Science.gov

Sample records for advanced intercross line

  1. QTL mapping of complex binary traits in an advanced intercross line.

    PubMed

    Moradi Marjaneh, M; Martin, I C A; Kirk, E P; Harvey, R P; Moran, C; Thomson, P C

    2012-07-01

    An advanced intercross line (AIL) is an easier and more cost-effective approach compared to recombinant inbred lines for fine mapping of quantitative trait loci (QTL) identified by F(2) designs. In an AIL, a complex binary trait can be mapped through analysis of either continuously distributed proxy traits for the liability of the binary trait or the liability itself, the latter presenting the greater statistical challenge. In another work, we successfully applied both approaches in an AIL to fine map previously identified QTL underlying anatomical parameters of the cardiac inter-atrial septum including patent foramen ovale. Here, we describe the statistical methods that we used to analyse complex binary traits in our AIL design. This is achieved using a likelihood-based method, with the expectation-maximisation algorithm allowing use of standard logistic regression methods for model fitting.

  2. QTL Mapping in New Arabidopsis thaliana Advanced Intercross-Recombinant Inbred Lines

    PubMed Central

    Singh, Anandita; Warthmann, Norman; Kim, Min Chul; Maloof, Julin N.; Loudet, Olivier; Trainer, Gabriel T.; Dabi, Tsegaye; Borevitz, Justin O.; Chory, Joanne; Weigel, Detlef

    2009-01-01

    Background Even when phenotypic differences are large between natural or domesticated strains, the underlying genetic basis is often complex, and causal genomic regions need to be identified by quantitative trait locus (QTL) mapping. Unfortunately, QTL positions typically have large confidence intervals, which can, for example, lead to one QTL being masked by another, when two closely linked loci are detected as a single QTL. One strategy to increase the power of precisely localizing small effect QTL, is the use of an intercross approach before inbreeding to produce Advanced Intercross RILs (AI-RILs). Methodology/Principal Findings We present two new AI-RIL populations of Arabidopsis thaliana genotyped with an average intermarker distance of 600 kb. The advanced intercrossing design led to expansion of the genetic map in the two populations, which contain recombination events corresponding to 50 kb/cM in an F2 population. We used the AI-RILs to map QTL for light response and flowering time, and to identify segregation distortion in one of the AI-RIL populations due to a negative epistatic interaction between two genomic regions. Conclusions/Significance The two new AI-RIL populations, EstC and KendC, derived from crosses of Columbia (Col) to Estland (Est-1) and Kendallville (Kend-L) provide an excellent resource for high precision QTL mapping. Moreover, because they have been genotyped with over 100 common markers, they are also excellent material for comparative QTL mapping. PMID:19183806

  3. New Arabidopsis Advanced Intercross Recombinant Inbred Lines Reveal Female Control of Nonrandom Mating1[OPEN

    PubMed Central

    Fitz Gerald, Jonathan Nesbit; Carlson, Ann Louise; Smith, Evadne; Maloof, Julin N.; Weigel, Detlef; Chory, Joanne; Borevitz, Justin O.; Swanson, Robert John

    2014-01-01

    Female control of nonrandom mating has never been genetically established, despite being linked to inbreeding depression and sexual selection. In order to map the loci that control female-mediated nonrandom mating, we constructed a new advanced intercross recombinant inbred line (RIL) population derived from a cross between Arabidopsis (Arabidopsis thaliana) accessions Vancouver (Van-0) and Columbia (Col-0) and mapped quantitative trait loci (QTLs) responsible for nonrandom mating and seed yield traits. We genotyped a population of 490 RILs. A subset of these lines was used to construct an expanded map of 1,061.4 centimorgans with an average interval of 6.7 ± 5.3 centimorgans between markers. QTLs were then mapped for female- and male-mediated nonrandom mating and seed yield traits. To map the genetic loci responsible for female-mediated nonrandom mating and seed yield, we performed mixed pollinations with genetically marked Col-0 pollen and Van-0 pollen on RIL pistils. To map the loci responsible for male-mediated nonrandom mating and seed yield, we performed mixed pollinations with genetically marked Col-0 and RIL pollen on Van-0 pistils. Composite interval mapping of these data identified four QTLs that control female-mediated nonrandom mating and five QTLs that control female-mediated seed yield. We also identified four QTLs that control male-mediated nonrandom mating and three QTLs that control male-mediated seed yield. Epistasis analysis indicates that several of these loci interact. To our knowledge, the results of these experiments represent the first time female-mediated nonrandom mating has been genetically defined. PMID:24623850

  4. Common determinants of body size and eye size in chickens from an advanced intercross line.

    PubMed

    Prashar, Ankush; Hocking, Paul M; Erichsen, Jonathan T; Fan, Qiao; Saw, Seang Mei; Guggenheim, Jeremy A

    2009-06-15

    Myopia development is characterised by an increased axial eye length. Therefore, identifying factors that influence eye size may provide new insights into the aetiology of myopia. In humans, axial length is positively correlated to height and weight, and in mice, eye weight is positively correlated with body weight. The purpose of this study was to examine the relationship between eye size and body size in chickens from a genetic cross in which alleles with major effects on eye and body size were segregating. Chickens from a cross between a layer line (small body size and eye size) and a broiler line (large body and eye size) were interbred for 10 generations so that alleles for eye and body size would have the chance to segregate independently. At 3 weeks of age, 510 chicks were assessed using in vivo high resolution A-scan ultrasonography and keratometry. Equatorial eye diameter and eye weight were measured after enucleation. The variations in eye size parameters that could be explained by body weight (BW), body length (BL), head width (HW) and sex were examined using multiple linear regression. It was found that BW, BL and HW and sex together predicted 51-56% of the variation in eye weight, axial length, corneal radius, and equatorial eye diameter. By contrast, the same variables predicted only 22% of the variation in lens thickness. After adjusting for sex, the three body size parameters predicted 45-49% of the variation in eye weight, axial length, corneal radius, and eye diameter, but only 0.4% of the variation in lens thickness. In conclusion, about half of the variation in eye size in the chickens of this broiler-layer advanced intercross line is likely to be determined by pleiotropic genes that also influence body size. Thus, mapping the quantitative trait loci (QTL) that determine body size may be useful in understanding the genetic determination of eye size (a logical inference of this result is that the 20 or more genetic variants that have recently

  5. Fine mapping of quantitative trait loci using advanced intercross lines of mice and positional cloning of the corresponding genes.

    PubMed

    Iraqi, F

    2000-12-01

    High-resolution mapping of quantitative trait loci (QTLs) is an essential step towards positional cloning and identification of the corresponding genes. Most QTL detection and mapping studies in mice have been carried out using F2 intercross and backcross populations. As a consequence of the limited number of recombination events in small chromosomal regions, this has generally permitted mapping to only relatively large confidence intervals of 20 to 40 cM. A number of population designs have been proposed to increase recombination level in crosses. This includes advanced intercross lines (AIL) described by Darvasi and Soller [Genomics. 1995; 141: 1199-1207]. In this report demonstration of the utility of the AIL approach for fine mapping of QTL, which previously had been mapped with 95% confidence interval to 20 to 40 cM in a F2 intercross, will be presented. The methodological approaches to go from the fine-mapped QTL to the identification of the actual genes and mutations are discussed.

  6. Use of an Advanced Intercross Line Population for Precise Mapping of Quantitative Trait Loci for Gray Leaf Spot Resistance in Maize

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Grey leaf spot (GLS) (caused by Cercospora zeae-maydis) of maize (Zea mays L.)is an important fungal disease of maize in the U.S. and worldwide. The IBM population, an advanced intercross recombinant inbred line population derived from a cross between the maize lines Mo17 (resistant) and B73 (sus...

  7. Quantitative trait loci for energy balance traits in an advanced intercross line derived from mice divergently selected for heat loss.

    PubMed

    Leamy, Larry J; Elo, Kari; Nielsen, Merlyn K; Thorn, Stephanie R; Valdar, William; Pomp, Daniel

    2014-01-01

    Obesity in human populations, currently a serious health concern, is considered to be the consequence of an energy imbalance in which more energy in calories is consumed than is expended. We used interval mapping techniques to investigate the genetic basis of a number of energy balance traits in an F11 advanced intercross population of mice created from an original intercross of lines selected for increased and decreased heat loss. We uncovered a total of 137 quantitative trait loci (QTLs) for these traits at 41 unique sites on 18 of the 20 chromosomes in the mouse genome, with X-linked QTLs being most prevalent. Two QTLs were found for the selection target of heat loss, one on distal chromosome 1 and another on proximal chromosome 2. The number of QTLs affecting the various traits generally was consistent with previous estimates of heritabilities in the same population, with the most found for two bone mineral traits and the least for feed intake and several body composition traits. QTLs were generally additive in their effects, and some, especially those affecting the body weight traits, were sex-specific. Pleiotropy was extensive within trait groups (body weights, adiposity and organ weight traits, bone traits) and especially between body composition traits adjusted and not adjusted for body weight at sacrifice. Nine QTLs were found for one or more of the adiposity traits, five of which appeared to be unique. The confidence intervals among all QTLs averaged 13.3 Mb, much smaller than usually observed in an F2 cross, and in some cases this allowed us to make reasonable inferences about candidate genes underlying these QTLs. This study combined QTL mapping with genetic parameter analysis in a large segregating population, and has advanced our understanding of the genetic architecture of complex traits related to obesity.

  8. Genome-Wide Association Studies and the Problem of Relatedness Among Advanced Intercross Lines and Other Highly Recombinant Populations

    PubMed Central

    Cheng, Riyan; Lim, Jackie E.; Samocha, Kaitlin E.; Sokoloff, Greta; Abney, Mark; Skol, Andrew D.; Palmer, Abraham A.

    2010-01-01

    Model organisms offer many advantages for the genetic analysis of complex traits. However, identification of specific genes is often hampered by a lack of recombination between the genomes of inbred progenitors. Recently, genome-wide association studies (GWAS) in humans have offered gene-level mapping resolution that is possible because of the large number of accumulated recombinations among unrelated human subjects. To obtain analogous improvements in mapping resolution in mice, we used a 34th generation advanced intercross line (AIL) derived from two inbred strains (SM/J and LG/J). We used simulations to show that familial relationships among subjects must be accounted for when analyzing these data; we then used a mixed model that included polygenic effects to address this problem in our own analysis. Using a combination of F2 and AIL mice derived from the same inbred progenitors, we identified genome-wide significant, subcentimorgan loci that were associated with methamphetamine sensitivity, (e.g., chromosome 18; LOD = 10.5) and non-drug-induced locomotor activity (e.g., chromosome 8; LOD = 18.9). The 2-LOD support interval for the former locus contains no known genes while the latter contains only one gene (Csmd1). This approach is broadly applicable in terms of phenotypes and model organisms and allows GWAS to be performed in multigenerational crosses between and among inbred strains where familial relatedness is often unavoidable. PMID:20439773

  9. QTLs for murine red blood cell parameters in LG/J and SM/J F(2) and advanced intercross lines.

    PubMed

    Bartnikas, Thomas B; Parker, Clarissa C; Cheng, Riyan; Campagna, Dean R; Lim, Jackie E; Palmer, Abraham A; Fleming, Mark D

    2012-06-01

    Red blood cells are essential for oxygen transport and other physiologic processes. Red cell characteristics are typically determined by complete blood counts which measure parameters such as hemoglobin levels and mean corpuscular volumes; these parameters reflect the quality and quantity of red cells in the circulation at any particular moment. To identify the genetic determinants of red cell parameters, we performed genome-wide association analysis on LG/J×SM/J F2 and F34 advanced intercross lines using single nucleotide polymorphism genotyping and a novel algorithm for mapping in the combined populations. We identified significant quantitative trait loci for red cell parameters on chromosomes 6, 7, 8, 10, 12, and 17; our use of advanced intercross lines reduced the quantitative trait loci interval width from 1.6- to 9.4-fold. Using the genomic sequences of LG/J and SM/J mice, we identified nonsynonymous coding single nucleotide polymorphisms in candidate genes residing within quantitative trait loci and performed sequence alignments and molecular modeling to gauge the potential impact of amino acid substitutions. These results should aid in the identification of genes critical for red cell physiology and metabolism and demonstrate the utility of advanced intercross lines in uncovering genetic determinants of inherited traits.

  10. Fine-mapping alleles for body weight in LG/J × SM/J F₂ and F(34) advanced intercross lines.

    PubMed

    Parker, Clarissa C; Cheng, Riyan; Sokoloff, Greta; Lim, Jackie E; Skol, Andrew D; Abney, Mark; Palmer, Abraham A

    2011-10-01

    The present study measured variation in body weight using a combined analysis in an F(2) intercross and an F(34) advanced intercross line (AIL). Both crosses were derived from inbred LG/J and SM/J mice, which were selected for large and small body size prior to inbreeding. Body weight was measured at 62 (± 5) days of age. Using an integrated GWAS and forward model selection approach, we identified 11 significant QTLs that affected body weight on ten different chromosomes. With these results we developed a full model that explained over 18% of the phenotypic variance. The median 1.5-LOD support interval was 5.55 Mb, which is a significant improvement over most prior body weight QTLs. We identified nonsynonymous coding SNPs between LG/J and SM/J mice in order to further narrow the list of candidate genes. Three of the genes with nonsynonymous coding SNPs (Rad23b, Stk33, and Anks1b) have been associated with adiposity, waist circumference, and body mass index in human GWAS, thus providing evidence that these genes may underlie our QTLs. Our results demonstrate that a relatively small number of loci contribute significantly to the phenotypic variance in body weight, which is in marked contrast to the situation in humans. This difference is likely to be the result of strong selective pressure and the simplified genetic architecture, both of which are important advantages of our system.

  11. Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

    PubMed Central

    Cheverud, J M; Lawson, H A; Bouckaert, K; Kossenkov, A V; Showe, L C; Cort, L; Blankenhorn, E P; Bedelbaeva, K; Gourevitch, D; Zhang, Y; Heber-Katz, E

    2014-01-01

    External ear hole closure in LG/J mice represents a model of regenerative response. It is accompanied by the formation of a blastema-like structure and the re-growth of multiple tissues, including cartilage. The ability to regenerate tissue is heritable. An F34 advanced intercross line of mice (Wustl:LG,SM-G34) was generated to identify genomic loci involved in ear hole closure over a 30-day healing period. We mapped 19 quantitative trait loci (QTL) for ear hole closure. Individual gene effects are relatively small (0.08 mm), and most loci have co-dominant effects with phenotypically intermediate heterozygotes. QTL support regions were limited to a median size of 2 Mb containing a median of 19 genes. Positional candidate genes were evaluated using differential transcript expression between LG/J and SM/J healing tissue, function analysis and bioinformatic analysis of single-nucleotide polymorphisms in and around positional candidate genes of interest. Analysis of the set of 34 positional candidate genes and those displaying expression differences revealed over-representation of genes involved in cell cycle regulation/DNA damage, cell migration and adhesion, developmentally related genes and metabolism. This indicates that the healing phenotype in LG/J mice involves multiple physiological mechanisms. PMID:24569637

  12. Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line.

    PubMed

    Cheverud, J M; Lawson, H A; Bouckaert, K; Kossenkov, A V; Showe, L C; Cort, L; Blankenhorn, E P; Bedelbaeva, K; Gourevitch, D; Zhang, Y; Heber-Katz, E

    2014-05-01

    External ear hole closure in LG/J mice represents a model of regenerative response. It is accompanied by the formation of a blastema-like structure and the re-growth of multiple tissues, including cartilage. The ability to regenerate tissue is heritable. An F34 advanced intercross line of mice (Wustl:LG,SM-G34) was generated to identify genomic loci involved in ear hole closure over a 30-day healing period. We mapped 19 quantitative trait loci (QTL) for ear hole closure. Individual gene effects are relatively small (0.08 mm), and most loci have co-dominant effects with phenotypically intermediate heterozygotes. QTL support regions were limited to a median size of 2 Mb containing a median of 19 genes. Positional candidate genes were evaluated using differential transcript expression between LG/J and SM/J healing tissue, function analysis and bioinformatic analysis of single-nucleotide polymorphisms in and around positional candidate genes of interest. Analysis of the set of 34 positional candidate genes and those displaying expression differences revealed over-representation of genes involved in cell cycle regulation/DNA damage, cell migration and adhesion, developmentally related genes and metabolism. This indicates that the healing phenotype in LG/J mice involves multiple physiological mechanisms.

  13. Fine mapping of complex traits in non-model species: using next generation sequencing and advanced intercross lines in Japanese quail

    PubMed Central

    2012-01-01

    Background As for other non-model species, genetic analyses in quail will benefit greatly from a higher marker density, now attainable thanks to the evolution of sequencing and genotyping technologies. Our objective was to obtain the first genome wide panel of Japanese quail SNP (Single Nucleotide Polymorphism) and to use it for the fine mapping of a QTL for a fear-related behaviour, namely tonic immobility, previously localized on Coturnix japonica chromosome 1. To this aim, two reduced representations of the genome were analysed through high-throughput 454 sequencing: AFLP (Amplified Fragment Length Polymorphism) fragments as representatives of genomic DNA, and EST (Expressed Sequence Tag) as representatives of the transcriptome. Results The sequencing runs produced 399,189 and 1,106,762 sequence reads from cDNA and genomic fragments, respectively. They covered over 434 Mb of sequence in total and allowed us to detect 17,433 putative SNP. Among them, 384 were used to genotype two Advanced Intercross Lines (AIL) obtained from three quail lines differing for duration of tonic immobility. Despite the absence of genotyping for founder individuals in the analysis, the previously identified candidate region on chromosome 1 was refined and led to the identification of a candidate gene. Conclusions These data confirm the efficiency of transcript and AFLP-sequencing for SNP discovery in a non-model species, and its application to the fine mapping of a complex trait. Our results reveal a significant association of duration of tonic immobility with a genomic region comprising the DMD (dystrophin) gene. Further characterization of this candidate gene is needed to decipher its putative role in tonic immobility in Coturnix. PMID:23066875

  14. The heritability of oxycodone reward and concomitant phenotypes in a LG/J × SM/J mouse advanced intercross line.

    PubMed

    Bryant, Camron D; Guido, Michael A; Kole, Loren A; Cheng, Riyan

    2014-07-01

    The rewarding property of opioids likely contributes to their abuse potential. Therefore, determining the genetic basis of opioid reward could aid in understanding the neurobiological mechanisms of opioid addiction, provided that it is a heritable trait. Here, we characterized the rewarding property of the widely abused prescription opioid oxycodone (OXY) in the conditioned place preference (CPP) assay using LG/J and SM/J parental inbred mouse strains and 17 parent-offspring families of a LG/J × SM/J F47 /F48 advanced intercross line (AIL). Following OXY training (5 mg/kg, i.p.), SM/J mice and AIL mice, but not LG/J mice, showed an increase in preference for the OXY-paired side, suggesting a genetic basis for OXY-CPP. SM/J mice showed greater locomotor activity than LG/J mice in response to both saline and OXY. LG/J, SM/J, and AIL mice all exhibited robust OXY-induced locomotor sensitization. Narrow-sense heritability (h(2) ) estimates of the phenotypes using linear regression and maximum likelihood estimation showed good agreement (r = 0.91). OXY-CPP was clearly not a heritable trait whereas drug-free- and OXY-induced locomotor activity and sensitization were significantly and sometimes highly heritable (h(2)  = 0.30-0.84). Interestingly, the number of transitions between the saline- and OXY-paired sides emerged as a reliably heritable trait following OXY training (h(2)  = 0.46-0.66) and could represent a genetic component of drug-seeking behavior. Thus, although OXY-CPP does not appear to be amenable to genome-wide quantitative trait locus mapping, this protocol will be useful for mapping other traits potentially relevant to opioid abuse.

  15. Fine mapping of QTL for prepulse inhibition in LG/J and SM/J mice using F(2) and advanced intercross lines.

    PubMed

    Samocha, K E; Lim, J E; Cheng, R; Sokoloff, G; Palmer, A A

    2010-10-01

    Prepulse inhibition (PPI) of the startle response is a measure of sensorimotor gating, a process that filters out extraneous sensory, motor and cognitive information. Humans with neurological and psychiatric disorders, including schizophrenia, obsessive-compulsive disorder and Huntington's disease, exhibit a reduction in PPI. Habituation of the startle response is also disrupted in schizophrenic patients. In order to elucidate the genes involved in sensorimotor gating, we phenotyped 472 mice from an F(2) cross between LG/J × SM/J for PPI and genotyped these mice genome-wide using 162 single nucleotide polymorphism (SNP) markers. We used prepulse intensity levels that were 3, 6 and 12 dB above background (PPI3, PPI6 and PPI12, respectively). We identified a significant quantitative trait locus (QTL) on chromosome 12 for all three prepulse intensities as well as a significant QTL for both PPI6 and PPI12 on chromosome 11. We identified QTLs on chromosomes 7 and 17 for the startle response when sex was included as an interactive covariate and found a QTL for habituation of the startle response on chromosome 4. We also phenotyped 135 mice from an F(34) advanced intercross line (AIL) between LG/J × SM/J for PPI and genotyped them at more than 3000 SNP markers. Inclusions of data from the AIL mice reduced the size of several of these QTLs to less than 5 cM. These results will be useful for identifying genes that influence sensorimotor gaiting and show the power of AIL for fine mapping of QTLs.

  16. Methamphetamine-induced conditioned place preference in LG/J and SM/J mouse strains and an F45/F46 advanced intercross line.

    PubMed

    Bryant, Camron D; Kole, Loren A; Guido, Michael A; Cheng, Riyan; Palmer, Abraham A

    2012-01-01

    The conditioned place preference (CPP) test is frequently used to evaluate the rewarding properties of drugs of abuse in mice. Despite its widespread use in transgenic and knockout experiments, there are few forward genetic studies using CPP to identify novel genes contributing to drug reward. In this study, we tested LG/J and SM/J inbred strains and the parents/offspring of 10 families of an F(45)/F(46) advanced intercross line (AIL) for methamphetamine-induced CPP (MA-CPP) once per week over 2 weeks. Both LG/J and SM/J mice exhibited significant MA-CPP that was not significantly different between the two strains. Furthermore, LG/J mice showed significantly less acute MA-induced locomotor activity as well as locomotor sensitization following subsequent MA injections. AIL mice (N = 105) segregating LG/J and SM/J alleles also demonstrated significant MA-CPP that was equal in magnitude between the first and second week of training. Importantly, MA-CPP in AIL mice did not correlate with drug-free or MA-induced locomotor activity, indicating that MA-CPP was not confounded by test session activity and implying that MA-CPP is genetically distinct from acute psychomotor sensitivity. We estimated the heritability of MA-CPP and locomotor phenotypes using midparent-offspring regression and maximum likelihood estimates derived from the kinship coefficients of the AIL pedigree. Heritability estimates of MA-CPP were low (0-0.21) and variable (SE = 0-0.33) which reflected our poor power to estimate heritability using only 10 midparent-offspring observations. In sum, we established a short-term protocol for MA-CPP in AIL mice that could reveal LG/J and SM/J alleles important for MA reward. The use of highly recombinant genetic populations like AIL should facilitate the identification of these genes and may have implications for understanding psychostimulant abuse in humans.

  17. Precise mapping of Quantitative Trait Loci for Resistance to Southern Leaf Blight, caused by Cochliobolus heterostrophus race O, using an Advanced Intercross Maize Population.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The IBM population, an advanced intercross recombinant inbred line population derived from a cross between the maize lines Mo17 (resistant) and B73 (susceptible), was evaluated in four environments for resistance to southern leaf blight (SLB) disease caused by Cochliobolus heterostrophus race O. ...

  18. Genetic factors and diet affect long-bone length in the F34 LG,SM advanced intercross.

    PubMed

    Norgard, Elizabeth A; Lawson, Heather A; Pletscher, L Susan; Wang, Bing; Brooks, Victoria R; Wolf, Jason B; Cheverud, James M

    2011-04-01

    Previous studies on the LG,SM advanced intercross line have identified approximately 40 quantitative trait loci (QTL) for long -bone (humerus, ulna, femur, and tibia) lengths. In this study, long-bone-length QTL were fine-mapped in the F(34) generation (n = 1424) of the LG,SM advanced intercross. Environmental effects were assessed by dividing the population by sex between high-fat and low-fat diets, producing eight sex/diet cohorts. We identified 145 individual bone-length QTL comprising 45 pleiotropic QTL; 69 replicated QTL from previous studies, 35 were new traits significant at previously identified loci, and 41 were novel QTL. Many QTL affected only a subset of the population based on sex and/or diet. Eight of ten known skeletal growth genes were upregulated in 3-week-old LG/J male proximal tibial growth plates relative to SM/J. The sequences of parental strains LG/J and SM/J indicated the presence of over half a million polymorphisms in the confidence intervals of these 45 QTL. We examined 526 polymorphisms and found that 97 represented radical changes to amino acid composition while 40 were predicted to be deleterious to protein function. Additional experimentation is required to understand how changes in gene regulation or protein function can alter the genetic architecture and interact with the environment to produce phenotypic variation.

  19. High-Resolution Genetic Mapping of Complex Traits from a Combined Analysis of F2 and Advanced Intercross Mice

    PubMed Central

    Parker, Clarissa C.; Carbonetto, Peter; Sokoloff, Greta; Park, Yeonhee J.; Abney, Mark; Palmer, Abraham A.

    2014-01-01

    Genetic influences on anxiety disorders are well documented; however, the specific genes underlying these disorders remain largely unknown. To identify quantitative trait loci (QTL) for conditioned fear and open field behavior, we used an F2 intercross (n = 490) and a 34th-generation advanced intercross line (AIL) (n = 687) from the LG/J and SM/J inbred mouse strains. The F2 provided strong support for several QTL, but within wide chromosomal regions. The AIL yielded much narrower QTL, but the results were less statistically significant, despite the larger number of mice. Simultaneous analysis of the F2 and AIL provided strong support for QTL and within much narrower regions. We used a linear mixed-model approach, implemented in the program QTLRel, to correct for possible confounding due to familial relatedness. Because we recorded the full pedigree, we were able to empirically compare two ways of accounting for relatedness: using the pedigree to estimate kinship coefficients and using genetic marker estimates of “realized relatedness.” QTL mapping using the marker-based estimates yielded more support for QTL, but only when we excluded the chromosome being scanned from the marker-based relatedness estimates. We used a forward model selection procedure to assess evidence for multiple QTL on the same chromosome. Overall, we identified 12 significant loci for behaviors in the open field and 12 significant loci for conditioned fear behaviors. Our approach implements multiple advances to integrated analysis of F2 and AILs that provide both power and precision, while maintaining the advantages of using only two inbred strains to map QTL. PMID:25236452

  20. Replication of long-bone length QTL in the F9-F10 LG,SM advanced intercross.

    PubMed

    Norgard, Elizabeth A; Jarvis, Joseph P; Roseman, Charles C; Maxwell, Taylor J; Kenney-Hunt, Jane P; Samocha, Kaitlin E; Pletscher, L Susan; Wang, Bing; Fawcett, Gloria L; Leatherwood, Christopher J; Wolf, Jason B; Cheverud, James M

    2009-04-01

    Quantitative trait locus (QTL) mapping techniques are frequently used to identify genomic regions associated with variation in phenotypes of interest. However, the F(2) intercross and congenic strain populations usually employed have limited genetic resolution resulting in relatively large confidence intervals that greatly inhibit functional confirmation of statistical results. Here we use the increased resolution of the combined F(9) and F(10) generations (n = 1455) of the LG,SM advanced intercross to fine-map previously identified QTL associated with the lengths of the humerus, ulna, femur, and tibia. We detected 81 QTL affecting long-bone lengths. Of these, 49 were previously identified in the combined F(2)-F(3) population of this intercross, while 32 represent novel contributors to trait variance. Pleiotropy analysis suggests that most QTL affect three to four long bones or serially homologous limb segments. We also identified 72 epistatic interactions involving 38 QTL and 88 novel regions. This analysis shows that using later generations of an advanced intercross greatly facilitates fine-mapping of confidence intervals, resolving three F(2)-F(3) QTL into multiple linked loci and narrowing confidence intervals of other loci, as well as allowing identification of additional QTL. Further characterization of the biological bases of these QTL will help provide a better understanding of the genetics of small variations in long-bone length.

  1. REPLICATION OF LONG BONE LENGTH QTL IN THE F9 - F10 LG,SM ADVANCED INTERCROSS

    PubMed Central

    Norgard, Elizabeth A.; Jarvis, Joseph P.; Roseman, Charles C.; Maxwell, Taylor J.; Kenney-Hunt, Jane P.; Samocha, Kaitlin E.; Pletscher, L. Susan; Wang, Bing; Fawcett, Gloria L.; Leatherwood, Christopher J.; Wolf, Jason B.; Cheverud, James M.

    2009-01-01

    Quantitative trait locus (QTL) mapping techniques are frequently used to identify genomic regions associated with variation in phenotypes of interest. However, the F2 intercross and congenic strain populations usually employed have limited genetic resolution resulting in relatively large confidence intervals that greatly inhibit functional confirmation of statistical results. Here, we use the increased resolution of the combined F9 and F10 generations (n=1,455) of the LG,SM advanced intercross to fine-map previously identified QTL associated with the lengths of the humerus, ulna, femur, and tibia. We detected 81 QTL affecting long bone lengths. Of these, 49 were previously identified in the combined F2-F3 population of this intercross while 32 represent novel contributors to trait variance. Pleiotropy analysis suggests that most QTL affect 3-4 long bones or serially homologous limb segments. We also identified 72 epistatic interactions involving 38 QTL and 88 novel regions. This analysis shows that using later generations of an advanced intercross greatly facilitates fine-mapping of confidence intervals, resolving 3 F2-F3 QTL into multiple linked loci and narrowing confidence intervals of other loci, as well as allowing identification of additional QTL. Further characterization of the biological bases of these QTL will help provide a better understanding of the genetics of small variations in long bone length. PMID:19306044

  2. A multiparent advanced generation inter-cross population for genetic analysis in wheat.

    PubMed

    Huang, Bevan E; George, Andrew W; Forrest, Kerrie L; Kilian, Andrzej; Hayden, Matthew J; Morell, Matthew K; Cavanagh, Colin R

    2012-09-01

    We present the first results from a novel multiparent advanced generation inter-cross (MAGIC) population derived from four elite wheat cultivars. The large size of this MAGIC population (1579 progeny), its diverse genetic composition and high levels of recombination all contribute to its value as a genetic resource. Applications of this resource include interrogation of the wheat genome and the analysis of gene-trait association in agronomically important wheat phenotypes. Here, we report the utilization of a MAGIC population for the first time for linkage map construction. We have constructed a linkage map with 1162 DArT, single nucleotide polymorphism and simple sequence repeat markers distributed across all 21 chromosomes. We benchmark this map against a high-density DArT consensus map created by integrating more than 100 biparental populations. The linkage map forms the basis for further exploration of the genetic architecture within the population, including characterization of linkage disequilibrium, founder contribution and inclusion of an alien introgression into the genetic map. Finally, we demonstrate the application of the resource for quantitative trait loci mapping using the complex traits plant height and hectolitre weight as a proof of principle.

  3. A Random-Model Approach to QTL Mapping in Multiparent Advanced Generation Intercross (MAGIC) Populations.

    PubMed

    Wei, Julong; Xu, Shizhong

    2016-02-01

    Most standard QTL mapping procedures apply to populations derived from the cross of two parents. QTL detected from such biparental populations are rarely relevant to breeding programs because of the narrow genetic basis: only two alleles are involved per locus. To improve the generality and applicability of mapping results, QTL should be detected using populations initiated from multiple parents, such as the multiparent advanced generation intercross (MAGIC) populations. The greatest challenges of QTL mapping in MAGIC populations come from multiple founder alleles and control of the genetic background information. We developed a random-model methodology by treating the founder effects of each locus as random effects following a normal distribution with a locus-specific variance. We also fit a polygenic effect to the model to control the genetic background. To improve the statistical power for a scanned marker, we release the marker effect absorbed by the polygene back to the model. In contrast to the fixed-model approach, we estimate and test the variance of each locus and scan the entire genome one locus at a time using likelihood-ratio test statistics. Simulation studies showed that this method can increase statistical power and reduce type I error compared with composite interval mapping (CIM) and multiparent whole-genome average interval mapping (MPWGAIM). We demonstrated the method using a public Arabidopsis thaliana MAGIC population and a mouse MAGIC population.

  4. Association mapping for frost tolerance using multi-parent advanced generation inter-cross (MAGIC) population in faba bean (Vicia faba L.).

    PubMed

    Sallam, Ahmed; Martsch, Regina

    2015-08-01

    A multi-parent advanced generation inter-cross (MAGIC) derived from 11 founder lines in faba bean was used in this study to identify quantitative trait loci (QTL) for frost tolerance traits using the association mapping method with 156 SNP markers. This MAGIC population consists of a set of 189 genotypes from the Göttingen Winter Bean Population. The association panel was tested in two different experiments, i.e. a frost and a hardening experiment. Six morphological traits, leaf fatty acid composition, relative water content in shoots were scored in this study. The genotypes presented a large genetic variation for all traits that were highly heritable after frost and after hardening. High phenotypic significant correlations were established between traits. The principal coordinates analysis resulted in no clear structure in the current population. Association mapping was performed using a general linear model and mixed linear model with kinship. A False discovery rate of 0.20 (and 0.05) was used to test the significance of marker-trait association. As a result, many putative QTLs for 13 morphological and physiological traits were detected using both models. The results reveal that QTL mapping by association analysis is a powerful method of detecting the alleles associated with frost tolerance in the winter faba bean which can be used in accelerating breeding programs.

  5. Mapping of quantitative trait loci affecting eggshell quality on chromosome 9 in an F(2) intercross between two chicken lines divergently selected for eggshell strength.

    PubMed

    Takahashi, H; Yang, D; Sasaki, O; Furukawa, T; Nirasawa, K

    2009-10-01

    Broken and cracked eggshells are major causes of significant economic losses to the egg production industry. The quantitative trait loci (QTL) on chromosome 9 influencing the quality of eggshells were identified by analysing an intercross between two parent lines developed from the same founder population by a two-way selection for eggshell strength with non-destructive deformation conducted over 14 generations. Chromosome-wide highly significant (P < 0.01) QTL associated with egg weight (EW), short length of egg (SLE), long length of egg (LLE) and eggshell weight were mapped to the distal region of chromosome 9. Among the QTL affecting EW, SLE and LLE, ovocalyxin-32 was identified as a potential candidate gene influencing eggshell traits. Marker-assisted selection based on these QTL could be used to develop strategies for reducing the breakage and cracking of eggs in commercial layer houses. PMID:19780721

  6. Association between ovocalyxin-32 gene haplotypes and eggshell quality traits in an F2 intercross between two chicken lines divergently selected for eggshell strength.

    PubMed

    Takahashi, H; Sasaki, O; Nirasawa, K; Furukawa, T

    2010-10-01

    Broken and cracked eggshells contribute significantly to economic losses in the egg production industry. We previously identified ovocalyxin-32 as a potential gene influencing eggshell traits, by analysing an intercross between two parent lines developed from the same founder population by a two-way selection for eggshell strength with non-destructive deformation (DEF) conducted over 14 generations. We determined the nucleotide sequences of six ovocalyxin-32 exons in the parent individuals and analysed the association between ovocalyxin-32 and eggshell traits in the F2 individuals. We identified three haplotypes (W, M and S) of ovocalyxin-32 in the parent individuals. A mismatch amplification mutation assay was performed to distinguish six diplotype individuals (WW, MM, SS, WM, MS and WS) inthe F2 population. The egg weight (EW) of SS-diplotype individuals was significantly higher than that of WW-, WM- and WS-diplotypes. Short length of the egg (SLE) of SS-diplotype individuals was significantly higher than that of WW-, WM- and MS-diplotypes. Long length of the egg (LLE) of SS-diplotype individuals was significantly higher than that of WM and WS-diplotypes. DEF of WW-diplotype individuals was significantly higher than that ofSS-, WM, MS and WM-diplotypes. Haplotypic effect analyses showed significant differences between the W-haplotype and the S-haplotypes in the EW, SLE, LLE and DEF. The DEF of M-haplotype was significantly lower than that of W- and S-haplotypes. These results suggest that S- and M-haplotypes are critical for high quality of eggshells in the F2 population. In conclusion, ovocalyxin-32 is a useful marker of eggshell traits and can be used to develop strategies for improving eggshell traits in commercial layer houses. PMID:20331600

  7. Genetic loci that regulate ectopic calcification in response to knee trauma in LG/J by SM/J advanced intercross mice.

    PubMed

    Rai, Muhammad Farooq; Schmidt, Eric J; Hashimoto, Shingo; Cheverud, James M; Sandell, Linda J

    2015-10-01

    This study reports on genetic susceptibility to ectopic calcification in the LG/J and SM/J advanced intercross mice. Using 347 mice in 98 full-sibships, destabilization of medial meniscus (DMM) was performed to induce joint injury. We found that joint destabilization instigated ectopic calcifications as detected and quantified by micro-CT. We performed quantitative trait locus (QTL) analysis to map ectopic calcification phenotypes to discrete genomic locations. To validate the functional significance of the selected QTL candidate genes, we compared mRNA expression between parental LG/J and SM/J inbred strains. Overall, we detected 20 QTLs affecting synovial and meniscus calcification phenotypes with 11 QTLs linked to synovial calcification. Functional and bioinformatic analyses of single nucleotide polymorphism (SNP) identified functional classifications relevant to angiogenesis (Myo1e, Kif26b, Nprl3, Stab2, Fam105b), bone metabolism/calcification (Tle3, Tgfb2, Lipc, Nfe2l1, Ank, Fam105b), arthritis (Stab2, Tbx21, Map4k4, Hoxb9, Larp6, Col1a2, Adam10, Timp3, Nfe2l1, Trpm3), and ankylosing-spondylitis (Ank, Pon1, Il1r2, Tbkbp1) indicating that ectopic calcification involves multiple mechanisms. Furthermore, the expression of 11 out of 78 candidate genes was significantly different between LG/J and SM/J. Correlation analysis showed that Aff3, Fam81a, Syn3, and Ank were correlated with synovial calcification. Taken together, our findings of multiple genetic loci suggest the involvement of multiple genes contributing to ectopic calcification.

  8. Genetic Loci that Regulate Ectopic Calcification in Response to Knee Trauma in LG/J by SM/J Advanced Intercross Mice

    PubMed Central

    Rai, Muhammad Farooq; Schmidt, Eric J.; Hashimoto, Shingo; Cheverud, James M.; Sandell, Linda J.

    2016-01-01

    This study reports on genetic susceptibility to ectopic calcification in the LG/J and SM/J advanced intercross mice. Using 347 mice in 98 full-sibships, destabilization of medial meniscus (DMM) was performed to induce joint injury. We performed quantitative trait locus (QTL) analysis to map ectopic calcification phenotypes to discrete genomic locations. To validate the functional significance of the selected QTL candidate genes, we compared mRNA expression between parental LG/J and SM/J inbred strains. We found that joint destabilization instigated ectopic calcifications as detected and quantified by micro-CT. Overall, we detected 20 QTLs affecting synovial and meniscus calcification phenotypes with 11 QTLs linked to synovial calcification. Functional and bioinformatic analyses of single nucleotide polymorphism identified functional classifications relevant to angiogenesis (Myo1e, Kif26b, Nprl3, Stab2, Fam105b), bone metabolism/calcification (Tle3, Tgfb2, Lipc, Nfe2l1, Ank, Fam105b), arthritis (Stab2, Tbx21, Map4k4, Hoxb9, Larp6, Col1a2, Adam10, Timp3, Nfe2l1, Trpm3), and ankylosing-spondylitis (Ank, Pon1, Il1r2, Tbkbp1) indicating that ectopic calcification involves multiple mechanisms. Furthermore, the expression of 11 candidate genes was significantly different between LG/J and SM/J. Correlation analysis showed that Aff3, Fam81a, Syn3, and Ank were correlated with synovial calcification. Taken together, our findings of multiple genetic loci suggest the involvement of multiple genes contributing to ectopic calcification. PMID:25989359

  9. Fine mapping QTLs in advanced interbred lines and other outbred populations

    PubMed Central

    Gonzales, Natalia M.; Palmer, Abraham A.

    2014-01-01

    Quantitative genetic studies in model organisms, particularly in mice, have been extremely successful in identifying chromosomal regions that are associated with a wide variety of behavioral and other traits. However, it is now widely understood that identification of the underlying genes will be far more challenging. In the last few years, a variety of populations have been utilized in an effort to more finely map these chromosomal regions with the goal of identifying specific genes. The common property of these newer populations is that linkage disequilibrium spans relatively short distances, which permits fine-scale mapping resolution. This review focuses on advanced intercross lines (AILs) which are the simplest such population. As originally proposed in 1995 by Darvasi and Soller, an AIL is the product of intercrossing two inbred strains beyond the F2 generation. Unlike recombinant inbred strains, AILs are maintained as outbred populations; brother-sister matings are specifically avoided. Each generation of intercrossing beyond the F2 further degrades linkage disequilibrium between adjacent makers, which allows for fine scale mapping of quantitative trait loci (QTLs). Advances in genotyping technology and techniques for the statistical analysis of AILs have permitted rapid advances in the application of AILs. We review some of the analytical issues and available software, including QTLRel, EMMA, EMMAX, GEMMA, TASSEL, GRAMMAR, WOMBAT, Mendel and others. PMID:24906874

  10. Fine-Mapping the Wheat Snn1 Locus Conferring Sensitivity to the Parastagonospora nodorum Necrotrophic Effector SnTox1 Using an Eight Founder Multiparent Advanced Generation Inter-Cross Population

    PubMed Central

    Cockram, James; Scuderi, Alice; Barber, Toby; Furuki, Eiko; Gardner, Keith A.; Gosman, Nick; Kowalczyk, Radoslaw; Phan, Huyen P.; Rose, Gemma A.; Tan, Kar-Chun; Oliver, Richard P.; Mackay, Ian J.

