. FRaC is based on using normal instances to build an ensemble of feature models, and then identifying instances that disagree with those models as anomalous. In this paper, we investigate the behavior of FRaC experimentally and explain why FRaC is so successful. We also show that FRaC is a superior approach for the unsupervised as well as the semi-supervised anomaly detection task, compared to well-known state-of-the-art anomaly detection methods, LOF and one-class support vector machines, and to an existing feature-modeling approach. PMID:22639542

  13. Fra(10)(q25): the BrdU effect is substitution-dependent.

    PubMed Central

    Gollin, S M; Holmquist, G P; Ledbetter, D H

    1985-01-01

    Expression in the majority of fra(10)(q25) cases is either induced or enhanced by the presence of bromodeoxyuridine (BrdU) in the culture medium. BrdU is known to exert its effects on cells via two primary mechanisms: substitution-dependent and concentration-dependent. BrdU incorporation into DNA and BrdU concentration in the culture medium can be resolved as independent variables. The results of such experiments indicate that at three fixed levels of BrdU substitution, 100-fold variation of BrdU concentration had little or no effect on fra(10)(q25) expression. At a fixed BrdU concentration, the level of fra(10)(q25) expression rises as a function of increased BrdU substitution, approaching 100% expression at 100% substitution. Thus, BrdU induction or enhancement of fra(10)(q25) expression is clearly substitution-dependent. Iododeoxyuridine, another halogenated pyrimidine, has a similar effect. The critical time of incorporation is between 8 and 9 hrs before mitosis. After this time, removal of BrdU (and fluorodeoxyuridine [FdU]) from the culture medium followed by addition of deoxythymidine does not reverse the BrdU effect on fra(10)(q25) expression. PMID:3976659

  14. Transcriptional activation of the fra-1 gene by AP-1 is mediated by regulatory sequences in the first intron.

    PubMed Central

    Bergers, G; Graninger, P; Braselmann, S; Wrighton, C; Busslinger, M

    1995-01-01

    Constitutive expression of c-Fos, FosB, Fra-1, or c-Jun in rat fibroblasts leads to up-regulation of the immediate-early gene fra-1. Using the posttranslational FosER induction system, we demonstrate that this AP-1-dependent stimulation of fra-1 expression is rapid, depends on a functional DNA-binding domain of FosER, and is a general phenomenon observed in different cell types. In vitro mutagenesis and functional analysis of the rat fra-1 gene in stably transfected Rat-1A-FosER fibroblasts indicated that basal and AP-1-regulated expression of the fra-1 gene depends on regulatory sequences in the first intron which comprise a consensus AP-1 site and two AP-1-like elements. We have also investigated the transactivating and transforming properties of the Fra-1 protein to address the significance of fra-1 up-regulation. The entire Fra-1 protein fused to the DNA-binding domain of Ga14 is shown to lack any transactivation function, and yet it possesses oncogenic potential, as overexpression of Fra-1 in established rat fibroblasts results in anchorage-independent growth in vitro and tumor development in athymic mice, fra-1 is therefore not only induced by members of the Fos family, but its gene product may also contribute to cellular transformation by these proteins. Together, these data identify fra-1 as a unique member of the fos gene family which is under positive control by AP-1 activity. PMID:7791782

  15. Role of heterodimerization of c-Fos and Fra1 proteins in osteoclast differentiation.

    PubMed

    Bakiri, Latifa; Takada, Yasunari; Radolf, Martin; Eferl, Robert; Yaniv, Moshe; Wagner, Erwin F; Matsuo, Koichi

    2007-04-01

    Bone resorbing osteoclasts are specialized macrophages that cannot differentiate in the absence of c-Fos, a member of the dimeric transcription factor AP-1 (activator protein-1). However, osteoclast differentiation in the absence of c-Fos can be rescued in vitro and in vivo by Fra1, a Fos-like protein and transcriptional target of c-Fos. To enable AP-1 proteins binding to DNA, c-Fos or Fra1 must heterodimerize with a partner such as c-Jun, JunB and JunD. In this study, we investigated the dimerization partners of c-Fos and Fra1 required for osteoclast differentiation using synthetic "single-chain" AP-1 dimers in which c-Fos or Fra1 is tethered via a linker to Jun proteins. When c-Fos was analyzed in combination with any Jun protein, including a c-Jun mutant lacking major phosphorylation sites for c-Jun amino-terminal kinase (JNK), osteoclasts were efficiently formed from c-Fos-deficient hematopoietic precursors. However, Fra1 in combination with any Jun protein could not rescue osteoclastogenesis. The ability to rescue was compared to transcriptional activity measured in transient transfection assays using promoters driven by consensus AP-1 sites or a composite AP-1/NFAT binding site. These data show that a single Jun/c-Fos dimer is sufficient for osteoclast differentiation, likely due to its transactivation ability for a broader range of promoters, in particular consensus AP-1 sites. We propose that Fra1 together with a dimerization partner different from Jun proteins can rescue osteoclast differentiation in c-Fos-deficient precursors. PMID:17189721

  16. 49 CFR 229.207 - New locomotive crashworthiness design standards and changes to existing FRA-approved locomotive...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...-approved locomotive crashworthiness design standards. (a) General. The following procedures govern... approval of a locomotive crashworthiness design standard must be titled “Petition for FRA Approval of a New... petition for approval of a substantive change to an FRA-approved locomotive crashworthiness design...

  17. 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...

  18. 49 CFR 229.207 - New locomotive crashworthiness design standards and changes to existing FRA-approved locomotive...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false New locomotive crashworthiness design standards... Design Requirements § 229.207 New locomotive crashworthiness design standards and changes to existing FRA... consideration and action upon requests for FRA approval of new locomotive crashworthiness design standards...

  19. 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

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Analysis of work schedules; submissions; FRA... Employees Engaged in Commuter or Intercity Rail Passenger Transportation § 228.407 Analysis of work schedules; submissions; FRA review and approval of submissions; fatigue mitigation plans. (a) Analysis...

  20. Expression profiling of genes regulated by Fra-1/AP-1 transcription factor during bleomycin-induced pulmonary fibrosis

    PubMed Central

    2013-01-01

    Background The Fra-1/AP-1 transcription factor regulates the expression of genes controlling various processes including migration, invasion, and survival as well as extracellular remodeling. We recently demonstrated that loss of Fra-1 leads to exacerbated bleomycin-induced pulmonary fibrosis, accompanied by enhanced expression of various inflammatory and fibrotic genes. To better understand the molecular mechanisms by which Fra-1 confers protection during bleomycin-induced lung injury, genome-wide mRNA expression profiling was performed. Results We found that Fra-1 regulates gene expression programs that include: 1) several cytokines and chemokines involved in inflammation, 2) several genes involved in the extracellular remodeling and cell adhesion, and 3) several genes involved in programmed cell death. Conclusion Loss of Fra-1 leads to the enhanced expression of genes regulating inflammation and immune responses and decreased the expression of genes involved in apoptosis, suggesting that this transcription factor distinctly modulates early pro-fibrotic cellular responses. PMID:23758685

  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 209 - FRA's Policy Statement Concerning Small Entities

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... hazardous materials shippers meeting the economic criteria established for Class III railroads in 49 CFR... described in Appendix A to 49 CFR part 209, it is FRA's policy to consider a variety of factors in... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY ENFORCEMENT PROCEDURES Pt. 209,...

  4. 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

    ...Under this Notice, the FRA is soliciting applications from interested and responsible parties for two grants: (1) To conduct a Locomotive Biofuel Study, and (2) to conduct a Study of the Use of Bio- based Technologies (Lubricants) that can be used in locomotives, rolling stock and other rail...

  5. 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

    ... Buy America & FRA's High-Speed Intercity Passenger Rail Program AGENCY: Federal Railroad...'s High Speed Intercity ] Passenger Rail Program. The Answers to Frequently Asked Questions can be... to support intercity passenger rail service (Sec. 301), high-speed corridor development (Sec....

  6. 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.

  7. 49 CFR Appendix C to Part 209 - FRA's Policy Statement Concerning Small Entities

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... hazardous materials shippers meeting the economic criteria established for Class III railroads in 49 CFR... described in Appendix A to 49 CFR part 209, it is FRA's policy to consider a variety of factors in... provide oral and written responses to questions raised by small entities concerning the plain meaning...

  8. 49 CFR Appendix C to Part 209 - FRA's Policy Statement Concerning Small Entities

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... hazardous materials shippers meeting the economic criteria established for Class III railroads in 49 CFR... described in Appendix A to 49 CFR part 209, it is FRA's policy to consider a variety of factors in... provide oral and written responses to questions raised by small entities concerning the plain meaning...

  9. 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...

  10. 49 CFR 219.608 - FRA Administrator's determination of random alcohol testing rate.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.608 FRA Administrator's determination of random alcohol... random selection, with each pool containing the covered employees who are subject to testing at the...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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)...

  17. FRA2A is a CGG repeat expansion associated with silencing of AFF3.

    PubMed

    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

    2014-04-01

    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

  18. 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

  19. 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

  20. 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

  1. Osteoblast-specific expression of Fra-2/AP-1 controls adiponectin and osteocalcin expression and affects metabolism.

    PubMed

    Bozec, Aline; Bakiri, Latifa; Jimenez, Maria; Rosen, Evan D; Catalá-Lehnen, Philip; Schinke, Thorsten; Schett, Georg; Amling, Michael; Wagner, Erwin F

    2013-12-01

    Recent studies have established that the skeleton functions as an endocrine organ affecting metabolism through the osteoblast-derived hormone osteocalcin (Ocn). However, it is not fully understood how many transcription factors expressed in osteoblasts regulate the endocrine function. Here, we show that mice with osteoblast-specific deletion of Fra-2 (Fosl2) have low bone mass but increased body weight. In contrast, transgenic expression of Fra-2 in osteoblasts leads to increased bone mass and decreased body weight accompanied by reduced serum glucose and insulin levels, improved glucose tolerance and insulin sensitivity. In addition, mice lacking Fra-2 have reduced levels of circulating Ocn, but high adiponectin (Adipoq), whereas Fra-2 transgenic mice exhibit high Ocn and low Adipoq levels. Moreover, we found that Adipoq was expressed in osteoblasts and that this expression was transcriptionally repressed by Fra-2. These results demonstrate that Fra-2 expression in osteoblasts represents a novel paradigm for a transcription factor controlling the endocrine function of the skeleton. PMID:24046454

  2. The Strawberry Pathogenesis-related 10 (PR-10) Fra a Proteins Control Flavonoid Biosynthesis by Binding to Metabolic Intermediates*

    PubMed Central

    Casañal, Ana; Zander, Ulrich; Muñoz, Cristina; Dupeux, Florine; Luque, Irene; Botella, Miguel Angel; Schwab, Wilfried; Valpuesta, Victoriano; Marquez, José A.

    2013-01-01

    Pathogenesis-related 10 (PR-10) proteins are involved in many aspects of plant biology but their molecular function is still unclear. They are related by sequence and structural homology to mammalian lipid transport and plant abscisic acid receptor proteins and are predicted to have cavities for ligand binding. Recently, three new members of the PR-10 family, the Fra a proteins, have been identified in strawberry, where they are required for the activity of the flavonoid biosynthesis pathway, which is essential for the development of color and flavor in fruits. Here, we show that Fra a proteins bind natural flavonoids with different selectivity and affinities in the low μm range. The structural analysis of Fra a 1 E and a Fra a 3-catechin complex indicates that loops L3, L5, and L7 surrounding the ligand-binding cavity show significant flexibility in the apo forms but close over the ligand in the Fra a 3-catechin complex. Our findings provide mechanistic insight on the function of Fra a proteins and suggest that PR-10 proteins, which are widespread in plants, may play a role in the control of secondary metabolic pathways by binding to metabolic intermediates. PMID:24133217

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

    PubMed

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

    2015-02-01

    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

  4. 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

  5. Dual role for mitogen-activated protein kinase (Erk) in insulin-dependent regulation of Fra-1 (fos-related antigen-1) transcription and phosphorylation.