    2015-01-01

    The necrotrophic fungus Parastagonospora nodorum is an important pathogen of one of the world’s most economically important cereal crops, wheat (Triticum aestivum L.). P. nodorum produces necrotrophic protein effectors that mediate host cell death, providing nutrients for continuation of the infection process. The recent discovery of pathogen effectors has revolutionized disease resistance breeding for necrotrophic diseases in crop species, allowing often complex genetic resistance mechanisms to be broken down into constituent parts. To date, three effectors have been identified in P. nodorum. Here we use the effector, SnTox1, to screen 642 progeny from an eight-parent multiparent advanced generation inter-cross (i.e., MAGIC) population, genotyped with a 90,000-feature single-nucleotide polymorphism array. The MAGIC founders showed a range of sensitivity to SnTox1, with transgressive segregation evident in the progeny. SnTox1 sensitivity showed high heritability, with quantitative trait locus analyses fine-mapping the Snn1 locus to the short arm of chromosome 1B. In addition, a previously undescribed SnTox1 sensitivity locus was identified on the long arm of chromosome 5A, termed here QSnn.niab-5A.1. The peak single-nucleotide polymorphism for the Snn1 locus was converted to the KASP genotyping platform, providing breeders and researchers a simple and cheap diagnostic marker for allelic state at Snn1. PMID:26416667

  11. Advanced Nacelle Acoustic Lining Concepts Development

    NASA Technical Reports Server (NTRS)

    Bielak, G.; Gallman, J.; Kunze, R.; Murray, P.; Premo, J.; Kosanchick, M.; Hersh, A.; Celano, J.; Walker, B.; Yu, J.; Parrott, Tony L. (Technical Monitor)

    2002-01-01

    The work reported in this document consisted of six distinct liner technology development subtasks: 1) Analysis of Model Scale ADP Fan Duct Lining Data (Boeing): An evaluation of an AST Milestone experiment to demonstrate 1995 liner technology superiority relative to that of 1992 was performed on 1:5.9 scale model fan rig (Advanced Ducted Propeller) test data acquired in the NASA Glenn 9 x 15 foot wind tunnel. The goal of 50% improvement was deemed satisfied. 2) Bias Flow Liner Investigation (Boeing, VCES): The ability to control liner impedance by low velocity bias flow through liner was demonstrated. An impedance prediction model to include bias flow was developed. 3) Grazing Flow Impedance Testing (Boeing): Grazing flow impedance tests were conducted for comparison with results achieved at four different laboratories. 4) Micro-Perforate Acoustic Liner Technology (BFG, HAE, NG): Proof of concept testing of a "linear liner." 5) Extended Reaction Liners (Boeing, NG): Bandwidth improvements for non-locally reacting liner were investigated with porous honeycomb core test liners. 6) Development of a Hybrid Active/Passive Lining Concept (HAE): Synergism between active and passive attenuation of noise radiated by a model inlet was demonstrated.

  12. Advances in gamma-ray line astronomy

    NASA Technical Reports Server (NTRS)

    Ramaty, R.; Lingenfelter, R. E.

    1983-01-01

    Gamma ray line observations of solar flares, gamma ray transients, and the galactic center are reviewed and interpreted. Prospects of future line detections are discussed. Previously announced in STAR as N82-27200

  13. Expanding the genetic variability of flatpea using tissues culture, mutagenesis, and intercrossing techniques

    SciTech Connect

    Coulombe, B.A.

    1988-01-01

    Flatpea (Lathyrus sylvestris L.) is a potentially valuable forage legume but contains high levels of 2,4-diaminobutyric acid (DABA), a compound that can have adverse effects on some animals, including rats and poultry. To increase genetic variability in foliar DABA content and other traits of interest, three approaches were utilized: (1) regeneration of flatpea plants from tissue culture to produce potential somaclonal variants, (2) seed irradiation and screening of potentially mutated progeny, and (3) intercrossing among flatpea accessions. Low-frequency whole plant regeneration of flatpea was obtained from hypocotyl-derived callus cultures. Initial tests established that the effective range of gamma-irradiation for seed treatment was between 10.0 and 17.5 kR. Within this range, reduction in percentage of both seedling height and plant survival was a linear function of dose. Individual M{sub 2} plants that contained reduced levels of DABA were identified. No significant trend in DABA concentration with increasing gamma irradiation was apparent. Flatpea pollination methods were evaluated prior to utilization of intercrossing for inducing genetic variability. Appropriate flower stages for emasculation were determined by in vitro germination of pollen. Lines that produced high numbers of seeds per pollination were identified by crossing in all possible combinations among seven flatpea accessions.

  14. Fine-mapping of muscle weight QTL in LG/J and SM/J intercrosses.

    PubMed

    Lionikas, A; Cheng, R; Lim, J E; Palmer, A A; Blizard, D A

    2010-09-01

    Genetic variation plays a substantial role in variation in strength, but the underlying mechanisms remain poorly understood. The objective of the present study was to examine the mechanisms underlying variation in muscle mass, a predictor of strength, between LG/J and SM/J strains, which are the inbred progeny of mice selected, respectively, for high and low body weight. We measured weight of five hindlimb muscles in LG/J and SM/J males and females, in F(1) and F(2) intercrosses, and in an advanced intercross (AI), F(34), between the two. F(2) mice were genotyped using 162 SNPs throughout the genome; F(34) mice were genotyped at 3,015 SNPs. A twofold difference in muscle mass between the LG/J and SM/J mouse strains was observed. Integrated genome-wide association analysis in the combined population of F(2) and AI identified 22 quantitative trait loci (QTL; genome-wide P < 0.05) affecting muscle weight on Chr 2 (2 QTL), 4, 5, 6 (7 QTL), 7 (4 QTL), 8 (4 QTL), and 11 (3 QTL). The LG/J allele conferred greater muscle weight in all cases. The 1.5-LOD QTL support intervals ranged between 0.3 and 13.4 Mb (median 3.7 Mb) restricting the list of candidates to between 5 and 97 genes. Selection for body weight segregated the alleles affecting skeletal muscle, the most abundant tissue in the body. Combination of analyses in an F(2) and AI was an effective strategy to detect and refine the QTL in a genome-wide manner. The achieved resolution facilitates further elucidation of the underlying genetic mechanisms affecting muscle mass.

  15. [Intercross cascaded dual-layer resonant sub-wavelength gratings].

    PubMed

    Chen, Yong-li; Zhao, Da-zun

    2009-04-01

    A security grating structure, intercross cascaded dual-layer resonant sub-wavelength grating structure, is presented. It can broaden the resonant wavelength width of resonant sub-wavelength gratings and obtain the better optical variable effect. The full-width-at half-maximum (FWHM) broadening mechanism of security grating structures is analyzed. The FWHM is dependent on the energy coupled into the grating waveguide layer. The grating structure parameters are optimized and designed. The resonance performance and grating fabrication tolerances are also studied numerically using the vector diffraction theory (the rigorous coupled wave theory). Simulation results indicate that the value of the spectral resonant peak for the security grating structure is not decreased as the incident angle increases or decreases and the maximum FWHM of different depth of grating grooves is about seven times that of the basic resonant grating structure. The resonant dual grating waveguide structure is a kind of security grating configuration with the potential to achieve higher industry application value and its resonance performance is not sensitive to manufacture errors. PMID:19626922

  16. On-Line NDE for Advanced Reactor Designs

    NASA Astrophysics Data System (ADS)

    Nakagawa, N.; Inanc, F.; Thompson, R. B.; Junker, W. R.; Ruddy, F. H.; Beatty, J. M.; Arlia, N. G.

    2003-03-01

    This expository paper introduces the concept of on-line sensor methodologies for monitoring the integrity of components in next generation power systems, and explains general benefits of the approach, while describing early conceptual developments of suitable NDE methodologies. The paper first explains the philosophy behind this approach (i.e. the design-for-inspectability concept). Specifically, we describe where and how decades of accumulated knowledge and experience in nuclear power system maintenance are utilized in Generation IV power system designs, as the designs are being actively developed, in order to advance their safety and economy. Second, we explain that Generation IV reactor design features call for the replacement of the current outage-based maintenance by on-line inspection and monitoring. Third, the model-based approach toward design and performance optimization of on-line sensor systems, using electromagnetic, ultrasonic, and radiation detectors, will be explained. Fourth, general types of NDE inspections that are considered amenable to on-line health monitoring will be listed. Fifth, we will describe specific modeling developments to be used for radiography, EMAT UT, and EC detector design studies.

  17. Raman mapping using advanced line-scanning systems: geological applications.

    PubMed

    Bernard, Sylvain; Beyssac, Olivier; Benzerara, Karim

    2008-11-01

    By allowing nondestructive chemical and structural imaging of heterogeneous samples with a micrometer spatial resolution, Raman mapping offers unique capabilities for assessing the spatial distribution of both mineral and organic phases within geological samples. Recently developed line-scanning Raman mapping techniques have made it possible to acquire Raman maps over large, millimeter-sized, zones of interest owing to a drastic decrease of the data acquisition time without losing spatial or spectral resolution. The synchronization of charge-coupled device (CCD) measurements with x,y motorized stage displacement has allowed dynamic line-scanning Raman mapping to be even more efficient: total acquisition time may be reduced by a factor higher than 100 compared to point-by-point mapping. Using two chemically and texturally complex geological samples, a fossil megaspore in a metamorphic rock and aragonite-garnet intergrowths in an Eclogitic marble, we compare here two recent versions of line-scanning Raman mapping systems and discuss their respective advantages and disadvantages in terms of acquisition time, image quality, spatial and imaging resolutions, and signal-to-noise ratio. We show that line-scanning Raman mapping techniques are particularly suitable for the characterization of such samples, which are representative of the general complexity of geological samples. PMID:19007458

  18. Raman mapping using advanced line-scanning systems: geological applications.

    PubMed

    Bernard, Sylvain; Beyssac, Olivier; Benzerara, Karim

    2008-11-01

    By allowing nondestructive chemical and structural imaging of heterogeneous samples with a micrometer spatial resolution, Raman mapping offers unique capabilities for assessing the spatial distribution of both mineral and organic phases within geological samples. Recently developed line-scanning Raman mapping techniques have made it possible to acquire Raman maps over large, millimeter-sized, zones of interest owing to a drastic decrease of the data acquisition time without losing spatial or spectral resolution. The synchronization of charge-coupled device (CCD) measurements with x,y motorized stage displacement has allowed dynamic line-scanning Raman mapping to be even more efficient: total acquisition time may be reduced by a factor higher than 100 compared to point-by-point mapping. Using two chemically and texturally complex geological samples, a fossil megaspore in a metamorphic rock and aragonite-garnet intergrowths in an Eclogitic marble, we compare here two recent versions of line-scanning Raman mapping systems and discuss their respective advantages and disadvantages in terms of acquisition time, image quality, spatial and imaging resolutions, and signal-to-noise ratio. We show that line-scanning Raman mapping techniques are particularly suitable for the characterization of such samples, which are representative of the general complexity of geological samples.

  19. Cell line development for biomanufacturing processes: recent advances and an outlook.

    PubMed

    Le, Huong; Vishwanathan, Nandita; Jacob, Nitya M; Gadgil, Mugdha; Hu, Wei-Shou

    2015-08-01

    At the core of a biomanufacturing process for recombinant proteins is the production cell line. It influences the productivity and product quality. Its characteristics also dictate process development, as the process is optimized to complement the producing cell to achieve the target productivity and quality. Advances in the past decade, from vector design to cell line screening, have greatly expanded our capability to attain producing cell lines with certain desired traits. Increasing availability of genomic and transcriptomic resources for industrially important cell lines coupled with advances in genome editing technology have opened new avenues for cell line development. These developments are poised to help biosimilar manufacturing, which requires targeting pre-defined product quality attributes, e.g., glycoform, to match the innovator's range. This review summarizes recent advances and discusses future possibilities in this area.

  20. Disease evaluations and agronomic traits of advanced peanut breeding lines in 2012

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A total of 38 peanut cultivars and high-oleic advanced breeding lines were evaluated in small field plots in 2012 for yield, seed grade and size, and resistance to Sclerotinia minor and Sclerotium rolfsii. Among the 14 Spanish entries, the cultivar Tamnut 06 (3258 lbs/acre) and breeding line 140-1O...

  1. Integrating first-line treatment options into clinical practice: what's new in advanced melanoma?

    PubMed

    Dummer, Reinhard; Schadendorf, Dirk; Ascierto, Paolo A; Larkin, James; Lebbé, Celeste; Hauschild, Axel

    2015-12-01

    Melanoma remains a serious form of skin cancer in Europe and worldwide. Localized, early-stage melanomas can usually be treated with surgical excision. However, the prognosis is poorer for patients with advanced disease. Before 2011, treatment for advanced melanoma included palliative surgery and/or radiotherapy, and chemotherapy with or without immunotherapy, such as interleukin-2. As none of these treatments had shown survival benefits in patients with advanced melanoma, European guidelines had recommended that patients be entered into clinical trials. The lack of approved first-line options and varying access to clinical trials meant that European clinicians relied on experimental regimens and chemotherapy-based treatments when no other options were available. Since 2011, ipilimumab, an immuno-oncology therapy, and vemurafenib and dabrafenib, targeted agents that inhibit mutant BRAF, have been approved by the European Medicines Agency for the treatment of advanced melanoma. More recently, the MEK inhibitor, trametinib, received European marketing authorization for use in patients with BRAF mutation-positive advanced melanoma. In 2014, the anti-PD-1 antibody nivolumab was approved as a first-line therapy in Japan. Whereas nivolumab and another anti-PD-1 antibody, pembrolizumab, were approved as second-line therapies in the USA, their recent approval in Europe are for first-line use based on new clinical trial data in this setting. Together these agents are changing clinical practice and making therapeutic decisions more complex. Here, we discuss current and emerging therapeutic options for the first-line treatment of advanced melanoma, and how these therapies can be optimized to provide the best possible outcomes for patients. PMID:26426764

  2. Disease evaluations and agronomic traits of advanced peanut breeding lines in 2015

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A total of 20 commercially available peanut cultivars and high-oleic advanced breeding lines were evaluated in small field plots in 2015 for agronomic traits (crop value, yield, seed grade, and characteristics). Environmental conditions in 2015 were not favorable for Sclerotinia blight, southern bl...

  3. Disease evaluations and agronomic traits of advanced peanut breeding lines in 2014

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A total of 23 commercially available peanut cultivars and high-oleic advanced breeding lines were evaluated in small field plots in 2014 for agronomic traits (crop value, yield, seed grade, and characteristics) and resistance to soilborne diseases. Among the 16 runner entries evaluated, Tamrun OL11...

  4. Pemetrexed Maintenance Therapy Following Bevacizumab-Containing First-Line Chemotherapy in Advanced Malignant Pleural Mesothelioma

    PubMed Central

    Jing, Xu-Quan; Zhou, Lei; Sun, Xin-Dong; Yu, Jin-Ming; Meng, Xue

    2016-01-01

    Abstract Malignant pleural mesothelioma (MPM) is a lethal disease with poor prognosis. The combination of cisplatin and pemetrexed has been confirmed as the standard of care for nonoperable MPM. Data have shown that the adoption of pemetrexed maintenance therapy (PMT) following first-line treatment appears extremely promising. We describe a 57-year-old man diagnosed as advanced MPM. We treated this patient with PMT after first-line cisplatin-based bevacizumab-containing chemotherapy and residual tumor disappeared after 6 course of PMT. A perfect response and a long progression-free survival (PFS) were reached with tumor mass disappearing and 14 months duration of PFS. This case suggests that adding bevacizumab to standard first-line chemotherapy is feasible and that PMT could be promising and useful for treating advanced MPM. We further entail a review of the literature on the first-line treatment, continuation maintenance therapy, switch maintenance therapy, and second-line treatment of patients with advanced MPM. PMID:27057918

  5. SunLine Transit Agency Advanced Technology Fuel Cell Bus Evaluation: Fourth Results Report

    SciTech Connect

    Eudy, L.; Chandler, K.

    2013-01-01

    SunLine Transit Agency, which provides public transit services to the Coachella Valley area of California, has demonstrated hydrogen and fuel cell bus technologies for more than 10 years. In May 2010, SunLine began demonstrating the advanced technology (AT) fuel cell bus with a hybrid electric propulsion system, fuel cell power system, and lithium-based hybrid batteries. This report describes operations at SunLine for the AT fuel cell bus and five compressed natural gas buses. The U.S. Department of Energy's National Renewable Energy Laboratory (NREL) is working with SunLine to evaluate the bus in real-world service to document the results and help determine the progress toward technology readiness. NREL has previously published three reports documenting the operation of the fuel cell bus in service. This report provides a summary of the results with a focus on the bus operation from February 2012 through November 2012.

  6. Advances in Mammalian Cell Line Development Technologies for Recombinant Protein Production

    PubMed Central

    Lai, Tingfeng; Yang, Yuansheng; Ng, Say Kong

    2013-01-01

    From 2006 to 2011, an average of 15 novel recombinant protein therapeutics have been approved by US Food and Drug Administration (FDA) annually. In addition, the expiration of blockbuster biologics has also spurred the emergence of biosimilars. The increasing numbers of innovator biologic products and biosimilars have thus fuelled the demand of production cell lines with high productivity. Currently, mammalian cell line development technologies used by most biopharmaceutical companies are based on either the methotrexate (MTX) amplification technology or the glutamine synthetase (GS) system. With both systems, the cell clones obtained are highly heterogeneous, as a result of random genome integration by the gene of interest and the gene amplification process. Consequently, large numbers of cell clones have to be screened to identify rare stable high producer cell clones. As such, the cell line development process typically requires 6 to 12 months and is a time, capital and labour intensive process. This article reviews established advances in protein expression and clone screening which are the core technologies in mammalian cell line development. Advancements in these component technologies are vital to improve the speed and efficiency of generating robust and highly productive cell line for large scale production of protein therapeutics. PMID:24276168

  7. SunLine Transit Agency Advanced Technology Fuel Cell Bus Evaluation: First Results Report

    SciTech Connect

    Eudy, L.; Chandler, K.

    2011-03-01

    This report describes operations at SunLine Transit Agency for their newest prototype fuel cell bus and five compressed natural gas (CNG) buses. In May 2010, SunLine began operating its sixth-generation hydrogen fueled bus, an Advanced Technology (AT) fuel cell bus that incorporates the latest design improvements to reduce weight and increase reliability and performance. The agency is collaborating with the U.S. Department of Energy's (DOE) National Renewable Energy Laboratory (NREL) to evaluate the bus in revenue service. This report provides the early data results and implementation experience of the AT fuel cell bus since it was placed in service.

  8. Optimal indications for second-line chemotherapy in advanced gastric cancer.

    PubMed

    Hasegawa, Hiroko; Fujitani, Kazumasa; Nakazuru, Shoichi; Hirao, Motohiro; Mita, Eiji; Tsujinaka, Toshimasa

    2012-04-01

    As it remains uncertain whether patients with advanced gastric cancer who progress after first-line chemotherapy should receive second-line chemotherapy, we attempted to identify the optimal indications for second-line chemotherapy. In this retrospective study, 101 patients were included in univariate and multivariate analyses to identify clinicopathological variables independently associated with longer survival postprogression (SPP), defined as the time from recognition of disease progression on first-line chemotherapy to death from any cause or last follow-up. The median SPP was 340 days. On multivariate analysis, performance status 2 [hazard ratio (HR), 14.234; 95% confidence interval (CI), 2.766-73.258], serum albumin level less than 3.5 g/dl (HR, 2.088; 95% CI, 1.047-4.060) at initiation of second-line chemotherapy, and time to progression less than 170 days on first-line chemotherapy (HR, 2.497; 95% CI, 1.227-5.083) were identified as independent prognostic factors associated with shorter SPP. The median SPP was 496, 375, and 232 days in patients with 0, 1, and 2 of these 3 negative prognostic factors, respectively (P=0.0002). The present study suggests that second-line chemotherapy would not be beneficial in patients with two or more of the following three negative prognostic factors: performance status 2, serum albumin less than 3.5 g/dl at initiation of second-line chemotherapy and time to progression less than 170 days on first-line chemotherapy.

  9. Advanced Learners' Comprehension of Discourse Connectives: The Role of L1 Transfer across On-Line and Off-Line Tasks

    ERIC Educational Resources Information Center

    Zufferey, Sandrine; Mak, Willem; Degand, Liesbeth; Sanders, Ted

    2015-01-01

    Discourse connectives are important indicators of textual coherence, and mastering them is an essential part of acquiring a language. In this article, we compare advanced learners' sensitivity to the meaning conveyed by connectives in an off-line grammaticality judgment task and an on-line reading experiment using eye-tracking. We also assess the…

  10. Two genes required for diabetes in BB rats. Evidence from cyclical intercrosses and backcrosses

    PubMed Central

    1984-01-01

    The BB rat develops a syndrome of autoimmune diabetes similar to Type I diabetes of man. It also has a severe T cell lymphopenia. As part of an ongoing breeding program to transfer the diabetogenic genes of the BB rat onto inbred rat strain backgrounds, diabetic animals were used in a backcross (BC)- intercross (IC)-backcross breeding scheme with Brown Norway (BN), Lewis (L), and Wistar-Furth (WF) inbred rats. We have used monoclonal antibodies to analyze both lymphopenia and major histocompatibility (MHC) antigens (the RT1 locus in the rat) in relation to the development of diabetes. To examine T cell subsets we used a panel of monoclonal antibodies, in particular W3/25 and OX19 , which discriminate the abnormal phenotype better than W3/13. In our breeding program, at least two independent genes or gene complexes are required for the expression of diabetes. One gene determines the lymphopenia, is inherited by simple autosomal recessive genetics and is not linked to the MHC. The second gene is linked to the MHC. Both genes are necessary, but neither gene is sufficient by itself for the development of diabetes. PMID:6202817

  11. Body Composition QTLs Identified in Intercross Populations Are Reproducible in Consomic Mouse Strains

    PubMed Central

    Lin, Cailu; Fesi, Brad D.; Marquis, Michael; Bosak, Natalia P.; Theodorides, Maria L.; Avigdor, Mauricio; McDaniel, Amanda H.; Duke, Fujiko F.; Lysenko, Anna; Khoshnevisan, Amin; Gantick, Brian R.; Arayata, Charles J.; Nelson, Theodore M.; Bachmanov, Alexander A.; Reed, Danielle R.

    2015-01-01

    Genetic variation contributes to individual differences in obesity, but defining the exact relationships between naturally occurring genotypes and their effects on fatness remains elusive. As a step toward positional cloning of previously identified body composition quantitative trait loci (QTLs) from F2 crosses of mice from the C57BL/6ByJ and 129P3/J inbred strains, we sought to recapture them on a homogenous genetic background of consomic (chromosome substitution) strains. Male and female mice from reciprocal consomic strains originating from the C57BL/6ByJ and 129P3/J strains were bred and measured for body weight, length, and adiposity. Chromosomes 2, 7, and 9 were selected for substitution because previous F2 intercross studies revealed body composition QTLs on these chromosomes. We considered a QTL confirmed if one or both sexes of one or both reciprocal consomic strains differed significantly from the host strain in the expected direction after correction for multiple testing. Using these criteria, we confirmed two of two QTLs for body weight (Bwq5-6), three of three QTLs for body length (Bdln3-5), and three of three QTLs for adiposity (Adip20, Adip26 and Adip27). Overall, this study shows that despite the biological complexity of body size and composition, most QTLs for these traits are preserved when transferred to consomic strains; in addition, studying reciprocal consomic strains of both sexes is useful in assessing the robustness of a particular QTL. PMID:26551037

  12. Genomic Prediction of Seed Quality Traits Using Advanced Barley Breeding Lines

    PubMed Central

    Nielsen, Nanna Hellum; Jahoor, Ahmed; Jensen, Jens Due; Orabi, Jihad; Cericola, Fabio; Edriss, Vahid; Jensen, Just

    2016-01-01

    Genomic selection was recently introduced in plant breeding. The objective of this study was to develop genomic prediction for important seed quality parameters in spring barley. The aim was to predict breeding values without expensive phenotyping of large sets of lines. A total number of 309 advanced spring barley lines tested at two locations each with three replicates were phenotyped and each line was genotyped by Illumina iSelect 9Kbarley chip. The population originated from two different breeding sets, which were phenotyped in two different years. Phenotypic measurements considered were: seed size, protein content, protein yield, test weight and ergosterol content. A leave-one-out cross-validation strategy revealed high prediction accuracies ranging between 0.40 and 0.83. Prediction across breeding sets resulted in reduced accuracies compared to the leave-one-out strategy. Furthermore, predicting across full and half-sib-families resulted in reduced prediction accuracies. Additionally, predictions were performed using reduced marker sets and reduced training population sets. In conclusion, using less than 200 lines in the training set can result in low prediction accuracy, and the accuracy will then be highly dependent on the family structure of the selected training set. However, the results also indicate that relatively small training sets (200 lines) are sufficient for genomic prediction in commercial barley breeding. In addition, our results indicate a minimum marker set of 1,000 to decrease the risk of low prediction accuracy for some traits or some families. PMID:27783639

  13. Learned fear, emotional reactivity and fear of heights: a factor analytic map from a large F(2) intercross of Roman rat strains.

    PubMed

    Aguilar, Raúl; Gil, Luis; Flint, Jonathan; Gray, Jeffrey A; Dawson, Gerard R; Driscoll, Peter; Giménez-Llort, Lydia; Escorihuela, Rosa M; Fernández-Teruel, Alberto; Tobeña, Adolf

    2002-01-01

    Anxiety-related behaviours were evaluated across various tests in a 800 F(2)-intercross of the Roman high- and low-avoidance inbred rats. These tests either evoke unlearned (open field [OF]; plus-maze [PM]; hole-board [HB]; spontaneous activity [A]; and acoustic startle reflex [ASR]) or learned (classical fear conditioning [CFC]; and shuttlebox avoidance conditioning [SAC]), anxious/fearful responses. Using factor analysis (oblique rotation), we obtained a six-fold solution with 14 variables derived from all tests. These six factors represented SAC, CFC, PM anxiety, PM and OF activity, ASR anxiety, plus a mixed whole of anxious and activity variables (from OF and A), respectively. In searching for a smaller number of meaningful factors, we applied a three-factor solution that coherently corresponded with differentiated facets of fearfulness, rather than with the tests. Results showed that (1) measures of SAC and CFC strongly loaded onto Factor 1, labelled as "Learned Fear"; (2) a blend of almost all variables loaded onto Factor 2, called "Emotional Reactivity"; and (3) open arm behaviour in the PM loaded onto Factor 3, called "Fear of Heights." After discussing limitations of this apparently consistent behavioural map of anxiety, we advance some connections between those factors with quantitative trait loci candidates (genetic markers) as detected in the same sample.

  14. Synthesis and characterization of advanced durum wheat hybrids and addition lines with thinopyrum chromosomes.

    PubMed

    Jauhar, Prem P; Peterson, Terrance S

    2013-01-01

    Durum wheat (Triticum turgidum L., 2n = 4x = 28; AABB genomes) is a natural hybrid-an allotetraploid between 2 wild species, Triticum urartu Tumanian (AA genome) and Aegilops speltoides Tausch (BB genome). Even at the allotetraploid level, durum wheat can tolerate chromosomal imbalance, for example, addition of alien chromosome 1E of diploid wheatgrass, Lophopyrum elongatum. Therefore, one way to broaden its genetic base is to add a desirable chromosome(s) from diploid wild relatives. We attempted chromosomal engineering with chromosomes of a diploid wheatgrass, Thinopyrum bessarabicum-a source of resistance to some diseases including Fusarium head blight. Several advanced hybrids and alien addition lines were studied using traditional cytology, multicolor fluorescent genomic in situ hybridization, and molecular markers. Hybrid derivatives varied in chromosome number from F1 to F8 generations and in backcross generations. In advanced generations, we exercised selection against 28-chromosome plants and in favor of 30-chromosome plants that helped recover 14 addition lines in the F8 generation, as indicated by the absence of segregation for 29-chromosome plants. Disomic additions showed regular meiosis with 15 bivalents, 14 of durum wheat, and 1 of Th. bessarabicum. The addition lines will facilitate further chromosome engineering work on durum wheat for broadening its genetic base. PMID:23396879

  15. Tungsten Contact and Line Resistance Reduction with Advanced Pulsed Nucleation Layer and Low Resistivity Tungsten Treatment

    NASA Astrophysics Data System (ADS)

    Chandrashekar, Anand; Chen, Feng; Lin, Jasmine; Humayun, Raashina; Wongsenakhum, Panya; Chang, Sean; Danek, Michal; Itou, Takamasa; Nakayama, Tomoo; Kariya, Atsushi; Kawaguchi, Masazumi; Hizume, Shunichi

    2010-09-01

    This paper describes electrical testing results of new tungsten chemical vapor deposition (CVD-W) process concepts that were developed to address the W contact and bitline scaling issues on 55 nm node devices. Contact resistance (Rc) measurements in complementary metal oxide semiconductor (CMOS) devices indicate that the new CVD-W process for sub-32 nm and beyond - consisting of an advanced pulsed nucleation layer (PNL) combined with low resistivity tungsten (LRW) initiation - produces a 20-30% drop in Rc for diffused NiSi contacts. From cross-sectional bright field and dark field transmission electron microscopy (TEM) analysis, such Rc improvement can be attributed to improved plugfill and larger in-feature W grain size with the advanced PNL+LRW process. More experiments that measured contact resistance for different feature sizes point to favorable Rc scaling with the advanced PNL+LRW process. Finally, 40% improvement in line resistance was observed with this process as tested on 55 nm embedded dynamic random access memory (DRAM) devices, confirming that the advanced PNL+LRW process can be an effective metallization solution for sub-32 nm devices.

  16. SunLine Transit Agency Advanced Technology Fuel Cell Bus Evaluation: Second Results Report and Appendices

    SciTech Connect

    Eudy, L.; Chandler, K.

    2011-10-01

    This report describes operations at SunLine Transit Agency for their newest prototype fuel cell bus and five compressed natural gas (CNG) buses. In May 2010, SunLine began operating its sixth-generation hydrogen fueled bus, an Advanced Technology (AT) fuel cell bus that incorporates the latest design improvements to reduce weight and increase reliability and performance. The agency is collaborating with the U.S. Department of Energy's (DOE) National Renewable Energy Laboratory (NREL) to evaluate the bus in revenue service. This is the second results report for the AT fuel cell bus since it was placed in service, and it focuses on the newest data analysis and lessons learned since the previous report. The appendices, referenced in the main report, provide the full background for the evaluation. They will be updated as new information is collected but will contain the original background material from the first report.

  17. SunLine Transit Agency Advanced Technology Fuel Cell Bus Evaluation: Third Results Reports

    SciTech Connect

    Eudy, L.; Chandler, K.

    2012-05-01

    This report describes operations at SunLine Transit Agency for their newest prototype fuel cell bus and five compressed natural gas (CNG) buses. In May 2010, SunLine began operating its sixth-generation hydrogen fueled bus, an Advanced Technology (AT) fuel cell bus that incorporates the latest design improvements to reduce weight and increase reliability and performance. The agency is collaborating with the U.S. Department of Energy's (DOE) National Renewable Energy Laboratory (NREL) to evaluate the bus in revenue service. NREL has previously published two reports documenting the operation of the fuel cell bus in service. This report provides a summary of the results with a focus on the bus operation from July 2011 through January 2012.

  18. A systematic approach to advanced cockpit warning systems for air transport operations: Line pilot preferences

    NASA Technical Reports Server (NTRS)

    Williams, D. H.; Simpson, C. A.

    1976-01-01

    Line pilots (fifty captains, first officers, and flight engineers) from 8 different airlines were administered a structured questionnaire relating to future warning system design and solutions to current warning system problems. This was followed by a semantic differential to obtain a factor analysis of 18 different cockpit warning signals on scales such as informative/distracting, annoying/soothing. Half the pilots received a demonstration of the experimental text and voice synthesizer warning systems before answering the questionnaire and the semantic differential. A control group answered the questionnaire and the semantic differential first, thus providing a check for the stability of pilot preferences with and without actual exposure to experimental systems. Generally, the preference data obtained revealed much consistency and strong agreement among line pilots concerning advance cockpit warning system design.

  19. Synchrotron X-Ray Microdiffraction Studies of Electromigration in Interconnect lines at the Advanced Light Source

    SciTech Connect

    Tamura, Nobumichi; Chen, Kai; Kunz, Martin

    2009-12-01

    Synchrotron polychromatic X-ray microdiffraction is a particularly suitable technique to study in situ the effect of electromigration in metal interconnects as add spatial resolution to grain orientation and strain sensitivity. This technique has been extensively used at the Advanced Light Source to monitor changes in aluminum and copper interconnect test structures while high-density current is passed into them during accelerated tests at elevated temperature. One of the principal findings is the observation of electromigration-induced plasticity in the metal lines that appear during the very early stages of electromigration. In some of the lines, high density of geometrically necessary dislocation are formed leading to additional diffusion paths causing an enhancement of electromigration effect at test temperature.

  20. The use of safeguards data for process monitoring in the Advanced Test Line for Actinide Separations

    SciTech Connect

    Barnes, J.W.; Yarbro, S.L.

    1987-01-01

    Los Alamos is constructing an integrated process monitoring/materials control and accounting (PM/MC and A) system in the Advanced Testing Line for Actinide Separations (ATLAS) at the Los Alamos Plutonium Facility. The ATLAS will test and demonstrate new methods for aqueous processing of plutonium. The ATLAS will also develop, test, and demonstrate the concepts for integrated process monitoring/materials control and accounting. We describe how this integrated PM/MC and A system will function and provide benefits to both process research and materials accounting personnel.

  1. Analysis of line integrated electron density using plasma position data on Korea Superconducting Tokamak Advanced Research

    SciTech Connect

    Nam, Y. U.; Chung, J.

    2010-10-15

    A 280 GHz single-channel horizontal millimeter-wave interferometer system has been installed for plasma electron density measurements on the Korea Superconducting Tokamak Advanced Research (KSTAR) device. This system has a triangular beam path that does not pass through the plasma axis due to geometrical constraints in the superconducting tokamak. The term line density on KSTAR has a different meaning from the line density of other tokamaks. To estimate the peak density and the mean density from the measured line density, information on the position of the plasma is needed. The information has been calculated from tangentially viewed visible images using the toroidal symmetry of the plasma. Interface definition language routines have been developed for this purpose. The calculated plasma position data correspond well to calculation results from magnetic analysis. With the position data and an estimated plasma profile, the peak density and the mean density have been obtained from the line density. From these results, changes of plasma density themselves can be separated from effects of the plasma movements, so they can give valuable information on the plasma status.

  2. A phase II study of carboplatin and vinorelbine as second-line treatment for advanced breast cancer.

    PubMed Central

    Iaffaioli, R. V.; Tortoriello, A.; Facchini, G.; Santangelo, M.; De Sena, G.; Gesue, G.; Bucci, L.; Scaramellino, G.; Anastasio, E.; Finizio, A.

    1995-01-01

    Forty-one patients with advanced breast cancer were given carboplatin and vinorelbine as second-line therapy. Overall objective response rate was 46% (95% confidence interval 26-56%). Myelotoxicity was the most frequently observed toxic effect; grade III-IV leucopenia occurred in 46% of the patients. Our regimen is active as second-line chemotherapy for advanced breast cancer and warrants further evaluation. PMID:7577478

  3. Radiological study on newly developed composite corn advance lines in Malaysia

    NASA Astrophysics Data System (ADS)

    Adekunle Olatunji, Michael; Bemigho Uwatse, Onosohwo; Uddin Khandaker, Mayeen; Amin, Y. M.; Faruq, G.

    2014-12-01

    Owing to population growth, there has been high demand for food across the world, and hence, different agricultural activities such as use of phosphate fertilizers, recycling of organic matters, etc, have been deployed to increase crop yields. In Malaysia, a total of nine composite corn advance lines have been developed at the Institute of Biological Sciences, University of Malaya and are being grown under different conditions with a bid to meet the average daily human need for energy and fiber intake. To this end, the knowledge of radioactivity levels in these corn advance lines are of paramount importance for the estimation of possible radiological hazards due to its consumption. Hence, the radioactivity concentrations of 226Ra, 228Ra and 40K in the corn have been determined using HPGe γ-ray spectrometry. The activity concentrations in the corn ranged from 0.05 to 19.18 Bq kg-1 for 226Ra, from 0.10 to 3.22 Bq kg-1 for 228Ra and from 26.4 to 129 Bq kg-1 for 40K. In order to ascertain the radiological safety of the population regarding maize consumption, the daily intakes of these radionuclides as well as the annual effective dose were estimated. The total effective dose obtained due to the ingestion of radionuclides via maize consumption is 15.39 μSv y-1, which is less than the international recommendations.

  4. Paclitaxel-based regimens as first-line treatment in advanced gastric cancer.

    PubMed

    Guo, Zengqing; Wang, Xiaojie; Lin, Rongbo; Chen, Ling; Fan, Nanfeng; Chen, Yu; Lin, Jinyuan; Yu, Jiami

    2015-02-01

    The aim of this study was to evaluate the efficacy and safety of paclitaxel-based regimens as first-line treatments in advanced gastric cancer. We reviewed 397 previously untreated patients with advanced gastric cancer, who non-randomly received one of three paclitaxel-based regimens: paclitaxel plus fluorouracil/leucovorin (PF), paclitaxel plus oxaliplatin (PO), and paclitaxel plus oxaliplatin plus fluorouracil/leucovorin (POF) between January 2003 and December 2010. The PF, PO, and POF response rates were 47.13, 52.08, and 63.78%, respectively. Overall survivals (OS) were 11.2, 11.7, and 11.7 months, respectively. Progression-free survivals (PFS) were 6.6, 7.2, and 7.1 months, respectively. Leucopenia was higher on the triplet regimen than the doublet regimens. The paclitaxel-based regimens appeared to be effective in patients with advanced gastric cancer. The triplet regimen produced a higher response rate than either doublet regimen with more side effects, while survivals were similar among all three treatments.

  5. Development Status of the Advanced Life Support On-Line Project Information System

    NASA Technical Reports Server (NTRS)

    Levri, Julie A.; Hogan, John A.; Cavazzoni, Jim; Brodbeck, Christina; Morrow, Rich; Ho, Michael; Kaehms, Bob; Whitaker, Dawn R.

    2005-01-01

    The Advanced Life Support Program has recently accelerated an effort to develop an On-line Project Information System (OPIS) for research project and technology development data centralization and sharing. The core functionality of OPIS will launch in October of 2005. This paper presents the current OPIS development status. OPIS core functionality involves a Web-based annual solicitation of project and technology data directly from ALS Principal Investigators (PIS) through customized data collection forms. Data provided by PIs will be reviewed by a Technical Task Monitor (TTM) before posting the information to OPIS for ALS Community viewing via the Web. The data will be stored in an object-oriented relational database (created in MySQL(R)) located on a secure server at NASA ARC. Upon launch, OPIS can be utilized by Managers to identify research and technology development gaps and to assess task performance. Analysts can employ OPIS to obtain.

  6. Effect of tree line advance on carbon storage in NW Alaska

    USGS Publications Warehouse

    Wilmking, M.; Harden, J.; Tape, K.

    2006-01-01

    We investigated the size, distribution, and temporal dynamics of ecosystem carbon (C) pools in an area of recent tree line advance, northwest Alaska. Repeat aerial photographs show forest cover increased ???10% in our study area since 1949. We sampled C pools of four principal ecosystem types, tussock tundra, shrub tundra, woodland, and forest, all located on a 600-800 year old river terrace. Significant differences between ecosystem C pools, both above ground and below ground existed. Tundra sites store >22.2 kg C/m2, shrub tundra sites and woodland sites store 9.7 kg C/m2 and 14.3 kg C/m2, respectively, and forest sites store 14.4 kg C/m2. Landscape variation of total ecosystem C was primarily due to organic soil C and was secondarily due to C stored in trees. Soil C/N profiles of shrub tundra sites and woodland sites showed similarities with forest site soils at surface and tundra site soils at depth. We hypothesize that tundra systems transformed to forest systems in this area under a progression of permafrost degradation and enhanced drainage. On the basis of C pool estimates for the different ecosystem types, conversion of tundra sites to forest may have resulted in a net loss of > 7.8 kg C/m2, since aboveground C gains were more than offset by belowground C losses to decomposition in the tundra sites. Tree line advance therefore might not increase C storage in high-latitude ecosystems and thus might not, as previously suggested, act as a negative feedback to warming. Key to this hypothesis and to its projection to future climate response is the fate of soil carbon upon warming and permafrost drainage. Copyright 2006 by the American Geophysical Union.

  7. Synchrotron X-Ray Microdiffraction Studies of Electromigration in Interconnect lines at the Advanced Light Source

    SciTech Connect

    Tamura, Nobumichi; Chen, Kai; Kunz, Martin

    2009-05-01

    Synchrotron polychromatic X-ray microdiffraction is a particularly suitable technique to study in situ the effect of electromigration in metal interconnects as add spatial resolution to grain orientation and strain sensitivity. This technique has been extensively used at the Advanced Light Source to monitor changes in aluminum and copper interconnect test structures while high-density current is passed into them during accelerated tests at elevated temperature. One of the principal findings is the observation of electromigration-induced plasticity in the metal lines that appear during the very early stages of electromigration. In some of the lines, high density of geometrically necessary dislocation are formed leading to additional diffusion paths causing an enhancement of electromigration effect at test temperature. This paper presents an overview of the principal results obtained from X-ray microdiffraction studies of electromigration effects on aluminum and copper interconnects at the ALS throughout continuous efforts that spanned over a decade (1998-2008) from approximately 40 weeks of combined beamtime.

  8. Field Trial of LANL On-Line Advanced Enrichment Monitor for UF6 GCEP

    SciTech Connect

    Ianakiev, Kiril D.; Lombardi, Marcie; MacArthur, Duncan W.; Parker, Robert F.; Smith, Morag K.; Keller, Clifford; Friend, Peter; Dunford, Andrew

    2012-07-13

    The outline of this presentation is: (1) Technology basis of on-line enrichment monitoring; (2) Timescale of trial; (3) Description of installed equipment; (4) Photographs; (5) Results; (6) Possible further development; and (7) Conclusions. Summary of the good things about the Advanced Enrichment Monitor (AEM) performance is: (1) High accuracy - normally better than 1% relative, (2) Active system as accurate as passive system, (3) Fast and accurate detection of enrichment changes, (4) Physics is well understood, (5) Elegant method for capturing pressure signal, and (6) Data capture is automatic, low cost and fast. A couple of negative things are: (1) Some jumps in measured passive enrichment - of around +2% relative (due to clock errors?); and (2) Data handling and evaluation is off-line, expensive and very slow. Conclusions are: (1) LANL AEM is being tested on E23 plant at Capenhurst; (2) The trial is going very well; (3) AEM could detect production of HEU at potentially much lower cost than existing CEMO; (4) AEM can measure {sup 235}U assay accurately; (5) Active system using X-Ray source would avoid need for pressure measurement; (6) Substantial work lies ahead to go from current prototype to a production instrument.

  9. Development Approach of the Advanced Life Support On-line Project Information System

    NASA Technical Reports Server (NTRS)

    Levri, Julie A.; Hogan, John A.; Morrow, Rich; Ho, Michael C.; Kaehms, Bob; Cavazzoni, Jim; Brodbeck, Christina A.; Whitaker, Dawn R.

    2005-01-01

    The Advanced Life Support (ALS) Program has recently accelerated an effort to develop an On-line Project Information System (OPIS) for research project and technology development data centralization and sharing. There has been significant advancement in the On-line Project Information System (OPIS) over the past year (Hogan et al, 2004). This paper presents the resultant OPIS development approach. OPIS is being built as an application framework consisting of an uderlying Linux/Apache/MySQL/PHP (LAMP) stack, and supporting class libraries that provides database abstraction and automatic code generation, simplifying the ongoing development and maintenance process. Such a development approach allows for quick adaptation to serve multiple Programs, although initial deployment is for an ALS module. OPIS core functionality will involve a Web-based annual solicitation of project and technology data directly from ALS Principal Investigators (PIs) through customized data collection forms. Data provided by PIs will be reviewed by a Technical Task Monitor (TTM) before posting the information to OPIS for ALS Community viewing via the Web. Such Annual Reports will be permanent, citable references within OPIS. OPlS core functionality will also include Project Home Sites, which will allow PIS to provide updated technology information to the Community in between Annual Report updates. All data will be stored in an object-oriented relational database, created in MySQL(Reistered Trademark) and located on a secure server at NASA Ames Research Center (ARC). Upon launch, OPlS can be utilized by Managers to identify research and technology development (R&TD) gaps and to assess task performance. Analysts can employ OPlS to obtain the current, comprehensive, accurate information about advanced technologies that is required to perform trade studies of various life support system options. ALS researchers and technology developers can use OPlS to achieve an improved understanding of the NASA

  10. Advanced in-line metrology strategy for self-aligned quadruple patterning

    NASA Astrophysics Data System (ADS)

    Chao, Robin; Breton, Mary; L'herron, Benoit; Mendoza, Brock; Muthinti, Raja; Nelson, Florence; De La Pena, Abraham; Le, Fee li; Miller, Eric; Sieg, Stuart; Demarest, James; Gin, Peter; Wormington, Matthew; Cepler, Aron; Bozdog, Cornel; Sendelbach, Matthew; Wolfling, Shay; Cardinal, Tom; Kanakasabapathy, Sivananda; Gaudiello, John; Felix, Nelson

    2016-03-01

    Self-Aligned Quadruple Patterning (SAQP) is a promising technique extending the 193-nm lithography to manufacture structures that are 20nm half pitch or smaller. This process adopts multiple sidewall spacer image transfers to split a rather relaxed design into a quarter of its original pitch. Due to the number of multiple process steps required for the pitch splitting in SAQP, the process error propagates through each deposition and etch, and accumulates at the final step into structure variations, such as pitch walk and poor critical dimension uniformity (CDU). They can further affect the downstream processes and lower the yield. The impact of this error propagation becomes significant for advanced technology nodes when the process specifications of device design CD requirements are at nanometer scale. Therefore, semiconductor manufacturing demands strict in-line process control to ensure a high process yield and improved performance, which must rely on precise measurements to enable corrective actions and quick decision making for process development. This work aims to provide a comprehensive metrology solution for SAQP. During SAQP process development, the challenges in conventional in-line metrology techniques start to surface. For instance, critical-dimension scanning electron microscopy (CDSEM) is commonly the first choice for CD and pitch variation control. However, it is found that the high aspect ratio at mandrel level processes and the trench variations after etch prevent the tool from extracting the true bottom edges of the structure in order to report the position shift. On the other hand, while the complex shape and variations can be captured with scatterometry, or optical CD (OCD), the asymmetric features, such as pitch walk, show low sensitivity with strong correlations in scatterometry. X-ray diffraction (XRD) is known to provide useful direct measurements of the pitch walk in crystalline arrays, yet the data analysis is influenced by the incoming

  11. Advancement and results in hostile fire indication using potassium line missile warning sensors

    NASA Astrophysics Data System (ADS)

    Montgomery, Joel; Montgomery, Marjorie; Hardie, Russell

    2014-06-01

    M&M Aviation has been developing and conducting Hostile Fire Indication (HFI) tests using potassium line emission sensors for the Air Force Visible Missile Warning System (VMWS) to advance both algorithm and sensor technologies for UAV and other airborne systems for self protection and intelligence purposes. Work began in 2008 as an outgrowth of detecting and classifying false alarm sources for the VMWS using the same K-line spectral discrimination region but soon became a focus of research due to the high interest in both machine-gun fire and sniper geo-location via airborne systems. Several initial tests were accomplished in 2009 using small and medium caliber weapons including rifles. Based on these results, the Air Force Research Laboratory (AFRL) funded the Falcon Sentinel program in 2010 to provide for additional development of both the sensor concept, algorithm suite changes and verification of basic phenomenology including variance based on ammunition type for given weapons platform. Results from testing over the past 3 years have showed that the system would be able to detect and declare a sniper rifle at upwards of 3km, medium machine gun at 5km, and explosive events like hand-grenades at greater than 5km. This paper will outline the development of the sensor systems, algorithms used for detection and classification, and test results from VMWS prototypes as well as outline algorithms used for the VMWS. The Falcon Sentinel Program will be outlined and results shown. Finally, the paper will show the future work for ATD and transition efforts after the Falcon Sentinel program completed.

  12. Doublet Versus Single Agent as Second-Line Treatment for Advanced Gastric Cancer

    PubMed Central

    Zhang, Yong; Ma, Bing; Huang, Xiao-Tian; Li, Yan-Song; Wang, Yu; Liu, Zhou-Lu

    2016-01-01

    Abstract The purpose of this study was to perform a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of doublet versus single agent as second-line treatment for advanced gastric cancer (AGC). A comprehensive literature search was performed to identify relevant RCTs. All clinical studies were independently identified by 2 authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), and progression-free survival (PFS) and overall survival (OS) were extracted and analyzed using Comprehensive Meta-Analysis software (Version 2.0). Ten RCTs involving 1698 pretreated AGC patients were ultimately identified. The pooled results demonstrated that doublet combination therapy as second-line treatment for AGC significantly improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI]: 0.78–0.97, P = 0.011), PFS (HR 0.79, 95% CI: 0.72–0.87, P < 0.001), and ORR (relative risk [RR] 1.57, 95% CI: 1.27–1.95, P < 0.001). Sub-group analysis according to treatment regimens also showed that targeted agent plus chemotherapy significantly improve OS, PFS, and ORR. However, no significant survival benefits had been observed in doublet cytotoxic chemotherapy when compared with single cytotoxic agent. Additionally, more incidences of grade 3 or 4 myelosuppression toxicities, diarrhea, and fatigue were observed in doublet combination groups, while equivalent frequencies of grade 3 or 4 thrombocytopenia and nausea were found between the 2 groups. In comparison with single cytotoxic agent alone, the addition of targeted agent to mono-chemotherapy as salvage treatment for pretreated AGC patients provide substantial survival benefits, while no significant survival benefits were observed in doublet cytotoxic chemotherapy regimens. PMID:26937908

  13. Novel conformal organic antireflective coatings for advanced I-line lithography

    NASA Astrophysics Data System (ADS)

    Deshpande, Shreeram V.; Nowak, Kelly A.; Fowler, Shelly; Williams, Paul; Arjona, Mikko

    2001-08-01

    Flash memory chips are playing a critical role in semiconductor devices due to increased popularity of hand held electronic communication devices such as cell phones and PDAs (personal Digital Assistants). Flash memory offers two primary advantages in semiconductor devices. First, it offers flexibility of in-circuit programming capability to reduce the loss from programming errors and to significantly reduce commercialization time to market for new devices. Second, flash memory has a double density memory capability through stacked gate structures which increases the memory capability and thus saves significantly on chip real estate. However, due to stacked gate structures the requirements for manufacturing of flash memory devices are significantly different from traditional memory devices. Stacked gate structures also offer unique challenges to lithographic patterning materials such as Bottom Anti-Reflective Coating (BARC) compositions used to achieve CD control and to minimize standing wave effect in photolithography. To be applicable in flash memory manufacturing a BARC should form a conformal coating on high topography of stacked gate features as well as provide the normal anti-reflection properties for CD control. In this paper we report on a new highly conformal advanced i-line BARC for use in design and manufacture of flash memory devices. Conformal BARCs being significantly thinner in trenches than the planarizing BARCs offer the advantage of reducing BARC overetch and thus minimizing resist thickness loss.

  14. The Effects of an Advance Organizer on Learning To Graphically Analyze Straight Line Kinematics by Classroom Instruction or Programed Instruction.

    ERIC Educational Resources Information Center

    Townsend, Ronald Dee

    Described is a study in which 137 undergraduate co-ed students were randomly assigned printed introductory material to the graphical analysis of straight line kinematics. One type of introduction was the traditional form and the other an advanced organizer. Students in three sections worked through printed programs and those in the other three…

  15. An On-line Technology Information System (OTIS) for Advanced Life Support

    NASA Technical Reports Server (NTRS)

    Levri, Julie A.; Boulanger, Richard; Hogan, John A.; Rodriquez, Luis

    2003-01-01

    OTIS is an on-line communication platform designed for smooth flow of technology information between advanced life support (ALS) technology developers, researchers, system analysts, and managers. With pathways for efficient transfer of information, several improvements in the ALS Program will result. With OTIS, it will be possible to provide programmatic information for technology developers and researchers, technical information for analysts, and managerial decision support. OTIS is a platform that enables the effective research, development, and delivery of complex systems for life support. An electronic data collection form has been developed for the solid waste element, drafted by the Solid Waste Working Group. Forms for other elements (air revitalization, water recovery, food processing, biomass production and thermal control) will also be developed, based on lessons learned from the development of the solid waste form. All forms will be developed by consultation with other working groups, comprised of experts in the area of interest. Forms will be converted to an on-line data collection interface that technology developers will use to transfer information into OTIS. Funded technology developers will log in to OTIS annually to complete the element- specific forms for their technology. The type and amount of information requested expands as the technology readiness level (TRL) increases. The completed forms will feed into a regularly updated and maintained database that will store technology information and allow for database searching. To ensure confidentiality of proprietary information, security permissions will be customized for each user. Principal investigators of a project will be able to designate certain data as proprietary and only technical monitors of a task, ALS Management, and the principal investigator will have the ability to view this information. The typical OTIS user will be able to read all non-proprietary information about all projects

  16. Selection of a patient subgroup with advanced esophageal squamous carcinoma who could benefit from second-line chemotherapy.

    PubMed

    Kim, Seung Tae; Park, Kyong Hwa; Oh, Sang Cheul; Seo, Jae Hong; Shin, Sang Won; Kim, Jun Suk; Kim, Yeul Hong

    2010-01-01

    Despite first-line therapy, most patients with advanced esophageal squamous cell carcinoma (ESCC) experience disease progression and may become eligible for second-line chemotherapy. Although commonly used, the role of salvage chemotherapy in patients with recurrent or metastatic ESCC has not yet been established. We analyzed 53 patients who had received second-line chemotherapy after the failure of cisplatin-based combination chemotherapy with or without radiotherapy as first-line therapy in ESCC between March 2000 and June 2008. Median progression-free survival (PFS) and overall survival (OS) for second-line chemotherapy were 2.4 and 5.2 months, respectively, with an overall response rate of 18.9%. In multivariate analysis, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 2 or more and PFS under first-line therapy <4 months were independent prognostic factors for decreased OS. OS was estimated based on the number of adverse prognostic factors: 0 = good; 1 = intermediate, and 2 = poor. The median OS for the good, intermediate, and poor prognostic groups were 11.2, 4.5 and 4.3 months, respectively (p < 0.001). The good prognostic group showed better OS than the intermediate or poor groups (p < 0.001). Second-line chemotherapy may be beneficial for OS in ESCC patients with ECOG PS 0-1 and PFS under first-line therapy ≥4 months.

  17. Lines

    ERIC Educational Resources Information Center

    Mires, Peter B.

    2006-01-01

    National Geography Standards for the middle school years generally stress the teaching of latitude and longitude. There are many creative ways to explain the great grid that encircles our planet, but the author has found that students in his college-level geography courses especially enjoy human-interest stories associated with lines of latitude…

  18. Architecture and Functionality of the Advanced Life Support On-Line Project Information System (OPIS)

    NASA Technical Reports Server (NTRS)

    Hogan, John A.; Levri, Julie A.; Morrow, Rich; Cavazzoni, Jim; Rodriquez, Luis F.; Riano, Rebecca; Whitaker, Dawn R.

    2004-01-01

    An ongoing effort is underway at NASA Amcs Research Center (ARC) tu develop an On-line Project Information System (OPIS) for the Advanced Life Support (ALS) Program. The objective of this three-year project is to develop, test, revise and deploy OPIS to enhance the quality of decision-making metrics and attainment of Program goals through improved knowledge sharing. OPIS will centrally locate detailed project information solicited from investigators on an annual basis and make it readily accessible by the ALS Community via a web-accessible interface. The data will be stored in an object-oriented relational database (created in MySQL(Trademark) located on a secure server at NASA ARC. OPE will simultaneously serve several functions, including being an R&TD status information hub that can potentially serve as the primary annual reporting mechanism. Using OPIS, ALS managers and element leads will be able to carry out informed research and technology development investment decisions, and allow analysts to perform accurate systems evaluations. Additionally, the range and specificity of information solicited will serve to educate technology developers of programmatic needs. OPIS will collect comprehensive information from all ALS projects as well as highly detailed information specific to technology development in each ALS area (Waste, Water, Air, Biomass, Food, Thermal, and Control). Because the scope of needed information can vary dramatically between areas, element-specific technology information is being compiled with the aid of multiple specialized working groups. This paper presents the current development status in terms of the architecture and functionality of OPIS. Possible implementation approaches for OPIS are also discussed.

  19. An On-Line Technology Information System (OTIS) for Advanced Life Support

    NASA Technical Reports Server (NTRS)

    Levri, Julie A.; Boulanger, Richard; Hoganm John A.; Rodriquez, Luis

    2003-01-01

    An On-line Technology Information System (OTIS) is currently being developed for the Advanced Life Support (ALS) Program. This paper describes the preliminary development of OTIS, which is a system designed to provide centralized collection and organization of technology information. The lack of thorough, reliable and easily understood technology information is a major obstacle in effective assessment of technology development progress, trade studies, metric calculations, and technology selection for integrated testing. OTIS will provide a formalized, well-organized protocol to communicate thorough, accurate, current and relevant technology information between the hands-on technology developer and the ALS Community. The need for this type of information transfer system within the Solid Waste Management (SWM) element was recently identified and addressed. A SWM Technology Information Form (TIF) was developed specifically for collecting detailed technology information in the area of SWM. In the TIF, information is requested from SWM technology developers, based upon the Technology Readiness Level (TRL). Basic information is requested for low-TRL technologies, and more detailed information is requested as the TRL of the technology increases. A comparable form is also being developed for the wastewater processing element. In the future, similar forms will also be developed for the ALS elements of air revitalization, food processing, biomass production and thermal control. These ALS element-specific forms will be implemented in OTIS via a web-accessible interface,with the data stored in an object-oriented relational database (created in MySQLTM) located on a secure server at NASA Ames Research Center. With OTIS, ALS element leads and managers will be able to carry out informed research and development investment, thereby promoting technology through the TRL scale. OTIS will also allow analysts to make accurate evaluations of technology options. Additionally, the range

  20. Architecture and Functionality of the Advanced Life Support On-Line Project Information System

    NASA Technical Reports Server (NTRS)

    Hogan, John A.; Levri, Julie A.; Morrow, Rich; Cavazzoni, Jim; Rodriguez, Luis F.; Riano, Rebecca; Whitaker, Dawn R.

    2004-01-01

    An ongoing effort is underway at NASA Ames Research Center (ARC) to develop an On-line Project Information System (OPIS) for the Advanced Life Support (ALS) Program. The objective of this three-year project is to develop, test, revise and deploy OPIS to enhance the quality of decision-making metrics and attainment of Program goals through improved knowledge sharing. OPIS will centrally locate detailed project information solicited from investigators on an annual basis and make it readily accessible by the ALS Community via a Web-accessible interface. The data will be stored in an object-oriented relational database (created in MySQL) located on a secure server at NASA ARC. OPE will simultaneously serve several functions, including being an research and technology development (R&TD) status information hub that can potentially serve as the primary annual reporting mechanism for ALS-funded projects. Using OPIS, ALS managers and element leads will be able to carry out informed R&TD investment decisions, and allow analysts to perform accurate systems evaluations. Additionally, the range and specificity of information solicited will serve to educate technology developers of programmatic needs. OPIS will collect comprehensive information from all ALS projects as well as highly detailed information specific to technology development in each ALS area (Waste, Water, Air, Biomass, Food, Thermal, Controls and Systems Analysis). Because the scope of needed information can vary dramatically between areas, element-specific technology information is being compiled with the aid of multiple specialized working groups. This paper presents the current development status in terms of the architecture and functionality of OPIS. Possible implementation approaches for OPIS are also discussed.

  1. Advanced Line Die Forming Simulation Technology and Its Impact on Stamping Automotive Body Panels

    NASA Astrophysics Data System (ADS)

    Zhang, Jimmy; Wang, Chuantao; Xu, Siguang; Joshi, Ramesh; Goan, Norman

    2005-08-01

    Line die forming simulation and validation create tremendous business values for automotive die developments and production stamping while they pose a great technological challenge to stamping CAE community. GM Manufacturing Engineering Die Center has developed an integrated line die analysis technology to validate die lines as a productionized business process. In this process, a finished stamping body panel can be streamline analyzed with required time, accuracy, and quality. This paper presents critical issues in line die analysis, discusses technical challenges in production applications and software development, and finally demonstrates the impact of line die forming simulation and validations on automotive body styling and tooling developments.

  2. New advances in on-line sample preconcentration by capillary electrophoresis using dynamic pH junction.

    PubMed

    Ptolemy, Adam S; Britz-McKibbin, Philip

    2008-12-01

    The small injection volumes and narrow dimensions characteristic of microseparation techniques place constraints on concentration sensitivity that is required for trace chemical analyses. On-line sample preconcentration techniques using dynamic pH junction and its variants have emerged as simple yet effective strategies for enhancing concentration sensitivity of weakly ionic species by capillary electrophoresis (CE). Dynamic pH junction offers a convenient format for electrokinetic focusing of dilute sample plugs directly in-capillary for improved detection without off-line sample pretreatment. In this report, we highlight new advances in dynamic pH junction which have been reported to enhance method performance while discussing challenges for future research.

  3. Percutaneous CT-guided microwave ablation as maintenance after first-line treatment for patients with advanced NSCLC

    PubMed Central

    Ni, Xiang; Han, Jun-Qing; Ye, Xin; Wei, Zhi-Gang

    2015-01-01

    Background Systemic therapy is recommended for advanced non-small-cell lung cancer (NSCLC). However, conventional first-line treatment has generated a plateau in response rate of 25% to 35%. Few studies have shown patients benefit from microwave ablation (MWA) in combination with radiotherapy and chemotherapy. This study aims to evaluate safety and efficacy of percutaneous computed tomography-guided MWA as maintenance after first-line treatment for patients with advanced NSCLC. Methods Patients with histologically verified NSCLC stage IIIB or IV between January 2010 and March 2014 were involved. After completion of first-line treatment with partial response or stable disease, 35 patients with 39 tumors underwent 39 MWA procedures. Complications, progression-free survival (PFS), overall survival (OS), and correlated predictors were analyzed. Results During a median follow-up of 17.7 months and 10.8 months after initial MWA, local efficacy was 87.2%, median MWA-related local control time was 10.6 months, and tumor size was the only predictor (P=0.002). Median MWA-related PFS, MWA-related OS, PFS, and OS were 5.4, 10.6, 11.8 and 17.7 months, respectively. Local efficacy was significantly correlated with MWA-related PFS (P=0.003), MWA-related OS (P=0.000), and OS (P=0.001). There were no procedure-specific deaths. Total incidence of major complications was 12.8%, including pneumothorax resolved by closed pleural drainage and pneumonia controlled by antibiotics in a short time. Conclusion This study concluded two points, including: 1) patients benefited from MWA as maintenance both in local control and survival; 2) as maintenance MWA was superior to conventional maintenance therapy with improved survival and well-tolerated complications. Therefore, MWA was a safe and effective maintenance after first-line treatment in patients with advanced NSCLC. PMID:26604789

  4. Identification of null alleles and deletions from SNP genotypes for an intercross between domestic and wild chickens.

    PubMed

    Crooks, Lucy; Carlborg, Örjan; Marklund, Stefan; Johansson, Anna M

    2013-08-01

    We analyzed genotypes from ~10K single-nucleotide polymorphisms (SNPs) in two families of an F2 intercross between Red Junglefowl and White Leghorn chickens. Possible null alleles were found by patterns of incompatible and missing genotypes. We estimated that 2.6% of SNPs had null alleles compared with 2.3% with genotyping errors and that 40% of SNPs in which a parent and offspring were genotyped as different homozygotes had null alleles. Putative deletions were identified by null alleles at adjacent markers. We found two candidate deletions that were supported by fluorescence intensity data from a 60K SNP chip. One of the candidate deletions was from the Red Junglefowl, and one was present in both the Red Junglefowl and White Leghorn. Both candidate deletions spanned protein-coding regions and were close to a previously detected quantitative trait locus affecting body weight in this population. This study demonstrates that the ~50K SNP genotyping arrays now available for several agricultural species can be used to identify null alleles and deletions in data from large families. We suggest that our approach could be a useful complement to linkage analysis in experimental crosses. PMID:23708300

  5. Identification of null alleles and deletions from SNP genotypes for an intercross between domestic and wild chickens.

    PubMed

    Crooks, Lucy; Carlborg, Örjan; Marklund, Stefan; Johansson, Anna M

    2013-08-07

    We analyzed genotypes from ~10K single-nucleotide polymorphisms (SNPs) in two families of an F2 intercross between Red Junglefowl and White Leghorn chickens. Possible null alleles were found by patterns of incompatible and missing genotypes. We estimated that 2.6% of SNPs had null alleles compared with 2.3% with genotyping errors and that 40% of SNPs in which a parent and offspring were genotyped as different homozygotes had null alleles. Putative deletions were identified by null alleles at adjacent markers. We found two candidate deletions that were supported by fluorescence intensity data from a 60K SNP chip. One of the candidate deletions was from the Red Junglefowl, and one was present in both the Red Junglefowl and White Leghorn. Both candidate deletions spanned protein-coding regions and were close to a previously detected quantitative trait locus affecting body weight in this population. This study demonstrates that the ~50K SNP genotyping arrays now available for several agricultural species can be used to identify null alleles and deletions in data from large families. We suggest that our approach could be a useful complement to linkage analysis in experimental crosses.

  6. Worse renal disease in postmenopausal F2[Dahl S x R]-intercross rats: detection of novel QTLs affecting hypertensive kidney disease.

    PubMed

    Herrera, Victoria L M; Pasion, Khristine A; Moran, Ann Marie; Ruiz-Opazo, Nelson

    2013-01-01

    The prevalence of hypertension increases after menopause with 75% of postmenopausal women developing hypertension in the United States, along with hypertensive end organ diseases. While human and animal model studies have indicated a protective role for estrogen against cardiovascular disease and glomerulosclerosis, clinical studies of hormone replacement therapy in postmenopausal women have shown polar results with some improvement in hypertension but worsening of hypertensive kidney disease, or no effect at all. These observations suggest that the pathogenesis of postmenopausal hypertension and its target organ complications is more complex than projected, and that loss of endogenous estrogens induces epigenetic changes that alter genetic susceptibility to end-organ complications per se resulting in pathogenetic mechanisms beyond correction by hormone replacement. We studied postmenopausal-induced changes in renal disease and performed a total genome scan for quantitative trait loci (QTLs) affecting kidney disease in postmenopausal 16m-old F2[Dahl S x R]-intercross female rats. We used glomerular injury score (GIS) as quantitative trait. We compared QTLs amongst premenopausal, ovariectomized and postmenopausal F2[Dahl S x R]-intercross rats using identical phenotype characterization. Postmenopausal F2[Dahl S x R]-intercross rats exhibited increased hypertensive glomerulosclerosis (P<0.01) and equivalent levels of kidney disease when compared to premenopausal and ovariectomized F2[Dahl S x R]-intercross rats respectively. We detected three significant to highly significant GIS-QTLs (GIS-pm1 on chromosome 4, LOD 3.54; GIS-pm2 on chromosome 3, LOD 2.72; GIS-pm3 on chromosome 5, LOD 2.37) and two suggestive GIS-QTLs (GIS-pm4 on chromosome 2, LOD 1.70; GIS-pm5 on chromosome 7, LOD 1.28), all of which were unique to this postmenopausal population. Detection of increased renal disease phenotype in postmenopausal and ovariectomized subjects suggests a protective role of

  7. Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma

    PubMed Central

    Trojan, Jörg; Waidmann, Oliver

    2016-01-01

    Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC. PMID:27703962

  8. Advanced CD-SEM metrology for qualification of DSA patterns using coordinated line epitaxy (COOL) process

    NASA Astrophysics Data System (ADS)

    Kato, Takeshi; Konishi, Junko; Ikota, Masami; Yamaguchi, Satoru; Seino, Yuriko; Sato, Hironobu; Kasahara, Yusuke; Azuma, Tsukasa

    2016-03-01

    Directed self-assembly (DSA) applying chemical epitaxy is one of the promising lithographic solutions for next generation semiconductor device manufacturing. Especially, DSA lithography using coordinated line epitaxy (COOL) process is obviously one of candidates which could be the first generation of DSA applying PS-b-PMMA block copolymer (BCP) for sub-15nm dense line patterning . DSA can enhance the pitch resolutions, and can mitigate CD errors to the values much smaller than those of the originally exposed guiding patterns. On the other hand, local line placement error often results in a worse value, with distinctive trends depending on the process conditions. To address this issue, we introduce an enhanced measurement technology of DSA line patterns with distinguishing their locations in order to evaluate nature of edge placement and roughness corresponding to individual pattern locations by using images of CD-SEM. Additionally correlations among edge roughness of each line and each space are evaluated and discussed. This method can visualize features of complicated roughness easily to control COOL process. As a result, we found the followings. (1) Line placement error and line placement roughness of DSA were slightly different each other depending on their relative position to the chemical guide patterns. (2) In middle frequency area of PSD (Power Spectral Density) analysis graphs, it was observed that shapes were sensitively changed by process conditions of chemical stripe guide size and anneals temperature. (3) Correlation coefficient analysis using PSD was able to clarify characteristics of latent defect corresponding to physical and chemical property of BCP materials.

  9. New advances in on-line sample preconcentration by capillary electrophoresis using dynamic pH junction.

    PubMed

    Ptolemy, Adam S; Britz-McKibbin, Philip

    2008-12-01

    The small injection volumes and narrow dimensions characteristic of microseparation techniques place constraints on concentration sensitivity that is required for trace chemical analyses. On-line sample preconcentration techniques using dynamic pH junction and its variants have emerged as simple yet effective strategies for enhancing concentration sensitivity of weakly ionic species by capillary electrophoresis (CE). Dynamic pH junction offers a convenient format for electrokinetic focusing of dilute sample plugs directly in-capillary for improved detection without off-line sample pretreatment. In this report, we highlight new advances in dynamic pH junction which have been reported to enhance method performance while discussing challenges for future research. PMID:19082065

  10. The role of maintenance treatment in advanced non-small-cell lung cancer: reality or early second line?

    PubMed

    Gridelli, Cesare; Rossi, Antonio; Maione, Paolo; Ambrosio, Rita; Barbato, Valentina; Bareschino, Maria Anna; Schettino, Clorinda; Palazzolo, Giovanni; Sacco, Paola Claudia

    2010-11-01

    First-line platinum-based chemotherapy has reached a plateau of effectiveness for the treatment of patients with advanced non-small-cell lung cancer (NSCLC). In patients who reported a stable disease, no more than 4 cycles of chemotherapy are recommended while a maximum of 6 cycles is recommended in patients who are responding to therapy. A potential strategy with the aim of improving outcomes for NSCLC patients is to administer more therapy. This term includes different approaches: duration of therapy, sequential therapy, consolidation therapy, and maintenance therapy. Here, we attempt to define the different approaches that fall under the rubric of maintenance strategy, and discuss the results available to date.

  11. Rapid Response of Advanced Squamous Non-Small Cell Lung Cancer with Thrombocytopenia after First-Line Treatment with Pembrolizumab Plus Autologous Cytokine-Induced Killer Cells.

    PubMed

    Hui, Zhenzhen; Zhang, Xinwei; Ren, Baozhu; Li, Runmei; Ren, Xiubao

    2015-01-01

    We present the first clinical evidence of advanced squamous non-small cell lung cancer with severe thrombocytopenia showing dramatic improvement after first-line treatment with pembrolizumab plus autologous cytokine-induced killer cells.

  12. Evaluation of verticillium wilt resistance in commercial cultivars and advanced breeding lines of cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Verticillium wilt (VW), caused by Verticillium dahliae Kleb, is one of the most destructive diseases in cotton (Gossypium spp.). The most efficient and cost-effective method of controlling the disease is the use of resistant cotton cultivars. Most commercial cultivars and elite breeding lines are de...

  13. First-line cetuximab-based chemotherapies for patients with advanced or metastatic KRAS wild-type colorectal cancer

    PubMed Central

    Uemura, Mamoru; Kim, Ho Min; Hata, Tsuyoshi; Sakata, Kazuya; Okuyama, Masaki; Takemoto, Hiroyoshi; Fujii, Hitoshi; Fukuzaki, Takayuki; Morita, Tetsushi; Hata, Taishi; Takemasa, Ichiro; Satoh, Taroh; Mizushima, Tsunekazu; Doki, Yuichiro; Mori, Maski

    2016-01-01

    Colorectal cancer (CRC) is one of the most commonly occurring cancers worldwide. A burgeoning number of studies have demonstrated that the addition of cetuximab to another standard first-line regimen markedly improves the outcome of CRC treatment. However, at present, the efficacy and safety of cetuximab-based combination chemotherapy has not been well described in Japan. The aim of the present study was to evaluate the efficacy and safety of first-line chemotherapies that included cetuximab for patients with advanced or metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type CRC in Japan. This prospective multicenter observational study was conducted at 13 affiliated medical institutions. A total of 64 patients were enrolled between 2010 and 2013. The patients met the following criteria for eligibility: i) histologically confirmed, advanced or metastatic KRAS wild-type CRC; and ii) cetuximab-based chemotherapies administered as a first-line treatment. First-line cetuximab-based treatments were administered as follows: 29 patients (45.3%) received a combination of infusional fluorouracil, leucovorin and oxaliplatin; 14 patients (21.9%) received a combination of capecitabine and oxaliplatin; and 10 patients (15.6%) received a combination of infusional fluorouracil, leucovorin and irinotecan. The overall response rate (including complete plus partial responses) was 50% (32/64 patients). Initially, 48 lesions were diagnosed as unresectable. Among those, 13 lesions (27.1%) were converted to a resectable status following cetuximab-based combination chemotherapy treatments. The median overall survival time and the progression-free survival time were 1,189 and 359 days, respectively. The most frequent grade 3/4 adverse event was neutropenia, which occurred in 20.3% of the patients. The incidence of grade 3/4 skin toxicity was 17.2% (11/64 patients). Cetuximab-based therapies may represent a promising first-line regimen for patients with advanced or

  14. Advances in fibers and transmission line technology for long haul submarine systems

    NASA Astrophysics Data System (ADS)

    Peckham, David W.; Kim, Jinkee; Sun, Yi; Lingle, Robert L., Jr.; Levring, Ole

    2007-11-01

    The 7.1-magnitude earthquake on December 26, 2006 in the Strait of Luzon resulted in the failure of several submarine cable systems. Seven of the nine cables that pass through the strait were damaged, disrupting communications to China, Taiwan, Japan, Korea and Singapore. This recent event highlighted the dependence of international communications on submarine fiber optic transmission systems. This paper will review the evolution of optical fiber transmission line technology that has been deployed in the long haul undersea telecommunications network. It will start with a discussion of the chronological evolution of the optical fiber transmission line architecture in section one, then give more detail regarding the technology that is still being deployed today.

  15. Phase II trial of bevacizumab and erlotinib as a second-line therapy for advanced hepatocellular carcinoma

    PubMed Central

    Kaseb, Ahmed O; Morris, Jeffrey S; Iwasaki, Michiko; Al-Shamsi, Humaid O; Raghav, Kanwal Pratap Singh; Girard, Lauren; Cheung, Sheree; Nguyen, Van; Elsayes, Khaled M; Xiao, Lianchun; Abdel-Wahab, Reham; Shalaby, Ahmed S; Hassan, Manal; Hassabo, Hesham M; Wolff, Robert A; Yao, James C

    2016-01-01

    Trial registry Clinicaltrials.gov #NCT01180959. Background Early clinical studies of bevacizumab and erlotinib in advanced hepatocellular carcinoma (HCC) have a tolerable toxicity and a promising clinical outcome. We evaluated the efficacy and tolerability of this combination as a second-line therapy for HCC refractory to sorafenib. Methods For this single-arm, Phase II study, we recruited patients with Child–Pugh class A or B liver disease, Eastern Cooperative Oncology Group performance status 0–2, and advanced HCC that was not amenable to surgical or regional therapies and treatment with sorafenib had failed (disease progressed or patient could not tolerate sorafenib). Patients received 10 mg/kg intravenous bevacizumab every 14 days and 150 mg oral erlotinib daily for 28-day cycles until progression. Tumor response was evaluated every two cycles using Response Evaluation Criteria in Solid Tumors. The primary end point was the 16-week progression-free survival rate. Secondary end points included time to progression and overall survival. Results A total of 44 patients were enrolled and had a median follow-up time of 33.8 months (95% confidence interval [CI]: 23.5 months – not defined). The 16-week progression-free survival rate was 43% (95% CI: 28%–59%), median time to progression was 3.9 months (95% CI: 2.0–8.3 months), and median overall survival duration was 9.9 months (95% CI: 8.3–15.5 months). Grade 3–4 adverse events included fatigue (13%), acne (11%), diarrhea (9%), anemia (7%), and upper gastrointestinal hemorrhage (7%). Conclusion Bevacizumab plus erlotinib was tolerable and showed a signal of survival benefit in the second-line setting for patients with advanced HCC. Because standard-of-care options are lacking in this setting, further studies to identify predictors of response to this regimen are warranted. PMID:26929648

  16. Role of erlotinib in first-line and maintenance treatment of advanced non-small-cell lung cancer

    PubMed Central

    Reguart, Noemí; Cardona, Andrés Felipe; Rosell, Rafael

    2010-01-01

    Erlotinib hydrochloride (Tarceva®) is a member of a class of small molecule inhibitors that targets the tyrosine kinase domain of the epidermal growth factor receptor (EGFR), with anti-tumor activity in preclinical models. Erlotinib represents a new-generation of agents known as “targeted therapies” designed to act upon cancer cells by interfering with aberrant specific activated pathways needed for tumor growth, angiogenesis and cell survival. Since its approval in November 2004 for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after the failure of at least one prior chemotherapy regimen and with a view to improving patients’ outcomes and prevent symptoms, the scientific community has evaluated the potential role of erlotinib in other scenarios such as in maintenance therapy and, in first-line setting for a selected population based on biological markers of response such as mutations of the EGFR. The convenient once-a-day pill administration and the good toxicity profile of erlotinib make it a reasonable candidate for testing in this context. This report provides a review of the role of erlotinib therapy in advanced NSCLC. It summarizes current data and perspectives of erlotinib in upfront treatment and maintenance for advanced NSCLC as well as looking at candidate biomarkers of response to these new targeted-agents. PMID:21188105

  17. Advances in First-Line Treatment for Patients with HER-2+ Metastatic Breast Cancer

    PubMed Central

    De Mattos-Arruda, Leticia

    2012-01-01

    Background. The prognosis for breast cancer patients overexpressing human epidermal growth factor receptor (HER)-2 has changed with anti–HER-2–targeted therapy. Although anti–HER-2 therapy with trastuzumab and chemotherapy is the standard first-line treatment, the best therapeutic regimen has yet to be defined, and new strategies are evolving. Methods. A literature review of well-established and recently published trials, reviews, and ongoing clinical trials addressing first-line treatment for HER-2+ metastatic breast cancer patients was performed. Results. Taxanes are the agents most commonly used in combination with trastuzumab, but other chemotherapy drugs, such as anthracyclines, vinorelbine, and gemcitabine and triple-combination therapies including platinum compounds, capecitabine, and taxanes have been studied. The combination of aromatase inhibitors with anti–HER-2 therapies is a new therapeutic option for some patients who coexpress HER-2 and hormone receptors, although its activity observed in randomized clinical trials seems to be inferior to that of chemotherapy plus anti–HER-2 therapies. In addition, new anti–HER-2 therapies have shown activity in HER-2+ tumors, both alone and in combination with trastuzumab. Conclusions. Trastuzumab plus chemotherapy is the current standard of care for the upfront treatment of HER-2+ breast cancer patients, though other anti–HER-2–targeting agents may appear as new standards in the upcoming years. PMID:22523199

  18. First-line erlotinib and fixed dose-rate gemcitabine for advanced pancreatic cancer

    PubMed Central

    Vaccaro, Vanja; Bria, Emilio; Sperduti, Isabella; Gelibter, Alain; Moscetti, Luca; Mansueto, Giovanni; Ruggeri, Enzo Maria; Gamucci, Teresa; Cognetti, Francesco; Milella, Michele

    2013-01-01

    AIM: To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer. METHODS: We designed a single-arm prospective, multicentre, open-label phase II study to evaluate the combination of erlotinib (100 mg/d, orally) and weekly FDR-Gem (1000 mg/m2, infused at 10 mg/m2 per minute) in a population of previously untreated patients with locally advanced, inoperable, or metastatic pancreatic cancer. Primary endpoint was the rate of progression-free survival at 6 mo (PFS-6); secondary endpoints were overall response rate (ORR), response duration, tolerability, overall survival (OS), and clinical benefit. Treatment was not considered to be of further interest if the PFS-6 was < 20% (p0 = 20%), while a PFS-6 > 40% would be of considerable interest (p1 = 40%); with a 5% rejection error (α = 5%) and a power of 80%, 35 fully evaluable patients with metastatic disease were required to be enrolled in order to complete the study. Analysis of prognostic factors for survival was also carried out. RESULTS: From May 2007 to September 2009, 46 patients were enrolled (male/female: 25/21; median age: 64 years; median baseline carbohydrate antigen 19-9 (CA 19-9): 897 U/mL; locally advanced/metastatic disease: 5/41). PFS-6 and median PFS were 30.4% and 14 wk (95%CI: 10-19), respectively; 1-year and median OS were 20.2% and 26 wk (95%CI: 8-43). Five patients achieved an objective response (ORR: 10.9%, 95%CI: 1.9-19.9); disease control rate was 56.5% (95%CI: 42.2-70.8); clinical benefit rate was 43.5% (95%CI: 29.1-57.8). CA 19-9 serum levels were decreased by > 25% as compared to baseline in 14/23 evaluable patients (63.6%). Treatment was well-tolerated, with skin rash being the most powerful predictor of both longer PFS (P < 0.0001) and OS (P = 0.01) at multivariate analysis (median OS for patients with or without rash: 42 wk vs 15 wk, respectively, Log-rank P = 0.03). Additional predictors of

  19. Dose escalation for unresectable locally advanced non-small cell lung cancer: end of the line?

    PubMed Central

    Hong, Julian C.

    2016-01-01

    Radiation Therapy Oncology Group (RTOG) 0617 was a randomized trial that investigated both the impact of radiation dose-escalation and the addition of cetuximab on the treatment of non-small cell lung cancer (NSCLC). The results of RTOG 0617 were surprising, with the dose escalation randomization being closed prematurely due to futility stopping rules, and cetuximab ultimately showing no overall survival benefit. Locally advanced unresectable NSCLC has conventionally been treated with concurrent chemoradiation. Though advances in treatment technology have improved the ability to deliver adequate treatment dose, the foundation for radiotherapy (RT) has remained the same since the 1980s. Since then, progressive studies have sought to establish the safety and efficacy of escalating radiation dose to loco-regional disease. Though RTOG 0617 did not produce the anticipated result, much interest remains in dose escalation and establishing an explanation for the findings of this study. Cetuximab was also not found to provide a survival benefit when applied to an unselected population. However, planned retrospective analysis suggests that those patients with high epidermal growth factor receptor (EGFR) expression may benefit, suggesting that cetuximab should be applied in a targeted fashion. We discuss the results of RTOG 0617 and additional findings from post-hoc analysis that suggest that dose escalation may be limited by normal tissue toxicity. We also present ongoing studies that aim to address potential causes for mortality in the dose escalation arm through adaptive or proton therapy, and are also leveraging additional concurrent systemic agents such as tyrosine kinase inhibitors (TKIs) for EGFR-activating mutations or EML4-ALK rearrangements, and poly (ADP-ribose) polymerase (PARP) inhibitors. PMID:26958507

  20. Dose escalation for unresectable locally advanced non-small cell lung cancer: end of the line?

    PubMed

    Hong, Julian C; Salama, Joseph K

    2016-02-01

    Radiation Therapy Oncology Group (RTOG) 0617 was a randomized trial that investigated both the impact of radiation dose-escalation and the addition of cetuximab on the treatment of non-small cell lung cancer (NSCLC). The results of RTOG 0617 were surprising, with the dose escalation randomization being closed prematurely due to futility stopping rules, and cetuximab ultimately showing no overall survival benefit. Locally advanced unresectable NSCLC has conventionally been treated with concurrent chemoradiation. Though advances in treatment technology have improved the ability to deliver adequate treatment dose, the foundation for radiotherapy (RT) has remained the same since the 1980s. Since then, progressive studies have sought to establish the safety and efficacy of escalating radiation dose to loco-regional disease. Though RTOG 0617 did not produce the anticipated result, much interest remains in dose escalation and establishing an explanation for the findings of this study. Cetuximab was also not found to provide a survival benefit when applied to an unselected population. However, planned retrospective analysis suggests that those patients with high epidermal growth factor receptor (EGFR) expression may benefit, suggesting that cetuximab should be applied in a targeted fashion. We discuss the results of RTOG 0617 and additional findings from post-hoc analysis that suggest that dose escalation may be limited by normal tissue toxicity. We also present ongoing studies that aim to address potential causes for mortality in the dose escalation arm through adaptive or proton therapy, and are also leveraging additional concurrent systemic agents such as tyrosine kinase inhibitors (TKIs) for EGFR-activating mutations or EML4-ALK rearrangements, and poly (ADP-ribose) polymerase (PARP) inhibitors.

  1. A strategy to rotate the Mars Observer orbit node line to advance the mapping schedule

    NASA Technical Reports Server (NTRS)

    Pernicka, Henry J.; Sweetser, Theodore H.; Roncoli, Ralph B.