    PubMed Central

    Hurd, Toby W; Culbert, Ainsley A; Webster, Kenneth J; Tavaré, Jeremy M

    2002-01-01

    Insulin regulates the activity of the AP-1 (activator protein-1) transcriptional complex in several cell types. One component of the AP-1 complex is the transcription factor Fra-1 (fos-related antigen-1), and we have demonstrated previously that insulin stimulates the expression of Fra-1 mRNA in CHO.T cells [Griffiths, Black, Culbert, Dickens, Shaw, Gillespie and Tavaré (1998) Biochem. J. 335, 19-26]. Here we demonstrate that insulin stimulates the activity of a fra-1 promoter linked to a luciferase reporter gene, indicating that the ability of insulin to induce expression of Fra-1 mRNA is due, at least in part, to an increase in gene transcription. Furthermore, we found that insulin induces the serine phosphorylation of Fra-1 and reduces its mobility during SDS/PAGE as a result of phosphorylation. The ability of insulin to induce the accumulation of Fra-1 mRNA, stimulate the fra-1 promoter and stimulate phosphorylation of Fra-1 all require the mitogen-activated protein (MAP) kinase cascade, which leads to the activation of extracellular-signal-regulated kinase (Erk) 1/2. Consequently, our results demonstrate that the Erk cascade plays a dual role in the co-ordinated regulation of the transcription and the phosphorylation of Fra-1 by insulin. PMID:12197835

  6. 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.

  7. Pores of the toxin FraC assemble into 2D hexagonal clusters in both crystal structures and model membranes.

    PubMed

    Mechaly, Ariel E; Bellomio, Augusto; Morante, Koldo; Agirre, Jon; Gil-Cartón, David; Valle, Mikel; González-Mañas, Juan Manuel; Guérin, Diego M A

    2012-11-01

    The recent high-resolution structure of the toxin FraC derived from the sea anemone Actinia fragacea has provided new insight into the mechanism of pore formation by actinoporins. In this work, we report two new crystal forms of FraC in its oligomeric prepore conformation. Together with the previously reported structure, these two new structures reveal that ring-like nonamers of the toxin assemble into compact two-dimensional hexagonal arrays. This supramolecular organization is maintained in different relative orientations adopted by the oligomers within the crystal layers. Analyses of the aggregation of FraC pores in both planar and curved (vesicles) model membranes show similar 2D hexagonal arrangements. Our observations support a model in which hexagonal pore-packing is a clustering mechanism that maximizes toxin-driven membrane damage in the target cell. PMID:22728830

  8. FRA-1 as a driver of tumour heterogeneity: a nexus between oncogenes and embryonic signalling pathways in cancer.

    PubMed

    Dhillon, A S; Tulchinsky, E

    2015-08-20

    Tumour heterogeneity is a major factor undermining the success of therapies targeting metastatic cancer. Two major theories are thought to explain the phenomenon of heterogeneity in cancer--clonal evolution and cell plasticity. In this review, we examine a growing body of work implicating the transcription factor FOS-related antigen 1 (FRA-1) as a central node in tumour cell plasticity networks, and discuss mechanisms regulating its activity in cancer cells. We also discuss evidence from the FRA-1 perspective supporting the notion that clonal selection and cell plasticity represent two sides of the same coin. We propose that FRA-1-overexpressing clones featuring high plasticity undergo positive selection during consecutive stages of multistep tumour progression. This model underscores a potential mechanism through which tumour cells retaining elevated levels of plasticity acquire a selective advantage over other clonal populations within a tumour. PMID:25381818

  9. Terminal epidermal differentiation is regulated by the interaction of Fra-2/AP-1 with Ezh2 and ERK1/2

    PubMed Central

    Wurm, Stefanie; Zhang, Jisheng; Guinea-Viniegra, Juan; García, Fernando; Muñoz, Javier; Bakiri, Latifa; Ezhkova, Elena

    2015-01-01

    Altered epidermal differentiation characterizes numerous skin diseases affecting >25% of the human population. Here we identified Fra-2/AP-1 as a key regulator of terminal epidermal differentiation. Epithelial-restricted, ectopic expression of Fra-2 induced expression of epidermal differentiation genes located within the epidermal differentiation complex (EDC). Moreover, in a papilloma-prone background, a reduced tumor burden was observed due to precocious keratinocyte differentiation by Fra-2 expression. Importantly, loss of Fra-2 in suprabasal keratinocytes is sufficient to cause skin barrier defects due to reduced expression of differentiation genes. Mechanistically, Fra-2 binds and transcriptionally regulates EDC gene promoters, which are co-occupied by the transcriptional repressor Ezh2. Fra-2 remains transcriptionally inactive in nondifferentiated keratinocytes, where it was found monomethylated and dimethylated on Lys104 and interacted with Ezh2. Upon keratinocyte differentiation, Fra-2 is C-terminally phosphorylated on Ser320 and Thr322 by ERK1/2, leading to transcriptional activation. Thus, the induction of epidermal differentiation by Fra-2 is controlled by a dual mechanism involving Ezh2-dependent methylation and activation by ERK1/2-dependent phosphorylation. PMID:25547114

  10. Terminal epidermal differentiation is regulated by the interaction of Fra-2/AP-1 with Ezh2 and ERK1/2.

    PubMed

    Wurm, Stefanie; Zhang, Jisheng; Guinea-Viniegra, Juan; García, Fernando; Muñoz, Javier; Bakiri, Latifa; Ezhkova, Elena; Wagner, Erwin F

    2015-01-15

    Altered epidermal differentiation characterizes numerous skin diseases affecting >25% of the human population. Here we identified Fra-2/AP-1 as a key regulator of terminal epidermal differentiation. Epithelial-restricted, ectopic expression of Fra-2 induced expression of epidermal differentiation genes located within the epidermal differentiation complex (EDC). Moreover, in a papilloma-prone background, a reduced tumor burden was observed due to precocious keratinocyte differentiation by Fra-2 expression. Importantly, loss of Fra-2 in suprabasal keratinocytes is sufficient to cause skin barrier defects due to reduced expression of differentiation genes. Mechanistically, Fra-2 binds and transcriptionally regulates EDC gene promoters, which are co-occupied by the transcriptional repressor Ezh2. Fra-2 remains transcriptionally inactive in nondifferentiated keratinocytes, where it was found monomethylated and dimethylated on Lys104 and interacted with Ezh2. Upon keratinocyte differentiation, Fra-2 is C-terminally phosphorylated on Ser320 and Thr322 by ERK1/2, leading to transcriptional activation. Thus, the induction of epidermal differentiation by Fra-2 is controlled by a dual mechanism involving Ezh2-dependent methylation and activation by ERK1/2-dependent phosphorylation. PMID:25547114

  11. 49 CFR Appendix F to Part 236 - Minimum Requirements of FRA Directed Independent Third-Party Assessment of PTC System Safety...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Minimum Requirements of FRA Directed Independent... F to Part 236—Minimum Requirements of FRA Directed Independent Third-Party Assessment of PTC System... independent third-party assessment of PTC system safety verification and validation pursuant to subpart H or...

  12. 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

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Minimum Requirements of FRA Directed Independent... F to Part 236—Minimum Requirements of FRA Directed Independent Third-Party Assessment of PTC System... independent third-party assessment of PTC system safety verification and validation pursuant to subpart H or...

  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, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Minimum Requirements of FRA Directed Independent... F to Part 236—Minimum Requirements of FRA Directed Independent Third-Party Assessment of PTC System... independent third-party assessment of PTC system safety verification and validation pursuant to subpart H or...

  14. 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

  15. The Yeast Iron Regulatory Proteins Grx3/4 and Fra2 Form Heterodimeric Complexes Containing a [2Fe-2S] Cluster with Cysteinyl and Histidyl Ligation†

    PubMed Central

    Li, Haoran; Mapolelo, Daphne T.; Dingra, Nin N.; Naik, Sunil G.; Lees, Nicolas S.; Hoffman, Brian M.; Riggs-Gelasco, Pamela J.; Huynh, Boi Hanh; Johnson, Michael K.; Outten, Caryn E.

    2009-01-01

    The transcription of iron uptake and storage genes in S. cerevisiae is primarily regulated by the transcription factor Aft1. Nucleocytoplasmic shuttling of Aft1 is dependent upon mitochondrial Fe-S cluster biosynthesis via a signaling pathway that includes the cytosolic monothiol glutaredoxins (Grx3 and Grx4) and the BolA homologue Fra2. However the interactions between these proteins and the iron-dependent mechanism by which they control Aft1 localization are unclear. To reconstitute and characterize components of this signaling pathway in vitro, we have overexpressed yeast Fra2 and Grx3/4 in E. coli. We have shown that co-expression of recombinant Fra2 with Grx3 or Grx4 allows purification of a stable [2Fe-2S]2+ cluster-containing Fra2-Grx3 or Fra2-Grx4 heterodimeric complex. Reconstitution of a [2Fe-2S] cluster on Grx3 or Grx4 without Fra2 produces a [2Fe-2S]-bridged homodimer. UV-visible absorption and CD, resonance Raman, EPR, ENDOR, Mössbauer, and EXAFS studies of [2Fe-2S] Grx3/4 homodimers and the [2Fe-2S] Fra2-Grx3/4 heterodimers indicate that inclusion of Fra2 in the Grx3/4 Fe-S complex causes a change in the cluster stability and coordination environment. Taken together, our analytical, spectroscopic, and mutagenesis data indicate that Grx3/4 and Fra2 form a Fe-S-bridged heterodimeric complex with Fe ligands provided by the active site cysteine of Grx3/4, glutathione, and a histidine residue. Overall, these results suggest that the ability of the Fra2-Grx3/4 complex to assemble a [2Fe-2S] cluster may act as a signal to control the iron regulon in response to cellular iron status in yeast. PMID:19715344

  16. 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

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Analysis of work schedules; submissions; FRA review and approval of submissions; fatigue mitigation plans. 228.407 Section 228.407 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HOURS OF SERVICE OF...

  17. 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.

  18. Cancer-Associated Fibroblasts Regulate Tumor-Initiating Cell Plasticity in Hepatocellular Carcinoma through c-Met/FRA1/HEY1 Signaling.

    PubMed

    Lau, Eunice Yuen Ting; Lo, Jessica; Cheng, Bowie Yik Ling; Ma, Mark Kin Fai; Lee, Joyce Man Fong; Ng, Johnson Kai Yu; Chai, Stella; Lin, Chi Ho; Tsang, Suk Ying; Ma, Stephanie; Ng, Irene Oi Lin; Lee, Terence Kin Wah

    2016-05-10

    Like normal stem cells, tumor-initiating cells (T-ICs) are regulated extrinsically within the tumor microenvironment. Because HCC develops primarily in the context of cirrhosis, in which there is an enrichment of activated fibroblasts, we hypothesized that cancer-associated fibroblasts (CAFs) would regulate liver T-ICs. We found that the presence of α-SMA(+) CAFs correlates with poor clinical outcome. CAF-derived HGF regulates liver T-ICs via activation of FRA1 in an Erk1,2-dependent manner. Further functional analysis identifies HEY1 as a direct downstream effector of FRA1. Using the STAM NASH-HCC mouse model, we find that HGF-induced FRA1 activation is associated with the fibrosis-dependent development of HCC. Thus, targeting the CAF-derived, HGF-mediated c-Met/FRA1/HEY1 cascade may be a therapeutic strategy for the treatment of HCC. PMID:27134167

  19. 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.