    1993-01-01

    The Mars Observer (MO) spacecraft was successfully launched on September 25, 1992 and will arrive at Mars on August 24, 1993. At Mars, the spacecraft will study the planet's surface, atmosphere, and gravitational and magnetic fields. In order to achieve these scientific objectives, MO will be placed in a 2 PM (descending node) sun-synchronous orbit. Upon arrival at Mars, however, the longitude of the descending node will be approximately 15 deg greater than the desired value. The baseline plan requires a 59 day `waiting' period for the correct solar orientation to occur. During this period, 28 days are required for scientific experimentation but the remaining 30.6 days potentially could be eliminated. The strategy developed in this study examined the possibility of using any `excess' Delta-V available at Mars arrival to rotate the node line to the desired value and thus allow mapping to begin earlier. A preliminary analysis completed prior to launch is described that examined the entire launch period including the required Delta-V to perform the needed nodal rotation. A more detailed study performed after launch is also summarized.

  2. Pemetrexed/cisplatin as first-line chemotherapy for advanced lung cancer with brain metastases

    PubMed Central

    He, Guangzhao; Xiao, Xiaoguang; Zou, Man; Zhang, Chengliang; Xia, Shu

    2016-01-01

    Abstract Background: Brain metastases (BMs) are a common and serious complication of non-small cell lung cancer (NSCLC). Whole-brain radiotherapy (WBRT), surgery, and molecular targeted therapy are usually used to treat NSCLC with BM. Chemotherapeutic options for BM are limited by tumor resistance, ineffective agents, and the blood–brain barrier. Pemetrexed/cisplatin is the preferred chemotherapy in nonsquamous NSCLC, but the efficacy of this treatment for nonsquamous NSCLC with BM is uncertain. Methods: We present a case of nonsquamous NSCLC with asymptomatic BM presenting with irritating cough and right shoulder back pain (unknown sensitizing epidermal growth factor receptor mutations or anaplastic lymphoma kinase). Results: He benefited from administration of first-line chemotherapy of pemetrexed/cisplatin. Partial remission was achieved in the primary lesion of the lungs and BM lesion. He was further given 3 cycles of pemetrexed monotherapy and WBRT. Complete remission was further achieved in BM lesion. Conclusion: The findings of clinical trials and theoretical studies about the current pemetrexed/cisplatin in the treatment of nonsquamous NSCLC with BM are also summarized to provide a reference for the application of pemetrexed/cisplatin in nonsquamous NSCLC with BM. Whether or not pemetrexed/cisplatin is definitely effective in nonsquamous NSCLC with BM must be proven by subsequent phase III clinical trials. PMID:27512852

  3. Development of an advanced multimode automatic ultrasonic texture measurement system for laboratory and production line application.

    PubMed

    Potter, M D G; Dixon, S; Morrison, J P; Suliamann, A S

    2006-12-22

    We present work on the development of an ultrasonic texture measurement system for sheet metals using non-contact transducers, suitable for use both in the laboratory and on the production line. Variation of the velocity of the zero-order symmetric (S0) Lamb wave is used to determine the crystallographic texture of polycrystalline metal sheets ranging in thickness from 0.1 to 3 mm. This system features improvements on previous state-of-the-art ultrasonic technology in that it probes velocity over a continuous range of angles using only two electromagnetic acoustic transducers (EMATs). This is demonstrated to offer a significant improvement in accuracy and allows the detection and investigation of asymmetric anisotropies in the sheets. Another advantage of the system is its potential for combining several different measurements using a single pair of transducers. The capability is demonstrated for through-thickness shear wave measurements as well as the zero-order symmetric Lamb wave measurements which are the primary means of determining the texture. The change between generating Lamb and through-thickness bulk waves can be made entirely by changing the electrical circuit connected to the EMATs without modifying the transducer assembly in any way. Measurement of all of the above waves can provide information on the sheet thickness and other physical properties of the sheet in addition to texture. Certain texture parameters can be calculated from both Lamb and shear wave velocities, allowing self-calibration of the system.

  4. On-line sensor monitoring for chemical contaminant attenuation during UV/H2O2 advanced oxidation process.

    PubMed

    Yu, Hye-Weon; Anumol, Tarun; Park, Minkyu; Pepper, Ian; Scheideler, Jens; Snyder, Shane A

    2015-09-15

    A combination of surrogate parameters and indicator compounds were measured to predict the removal efficiency of trace organic compounds (TOrCs) using low pressure (LP)-UV/H2O2 advanced oxidation process (AOP), engaged with online sensor-based monitoring system. Thirty-nine TOrCs were evaluated in two distinct secondary wastewater effluents in terms of estimated photochemical reactivity, as a function of the rate constants of UV direct photolysis (kUV) and hydroxyl radical (OH) oxidation (kOH). The selected eighteen TOrCs were classified into three groups that served as indicator compounds: Group 1 for photo-susceptible TOrCs but with minor degradation by OH oxidation (diclofenac, fluoxetine, iohexol, iopamidol, iopromide, simazine and sulfamethoxazole); Group 2 for TOrCs susceptible to both direct photolysis and OH oxidation (benzotriazole, diphenhydramine, ibuprofen, naproxen and sucralose); and Group 3 for photo-resistant TOrCs showing dominant degradation by OH oxidation (atenolol, carbamazepine, DEET, gemfibrozil, primidone and trimethoprim). The results indicate that TOC (optical-based measurement), UVA254 or UVT254 (UV absorbance or transmittance at 254 nm), and total fluorescence can all be used as suitable on-line organic surrogate parameters to predict the attenuation of TOrCs. Furthermore, the automated real-time monitoring via on-line surrogate sensors and equipped with the developed degradation profiles between sensor response and a group of TOrCs removal can provide a diagnostic tool for process control during advanced treatment of reclaimed waters.

  5. On-line sensor monitoring for chemical contaminant attenuation during UV/H2O2 advanced oxidation process.

    PubMed

    Yu, Hye-Weon; Anumol, Tarun; Park, Minkyu; Pepper, Ian; Scheideler, Jens; Snyder, Shane A

    2015-09-15

    A combination of surrogate parameters and indicator compounds were measured to predict the removal efficiency of trace organic compounds (TOrCs) using low pressure (LP)-UV/H2O2 advanced oxidation process (AOP), engaged with online sensor-based monitoring system. Thirty-nine TOrCs were evaluated in two distinct secondary wastewater effluents in terms of estimated photochemical reactivity, as a function of the rate constants of UV direct photolysis (kUV) and hydroxyl radical (OH) oxidation (kOH). The selected eighteen TOrCs were classified into three groups that served as indicator compounds: Group 1 for photo-susceptible TOrCs but with minor degradation by OH oxidation (diclofenac, fluoxetine, iohexol, iopamidol, iopromide, simazine and sulfamethoxazole); Group 2 for TOrCs susceptible to both direct photolysis and OH oxidation (benzotriazole, diphenhydramine, ibuprofen, naproxen and sucralose); and Group 3 for photo-resistant TOrCs showing dominant degradation by OH oxidation (atenolol, carbamazepine, DEET, gemfibrozil, primidone and trimethoprim). The results indicate that TOC (optical-based measurement), UVA254 or UVT254 (UV absorbance or transmittance at 254 nm), and total fluorescence can all be used as suitable on-line organic surrogate parameters to predict the attenuation of TOrCs. Furthermore, the automated real-time monitoring via on-line surrogate sensors and equipped with the developed degradation profiles between sensor response and a group of TOrCs removal can provide a diagnostic tool for process control during advanced treatment of reclaimed waters. PMID:26074188

  6. The correlation between LDH serum levels and clinical outcome in advanced biliary tract cancer patients treated with first line chemotherapy

    PubMed Central

    Faloppi, Luca; Del Prete, Michela; Gardini, Andrea Casadei; Santini, Daniele; Silvestris, Nicola; Bianconi, Maristella; Giampieri, Riccardo; Valgiusti, Martina; Brunetti, Oronzo; Bittoni, Alessandro; Andrikou, Kalliopi; Lai, Eleonora; Dessì, Alessandra; Cascinu, Stefano; Scartozzi, Mario

    2016-01-01

    LDH may represent an indirect marker of neo-angiogenesis and worse prognosis in many tumour types. We assessed the correlation between LDH and clinical outcome for biliary tract cancer (BTC) patients treated with first-line chemotherapy. Overall, 114 advanced BTC patients treated with first-line gemcitabine and cisplatin were included. Patients were divided into two groups (low vs. high LDH), according to pre-treatment LDH values. Patients were also classified according to pre- and post-treatment variation in LDH serum levels (increased vs. decreased). Median progression free survival (PFS) was 5.0 and 2.6 months respectively in patients with low and high pre-treatment LDH levels (p = 0.0042, HR = 0.56, 95% CI: 0.37–0.87). Median overall survival (OS) was 7.7 and 5.6 months (low vs. high LDH) (p = 0.324, HR = 0.81, 95% CI: 0.54–1.24). DCR was 71% vs. 43% (low vs. high LDH) (p = 0.002). In 38 patients with decreased LDH values after treatment, PFS and OS were respectively 6.2 and 12.1 months, whereas in 76 patients with post-treatment increased LDH levels, PFS and OS were respectively 3.0 and 5.1 months (PFS: p = 0.0009; HR = 0.49; 95% IC: 0.33–0.74; OS: p < 0.0001; HR = 0.42; 95% IC: 0.27–0.63). Our data seem to suggest that LDH serum level may predict clinical outcome in BTC patients receiving first-line chemotherapy. PMID:27063994

  7. Budget impact analysis of first-line treatment with pazopanib for advanced renal cell carcinoma in Spain

    PubMed Central

    2013-01-01

    Background Due to economic constraints, cancer therapies are under close scrutiny by clinicians, pharmacists and payers alike. There is no published pharmacoeconomic evidence guiding the choice of first-line therapy for advanced renal cell carcinoma (RCC) in the Spanish setting. We aimed to develop a model describing the natural history of RCC that can be used in healthcare decision-making. We particularly analyzed the budget impact associated with the introduction of pazopanib compared to sunitinib under the Spanish National Healthcare System (NHS) perspective. Methods We developed a Markov model to estimate the future number of cases of advanced RCC (patients with favorable or intermediate risk) resulting either from initial diagnosis or disease progression after surgery. The model parameters were obtained from the literature. We assumed that patients would receive either pazopanib or sunitinib as first-line therapy until disease progression. Pharmacological costs and costs associated with the management of adverse events (AE) were considered. A univariate sensitivity analysis was undertaken in order to test the robustness of the results. Results The model predicted an adult RCC prevalence of 7.5/100,000 (1-year), 20.7/100,000 (3-year) and 32.5/100,000 (5-year). These figures are very close to GLOBOCAN reported RCC prevalence estimates of 7.6/100,000, 20.2/100,000 and 31.1/100,000, respectively. The model predicts 1,591 advanced RCC patients with favorable or intermediate risk in Spain in 2013. Annual per patient pharmacological costs were €32,365 and €39,232 with pazopanib and sunitinib, respectively. Annual costs associated with the management of AE were €662 and €974, respectively. Overall annual per patient costs were €7,179 (18%) lower with pazopanib compared to sunitinib. For every point increase in the percentage of patients treated with pazopanib, the NHS would save €67,236. If all the 1,591 patients predicted were treated with pazopanib, the

  8. A fast-time-response extreme ultraviolet spectrometer for measurement of impurity line emissions in the Experimental Advanced Superconducting Tokamak

    NASA Astrophysics Data System (ADS)

    Zhang, Ling; Morita, Shigeru; Xu, Zong; Wu, Zhenwei; Zhang, Pengfei; Wu, Chengrui; Gao, Wei; Ohishi, Tetsutarou; Goto, Motoshi; Shen, Junsong; Chen, Yingjie; Liu, Xiang; Wang, Yumin; Dong, Chunfeng; Zhang, Hongmin; Huang, Xianli; Gong, Xianzu; Hu, Liqun; Chen, Junlin; Zhang, Xiaodong; Wan, Baonian; Li, Jiangang

    2015-12-01

    A flat-field extreme ultraviolet (EUV) spectrometer working in the 20-500 Å wavelength range with fast time response has been newly developed to measure line emissions from highly ionized tungsten in the Experimental Advanced Superconducting Tokamak (EAST) with a tungsten divertor, while the monitoring of light and medium impurities is also an aim in the present development. A flat-field focal plane for spectral image detection is made by a laminar-type varied-line-spacing concave holographic grating with an angle of incidence of 87°. A back-illuminated charge-coupled device (CCD) with a total size of 26.6 × 6.6 mm2 and pixel numbers of 1024 × 255 (26 × 26 μm2/pixel) is used for recording the focal image of spectral lines. An excellent spectral resolution of Δλ0 = 3-4 pixels, where Δλ0 is defined as full width at the foot position of a spectral line, is obtained at the 80-400 Å wavelength range after careful adjustment of the grating and CCD positions. The high signal readout rate of the CCD can improve the temporal resolution of time-resolved spectra when the CCD is operated in the full vertical binning mode. It is usually operated at 5 ms per frame. If the vertical size of the CCD is reduced with a narrow slit, the time response becomes faster. The high-time response in the spectral measurement therefore makes possible a variety of spectroscopic studies, e.g., impurity behavior in long pulse discharges with edge-localized mode bursts. An absolute intensity calibration of the EUV spectrometer is also carried out with a technique using the EUV bremsstrahlung continuum at 20-150 Å for quantitative data analysis. Thus, the high-time resolution tungsten spectra have been successfully observed with good spectral resolution using the present EUV spectrometer system. Typical tungsten spectra in the EUV wavelength range observed from EAST discharges are presented with absolute intensity and spectral identification.

  9. A fast-time-response extreme ultraviolet spectrometer for measurement of impurity line emissions in the Experimental Advanced Superconducting Tokamak.

    PubMed

    Zhang, Ling; Morita, Shigeru; Xu, Zong; Wu, Zhenwei; Zhang, Pengfei; Wu, Chengrui; Gao, Wei; Ohishi, Tetsutarou; Goto, Motoshi; Shen, Junsong; Chen, Yingjie; Liu, Xiang; Wang, Yumin; Dong, Chunfeng; Zhang, Hongmin; Huang, Xianli; Gong, Xianzu; Hu, Liqun; Chen, Junlin; Zhang, Xiaodong; Wan, Baonian; Li, Jiangang

    2015-12-01

    A flat-field extreme ultraviolet (EUV) spectrometer working in the 20-500 Å wavelength range with fast time response has been newly developed to measure line emissions from highly ionized tungsten in the Experimental Advanced Superconducting Tokamak (EAST) with a tungsten divertor, while the monitoring of light and medium impurities is also an aim in the present development. A flat-field focal plane for spectral image detection is made by a laminar-type varied-line-spacing concave holographic grating with an angle of incidence of 87°. A back-illuminated charge-coupled device (CCD) with a total size of 26.6 × 6.6 mm(2) and pixel numbers of 1024 × 255 (26 × 26 μm(2)/pixel) is used for recording the focal image of spectral lines. An excellent spectral resolution of Δλ0 = 3-4 pixels, where Δλ0 is defined as full width at the foot position of a spectral line, is obtained at the 80-400 Å wavelength range after careful adjustment of the grating and CCD positions. The high signal readout rate of the CCD can improve the temporal resolution of time-resolved spectra when the CCD is operated in the full vertical binning mode. It is usually operated at 5 ms per frame. If the vertical size of the CCD is reduced with a narrow slit, the time response becomes faster. The high-time response in the spectral measurement therefore makes possible a variety of spectroscopic studies, e.g., impurity behavior in long pulse discharges with edge-localized mode bursts. An absolute intensity calibration of the EUV spectrometer is also carried out with a technique using the EUV bremsstrahlung continuum at 20-150 Å for quantitative data analysis. Thus, the high-time resolution tungsten spectra have been successfully observed with good spectral resolution using the present EUV spectrometer system. Typical tungsten spectra in the EUV wavelength range observed from EAST discharges are presented with absolute intensity and spectral identification. PMID:26724029

  10. A fast-time-response extreme ultraviolet spectrometer for measurement of impurity line emissions in the Experimental Advanced Superconducting Tokamak

    SciTech Connect

    Zhang, Ling; Xu, Zong; Wu, Zhenwei; Zhang, Pengfei; Wu, Chengrui; Gao, Wei; Shen, Junsong; Chen, Yingjie; Liu, Xiang; Wang, Yumin; Gong, Xianzu; Hu, Liqun; Chen, Junlin; Zhang, Xiaodong; Wan, Baonian; Li, Jiangang; Morita, Shigeru; Ohishi, Tetsutarou; Goto, Motoshi; Dong, Chunfeng; and others

    2015-12-15

    A flat-field extreme ultraviolet (EUV) spectrometer working in the 20-500 Å wavelength range with fast time response has been newly developed to measure line emissions from highly ionized tungsten in the Experimental Advanced Superconducting Tokamak (EAST) with a tungsten divertor, while the monitoring of light and medium impurities is also an aim in the present development. A flat-field focal plane for spectral image detection is made by a laminar-type varied-line-spacing concave holographic grating with an angle of incidence of 87°. A back-illuminated charge-coupled device (CCD) with a total size of 26.6 × 6.6 mm{sup 2} and pixel numbers of 1024 × 255 (26 × 26 μm{sup 2}/pixel) is used for recording the focal image of spectral lines. An excellent spectral resolution of Δλ{sub 0} = 3-4 pixels, where Δλ{sub 0} is defined as full width at the foot position of a spectral line, is obtained at the 80-400 Å wavelength range after careful adjustment of the grating and CCD positions. The high signal readout rate of the CCD can improve the temporal resolution of time-resolved spectra when the CCD is operated in the full vertical binning mode. It is usually operated at 5 ms per frame. If the vertical size of the CCD is reduced with a narrow slit, the time response becomes faster. The high-time response in the spectral measurement therefore makes possible a variety of spectroscopic studies, e.g., impurity behavior in long pulse discharges with edge-localized mode bursts. An absolute intensity calibration of the EUV spectrometer is also carried out with a technique using the EUV bremsstrahlung continuum at 20-150 Å for quantitative data analysis. Thus, the high-time resolution tungsten spectra have been successfully observed with good spectral resolution using the present EUV spectrometer system. Typical tungsten spectra in the EUV wavelength range observed from EAST discharges are presented with absolute intensity and spectral identification.

  11. A fast-time-response extreme ultraviolet spectrometer for measurement of impurity line emissions in the Experimental Advanced Superconducting Tokamak.

    PubMed

    Zhang, Ling; Morita, Shigeru; Xu, Zong; Wu, Zhenwei; Zhang, Pengfei; Wu, Chengrui; Gao, Wei; Ohishi, Tetsutarou; Goto, Motoshi; Shen, Junsong; Chen, Yingjie; Liu, Xiang; Wang, Yumin; Dong, Chunfeng; Zhang, Hongmin; Huang, Xianli; Gong, Xianzu; Hu, Liqun; Chen, Junlin; Zhang, Xiaodong; Wan, Baonian; Li, Jiangang

    2015-12-01

    A flat-field extreme ultraviolet (EUV) spectrometer working in the 20-500 Å wavelength range with fast time response has been newly developed to measure line emissions from highly ionized tungsten in the Experimental Advanced Superconducting Tokamak (EAST) with a tungsten divertor, while the monitoring of light and medium impurities is also an aim in the present development. A flat-field focal plane for spectral image detection is made by a laminar-type varied-line-spacing concave holographic grating with an angle of incidence of 87°. A back-illuminated charge-coupled device (CCD) with a total size of 26.6 × 6.6 mm(2) and pixel numbers of 1024 × 255 (26 × 26 μm(2)/pixel) is used for recording the focal image of spectral lines. An excellent spectral resolution of Δλ0 = 3-4 pixels, where Δλ0 is defined as full width at the foot position of a spectral line, is obtained at the 80-400 Å wavelength range after careful adjustment of the grating and CCD positions. The high signal readout rate of the CCD can improve the temporal resolution of time-resolved spectra when the CCD is operated in the full vertical binning mode. It is usually operated at 5 ms per frame. If the vertical size of the CCD is reduced with a narrow slit, the time response becomes faster. The high-time response in the spectral measurement therefore makes possible a variety of spectroscopic studies, e.g., impurity behavior in long pulse discharges with edge-localized mode bursts. An absolute intensity calibration of the EUV spectrometer is also carried out with a technique using the EUV bremsstrahlung continuum at 20-150 Å for quantitative data analysis. Thus, the high-time resolution tungsten spectra have been successfully observed with good spectral resolution using the present EUV spectrometer system. Typical tungsten spectra in the EUV wavelength range observed from EAST discharges are presented with absolute intensity and spectral identification.

  12. Systematic review of aromatase inhibitors in the first-line treatment for hormone sensitive advanced or metastatic breast cancer.

    PubMed

    Riemsma, Rob; Forbes, C A; Kessels, A; Lykopoulos, K; Amonkar, M M; Rea, D W; Kleijnen, J

    2010-08-01

    To undertake a systematic review of three first-line treatments (letrozole, anastrozole and exemestane) for hormone sensitive advanced or metastatic breast cancer (MBC) in post-menopausal women. We searched six databases from inception up to January 2009 for relevant trials regardless of language or publication status. Randomised controlled clinical trials assessing the safety and efficacy of first-line AIs for post-menopausal women with hormone receptor-positive (HR+, i.e. ER+ and/or PgR+) with or without ErbB2 (HER2)-positive MBC, who have not received prior therapy for advanced or metastatic disease were included. Where meta-analysis using direct or indirect comparisons was considered unsuitable for some or all of the data, we employed a narrative synthesis method. Four studies (25 papers) met the inclusion criteria. From the available evidence, it was possible to directly compare the three AIs with tamoxifen. In addition, by using a network meta-analysis it was possible to compare the three AIs with each other. Based on direct evidence, letrozole seemed to be significantly better than tamoxifen in terms of time-to-progression (TTP) (HR = 0.70 (95% CI: 0.60, 0.82)), objective response rate (RR = 0.65 (95% CI: 0.52, 0.82)) and quality-adjusted time without symptoms or toxicity (Q-Twist difference = 1.5; P < 0.001). Exemestane seemed significantly superior to tamoxifen in terms of objective response rate (RR = 0.68 (95% CI: 0.53, 0.89)). Anastrozole seemed significantly superior to tamoxifen in terms of TTP in one trial (HR = 1.42 (95% CI: 1.15, NR)), but not in the other (HR = 1.01 (95% CI: 0.87, NR)). In terms of adverse events, no significant differences were found between letrozole and tamoxifen. Tamoxifen was associated with significantly more serious adverse events in comparison with exemestane (OR = 0.61 (95% CI: 0.38, 0.97)); while exemestane was associated with significantly more arthralgia in comparison with tamoxifen (OR = 2.33 (95% CI: 1.07, 5

  13. Pemetrexed Maintenance Therapy Following Bevacizumab-Containing First-Line Chemotherapy in Advanced Malignant Pleural Mesothelioma: A Case Report and Literatures Review.

    PubMed

    Jing, Xu-Quan; Zhou, Lei; Sun, Xin-Dong; Yu, Jin-Ming; Meng, Xue

    2016-04-01

    Malignant pleural mesothelioma (MPM) is a lethal disease with poor prognosis. The combination of cisplatin and pemetrexed has been confirmed as the standard of care for nonoperable MPM. Data have shown that the adoption of pemetrexed maintenance therapy (PMT) following first-line treatment appears extremely promising.We describe a 57-year-old man diagnosed as advanced MPM. We treated this patient with PMT after first-line cisplatin-based bevacizumab-containing chemotherapy and residual tumor disappeared after 6 course of PMT. A perfect response and a long progression-free survival (PFS) were reached with tumor mass disappearing and 14 months duration of PFS.This case suggests that adding bevacizumab to standard first-line chemotherapy is feasible and that PMT could be promising and useful for treating advanced MPM. We further entail a review of the literature on the first-line treatment, continuation maintenance therapy, switch maintenance therapy, and second-line treatment of patients with advanced MPM.

  14. Jet outflow and open field line measurements on the C-2U advanced beam-driven field-reversed configuration plasma experiment

    NASA Astrophysics Data System (ADS)

    Sheftman, D.; Gupta, D.; Roche, T.; Thompson, M. C.; Giammanco, F.; Conti, F.; Marsili, P.; Moreno, C. D.

    2016-11-01

    Knowledge and control of the axial outflow of plasma particles and energy along open-magnetic-field lines are of crucial importance to the stability and longevity of the advanced beam-driven field-reversed configuration plasma. An overview of the diagnostic methods used to perform measurements on the open field line plasma on C-2U is presented, including passive Doppler impurity spectroscopy, microwave interferometry, and triple Langmuir probe measurements. Results of these measurements provide the jet ion temperature and axial velocity, electron density, and high frequency density fluctuations.

  15. Advanced mask technique to improve bit line CD uniformity of 90 nm node flash memory in low-k1 lithography

    NASA Astrophysics Data System (ADS)

    Kim, Jong-doo; Choi, Jae-young; Kim, Jea-hee; Han, Jae-won

    2008-10-01

    As devices size move toward 90nm technology node or below, defining uniform bit line CD of flash devices is one of the most challenging features to print in KrF lithography. There are two principal difficulties in defining bit line on wafer. One is insufficient process margin besides poor resolution compared with ArF lithography. The other is that asymmetric bit line should be made for OPC(Optical Proximity Correction) modeling. Therefore advanced ArF lithography scanner should be used for define bit line with RETs (Resolution Enhancement Techniques) such as immersion lithography, OPC, PSM(Phase Shift Mask), high NA(Numerical Aperture), OAI(Off-Axis Illumination), SRAF(Sub-resolution Assistant Feature), and mask biasing.. Like this, ArF lithography propose the method of enhancing resolution, however, we must spend an enormous amount of CoC(cost of ownership) to utilize ArF photolithography process than KrF. In this paper, we suggest method to improve of bit line CD uniformity, patterned by KrF lithographic process in 90nm sFlash(stand alone Flash) devices. We applied new scheme of mask manufacturing, which is able to realize 2 different types of mask, binary and phase-shift, into one plate. Finally, we could get the more uniform bit lines and we expect to get more stable properties then before applying this technique.

  16. Efficacy and safety of trastuzumab combined with chemotherapy for first-line treatment and beyond progression of HER2-overexpressing advanced breast cancer

    PubMed Central

    Shao, Bin; Yan,, Yin; Song, Guohong; Liu, Xiaoran; Wang, Jing; Liang, Xu

    2016-01-01

    Objective To observe the efficacy and safety of trastuzumab combined with chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing advanced breast cancer. Methods A total of 90 patients with HER2-overexpressing advanced breast cancer were enrolled in this study. All patients were diagnosed with ductal invasive breast cancer by pathological analysis, and were aged between 31–73 years with a median of 51 years. HER2-positivity was defined as 3(+) staining in immunochemistry or amplification of fluorescence in situ hybridization (FISH, ratio ≥2.0). Trastuzumab was administered in combination with chemotherapy as first-line treatment and beyond progression as a secondline, third-line, and above treatment in 90, 34, 14, and 6 patients, respectively. The chemotherapy regimen was given according to normal clinical practice. The response rate was evaluated every two cycles, and the primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival curves were estimated by using Kaplan-Meier graphs and were compared by using log-rank test statistics. Multivariate analysis was done using Cox’s proportional hazards regression model, and the level of significance was P<0.05. Results All 90 patients received at least one dose of trastuzumab, and efficacy could be evaluated in 85 patients. The median follow-up was 50 months. In total, 72 (80.00%) patients had visceral metastasis, and 43 (47.78%) patients had progressed after one or more extensive chemotherapy regimens for metastatic diseases. The median PFS for first-line trastuzumab was 10 months (range, 2–59 months), and the median OS after metastasis or initially local advanced disease was 22 months (range, 2–116 months). Conclusions Trastuzumab combined with chemotherapy was active and well-tolerated as a first-line treatment and even beyond progression in HER2-overexpressing advanced breast cancer as a second-line or third-line treatment. However, its

  17. Second- and Further-Line Therapy with Erlotinib in Patients with Advanced Non-Small-Cell Lung Cancer in Daily Clinical Practice

    PubMed Central

    Krainhöfer, Josephine; Steinert, Matthias; Reissig, Angelika

    2014-01-01

    Introduction. The aim of this retrospective study was to examine effect of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) in second-line and further therapy in daily clinical practice. Methods. Patients with histologically or cytologically proven NSCLC (n = 84) treated with erlotinib in second-line (n = 34), third-line (n = 36), and more-line therapy (n = 14) were examined for progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of therapy, and adverse effects. Results. Median PFS of all lines was 83 days (CI 70.0–96.0), OS was 7 months (CI 4.7–9.3), DCR was 66.2% (CI 55–77%), and 1-year survival rate was 33% (CI 22–43%), with no significant difference between therapy lines. Median duration of treatment was 76 days (IQR 39–139.5). Patients with epidermal growth factor receptor mutation (EGFR-M) reached the highest PFS (204 days), as did patients with good performance status (ECOG 0-1: 94 versus ECOG 2-3: 65 days, P = 0.035). Patients with EGFR-M also revealed a DCR of 100%. The most frequent side effects were rash (69%) and diarrhoea (41%), without any significant difference between therapy lines. In 24 patients, the treatment dose was reduced and in 18, the therapy was paused. Conclusion. Erlotinib works in all therapy lines without any significant differences in efficacy and side effects. PMID:25028671

  18. Efficacy and safety of pharmacological interventions in second- or later-line treatment of patients with advanced soft tissue sarcoma: a systematic review

    PubMed Central

    2013-01-01

    Background Current guidelines recommend anthracycline-based chemotherapy primarily with doxorubicin either as monotherapy or in combination with ifosfamide as the first-line treatment for most advanced STS subtypes. Therapeutic options after failure of doxorubicin and/or ifosfamide are limited. This study aimed to comprehensively review available data on the activity and safety of interventions in second- or later-line treatment of advanced STS. Methods Electronic literature databases (Embase®, MEDLINE®, MEDLINE® In-Process, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews) were searched from 1980 to 01 March 2012 to identify randomised controlled trials (RCTs) and non-randomised studies (both prospective and retrospective) evaluating pharmacological interventions in patients with advanced STS pre-treated with anthracycline- and/or ifosfamide-based therapy. Results The review identified six RCTs (one phase III and five phase II trials) and 94 non-randomised studies. Based on the primary trial endpoints, RCTs demonstrated favourable efficacy for pazopanib over placebo (PFS: 4.6 months vs. 1.6 months), gemcitabine plus dacarbazine over dacarbazine monotherapy (3-month PFS rate: 54.2% vs. 35.2%), and trabectedin 3-weekly schedule over weekly schedule (TTP: 3.7 months vs. 2.3 months. The non-randomised studies demonstrated heterogeneity in efficacy and safety results. Conclusions Across the RCTs, pazopanib over placebo, gemcitabine-dacarbazine over dacarbazine, and trabectedin 3-weekly over weekly regimen clearly demonstrated a PFS advantage in the second- and later-line treatment of advanced STS. With only one phase III trial in this setting, there is a clear need for additional comparative trials to better understand the risk: benefit ratios of available agents and combinations. PMID:23937858

  19. Post-study therapy as a source of confounding in survival analysis of first-line studies in patients with advanced non-small-cell lung cancer

    PubMed Central

    Zietemann, Vera D; Schuster, Tibor; Duell, Thomas HG

    2011-01-01

    Clinical trials exploring the long-term effects of first-line therapy in patients with advanced non-small-cell lung cancer generally disregard subsequent treatment although most patients receive second and third-line therapies. The choice of further therapy depends on critical intermediate events such as disease progression and it is usually left at the physician’s discretion. Time-dependent confounding may then arise with standard survival analyses producing biased effect estimates, even in randomized trials. Herein we describe the concept of time-dependent confounding in detail and discuss whether the response to first-line treatment may be a potential time-dependent confounding factor for survival in the context of subsequent therapy. A prospective observational study of 406 patients with advanced non-small-cell lung cancer served as an example base. There is evidence that time-dependent confounding may occur in multivariate survival analysis after first-line therapy when disregarding subsequent treatment. In the light of this important but underestimated aspect some of the large and meaningful recent clinical first-line lung cancer studies are discussed, focussing on subsequent treatment and its potential impact on the survival of the study patients. No recently performed lung cancer trial applied adequate statistical analyses despite the frequent use of subsequent therapies. In conclusion, effect estimates from standard survival analysis may be biased even in randomized controlled trials because of time-dependent confounding. To adequately assess treatment effects on long-term outcomes appropriate statistical analyses need to take subsequent treatment into account. PMID:22263071

  20. Genetic linkage of hyperglycemia, body weight and serum amyloid-P in an intercross between C57BL/6 and C3H apolipoprotein E-deficient mice.

    PubMed

    Su, Zhiguang; Li, Yuhua; James, Jessica C; Matsumoto, Alan H; Helm, Gregory A; Lusis, Aldons J; Shi, Weibin

    2006-05-15

    Dyslipidemia and hyperglycemia are integral components of the metabolic perturbations in type 2 diabetes. Apolipoprotein E-deficient (apoE(-/-)) mice develop severe hyperlipidemia and significant hyperglycemia when fed a western diet containing 21% fat (w/w), 0.15% cholesterol and 19.5% casein. Using an intercross between C57BL/6J (B6) and C3H/HeJ (C3H) apoE(-/-) mice, we performed quantitative trait locus (QTL) analysis to identify loci contributing to hyperglycemia and associated traits. Fasting plasma levels of glucose, insulin and serum amyloid-P (SAP) and body weight in 234 female F2 mice were measured after being fed the western diet for 12 weeks. QTL analysis revealed one significant QTL, named Bglu3 [95.8 cM, logarithm of odds ratio (OR)(LOD) 4.1], on chromosome 1 and a suggestive QTL on chromosome 9 (38 cM, LOD 2.3) that influenced plasma glucose levels. Bglu3 coincided with loci on distal chromosomal 1 that had a major influence on plasma SAP levels and body weight. Significant correlations between plasma glucose, SAP and body weight were observed in F2 mice. Thus, these results demonstrate genetic linkages of hyperglycemia and body weight with SAP, a marker of the acute-phase response, in hyperlipidemic apoE(-/-) mice and suggest a probability for the Sap gene to be a positional candidate of Bglu3.

  1. Genome-wide SNP scan in a porcine Large White×Minzhu intercross population reveals a locus influencing muscle mass on chromosome 2.

    PubMed

    Liu, Xin; Wang, Li Gang; Luo, Wei Zhen; Li, Yong; Liang, Jing; Yan, Hua; Zhao, Ke Bin; Wang, Li Xian; Zhang, Long Chao

    2014-12-01

    A high-density single nucleotide polymorphism (SNP) array containing 62 163 markers was employed for a genome-wide association study (GWAS) to identify variants associated with lean meat in ham (LMH, %) and lean meat percentage (LMP, %) within a porcine Large White×Minzhu intercross population. For each individual, LMH and LMP were measured after slaughter at the age of 240±7 days. A total of 557 F2 animals were genotyped. The GWAS revealed that 21 SNPs showed significant genome-wide or chromosome-wide associations with LMH and LMP by the Genome-wide Rapid Association using Mixed Model and Regression-Genomic Control approach. Nineteen significant genome-wide SNPs were mapped to the distal end of Sus Scrofa Chromosome (SSC) 2, where a major known gene responsible for muscle mass, IGF2 is located. A conditioned analysis, in which the genotype of the strongest associated SNP is included as a fixed effect in the model, showed that those significant SNPs on SSC2 were derived from a single quantitative trait locus. The two chromosome-wide association SNPs on SSC1 disappeared after conditioned analysis suggested the association signal is a false association derived from using a F2 population. The present result is expected to lead to novel insights into muscle mass in different pig breeds and lays a preliminary foundation for follow-up studies for identification of causal mutations for subsequent application in marker-assisted selection programs for improving muscle mass in pigs.

  2. Installation and Final Testing of an On-Line, Multi-Spectrometer Fission Product Monitoring System (FPMS) to Support Advanced Gas Reactor (AGR) Fuel Testing and Qualification in the Advanced Test Reactor

    SciTech Connect

    J. K. Hartwell; D. M. Scates; M. W. Drigert; J. B. Walter

    2006-10-01

    The US Department of Energy (DOE) is initiating tests of reactor fuel for use in an Advanced Gas Reactor (AGR). The AGR will use helium coolant, a low-power-density ceramic core, and coated-particle fuel. A series of eight (8) fuel irradiation tests are planned for the Idaho National Laboratory’s (INL’s) Advanced Test Reactor (ATR). One important measure of fuel performance in these tests is quantification of the fission gas releases over the nominal 2-year duration of each irradiation experiment. This test objective will be met using the AGR Fission Product Monitoring System (FPMS) which includes seven (7) on-line detection stations viewing each of the six test capsule effluent lines (plus one spare). Each station incorporates both a heavily-shielded high-purity germanium (HPGe) gamma-ray spectrometer for quantification of the isotopic releases, and a NaI(Tl) scintillation detector to monitor the total count rate and identify the timing of the releases. The AGR-1 experiment will begin irradiation after October 1, 2006. To support this experiment, the FPMS has been completely assembled, tested, and calibrated in a laboratory at the INL, and then reassembled and tested in its final location in the ATR reactor basement. This paper presents the details of the equipment performance, the control and acquisition software, the test plan for the irradiation monitoring, and the installation in the ATR basement. Preliminary on-line data may be available by the Conference date.

  3. On the theory for the arrest of an advancing molten contact line on a cold solid of the same material

    NASA Astrophysics Data System (ADS)

    Schiaffino, Stefano; Sonin, Ain A.

    1997-08-01

    We show that a conventional continuum formulation of the equations and boundary conditions for the spreading of a pure molten material over a cold, solid substrate of its own kind has no meaningful solution for the angle of attack θs of the fusion front at the contact line, which is the quantity that determines contact-line arrest. θs is determined by the heat flux just behind the contact line, and the heat flux in the mathematical model is singular at the contact line. The scale of the physical mechanism which limits the heat flux at the contact line and removes the singularity is estimated by computing the point where the continuum model must be cut off in order to bring it into agreement with the experimental data for a microcrystalline wax. The cutoff scale is in the range 0.1-1 μm, that is, much larger than molecular dimensions, but of order 10-2-10-1 times the convective thermal length scale α/U.

  4. Prognostic models to predict survival in patients with advanced non-small cell lung cancer treated with first-line chemo- or targeted therapy

    PubMed Central

    Berardi, Rossana; Rinaldi, Silvia; Santoni, Matteo; Newsom-Davis, Thomas; Tiberi, Michela; Morgese, Francesca; Caramanti, Miriam; Savini, Agnese; Ferrini, Consuelo; Torniai, Mariangela; Fiordoliva, Ilaria; Bower, Marc; Cascinu, Stefano

    2016-01-01

    Background We aimed to assess the prognostic role of neutrophilia, lymphocytopenia and the neutrophil-to-lymphocyte ratio (NLR), and to design models to define the prognosis of patients receiving first-line chemo- or targeted therapy for advanced non-small cell lung cancer (NSCLC). Materials and Methods We retrospectively analysed 401 consecutive patients with advanced NSCLC treated with first line chemo- or targeted therapy. Patients were stratified into two groups with pre-treatment NLR ≥ 3.7 (Group A) vs. < 3.7 (Group B). The best NLR cut-off was identified by ROC curve analysis. Results At baseline 264 patients had NLR≥3.7 (Group A), whilst 137 had lower NLR (Group B). Median OS was 10.8 months and 19.4 months in the two groups (p < 0.001), while median PFS was 3.6 months and 5.6 months, respectively (p = 0.012). At multivariate analysis, ECOG-PS≥2, stage IV cancer, non-adenocarcinoma histology, EGFR wild-type status and NLR were predictors of worse OS. Stage IV cancer, wild type EGFR status and NLR≥3.7 were independent prognostic factors for worse PFS. Patients were stratified according to the presence of 0-1 prognostic factors (8%), 2-3 factors (73%) and 4-5 factors (19%) and median OS in these groups was 33.7 months, 14.6 months and 6.6 months, respectively (p < 0.001). Similarly, patients were stratified for PFS based on the presence of 0-1 prognostic factor (15%), 2 factors (41%) and 3 factors (44%). The median PFS was 8.3 months, 4.6 months and 3.3 months respectively (p < 0.001). Conclusion Pre-treatment NLR is an independent prognostic factor for patients with advanced NSCLC treated with first-line therapies. PMID:27029035

  5. Correlation Between E-cadherin Immunoexpression and Efficacy of First Line Platinum-Based Chemotherapy in Advanced High Grade Serous Ovarian Cancer.

    PubMed

    Miše, Branka Petrić; Telesmanić, Vesna Dobrić; Tomić, Snježana; Šundov, Dinka; Čapkun, Vesna; Vrdoljak, Eduard

    2015-04-01

    To analyze correlation between immunoexpression of E-cadherin and efficacy of first line platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma. The expression of E-cadherin was analyzed immunohistochemically in formalin-fixed, paraffin-embedded samples from 98 patients with advanced-stage high-grade serous ovarian cancer and related to clinical features (stage according to the International Federation of Gynecology and Obstetrics (FIGO) and residual tumors after initial cytoreductive surgery), response to platinum-based chemotherapy (according to Response Evaluation Criteria in Solid tumors (RECIST 1.1 criteria)), platinum sensitivity (according to platinum free interval (PFI) as platinum-refractory, platinum-resistant and platinum-sensitive) and patients progression free survival (PFS) and overall survival (OS). E-cadherin immunostaining was positive in 74 and negative in 24 serous ovarian carcinomas. E-cadherin immunoreactivity was not associated with FIGO stage, residual tumor after initial cytoreductive surgery and number of chemotherapy cycles. Positive E-cadherin expression predict significantly better response to first line platinum-based chemotherapy (p < 0.001) and platinum sensitivity (p < 0.001). Moreover, positive E-cadherin expression predict significantly longer PFS (p < 0.001) and OS (p < 0.001). The multivariate analysis for OS showed that positive E-cadherin expression is predictor to platinum sensitivity (p < 0.001) and longer OS (p = 0.01). Positive E-cadherin expression seems to be a predictor of better response to first line platinum-based chemotherapy, platinum sensitivity and favorable clinical outcome in patients with advanced-stage serous ovarian cancer. Negative E-cadherin expression was shown to be significant, independent predictor of poorer PFS and OS. E-cadherin as a marker has predictive and prognostic value.

  6. The Effects of Advance Stop Lines and Sign Prompts on Pedestrian Safety in a Crosswalk on a Multilane Highway.

    ERIC Educational Resources Information Center

    Van Houten, Ron

    1988-01-01

    Introduction of prompts in the form of specific signs and stop line bars at a crosswalk was designed to influence motorists to stop further back when yielding right-of-way to pedestrians, and resulted in an almost 80 percent reduction in motor vehicle-pedestrian conflicts at the selected location. (JW)

  7. Participants' engagement with and reactions to the use of on-line action learning sets to support advanced nursing role development.

    PubMed

    Currie, Kay; Biggam, John; Palmer, Janette; Corcoran, Terry

    2012-04-01

    Professional role development in nursing is occurring at a rapid pace in the UK as elsewhere. Internationally, finding relevant, flexible, sustainable educational solutions to support the preparation of nurses for new roles presents significant challenges for Higher Education Institutions, health service managers and the clinical practitioners who are would-be students. The use of on-line learning is frequently advocated as one means of resolving these difficulties. This paper discusses participants' engagement with, and reactions to, the use of on-line Action Learning Sets (ALS) as part of a national pilot development pathway for Advanced Nursing Practice in Scotland. Data collection included: survey of participants' views of on-line ALS; survey comparing perceptions of ALS with other educational experiences within the pathway; in-depth interviews with case-site participants. A range of benefits and limitations of on-line ALS was identified. The benefit of flexible access and sharing experiences with others was emphasised. Conversely, multiple commitments and lack of group cohesiveness significantly interfered with the effectiveness of this process. Key recommendations for future implementation acknowledge participants' preference for a blended approach, with face-to-face sessions to provide 'getting-to-know-you' opportunities, enhancing commitment to the group process.

  8. Identification and time dependence of quantitative trait loci for basal locomotor activity in the BXD recombinant inbred series and a B6D2 F2 intercross.

    PubMed

    Koyner, J; Demarest, K; McCaughran, J; Cipp, L; Hitzemann, R

    2000-05-01

    A complimentary two-phase strategy was used to detect and map quantitative trait loci (QTLs) associated with the basal locomotor response to a saline challenge (10 ml/kg). In phase 1, putative QTLs, significant at p < 0.01 or better, were identified by analysis of the strain means for 25 strains of the B x D recombinant inbred series. QTLs were identified on chromosomes 1, 3, 5, 9, 10, 16, and 18. Some of these QTLs were detected across the entire experimental period (0-20 min), while others were associated with specific 5-min blocks. Eighteen hundred C57BL/6J (B6) x DBA/2J (D2) F2 intercross animals were phenotyped for the basal locomotor response, and of this group, 500 to 700 individuals, pseudo-randomly selected, were used for a genomewide scan to confirm the RI-generated QTLs and to detect new QTLs. No new QTLs were detected but the QTLs on chromosome 1 were confirmed at p < 10(-5) to p < 10(-9), depending on the time interval. In addition, the QTLs on chromosomes 5 and 9 were confirmed at p < 0.001, providing a combined probability (RI + F2) which exceeds the threshold for a significant association. Two additional phenotypes which showed significant RI strain differences were examined--adaptation and thigmotaxis. Adaptation mapped to the same region of chromosome 9 and thigmotaxis to the same region of chromosome 1 as the distance-traveled QTL. Overall, the data presented here and elsewhere (Flint et al., 1995; Gershenfeld et al., 1997) illustrate that QTLs for basal activity are both robust and reliable.

  9. QTL analysis of body weight and carcass body length traits in an F2 intercross between Landrace and Korean native pigs.

    PubMed

    Yoo, C K; Park, H B; Lee, J B; Jung, E J; Kim, B M; Kim, H I; Ahn, S J; Ko, M S; Cho, I C; Lim, H T

    2014-08-01

    Growth traits, such as body weight and carcass body length, directly affect productivity and economic efficiency in the livestock industry. We performed a genome-wide linkage analysis to detect the quantitative trait loci (QTL) that affect body weight, growth curve parameters and carcass body length in an F2 intercross between Landrace and Korean native pigs. Eight phenotypes related to growth were measured in approximately 1000 F2 progeny. All experimental animals were subjected to genotypic analysis using 173 microsatellite markers located throughout the pig genome. The least squares regression approach was used to conduct the QTL analysis. For body weight traits, we mapped 16 genome-wide significant QTL on SSC1, 3, 5, 6, 8, 9 and 12 as well as 22 suggestive QTL on SSC2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 17. On SSC12, we identified a major QTL affecting body weight at 140 days of age that accounted for 4.3% of the phenotypic variance, which was the highest test statistic (F-ratio = 45.6 under the additive model, nominal P = 2.4 × 10(-11) ) observed in this study. We also showed that there were significant QTL on SSC2, 5, 7, 8, 9 and 12 affecting carcass body length and growth curve parameters. Interestingly, the QTL on SSC2, 3, 5, 6, 8, 9, 10, 12 and 17 influencing the growth-related traits showed an obvious trend for co-localization. In conclusion, the identified QTL may play an important role in investigating the genetic structure underlying the phenotypic variation of growth in pigs.

  10. Genome-wide association study of meat quality traits in a White Duroc×Erhualian F2 intercross and Chinese Sutai pigs.

    PubMed

    Ma, Junwu; Yang, Jie; Zhou, Lisheng; Zhang, Zhiyan; Ma, Huanban; Xie, Xianhua; Zhang, Feng; Xiong, Xinwei; Cui, Leilei; Yang, Hui; Liu, Xianxian; Duan, Yanyu; Xiao, Shijun; Ai, Huashui; Ren, Jun; Huang, Lusheng

    2013-01-01

    Thousands of QTLs for meat quality traits have been identified by linkage mapping studies, but most of them lack precise position or replication between populations, which hinder their application in pig breeding programs. To localize QTLs for meat quality traits to precise genomic regions, we performed a genome-wide association (GWA) study using the Illumina PorcineSNP60K Beadchip in two swine populations: 434 Sutai pigs and 933 F2 pigs from a White Duroc×Erhualian intercross. Meat quality traits, including pH, color, drip loss, moisture content, protein content and intramuscular fat content (IMF), marbling and firmness scores in the M. longissimus (LM) and M. semimembranosus (SM) muscles, were recorded on the two populations. In total, 127 chromosome-wide significant SNPs for these traits were identified. Among them, 11 SNPs reached genome-wise significance level, including 1 on SSC3 for pH, 1 on SSC3 and 3 on SSC15 for drip loss, 3 (unmapped) for color a*, and 2 for IMF each on SSC9 and SSCX. Except for 11 unmapped SNPs, 116 significant SNPs fell into 28 genomic regions of approximately 10 Mb or less. Most of these regions corresponded to previously reported QTL regions and spanned smaller intervals than before. The loci on SSC3 and SSC7 appeared to have pleiotropic effects on several related traits. Besides them, a few QTL signals were replicated between the two populations. Further, we identified thirteen new candidate genes for IMF, marbling and firmness, on the basis of their positions, functional annotations and reported expression patterns. The findings will contribute to further identification of the causal mutation underlying these QTLs and future marker-assisted selection in pigs.

  11. QTL analysis of body weight and carcass body length traits in an F2 intercross between Landrace and Korean native pigs.

    PubMed

    Yoo, C K; Park, H B; Lee, J B; Jung, E J; Kim, B M; Kim, H I; Ahn, S J; Ko, M S; Cho, I C; Lim, H T

    2014-08-01

    Growth traits, such as body weight and carcass body length, directly affect productivity and economic efficiency in the livestock industry. We performed a genome-wide linkage analysis to detect the quantitative trait loci (QTL) that affect body weight, growth curve parameters and carcass body length in an F2 intercross between Landrace and Korean native pigs. Eight phenotypes related to growth were measured in approximately 1000 F2 progeny. All experimental animals were subjected to genotypic analysis using 173 microsatellite markers located throughout the pig genome. The least squares regression approach was used to conduct the QTL analysis. For body weight traits, we mapped 16 genome-wide significant QTL on SSC1, 3, 5, 6, 8, 9 and 12 as well as 22 suggestive QTL on SSC2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 17. On SSC12, we identified a major QTL affecting body weight at 140 days of age that accounted for 4.3% of the phenotypic variance, which was the highest test statistic (F-ratio = 45.6 under the additive model, nominal P = 2.4 × 10(-11) ) observed in this study. We also showed that there were significant QTL on SSC2, 5, 7, 8, 9 and 12 affecting carcass body length and growth curve parameters. Interestingly, the QTL on SSC2, 3, 5, 6, 8, 9, 10, 12 and 17 influencing the growth-related traits showed an obvious trend for co-localization. In conclusion, the identified QTL may play an important role in investigating the genetic structure underlying the phenotypic variation of growth in pigs. PMID:24797173

  12. Quantitative Trait Loci Affecting Atherosclerosis at the Aortic Root Identified in an Intercross between DBA2J and 129S6 Apolipoprotein E-Null Mice

    PubMed Central

    Kayashima, Yukako; Tomita, Hirofumi; Zhilicheva, Svetlana; Kim, Shinja; Kim, Hyung-Suk; Bennett, Brian J.; Maeda, Nobuyo

    2014-01-01

    Apolipoprotein E-null mice on a DBA/2J genetic background (DBA-apoE) are highly susceptible to atherosclerosis in the aortic root area compared with those on a 129S6 background (129-apoE). To explore atherosclerosis-responsible genetic regions, we performed a quantitative trait locus (QTL) analysis using 172 male and 137 female F2 derived from an intercross between DBA-apoE and 129-apoE mice. A genome-wide scan identified two significant QTL for the size of lesions at the root: one is Ath44 on Chromosome (Chr) 1 at 158 Mb, and the other Ath45 on Chr 2 at 162 Mb. Ath44 co-localizes with but appears to be independent of a previously reported QTL, Ath1, while Ath45 is a novel QTL. DBA alleles of both Ath44 and Ath45 confer atherosclerosis-susceptibility. In addition, a QTL on Chr 14 at 73 Mb was found significant only in males, and 129 allele conferring susceptibility. Further analysis detected female-specific interactions between a second QTL on Chr 1 at 73 Mb and a QTL on Chr 3 at 21 Mb, and between Chr 7 at 84 Mb and Chr 12 at 77 Mb. These loci for the root atherosclerosis were independent of QTLs for plasma total cholesterol and QTLs for triglycerides, but a QTL for HDL (Chr 1 at 126 Mb) overlapped with the Ath44. Notably, haplotype analysis among 129S6, DBA/2J and C57BL/6 genomes and their gene expression data narrowed the candidate regions for Ath44 and Ath45 to less than 5 Mb intervals where multiple genome wide associations with cardiovascular phenotypes have also been reported in humans. SNPs in or near Fmo3, Sele and Selp for Ath44, and Lbp and Pkig for Ath45 were suggested for further investigation as potential candidates underlying the atherosclerosis susceptibility. PMID:24586312

  13. First-line systemic treatment of advanced stage non-small-cell lung cancer in Asia: consensus statement from the Asian Oncology Summit 2009.

    PubMed

    Soo, Ross A; Anderson, Benjamin O; Cho, Byoung Chul; Yang, Chih-Hsin; Liao, Meilin; Lim, Wan-Teck; Goldstraw, Peter; Mok, Tony S

    2009-11-01

    Non-small-cell lung cancer (NSCLC) is an increasing global challenge, especially in low-income countries. Most guidelines for the management of advanced-stage NSCLC have limited effect in countries with resource constraints. Following a systematic literature search, we present an overview of the management of advanced-stage NSCLC in the first-line setting, discuss resources required for systemic therapy, and provide treatment recommendations stratified to four resources levels. Treatment guidelines appropriate for different resource levels offer a realistic approach to management of advanced-stage NSCLC, by recognising the limitations of a particular health-care system. Although there are many barriers to cancer control in low-resource countries, these can be overcome by using measures that are culturally appropriate, economically feasible, and evidence-based. Initiatives include strategic planning, tobacco control, training of health-care workers, access to therapeutic agents, acquisition of information, public education, and alliances with established institutions and international organisations. PMID:19880064

  14. An exploratory study of sunitinib plus paclitaxel as first-line treatment for patients with advanced breast cancer

    PubMed Central

    Kozloff, M.; Chuang, E.; Starr, A.; Gowland, P. A.; Cataruozolo, P. E.; Collier, M.; Verkh, L.; Huang, X.; Kern, K. A.; Miller, K.

    2010-01-01

    Background: Sunitinib has shown single-agent activity in patients with previously treated metastatic breast cancer (MBC). We investigated the safety of the combination of sunitinib and paclitaxel in an exploratory study of patients with locally advanced or MBC. Methods: Patients received oral sunitinib 25 mg/day (with escalation to 37.5 mg/day as tolerated) on a continuous daily dosing schedule and paclitaxel 90 mg/m2 on days 1, 8, and 15 of each 28-day cycle. Study endpoints included safety (primary endpoint), pharmacokinetics, and antitumor activity. Results: Twenty-two patients were enrolled. The most frequent adverse events (AEs) were fatigue/asthenia (77%), dysgeusia (68%), and diarrhea (64%). Grade 3 AEs included neutropenia (43%), fatigue/asthenia (27%), neuropathy (18%), and diarrhea (14%). No drug–drug interaction was observed on the basis of pharmacokinetic analysis. Of 18 patients with measurable disease at baseline, 7 (38.9%) achieved objective responses (including 2 complete and 5 partial responses). Clinical responses were observed in three of nine patients with triple-negative receptor status (estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor-2 negative). Conclusions: These data indicate that sunitinib and paclitaxel in combination are well tolerated in patients with locally advanced or MBC. No drug–drug interaction was detected and there was preliminary evidence of antitumor activity. PMID:20032126

  15. Advances in cell culture process development: tools and techniques for improving cell line development and process optimization.

    PubMed

    Sharfstein, Susan T

    2008-01-01

    At the 234th National Meeting of the American Chemical Society, held in Boston, MA, August 19-23, 2007, the ACS BIOT division held two oral sessions on Cell Culture Process Development. In addition, a number of posters were presented in this area. The critical issues facing cell culture process development today are how to effectively respond to the increase in product demands and decreased process timelines while maintaining robust process performance and product quality and responding to the Quality by Design initiative promulgated by the Food and Drug Administration. Two main areas were addressed in the presentations: first, to understand the effects of process conditions on productivity and product quality, and second, to achieve improved production cell lines. A variety of techniques to achieve these goals were presented, including automated flow cytometric analysis, a high-throughput cell analysis and selection method, transcriptional and epigenetic techniques for analysis of cell lines and cell culture systems, and novel techniques for glycoform analysis. PMID:18426245

  16. Integration of Photo-Patternable Low-κ Material into Advanced Cu Back-End-Of-The-Line

    NASA Astrophysics Data System (ADS)

    Lin, Qinghuang; Nelson, Alshakim; Chen, Shyng-Tsong; Brock, Philip; Cohen, Stephan A.; Davis, Blake; Kaplan, Richard; Kwong, Ranee; Liniger, Eric; Neumayer, Debra; Patel, Jyotica; Shobha, Hosadurga; Sooriyakumaran, Ratnam; Purushothaman, Sampath; Miller, Robert; Spooner, Terry; Wisnieff, Robert

    2010-05-01

    We report herein the demonstration of a simple, low-cost Cu back-end-of-the-line (BEOL) dual-damascene integration using a novel photo-patternable low-κ dielectric material concept that dramatically reduces Cu BEOL integration complexity. This κ=2.7 photo-patternable low-κ material is based on the SiCOH-based material platform and has sub-200 nm resolution capability with 248 nm optical lithography. Cu/photo-patternable low-κ dual-damascene integration at 45 nm node BEOL fatwire levels has been demonstrated with very high electrical yields using the current manufacturing infrastructure. The photo-patternable low-κ concept is, therefore, a promising technology for highly efficient semiconductor Cu BEOL manufacturing.

  17. Advances in the helium-jet coupled on-line mass separator RAMA. [Recoil Atom Mass Analyzer

    SciTech Connect

    Moltz, D M; Aysto, J; Cable, M D; Parry, R F; Haustein, P E; Wouters, J M; Cerny, J

    1980-01-01

    General improvements to the on-line mass separator RAMA (Recoil Atom Mass Analyzer) have yielded a greater reliability and efficiency for some elements. A new utilitarian helium-jet chamber has been installed to facilitate quick target and degrader foil changes in addition to a new ion source holder. A higher efficiency hollow-cathode, cathode-extraction ion source, for lower melting point elements (< 1200/sup 0/C) has also been designed. Tests with the beta-delayed proton emitter /sup 37/Ca showed a factor of five increase in yield over the old hollow-cathode, anode-extraction source. A differentially-pumped-tape drive system compatible with both ..gamma..-..gamma.. and ..beta..-..gamma.. experiments has been incorporated into the general detection system. All major operating parameters will soon be monitored by a complete stand-alone microprocessor system which will eventually be upgraded to a closed-loop control system.

  18. A Systematic Review and Network Meta-Analysis of Biologic Agents in the First Line Setting for Advanced Colorectal Cancer

    PubMed Central

    Kumachev, Alexander; Yan, Marie; Berry, Scott; Ko, Yoo-Joung; Martinez, Maria C. R.; Shah, Keya; Chan, Kelvin K. W.

    2015-01-01

    Background Epithelial growth factor receptor inhibitors (EGFRis) and bevacizumab (BEV) are used in combination with chemotherapy for the treatment of metastatic colorectal cancer (mCRC). However, few randomized controlled trials (RCTs) have directly compared their relative efficacy on progression-free survival (PFS) and overall survival (OS). Methods We conducted a systematic review of first-line RCTs comparing (1) EGFRis vs. BEV, with chemotherapy in both arms (2) EGFRis + chemotherapy vs. chemotherapy alone, or (3) BEV + chemotherapy vs. chemotherapy alone, using Cochrane methodology. Data on and PFS and OS were extracted using the Parmar method. Pairwise meta-analyses and Bayesian network meta-analyses (NMA) were conducted to estimate the direct, indirect and combined PFS and OS hazard ratios (HRs) comparing EGFRis to BEV. Results Seventeen RCTs contained extractable data for quantitative analysis. Combining direct and indirect data using an NMA did not show a statistical difference between EGFRis versus BEV (PFS HR = 1.11 (95% CR: 0.92–1.36) and OS HR = 0.91 (95% CR: 0.75–1.09)). Direct meta-analysis (3 RCTs), indirect (14 RCTs) and combined (17 RCTs) NMA of PFS HRs were concordant and did not show a difference between EGFRis and BEV. Meta-analysis of OS using direct evidence, largely influenced by one trial, showed an improvement with EGFRis therapy (HR = 0.79 (95% CR: 0.65–0.98)), while indirect and combined NMA of OS did not show a difference between EGFRis and BEV Successive inclusions of trials over time in the combined NMA did not show superiority of EGFRis over BEV. Conclusions Our findings did not support OS or PFS benefits of EGFRis over BEV in first-line mCRC. PMID:26474403

  19. First line treatment of advanced non-small-cell lung cancer - specific focus on albumin bound paclitaxel.

    PubMed

    Gupta, Neha; Hatoum, Hassan; Dy, Grace K

    2014-01-01

    Lung cancer is the leading cause of cancer mortality worldwide in both men and women. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for more than 80% of cases. Paclitaxel has a broad spectrum of activity against various malignancies, including NSCLC. Paclitaxel is poorly soluble in water and thus, until recently, its commercially available preparations contained a non-ionic solvent Cremophor EL®. Cremophor EL® improves the solubility of paclitaxel and allows its intravenous administration. However, certain side-effects associated with paclitaxel, such as hypersensitivity reactions, myelosuppression, and peripheral neuropathy, are known to be worsened by Cremophor®. Nanoparticle albumin-bound paclitaxel ([nab-paclitaxel] ABRAXANE® ABI-007) is a new generation formulation of paclitaxel that obviates the need for Cremophor®, resulting in a safer and faster infusion without requiring the use of premedications to avoid hypersensitivity. Albumin-binding receptor-mediated delivery and lack of sequestering Cremophor® micelles allow higher intratumoral concentration of pharmacologically active paclitaxel. Multiple clinical trials have demonstrated a superior tolerability profile of nab-paclitaxel in comparison to solvent-bound paclitaxel (sb-paclitaxel). A recent Phase III trial compared the effects of weekly nab-paclitaxel in combination with carboplatin versus sb-paclitaxel in combination with carboplatin given every 3 weeks for first line treatment of NSCLC. This trial highlights the weekly nab-paclitaxel combination as an alternate treatment option for NSCLC, with higher response rate in squamous cell NSCLC and longer survival in elderly patients. This review will focus on the properties of nab-paclitaxel and its use in the first line treatment of NSCLC.

  20. Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: follow-up analysis from the randomized 'FIRST' study.

    PubMed

    Robertson, John F R; Lindemann, Justin P O; Llombart-Cussac, Antonio; Rolski, Janusz; Feltl, David; Dewar, John; Emerson, Laura; Dean, Andrew; Ellis, Matthew J

    2012-11-01

    Fulvestrant fIRst-line Study comparing endocrine Treatments is a phase II, randomized, open-label study comparing fulvestrant 500 mg with anastrozole 1 mg as first-line endocrine therapy for postmenopausal women with hormone receptor-positive (HR+) advanced breast cancer. At data cut-off, only 36 % of patients had progressed and the median time to progression (TTP) had not been reached for fulvestrant. Here, we report follow-up data for TTP for fulvestrant 500 mg versus anastrozole 1 mg. Key inclusion criteria were postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive locally advanced or metastatic breast cancer and no prior endocrine therapy. Key exclusion criteria were presence of life-threatening metastases and prior treatment with a non-approved drug. Fulvestrant was administered 500 mg/month plus 500 mg on day 14 of month 1; anastrozole was administered 1 mg/day. TTP was defined by modified Response Evaluation Criteria in Solid Tumors v1.0 before data cut-off for the primary analysis, and investigator opinion after data cut-off. Best overall response to subsequent therapy and serious adverse events are also reported. In total, 205 patients received fulvestrant 500 mg (n = 102) or anastrozole (n = 103). Follow-up analysis was performed when 79.5 % of patients had discontinued study treatment. Median TTP was 23.4 months for fulvestrant versus 13.1 months for anastrozole; a 34 % reduction in risk of progression (hazard ratio 0.66; 95 % confidence interval: 0.47, 0.92; P = 0.01). Best overall response to subsequent therapy and clinical benefit rate for subsequent endocrine therapy was similar between the treatment groups. No new safety concerns for fulvestrant 500 mg were documented. These longer-term, follow-up results confirm efficacy benefit for fulvestrant 500 mg versus anastrozole as first-line endocrine therapy for HR+ advanced breast cancer in terms of TTP, and, importantly, show similar best overall response rates to

  1. Fulvestrant 500 mg Versus Anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall Survival Analysis From the Phase II FIRST Study

    PubMed Central

    Ellis, Matthew J.; Llombart-Cussac, Antonio; Feltl, David; Dewar, John A.; Jasiówka, Marek; Hewson, Nicola; Rukazenkov, Yuri; Robertson, John F.R.

    2015-01-01

    Purpose To compare overall survival (OS) for fulvestrant 500 mg versus anastrozole as first-line endocrine therapy for advanced breast cancer. Patients and Methods The Fulvestrant First-Line Study Comparing Endocrine Treatments (FIRST) was a phase II, randomized, open-label, multicenter trial. Postmenopausal women with estrogen receptor–positive, locally advanced/metastatic breast cancer who had no previous therapy for advanced disease received either fulvestrant 500 mg (days 0, 14, 28, and every 28 days thereafter) or anastrozole 1 mg (daily). The primary end point (clinical benefit rate [72.5% and 67.0%]) and a follow-up analysis (median time to progression [23.4 months and 13.1 months]) have been reported previously for fulvestrant 500 mg and anastrozole, respectively. Subsequently, the protocol was amended to assess OS by unadjusted log-rank test after approximately 65% of patients had died. Treatment effect on OS across several subgroups was examined. Tolerability was evaluated by adverse event monitoring. Results In total, 205 patients were randomly assigned (fulvestrant 500 mg, n = 102; anastrozole, n = 103). At data cutoff, 61.8% (fulvestrant 500 mg, n = 63) and 71.8% (anastrozole, n = 74) had died. The hazard ratio (95% CI) for OS with fulvestrant 500 mg versus anastrozole was 0.70 (0.50 to 0.98; P = .04; median OS, 54.1 months v 48.4 months). Treatment effects seemed generally consistent across the subgroups analyzed. No new safety issues were observed. Conclusion There are several limitations of this OS analysis, including that it was not planned in the original protocol but instead was added after time-to-progression results were analyzed, and that not all patients participated in additional OS follow-up. However, the present results suggest fulvestrant 500 mg extends OS versus anastrozole. This finding now awaits prospective confirmation in the larger phase III FALCON (Fulvestrant and Anastrozole Compared in Hormonal Therapy Naïve Advanced Breast

  2. Generation of a Multi-Locus Chicken Introgression Line to Study the Effects of Genetic Interactions on Metabolic Phenotypes in Chickens

    PubMed Central

    Ek, Weronica; Marklund, Stefan; Ragavendran, Ashok; Siegel, Paul; Muir, William; Carlborg, Örjan

    2012-01-01

    Most biological traits are regulated by a complex interplay between genetic and environmental factors. By intercrossing divergent lines, it is possible to identify individual and interacting QTL involved in the genetic architecture of these traits. When the loci have been mapped, alternative strategies are needed for fine-mapping and studying the individual and interactive effects of the QTL in detail. We have previously identified, replicated, and fine mapped a four-locus QTL network that determines nearly half of the eightfold difference in body weight at 56 days of age between two divergently selected chicken lines. Here, we describe, to our knowledge, the first generation of a three-locus QTL introgression line in chickens. Recurrent marker-assisted backcrossing was used to simultaneously transfer QTL alleles from the low-weight selected line into the high-weight selected line. Three generations of backcrossing and one generation of intercrossing resulted in an introgression line where all three introgressed QTL and several unlinked and linked control-loci were segregating at nearly expected allele frequencies. We show how intensive selection can be applied using artificial insemination to rapidly generate a multi-locus introgression line and provide recommendations for future breeding of introgression lines. This confirmed introgression line will facilitate later detailed studies of the effects of genetic interactions on complex traits in this population, including growth, and body-composition traits. PMID:22403584

  3. Operation of beam line facilities for real-time x-ray studies at Sector 7 of the advanced photon source. Final Report

    SciTech Connect

    Clarke, Roy

    2003-09-10

    This Final Report documents the research accomplishments achieved in the first phase of operations of a new Advanced Photon Source beam line (7-ID MHATT-CAT) dedicated to real-time x-ray studies. The period covered by this report covers the establishment of a world-class facility for time-dependent x-ray studies of materials. During this period many new and innovative research programs were initiated at Sector 7 with support of this grant, most notably using a combination of ultrafast lasers and pulsed synchrotron radiation. This work initiated a new frontier of materials research: namely, the study of the dynamics of materials under extreme conditions of high intensity impulsive laser irradiation.

  4. Advanced in-line optical metrology of sub-10nm structures for gate all around devices (GAA)

    NASA Astrophysics Data System (ADS)

    Muthinti, Raja; Loubet, Nicolas; Chao, Robin; Ott, John; Guillorn, Michael; Felix, Nelson; Gaudiello, John; Lund, Parker; Cepler, Aron; Sendelbach, Matthew; Cohen, Oded; Wolfling, Shay; Bozdog, Cornel; Klare, Mark

    2016-03-01

    Gate-all-around (GAA) nanowire (NW) devices have long been acknowledged as the ultimate device from an electrostatic scaling point of view. The GAA architecture offers improved short channel effect (SCE) immunity compared to single and double gate planar, FinFET, and trigate structures. One attractive proposal for making GAA devices involves the use of a multilayer fin-like structure consisting of layers of Si and SiGe. However, such structures pose various metrology challenges, both geometrical and material. Optical Scatterometry, also called optical critical dimension (OCD) is a fast, accurate and non-destructive in-line metrology technique well suited for GAA integration challenges. In this work, OCD is used as an enabler for the process development of nanowire devices, extending its abilities to learn new material and process aspects specific to this novel device integration. The specific metrology challenges from multiple key steps in the process flow are detailed, along with the corresponding OCD solutions and results. In addition, Low Energy X-Ray Fluorescence (LE-XRF) is applied to process steps before and after the removal of the SiGe layers in order to quantify the amount of Ge present at each step. These results are correlated to OCD measurements of the Ge content, demonstrating that both OCD and LE-XRF are sensitive to Ge content for these applications.

  5. Differential effects of "Advanced glycation endproducts" and beta-amyloid peptide on glucose utilization and ATP levels in the neuronal cell line SH-SY5Y.

    PubMed

    Kuhla, B; Loske, C; Garcia De Arriba, S; Schinzel, R; Huber, J; Münch, G

    2004-03-01

    Beta-amyloid peptide (Abeta) and "Advanced glycation endproducts" (AGEs) are components of the senile plaques in Alzheimer's disease patients. It has been proposed that both AGEs and Abeta exert many of their effects, which include the upregulation of pro-inflammatory cytokines, through RAGE ("receptor for advanced glycation endproducts"). To investigate whether Abeta and AGEs cause similar or identical effects on cell survival and energy metabolism, we have compared the effects of a model-AGE and Abeta on cell viability, ATP level, glucose consumption and lactate production in the neuroblastoma cell line SH-SY5Y. The results show that AGEs and Abeta increase glucose consumption and decrease ATP levels in a dose dependent manner. Furthermore, both compounds decrease mitochondrial activity measured by the MTT assay. However, only AGEs decrease the number of cells and significantly increase lactate production. These data indicate that both AGEs and Abeta can cause differential disturbances in neuronal metabolism, which may contribute to the pathophysiological findings in Alzheimer's disease. However, their signalling pathways are apparently quite distinct, a fact which should stimulate a more detailed investigation in this field, e.g. for the purpose of a rational design of potential "neuroprotective" RAGE antagonists. PMID:14991463

  6. QTL analysis of a red junglefowl x White Leghorn intercross reveals trade-off in resource allocation between behavior and production traits.

    PubMed

    Schütz, Karin; Kerje, Susanne; Carlborg, Orjan; Jacobsson, Lina; Andersson, Leif; Jensen, Per

    2002-11-01

    Behaviors with high energetic costs may decrease in frequency in domestic animals as a response to selection for increased production. The aim of this study was to quantify production traits, foraging behavior, and social motivation in F2 progeny from a White Leghorn x red junglefowl intercross (n = 751-1046) and to perform QTL analyses on the behavioral traits. A foraging-social maze was used for behavioral testing, which consisted of four identical arms and a central box. In two arms there was ad libitum access to the birds' usual food, and in the other two there was novel food (sunflower seeds) mixed with cat litter. In one arm with each of the two food sources, social stimuli were simulated by the presence of a mirror. Each bird could therefore feed on novel or well known food either alone or in the perceived company of a conspecific. Egg production, sexual maturity (females), food intake, and growth were measured individually, and residual food intake and metabolic body weight were estimated using standard methods. A genome scan using 104 microsatellite markers was carried out to identify QTLs affecting behavioral traits. Phenotypic growth rates at different ages showed weak associations in both sexes. Sexual maturity and egg weight were not strongly correlated to growth, indicating that these traits are not genetically linked. Time spent in each arm and in the central part of the maze was analyzed using principal component analyses. Four principal components (PC) were extracted, each reflecting a pattern of behavior in the maze. Females with early onset of sexual maturity scored higher on the PC1 reflecting preference for free food without social stimuli, and females with higher egg production scored higher on the PC2 reflecting exploration. Males with an overall higher growth rate and higher residual food intake scored higher on the PC3, which possibly reflected fear of the test situation, and tended to score higher on the PC4 reflecting low

  7. Phase I dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer

    PubMed Central

    Chi, Yihebali; Yang, Jianliang; Yang, Sheng; Sun, Yongkun; Jia, Bo

    2015-01-01

    Objective To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. Methods According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. Results In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea. Conclusions Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies. PMID:26157320

  8. Preliminary Results of an On-Line, Multi-Spectrometer Fission Product Monitoring System to Support Advanced Gas Reactor Fuel Testing and Qualification in the Advanced Test Reactor at the Idaho National Laboratory

    SciTech Connect

    Dawn M. Scates; John K. Hartwell; John B. Walter; Mark W. Drigert

    2007-10-01

    The Advanced Gas Reactor -1 (AGR-1) experiment is the first experiment in a series of eight separate low enriched uranium (LEU) oxycarbide (UCO) tri-isotropic (TRISO) particle fuel (in compact form) experiments scheduled for placement in the Advanced Test Reactor (ATR) located at the Idaho National Laboratory (INL). The experiment began irradiation in the ATR with a cycle that reached full power on December 26, 2006 and will continue irradiation for about 2.5 years. During this time six separate capsules, will be irradiated in an inert sweep gas atmosphere with individual on-line fission product monitoring on its effluent to track performance of the fuel in each individual capsule during irradiation. The goals of the irradiation experiment is to provide irradiation performance data to support fuel process development, to qualify fuel for normal operating conditions, to support development and validation of fuel, and to provide irradiated fuel and materials for post irradiation examination (PIE) and safety testing. This paper presents the preliminary test details of the fuel performance, as measured by the control and acquisition software.

  9. Clinical effect of pemetrexed as the first‐line treatment in Chinese patients with advanced anaplastic lymphoma kinase‐positive non‐small cell lung cancer

    PubMed Central

    Ma, Di; Hao, Xuezhi; Wang, Yan; Xing, Puyuan

    2016-01-01

    Background The efficacy of pemetrexed‐based first‐line chemotherapy in anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC) has been demonstrated in several studies; however, there is a lack of data from Chinese populations. Methods The clinicopathological characteristics and treatment outcomes of 52 patients with ALK‐positive advanced NSCLC who received pemetrexed as first‐line chemotherapy at the Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively reviewed. The primary end points were response rate and progression‐free survival (PFS). Results The gender proportion was balanced and the median age was 51 years (range 26–76). Of the 52 patients, 46 (88.5%) had stage IV disease, predominantly adenocarcinoma (98.1%). Sixteen patients were current/former smokers and 36 were never/light smokers. The most common sites of metastasis were the pleura (36.5%), bone (30.8%), lung (26.9%), and brain (17.3%). The median PFS was 9.5 months (95% confidence interval 7.454–11.536). At the time of analysis, partial remission was achieved in 18 (34.6%) patients, stable disease in 26 (50.0%), and progressive disease in eight (15.4%); none of the patients achieved complete remission. The objective response rate was 34.6% and the disease control rate was 84.6%. Common adverse events with pemetrexed were neutropenia (53.8%), nausea and vomiting (51.9%), leukopenia (32.7%), and fatigue (25.0%), mainly at grades 1 or 2. Conclusions Pemetrexed is efficient and tolerated as first‐line treatment for ALK‐positive NSCLC in a cohort of Chinese patients and may prove to be an alternative option for the treatment of ALK‐positive NSCLC. PMID:27385988

  10. Vorinostat and bortezomib as third-line therapy in patients with advanced non-small cell lung cancer: a Wisconsin Oncology Network Phase II study

    PubMed Central

    Campbell, Toby C.; Zhang, Chong; Kim, KyungMann; Kolesar, Jill M.; Oettel, Kurt R.; Blank, Jules H.; Robinson, Emily G.; Ahuja, Harish G.; Kirschling, Ron J.; Johnson, Peter H.; Huie, Michael S.; Wims, Mary E.; Larson, Martha M.; Hernan, Hilary R.; Traynor, Anne M.

    2014-01-01

    Summary Introduction The primary objective of this phase II trial was to evaluate the efficacy and tolerability of vorinostat and bortezomib as third-line therapy in advanced non-small cell lung cancer (NSCLC) patients. Methods Eligibility criteria included recurrent/metastatic NSCLC, having received 2 prior systemic regimens, and performance status 0–2. Patients took vorinostat 400 mg PO daily days 1–14 and bortezomib 1.3 mg/m2 IV day 1, 4, 8 and 11 in a 21-day cycle. Primary endpoint was 3-month progression free survival (3m-PFS), with a goal of at least 40 % of patients being free of progression at that time point. This study followed a two-stage minimax design. Results Eighteen patients were enrolled in the first stage. All patients had two prior lines of treatment. Patients received a median of two treatment cycles (range: 1–6) on study. There were no anti-tumor responses; stable disease was observed in 5 patients (27.8 %). Median PFS was 1.5 months, 3m-PFS rate 11.1 %, and median overall survival 4.7 months. The most common grade 3/4 toxicities were thrombocytopenia and fatigue. Two patients who had baseline taxane-related grade 1 peripheral neuropathy developed grade 3 neuropathy. The study was closed at its first interim analysis for lack of efficacy. Conclusions Bortezomib and vorinostat displayed minimal anti-tumor activity as third-line therapy in NSCLC. We do not recommend this regimen for further investigation in unselected patients. PMID:23728919

  11. Necessity of re-evaluation of estramustine phosphate sodium (EMP) as a treatment option for first-line monotherapy in advanced prostate cancer.

    PubMed

    Kitamura, T

    2001-02-01

    Estramustine phosphate sodium (EMP) was first introduced in the early 1970s for the treatment of prostate cancer, when EMP was supposed to have the dual effect of estrogenic activity and cytotoxicity. For the following decades, it was used mainly in hormone-refractory cases, with a conventional dosage of 4-9 capsules/day, which showed a 30-35% objective response rate. However, a very limited number of cases have been reported that used EMP as a first-line monotherapy in the conventional dosage. One study showed a response rate of 82%, which is at least as effective as conventional estrogen (diethylstilbestrol; DES) monotherapy. Nevertheless, EMP was almost abandoned for the treatment of prostate cancer because of severe adverse side-effects, especially in the cardiovascular system and gastrointestinal tract. Recently, two facts have become evident. First, EMP interferes with cellular microtubule dynamics but does not show alkylating effects. Second, EMP is able to produce a complex with calcium when dairy products are taken concomitantly with EMP, resulting in a decrease in the absorption rate of EMP from the gut. Many clinical trials have been undertaken without warning against concomitant dairy product intake since the introduction of EMP. This fact will jeopardize almost all the clinical trials performed before 1990. It is considered that response rates have been underestimated and better results could have been obtained because side-effects decrease dose-dependently. Low-dose EMP monotherapy (2 capsules/day) has been performed infrequently in previously untreated advanced prostate cancer. The only large trial by the European Organization for Research and Treatment of Cancer in 1984 was biased in selecting patients. Nevertheless, the response rate of EMP is comparable to that of DES. In this study, the adverse side-effects of EMP were less than that of DES. Recently, a study was conducted at the University of Tokyo of 11 patients with advanced prostate cancer on

  12. Phase I/II study of bortezomib in combination with carboplatin and bevacizumab as first line therapy in patients with advanced non-small cell lung cancer (NSCLC)

    PubMed Central

    Piperdi, Bilal; Walsh, William V; Bradley, Kendra; Zhou, Zheng; Bathini, Venu; Hanrahan-Boshes, Meredith; Hutchinson, Lloyd; Perez-Soler, Roman

    2013-01-01

    Purpose To establish the maximum tolerated dose (MTD) of weekly bortezomib in combination with fixed standard doses of carboplatin and bevacizumab and to estimate the efficacy (response rate and progression free survival) and safety of combination therapy with carboplatin, bortezomib and bevacizumab as first line therapy in patients with advanced NSCLC. Experimental Design Patients were assigned to three dose levels of weekly bortezomib with the fixed standard doses of carboplatin (AUC 6) and bevacizumab (15 mg/kg) q 3 wks using a standard phase I design. Bortezomib doses were 1.3 mg/m21.6 mg/m2 and 1.8 mg/m2 weekly on D1 and D8 of q 3wk cycle. A maximum of six cycles was administered. Patients with complete, partial response (PR) or stable disease were continued on single agent bevacizumab (15 mg/kg q 3 wks) as maintenance therapy. In phase II, either level III or MTD was administered to evaluate the efficacy and safety of the combination in first line treatment of advanced NSCLC. Results 16 patients were enrolled (3, 4 and 9 pts in dose level I, II and III respectively). There was no pre-defined dose limiting toxicity in cycle 1 in all 16 patients. The recommended phase II dose is bortezomib 1.8 mg/m2 weekly on day 1 and day 8 in combination with carboplatin AUC of 6 and bevacizumab 15 mg/kg on every 21 day cycle. Total of 9 patients were treated at the recommended phase II dose level. The most common treatment related grade 3/4 toxicities during the subsequent cycles were thrombocytopenia (58%), lymphopenia (25%), neutropenia (12%) and diarrhea (25%). The grade 1/2 neuropathy was seen in 7 out of 16 pts (44%). The response rate, PFS and OS in all patients were 37.5% (95%CI 13.8% - 61.2%), 5.0 months (m) (95%CI: 3.1-8.4), 9.9 m (95% CI: 8.2-14.1) and the 9 patients in phase II portion are 44% (95%CI 15.3% - 77.3%), 5.5 m (95%CI: 3.1-12.2) and 10.9 months (95%CI: 8.0-14.1). Conclusion The recommended phase II dose for this combination is: carboplatin AUC 6

  13. Nintedanib in combination with docetaxel for second-line treatment of advanced non-small-cell lung cancer; GENESIS-SEFH drug evaluation report.

    PubMed

    Espinosa Bosch, María; Asensi Diez, Rocío; García Agudo, Sara; Clopes Estela, Ana

    2016-01-01

    Nintedanib is a triple angiokinase inhibitor that has been approved by the European Agency Medicines (EMA) in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non small cell lung cancer (NSCLC) of adenocarcinoma tumour histology, after first-line chemotherapy. In LUME-Lung 1 clinical trial, the combination of nintedanib plus docetaxel vs. placebo plus docetaxel improved progression free survival (PFS) in NSCLC patients, and improved overall survival in the population of adenocarcinoma patients, particularly in those with progression within 9 months after first line treatment initiation, median 10.9 months ( [95% CI 8.5-12.6] vs. 7.9 months [6.7-9.1]; HR 0.75 [95% CI 0.60-0.92], p=0.0073). The toxicity profile of the combination included a higher incidence of neutropenia, gastro-intestinal (GI) disorders, and liver enzyme elevations; however, this did not cause a detrimental effect on patient quality of life. According to data from the clinical trial mentioned, the addition of nintedanib to docetaxel would lead to an estimated incremental cost-effectiveness ratio (ICER) per year of life with PFS in the overall population of 134,274.47 € (notified price). In the adenocarcinoma population per each life of year gained (LYG), the ICER of adding nintedanib to docetaxel would be 40,886.14 €; while by implementing a sensitivity analysis with a 25% discount in the drug price, the cost per LYG would be 32,364.05 €, and would place it close to the threshold of cost-effectiveness usually considered acceptable in our setting. In view of efficacy and safety results the proposed positioning is to recommend its inclusion in the Hospital Formulary only for adult patients with metastatic or locally recurrent NSCLC with adenocarcinoma histology after first line chemotherapy, with progression < 9 months from the initiation of first line treatment, taking into account the inclusion and exclusion criteria in the

  14. Nintedanib in combination with docetaxel for second-line treatment of advanced non-small-cell lung cancer; GENESIS-SEFH drug evaluation report.