  20. SIRT1 promotes epithelial-mesenchymal transition and metastasis in colorectal cancer by regulating Fra-1 expression.

    PubMed

    Cheng, Feifei; Su, Li; Yao, Chao; Liu, Limei; Shen, Junjie; Liu, Chungang; Chen, Xuejiao; Luo, Yongli; Jiang, Lupin; Shan, Juanjuan; Chen, Jun; Zhu, Wei; Shao, Jimin; Qian, Cheng

    2016-06-01

    Understanding molecular mechanisms of colorectal cancer (CRC) metastasis is urgently required for targeted therapy and prognosis of metastatic CRC. In this study, we explored potential effects of silent mating type information regulation 2 homolog 1 (SIRT1) on CRC metastasis. Our data showed that ectopic expression of SIRT1 markedly increased the migration and invasion of CRC cells. In contrast, silencing SIRT1 repressed this behavior in aggressive CRC cells. Tumor xenograft experiments revealed that knockdown of SIRT1 impaired CRC metastasis in vivo. Silencing SIRT1 in CRC cells induced mesenchymal-epithelial transition (MET), which is the reverse process of epithelial-mesenchymal transition (EMT) and characterized by a gain of epithelial and loss of mesenchymal markers. We provided a mechanistic insight toward regulation of Fra-1 by SIRT1 and demonstrated a direct link between the SIRT1-Fra-1 axis and EMT. Moreover, SIRT1 expression correlated positively with Fra-1 expression, metastasis and overall survival in patients with CRC. Taken together, our data provide a novel mechanistic role of SIRT1 in CRC metastasis, suggesting that SIRT1 may serve as a potential therapeutic target for metastatic CRC. PMID:26975631

  1. 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.

  2. Correlated break at PARK2/FRA6E and loss of AF-6/Afadin protein expression are associated with poor outcome in breast cancer.

    PubMed

    Letessier, A; Garrido-Urbani, S; Ginestier, C; Fournier, G; Esterni, B; Monville, F; Adélaïde, J; Geneix, J; Xerri, L; Dubreuil, P; Viens, P; Charafe-Jauffret, E; Jacquemier, J; Birnbaum, D; Lopez, M; Chaffanet, M

    2007-01-11

    Common fragile sites (CFSs) are regions of chromosomal break that may play a role in oncogenesis. The most frequent alteration occurs at FRA3B, within the FHIT gene, at chromosomal region 3p14. We studied a series of breast carcinomas for break of a CFS at 6q26, FRA6E, and its associated gene PARK2, using fluorescence in situ hybridization on tissue microarrays (TMA). We found break of PARK2 in 6% of cases. We studied the PARK2-encoded protein Parkin by using immunohistochemistry on the same TMA. Loss of Parkin was found in 13% of samples but was not correlated with PARK2 break. PARK2 break but not Parkin expression was correlated with prognosis. Alteration of PARK2/FRA6E may cause haplo-insufficiency of one or several telomeric potential tumor suppressor genes (TSG). The AF-6/MLLT4 gene, telomeric of PARK2, encodes the Afadin scaffold protein, which is essential for epithelial integrity. Loss of Afadin was found in 14.5% of cases, and 36% of these cases showed PARK2 break. Loss of Afadin had prognostic impact, suggesting that AF-6 may be a TSG. Loss of Afadin was correlated with loss of FHIT expression, suggesting fragility of FRA6E and FRA3B in a certain proportion of breast tumors. PMID:16819513

  3. 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

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

    PubMed Central

    Zhu, Jie; Pearce, Stephen; Burke, Adrienne; See, Deven Robert; Skinner, Daniel Z.; Dubcovsky, Jorge; Campbell, Kimberly Garland

    2016-01-01

    Frost tolerance is critical for wheat survival during cold winters. 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 including several tandemly duplicated C-REPEAT BINDING FACTOR (CBF) transcription factors, regulates the expression of Cold regulated genes. We identified sequence and copy number variation at these two loci among winter and spring wheat varieties and characterized their association with frost tolerance. We identified two FR-A2 haplotypes – ‘FR-A2-S’ and ‘FR-A2-T’ – distinguished by two insertion/deletions and ten single nucleotide polymorphisms within the CBF-A12 and CBF-A15 genes. Increased copy number of CBF-A14 was frequently associated with the FR-A2-T haplotypes and with higher CBF14 transcript levels in response to cold. Factorial ANOVAs revealed significant interactions between VRN1 and FR-A2 for frost tolerance in both winter and spring panels suggesting a crosstalk between vernalization and cold acclimation pathways. The model including these two loci and their interaction explained 32.0 and 20.7% of the variation in frost tolerance in the winter and spring panels, respectively. The interaction was validated in a winter wheat F4:5 population segregating for both genes. Increased VRN-A1 copy number was associated with improved frost tolerance among varieties carrying the FR-A2-T allele but not among those carrying the FR-A2-S allele. These results suggest that selection of varieties carrying the FR-A2-T allele and three copies of the recessive vrn-A1 allele would be a good strategy to improve frost tolerance in wheat. PMID:24626953

  5. MEKK1 regulates the AP-1 dimer repertoire via control of JunB transcription and Fra-2 protein stability.

    PubMed

    Cuevas, Bruce D; Uhlik, Mark T; Garrington, Timothy P; Johnson, Gary L

    2005-01-27

    Activator protein 1 (AP-1) transcription factor dimers are composed of Jun, Fos, and ATF member proteins, but the mechanisms that determine AP-1 composition are not clearly defined and the function of specific dimers is not well understood. MEKK1 is a mitogen-activated protein kinase (MAPK) kinase kinase and an ubiquitin ligase that regulates both the extracellular signal-regulated kinase 1/2 and the c-Jun amino-terminal kinase. Herein, we demonstrate that MEKK1 regulates the AP-1 protein repertoire. Both FGF-2 and phorbol ester-inducible urokinase-type plasminogen activator (uPA) expression requires AP-1 binding to an enhancer element in the uPA promoter, and we have previously shown that FGF-2 or PMA induction of uPA expression is strongly dependent on MEKK1. JunB mRNA is significantly increased in MEKK1-/- cells, demonstrating that MEKK1 suppresses JunB mRNA expression. Upregulation of JunB expression in MEKK1-/- cells forms an inhibitory AP-1 complex that binds to the uPA promoter and inhibits uPA transcription. MEKK1 also regulates Fra-2 protein stability by inducing Fra-2 ubiquitination and degradation. MEKK1 regulates AP-1-dependent gene expression by regulating the expression, activity and degradation of component members of the AP-1 complex. Controlling the repertoire of a transcription factor complex is a newly defined function for an MAPK kinase kinase. PMID:15558021

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

    PubMed

    Richards, Robert I; Choo, Amanda; Lee, Cheng Shoou; Dayan, Sonia; O'Keefe, Louise

    2015-03-01

    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

  7. 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

  8. WWOX, the common fragile site FRA16D gene product, regulates ATM activation and the DNA damage response

    PubMed Central

    Abu-Odeh, Mohammad; Salah, Zaidoun; Herbel, Christoph; Hofmann, Thomas G.; Aqeilan, Rami I.

    2014-01-01

    Genomic instability is a hallmark of cancer. The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor spanning the common chromosomal fragile site FRA16D. Here, we report a direct role of WWOX in DNA damage response (DDR) and DNA repair. We show that Wwox deficiency results in reduced activation of the ataxia telangiectasia-mutated (ATM) checkpoint kinase, inefficient induction and maintenance of γ-H2AX foci, and impaired DNA repair. Mechanistically, we show that, upon DNA damage, WWOX accumulates in the cell nucleus, where it interacts with ATM and enhances its activation. Nuclear accumulation of WWOX is regulated by its K63-linked ubiquitination at lysine residue 274, which is mediated by the E3 ubiquitin ligase ITCH. These findings identify a novel role for the tumor suppressor WWOX and show that loss of WWOX expression may drive genomic instability and provide an advantage for clonal expansion of neoplastic cells. PMID:25331887

  9. 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.

  10. [Biological and physico-chemical properties of Yersinia pseudotuberculosis bacterial culture having the fra-operon Yersinia pestis].

    PubMed

    Byvalov, A A; Gavrilov, K E; Krupin, V V; Chebotarev, E V; Zheludkova, E V; Drubkov, V I; Smirnov, A E; Mal'kov, V N; Dupiasheva, T Iu; Pechenkin, D V; Bondarev, V P

    2008-01-01

    The biological and physico-chemical properties of cultures of two isogenous recombinant variants of Yersinia pseudotuberculosis were studied. The cell genomes of the cultures are distinguished from one another only by the presence or by the absence of the fra-operon, which is a determined attribute of the plague microbe capsule-forming process. The expression of the attribute is amplified by rising the microbial biomass cultivation temperature and stimulates the decrease in the viability of the bacteria and adaptation potential in vitro. In the warm-blooded owner organism the microbes of the capsule-forming recombinant variant are characterized by the greater residual pathogenicity and immunogenic ability to the experimental plague of the laboratory animals as compared to the reference-variant cells. These specific features could be explained by more expressed colonizing ability of the capsule-forming microbes provided by owner cells' stability to the phagocyte process. PMID:18368776

  11. Insulin-stimulated expression of c-fos, fra1 and c-jun accompanies the activation of the activator protein-1 (AP-1) transcriptional complex.

    PubMed Central

    Griffiths, M R; Black, E J; Culbert, A A; Dickens, M; Shaw, P E; Gillespie, D A; Tavaré, J M

    1998-01-01

    The activator protein-1 (AP-1) transcriptional complex is made up of members of the Fos (c-Fos, FosB, Fra1, Fra2) and Jun (c-Jun, JunB, JunD) families and is stimulated by insulin in several cell types. The mechanism by which insulin activates this complex is not well understood but it is dependent on the activation of the Erk1 and Erk2 isoforms of mitogen-activated protein kinases. In the current study we show that the AP-1 complex isolated from insulin-stimulated cells contained c-Fos, Fra1, c-Jun and JunB. The activation of the AP-1 complex by insulin was accompanied by (i) a transient increase in c-fos expression, and the transactivation of the ternary complex factors Elk1 and Sap1a, in an Erk1/Erk2-dependent fashion; (ii) a substantial increase in the expression of Fra1 protein and mRNA, which was preceded by a transient decrease in its electrophoretic mobility upon SDS/PAGE, indicative of phosphorylation; and (iii) a sustained increase in c-jun expression without increasing c-Jun phosphorylation on serines 63 and 73 or activation of the stress-activated kinase JNK/SAPK. In conclusion, insulin appears to stimulate the activity of the AP-1 complex primarily through a change in the abundance of the components of this complex, although there may be an additional role for Fra1 phosphorylation. PMID:9742208

  12. 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

  13. A comparison of forest cover maps in Mainland Southeast Asia from multiple sources: PALSAR, MERIS, MODIS and FRA

    NASA Astrophysics Data System (ADS)

    Dong, J.; Xiao, X.; Sheldon, S. L.; Biradar, C. M.; Duong, N. D.; Hazarika, M.