    PubMed

    Espinosa Bosch, María; Asensi Diez, Rocío; García Agudo, Sara; Clopes Estela, Ana

    2016-06-01

    Nintedanib is a triple angiokinase inhibitor that has been approved by the European Agency Medicines (EMA) in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non small cell lung cancer (NSCLC) of adenocarcinoma tumour histology, after first-line chemotherapy. In LUME-Lung 1 clinical trial, the combination of nintedanib plus docetaxel vs. placebo plus docetaxel improved progression free survival (PFS) in NSCLC patients, and improved overall survival in the population of adenocarcinoma patients, particularly in those with progression within 9 months after first line treatment initiation, median 10.9 months ( [95% CI 8.5-12.6] vs. 7.9 months [6.7-9.1]; HR 0.75 [95% CI 0.60-0.92], p=0.0073). The toxicity profile of the combination included a higher incidence of neutropenia, gastro-intestinal (GI) disorders, and liver enzyme elevations; however, this did not cause a detrimental effect on patient quality of life. According to data from the clinical trial mentioned, the addition of nintedanib to docetaxel would lead to an estimated incremental cost-effectiveness ratio (ICER) per year of life with PFS in the overall population of 134,274.47 € (notified price). In the adenocarcinoma population per each life of year gained (LYG), the ICER of adding nintedanib to docetaxel would be 40,886.14 €; while by implementing a sensitivity analysis with a 25% discount in the drug price, the cost per LYG would be 32,364.05 €, and would place it close to the threshold of cost-effectiveness usually considered acceptable in our setting. In view of efficacy and safety results the proposed positioning is to recommend its inclusion in the Hospital Formulary only for adult patients with metastatic or locally recurrent NSCLC with adenocarcinoma histology after first line chemotherapy, with progression < 9 months from the initiation of first line treatment, taking into account the inclusion and exclusion criteria in the

  15. A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours.

    PubMed

    Contreras-Hernández, I; Mould-Quevedo, J F; Silva, A; Salinas-Escudero, G; Villasís-Keever, M A; Granados-García, V; Dávila-Loaiza, G; Petersen, J A; Garduño-Espinosa, J

    2008-06-01

    Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day(-1) of imatinib mesylate, 50 mg day(-1) of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day(-1) of imatinib had the highest MC (+/-s.d.) of treatment at $35,225.61 USD (+/-1253.65 USD); while sunitinib incurred a median MC of $17,805.87 USD (+/-694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (+/-472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients.

  16. Doublet Versus Single Agent as Second-Line Treatment for Advanced Gastric Cancer: A Meta-Analysis of 10 Randomized Controlled Trials.

    PubMed

    Zhang, Yong; Ma, Bing; Huang, Xiao-Tian; Li, Yan-Song; Wang, Yu; Liu, Zhou-Lu

    2016-02-01

    The purpose of this study was to perform a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of doublet versus single agent as second-line treatment for advanced gastric cancer (AGC).A comprehensive literature search was performed to identify relevant RCTs. All clinical studies were independently identified by 2 authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), and progression-free survival (PFS) and overall survival (OS) were extracted and analyzed using Comprehensive Meta-Analysis software (Version 2.0).Ten RCTs involving 1698 pretreated AGC patients were ultimately identified. The pooled results demonstrated that doublet combination therapy as second-line treatment for AGC significantly improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI]: 0.78-0.97, P = 0.011), PFS (HR 0.79, 95% CI: 0.72-0.87, P < 0.001), and ORR (relative risk [RR] 1.57, 95% CI: 1.27-1.95, P < 0.001). Sub-group analysis according to treatment regimens also showed that targeted agent plus chemotherapy significantly improve OS, PFS, and ORR. However, no significant survival benefits had been observed in doublet cytotoxic chemotherapy when compared with single cytotoxic agent. Additionally, more incidences of grade 3 or 4 myelosuppression toxicities, diarrhea, and fatigue were observed in doublet combination groups, while equivalent frequencies of grade 3 or 4 thrombocytopenia and nausea were found between the 2 groups.In comparison with single cytotoxic agent alone, the addition of targeted agent to mono-chemotherapy as salvage treatment for pretreated AGC patients provide substantial survival benefits, while no significant survival benefits were observed in doublet cytotoxic chemotherapy regimens. PMID:26937908

  17. Unilateral cleft lip/nose repair using an equal bows /straight line advancement technique - A preliminary report and postoperative symmetry-based anthropometry.

    PubMed

    Hakim, Samer George; Aschoff, Horst Heinrich; Jacobsen, Hans-Christian; Sieg, Peter

    2014-04-01

    In the evolution of cleft lip repair there has been continuous attempt to minimize local trauma, improve lip and nasal appearance and, especially, prevent conspicuous scars. The surgical technique presented meets these criteria, resulting in an appropriate scar course in children with a specific philtral ridge shape. Postoperative digital anthropometry was performed in 18 patients who underwent unilateral cleft lip repair using the equal bows/straight line advancement technique and in matched healthy control individuals. Symmetry values were assessed for lip length, philtral ridge length, vermilion height, width of the alar base, nasocanthal length, circumference of the nostrils, nostril width and height in both cleft and control groups. Evaluation revealed no significant differences in the symmetry values between cleft patients and control group (lip length: p = 0.71, philtral ridge length: p = 0.52, vermilion height: p = 0.23, alar base width: p = 0.69, nasocanthal length: p = 0.25, nostril circumference: p = 0.17, nostril width: p = 0.34, nostril height: p = 0.33). Principles of cleft lip repair can be achieved using the described technique which provides adequate lip length and natural nasal appearance in patients with a parallel-shaped philtral ridge.

  18. A new primary cleft lip repair technique tailored for Asian patients that combines three surgical concepts: Comparison with rotation--advancement and straight-line methods.

    PubMed

    Funayama, Emi; Yamamoto, Yuhei; Furukawa, Hiroshi; Murao, Naoki; Shichinohe, Ryuji; Hayashi, Toshihiko; Oyama, Akihiko

    2016-01-01

    Various techniques have been described for unilateral cleft lip repair. These may be broadly classified into three types of procedure/concept: the straight-line method (SL; Rose-Thompson effect); rotation-advancement (RA; upper-lip Z-plasty); and the triangular flap method (TA; lower-lip Z-plasty). Based on these procedures, cleft lip repair has evolved in recent decades. The cleft lip repair method in our institution has also undergone several changes. However, we have found that further modifications are needed for Asian patients who have wider philtral dimples and columns than Caucasians, while following the principles of the original techniques mentioned above. Here, we have incorporated the advantages of each procedure and propose a refined hybrid operating technique, seeking a more appropriate procedure for Asian patients. To evaluate our new technique, a comparison study was performed to evaluate RA, SL, and our technique. We have used our new technique to treat 137 consecutive cleft lip cases of all types and degrees of severity, with or without a cleft palate, since 2009. In the time since we adopted the hybrid technique, we have observed improved esthetics of the repaired lip. Our technique demonstrated higher glance impression average scores than RA/SL.

  19. Activity of pemetrexed-based regimen as first-line chemotherapy for advanced non-small cell lung cancer with asymptomatic inoperable brain metastasis: a retrospective study.

    PubMed

    Zhu, Weiyou; Røe, Oluf Dimitri; Wu, Chen; Li, Wei; Guo, Renhua; Gu, Yanhong; Liu, Yiqian; Shu, Yongqian; Chen, Xiaofeng

    2015-08-01

    This retrospective study was conducted to assess the efficacy of combination of pemetrexed and cisplatin/carboplatin as first-line treatment in inoperable and asymptomatic brain metastasis (BM) from non-small cell lung cancer (NSCLC). A total of 30 patients with adenocarcinoma were included. Nine patients had solitary, and 21 patients had multiple BM. At evaluation after two cycles, the complete response (CR) rate, partial response (PR) rate, and stable disease (SD) for brain lesions was 0, 33.3, and 46.7%, respectively. The overall CR, PR, and SD were 0, 23.3, and 46.7%, respectively. The median time to tumour progression of BM (TTP-BM) was 6.0 months (95% CI 4.068-7.932). The median progression-free survival (PFS) and overall survival (OS) were 5.0 months (95% CI 4.197-5.803) and 11.0 months (95% CI 7.398-14.602), respectively. Pemetrexed has comparable activity on brain lesions as on extracranial tumours in advanced lung adenocarcinoma patients with inoperable and asymptomatic BM.

  20. Novel analytical approach to monitoring advanced glycosylation end products in human serum with on-line spectrophotometric and spectrofluorometric detection in a flow system.

    PubMed

    Wróbel, K; Wróbel, K; Garay-Sevilla, M E; Nava, L E; Malacara, J M

    1997-09-01

    We proposed a simple analytical procedure for measurement of serum advanced glycosylation end products (AGEs) based on simultaneous detection of low-molecular-mass peptides and AGEs with a flow system and two detectors connected on-line: spectrophotometric for peptides (lambda = 280 nm) and spectrofluorometric for AGEs (lambda ex = 247 nm, lambda em = 440 nm). Sample pretreatment was carried out in microcentrifuge tubes: Serum (20 microL) was deproteinized with trichloroacetic acid (480 microL, 0.15 mol/L) and lipids were extracted with chloroform (100 microL). Twenty microliters of the filtered aqueous layer was injected to the flow system and the relation between fluorescence and absorption signals was measured. A peptide-derived AGE calibrator was used for calibration. Within-day and between-day CVs were 6.7% and 9.1%, respectively, at an AGE concentration corresponding approximately to that in healthy individuals. Mean results (+/-SD) in 10 healthy individuals were 10.1% +/- 1.0%, in 21 patients with diabetes without complications 18.0% +/- 6.2%, in 25 patients with complications 24.1% +/- 15.4%, and in 12 diabetic patients in end-stage renal disease 92% +/- 30%. Comparison with an ELISA procedure (x, in arbitrary units/L) yields a regression equation y = 0.713x + 1.24 (Sy [symbol: see text] x = 6777, r = 0.8477, n = 41).

  1. Development of Gene-Pyramid Lines of the Elite Restorer Line, RPHR-1005 Possessing Durable Bacterial Blight and Blast Resistance.

    PubMed

    Abhilash Kumar, V; Balachiranjeevi, C H; Bhaskar Naik, S; Rambabu, R; Rekha, G; Harika, G; Hajira, S K; Pranathi, K; Anila, M; Kousik, M; Vijay Kumar, S; Yugander, A; Aruna, J; Dilip Kumar, T; Vijaya Sudhakara Rao, K; Hari Prasad, A S; Madhav, M S; Laha, G S; Balachandran, S M; Prasad, M S; Viraktamath, B C; Ravindra Babu, V; Sundaram, R M

    2016-01-01

    RPHR-1005, the stable restorer line of the popular medium slender (MS) grain type rice hybrid, DRRH-3 was improved in this study for resistance against bacterial blight (BB) and blast diseases through marker-assisted backcross breeding (MABB). In this study, four major resistance genes (i.e., Xa21 and Xa33 for BB resistance and Pi2 and Pi54 for blast resistance) have been transferred to RPHR-1005 using RPBio Patho-1 (possessing Xa21 + Pi2), RPBio Patho-2 (possessing Xa21 + Pi54) and FBR1-15EM (possessing Xa33) as the donors. Foreground selection was carried out using PCR-based molecular markers specific for the target resistance genes and the major fertility restorer genes, Rf3 and Rf4, while background selection was carried out using a set of parental polymorphic rice SSR markers and backcrossing was continued uptoBC2 generation. At BC2F2, plants possessing the gene combination- Xa21 + Pi2, Xa21 + Pi54 and Xa33 in homozygous condition and with >92% recovery of the recurrent parent genome (RPG) were identified and intercrossed to combine all the four resistance genes. Twenty-two homozygous, pyramid lines of RPHR-1005 comprising of three single-gene containing lines, six 2-gene containing lines, eight 3-gene containing lines, and five 4-gene containing lines were identified among the double intercross lines at F3 generation (DICF3). They were then evaluated for their resistance against BB and blast, fertility restoration ability and for key agro-morphological traits. While single gene containing lines were resistant to either BB or blast, the 2-gene, 3-gene, and 4-gene pyramid lines showed good level of resistance against both and/or either of the two diseases. Most of the 2-gene, 3-gene, and 4-gene containing pyramid lines showed yield levels and other key agro-morphological and grain quality traits comparable to the original recurrent parent and showed complete fertility restoration ability, with a few showing higher yield as compared to RPHR-1005. Further, the

  2. Development of Gene-Pyramid Lines of the Elite Restorer Line, RPHR-1005 Possessing Durable Bacterial Blight and Blast Resistance

    PubMed Central

    Abhilash Kumar, V.; Balachiranjeevi, C. H.; Bhaskar Naik, S.; Rambabu, R.; Rekha, G.; Harika, G.; Hajira, S. K.; Pranathi, K.; Anila, M.; Kousik, M.; Vijay Kumar, S.; Yugander, A.; Aruna, J.; Dilip Kumar, T.; Vijaya Sudhakara Rao, K.; Hari Prasad, A. S.; Madhav, M. S.; Laha, G. S.; Balachandran, S. M.; Prasad, M. S.; Viraktamath, B. C.; Ravindra Babu, V.; Sundaram, R. M.

    2016-01-01

    RPHR-1005, the stable restorer line of the popular medium slender (MS) grain type rice hybrid, DRRH-3 was improved in this study for resistance against bacterial blight (BB) and blast diseases through marker-assisted backcross breeding (MABB). In this study, four major resistance genes (i.e., Xa21 and Xa33 for BB resistance and Pi2 and Pi54 for blast resistance) have been transferred to RPHR-1005 using RPBio Patho-1 (possessing Xa21 + Pi2), RPBio Patho-2 (possessing Xa21 + Pi54) and FBR1-15EM (possessing Xa33) as the donors. Foreground selection was carried out using PCR-based molecular markers specific for the target resistance genes and the major fertility restorer genes, Rf3 and Rf4, while background selection was carried out using a set of parental polymorphic rice SSR markers and backcrossing was continued uptoBC2 generation. At BC2F2, plants possessing the gene combination- Xa21 + Pi2, Xa21 + Pi54 and Xa33 in homozygous condition and with >92% recovery of the recurrent parent genome (RPG) were identified and intercrossed to combine all the four resistance genes. Twenty-two homozygous, pyramid lines of RPHR-1005 comprising of three single-gene containing lines, six 2-gene containing lines, eight 3-gene containing lines, and five 4-gene containing lines were identified among the double intercross lines at F3 generation (DICF3). They were then evaluated for their resistance against BB and blast, fertility restoration ability and for key agro-morphological traits. While single gene containing lines were resistant to either BB or blast, the 2-gene, 3-gene, and 4-gene pyramid lines showed good level of resistance against both and/or either of the two diseases. Most of the 2-gene, 3-gene, and 4-gene containing pyramid lines showed yield levels and other key agro-morphological and grain quality traits comparable to the original recurrent parent and showed complete fertility restoration ability, with a few showing higher yield as compared to RPHR-1005. Further, the

  3. Development of Gene-Pyramid Lines of the Elite Restorer Line, RPHR-1005 Possessing Durable Bacterial Blight and Blast Resistance.

    PubMed

    Abhilash Kumar, V; Balachiranjeevi, C H; Bhaskar Naik, S; Rambabu, R; Rekha, G; Harika, G; Hajira, S K; Pranathi, K; Anila, M; Kousik, M; Vijay Kumar, S; Yugander, A; Aruna, J; Dilip Kumar, T; Vijaya Sudhakara Rao, K; Hari Prasad, A S; Madhav, M S; Laha, G S; Balachandran, S M; Prasad, M S; Viraktamath, B C; Ravindra Babu, V; Sundaram, R M

    2016-01-01

    RPHR-1005, the stable restorer line of the popular medium slender (MS) grain type rice hybrid, DRRH-3 was improved in this study for resistance against bacterial blight (BB) and blast diseases through marker-assisted backcross breeding (MABB). In this study, four major resistance genes (i.e., Xa21 and Xa33 for BB resistance and Pi2 and Pi54 for blast resistance) have been transferred to RPHR-1005 using RPBio Patho-1 (possessing Xa21 + Pi2), RPBio Patho-2 (possessing Xa21 + Pi54) and FBR1-15EM (possessing Xa33) as the donors. Foreground selection was carried out using PCR-based molecular markers specific for the target resistance genes and the major fertility restorer genes, Rf3 and Rf4, while background selection was carried out using a set of parental polymorphic rice SSR markers and backcrossing was continued uptoBC2 generation. At BC2F2, plants possessing the gene combination- Xa21 + Pi2, Xa21 + Pi54 and Xa33 in homozygous condition and with >92% recovery of the recurrent parent genome (RPG) were identified and intercrossed to combine all the four resistance genes. Twenty-two homozygous, pyramid lines of RPHR-1005 comprising of three single-gene containing lines, six 2-gene containing lines, eight 3-gene containing lines, and five 4-gene containing lines were identified among the double intercross lines at F3 generation (DICF3). They were then evaluated for their resistance against BB and blast, fertility restoration ability and for key agro-morphological traits. While single gene containing lines were resistant to either BB or blast, the 2-gene, 3-gene, and 4-gene pyramid lines showed good level of resistance against both and/or either of the two diseases. Most of the 2-gene, 3-gene, and 4-gene containing pyramid lines showed yield levels and other key agro-morphological and grain quality traits comparable to the original recurrent parent and showed complete fertility restoration ability, with a few showing higher yield as compared to RPHR-1005. Further, the

  4. A Phase II First-Line Study of Gemcitabine, Carboplatin, and Bevacizumab in Advanced Stage Non-squamous Non-small Cell Lung Cancer

    PubMed Central

    Clément-Duchêne, Christelle; Krupitskaya, Yelena; Ganjoo, Kristen; Lavori, Philip; McMillan, Alex; Kumar, Atul; Zhao, Gary; Padda, Sukhmani; Zhou, Lisa; Pedro-Salcedo, Melanie San; Colevas, A. Dimitrios; Wakelee, Heather A.

    2014-01-01

    Background Bevacizumab improves responses and progression-free survival when added to first-line paclitaxel/carboplatin or cisplatin/gemcitabine for patients with advanced nonsquamous non-small cell lung cancer. This study was designed to evaluate toxicities and efficacy of gemcitabine/carboplatin/bevacizumab. Methods Patients with untreated advanced nonsquamous non-small cell lung cancer, with no evidence of brain metastases and not on anticoagulation were eligible. Patients received gemcitabine 1000 mg/m2 on days 1 and 8; carboplatin area under the curve 5 day 1; and bevacizumab 15 mg/kg day 1 every 3 weeks for up to six cycles. Bevacizumab was then continued every 3 weeks until disease progression or unacceptable toxicity. Results From July 2006 to December 2008, 48 patients were enrolled: 23 (48%) men, 25 (52%) women, and 19 (40%) never smokers. One patient never received therapy and is not included in the analysis. Median cycle number was 8 (1– 42) with 37 patients (78.7%) completing ≥4 cycles of three drugs. Dose reductions occurred in 34 (72.3%) patients. Grade 3/4 toxicities included neutropenia (47%/15%), thrombocytopenia (11%/15%), anemia (6%/0%), dyspnea (6%/2%), bacterial pneumonia (4%/0%), and hypertension (4%/2%). No neutropenic fevers occurred. One patient died of hemoptysis. Grade 3 bleeding occurred in three other patients. There were seven (14.9%) partial responses. Median time to first event (progression/death/toxicity requiring discontinuation) was 6.4 months (95% confidence interval: 4.8 –7.9 months). The median overall survival (OS) was 12.8 months (95% confidence interval: 10.0 –16.5). The OS is 57% at 1 year and 10% at 2 years. Conclusions Although perhaps skewed by a high proportion of nonsmokers and women, treatment with gemcitabine/carboplatin/bevacizumab has an acceptable toxicity profile with promising median OS despite a low response rate. PMID:20881641

  5. Pazopanib for the first-line treatment of patients with advanced and/or metastatic renal cell carcinoma : a NICE single technology appraisal.

    PubMed

    Kilonzo, Mary; Hislop, Jenni; Elders, Andrew; Fraser, Cynthia; Bissett, Donald; McClinton, Samuel; Mowatt, Graham; Vale, Luke

    2013-01-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of pazopanib hydrochloride (GlaxoSmithKline) to submit evidence of the clinical and cost effectiveness of the drug for the first-line treatment of advanced and/or metastatic renal cell carcinoma, as part of the Institute's single technology appraisal (STA) process. The Aberdeen Health Technology Assessment Group were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE's subsequent decisions. The objective of this paper is to summarize the independent review and critique of the evidence submitted for the consideration of the NICE Appraisal Committee and NICE's subsequently issued guidance. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer's submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer's decision analytic model to examine the impact of altering some of the key assumptions. For progression-free survival (PFS), there was a statistically significant longer survival for pazopanib compared with placebo (as assessed by the ERG, based upon the original manufacturer submission with a clinical cut-off date of 23 May 2008) [median 11.1 vs. 2.8 months; hazard ratio (HR) 0.40; 95 % CI 0.27, 0.60]. Data from the indirect comparison suggested that pazopanib had a greater survival than interferon alpha (IFN-α) [HR 0.512; 95 % CI 0.326, 0.802] but provided no evidence of any difference compared with sunitinib (HR 0.949; 95 % CI 0.575, 1.568). With regard to overall survival, 64 % (n = 99) of patients in the pazopanib arm and 63 % (n = 49) of patients in the placebo arm had died and a total of 51 % (n = 40) of placebo patients had crossed over to receive pazopanib. Although data were provided on an intention-to-treat basis, crossover between therapies

  6. A Phase II Clinical Study of mFOLFOX6 Plus Bevacizumab as First-line Therapy for Japanese Advanced/Recurrent Colorectal Cancer Patients

    PubMed Central

    Nishina, Tomohiro; Takano, Yoshinao; Denda, Tadamichi; Yasui, Hisateru; Takeda, Koji; Ura, Takashi; Esaki, Taito; Okuyama, Yusuke; Kondo, Ken; Takahashi, Yasuo; Sugiyama, Yasuyuki; Muro, Kei

    2013-01-01

    Objective In Japan, there had been no prospective clinical studies conducted in terms of modified FOLFOX6 + bevacizumab therapy. We performed a post-marketing Phase II multicenter clinical study to examine the efficacy and safety of this regimen as first-line therapy for Japanese patients with advanced/recurrent colorectal cancer. Methods Bevacizumab (5 mg/kg) was administered intravenously, and then oxaliplatin (85 mg/m2) and levofolinate calcium (200 mg/m2) were infused intravenously over 2 h. Subsequently, a bolus dose of 5-fluorouracil (400 mg/m2) was injected, followed by infusion of 5-fluorouracil (2400 mg/m2) for 46 h. This regimen was repeated every 2 weeks until 24 cycles unless there was disease progression, unacceptable toxicity or patient refusal. The primary end point was the response rate. Results Among the 70 patients enrolled, two patients withdrew the study before treatment, and 68 patients were eligible for analysis of efficacy and safety. The response rate was 51.5% (95% confidence interval: 39.0–63.8%). The median progression-free survival and median overall survival time were 12.6 months (95% confidence interval: 10.4–14.5 months) and 28.5 months [95% confidence interval: 23.1 months–(not applicable)], respectively. There were no treatment-related deaths observed. The most common Grade 3 and 4 adverse events included neutropenia in 35.3% of the patients, peripheral neuropathy in 16.2% and hypertension in 16.2%. All adverse events were manageable and tolerable. The exploratory analysis of polymorphisms of three genes, ERCC1, XPD and GSTP1, did not show any trends in terms of correlation with the efficacy or safety of modified FOLFOX6 + bevacizumab therapy. Conclusions Modified FOLFOX6 + bevacizumab therapy was manageable and tolerable in Japanese patients, achieving a high response rate. PMID:23999770

  7. STAT3 polymorphisms may predict an unfavorable response to first-line platinum-based therapy for women with advanced serous epithelial ovarian cancer.

    PubMed

    Permuth-Wey, Jennifer; Fulp, William J; Reid, Brett M; Chen, Zhihua; Georgeades, Christina; Cheng, Jin Q; Magliocco, Anthony; Chen, Dung-Tsa; Lancaster, Johnathan M

    2016-02-01

    Cancer stem cells (CSC) contribute to epithelial ovarian cancer (EOC) progression and therapeutic response. We hypothesized that germline single nucleotide polymorphisms (SNPs) in CSC-related genes may predict an initial therapeutic response for women newly diagnosed with EOC. A nested case-control design was used to study 361 women with advanced-stage serous EOC treated with surgery followed by first-line platinum-based combination therapy at Moffitt Cancer Center or as part of The Cancer Genome Atlas Study. "Cases" included 102 incomplete responders (IRs) and "controls" included 259 complete clinical responders (CRs) to therapy. Using Illumina genotyping arrays and imputation, DNA samples were evaluated for 5,509 SNPs in 24 ovarian CSC-related genes. We also evaluated the overall significance of each CSC gene using the admixture maximum likelihood (AML) test, and correlated genotype with EOC tumor tissue expression. The strongest SNP-level associations with an IR to therapy were identified for correlated (r(2) > 0.80) SNPs within signal transducer and activator of transcription 3 (STAT3) [odds ratio (OR), 2.24; 95% confidence interval (CI), 1.32-3.78; p = 0.0027], after adjustment for age, population stratification, grade and residual disease. At the gene level, STAT3 was significantly associated with an IR to therapy (pAML = 0.006). rs1053004, a STAT3 SNP in a putative miRNA-binding site, was associated with STAT3 expression (p = 0.057). This is the first study to identify germline STAT3 variants as independent predictors of an unfavorable therapeutic response for EOC patients. Findings suggest that STAT3 genotype may identify high-risk women likely to respond more favorably to novel therapeutic combinations that include STAT3 inhibitors. PMID:26264211

  8. Live cumulative network meta-analysis: protocol for second-line treatments in advanced non-small-cell lung cancer with wild-type or unknown status for epidermal growth factor receptor

    PubMed Central

    Créquit, Perrine; Trinquart, Ludovic; Ravaud, Philippe

    2016-01-01

    Introduction Many second-line treatments for advanced non-small-cell lung cancer (NSCLC) have been assessed in randomised controlled trials, but which treatments work the best remains unclear. Novel treatments are being rapidly developed. We need a comprehensive up-to-date evidence synthesis of all these treatments. We present the protocol for a live cumulative network meta-analysis (NMA) to address this need. Methods and analysis We will consider trials of second-line treatments in patients with advanced NSCLC with wild-type or unknown epidermal growth factor receptor status. We will consider any single agent of cytotoxic chemotherapy, targeted therapy, combination of cytotoxic chemotherapy and targeted therapy and any combination of targeted therapies. The primary outcomes will be overall survival and progression-free survival. The live cumulative NMA will be initiated with a NMA and then iterations will be repeated at regular intervals to keep the NMA up-to-date over time. We have defined the update frequency as 4 months, based on an assessment of the pace of evidence production on this topic. Each iteration will consist of six methodological steps: adaptive search for treatments and trials, screening of reports and selection of trials, data extraction, assessment of risk of bias, update of the network of trials and synthesis, and dissemination. We will set up a research community in lung cancer, with different groups of contributors of different skills. We will distribute tasks through online crowdsourcing. This proof-of-concept study in second-line treatments of advanced NSCLC will allow one for assessing the feasibility of live cumulative NMA and opening the path for this new form of synthesis. Ethics and dissemination Ethical approval is not required because our study will not include confidential participant data and interventions. The description of all the steps and the results of this live cumulative NMA will be available online. Trial registration

  9. Detection of the "cp4 epsps" Gene in Maize Line NK603 and Comparison of Related Protein Structures: An Advanced Undergraduate Experiment

    ERIC Educational Resources Information Center

    Swope, Nicole K.; Fryfogle, Patrick J.; Sivy, Tami L.

    2015-01-01

    A flexible, rigorous laboratory experiment for upper-level biochemistry undergraduates is described that focuses on the Roundup Ready maize line. The work is appropriate for undergraduate laboratory courses that integrate biochemistry, molecular biology, or bioinformatics. In this experiment, DNA is extracted and purified from maize kernel and…

  10. Sub-0.35-μm i-line lithography with new advanced bottom antireflective coatings optimized for high-topography and dual-damascene applications

    NASA Astrophysics Data System (ADS)

    Deshpande, Shreeram V.; Brakensiek, Nickolas L.; Williams, Paul; Nowak, Kelly A.; Fowler, Shelly

    2001-04-01

    This paper describes the development of a new conformal i- line BARC. With the advent of flash memory deices the topography can be greater than 0.5 micrometers . Maintaining CD control through the BARC etch step over such a high topography can be a challenge. In order to meet these needs, Brewer Science has developed a highly conformal, spin bowl compatible BARC with increased baseline etch rate. This new BARC exhibits excellent coverage on high topographies and thus reduces the need for over-etch due to its conformality , and also increase the throughput due to its higher etch rate. As the circuit density on the chip increases copper is being implemented as the metal of choice for interconnects to reduce line resistance in semiconductor devices. This paper also describes the development of an organic BARC for applications in dual damascene processing. Via first dual damascene processes used for copper integration requires materials which can provide anti-reflection properties as well as act as etch blocks by filling the vias. The dual damascene BARC reported in this paper exhibits excellent via fill properties to reduce resist thickness variations as well as provide anti-reflective and via etch block properties. This paper outlines the design, development, and performance characterization of the new i-line BARC platforms for both high topography as well as dual damascene applications in sub 0.35 (Mu) m i-line lithography.

  11. First-Line Cetuximab Plus Capecitabine in Elderly Patients with Advanced Colorectal Cancer: Clinical Outcome and Subgroup Analysis According to KRAS Status from a Spanish TTD Group Study

    PubMed Central

    Grávalos, Cristina; Rivera, Fernando; Massuti, Bartomeu; Valladares-Ayerbes, Manuel; Marcuello, Eugenio; Manzano, José L.; Benavides, Manuel; Hidalgo, Manuel; Díaz-Rubio, Eduardo; Aranda, Enrique

    2012-01-01

    Single-agent cetuximab is safe and active in elderly patients with advanced colorectal cancer (CRC). A cetuximab–capecitabine combination has not previously been tested in elderly patients with advanced CRC. Material and Methods. Sixty-six patients with advanced CRC were treated with cetuximab as a 400 mg/m2 i.v. infusion followed by 250 mg/m2 i.v. weekly plus capecitabine at a dose of 1,250 mg/m2 every 12 hours. After the inclusion of 27 patients, the protocol was amended for safety reasons, reducing the dose of capecitabine to 1,000 mg/m2 every 12 hours. Thirty-nine additional patients were treated with the reduced dose of capecitabine. Results. The overall response rate was 31.8%. KRAS status was determined in 58 patients (88%). Fourteen of 29 patients with wild-type KRAS tumors responded (48.3%; 95% confidence interval [CI], 29.4%–67.5%), compared with six of 29 patients with mutant KRAS tumors (20.7%; 95% CI, 8.0%–39.7%). The median progression-free survival (PFS) interval was 7.1 months. The median PFS interval for patients whose tumors were wild-type KRAS was significantly longer than for those with mutant KRAS tumors (8.4 months versus 6.0 months; p = .024). The high incidence of severe paronychia (29.6%) declined (7.7%) after capecitabine dose adjustment. Conclusions. Cetuximab plus capecitabine at a dose of 1,000 mg/m2 every 12 hours may be an alternative to more aggressive regimens in elderly patients with advanced wild-type KRAS CRC. PMID:22363067

  12. AISI/DOE Advanced Process Control Program Vol. 4 of 6: ON-LINE, NON-DESTRUCTIVE MECHANICAL PROPERTY MEASUREMENT USING LASER-ULTRASOUND

    SciTech Connect

    Andre' Moreau; Martin Lord; Daniel Levesqure; Marc Dubois; Jean Bussiere; Jean-Pierre Monchalin; Christian Padioleau; Guy Lamouche; Teodor Veres; Martin Viens; Harold Hebert; Pierre Basseras; Cheng-Kuei Jen

    2001-03-31

    The goal of this project was to demonstrate the feasibility to measure the mechanical properties, such as yield strength, tensile strength, elongation, strain hardening exponent and plastic strain ratio parameters, of low carbon steel sheets on the production line using laser ultrasound. The ultrasound generated by the developed apparatus travels mostly back and forth in the thickness of the steel sheet. By measuring the time delay between two echoes, and the relative amplitude of these two echoes, one can measure ultrasound velocity and attenuation. These are governed by the microstructure: grain size, crystallographic texture, dislocations, etc. Thus, by recording the time behavior of the ultrasonic signal, one can extract microstructural information. These microstructural information together with the modified Hall-Petch equation allow measurement of the mechanical properties. Through laboratory investigations with a laboratory laser ultrasound system, followed by the installation of a prototype system at LTV Steel Company's No.1 Inspection Line in Cleveland, all target mechanical properties of ultra low carbon (ULC), low carbon (LC) and high strength low alloy (HSLA) steel sample lots were measured meeting or nearly meeting all the target accuracies. Thus, the project realized its goal to demonstrate that the mechanical properties of low carbon steel sheets can be measured on-line using laser ultrasound

  13. Exploring alternative models for sex-linked quantitative trait loci in outbred populations: application to an iberian x landrace pig intercross.

    PubMed Central

    Pérez-Enciso, Miguel; Clop, Alex; Folch, Josep M; Sánchez, Armand; Oliver, Maria A; Ovilo, Cristina; Barragán, C; Varona, Luis; Noguera, José L

    2002-01-01

    We present a very flexible method that allows us to analyze X-linked quantitative trait loci (QTL) in crosses between outbred lines. The dosage compensation phenomenon is modeled explicitly in an identity-by-descent approach. A variety of models can be fitted, ranging from considering alternative fixed alleles within the founder breeds to a model where the only genetic variation is within breeds, as well as mixed models. Different genetic variances within each founder breed can be estimated. We illustrate the method with data from an F(2) cross between Iberian x Landrace pigs for intramuscular fat content and meat color component a*. The Iberian allele exhibited a strong overdominant effect for intramuscular fat in females. There was also limited evidence of one or more regions affecting color component a*. The analysis suggested that the QTL alleles were fixed in the Iberian founders, whereas there was some evidence of segregation in Landrace for the QTL affecting a* color component. PMID:12196405

  14. Comparison of cisplatinum/paclitaxel with cisplatinum/5-fluorouracil as first-line therapy for nonsurgical locally advanced esophageal squamous cell carcinoma patients

    PubMed Central

    Hu, Guofang; Wang, Zhehai; Wang, Yuan; Zhang, Qingqing; Tang, Ning; Guo, Jun; Liu, Liyan; Han, Xiao

    2016-01-01

    Background To retrospectively evaluate the efficacy and toxicity of definitive concurrent chemoradiotherapy (dCRT) with cisplatinum/paclitaxel versus cisplatinum/5-fluorouracil in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who received nonsurgical treatment. Methods This study retrospectively evaluated 202 patients with locally advanced ESCC treated at Shandong Cancer Hospital between January 2009 and December 2013. All the patients initially received dCRT, including platinum and paclitaxel or 5-fluorouracil, with concurrent 1.8 or 2 Gy/fraction radiation (total dose, 54–60 Gy). The patient population was divided into two treatment groups: 105 patients who received the cisplatinum/paclitaxel regimen were allocated to group A, and 97 patients who received the cisplatinum/5-fluorouracil regimen were allocated to group B. We compared the progression-free survival (PFS) and overall survival (OS) by various clinical variables, including prior treatment characteristics, major toxicities (mainly in grade 3 and 4 hematological), and response to dCRT. We used the receiver operating curve analysis to determine the optimal cutoff value of clinical stage and radiation dose. The Kaplan–Meier method was used for survival comparison and Cox regression for multivariate analysis. Results Median PFS and OS in group A were significantly better compared with group B (median PFS, 15.9 versus 13.0 months, P=0.016 and median OS, 33.9 versus 23.1 months, P=0.014, respectively). The 1- and 2-year survival rates of the two groups were 82.9% versus 76.3%, and 61.9% versus 47.6%, respectively. The complete response and response rate were 17.1% versus 7.2% (P=0.032) and 52.4% versus 30.9% (P=0.042) in group A and B, respectively. Meanwhile, group B was associated with a significantly lower rate of grade 3/4 overall toxicity than group A (P=0.039). Conclusion Our data showed that patients with locally advanced ESCC in group A had longer PFS and OS compared with

  15. Amyloid-beta mediates the receptor of advanced glycation end product-induced pro-inflammatory response via toll-like receptor 4 signaling pathway in retinal ganglion cell line RGC-5.

    PubMed

    Lee, Jong-Jer; Wang, Pei-Wen; Yang, I-Hui; Wu, Chia-Lin; Chuang, Jiin-Haur

    2015-07-01

    Patients with diabetes mellitus have an increased risk of developing Alzheimer's disease. Amyloid-β, a product of amyloid precursor protein, is associated with neuro-inflammation in patients with Alzheimer's diseases. The correlation between amyloid-beta and advanced glycation end products, which accumulate in tissue of diabetic patients, is not clear. The aims of this study were to determine the effect of advanced glycation end product on the expression of amyloid precursor protein/amyloid-beta and associated pro-inflammatory responses in retinal ganglion cell line RGC-5. Treatment with advanced glycation end product produced upregulation of amyloid precursor protein and increased secretion of amyloid-β(1-40). Additionally, amyloid-β(1-40) induced toll-like receptor 4-dependent phosphorylation of tyrosine in myeloid differentiation primary response gene (88). We found that N-[N-(3,5-Difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester, a γ-secretase inhibitor, reduced the secretion of amyloid-β(1-40) and inhibited the advanced glycation end product-induced activation of myeloid differentiation primary response gene (88). Amyloid-β(1-40) induced the activation of NF-κB and the expression of TNFα mRNA. Knockdown of toll-like receptor 4 inhibited the amyloid-β(1-40)-induced phosphorylation of p65 in NF-κB. Additionally, the nuclear translocation of p65 and transcriptions of TNFα were inhibited by siRNA knockdown of receptor of advanced glycation end product or toll-like receptor 4. The advanced glycation end product-induced secretion of VEGF-A was also reduced by knockdown of toll-like receptor 4. Taken together, our data suggested that amyloid-β(1-40) mediates the interaction between receptor of advanced glycation end product and toll-like receptor 4. Inhibition of the toll-like receptor 4 is an effective method for suppressing the amyloid-β(1-40)-induced pro-inflammatory responses in RGC-5 cells.

  16. Advancement in recombinant protein production using a marine oxygen carrier to enhance oxygen transfer in a CHO-S cell line.

    PubMed

    Le Pape, Fiona; Bossard, Morgane; Dutheil, Delphine; Rousselot, Morgane; Polard, Valérie; Férec, Claude; Leize, Elisabeth; Delépine, Pascal; Zal, Franck

    2015-06-01

    Recombinant proteins, particularly proteins used as therapeutics, are widely expressed for bioprocessing manufacturing processes. Mammalian cell lines represent the major host cells for bioproduction, according to their capacities of post-translational modifications and folding of secreted proteins. Many parameters can affect cell productivity, especially the rate of oxygen transfer. Dissolved oxygen, in high or low proportions, is a crucial parameter which can affect cell viability and thus productivity. HEMARINA has developed a new technology, commercially proposed as HEMOXCell(®), to improve cell culture at a large production scale. HEMOXCell(®) is a marine oxygen carrier having properties of high oxygen sensitivity, to be used as an oxygen additive during cell culture manufacturing. In this study, we investigated the effects of HEMOXCell(®) on the culture of the commonly used CHO-S cell line. Two main objectives were pursued: 1) cell growth rate and viability during a batch mode process, and 2) the determination of the effect of this oxygen carrier on recombinant protein production from a CHO-transfected cell line. Our results show an increase of CHO-S cellular growth at a rate of more than four-fold in culture with HEMOXCell(®). Moreover, an extension of the growth exponential phase and high cell viability were observed. All of these benefits seem to contribute to the improvement of recombinant protein production. This work underlines several applications using this marine-type oxygen carrier for large biomanufacturing. It is a promising cell culture additive according to the increasing demand for therapeutic products such as monoclonal antibodies.