    2012-12-01

    The uncertainty in tracking tropical forest extent and changes substantially affects our assessment of the consequences of forest change on the global carbon cycle, biodiversity and ecosystem services. Recently cloud-free imagery useful for tropical forest mapping from the Phased Array Type L-band Synthetic Aperture Radar (PALSAR) onboard the Advanced Land Observing Satellite (ALOS) has become available. We used PALSAR 50-m Orthorectified mosaic imagery in 2009 and a decision tree method to conduct land cover classification and generate a 2009 forest map, which was evaluated using 2106 field photos from the Global Geo-referenced Field Photo Library (http://www.eomf.ou.edu/photos). The resulting land cover classification had a high overall accuracy of 93.3 % and a Kappa Coefficient of 0.9. The PALSAR-based forest map was then compared with three existing forest cover products at three scales (regional, national, and continental): the Food and Agriculture Organization of the United Nations (FAO) Forest Resources Assessments (FRA) 2010, Global Land Cover Map with MERIS (GlobCover) 2009, and the MODIS Terra + Aqua Land Cover Type product (MCD12Q1) 2009. The intercomparison results show that these four forest datasets differ. The PALSAR-based forest area estimate is within the range (6.1 ~ 9.0 ×105 km2) of the other three products and closest to the FAO FRA 2010 estimate. The spatial disagreements of the PALSAR-based forest, MCD12Q1 forest and GlobCover forest are evident; however, the PALSAR-based forest map provides more detail (50-m spatial resolution) and high accuracy (the Producer's and the User's Accuracies were 88 % and 95 %, respectively) and PALSAR can be used to evaluate MCD12Q1 2009 and GlobCover 2009 forest maps. Given the higher spatial resolution, PALSAR-based forest products could further improve the modeling accuracy of carbon cycle in tropical forests.

  14. Mental retardation, acromegalic face, and megalotestes in two half-brothers: a specific form of X-linked mental retardation without fra(X) (q)?

    PubMed

    Tariverdian, G; Froster-Iskenius, U; Deuschl, G; Wolff, G

    1991-01-01

    We describe a family with two half-brothers affected with severe mental retardation. The phenotype in the affected individuals is characterized by apparent acromegaly, profound mental retardation, and hyperactivity. The mother has analogous but less severe facial anomalies and mild mental impairment. Screening for fra(X) (q) was negative in peripheral lymphocytes using methotrexate for fra(X) enhancement. The clinical findings in our patients are similar to those described by Fryns et al. [1986] in two patients with acquired lesions of the central nervous system. CT investigations in one of our patients showed areas of hyperdensity in the pontine region and a small subarachnoid cyst. The pedigree suggests X-linked inheritance. The association of apparent acromegaly, CNS anomalies, megalotestes, and mental retardation in this family supports the hypothesis that a distinct syndrome may exist with phenotype anomalies more severe than those characteristic for the Martin-Bell syndrome but without fragile X. PMID:2018059

  15. 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

  16. 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

  17. 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.

  18. Transcriptional profiling of genes at the human common fragile site FRA1H in tumor-derived cell lines.

    PubMed

    Pelliccia, Franca; Curatolo, Angela; Limongi, Zaira M; Bosco, Nazario; Rocchi, Angela

    2007-10-15

    Common fragile sites (CFSs) are chromosome regions that exhibit gaps and breaks when the cells are exposed to replication stress and to some DNA-binding compounds. In cancer cells, the CFSs are frequently involved in recurrent chromosome rearrangements. Furthermore, altered expression of associated genes, known or potential oncogenes, and tumor-suppressor genes has often been observed. Seventeen of the 88 listed CFSs have been analyzed at the molecular level, but the basis of their fragility has not been clarified. In the present work, the nine genes TGFB2, IARS2, MARK1, TAF1A, TP53BP2, ADPRT, including a very large gene ESRRG and two microRNA genes, MIRN194-1 and MIRN215, localized in the fragile site FRA1H, were investigated by polymerase chain reaction (PCR) for homozygous deletions and by real-time PCR for modification or loss of gene expression in a panel of 19 cancer cell lines. The expression level of five (ESRRG, TGFB2, MIRN194-1, MIRN215, and MARK1) of the nine genes studied presented significant modifications in some of the 19 examined tumor-derived cell lines compared to their normal control tissues. Because of their function, these genes could have a role in neoplastic transformation. PMID:17954271

  19. Serum from patients with ankylosing spondylitis can increase PPARD, fra-1, MMP7, OPG and RANKL expression in MG63 cells

    PubMed Central

    Hu, Zaiying; Lin, Dongfang; Qi, Jun; Qiu, Minli; Lv, Qing; Li, Qiuxia; Lin, Zhiming; Liao, Zetao; Pan, Yunfeng; Jin, Ou; Wu, Yuqiong; Gu, Jieruo

    2015-01-01

    OBJECTIVES: To explore the effects of serum from patients with ankylosing spondylitis on the canonical Wnt/β-catenin pathway and to assess whether the serum has an osteogenic effect in MG63 cells. METHODS: MG63 cells were cultured with serum from 45 ankylosing spondylitis patients, 30 healthy controls, or 45 rheumatoid arthritis patients. The relative PPARD, fra-1, MMP7, OPG and RANKL mRNA levels were measured using quantitative real-time polymerase chain reaction. Associations between gene expression and patient demographics and clinical assessments were then analyzed. RESULTS: MG63 cells treated with serum from ankylosing spondylitis patients had higher PPARD, fra-1, MMP7 and OPG gene expression than did cells treated with serum from controls or rheumatoid arthritis patients (all p<0.05). RANKL expression was higher in MG63 cells treated with serum from patients with ankylosing spondylitis or rheumatoid arthritis than in those treated with serum from controls (both p<0.05). The OPG/RANKL ratio was also higher in MG63 cells treated with serum from ankylosing spondylitis patients than in those treated with serum from controls (p<0.05). No associations were found between the expression of the five genes and the patient demographics and clinical assessments (all p>0.05). CONCLUSIONS : Serum from ankylosing spondylitis patients increases PPARD, fra-1, MMP7, OPG and RANKL expression and the OPG/RANKL ratio in MG63 cells; these effects may be due to the stimulatory effect of the serum on the Wnt pathway. PMID:26602520

  20. 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

  1. 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.

  2. 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

  3. 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

  4. Human T-cell leukemia virus type 1 Tax activates transcription of the human fra-1 gene through multiple cis elements responsive to transmembrane signals.

    PubMed Central

    Tsuchiya, H; Fujii, M; Niki, T; Tokuhara, M; Matsui, M; Seiki, M

    1993-01-01

    We have shown that Tax1 of human T-cell leukemia virus type 1 stimulates the expression of several cellular immediate-early genes (M. Fujii, T. Niki, T. Mori, T. Matsuda, M. Matsui, N. Nomura, and M. Seiki, Oncogene 6:1023-1029, 1991). In this study, the 5'-flanking region of the human fra-1 gene, which is a Tax1-inducible fos-related gene, was isolated and Tax1 or serum-responsive cis elements were analyzed to obtain further insight into the mechanism of Tax1 action. The 62-bp sequence starting 46 nucleotides upstream from the translation initiation site showed 71% homology with the sequence surrounding the TATA box of the c-fos promoter. Regulatory motifs identified in the c-fos promoter, such as an Ets-binding site, E boxes, a CArG box, c-fos AP-1 sites, and two retinoblastoma control elements, were also found upstream of the c-fos homology region. A 502-bp fragment containing these motifs mediated transcriptional activation by Tax1 or by serum in a transient transfection assay. Three independent Tax1-responsive regions (TRRs) were identified, and mutations in each revealed that one of the retinoblastoma control elements in TRR1 and the c-fos AP-1 sites in TRR2 and TRR3 were essential for the activation. Although TRR2 contains a CArG box-like sequence, it was a weak binding site for p67SRF, if it bound at all, and was not required for activation. All three TRRs could also mediate the signals stimulated by serum. Thus, Tax1 appears to activate fra-1 gene expression by means of a part of the cellular machinery similar to that which mediates growth signals. Images PMID:8230424

  5. 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

  6. Monitoring thermal stresses and incipient buckling of continuous-welded rails: results from the UCSD/BNSF/FRA large-scale laboratory test track

    NASA Astrophysics Data System (ADS)

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

    2011-04-01

    Most modern railways use Continuous Welded Rail (CWR). A major problem is the almost total absence of expansion joints that can create buckling in hot weather and breakage in cold weather due to the rail thermal stresses. In June 2008 the University of California, San Diego (UCSD), under the sponsorship of a Federal Railroad Administration (FRA) Office of Research and Development (R&D) grant, began work to develop a technique for in-situ measurement of stress and detection of incipient buckling in CWR. The method under investigation is based on ultrasonic guided waves, and the ultimate goal is to develop a prototype that can be used in motion. A large-scale full rail track (70 feet in length) has been constructed at UCSD's Powell Structural Laboratories, the largest laboratories in the country for structural testing, to validate the CWR stress measurement and buckling detection technique under rail heating conditions well controlled in the laboratory. This paper will report on the results obtained from this unique large-scale test track to date. These results will pave the road for the future development of the rail stress measurement & buckling detection prototype.

  7. A Comparison of Forest Cover Maps in China in 2010 from Multi-source: Landsat, PALSAR, MCD12Q1, FAO FRA, and National Forestry Inventory

    NASA Astrophysics Data System (ADS)

    Qin, Y.; Xiao, X.; Dong, J.; Zhang, G.

    2014-12-01

    Forests and their changes are quite important to global carbon cycle, biodiversity and ecological services. Some uncertainties about forest cover maps still exist in China, so an accurate and updated forest cover distribution map is necessary as a baseline for carbon cycle estimation, especially at a fine spatial resolution. In this study, we developed a decision tree classification algorithm to identify forest and non-forest land cover, based on the signature analysis of 50 m ALOS PLASAR backscatter data in 2010 for a few land cover types. We used MODIS-based NDVI dataset in 2010 (MOD13Q1) to generate a map of annual maximum NDVI and used it to mask out built-up lands, barren lands, and sparsely vegetated lands. We applied the PALSAR-based algorithm and produced a forest cover map in China in 2010. Several comparisons in forest area and spatial distribution between the resultant forest map with other forest maps were carried out. The results show that the total forest area in China from the PALSAR-based forest map in 2010 is close to those of JAXA, FAO FRA, and National Forestry Inventory, and there are good linear relationships between the PALSAR-based forest map with the JAXA, MCD12Q1, and NLCD-China forest areas at province and county scales. All the forest maps have similar forest/non-forest distribution, but our PALSAR-based forest map recognizes well the agro-forests. The results of this study provide a baseline map of forest cover in China in 2010, which can be used for the studies of forest disturbance, carbon cycle, and ecological restoration projects in China.

  8. A functional activating protein 1 (AP-1) site regulates matrix metalloproteinase 2 (MMP-2) transcription by cardiac cells through interactions with JunB-Fra1 and JunB-FosB heterodimers.

    PubMed Central

    Bergman, Marina R; Cheng, Sunfa; Honbo, Norman; Piacentini, Lucia; Karliner, Joel S; Lovett, David H

    2003-01-01

    Enhanced synthesis of a specific matrix metalloproteinase, MMP-2, has been demonstrated in experimental models of ventricular failure and in cardiac extracts from patients with ischaemic cardiomyopathy. Cultured neonatal rat cardiac fibroblasts and myocytes were used to analyse the determinants of MMP-2 synthesis, including the effects of hypoxia. Culture of rat cardiac fibroblasts for 24 h in 1% oxygen enhanced MMP-2 synthesis by more than 5-fold and augmented the MMP-2 synthetic responses of these cells to endothelin-1, angiotensin II and interleukin 1beta. A series of MMP-2 promoter-luciferase constructs were used to map the specific enhancer element(s) that drive MMP-2 transcription in cardiac cells. Deletion studies mapped a region of potent transactivating function within the 91 bp region from -1433 to -1342 bp, the activity of which was increased by hypoxia. Oligonucleotides from this region were cloned in front of a heterologous simian-virus-40 (SV40) promoter and mapped the enhancer activity to a region between -1410 and -1362 bp that included a potential activating protein 1 (AP-1)-binding sequence, C(-1394)CTGACCTCC. Site-specific mutagenesis of the core TGAC sequence (indicated in bold) eliminated the transactivating activity within the -1410 to -1362 bp sequence. Electrophoretic mobility shift assays (EMSAs) using the -1410 to -1362 bp oligonucleotide and rat cardiac fibroblast nuclear extracts demonstrated specific nuclear-protein binding that was eliminated by cold competitor oligonucleotide, but not by the AP-1-mutated oligonucleotide. Antibody-supershift EMSAs of nuclear extracts from normoxic rat cardiac fibroblasts demonstrated Fra1 and JunB binding to the -1410 to -1362 bp oligonucleotide. Nuclear extracts isolated from hypoxic rat cardiac fibroblasts contained Fra1, JunB and also included FosB. Co-transfection of cardiac fibroblasts with Fra1-JunB and FosB-JunB expression plasmids led to significant increases in transcriptional activity. These

  9. 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

  10. Astrocytoma-associated antigens - IL13Rα2, Fra-1, and EphA2 as potential markers to monitor the status of tumour-derived cell cultures in vitro

    PubMed Central

    2014-01-01

    Background The molecular heterogeneity of high-grade astrocytomas underlies the difficulties in the development of representative and valuable in vitro experimental models for their studies. The purpose of our study was to estimate the value of astrocytoma-associated antigens (AAAs) - IL13Rα2, Fra-1, EphA2 - and the most common molecular aberrations typical for astrocytomas as potential markers to screen the status of tumour-derived cell cultures in vitro. Methods The tumour-derived cell cultures were established from high-grade astrocytomas. The expression analyses of the tested genes were performed via semi-quantitative real-time PCR and subsequently verified by immunohistochemical and immunocytochemical technique. The analyses of molecular aberrations at DNA level included gene dosage status evaluation based on real-time PCR, sequencing analysis, and loss of heterozygosity (LOH) assay. Results The expression analyses based on semi-quantitative real-time PCR showed that in the final stage of culture the expression level of all tested AAAs was significantly higher or at least comparable to that of primary tumours; however, two expression patterns were observed during cell culture establishment. Analysis at the single cell level via immunocytochemistry also demonstrated an increase of the level of tested proteins and/or selection of tumour cell populations strongly positive for AAAs vs. other cell types including admixed non-tumoural cells. Confrontation of AAA expression data with the results of molecular analyses at DNA level seems to support the latter, revealing that the expression pattern of astrocytoma-associated antigens in tumour-derived cells in subsequent stages of culture is convergent with changes in the molecular profile of examined cell populations. Conclusions The consistency of the obtained results seems to support the use of the selected AAAs, in particular IL13Rα2 and Fra-1, as tools facilitating the establishment of tumour-derived cultures

  11. 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

  12. 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…

  13. 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.

  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. 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.

  17. 49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE... of the selection process. (f) The railroad must randomly select a sufficient number of covered... objective, neutral criteria which ensures that every covered employee has a substantially equal...

  18. 49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE... of the selection process. (f) The railroad must randomly select a sufficient number of covered... objective, neutral criteria which ensures that every covered employee has a substantially equal...

  19. 49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    .... Stenciling 215.301Failure to stencil car number and built date on freight car as required. 215.303Failure to stencil restricted car as required. 215.305Failure to stencil maintenance-of-way equipment as required....

  20. 49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    .... Stenciling 215.301Failure to stencil car number and built date on freight car as required. 215.303Failure to stencil restricted car as required. 215.305Failure to stencil maintenance-of-way equipment as required....

  1. 49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    .... Stenciling 215.301Failure to stencil car number and built date on freight car as required. 215.303Failure to stencil restricted car as required. 215.305Failure to stencil maintenance-of-way equipment as required....

  2. 49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    .... Stenciling 215.301Failure to stencil car number and built date on freight car as required. 215.303Failure to stencil restricted car as required. 215.305Failure to stencil maintenance-of-way equipment as required....

  3. EXACT: EXercise or Advice after ankle fraCTure. Design of a randomised controlled trial

    PubMed Central

    2011-01-01

    Background Ankle fractures are common. Management of ankle fractures generally involves a period of immobilisation followed by rehabilitation to reduce pain, stiffness, weakness and swelling. The effects of a rehabilitation program are still unclear. However, it has been shown that important components of rehabilitation programs may not confer additional benefits over exercise alone. The primary aim of this trial is to determine the effectiveness and cost-effectiveness of an exercise-based rehabilitation program after ankle fracture, compared to advice alone. Methods/Design A pragmatic randomised trial will be conducted. Participants will be 342 adults with stiff, painful ankles after ankle fracture treated with immobilisation. They will be randomly allocated using a concealed randomisation procedure to either an Advice or Rehabilitation group. Participants in the Advice group will receive verbal and written advice about exercise at the time of removal of immobilisation. Participants in the Rehabilitation group will be provided with a 4-week rehabilitation program that is designed, monitored and progressed by a physiotherapist, in addition to verbal and written advice. Outcomes will be measured by a blinded assessor at 1, 3 and 6 months. The primary outcomes will be activity limitation and quality-adjusted life years. Discussion This pragmatic trial will determine if a rehabilitation program reduces activity limitation and improves quality of life, compared to advice alone, after immobilisation for ankle fracture. PMID:21726463

  4. 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.

  5. 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...

  6. 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...

  7. 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...

  8. "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)

  9. Methotrexate treatment of FraX fibroblasts results in FMR1 transcription but not in detectable FMR1 protein levels

    PubMed Central

    2013-01-01

    Background Fragile X syndrome is caused by the loss of FMRP expression due to methylation of the FMR1 promoter. Treatment of fragile X syndrome patients’ lymphoblastoid cells with 5-azadeoxycytidine results in demethylation of the promoter and reactivation of the gene. The aim of the study was to analyze if methotrexate, an agent which also reduces DNA methylation but with less toxicity than 5-azadeoxycytidine, has therapeutic potential in fragile X syndrome. Methods Fibroblasts of fragile X syndrome patients were treated with methotrexate in concentrations ranging from 1 to 4 μg/ml for up to 14 days. FMR1 and FMRP expression were analyzed by quantitative PCR and western blotting. Results FMR1 mRNA was detected and levels correlated positively with methotrexate concentrations and time of treatment, but western blotting did not show detectable FMRP levels. Conclusions We show that it is possible to reactivate FMR1 transcription in fibroblasts of fragile X syndrome patients by treatment with methotrexate. However, we were not able to show FMRP expression, possibly due to the reduced translation efficacy caused by the triplet repeat extension. Unless FMR1 reactivation is more effective in vivo our results indicate that methotrexate has no role in the treatment of fragile X syndrome. PMID:24020679

  10. 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

    ...) issued on July 15, 2009, by Fatigue Science, Inc. (with a fatigue threshold for the purpose of this.... Compliance with the fatigue mitigation plan is mandatory. The railroad shall review and, if necessary,...

  11. 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

    ...) issued on July 15, 2009, by Fatigue Science, Inc. (with a fatigue threshold for the purpose of this.... Compliance with the fatigue mitigation plan is mandatory. The railroad shall review and, if necessary,...

  12. The Frankfurt Patient Safety Climate Questionnaire for General Practices (FraSiK): analysis of psychometric properties.

    PubMed

    Hoffmann, Barbara; Domanska, Olga Maria; Albay, Zeycan; Mueller, Vera; Guethlin, Corina; Thomas, Eric J; Gerlach, Ferdinand M

    2011-09-01

    BACKGROUND Safety culture has been identified as having a major impact on how safety is managed in healthcare. However, it has not received much attention in general practices. Hence, no instrument yet exists to assess safety climate-the measurable artefact of safety culture-in this setting. This study aims to evaluate psychometric properties of a newly developed safety climate questionnaire for use in German general practices. METHODS The existing Safety Attitudes Questionnaire, Ambulatory Version, was considerably modified and enhanced in order to be applicable in general practice. After pilot tests and its application in a random sample of 400 German practices, a first psychometric analysis led to modifications in several items. A further psychometric analysis was conducted with an additional sample of 60 practices and a response rate of 97.08%. Exploratory factor analysis with orthogonal varimax rotation was carried out and the internal consistency of the identified factors was calculated. RESULTS Nine factors emerged, representing a wide range of dimensions associated with safety culture: teamwork climate, error management, safety of clinical processes, perception of causes of errors, job satisfaction, safety of office structure, receptiveness to healthcare assistants and patients, staff perception of management, and quality and safety of medical care. Internal consistency of factors is moderate to good. CONCLUSIONS This study demonstrates the development of a patient safety climate instrument. The questionnaire displays established features of safety climate and additionally contains features that might be specific to small-scale general practices. PMID:21571753

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  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...

  18. [Extravasation of radiopharmaceuticals: preventive measures and management recommended by SoFRa (Société Française de Radiopharmacie)].

    PubMed

    Barré, E; Nguyen, M-L; Bruel, D; Fournel, C; Hosten, B; Lao, S; Vercellino, L; Rizzo-Padoin, N

    2013-07-01

    Radiopharmaceuticals extravasation is rare but may have serious clinical issues. Because no specific recommendations are being proposed to date, the goals of our working group created within the French Society of Radiopharmacy are to determine preventive measures and to establish a pragmatic management of extravasation of these drugs. Our preventive measures are to recognize the symptoms (erythema, venous discoloration, swelling), to know the risk factors (which are related to radiopharmaceutical, patient, site of injection, injection technique) and severity (from erythema to skin necrosis, depending on the radionuclide) and how to avoid them (training and awareness of staff, choice of injection site, route of drug administration test, use of a catheter for administration of therapeutic radiopharmaceuticals). Management should be immediate. It can be facilitated by a specific emergency kit. General measures recommended are the immediate cessation of injection, aspiration of fluid extravasation, delimitation of the extravasated area with an indelible pen, informing the doctor. Specific measures taking into account the radiotoxicity of the radionuclide and the type of radiopharmaceutical were also established. The patient should be informed by the doctor about the risks and how to take care of. Traceability of the incident must be ensured. A multidisciplinary reflexion is essential to manage the extravasation as early and effectively as possible. PMID:23835019

  19. Heritable fragile sites on human chromosomes. VII. Children homozygous for the BrdU-requiring fra(10)q25 are phenotypically normal

    PubMed Central

    Sutherland, Grant R.

    1981-01-01

    A brother and sister have been detected who are homozygous for the bromodeoxyuridine (BrdU)-requiring fragile site at 10q25. The children are phenotypically normal, indicating that homozygosity for this fragile site is harmless, at least during childhood. ImagesFig. 2 PMID:7325157

  20. Yersinia pestis pFra Shows Biovar-Specific Differences and Recent Common Ancestry with a Salmonella enterica Serovar Typhi Plasmid

    PubMed Central

    Prentice, Michael B.; James, Keith D.; Parkhill, Julian; Baker, Stephen G.; Stevens, Kim; Simmonds, Mark N.; Mungall, Karen L.; Churcher, Carol; Oyston, Petra C. F.; Titball, Richard W.; Wren, Brendan W.; Wain, John; Pickard, Derek; Hien, Tran Tinh; Farrar, Jeremy J.; Dougan, Gordon

    2001-01-01

    Population genetic studies suggest that Yersinia pestis, the cause of plague, is a clonal pathogen that has recently emerged from Yersinia pseudotuberculosis. Plasmid acquisition is likely to have been a key element in this evolutionary leap from an enteric to a flea-transmitted systemic pathogen. However, the origin of Y. pestis-specific plasmids remains obscure. We demonstrate specific plasmid rearrangements in different Y. pestis strains which distinguish Y. pestis bv. Orientalis strains from other biovars. We also present evidence for plasmid-associated DNA exchange between Y. pestis and the exclusively human pathogen Salmonella enterica serovar Typhi. PMID:11274119

  1. Projektarbejde i fremmedsprogene: Rapport fra seminar pa Roskilde Universitetscenter (Project Work in Foreign Languages: Report from a Seminar at Roskilde University Center). ROLIG-papir 38.