  17. Paclitaxel plus valproic acid versus paclitaxel alone as second- or third-line therapy for advanced gastric cancer: a randomized Phase II trial

    PubMed Central

    Fushida, Sachio; Kinoshita, Jun; Kaji, Masahide; Oyama, Katsunobu; Hirono, Yasuo; Tsukada, Tomoya; Fujimura, Takashi; Ohta, Tetsuo

    2016-01-01

    Background Weekly paclitaxel (wPTX) is the preferred second-line chemotherapy for gastric cancer in Japan. Histone deacetylase inhibitors have been shown to decrease proliferation through cell-cycle arrest, differentiation, and apoptosis in gastric cancer cells. One histone deacetylase inhibitor, valproic acid (VPA), also inhibits tumor growth by inducing apoptosis and enhances the efficacy of paclitaxel (PTX), shown in a murine gastric cancer model. This Phase II trial was designed to evaluate the benefits of adding VPA to wPTX in patients with gastric cancer refractory to first-line treatment with fluoropyrimidine. Patients and methods The patients were randomly assigned in a 1:1 ratio to receive PTX 80 mg/m2 intravenously on days 1, 8, and 15, every 4 weeks, or a dose of PTX plus VPA taken everyday at 7.5 mg/kg twice daily. Random assignment was carried out at the data center with a minimization method adjusted by the Eastern Cooperative Oncology Group performance status (0–1 vs 2), prior chemotherapy (first-line vs second-line), and measurable lesions (presence vs absence). The primary end point was the overall survival (OS) rate, and the secondary end points were the progression-free survival rate and safety analysis. Results Sixty-six patients were randomly assigned to receive wPTX (n=33) or wPTX plus VPA (n=33). The median OS was 9.8 months in the wPTX group and 8.7 months in the wPTX plus VPA group (hazard ratio 1.19; 95% CI 0.702–2.026; P=0.51). The median progression-free survival was 4.5 months in the wPTX group and 3.0 months in the wPTX plus VPA group (hazard ratio 1.29; 95% CI 0.753–2.211; P=0.35). Grade 3–4 adverse events were neutropenia (3.1%), pneumonia (1.6%), liver injury (1.6%), brain infarction (1.6%), and rupture of aorta (1.6%). Conclusion No statistically significant difference was observed between wPTX and wPTX plus VPA for OS. PMID:27524882

  18. Comparative Proteomic Analysis of Advanced Ovarian Cancer Tissue to Identify Potential Biomarkers of Responders and Nonresponders to First-Line Chemotherapy of Carboplatin and Paclitaxel

    PubMed Central

    Sehrawat, Urmila; Pokhriyal, Ruchika; Gupta, Ashish Kumar; Hariprasad, Roopa; Khan, Mohd Imran; Gupta, Divya; Naru, Jasmine; Singh, Sundararajan Baskar; Mohanty, Ashok Kumar; Vanamail, Perumal; Kumar, Lalit; Kumar, Sunesh; Hariprasad, Gururao

    2016-01-01

    Conventional treatment for advanced ovarian cancer is an initial debulking surgery followed by chemotherapy combination of carboplatin and paclitaxel. Despite initial high response, three-fourths of these women experience disease recurrence with a dismal prognosis. Patients with advanced-stage ovarian cancer who underwent cytoreductive surgery were enrolled and tissue samples were collected. Post surgery, these patients were started on chemotherapy and followed up till the end of the cycle. Fluorescence-based differential in-gel expression coupled with mass spectrometric analysis was used for discovery phase of experiments, and real-time polymerase chain reaction, Western blotting, and pathway analysis were performed for expression and functional validation of differentially expressed proteins. While aldehyde reductase, hnRNP, cyclophilin A, heat shock protein-27, and actin are upregulated in responders, prohibitin, enoyl-coA hydratase, peroxiredoxin, and fibrin-β are upregulated in the nonresponders. The expressions of some of these proteins correlated with increased apoptotic activity in responders and decreased apoptotic activity in nonresponders. Therefore, the proteins qualify as potential biomarkers to predict chemotherapy response. PMID:26997873

  19. DESIGN OF AN ON-LINE, MULTI-SPECTROMETER FISSION PRODUCT MONITORING SYSTEM (FPMS) TO SUPPORT ADVANCED GAS REACTOR (AGR) FUEL TESTING AND QUALIFICATION IN THE ADVANCED TEST REACTOR

    SciTech Connect

    J. K. Hartwell; D. M. Scates; M. W. Drigert

    2005-11-01

    The US Department of Energy (DOE) is embarking on a series of tests of coated-particle reactor fuel for the Advanced Gas Reactor (AGR). As one part of this fuel development program a series of eight (8) fuel irradiation tests are planned for the Idaho National Laboratory’s (INL’s) Advanced Test Reactor (ATR). The first test in this series (AGR-1) will incorporate six separate “capsules” irradiated simultaneously, each containing about 51,000 TRISO-coated fuel particles supported in a graphite matrix and continuously swept with inert gas during irradiation. The effluent gas from each of the six capsules must be independently monitored in near real time and the activity of various fission gas nuclides determined and reported. A set of seven heavily-shielded high-purity germanium (HPGe) gamma-ray spectrometers and sodium iodide [NaI(Tl)] scintillation detector-based total radiation detectors have been designed, and are being configured and tested for use during the AGR-1 experiment. The AGR-1 test specification requires that the AGR-1 fission product measurement system (FPMS) have sufficient sensitivity to detect the failure of a single coated fuel particle and sufficient range to allow it to “count” multiple (up to 250) successive particle failures. This paper describes the design and expected performance of the AGR-1 FPMS.

  20. Comparison of the efficacy and tolerability of gefitinib with pemetrexed maintenance after first-line platinum-based doublet chemotherapy in advanced lung adenocarcinoma: single-center experience

    PubMed Central

    Lin, Liping; Zhao, Juanjuan; Hu, Jiazhu; Huang, Fuxi; Han, Jianjun; He, Yan; Cao, Xiaolong

    2016-01-01

    Purpose Both gefitinib and pemetrexed maintenance were effective therapies for advanced lung adenocarcinoma, but which is better is unclear. For patients with advanced lung adenocarcinoma, we have no idea whether we should choose gefitinib or pemetrexed maintenance in clinical practice. Here, we assessed the efficacy and tolerability of gefitinib versus pemetrexed maintenance in these patients. Patients and methods A total of 101 patients were identified and divided into gefitinib (n=53) or pemetrexed (n=48) maintenance. Epidermal growth factor receptor (EGFR) status of tumors was analyzed in 67 patients. Disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Results The results showed that DCR (79.2% vs 75%, P=0.642) was similar between gefitinib and pemetrexed groups. The PFS of gefitinib was significantly longer than that of pemetrexed (8 months vs 5.4 months, hazard ratio [HR]: 0.520, 95% confidence interval [CI]: 0.341–0.791, P=0.002); however, the OS was similar (19.9 months vs 18.8 months, HR: 1.006, 95% CI: 0.664–1.525, P=0.977). In EGFR mutation-positive patients, PFS was significantly longer in gefitinib (12 months vs 5.4 months; HR: 0.158, 95% CI: 0.074–0.333, P<0.001), whereas in EGFR wild-type subgroup gefitinib had a significantly shorter PFS than that by pemetrexed (2.5 months vs 5 months; HR: 2.822, 95% CI: 1.137–7.005, P=0.025). Cox multivariate regression analysis of PFS for overall population showed that smoking status (P=0.001) and maintenance regimens (P=0.013) were independent prognostic factors for PFS. Both gefitinib and pemetrexed were well tolerated. Conclusion Gefitinib compared with pemetrexed as maintenance therapy had a significantly longer PFS and a similar OS with good tolerability in patients with advanced lung adenocarcinoma. Moreover, for EGFR mutation-positive patients, gefitinib maintenance had a significantly longer PFS; however, pemetrexed

  1. CA19-9-related tumor kinetics after first-line chemotherapy of patients with advanced pancreatic cancer: a monoinstitutional experience.

    PubMed

    Colloca, Giuseppe; Venturino, Antonella; Guarneri, Domenico

    2016-09-01

    The absolute value of carbohydrate antigen 19-9 (CA19-9) pretreatment and its reduction after chemotherapy are established prognostic variables for patients with advanced pancreatic cancer. The present study is a retrospective monoinstitutional evaluation of the prognostic role of the CA19-9 reduction and some CA19-9-related tumor kinetics parameters, such as tumor growth rate constant (G), kinetic tumor response and log ratio. Forty-one cases met the selection criteria. After 8 weeks only G reported an inverse relationship with OS (r = -0.494) that was confirmed by regression analysis (R (2) = 0.192). G after 8 weeks of chemotherapy appears as a possible surrogate end point of overall survival. PMID:27522503

  2. A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer.

    PubMed

    Bramhall, S R; Schulz, J; Nemunaitis, J; Brown, P D; Baillet, M; Buckels, J A C

    2002-07-15

    Pancreatic cancer is the fifth most common cause of cancer death in the western world and the prognosis for unresectable disease remains poor. Recent advances in conventional chemotherapy and the development of novel 'molecular' treatment strategies with different toxicity profiles warrant investigation as combination treatment strategies. This randomised study in pancreatic cancer compares marimastat (orally administered matrix metalloproteinase inhibitor) in combination with gemcitabine to gemcitabine alone. Two hundred and thirty-nine patients with unresectable pancreatic cancer were randomised to receive gemcitabine (1000 mg m(-2)) in combination with either marimastat or placebo. The primary end-point was survival. Objective tumour response and duration of response, time to treatment failure and disease progression, quality of life and safety were also assessed. There was no significant difference in survival between gemcitabine and marimastat and gemcitabine and placebo (P=0.95 log-rank test). Median survival times were 165.5 and 164 days and 1-year survival was 18% and 17% respectively. There were no significant differences in overall response rates (11 and 16% respectively), progression-free survival (P=0.68 log-rank test) or time to treatment failure (P=0.70 log-rank test) between the treatment arms. The gemcitabine and marimastat combination was well tolerated with only 2.5% of patients withdrawn due to presumed marimastat toxicity. Grade 3 or 4 musculoskeletal toxicities were reported in only 4% of the marimastat treated patients, although 59% of marimastat treated patients reported some musculoskeletal events. The results of this study provide no evidence to support a combination of marimastat with gemcitabine in patients with advanced pancreatic cancer. The combination of marimastat with gemcitabine was well tolerated. Further studies of marimastat as a maintenance treatment following a response or stable disease on gemcitabine may be justified. PMID

  3. Economic Evaluation of Companion Diagnostic Testing for EGFR Mutations and First-Line Targeted Therapy in Advanced Non-Small Cell Lung Cancer Patients in South Korea

    PubMed Central

    Lim, Eun-A; Bae, Eunmi; Lim, Jaeok; Shin, Young Kee; Choi, Sang-Eun

    2016-01-01

    Background As targeted therapy becomes increasingly important, diagnostic techniques for identifying targeted biomarkers have also become an emerging issue. The study aims to evaluate the cost-effectiveness of treating patients as guided by epidermal growth factor receptor (EGFR) mutation status compared with a no-testing strategy that is the current clinical practice in South Korea. Methods A cost-utility analysis was conducted to compare an EGFR mutation testing strategy with a no-testing strategy from the Korean healthcare payer’s perspective. The study population consisted of patients with stage 3b and 4 lung adenocarcinoma. A decision tree model was employed to select the appropriate treatment regimen according to the results of EGFR mutation testing and a Markov model was constructed to simulate disease progression of advanced non-small cell lung cancer. The length of a Markov cycle was one month, and the time horizon was five years (60 cycles). Results In the base case analysis, the testing strategy was a dominant option. Quality-adjusted life-years gained (QALYs) were 0.556 and 0.635, and total costs were $23,952 USD and $23,334 USD in the no-testing and testing strategy respectively. The sensitivity analyses showed overall robust results. The incremental cost-effectiveness ratios (ICERs) increased when the number of patients to be treated with erlotinib increased, due to the high cost of erlotinib. Conclusion Treating advanced adenocarcinoma based on EGFR mutation status has beneficial effects and saves the cost compared to no testing strategy in South Korea. However, the cost-effectiveness of EGFR mutation testing was heavily affected by the cost-effectiveness of the targeted therapy. PMID:27483001

  4. First-line therapy for treatment-naive patients with advanced/metastatic renal cell carcinoma: a systematic review of published randomized controlled trials.

    PubMed

    Takyar, Shweta; Diaz, Jose; Sehgal, Manu; Sapunar, Francisco; Pandha, Hardev

    2016-06-01

    In the recent years, a number of targeted therapies have been approved for first-line treatment of patients with metastatic renal cell carcinoma. A systematic review was conducted to assess the clinical efficacy, safety and effect of all first-line treatments evaluated to date on health-related quality of life (HRQoL). A systematic search of Embase, Cochrane and MEDLINE databases was performed to identify randomized controlled trials (1980-2015) evaluating any targeted therapy/immunotherapy against placebo or any other targeted intervention/immunotherapy in treatment-naive patients with metastatic renal cell carcinoma. Conference proceedings from major cancer congresses (2007-2015) were handsearched. Sixteen randomized controlled trials were identified, mostly phase III. Overall, targeted therapies were associated with either improved [sunitinib, bevacizumab+interferon α (IFNα) and temsirolimus] or comparable (sorafenib) progression-free survival (PFS) versus IFNα monotherapy. Sunitinib demonstrated comparable PFS and overall survival to pazopanib, comparable PFS to sorafenib and shorter PFS compared with bevacizumab+IFNα (although no conclusions were made with regard to superiority/inferiority). Compared with sorafenib, tivozanib demonstrated a significantly longer PFS, and both tivozanib and axitinib demonstrated higher response rates. Nintedanib demonstrated comparable PFS and overall survival to sunitinib in a phase II trial. Temsirolimus, sunitinib and sorafenib treatment led to better HRQoL versus IFNα; pazopanib was associated with better HRQoL versus sunitinib. No direct meta-analyses or indirect treatment comparison analysis were undertaken because of noncomparability of the trials. In general, targeted therapies demonstrated favourable clinical efficacy and improved HRQoL compared with IFNα monotherapy. The newer therapies, tivozanib and axitinib (but not nintedanib), appeared to exhibit greater clinical benefit (response rate) than older tyrosine

  5. A meta-analysis of anastrozole in combination with fulvestrant in the first line treatment of hormone receptor positive advanced breast cancer.

    PubMed

    Tan, Pui San; Haaland, Benjamin; Montero, Alberto J; Lopes, Gilberto

    2013-04-01

    Fulvestrant is a highly active systemic therapy in patients with metastatic hormone receptor positive breast cancer. Preclinical work suggested potential synergy of fulvestrant in combination with aromatase inhibitor therapy and delayed development of endocrine resistance. The purpose of this meta-analysis is to evaluate the effectiveness of fulvestrant plus anastrozole, compared to anastrozole alone, as first line treatment of postmenopausal stage IV hormone receptor positive, HER2-negative breast cancer. The literature search was performed using PubMed, Google Scholar, Embase, ASCO, and ESMO to search for abstracts published during the last 10 years using relevant keywords. Two prospective randomized clinical trials were found to fulfill the search criteria for combination of anastrozole plus fulvestrant versus anastrozole alone. Meta-estimates were calculated by combining study estimates using the DerSimonian and Laird random effects model. The linear mixed-effects model was used to generate 95 % prediction intervals (PIs) for study-specific hazard and odds ratios. Pooled hazard ratio for progression-free survival is 0.88 (95 % CI 0.72-1.09, 95 % PI 0.65-1.21), overall survival 0.88 (95 % CI 0.72-1.08, 95 % PI 0.68-1.14) and pooled odds ratio for response rate is 1.13 (95 % CI 0.79-1.63, 95 % PI 0.78-1.65). A non-significant trend was observed with anastrozole plus fulvestrant being only marginally better than anastrozole alone in the endpoints of: progression-free survival, overall survival, and response rates. Based on these data, there is not solid evidence that the addition of fulvestrant at a dose of 250 mg monthly is better than anastrozole alone as first line therapy in women with postmenopausal hormone receptor positive breast cancer.

  6. Evaluation of Circulating Tumor Cells and Related Events as Prognostic Factors and Surrogate Biomarkers in Advanced NSCLC Patients Receiving First-Line Systemic Treatment

    PubMed Central

    Muinelo-Romay, Laura; Vieito, Maria; Abalo, Alicia; Alonso Nocelo, Marta; Barón, Francisco; Anido, Urbano; Brozos, Elena; Vázquez, Francisca; Aguín, Santiago; Abal, Miguel; López López, Rafael

    2014-01-01

    In the present study we investigated the prognostic value of Circulating Tumour Cells (CTC) and their utility for therapy monitoring in non-small cell lung cancer (NSCLC). A total of 43 patients newly diagnosed with NSCLC were prospectively enrolled. Blood samples were obtained before the 1st, 2nd and 5th cycles of chemotherapy and analyzed using CellSearch technology. Both CTC and CTC-related objects (not morphological standard or broken epithelial cells) were counted. At baseline 18 (41.9%) patients were positive for intact CTC count and 10 (23.2%) of them had ≥5 CTC, while CK positive events were found in 79.1% of patients. The group of patients with CTC ≥5 at baseline presented worse PFS and OS than those with <5 CTC (p = 0.034 and p = 0.008, respectively). Additionally, high levels of total CK positive events were associated with poor prognosis in the group of patients with <5 CTC. Regarding therapy monitoring, patients presenting increased levels of CTC during the treatment demonstrated lower OS and PFS rates. All these data supported the value of CTC as a prognostic biomarker and as a surrogate indicator of chemotherapy effectiveness in advanced NSCLC patients, with the additional value of analyzing other “objects” such as apoptotic CTC or CK fragments to guide the clinical management of these patients. PMID:24452143

  7. Evaluation of Circulating Tumor Cells and Related Events as Prognostic Factors and Surrogate Biomarkers in Advanced NSCLC Patients Receiving First-Line Systemic Treatment.

    PubMed

    Muinelo-Romay, Laura; Vieito, Maria; Abalo, Alicia; Nocelo, Marta Alonso; Barón, Francisco; Anido, Urbano; Brozos, Elena; Vázquez, Francisca; Aguín, Santiago; Abal, Miguel; López, Rafael López

    2014-01-01

    In the present study we investigated the prognostic value of Circulating Tumour Cells (CTC) and their utility for therapy monitoring in non-small cell lung cancer (NSCLC). A total of 43 patients newly diagnosed with NSCLC were prospectively enrolled. Blood samples were obtained before the 1st, 2nd and 5th cycles of chemotherapy and analyzed using CellSearch technology. Both CTC and CTC-related objects (not morphological standard or broken epithelial cells) were counted. At baseline 18 (41.9%) patients were positive for intact CTC count and 10 (23.2%) of them had ≥5 CTC, while CK positive events were found in 79.1% of patients. The group of patients with CTC ³5 at baseline presented worse PFS and OS than those with <5 CTC (p = 0.034 and p = 0.008, respectively). Additionally, high levels of total CK positive events were associated with poor prognosis in the group of patients with <5 CTC. Regarding therapy monitoring, patients presenting increased levels of CTC during the treatment demonstrated lower OS and PFS rates. All these data supported the value of CTC as a prognostic biomarker and as a surrogate indicator of chemotherapy effectiveness in advanced NSCLC patients, with the additional value of analyzing other "objects" such as apoptotic CTC or CK fragments to guide the clinical management of these patients.

  8. Comparative analysis of the efficacy and safety of modified FOLFOX-6 and DCF regimens as first-line treatment in advanced gastric cancer

    PubMed Central

    HACIBEKIROGLU, ILHAN; KODAZ, HILMI; ERDOGAN, BULENT; TURKMEN, ESMA; ESENKAYA, ASIM; ONAL, YILMAZ; UZUNOGLU, SERNAZ; CICIN, IRFAN

    2015-01-01

    The aim of this study was to retrospectively compare the efficacy and toxicity of the oxaliplatin + 5-fluorouracil (5-FU) + leucovorin (LV) regimen [modified (m)FOLFOX-6] with that of the docetaxel + cisplatin + 5-FU regimen (DCF) in patients with advanced gastric cancer (AGC). A total of 72 patients received DCF (75 mg/m2 docetaxel and 75 mg/m2 cisplatin on day 1 and 750 mg/m2 5-FU on days 1–5) every 21 days, whereas 54 patients received mFOLFOX-6 (85 mg/m2 oxaliplatin and 400 mg/m2 LV as a 2-h infusion, followed by a 5-FU bolus of 400 mg/m2 and 2,400 mg/m2 5-FU as a 46-h continuous infusion) every 14 days. In the DCF arm, 55 (76.4%) of the patients received prophylactic granulocyte colony-stimulating factor (G-CSF), 48–72 h following completion of chemotherapy. The median follow-up of the study was 12.1 months. The overall response rate (ORR) was 37.0% for mFOLFOX-6 and 40.3% for DCF (P=0.72). The median time to progression was 6.5 and 6.2 months in the mFOLFOX-6 and DCF arms, respectively (P=0.70). The median overall survival was 11.4 and 13.5 months in the mFOLFOX-6 and DCF arms, respectively (P=0.72). The rates of hematological toxicity did not differ between the two arms. However, in the subgroup analysis, grade 3–4 neutropenia and febrile neutropenia were significantly more common among patients who had not received G-CSF prophylaxis in the DCF arm. The incidence of grade 3–4 nausea/vomiting and diarrhea were significantly higher in the DCF arm. In conclusion, the present study demonstrated that the efficacy of the mFOLFOX-6 regimen was comparable to that of the DCF regimen in AGC patients. In addition, the benefit of G-CSF prophylaxis in conjunction with the DCF regimen was demonstrated. PMID:26623070

  9. Weekly nanoparticle albumin-bound paclitaxel in combination with cisplatin versus weekly solvent-based paclitaxel plus cisplatin as first-line therapy in Chinese patients with advanced esophageal squamous cell carcinoma

    PubMed Central

    Wang, Hai-ying; Yao, Zhi-hua; Tang, Hong; Zhao, Yan; Zhang, Xiao-san; Yao, Shu-na; Yang, Shu-jun; Liu, Yan-yan

    2016-01-01

    Objective More effective regimens for advanced esophageal squamous cell carcinoma (ESCC) are urgently needed. Therefore, a retrospective study concerning the efficacy and safety of nanoparticle albumin-bound paclitaxel plus cisplatin (nab-TP) versus solvent-based paclitaxel plus cisplatin (sb-TP) as a first-line therapy was conducted in Chinese patients with advanced ESCC. Methods From June 2009 to June 2015, 32 patients were treated with nab-paclitaxel (125 mg/m2) on the first and eighth days (30 minutes infusion) and cisplatin (75 mg/m2) on the second day every 21 days (nab-TP arm). Also, 43 patients were treated with solvent-based paclitaxel (80 mg/m2) intravenously on the first and eighth days and the same dose of cisplatin (sb-TP arm). The two groups were compared in terms of objective response rate (ORR), disease control rate, progression-free survival (PFS), overall survival (OS), and safety profile. OS and PFS were estimated using Kaplan–Meier methods to determine associations between chemotherapy regimens and survival outcomes. Results Nab-TP demonstrated a higher ORR (50% vs 30%; P=0.082) and disease control rate (81% vs 65%; P=0.124) than sb-TP. Median OS was similar for nab-TP and sb-TP (12.5 vs 10.7 months; P=0.269). However, nab-TP resulted in a longer median PFS (6.1 months [95% confidence interval: 5.3–6.9]) than sb-TP (5.0 months [95% confidence interval: 4.4–5.6]) (P=0.029). The most common adverse events included anemia, leukopenia, neutropenia, febrile neutropenia, and thrombocytopenia in both the groups and no statistically significant differences were observed between the groups. With statistically significant differences, significantly less grade ≥3 peripheral neuropathy, arthralgia, and myalgia occurred in the nab-TP arm (all P<0.05). Dose reduction, treatment delays, and second-line therapy were similar between the two regimens. There were no treatment-related deaths in either group. Conclusion Nab-paclitaxel plus cisplatin is found

  10. Advanced light element and low energy X-ray line analysis using Energy Dispersive Spectrometry (EDS) with Silicon Drift Detectors (SDD)

    NASA Astrophysics Data System (ADS)

    Salge, T.; Palasse, L.; Berlin, J.; Hansen, B.; Terborg, R.; Falke, M.

    2013-12-01

    Introduction: Characterization at the micro- to nano-scale is crucial for understanding many processes in earth, planetary, material and biological sciences. The composition of thin electron transparent samples can be analyzed in the nm-range using transmission electron microscopes (TEM) or, specific sample holders provided, in the field emission scanning electron microscope (FE-SEM). Nevertheless both methods often require complex sample preparation. An alternative method is to analyze bulk samples with a FE-SEM. In order to decrease the excitation volume for generated X-rays, low accelerating voltages (HV<10) are required. Consequently, only low to intermediate energy X-ray lines can be evaluated and many peak overlaps have to be deconvoluted since the high energy range is not available. Methods: A BRUKER Quantax EDS system with an XFlash Silicon Drift Detector acquired EDS spectra in spectrum images. To separate overlapping peaks, an extended atomic database [1] was used. For single channel EDS the electron beam current, solid angle, take-off angle and exposure time can be optimized to investigate the element composition. Multiple SDD setups ensure an even higher efficiency and larger collection angles for the X-ray analysis than single channel detectors. Shadowing effects are minimized in element distribution maps so that samples can be investigated quickly and sometimes in a close to natural state, with little preparation. A new type of EDS detector, the annular four channel SDD (XFlash 5060F), is placed between the pole piece and sample. It covers a very large solid angle (1.1 sr) and allows sufficient data collection at low beam currents on beam sensitive samples with substantial surface topography. Examples of applications: Results demonstrate that SDD-based EDS analysis contributes essential information on the structure at the micro- to nano scale of the investigated sample types. These include stardust analogue impact experiments [2], Chicxulub asteroid

  11. Measure Lines

    ERIC Educational Resources Information Center

    Crissman, Sally

    2011-01-01

    One tool for enhancing students' work with data in the science classroom is the measure line. As a coteacher and curriculum developer for The Inquiry Project, the author has seen how measure lines--a number line in which the numbers refer to units of measure--help students not only represent data but also analyze it in ways that generate…

  12. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial

    PubMed Central

    Herbst, Roy S; Sun, Yan; Eberhardt, Wilfried E E; Germonpré, Paul; Saijo, Nagahiro; Zhou, Caicun; Wang, Jie; Li, Longyun; Kabbinavar, Fairooz; Ichinose, Yukito; Qin, Shukui; Zhang, Li; Biesma, Bonne; Heymach, John V; Langmuir, Peter; Kennedy, Sarah J; Tada, Hiroomi; Johnson, Bruce E

    2011-01-01

    Summary Background Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection (RET) tyrosine kinases. In a randomised phase 2 study in patients with previously treated non-small-cell lung cancer (NSCLC), adding vandetanib 100 mg to docetaxel significantly improved progression-free survival (PFS) compared with docetaxel alone, including a longer PFS in women. These results supported investigation of the combination in this larger, definitive phase 3 trial (ZODIAC). Methods Between May, 2006, and April, 2008, patients with locally advanced or metastatic (stage IIIB–IV) NSCLC after progression following first-line chemotherapy were randomly assigned 1:1 through a third-party interactive voice system to receive vandetanib (100 mg/day) plus docetaxel (75 mg/m2 IV every 21 days; maximum six cycles) or placebo plus docetaxel. The primary objective was comparison of PFS between the two groups in the intention-to-treat population. Women were a coprimary analysis population. This study has been completed and is registered with ClinicalTrials.gov, number NCT00312377. Findings 1391 patients received vandetanib plus docetaxel (n=694 [197 women]) or placebo plus docetaxel (n=697 [224 women]). Vandetanib plus docetaxel led to a significant improvement in PFS versus docetaxel alone (hazard ratio [HR] 0·79, 97·58% CI 0·70–0·90; p<0·0001); median PFS was 4·0 months in the vandetanib group versus 3·2 months in placebo group. A similar improvement in PFS with vandetanib plus docetaxel versus placebo plus docetaxel was seen in women (HR 0·79, 0·62–1·00, p=0·024); median PFS was 4·6 months in the vandetanib group versus 4·2 months in the placebo group. Among grade 3 or higher adverse events, rash (63/689 [9%] vs 7/690 [1%]), neutropenia (199/689 [29%] vs 164/690 [24%]), and febrile neutropenia (61/689 [9%] vs 48/690 [7%]) were more common with vandetanib plus docetaxel

  13. Occurrence of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in N.E. Spanish surface waters and their removal in a drinking water treatment plant that combines conventional and advanced treatments in parallel lines.

    PubMed

    Flores, Cintia; Ventura, Francesc; Martin-Alonso, Jordi; Caixach, Josep

    2013-09-01

    Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are two emerging contaminants that have been detected in all environmental compartments. However, while most of the studies in the literature deal with their presence or removal in wastewater treatment, few of them are devoted to their detection in treated drinking water and fate during drinking water treatment. In this study, analyses of PFOS and PFOA have been carried out in river water samples and in the different stages of a drinking water treatment plant (DWTP) which has recently improved its conventional treatment process by adding ultrafiltration and reverse osmosis in a parallel treatment line. Conventional and advanced treatments have been studied in several pilot plants and in the DWTP, which offers the opportunity to compare both treatments operating simultaneously. From the results obtained, neither preoxidation, sand filtration, nor ozonation, removed both perfluorinated compounds. As advanced treatments, reverse osmosis has proved more effective than reverse electrodialysis to remove PFOA and PFOS in the different configurations of pilot plants assayed. Granular activated carbon with an average elimination efficiency of 64±11% and 45±19% for PFOS and PFOA, respectively and especially reverse osmosis, which was able to remove ≥99% of both compounds, were the sole effective treatment steps. Trace levels of PFOS (3.0-21 ng/L) and PFOA (<4.2-5.5 ng/L) detected in treated drinking water were significantly lowered in comparison to those measured in precedent years. These concentrations represent overall removal efficiencies of 89±22% for PFOA and 86±7% for PFOS.

  14. Receptor for advanced glycation endproducts signaling cascades are activated in pancreatic fibroblasts, but not in the INS1E insulinoma cell line: Are mesenchymal cells major players in chronic inflammation?

    PubMed Central

    Tago, Kazuma; Inoue, Ken-ichi; Ouchi, Motoshi; Miura, Yoshikazu; Kubota, Keiichi

    2016-01-01

    ABSTRACT The receptor for advanced glycation endproducts (RAGE) is a pattern recognition receptor that plays an important role in natural immunity. It is suggested that mesenchymal cells are the major players during inflammation. Previously, we reported that advanced glycation end products (AGE), known to be one of the ligands of RAGE, inhibited glucose-induced insulin secretion from ex vivo pancreatic islets, although the mechanism responsible remains largely unknown. In the present study, we examined the cascades operating downstream from RAGE using the insulinoma cell line INS1E and primary-cultured pancreatic fibroblasts as in vitro models for parenchymal (β) cells and mesenchymal cells, respectively. Phosphorylation of c-jun N-terminal kinase, inhibitor of nuclear factor κB kinase, and nuclear factor κB was stimulated by AGE or high mobility group binding 1 (HMGB1) in pancreatic fibroblasts, whereas no such effect was observed in INS1E cells. Expression of the Ccl5, Il-6, and Il-1b genes was increased by AGE/HMGB1 in fibroblasts, but not in INS1E cells. On the other hand, AGE inhibited the secretion of insulin from ex vivo pancreatic islets, and this effect was ameliorated by MK615, a Japanese apricot extract used as an anti-inflammatory agent. Glucose-induced insulin secretion from INS1E cells was not affected by direct administration of AGE/HMGB1, but was inhibited by fibroblast-conditioned medium. These results suggest that AGE suppresses glucose-induced insulin secretion from pancreatic islets through indirect mesenchymal RAGE signaling. PMID:27415824

  15. A randomized, double-blind, controlled study of exemestane versus anastrozole for the first-line treatment of postmenopausal Japanese women with hormone-receptor-positive advanced breast cancer.

    PubMed

    Iwata, Hiroji; Masuda, Norikazu; Ohno, Shinji; Rai, Yoshiaki; Sato, Yasuyuki; Ohsumi, Shozo; Hashigaki, Satoshi; Nishizawa, Yoshinori; Hiraoka, Masahiro; Morimoto, Tadaoki; Sasano, Hironobu; Saeki, Toshiaki; Noguchi, Shinzaburo

    2013-06-01

    The aromatase inhibitors exemestane and anastrozole are approved in Japan for first-line treatment of postmenopausal patients with advanced, hormone-receptor-positive breast cancer. This phase 3, randomized, double-blind study directly compared time to progression (TTP) for exemestane and anastrozole therapy in this patient population. Eligible patients were randomized to receive exemestane 25 mg or anastrozole 1 mg, each once daily. The primary endpoint was TTP based on assessment by an expert radiologic images review committee (ERIRC). Secondary endpoints included investigator-assessed TTP, time to treatment failure, overall survival, objective response rate, clinical benefit rate, and safety. A total 298 patients were randomized to receive exemestane (n = 149; mean age 63.4 years) or anastrozole (n = 149; mean age 64.0 years). Median ERIRC-assessed TTP was 13.8 and 11.1 months (hazard ratio = 1.007; 95 % confidence interval [CI]: 0.771, 1.317) and median investigator-assessed TTP was 13.8 and 13.7 months (hazard ratio = 1.059; 95 % CI: 0.816, 1.374) in the exemestane and anastrozole arms, respectively. Median overall survival was 60.1 months in the anastrozole arm and was not reached in the exemestane arm at data cutoff. The objective response rate was 43.9 % (95 % CI: 35.3, 52.8) and 39.1 % (95 % CI: 30.6, 48.1) in the exemestane and anastrozole arms, respectively. Treatment-related adverse events grade ≥3 occurred in 9.4 and 6.0 % of patients, and treatment-related serious adverse events occurred in 4.0 and 3.4 % of patients in the exemestane and anastrozole arms, respectively. In this study, the efficacy and safety profiles of exemestane were similar to those of anastrozole in Japanese patients with advanced, hormone-receptor-positive breast cancer; however, TTP non-inferiority of exemestane versus anastrozole was not confirmed.

  16. Randomized, Phase III Trial of First-Line Figitumumab in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone in Patients With Advanced Non–Small-Cell Lung Cancer

    PubMed Central

    Langer, Corey J.; Novello, Silvia; Park, Keunchil; Krzakowski, Maciej; Karp, Daniel D.; Mok, Tony; Benner, Rebecca J.; Scranton, Judith R.; Olszanski, Anthony J.; Jassem, Jacek

    2014-01-01

    Purpose Figitumumab (CP-751,871), a fully human immunoglobulin G2 monoclonal antibody, inhibits the insulin-like growth factor 1 receptor (IGF-1R). Our multicenter, randomized, phase III study compared figitumumab plus chemotherapy with chemotherapy alone as first-line treatment in patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Patients with stage IIIB/IV or recurrent NSCLC disease with nonadenocarcinoma histology received open-label figitumumab (20 mg/kg) plus paclitaxel (200 mg/m2) and carboplatin (area under the concentration-time curve, 6 mg · min/mL) or paclitaxel and carboplatin alone once every 3 weeks for up to six cycles. The primary end point was overall survival (OS). Results Of 681 randomly assigned patients, 671 received treatment. The study was closed early by an independent Data Safety Monitoring Committee because of futility and an increased incidence of serious adverse events (SAEs) and treatment-related deaths with figitumumab. Median OS was 8.6 months for figitumumab plus chemotherapy and 9.8 months for chemotherapy alone (hazard ratio [HR], 1.18; 95% CI, 0.99 to 1.40; P = .06); median progression-free survival was 4.7 months (95% CI, 4.2 to 5.4) and 4.6 months (95% CI, 4.2 to 5.4), respectively (HR, 1.10; P = .27); the objective response rates were 33% and 35%, respectively. The respective rates of all-causality SAEs were 66% and 51%; P < .01). Treatment-related grade 5 adverse events were also more common with figitumumab (5% v 1%; P < .01). Conclusion Adding figitumumab to standard chemotherapy failed to increase OS in patients with advanced nonadenocarcinoma NSCLC. Further clinical development of figitumumab is not being pursued. PMID:24888810

  17. Predictive and Prognostic Value of Ribonucleotide Reductase Regulatory Subunit M1 and Excision Repair Cross-Complementation Group 1 in Advanced Urothelial Carcinoma (UC) Treated with First-Line Gemcitabine Plus Platinum Combination Chemotherapy.

    PubMed

    Kim, Miso; Ku, Ja Hyeon; Kwak, Cheol; Kim, Hyeon Hoe; Lee, Eunsik; Keam, Bhumsuk; Kim, Tae Min; Heo, Dae Seog; Lee, Se-Hoon; Moon, Kyung Chul

    2015-01-01

    Preclinical and clinical studies have suggested that expression of ribonucleotide reductase regulatory subunit M1 (RRM1) and excision repair cross-complementation group 1 (ERCC1) is associated with resistance to gemcitabine and cisplatin, respectively. We evaluated the significance of RRM1 and ERCC1 expression to predict tumor response to gemcitabine plus platinum chemotherapy (GP) and survival in advanced UC. We retrospectively collected tumor samples and reviewed clinical data of 53 patients with unresectable or metastatic UC, who were treated with first-line GP. RRM1 and ERCC1 expression were measured by immunohistochemistry. Among 53 patients, 12 (22.6%) and 26 (49.1%) patients had tumors that demonstrated a high expression for RRM1 and ERCC1, respectively. Twenty-nine (70.7%) of 41 patients with low RRM1 expression achieved a clinical response (complete + partial responses), but only 3 (25.0%) of 12 patients with high RRM1 expression achieved a clinical response after GP (P=0.007). Nineteen (70.4%) of 27 patients with low ERCC1 expression achieved a clinical response, while 13 (50.0%) of 26 patients with high ERCC1 expression achieved a clinical response (P=0.130). High RRM1 expression was associated with shorter progression free survival and overall survival (PFS P=0.006, OS P=0.006). Multivariate analysis confirmed that patients with high RRM1 expression had a significantly greater risk of progression and death than those with low RRM1 expression. ERCC1 status was not a significant predictor for PFS and OS. RRM1 expression was predictive and prognostic of clinical outcome in advanced UC treated with gemcitabine plus platinum combination chemotherapy.

  18. Receptor for advanced glycation endproducts signaling cascades are activated in pancreatic fibroblasts, but not in the INS1E insulinoma cell line: Are mesenchymal cells major players in chronic inflammation?

    PubMed

    Tago, Kazuma; Inoue, Ken-Ichi; Ouchi, Motoshi; Miura, Yoshikazu; Kubota, Keiichi

    2016-09-01

    The receptor for advanced glycation endproducts (RAGE) is a pattern recognition receptor that plays an important role in natural immunity. It is suggested that mesenchymal cells are the major players during inflammation. Previously, we reported that advanced glycation end products (AGE), known to be one of the ligands of RAGE, inhibited glucose-induced insulin secretion from ex vivo pancreatic islets, although the mechanism responsible remains largely unknown. In the present study, we examined the cascades operating downstream from RAGE using the insulinoma cell line INS1E and primary-cultured pancreatic fibroblasts as in vitro models for parenchymal (β) cells and mesenchymal cells, respectively. Phosphorylation of c-jun N-terminal kinase, inhibitor of nuclear factor κB kinase, and nuclear factor κB was stimulated by AGE or high mobility group binding 1 (HMGB1) in pancreatic fibroblasts, whereas no such effect was observed in INS1E cells. Expression of the Ccl5, Il-6, and Il-1b genes was increased by AGE/HMGB1 in fibroblasts, but not in INS1E cells. On the other hand, AGE inhibited the secretion of insulin from ex vivo pancreatic islets, and this effect was ameliorated by MK615, a Japanese apricot extract used as an anti-inflammatory agent. Glucose-induced insulin secretion from INS1E cells was not affected by direct administration of AGE/HMGB1, but was inhibited by fibroblast-conditioned medium. These results suggest that AGE suppresses glucose-induced insulin secretion from pancreatic islets through indirect mesenchymal RAGE signaling. PMID:27415824

  19. Identification of trait-improving quantitative trait loci for grain yield components from a dent corn inbred line in an advanced backcross BC2F2 population and comparison with its F2:3 population in popcorn.

    PubMed

    Li, Y L; Niu, S Z; Dong, Y B; Cui, D Q; Wang, Y Z; Liu, Y Y; Wei, M G

    2007-06-01

    Normal maize germplasm could be used to improve the grain yield of popcorn inbreds. Our first objective was to locate genetic factors associated with trait variation and make first assessment on the efficiency of advanced backcross quantitative trait locus (AB-QTL) analysis for the identification and transfer of favorable QTL alleles for grain yield components from the dent corn inbred. A second objective was to compare the detection of QTL in the BC2F2 population with results using F(2:3) lines of the same parents. Two hundred and twenty selected BC2F2 families developed from a cross between Dan232 and an elite popcorn inbred N04 were evaluated for six grain yield components under two environments, and genotyped by means of 170 SSR markers. Using composite interval mapping (CIM), a total of 19 significant QTL were detected. Eighteen QTL had favorable alleles contributed by the dent corn parent Dan232. Sixteen of these favorable QTL alleles were not in the same or near marker intervals with QTL for popping characteristics. Six QTL were also detected in the F(2:3) population. Improved N04 could be developed from 210 and 208 families with higher grain weight per plant and/or 100-grain weight, respectively, and 35 families with the same or higher popping expansion volume than N04. In addition, near isogenic lines containing detected QTL (QTL-NILs) for grain weight per plant and/or 100-grain weight could be obtained from 12 families. Our study demonstrated that the AB-QTL method can be applied to identify and manipulate favorable QTL alleles from normal corn inbreds and combine QTL detection and popcorn breeding efficiently. PMID:17492267

  20. Association of advanced glycation end products with A549 cells, a human pulmonary epithelial cell line, is mediated by a receptor distinct from the scavenger receptor family and RAGE.

    PubMed

    Nakano, Nahoko; Fukuhara-Takaki, Kaori; Jono, Tadashi; Nakajou, Keisuke; Eto, Nobuaki; Horiuchi, Seikoh; Takeya, Motohiro; Nagai, Ryoji

    2006-05-01

    Cellular interactions with advanced glycation end products (AGE)-modified proteins are known to induce several biological responses, not only endocytic uptake and degradation, but also the induction of cytokines and growth factors, combined responses that may be linked to the development of diabetic vascular complications. In this study we demonstrate that A549 cells, a human pulmonary epithelial cell line, possess a specific binding site for AGE-modified bovine serum albumin (AGE-BSA) (K(d) = 27.8 nM), and additionally for EN-RAGE (extracellular newly identified RAGE binding protein) (K(d) = 118 nM). Western blot and RT-PCR analysis showed that RAGE (receptor for AGE) is highly expressed on A549 cells, while the expression of other known AGE-receptors such as galectin-3 and SR-A (class A scavenger receptor), are below the level of detection. The binding of (125)I-AGE-BSA to these cells is inhibited by unlabeled AGE-BSA, but not by EN-RAGE. In contrast, the binding of (125)I-EN-RAGE is significantly inhibited by unlabeled EN-RAGE and soluble RAGE, but not by AGE-BSA. Our results indicate that A549 cells possess at least two binding sites, one specific for EN-RAGE and the other specific for AGE-BSA. The latter receptor on A549 cells is distinct from the scavenger receptor family and RAGE.

  1. Correlations of survival with progression-free survival, response rate, and disease control rate in advanced biliary tract cancer: a meta-analysis of randomised trials of first-line chemotherapy

    PubMed Central

    Moriwaki, Toshikazu; Yamamoto, Yoshiyuki; Gosho, Masahiko; Kobayashi, Mariko; Sugaya, Akinori; Yamada, Takeshi; Endo, Shinji; Hyodo, Ichinosuke

    2016-01-01

    Background: The need to promote novel drug development for advanced biliary tract cancer (ABTC) has emphasised the importance of determining whether various efficacy end points can act as surrogates for overall survival (OS). Methods: We conducted a literature search of randomised trials of first-line chemotherapy for ABTC and investigated correlations between efficacy end points and OS using weighted linear regression analysis. The ratios of the median OS, median progression-free survival (PFS), response rate, and disease control rate in each trial were used to summarise treatment effects. The surrogate threshold effect (STE), which was the minimum treatment effect on PFS required to predict a non-zero treatment effect on OS, was calculated. Results: Seventeen randomised trials with 36 treatment arms were identified, and a sample size of 2148 patients with 19 paired arms was analysed. The strongest correlation between all evaluated efficacy end points was observed between median OS and median PFS ratios (r2=0.66). In trials with gemcitabine-containing therapies and targeted agents, the r2-values were 0.78. The STE was estimated at 0.83 for all trials and 0.81 for trials with gemcitabine-containing therapies, and was not calculated for trials with targeted agents. Conclusions: The median PFS ratio correlated well with the median OS ratio, and may be useful for planning a clinical trial for novel drug development. PMID:27031848

  2. Advanced stellarators

    NASA Astrophysics Data System (ADS)

    Schlüter, Arnulf

    1983-03-01

    Toroidal confinement of a plasma by an external magnetic field is not compatible with axisymmetry, in contrast to confinement by the pinch effect of induced electric currents as in a tokomak or by the reversed field pinch configuration. The existence of magnetic surfaces throughout the region in which grad p ≠ 0 is therefore not guaranteed in such configurations, though it is necessary for MHD-equilibrium when the lines of force possess a finite twist (or "rotational transform"). These twisted equilibria are called stellarators. The other type of external confinement requires all lines of force to be closed upon themselves and p to be function of the well defined quantity Q = φ d l/ B only. The resulting "bumpy" tori are sometimes also referred to as being M + S like. By discussing specific examples it is shown that stellarator configurations exist which retain as much as possible the properties of M + S like configurations, combine these with the magnetic well, and with an approximation to the isodynamic requirement of D. Palumbo. These so-called Advanced Stellarators shown an improvement in predicted particle confinement and beta-limit compared to the classical stellarators. They can also be viewed as forming a system of linked stabilized mirrors of small mirror ratio. These fields can be produced by modular coils. A prototype of such a configuration is being designed by the stellarator division of IPP under the name of Wendelstein VII-AS. Expected physical data and technical details of W VII-AS are given.