    ERIC Educational Resources Information Center

    Jakobsen, Karen Sonne, Ed.

    This report describes a seminar at Roskilde University Center (Denmark) on project work in foreign languages, which brought together language teachers and theorists from different schools, including universities, business schools, technical schools, merchants schools, and high schools, to discuss their experiences with project work in foreign…

  2. 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... Safety Verification and Validation (a) This appendix provides minimum requirements for mandatory independent third-party assessment of PTC system safety verification and validation pursuant to subpart H or...

  3. 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... Safety Verification and Validation (a) This appendix provides minimum requirements for mandatory independent third-party assessment of PTC system safety verification and validation pursuant to subpart H or...

  4. 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...

  5. 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...

  6. 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

  7. Dall'italo-austrliano all'italiano: apprendmento linguistico fra gli scolari della seconda generazione (From Italian-Australian to Italian: Language Acquisition among the Students of the Second Generation).

    ERIC Educational Resources Information Center

    Rubino, Antonia

    1989-01-01

    Discusses the results of research to determine the success of the efforts currently being made in schools to teach pure Italian to the second generation of Italians in Australia in order to replace Italian Australian, a mixture of Italian dialects, Italian, and English. 33 references. (CFM)

  8. 76 FR 71116 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-16

    ..., FRA published a final rule (FR) with procedures and requirements to cover applications of financial... Budget (OMB), FRA is soliciting public comment on specific aspects of the activities identified...

  9. 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...

  10. 49 CFR 230.59 - Fusible plugs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... removed and cleaned of scale each time the boiler is washed but not less frequently than during every 31 service day inspection. Their removal shall be noted on the FRA Form No. 1 or FRA Form No. 3....

  11. 49 CFR 230.59 - Fusible plugs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... removed and cleaned of scale each time the boiler is washed but not less frequently than during every 31 service day inspection. Their removal shall be noted on the FRA Form No. 1 or FRA Form No. 3....

  12. 49 CFR 230.59 - Fusible plugs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... removed and cleaned of scale each time the boiler is washed but not less frequently than during every 31 service day inspection. Their removal shall be noted on the FRA Form No. 1 or FRA Form No. 3....

  13. 49 CFR 230.59 - Fusible plugs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... removed and cleaned of scale each time the boiler is washed but not less frequently than during every 31 service day inspection. Their removal shall be noted on the FRA Form No. 1 or FRA Form No. 3....

  14. 49 CFR 230.59 - Fusible plugs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... removed and cleaned of scale each time the boiler is washed but not less frequently than during every 31 service day inspection. Their removal shall be noted on the FRA Form No. 1 or FRA Form No. 3....

  15. 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. PMID:26595060

  16. 76 FR 76218 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-06

    ... regulations contained at Title 49 U.S.C. Section 20302. FRA assigned the petition Docket Number FRA-2011-0091. Specifically, NJT is seeking relief from 49 U.S.C. 20302(1)(B). FRA has determined that NJT has...

  17. 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...

  18. 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...

  19. 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...

  20. 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…

  1. 49 CFR 225.21 - Forms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... following forms and copies of the “FRA Guide for Preparing Accident/Incident Reports” may be obtained from... the form and in the current “FRA Guide for Preparing Accident/Incident Reports.” The form shall be... Inquiry Form.—Form FRA F 6180.150 shall be sent to every potentially injured highway user, or...

  2. 49 CFR 225.21 - Forms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... following forms and copies of the “FRA Guide for Preparing Accident/Incident Reports” may be obtained from... the form and in the current “FRA Guide for Preparing Accident/Incident Reports.” The form shall be... Inquiry Form.—Form FRA F 6180.150 shall be sent to every potentially injured highway user, or...

  3. 77 FR 12645 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-01

    ... dated April 11, 2011, the City of Chandler, AZ, has petitioned the Federal Railroad Administration (FRA... contained at 49 CFR part 222. FRA assigned the petition Docket Number FRA-2011-0036. The City of Chandler is... highway speed limit is 45 mph instead of 40 mph as required in the definition. The City of Chandler...

  4. 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...

  5. 76 FR 77716 - Alternate Passenger Rail Service Pilot Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-14

    ... and Development, FRA, 1200 New Jersey Ave. SE., Washington, DC 20590 (telephone: (202) 493-6109); or... 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...

  6. 78 FR 2713 - Update to NEPA Implementing Procedures

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-14

    ... 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 FRA... the comment how electronics and communication systems could cause impacts related to...

  7. 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... System (C3RS) pilot project for the CP Portage, WI, terminal was initially approved by FRA on March 3, 2008. In Docket Number FRA-2007-0008, CP requested and received a waiver of compliance from...

  8. 78 FR 28284 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-14

    ...'s complete Privacy Act Statement in the Federal Register published on April 11, 2000 (65 FR 19477... April 11, 2013, Canadian Pacific Railway (CP) has petitioned the Federal Railroad Administration (FRA... Equipment; End-of-Train Devices. FRA assigned the petition Docket Number FRA-2013-0040. Specifically,...

  9. Free ferulic acid uptake in lactating cows.

    PubMed

    Soberon, M A; Cherney, J H; Liu, R H; Ross, D A; Cherney, D J R

    2012-11-01

    Ferulic acid (FRA), a phenolic compound with antioxidant and anticancer activities, naturally occurs in plants as a lignin precursor. Many veins of research have been devoted to releasing FRA from the lignin complex to improve digestibility of ruminant feeds. Thus, the objective of this research was to investigate the transfer of a given dosage of the free form of FRA into the milk of dairy cattle. Six mid- to late-lactation Holstein cows at the Cornell Research Farm (Harford, NY) were given 14-d adaptation to diet and stall position. Ad libitum access to a total mixed ration based on haylage and maize silage (31.1% neutral detergent fiber containing 5.52 mg of FRA/g) was provided during the study. A crossover design was implemented so that each cow alternated weekly between FRA-dosed and control. On d 1, jugular cannulas and urine catheters were placed in all cows. On d 2, FRA-dosed cows received a single dosage of 150 g of pure FRA powder at 0830 h via their fistula (n=4) or a balling gun for nonfistulated cows (n=2). Plasma, urine, feces, feed, orts, milk, and rumen fluid were sampled intensively for the next 36 h and analyzed for FRA concentration. On d 8, the cows crossed over and the experiment was repeated. When compared with the control, FRA administration did not have an effect on dry matter intake, milk yield, milk fat yield, milk protein yield, somatic cell count, or neutral detergent fiber content of orts and feces. The concentration of FRA in the feces did not change as a result of FRA dosage. As expected, FRA concentration increased dramatically upon FRA dosage and decreased over time until returning to basal levels in rumen fluid (4 h after dosage), plasma (5.5 h after dosage), urine (10 h after dosage), and milk (14 h after dosage). Baseline values for FRA in urine and rumen fluid were variable among cows and had an effect on FRA concentration in FRA-dosed cows. From this study, it is observed that orally ingested FRA can be transported into the

  10. 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

  11. 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

  12. Fe2+ chelator proferrorosamine A: a gene cluster of Erwinia rhapontici P45 involved in its synthesis and its impact on growth of Erwinia amylovora CFBP1430.

    PubMed

    Born, Yannick; Remus-Emsermann, Mitja N P; Bieri, Marco; Kamber, Tim; Piel, Jörn; Pelludat, Cosima

    2016-02-01

    Proferrorosamine A (proFRA) is an iron (Fe2+) chelator produced by the opportunistic plant pathogen Erwinia rhapontici P45. To identify genes involved in proFRA synthesis, transposon mutagenesis was performed. The identified 9.3 kb gene cluster, comprising seven genes, designated rosA-rosG, encodes proteins that are involved in proFRA synthesis. Based on gene homologies, a biosynthetic pathway model for proFRA is proposed. To obtain a better understanding of the effect of proFRA on non-proFRA producing bacteria, E. rhapontici P45 was co-cultured with Erwinia amylovora CFBP1430, a fire-blight-causing plant pathogen. E. rhapontici P45, but not corresponding proFRA-negative mutants, led to a pink coloration of E. amylovora CFBP1430 colonies on King's B agar, indicating accumulation of the proFRA-iron complex ferrorosamine, and growth inhibition in vitro. By saturating proFRA-containing extracts with Fe2+, the inhibitory effect was neutralized, suggesting that the iron-chelating capability of proFRA is responsible for the growth inhibition of E. amylovora CFBP1430. PMID:26732708

  13. Substrate cleavage profiling suggests a distinct function of Bacteroides fragilis metalloproteinases (fragilysin and metalloproteinase II) at the microbiome-inflammation-cancer interface.

    PubMed

    Shiryaev, Sergey A; Remacle, Albert G; Chernov, Andrei V; Golubkov, Vladislav S; Motamedchaboki, Khatereh; Muranaka, Norihito; Dambacher, Corey M; Capek, Petr; Kukreja, Muskan; Kozlov, Igor A; Perucho, Manuel; Cieplak, Piotr; Strongin, Alex Y

    2013-11-29

    Enterotoxigenic anaerobic Bacteroides fragilis is a significant source of inflammatory diarrheal disease and a risk factor for colorectal cancer. Two distinct metalloproteinase types (the homologous 1, 2, and 3 isoforms of fragilysin (FRA1, FRA2, and FRA3, respectively) and metalloproteinase II (MPII)) are encoded by the B. fragilis pathogenicity island. FRA was demonstrated to be important to pathogenesis, whereas MPII, also a potential virulence protein, remained completely uncharacterized. Here, we, for the first time, extensively characterized MPII in comparison with FRA3, a representative of the FRA isoforms. We employed a series of multiplexed peptide cleavage assays to determine substrate specificity and proteolytic characteristics of MPII and FRA. These results enabled implementation of an efficient assay of MPII activity using a fluorescence-quenched peptide and contributed to structural evidence for the distinct substrate cleavage preferences of MPII and FRA. Our data imply that MPII specificity mimics the dibasic Arg↓Arg cleavage motif of furin-like proprotein convertases, whereas the cleavage motif of FRA (Pro-X-X-Leu-(Arg/Ala/Leu)↓) resembles that of human matrix metalloproteinases. To the best of our knowledge, MPII is the first zinc metalloproteinase with the dibasic cleavage preferences, suggesting a high level of versatility of metalloproteinase proteolysis. Based on these data, we now suggest that the combined (rather than individual) activity of MPII and FRA is required for the overall B. fragilis virulence in vivo. PMID:24145028

  14. Substrate Cleavage Profiling Suggests a Distinct Function of Bacteroides fragilis Metalloproteinases (Fragilysin and Metalloproteinase II) at the Microbiome-Inflammation-Cancer Interface*

    PubMed Central

    Shiryaev, Sergey A.; Remacle, Albert G.; Chernov, Andrei V.; Golubkov, Vladislav S.; Motamedchaboki, Khatereh; Muranaka, Norihito; Dambacher, Corey M.; Capek, Petr; Kukreja, Muskan; Kozlov, Igor A.; Perucho, Manuel; Cieplak, Piotr; Strongin, Alex Y.

    2013-01-01

    Enterotoxigenic anaerobic Bacteroides fragilis is a significant source of inflammatory diarrheal disease and a risk factor for colorectal cancer. Two distinct metalloproteinase types (the homologous 1, 2, and 3 isoforms of fragilysin (FRA1, FRA2, and FRA3, respectively) and metalloproteinase II (MPII)) are encoded by the B. fragilis pathogenicity island. FRA was demonstrated to be important to pathogenesis, whereas MPII, also a potential virulence protein, remained completely uncharacterized. Here, we, for the first time, extensively characterized MPII in comparison with FRA3, a representative of the FRA isoforms. We employed a series of multiplexed peptide cleavage assays to determine substrate specificity and proteolytic characteristics of MPII and FRA. These results enabled implementation of an efficient assay of MPII activity using a fluorescence-quenched peptide and contributed to structural evidence for the distinct substrate cleavage preferences of MPII and FRA. Our data imply that MPII specificity mimics the dibasic Arg↓Arg cleavage motif of furin-like proprotein convertases, whereas the cleavage motif of FRA (Pro-X-X-Leu-(Arg/Ala/Leu)↓) resembles that of human matrix metalloproteinases. To the best of our knowledge, MPII is the first zinc metalloproteinase with the dibasic cleavage preferences, suggesting a high level of versatility of metalloproteinase proteolysis. Based on these data, we now suggest that the combined (rather than individual) activity of MPII and FRA is required for the overall B. fragilis virulence in vivo. PMID:24145028

  15. 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

  16. 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,...

  17. Deletion at Fragile Sites is a Common and Early Event in Barrett’s Esophagus

    PubMed Central

    Lai, Lisa A.; Kostadinov, Rumen; Barrett, Michael T.; Peiffer, Daniel A.; Pokholok, Dimitry; Odze, Robert; Sanchez, Carissa A.; Maley, Carlo C.; Reid, Brian J.; Gunderson, Kevin L.; Rabinovitch, Peter S.

    2011-01-01

    Barrett’s esophagus is a premalignant intermediate to esophageal adenocarcinoma, which develops in the context of chronic inflammation and exposure to bile and acid. We asked whether there might be common genomic alterations that could be identified as potential clinical biomarker(s) for Barrett’s esophagus by whole genome profiling. We detected copy number alterations and/or loss of heterozygosity (LOH) at fifty-six fragile sites in 20 patients with premalignant Barrett’s esophagus (BE). Chromosomal fragile sites are particularly sensitive to DNA breaks and have been shown to be frequent sites of rearrangement or loss in many human cancers. 78% of all genomic alterations detected by array-CGH were associated with fragile sites. Copy number losses in early BE were observed at particularly high frequency at FRA3B (81%), FRA9A/C (71.4%), FRA5E (52.4%) and FRA 4D (52.4%), and at lower frequencies in other fragile sites, including FRA1K (42.9%), FRAXC (42.9%), FRA 12B (33.3%) and FRA16D (33.3%). Due to the consistency of the region of copy number loss, we were able to verify these results by quantitative PCR which detected loss of FRA3B and FRA16D, in 83% and 40% of early molecular stage BE patients respectively. LOH in these cases was confirmed via pyrosequencing at FRA3B and FRA16D (75% and 70% respectively). Deletion and genomic instability at FRA3B and other fragile sites could thus be a biomarker of genetic damage in BE patients and a potential biomarker of cancer risk. PMID:20647332

  18. Deletion at fragile sites is a common and early event in Barrett's esophagus.

    PubMed

    Lai, Lisa A; Kostadinov, Rumen; Barrett, Michael T; Peiffer, Daniel A; Pokholok, Dimitry; Odze, Robert; Sanchez, Carissa A; Maley, Carlo C; Reid, Brian J; Gunderson, Kevin L; Rabinovitch, Peter S

    2010-08-01

    Barrett's esophagus (BE) is a premalignant intermediate to esophageal adenocarcinoma, which develops in the context of chronic inflammation and exposure to bile and acid. We asked whether there might be common genomic alterations that could be identified as potential clinical biomarker(s) for BE by whole genome profiling. We detected copy number alterations and/or loss of heterozygosity at 56 fragile sites in 20 patients with premalignant BE. Chromosomal fragile sites are particularly sensitive to DNA breaks and are frequent sites of rearrangement or loss in many human cancers. Seventy-eight percent of all genomic alterations detected by array-CGH were associated with fragile sites. Copy number losses in early BE were observed at particularly high frequency at FRA3B (81%), FRA9A/C (71.4%), FRA5E (52.4%), and FRA 4D (52.4%), and at lower frequencies in other fragile sites, including FRA1K (42.9%), FRAXC (42.9%), FRA 12B (33.3%), and FRA16D (33.3%). Due to the consistency of the region of copy number loss, we were able to verify these results by quantitative PCR, which detected the loss of FRA3B and FRA16D, in 83% and 40% of early molecular stage BE patients, respectively. Loss of heterozygosity in these cases was confirmed through pyrosequencing at FRA3B and FRA16D (75% and 70%, respectively). Deletion and genomic instability at FRA3B and other fragile sites could thus be a biomarker of genetic damage in BE patients and a potential biomarker of cancer risk. PMID:20647332

  19. 49 CFR 229.211 - Processing of petitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  20. 49 CFR 229.211 - Processing of petitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  1. 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...

  2. 49 CFR 232.15 - Movement of defective equipment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., an automated tracking system approved for use by FRA shall be provided. The tag, card, or automated tracking system shall contain the following information about the defective equipment: (i) The reporting... automated tracking system approved by FRA to meet the tagging requirements contained in paragraph (b)(1)...

  3. 49 CFR 232.15 - Movement of defective equipment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., an automated tracking system approved for use by FRA shall be provided. The tag, card, or automated tracking system shall contain the following information about the defective equipment: (i) The reporting... automated tracking system approved by FRA to meet the tagging requirements contained in paragraph (b)(1)...

  4. 49 CFR 232.15 - Movement of defective equipment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., an automated tracking system approved for use by FRA shall be provided. The tag, card, or automated tracking system shall contain the following information about the defective equipment: (i) The reporting... automated tracking system approved by FRA to meet the tagging requirements contained in paragraph (b)(1)...

  5. 77 FR 2120 - Environmental Impact Statement for New Orleans Rail Gateway (NORG), Jefferson and Orleans...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-13

    ...FRA is issuing this notice to advise the public that it will prepare an EIS with the Louisiana Department of Transportation and Development (LA DOTD) to evaluate environmental and related impacts of upgrading the New Orleans Rail Gateway (NORG) and infrastructure in Jefferson and Orleans Parishes, Louisiana (proposed action). FRA is also issuing this notice to solicit public and agency input......

  6. 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))....

  7. 77 FR 68883 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-16

    ... safety regulations contained at 49 CFR part 215. FRA assigned the petition Docket Number FRA-2012-0067. Caltrain seeks a waiver of compliance from the Railroad Freight Car Safety Standards contained in 49 CFR...-straight deck cars (Car Numbers JPBX 711 and JPBX 712). Caltrain also requested a Special Approval...

  8. 75 FR 73158 - Railroad Safety Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-29

    ...FRA announces the forty-third meeting of the RSAC, a Federal advisory committee that develops railroad safety regulations through a consensus process. The RSAC meeting topics will include opening remarks from the FRA Administrator, and status reports will be provided by the Passenger Hours of Service, Training Standards, Track Safety Standards, Passenger Safety, and Medical Standards Working......

  9. 77 FR 73456 - Update to the TR-12 Fuel Related Rate Adjustment Policy (SDDC Fuel Surcharge Policy)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-10

    ... Department of the Army Update to the TR-12 Fuel Related Rate Adjustment Policy (SDDC Fuel Surcharge Policy...: Reference: TR-12 Fuel Related Rate Adjustment Policy. Background: The following FRA policy applies to... increases in diesel fuel prices. Miscellaneous: A copy of the TR-12 FRA Policy can be accessed via the...

  10. 78 FR 54849 - Hazardous Materials: Rail Petitions and Recommendations To Improve the Safety of Railroad Tank...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-06

    ....gov/fdsys/pkg/FR-2000-04-11/pdf/00-8505.pdf . FOR FURTHER INFORMATION CONTACT: Karl Alexy, (202) 493... on July 18, 2013 (78 FR 42998) announcing a PHMSA and FRA public meeting scheduled for August 27-28... (HMG)--127 (77 FR 10799), which provides a standardized procedure developed by FRA to make the...

  11. 77 FR 22381 - Odorant Fade in Railroad Tank Cars

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-13

    ...FRA is issuing Safety Advisory 2012-01 to remind shippers and consignees of railroad tank cars containing odorized liquefied petroleum gas (LPG), of the importance of taking actions to ensure that a sufficient level of odorant remains in the LPG throughout the entire transportation cycle. FRA is issuing this notice to raise awareness within the hazardous materials community, of the potential......

  12. 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...

  13. 78 FR 22364 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-15

    ... (65 FR 19477). Issued in Washington, DC, on April 8, 2013. Robert C. Lauby, Deputy Associate... January 24, 2013, Steam Into History, Inc. (Steam) has petitioned the Federal Railroad Administration (FRA... assigned the petition Docket Number FRA-2011-0069. Kloke Locomotive Works is constructing for Steam a...

  14. 49 CFR 236.1019 - Main line track exceptions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... section. No track shall be designated as yard or terminal unless it is identified in an MTEA that is part of an FRA approved PTCIP. (b) Passenger terminal exception. FRA will consider an exception in the case of trackage used exclusively as yard or terminal tracks by or in support of regularly...

  15. 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...

  16. 49 CFR 225.27 - Retention of records.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Summary,” that the railroad submits to FRA on optical media (CD-ROM) or electronically via the Internet to... opts to submit the report to FRA electronically via the internet, the railroad must also retain a hard.../or surveillance activities under part 212 of this chapter or any other authorized representative...

  17. 49 CFR 225.27 - Retention of records.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Summary,” that the railroad submits to FRA on optical media (CD-ROM) or electronically via the Internet to... opts to submit the report to FRA electronically via the internet, the railroad must also retain a hard.../or surveillance activities under part 212 of this chapter or any other authorized representative...

  18. 49 CFR 225.27 - Retention of records.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Summary,” that the railroad submits to FRA on optical media (CD-ROM) or electronically via the Internet to... opts to submit the report to FRA electronically via the internet, the railroad must also retain a hard.../or surveillance activities under part 212 of this chapter or any other authorized representative...

  19. 49 CFR 225.37 - Optical media transfer and electronic submission.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... by means of electronic submission via the Internet: (1) The Rail Equipment Accident/Incident Report... Crossing Accident/Incident Report (Form FRA F 6180.57); and (5) The Employee Human Factor Attachment (Form... Summary (Form FRA F 6180.55) in .pdf or .jpg format only; and (2) The completed accident/incident...

  20. 49 CFR 225.37 - Optical media transfer and electronic submission.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... by means of electronic submission via the Internet: (1) The Rail Equipment Accident/Incident Report... Crossing Accident/Incident Report (Form FRA F 6180.57); and (5) The Employee Human Factor Attachment (Form... Summary (Form FRA F 6180.55) in .pdf or .jpg format only; and (2) The completed accident/incident...

  1. 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

  2. 76 FR 67020 - Railroad Safety Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-28

    ...FRA announces the forty-fifth meeting of the RSAC, a Federal Advisory Committee that develops railroad safety regulations through a consensus process. The RSAC meeting topics will include opening remarks from the FRA Administrator, and status reports will be provided by the Electronic Device Distraction, Critical Incident, Track Safety Standards, Dark Territory, Passenger Safety, and Medical......

  3. 77 FR 19054 - Railroad Safety Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-29

    ...FRA announces the forty-sixth meeting of the RSAC, a Federal Advisory Committee that develops railroad safety regulations through a consensus process. The RSAC meeting topics will include opening remarks from the FRA Administrator, and status reports will be provided by the Track Safety Standards, Critical Incident, Dark Territory, Fatigue Management, Risk Reduction, Electronic Device......

  4. 75 FR 3959 - Railroad Safety Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-25

    ...FRA announces the forty-first meeting of the RSAC, a Federal advisory committee that develops railroad safety regulations through a consensus process. The RSAC meeting topics will include opening remarks from the FRA Administrator, and status reports will be provided by the Locomotive Standards, Passenger Safety, Track Safety Standards, and Medical Standards Working Groups. Status updates will......

  5. 75 FR 8788 - Railroad Safety Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-25

    ...FRA announces the forty-first meeting of the RSAC, a Federal Advisory Committee that develops railroad safety regulations through a consensus process. This meeting has been rescheduled from the weather- postponed February 11, 2010, meeting (75 FR 3959). The RSAC meeting topics will include opening remarks from the FRA Associate Administrator for Railroad Safety, and status reports will be......

  6. 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

    ...To comply with the Federal Civil Penalties Inflation Adjustment Act of 1990, FRA is adjusting the aggravated maximum penalty that it will apply when assessing a civil penalty for a violation of a railroad safety statute, regulation, or order under its authority. In particular, FRA is increasing the aggravated maximum civil penalty (i.e., the maximum civil penalty per violation where a grossly......

  7. 49 CFR 260.35 - Environmental assessment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... replacement environmental review procedures that the FRA may later issue and the NEPA regulation of the Council on Environmental Quality (“CEQ Regulation”) (40 CFR Part 1500) will govern the FRA's compliance... 49 Transportation 4 2011-10-01 2011-10-01 false Environmental assessment. 260.35 Section...

  8. 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... U.S.C. 3506, 3507; 5 CFR 1320.5, 1320.8(d)(1), 1320.12. On April 20, 2011, FRA published a 60-day... approval. 76 FR 22165. FRA received no comments in response to this notice. Before OMB decides whether...

  9. 77 FR 40701 - Notification of Petition for Approval; Informational Filing and Request for Waiver

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-10

    ... conduct a high-speed rail (HSR) demonstration project. FRA has assigned the petition Docket Number FRA.... Louis, MO, as part of the high-speed rail program. The demonstration segments are on UP's Joliet... High Speed Rail 2A Route Construction Contract (the ``2A Agreement'') dated March 4, 2011, as...

  10. 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...-Nevada Interstate Maglev Project under the FRA's Next Generation High Speed Rail Technology Demonstration... magnetic levitation ] technology high-speed ground transportation system. During the late 1990s, FRA...

  11. 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

    ... passenger rail transportation between southern California and Las Vegas using proven high-speed rail... 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...

  12. 77 FR 64183 - Notice of Availability of a Final General Conformity Determination for the California High-Speed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-18

    ... General Conformity requirements. The California High Speed Rail Authority (Authority), as the Project... California High-Speed Train System Merced to Fresno Section AGENCY: Federal Railroad Administration (FRA... Section of the California High-Speed Train (HST) System on September 18, 2012. FRA is the lead...

  13. 77 FR 53164 - Railroad Workplace Safety; Adjacent-Track On-Track Safety for Roadway Workers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-31

    ... 76 FR 74586. In response, FRA received two petitions for reconsideration (Petitions) that raised... order to permit interested parties an opportunity to respond to the Petitions. See 77 FR 13978. FRA... Federal Railroad Administration 49 CFR Part 214 RIN 2130-AC37 Railroad Workplace Safety; Adjacent-Track...

  14. 49 CFR Appendix A to Part 231 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... where circumstances warrant. See 49 CFR part 209, appendix A. 2 This schedule uses section numbers from FRA's Safety Appliance Defect Code, a restatement of the CFR text in a reorganized format. For... than the CFR. FRA reserves the right, should litigation become necessary, to substitute in...

  15. 49 CFR Appendix A to Part 231 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... where circumstances warrant. See 49 CFR part 209, appendix A. 2 This schedule uses section numbers from FRA's Safety Appliance Defect Code, a restatement of the CFR text in a reorganized format. For... than the CFR. FRA reserves the right, should litigation become necessary, to substitute in...

  16. 49 CFR Appendix A to Part 231 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... where circumstances warrant. See 49 CFR part 209, appendix A. 2 This schedule uses section numbers from FRA's Safety Appliance Defect Code, a restatement of the CFR text in a reorganized format. For... than the CFR. FRA reserves the right, should litigation become necessary, to substitute in...

  17. 49 CFR Appendix A to Part 231 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... where circumstances warrant. See 49 CFR part 209, appendix A. 2 This schedule uses section numbers from FRA's Safety Appliance Defect Code, a restatement of the CFR text in a reorganized format. For... than the CFR. FRA reserves the right, should litigation become necessary, to substitute in...

  18. 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,...

  19. 49 CFR Appendix A to Part 231 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... where circumstances warrant. See 49 CFR part 209, appendix A. 2 This schedule uses section numbers from FRA's Safety Appliance Defect Code, a restatement of the CFR text in a reorganized format. For... than the CFR. FRA reserves the right, should litigation become necessary, to substitute in...

  20. 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

    ...According to data from FRA's Management Information System, the rail industry's random drug testing positive rate has remained below 1.0 percent for the last two years. FRA's Administrator has therefore determined that the minimum annual random drug testing rate for the period January 1, 2014, through December 31, 2014, will remain at 25 percent of covered railroad employees. In addition,......

  1. 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...

  2. 49 CFR 230.60 - Time of washing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Time of washing. 230.60 Section 230.60... 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 78 FR 25346 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-30

    ..., 2000 (65 FR 19477). Issued in Washington, DC, on April 24, 2013. Robert C. Lauby, Deputy Associate... Equipment; End-of-Train Devices. FRA assigned the petition Docket Number FRA-2013-0007. Specifically, ICR... currently operates a total of five cycle trains and requests to extend the required mileage interval of...

  8. 77 FR 64374 - Notification of Petition for Approval; Port Authority Trans-Hudson Product Safety Plan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-19

    ... a Product Safety Plan (PSP). FRA assigned the petition Docket Number FRA-2012-0075. PATH is... maintenance costs. PATH asserts that the PSP demonstrates that Digicode has been designed in a highly safe... Train Control Systems. The PSP itself provides the detailed description of the Digicode track...

  9. 77 FR 29307 - Control of Alcohol and Drug Use: Addition of Post-Accident Toxicological Testing for Non...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-17

    ...Since 1985, FRA has conducted post-accident toxicological testing (post-accident testing) on blood, urine, and, if an employee is deceased, tissue samples from railroad employees involved in serious train accidents. If an accident qualifies for post-accident testing, FRA routinely conducts tests for alcohol, marijuana, cocaine, phencyclidine (PCP), and certain amphetamines, opiates,......

  10. 76 FR 70532 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-14

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

  11. 76 FR 30855 - Accident/Incident Reporting Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-27

    ... and 13563 but also DOT policies and procedures. See 44 FR 11034; February 26, 1979. FRA has analyzed... recording standards and guidance. See 75 FR 68862. Following the publication of the final rule, FRA received... regulations and to enhance the quality of information available for railroad casualty analysis. See 73...

  12. 75 FR 43840 - Inflation Adjustment of the Ordinary Maximum and Aggravated Maximum Civil Monetary Penalties for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-27

    ... civil monetary penalties per the Inflation Act. See 74 FR 68701 (December 29, 2009). FRA's maximum and... materials violation was $275. 69 FR 30590, May 28, 2004. To implement these SAFETEA-LU amendments to the maximum and minimum penalties, FRA issued a final rule that was published on December 26, 2006, 71...

  13. 75 FR 4703 - Track Safety Standards; Continuous Welded Rail (CWR)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-29

    ...This document responds to a petition for reconsideration of FRA's final rule published on August 25, 2009, which revised the Track Safety Standards. FRA received one petition questioning the definitions of ``adjusting/de-stressing'' and ``buckling-prone condition'' as they are used with regard to continuous welded rail...

  14. 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... Federal Railroad Administration Adoption of the Environmental Impact Statement (EIS) and Participation in... Administration (FRA), Department of Transportation (DOT). ACTION: Notice of adoption and recirculation of...

  15. 77 FR 75696 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-21

    ... August 28, 2012, Capital Passenger Car, Inc. (CPC) of Orrville, OH, has petitioned the Federal Railroad.... FRA assigned the petition Docket Number FRA-2012-0072. CPC has petitioned for a permanent waiver of... Duplate ASI PPG Safety Glass. CPC states that barring one incident of vandalism in the spring of 2010...

  16. 77 FR 50323 - Railroad Workplace Safety; Roadway Worker Protection Miscellaneous Revisions (RRR)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-20

    ... hazards faced by roadway workers. 57 FR 54038. ] FRA held workshops to solicit the views of the railroad... regulatory negotiation. 59 FR 42200. The FAC was tasked with submitting a report, including proposed... as the basis for FRA's first RWP NPRM, which was published on March 14, 1996. 61 FR 10528....

  17. 77 FR 21311 - Locomotive Safety Standards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-09

    .... Brakes, General E. Locomotive Cab Temperature F. Headlights G. Alerters H. Locomotive Electronics I... a minimum permissible locomotive cab temperature. FRA also independently developed a proposal for... in the NPRM and retains it in this final rule. Locomotive Cab Temperature In 1998, FRA led an...

  18. 77 FR 64249 - Track Safety Standards; Improving Rail Integrity

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-19

    ... railroad safety.'' See 36 FR 20336. FRA envisioned the new Standards to be an evolving set of safety... the Standards in 1998. See 63 FR 34029, June 22, 1998; 63 FR 54078, Oct. 8, 1998. Pursuant to 49 U.S.C... track constructed with concrete crossties. See 76 FR 18073. FRA received two petitions...

  19. 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...

  20. 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...

  1. 77 FR 77181 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-31

    ...In accordance with the Paperwork Reduction Act of 1995 and its implementing regulations, the Federal Railroad Administration (FRA) hereby announces that it is seeking approval of the following proposed information collection activities. Before submitting this proposed information collection request (ICR) for clearance by the Office of Management and Budget (OMB), FRA is soliciting public......

  2. 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... Administrator of FRA on rulemakings and other safety program issues. 61 FR 9740 (Mar. 11, 1996). RSAC's charter under the Federal Advisory Committee Act (Pub. L. 92-463) was most recently renewed in 2012. 77 FR...

  3. 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... Drug and Alcohol Testing Rates In a final rule published on December 2, 1994 (59 FR 62218),...

  4. 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..., 1994 (59 FR 62218), FRA announced that it will set future minimum random drug and alcohol testing...

  5. 78 FR 76190 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-16

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

  6. 78 FR 36738 - Signal System Reporting Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-19

    ... modernize our regulatory system and to reduce unjustified regulatory burdens and costs.'' See 77 FR 28469... annually. See 61 FR 33871 (July 1, 1996). FRA determined that a five-year reporting period would...). In 1984, FRA amended its Signal and Train Control Regulations, including 49 CFR Part 233. See 49...

  7. 78 FR 12825 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-25

    ... (65 FR 19477). Issued in Washington, DC, on February 20, 2013. Robert C. Lauby, Deputy Associate... 5, 2011, the Central California Traction Company (CCT) and the United Transportation Union (UTU...). FRA assigned the petition Docket Number FRA-2009-0077. In their petition, CCT and UTU seek relief...

  8. 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

    ... progress towards completion of their PTCIP and TIP. 5. All other entities. Collaborative project... deployment within the 24 months after the grant award. FRA will give preference to collaborative projects by... maintainability), and fit within FRA's primary mission of ensuring the safety of the Nation's approximately...

  9. 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...

  10. 12 CFR 211.41 - Authority, purpose, and scope.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 2 2013-01-01 2013-01-01 false Authority, purpose, and scope. 211.41 Section... et seq.) (FRA), and the Bank Holding Company Act of 1956, as amended (12 U.S.C. 1841 et seq.) (BHC... the FRA (12 U.S.C. 601 through 604a) (Agreement Corporations); and bank holding companies (as...