  3. CLO: The cell line ontology

    PubMed Central

    2014-01-01

    Background Cell lines have been widely used in biomedical research. The community-based Cell Line Ontology (CLO) is a member of the OBO Foundry library that covers the domain of cell lines. Since its publication two years ago, significant updates have been made, including new groups joining the CLO consortium, new cell line cells, upper level alignment with the Cell Ontology (CL) and the Ontology for Biomedical Investigation, and logical extensions. Construction and content Collaboration among the CLO, CL, and OBI has established consensus definitions of cell line-specific terms such as ‘cell line’, ‘cell line cell’, ‘cell line culturing’, and ‘mortal’ vs. ‘immortal cell line cell’. A cell line is a genetically stable cultured cell population that contains individual cell line cells. The hierarchical structure of the CLO is built based on the hierarchy of the in vivo cell types defined in CL and tissue types (from which cell line cells are derived) defined in the UBERON cross-species anatomy ontology. The new hierarchical structure makes it easier to browse, query, and perform automated classification. We have recently added classes representing more than 2,000 cell line cells from the RIKEN BRC Cell Bank to CLO. Overall, the CLO now contains ~38,000 classes of specific cell line cells derived from over 200 in vivo cell types from various organisms. Utility and discussion The CLO has been applied to different biomedical research studies. Example case studies include annotation and analysis of EBI ArrayExpress data, bioassays, and host-vaccine/pathogen interaction. CLO’s utility goes beyond a catalogue of cell line types. The alignment of the CLO with related ontologies combined with the use of ontological reasoners will support sophisticated inferencing to advance translational informatics development. PMID:25852852

  4. Central line complications

    PubMed Central

    Kornbau, Craig; Lee, Kathryn C; Hughes, Gwendolyn D; Firstenberg, Michael S

    2015-01-01

    Central venous access is a common procedure performed in many clinical settings for a variety of indications. Central lines are not without risk, and there are a multitude of complications that are associated with their placement. Complications can present in an immediate or delayed fashion and vary based on type of central venous access. Significant morbidity and mortality can result from complications related to central venous access. These complications can cause a significant healthcare burden in cost, hospital days, and patient quality of life. Advances in imaging, access technique, and medical devices have reduced and altered the types of complications encountered in clinical practice; but most complications still center around vascular injury, infection, and misplacement. Recognition and management of central line complications is important when caring for patients with vascular access, but prevention is the ultimate goal. This article discusses common and rare complications associated with central venous access, as well as techniques to recognize, manage, and prevent complications. PMID:26557487

  5. A major QTL for acute ethanol sensitivity in the alcohol tolerant and non-tolerant selected rat lines.

    PubMed

    Radcliffe, R A; Erwin, V G; Bludeau, P; Deng, X; Fay, T; Floyd, K L; Deitrich, R A

    2009-08-01

    The Alcohol Tolerant and Alcohol Non-Tolerant rats (AT, ANT) were selectively bred for ethanol-induced ataxia as measured on the inclined plane. Here we report on a quantitative trait locus (QTL) study in an F(2) intercross population derived from inbred AT and ANT (IAT, IANT) and a follow-up study of congenics that were bred to examine one of the mapped QTLs. Over 1200 F(2) offspring were tested for inclined plane sensitivity, acute tolerance on the inclined plane, duration of the loss of righting reflex (LORR) and blood ethanol at regain of the righting reflex (BECRR). F(2) rats that were in the upper and lower 20% for inclined plane sensitivity were genotyped with 78 SSLP markers. Significant QTLs for inclined plane sensitivity were mapped on chromosomes 8 and 20; suggestive QTLs were mapped on chromosomes 1, 2 and 3. Highly significant QTLs for LORR duration (LOD = 12.4) and BECRR (LOD = 5.7) were mapped to the same locus on chromosome 1. Breeding and testing of reciprocal congenic lines confirmed the chromosome 1 LORR/BECRR QTL. A series of recombinant congenic sub-lines were bred to fine-map this QTL. Current results have narrowed the QTL to an interval of between 5 and 20 Mb. We expect to be able to narrow the interval to less than 5 Mb with additional genotyping and continued breeding of recombinant sub-congenic lines.

  6. Advanced concepts for acceleration

    SciTech Connect

    Keefe, D.

    1986-07-01

    Selected examples of advanced accelerator concepts are reviewed. Such plasma accelerators as plasma beat wave accelerator, plasma wake field accelerator, and plasma grating accelerator are discussed particularly as examples of concepts for accelerating relativistic electrons or positrons. Also covered are the pulsed electron-beam, pulsed laser accelerator, inverse Cherenkov accelerator, inverse free-electron laser, switched radial-line accelerators, and two-beam accelerator. Advanced concepts for ion acceleration discussed include the electron ring accelerator, excitation of waves on intense electron beams, and two-wave combinations. (LEW)

  7. Rationale and protocol of SOAP: a phase II study to evaluate the efficacy of sorafenib as second-line treatment after pazopanib in patients with advanced renal cell carcinoma.

    PubMed

    Iacovelli, Roberto; Verzoni, Elena; Grassi, Paolo; Farcomeni, Alessio; de Braud, Filippo; Procopio, Giuseppe

    2014-01-01

    The introduction of agents targeting vascular endothelial grow factors has radically changed the approach to metastatic renal cell carcinoma; however, cure is not within definitive reach. In many cases, the tumor will progress several months after the start of first-line therapy and new lines of therapy are required. Pazopanib and sorafenib are two frequently used targeted agents, and no sound data are currently available for patients who relapsed after pazopanib. In this paper we illustrate the SOAP study, which was designed to evaluate the safety and efficacy of sorafenib in terms of progression free-survival in 44 patients treated in 10 Italian centers who had relapsed after first-line pazopanib. Standard treatment with sorafenib will be administered until disease progression or unacceptable toxicity. Secondary endpoints include the evaluation of overall survival, safety and quality of life. A subanalysis to evaluate toxicities as predictive factors has also been planned.

  8. Advance care directives

    MedlinePlus

    ... advance directive; Do-not-resuscitate - advance directive; Durable power of attorney - advance care directive; POA - advance care directive; Health care agent - advance care directive; Health care proxy - ...

  9. The Efficacy of Combining Antiangiogenic Agents with Chemotherapy for Patients with Advanced Non-Small Cell Lung Cancer Who Failed First-Line Chemotherapy: A Systematic Review and Meta-Analysis

    PubMed Central

    Yang, Bijun; Zhang, Yaxiong; Kang, Shiyang; Zhou, Ting; Hong, Shaodong; Qin, Tao; Hu, Zhihuang; Fang, Wenfeng; Huang, Yan; Zhang, Li

    2015-01-01

    Background The clinical outcomes of patients with NSCLC who progressed after first-line treatments remain poor. The purpose of this study was to assess the advantage of antiangiogenic therapy plus standard treatment versus standard treatment alone for this population of patients. Methods We conducted a rigorous search using electronic databases for eligible studies reporting antiangiogenic therapy combined with standard second-line chemotherapy versus standard second-line treatment for patient who progressed after front-line treatment. Pooled risk ratio and 95% confidence intervals were calculated using proper statistical method. Predefined subgroup analyses were conducted to identify the potential proper patients. Results Thirteen phase II/III RCTs which involved a total of 8358 participants were included. Overall, there was significant improvement in OS (HR 0.94, 95%CI: 0.89-0.99, p=0.03), PFS (HR 0.80, 95%CI: 0.76-0.84, p<0.00001), ORR (RR 1.75, 95%CI: 1.55-1.98, p<0.00001) and DCR (RR 1.23, 95%CI: 1.18-1.28, p<0.00001) in the group with antiangiogenic therapy plus standard treatment versus the group with standard treatment alone. Subgroup analysis showed that OS benefit was presented only in patients treated with docetaxel plus antiangiogenic agents (HR 0.92, 95%CI: 0.86-0.99, p=0.02) and patients with non-squamous NSCLC (HR for OS 0.92, 95%CI: 0.86-0.99, p=0.02). Conclusions This study revealed that the addition of antiangiogenic agents to the standard treatments could provide clinical benefit to NSCLC patients who failed their first-line therapy. Furthermore, proper selection of the combined standard cytotoxic agent, as well as the patient population by tumor histology, is warranted for future studies and clinical application of antiangiogenic therapy. PMID:26034985

  10. Central line infections - hospitals

    MedlinePlus

    ... infection; CVC - infection; Central venous device - infection; Infection control - central line infection; Nosocomial infection - central line infection; Hospital acquired infection - central line infection; Patient safety - central ...

  11. Many QTLs with minor additive effects are associated with a large difference in growth between two selection lines in chickens.

    PubMed

    Jacobsson, Lina; Park, Hee-Bok; Wahlberg, Per; Fredriksson, Robert; Perez-Enciso, Miguel; Siegel, Paul B; Andersson, Leif

    2005-10-01

    Two growth-selected lines in chickens have been developed from a single founder population by divergent selection for body weight at 56 days of age. After more than 40 generations of selection they show a nine-fold difference in body weight at selection age and large differences in growth rate, appetite, fat deposition and metabolic characteristics. We have generated a large intercross between these lines comprising more than 800 F2 birds. QTL mapping revealed 13 loci affecting growth. The most striking observation was that the allele in the high weight line in all cases was associated with enhanced growth, but each locus explained only a small proportion of the phenotypic variance using a standard QTL model (1.3-3.1%). This result is in sharp contrast to our previous study where we reported that the two-fold difference in adult body size between the red junglefowl and White Leghorn domestic chickens is explained by a small number of QTLs with large additive effects. Furthermore, no QTLs for anorexia or antibody response were detected despite large differences for these traits between the founder lines. The result is an excellent example where a large phenotypic difference between populations occurs in the apparent absence of any single locus with large phenotypic effects. The study underscores the need for powerful experimental designs in genetic studies of multifactorial traits. No QTL at all would have reached genome-wide significance using a less powerful design (e.g. approx. 200 F2 individuals) regardless of the nine-fold phenotypic difference between the founder lines for the selected trait. PMID:16356285

  12. Advanced Microsensors

    NASA Technical Reports Server (NTRS)

    1991-01-01

    This video looks at a spinoff application of the technology from advanced microsensors -- those that monitor and determine conditions of spacecraft like the Space Shuttle. The application featured is concerned with the monitoring of the health of premature babies.

  13. Advanced Composition

    ERIC Educational Resources Information Center

    Sarantos, R. L.

    1974-01-01

    This is an excerpt from a course for advanced students, designed to teach proficiency in English composition by providing activities specifically geared to the elimination of native language interference. (LG)

  14. PEARS Emission Line Galaxies

    NASA Technical Reports Server (NTRS)

    Pirzkal, Nor; Rothberg, Barry; Ly, Chun; Rhoads, James E.; Malhotra, Sangeeta; Grogin, Norman A.; Dahlen, Tomas; Meurer, Gerhardt R.; Walsh, Jeremy; Hathi, Nimish P.; Cohen, Seth; Belini, Andrea; Holwerda, Benne W.; Straughn, Amber; Mechtley, Matthew

    2012-01-01

    We present a full analysis of the Probing Evolution And Reionization Spectroscopically (PEARS) slitless grism spectroscopic data obtained vl'ith the Advanced Camera for Surveys on HST. PEARS covers fields within both the Great Observatories Origins Deep Survey (GOODS) North and South fields, making it ideal as a random surveY of galaxies, as well as the availability of a wide variety of ancillary observations to support the spectroscopic results. Using the PEARS data we are able to identify star forming galaxies within the redshift volume 0 < z < 1.5. Star forming regions in the PEARS survey are pinpointed independently of the host galaxy. This method allOW8 us to detect the presence of multiple emission line regions (ELRs) within a single galaxy. 1162 [OII], [OIII] and/or H-alpha emission lines have been identified in the PEARS sample of approx 906 galaxies down to a limiting flux of approx 10 - 18 erg/s/sq cm . The ELRs have also been compared to the properties of the host galaxy, including morphology, luminosity, and mass. From this analysis we find three key results: 1) The computed line luminosities show evidence of a flattening in the luminosity function with increasing redshift; 2) The star forming systems show evidence of disturbed morphologies, with star formation occurring predominantly within one effective (half-light) radius. However, the morphologies show no correlation with host stellar mass; and 3) The number density of star forming galaxies with M(*) >= 10(exp 9) Solar M decreases by an order of magnitude at z<=0.5 relative to the number at 0.5 < z < 0.9 in support of the argument for galaxy downsizing.

  15. SUCCINCT: An Open-label, Single-arm, Non-randomised, Phase 2 Trial of Gemcitabine and Cisplatin Chemotherapy in Combination with Sunitinib as First-line Treatment for Patients with Advanced Urothelial Carcinoma

    PubMed Central

    Geldart, Thomas; Chester, John; Casbard, Angela; Crabb, Simon; Elliott, Tony; Protheroe, Andrew; Huddart, Robert A.; Mead, Graham; Barber, Jim; Jones, Robert J.; Smith, Joanna; Cowles, Robert; Evans, Jessica; Griffiths, Gareth

    2015-01-01

    Gemcitabine and cisplatin chemotherapy (GC regimen) represents a standard treatment for advanced urothelial carcinoma. We performed an open-label, single-arm, non-randomised, phase 2 trial evaluating the addition of sunitinib to standard GC chemotherapy (SGC regimen). Overall, 63 treatment-naïve participants were recruited and received up to six 21-d cycles of cisplatin 70 mg/m2 (intravenously [IV], day 1) and gemcitabine 1000 mg/m2 (IV, days 1 and 8) combined with sunitinib 37.5 mg (orally, days 2–15). Following review of toxicity after the first six patients, the sunitinib dose was reduced to 25 mg for all patients. Overall response rate was 64%, with response noted in 37 of 58 patients. At 6 mo, 30 of 58 assessable patients (52%; 90% confidence interval [CI], 40–63%) were progression free. Median overall survival was 12 mo (95% CI, 9–15) and was heavily influenced by Bajorin prognostic group. Grade 3–4 toxicities were predominantly haematologic and limited the deliverability of the triple SGC regimen. The trial did not meet its prespecified primary end point of >60% patients progression free at 6 mo. Cumulative myelosuppression led to treatment delays of gemcitabine and cisplatin and dose reduction and/or withdrawal of sunitinib in the majority of cases. The triple-drug combination was not well tolerated. Phase 3 evaluation of the triple SGC regimen in advanced transitional cell carcinoma is not recommended. Patient summary The addition of sunitinib to standard cisplatin and gemcitabine chemotherapy was poorly tolerated and did not improve outcomes in advanced urothelial carcinoma. Treatment delivery was limited by myelotoxicity. PMID:25465968

  16. Mental Number Line, Number Line Estimation, and Mathematical Achievement: Their Interrelations in Grades 5 and 6

    ERIC Educational Resources Information Center

    Schneider, Michael; Grabner, Roland H.; Paetsch, Jennifer

    2009-01-01

    As indicated by the distance effect and the spatial-numerical association of response codes (SNARC) effect, natural numbers are mentally represented on a number line. Purportedly, this number line underlies children's number sense, which supports the acquisition of more advanced mathematical competencies. In 3 studies with a total of 429 fifth and…

  17. Assessment of Labor Behavior Factors and Selecting Line Managers' Lines of Development at Russian Industrial Enterprises

    ERIC Educational Resources Information Center

    Zavyalova, Elena K.; Kosheleva, Sofia V.

    2009-01-01

    Purpose: The paper investigates personal and environmental factors providing for the efficiency of line managers' activity and contributing to their professional and career advancement. The paper studies the prognostic value of the assessment of personal and environmental factors providing for the efficiency of line managers' activity according to…

  18. Phase 2 Study of MK-2206, an Allosteric Inhibitor of AKT, as Second-Line Therapy for Advanced Gastric and Gastroesophageal Junction Cancer: A SWOG Cooperative Group Trial (S1005)

    PubMed Central

    Ramanathan, Ramesh K.; McDonough, Shannon L.; Kennecke, Hagen F.; Iqbal, Syma; Baranda, Joaquina C.; Seery, Tara E.; Lim, Howard J.; Hezel, Aram F.; Vaccaro, Gina M.; Blanke, Charles D.

    2015-01-01

    BACKGROUND The AKT inhibitor MK-2206 at a dose of 60 mg every other day was evaluated in gastric/gastroesophageal junction cancers. METHODS Patients who had progressed after first-line treatment were eligible. Pertinent eligibility criteria included adequate organ function, a fasting serum glucose level ≤ 150 mg/dL, and less than grade 2 malabsorption or chronic diarrhea. MK-2206 was given orally (60 evaluable patients required). The primary endpoint was overall survival, and a median survival of 6.5 months (power, 89%; significance level, 0.07) was considered encouraging for further investigation. RESULTS Seventy patients were included in the final analyses. The median age was 59.8 years (range, 30.4–86.7 years); 70% were male, 89% were white, and 7% were Asian. There were 2 deaths possibly related to the study drug (cardiac arrest and respiratory failure). Grade 4 adverse events included hyperglycemia, anemia, and lung infection (1 each). Grade 3 adverse events occurred in < 5% of patients except for fatigue (6%). Other adverse events (all grades) included anemia (17%), anorexia (30%), diarrhea (26%), fatigue (50%), hyperglycemia (30%), nausea (40%), vomiting (22%), dry skin (19%), maculopapular rash (30%), and acneiform rash (13%). The response rate was 1%, the median progression-free survival was 1.8 months (95% confidence interval, 1.7–1.8 months), and the median overall survival was 5.1 months (95% confidence interval, 3.7–9.4 months) CONCLUSIONS MK-2206 as second-line therapy was well tolerated by an unselected group of patients with gastric/gastroesophageal junction cancers, but it did not have sufficient activity (response rate, 1%; overall survival, 5.1 months) to warrant further testing in this population. PMID:25827820

  19. Erlotinib plus capecitabine as first-line treatment for older Chinese patients with advanced adenocarcinoma of the lung (C-TONG0807): an open-label, single arm, multicenter phase II study.

    PubMed

    Zhao, Hong-Yun; Chen, Gong-Yan; Huang, Yan; Li, Xiao-li; Feng, Ji-Feng; Shi, Mei-Qi; Cheng, Ying; Ma, Li-Xia; Zhang, Yi-Ping; Gu, Cui-Ping; Song, Xiang-Qun; Zhou, Da; Zhang, Li

    2015-01-01

    Preclinical studies have shown synergism between epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and antifolates in solid tumors. This study is to investigate the efficacy and tolerability of erlotinib plus capecitabine as first-line treatment in older Chinese patients (≥ 65 years) with lung adenocarcinoma. This is an open-label, single arm, multicenter phase II clinical trial. Sixty- two patients with previously untreated stage IIIB/IV adenocarcinoma and age 65 years or above were enrolled at four tertiary teaching hospitals and 2 provincial hospitals in China; 58 patients fulfilled the study requirements. Erlotinib (150 mg/day) and capecitabine (1000 mg/m2 twice daily on days 1-14) were administered during every 21-day cycle. The primary endpoint was the non-progression rate at 12 weeks. EGFR and K-ras mutation rates were determined using PCR. Tumor expression of different biomarkers was assessed using immunohistochemistry. In a cohort of 58 patients, 34 patients had no disease progression at 12 weeks following treatment. The objective response rate was 29.3%, and the disease control rate was 75.9%. The objective response rate was significantly higher in patients with EGFR mutations than in those with wild-type EGFR. Patients with thymidine phosphorylase-negative tumors had significantly longer overall survival after one year than patients with thymidine phosphorylase-positive tumors. Forty-four patients had at least one primary adverse events (AEs), including skin rash (n = 30), grade 3 AEs (n = 17), and grade 4 AEs (n = 7). This is the first phase II clinical trial to assess erlotinib plus capecitabine combination therapy as first-line treatment in older patients with lung adenocarcinoma. Erlotinib/capecitabine chemotherapy was significantly better in patients with EGFR mutations and in those with thymidine phosphorylase-negative tumors. The use of fluorouracil derivatives for the treatment of lung adenocarcinoma warrants further study.

  20. Advances in optoelectronic oscillators

    NASA Astrophysics Data System (ADS)

    Nguimdo, Romain M.; Saleh, Khaldoun; Lin, Guoping; Matinenghi, Romain; Chembo, Yanne K.

    2016-02-01

    Optoelectronic oscillators are used for a wide variety of applications in microwave photonics. We here report the latest advances in this technology from our research group, with emphasis on the analysis of phase noise performance. We present a stochastic modelling approach for phase noise performance analysis of optoelectronic oscillators based on whispering gallery mode resonators and/or optical fiber delay lines, and the theory is complemented with experimental measurements. We provide a detailed theoretical analysis which enables us to find the stationary states of the system as well as their stability. Our calculations also permit to find explicit formulas for the phase noise spectra, thereby allowing for their optimization.

  1. Technological Advancements

    ERIC Educational Resources Information Center

    Kennedy, Mike

    2010-01-01

    The influx of technology has brought significant improvements to school facilities. Many of those advancements can be found in classrooms, but when students head down the hall to use the washrooms, they are likely to find a host of technological innovations that have improved conditions in that part of the building. This article describes modern…

  2. Research Advances

    ERIC Educational Resources Information Center

    King, Angela G.

    2004-01-01

    Research advances, a new feature in Journal of Chemical Engineering that brings information about innovations in current areas of research to high school and college science faculty with an intent to provide educators with timely descriptions of latest progress in research that can be integrated into existing courses to update course content and…

  3. Peripheral intravenous line - infants

    MedlinePlus

    PIV - infants; Peripheral IV - infants; Peripheral line - infants; Peripheral line - neonatal ... A peripheral intravenous line (PIV) is a small, short, plastic tube, called a catheter. A health care provider puts ...

  4. Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation.

    PubMed

    You, Jia; Wang, Zai; Xu, Shiqing; Zhang, Wenjian; Fang, Qing; Liu, Honglin; Peng, Liang; Deng, Tingting; Lou, Jinning

    2016-01-01

    Advanced glycation end products (AGEs) are believed to be involved in diverse complications of diabetes mellitus. Overexposure to AGEs of pancreatic β-cells leads to decreased insulin secretion and cell apoptosis. Here, to understand the cytotoxicity of AGEs to pancreatic β-cells, we used INS-1-3 cells as a β-cell model to address this question, which was a subclone of INS-1 cells and exhibited high level of insulin expression and high sensitivity to glucose stimulation. Exposed to large dose of AGEs, even though more insulin was synthesized, its secretion was significantly reduced from INS-1-3 cells. Further, AGEs treatment led to a time-dependent increase of depolymerized microtubules, which was accompanied by an increase of activated p38/MAPK in INS-1-3 cells. Pharmacological inhibition of p38/MAPK by SB202190 reversed microtubule depolymerization to a stabilized polymerization status but could not rescue the reduction of insulin release caused by AGEs. Taken together, these results suggest a novel role of AGEs-induced impairment of insulin secretion, which is partially due to a disturbance of microtubule dynamics that resulted from an activation of the p38/MAPK pathway. PMID:27635403

  5. Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation

    PubMed Central

    You, Jia; Xu, Shiqing; Zhang, Wenjian; Fang, Qing; Liu, Honglin; Peng, Liang; Deng, Tingting

    2016-01-01

    Advanced glycation end products (AGEs) are believed to be involved in diverse complications of diabetes mellitus. Overexposure to AGEs of pancreatic β-cells leads to decreased insulin secretion and cell apoptosis. Here, to understand the cytotoxicity of AGEs to pancreatic β-cells, we used INS-1-3 cells as a β-cell model to address this question, which was a subclone of INS-1 cells and exhibited high level of insulin expression and high sensitivity to glucose stimulation. Exposed to large dose of AGEs, even though more insulin was synthesized, its secretion was significantly reduced from INS-1-3 cells. Further, AGEs treatment led to a time-dependent increase of depolymerized microtubules, which was accompanied by an increase of activated p38/MAPK in INS-1-3 cells. Pharmacological inhibition of p38/MAPK by SB202190 reversed microtubule depolymerization to a stabilized polymerization status but could not rescue the reduction of insulin release caused by AGEs. Taken together, these results suggest a novel role of AGEs-induced impairment of insulin secretion, which is partially due to a disturbance of microtubule dynamics that resulted from an activation of the p38/MAPK pathway.

  6. Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation

    PubMed Central

    You, Jia; Xu, Shiqing; Zhang, Wenjian; Fang, Qing; Liu, Honglin; Peng, Liang; Deng, Tingting

    2016-01-01

    Advanced glycation end products (AGEs) are believed to be involved in diverse complications of diabetes mellitus. Overexposure to AGEs of pancreatic β-cells leads to decreased insulin secretion and cell apoptosis. Here, to understand the cytotoxicity of AGEs to pancreatic β-cells, we used INS-1-3 cells as a β-cell model to address this question, which was a subclone of INS-1 cells and exhibited high level of insulin expression and high sensitivity to glucose stimulation. Exposed to large dose of AGEs, even though more insulin was synthesized, its secretion was significantly reduced from INS-1-3 cells. Further, AGEs treatment led to a time-dependent increase of depolymerized microtubules, which was accompanied by an increase of activated p38/MAPK in INS-1-3 cells. Pharmacological inhibition of p38/MAPK by SB202190 reversed microtubule depolymerization to a stabilized polymerization status but could not rescue the reduction of insulin release caused by AGEs. Taken together, these results suggest a novel role of AGEs-induced impairment of insulin secretion, which is partially due to a disturbance of microtubule dynamics that resulted from an activation of the p38/MAPK pathway. PMID:27635403

  7. Recent Advances in the Exploration of the Small-Scale Structure of the Quiet Solar Atmosphere: Vortex Flows, the Horizontal Magnetic Field, and the Stokes- V Line-Ratio Method

    NASA Astrophysics Data System (ADS)

    Steiner, O.; Rezaei, R.

    2012-05-01

    We review (i) observations and numerical simulations of vortical flows in the solar atmosphere and (ii) measurements of the horizontal magnetic field in quiet Sun regions. First, we discuss various manifestations of vortical flows and emphasize the role of magnetic fields in mediating swirling motion created near the solar surface to the higher layers of the photosphere and to the chromosphere. We reexamine existing simulation runs of solar surface magnetoconvection with regard to vortical flows and compare to previously obtained results. Second, we reviews contradictory results and problems associated with measuring the angular distribution of the magnetic field in quiet Sun regions. Furthermore, we review the Stokes-V-amplitude ratio method for the lines Fe i λλ 630.15 and 630.25 nm. We come to the conclusion that the recently discovered two distinct populations in scatter plots of this ratio must not bee interpreted in terms of “uncollapsed'' and “collapsed'' fields but stem from weak granular magnetic fields and weak canopy fields located at the boundaries between granules and the intergranular space. Based on new simulation runs, we reaffirm earlier findings of a predominance of the horizontal field components over the vertical one, particularly in the upper photosphere and at the base of the chromosphere.

  8. Palbociclib as a first-line treatment in oestrogen receptor-positive, HER2-negative, advanced breast cancer not cost-effective with current pricing: a health economic analysis of the Swiss Group for Clinical Cancer Research (SAKK).

    PubMed

    Matter-Walstra, K; Ruhstaller, T; Klingbiel, D; Schwenkglenks, M; Dedes, K J

    2016-07-01

    Endocrine therapy continues to be the optimal systemic treatment for metastatic ER(+)HER2(-) breast cancer. The CDK4/6 inhibitor palbociclib combined with letrozole has recently been shown to significantly improve progression-free survival. Here we examined the cost-effectiveness of this regimen for the Swiss healthcare system. A Markov cohort simulation based on the PALOMA-1 trial (Finn et al. in Lancet Oncol 16:25-35, 2015) was used as the clinical course. Input parameters were based on summary trial data. Costs were assessed from the Swiss healthcare system perspective. Adding palbociclib to letrozole (PALLET) compared to letrozole monotherapy was estimated to cost an additional CHF342,440 and gain 1.14 quality-adjusted life years, resulting in an incremental cost-effectiveness ratio (ICER) of CHF301,227/QALY gained. In univariate sensitivity analyses, no tested variation in key parameters resulted in an ICER below a willingness-to-pay threshold of CHF100,000/QALY. PALLET had a 0 % probability of being cost-effective in probabilistic sensitivity analyses. Lowering PALLET's price by 75 % resulted in an ICER of CHF73,995/QALY and a 73 % probability of being cost-effective. At current prices, PALLET would cost the Swiss healthcare system an additional CHF155 million/year. Palbociclib plus letrozole cannot be considered cost-effective for the first-line treatment of patients with metastatic breast cancer in the Swiss healthcare system. PMID:27277747

  9. Palbociclib as a first-line treatment in oestrogen receptor-positive, HER2-negative, advanced breast cancer not cost-effective with current pricing: a health economic analysis of the Swiss Group for Clinical Cancer Research (SAKK).

    PubMed

    Matter-Walstra, K; Ruhstaller, T; Klingbiel, D; Schwenkglenks, M; Dedes, K J

    2016-07-01

    Endocrine therapy continues to be the optimal systemic treatment for metastatic ER(+)HER2(-) breast cancer. The CDK4/6 inhibitor palbociclib combined with letrozole has recently been shown to significantly improve progression-free survival. Here we examined the cost-effectiveness of this regimen for the Swiss healthcare system. A Markov cohort simulation based on the PALOMA-1 trial (Finn et al. in Lancet Oncol 16:25-35, 2015) was used as the clinical course. Input parameters were based on summary trial data. Costs were assessed from the Swiss healthcare system perspective. Adding palbociclib to letrozole (PALLET) compared to letrozole monotherapy was estimated to cost an additional CHF342,440 and gain 1.14 quality-adjusted life years, resulting in an incremental cost-effectiveness ratio (ICER) of CHF301,227/QALY gained. In univariate sensitivity analyses, no tested variation in key parameters resulted in an ICER below a willingness-to-pay threshold of CHF100,000/QALY. PALLET had a 0 % probability of being cost-effective in probabilistic sensitivity analyses. Lowering PALLET's price by 75 % resulted in an ICER of CHF73,995/QALY and a 73 % probability of being cost-effective. At current prices, PALLET would cost the Swiss healthcare system an additional CHF155 million/year. Palbociclib plus letrozole cannot be considered cost-effective for the first-line treatment of patients with metastatic breast cancer in the Swiss healthcare system.

  10. NCCTG N0821 (Alliance): A phase II first-line study of pemetrexed, carboplatin and bevacizumab in elderly patients with advanced nonsquamous non-small cell lung cancer with good performance status

    PubMed Central

    Dy, Grace K.; Molina, Julian R.; Qi, Yingwei; Ansari, Rafat; Thomas, Sachdev; Ross, Helen J.; Soori, Gamini; Anderson, Daniel; Aubry, Marie Christine; Meyers, Jeffrey; Adjei, Araba A.; Mandrekar, Sumithra; Adjei, Alex A.

    2014-01-01

    PURPOSE We hypothesized that the combination of bevacizumab, carboplatin and pemetrexed will be an effective first-line regimen in fit, elderly patients with nonsquamous NSCLC. PATIENTS AND METHODS Treatment-naïve, stage IIIB/IV nonsquamous NSCLC patients ≥ 70 years old with good performance status (ECOG PS 0-1) and adequate organ function were eligible. Carboplatin AUC 6, pemetrexed 500 mg/m2 and bevacizumab 15 mg/kg were administered on day 1 of each 21-day cycle (up to 6 cycles) followed by maintenance pemetrexed and bevacizumab. The primary endpoint of 6-month progression-free survival rate (PFS6) of at least 70% was assessed using a one-stage binomial design. Quality of life (QOL) questionnaires were administered. Polymorphisms in genes encoding relevant proteins (drug targets, transport and metabolism proteins) were correlated with treatment outcome. RESULTS Fifty-seven eligible patients were enrolled. Median age was 74.5 years. Median treatment cycles received was 6. The most common grade 3 or higher non-hematologic adverse events were fatigue (26%) and hypertension (11%). 16% had grade 4 neutropenia and 6.5% had grade 4 thrombocytopenia. Three patients experienced grade 3/4 hemorrhagic events (one pulmonary, two gastrointestinal). Primary endpoint of PFS6 was 60% (95% CI: 45.9–73%). Median PFS was 7.0 months (95% CI: 5.9–10.1), median overall survival was 13.7 months (95% CI: 9.4–16.8). Polymorphic KDR and VEGFA variants correlated with survival and toxicity, respectively. There was no significant change in overall QOL scores over time. CONCLUSION This regimen is feasible and did not decrease the QOL in this study population. However, it did not meet the primary efficacy endpoint. PMID:25157767

  11. The prognostic role of baseline CEA and CA 19-9 values and their time-dependent variations in advanced colorectal cancer patients submitted to first-line therapy.

    PubMed

    Tampellini, M; Ottone, A; Alabiso, I; Baratelli, C; Forti, L; Berruti, A; Aroasio, E; Scagliotti, G V

    2015-03-01

    Serum marker evaluation is an easily available prognostic indicator that may help clinicians to discriminate patients with an aggressive disease; there are few and small-sized studies exploring the prognostic role of baseline carcinoembryonic antigen (CEA) values and their variations during first-line therapy, and even fewer data are available for carbohydrate antigen 19-9 (CA 19-9). Our aim was to analyze the role of those prognostic markers to exploit them in daily clinical practice. Data of 892 patients with marker determination before and 3 and/or 6 months during therapy were extracted from two institutional databases. Patients were grouped according to single marker variation as always negative (G0), decreasing (G1), stable (G2), or increasing (G3). We evaluated the progression-free survival (PFS) and the overall survival (OS) of all the patents and correlated them with CEA and CA 19-9 values. A concordance between response to therapy and marker decrease was evident in 50.2% and in 34.4% of the patients for CEA and CA 19-9. Patients with low CEA or CA 19-9 baseline values had a longer PFS (15.1 vs. 10.5; 13.6 vs. 10.2 months) and OS (32.0 vs. 22.3; 30.5 vs. 20.1 months). The same results of PFS and OS were obtained by analyzing the data of the four different groups. Multivariate analyses confirmed the independent prognostic role of CEA and CA 19-9. Baseline CEA and CA 19-9 levels and their kinetics demonstrated to be independent prognostic factors. CA 19-9 dosage is not recommended; a possible role of CA 19-9 in patients with negative CEA could be worth further evaluation.

  12. Advanced Combustion

    SciTech Connect

    Holcomb, Gordon R.

    2013-03-11

    The activity reported in this presentation is to provide the mechanical and physical property information needed to allow rational design, development and/or choice of alloys, manufacturing approaches, and environmental exposure and component life models to enable oxy-fuel combustion boilers to operate at Ultra-Supercritical (up to 650{degrees}C & between 22-30 MPa) and/or Advanced Ultra-Supercritical conditions (760{degrees}C & 35 MPa).

  13. Advanced computing

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Advanced concepts in hardware, software and algorithms are being pursued for application in next generation space computers and for ground based analysis of space data. The research program focuses on massively parallel computation and neural networks, as well as optical processing and optical networking which are discussed under photonics. Also included are theoretical programs in neural and nonlinear science, and device development for magnetic and ferroelectric memories.

  14. Advanced Nanoemulsions

    NASA Astrophysics Data System (ADS)

    Fryd, Michael M.; Mason, Thomas G.

    2012-05-01

    Recent advances in the growing field of nanoemulsions are opening up new applications in many areas such as pharmaceuticals, foods, and cosmetics. Moreover, highly controlled nanoemulsions can also serve as excellent model systems for investigating basic scientific questions about soft matter. Here, we highlight some of the most recent developments in nanoemulsions, focusing on methods of formation, surface modification, material properties, and characterization. These developments provide insight into the substantial advantages that nanoemulsions can offer over their microscale emulsion counterparts.

  15. Loudspeaker line array educational demonstration.

    PubMed

    Anderson, Brian E; Moser, Brad; Gee, Kent L

    2012-03-01

    This paper presents a physical demonstration of an audio-range line array used to teach interference of multiple sources in a classroom or laboratory exercise setting. Software has been developed that permits real-time control and steering of the array. The graphical interface permits a user to vary the frequency, the angular response by phase shading, and reduce sidelobes through amplitude shading. An inexpensive, eight-element loudspeaker array has been constructed to test the control program. Directivity measurements of this array in an anechoic chamber and in a large classroom are presented. These measurements have good agreement with theoretical directivity predictions, thereby allowing its use as a quantitative learning tool for advanced students as well as a qualitative demonstration of arrays in other settings. Portions of this paper are directed toward educators who may wish to implement a similar demonstration for their advanced undergraduate or graduate level course in acoustics.

  16. Abstract Line Designs

    ERIC Educational Resources Information Center

    Nevinskas, Nancy

    2011-01-01

    In this article, the author describes a unit on the exploration of line. The unit was composed of two individual line lessons. In the first lesson, students were introduced to line as an element of design. They were asked to describe different types of lines, and look for them in art reproductions. The second lesson in the unit involved painting…

  17. Advanced Subsonic Combustion Rig

    NASA Technical Reports Server (NTRS)

    Lee, Chi-Ming

    1998-01-01

    Researchers from the NASA Lewis Research Center have obtained the first combustion/emissions data under extreme future engine operating conditions. In Lewis' new world-class 60-atm combustor research facility--the Advanced Subsonic Combustion Rig (ASCR)--a flametube was used to conduct combustion experiments in environments as extreme as 900 psia and 3400 F. The greatest challenge for combustion researchers is the uncertainty of the effects of pressure on the formation of nitrogen oxides (NOx). Consequently, U.S. engine manufacturers are using these data to guide their future combustor designs. The flametube's metal housing has an inside diameter of 12 in. and a length of 10.5 in. The flametube can be used with a variety of different flow paths. Each flow path is lined with a high-temperature, castable refractory material (alumina) to minimize heat loss. Upstream of the flametube is the injector section, which has an inside diameter of 13 in. and a length of 0.5-in. It was designed to provide for quick changeovers. This flametube is being used to provide all U.S. engine manufacturers early assessments of advanced combustion concepts at full power conditions prior to engine production. To date, seven concepts from engine manufacturers have been evaluated and improved. This collaborated development can potentially give U.S. engine manufacturers the competitive advantage of being first in the market with advanced low-emission technologies.

  18. Stereocontrol within Polyketide Assembly Lines

    PubMed Central

    Keatinge-Clay, Adrian T.

    2015-01-01

    Most of the stereocenters of polyketide natural products are established during assembly line biosynthesis. The body of knowledge for how stereocenters are set is now large enough to begin constructing physical models of key reactions. Interactions between stereocenter-forming enzymes and polyketide intermediates are examined here at atomic resolution, drawing from the most current structural and functional information of ketosynthases (KSs), ketoreductases (KRs), dehydratases (DHs), enoylreductases (ERs), and related enzymes. While many details remain to be experimentally determined, our understanding of the chemical and physical mechanisms utilized by the chirality-molding enzymes of modular PKSs is rapidly advancing. PMID:26584443

  19. Scale Drift in On-Line Calibration.

    ERIC Educational Resources Information Center

    Stocking, Martha L.

    Recent advances in psychometrics and computer technology encourage the development of model-based methods of individualized testing on a microcomputer, where each examinee receives short tests and where the number of pretest items that can be administered is severely restricted. On-line (i.e., data is collected on operational equipment) methods…

  20. Advanced LIGO

    NASA Astrophysics Data System (ADS)

    LIGO Scientific Collaboration; Aasi, J.; Abbott, B. P.; Abbott, R.; Abbott, T.; Abernathy, M. R.; Ackley, K.; Adams, C.; Adams, T.; Addesso, P.; Adhikari, R. X.; Adya, V.; Affeldt, C.; Aggarwal, N.; Aguiar, O. D.; Ain, A.; Ajith, P.; Alemic, A.; Allen, B.; Amariutei, D.; Anderson, S. B.; Anderson, W. G.; Arai, K.; Araya, M. C.; Arceneaux, C.; Areeda, J. S.; Ashton, G.; Ast, S.; Aston, S. M.; Aufmuth, P.; Aulbert, C.; Aylott, B. E.; Babak, S.; Baker, P. T.; Ballmer, S. W.; Barayoga, J. C.; Barbet, M.; Barclay, S.; Barish, B. C.; Barker, D.; Barr, B.; Barsotti, L.; Bartlett, J.; Barton, M. A.; Bartos, I.; Bassiri, R.; Batch, J. C.; Baune, C.; Behnke, B.; Bell, A. S.; Bell, C.; Benacquista, M.; Bergman, J.; Bergmann, G.; Berry, C. P. L.; Betzwieser, J.; Bhagwat, S.; Bhandare, R.; Bilenko, I. A.; Billingsley, G.; Birch, J.; Biscans, S.; Biwer, C.; Blackburn, J. K.; Blackburn, L.; Blair, C. D.; Blair, D.; Bock, O.; Bodiya, T. P.; Bojtos, P.; Bond, C.; Bork, R.; Born, M.; Bose, Sukanta; Brady, P. R.; Braginsky, V. B.; Brau, J. E.; Bridges, D. O.; Brinkmann, M.; Brooks, A. F.; Brown, D. A.; Brown, D. D.; Brown, N. M.; Buchman, S.; Buikema, A.; Buonanno, A.; Cadonati, L.; Calderón Bustillo, J.; Camp, J. B.; Cannon, K. C.; Cao, J.; Capano, C. D.; Caride, S.; Caudill, S.; Cavaglià, M.; Cepeda, C.; Chakraborty, R.; Chalermsongsak, T.; Chamberlin, S. J.; Chao, S.; Charlton, P.; Chen, Y.; Cho, H. S.; Cho, M.; Chow, J. H.; Christensen, N.; Chu, Q.; Chung, S.; Ciani, G.; Clara, F.; Clark, J. A.; Collette, C.; Cominsky, L.; Constancio, M., Jr.; Cook, D.; Corbitt, T. R.; Cornish, N.; Corsi, A.; Costa, C. A.; Coughlin, M. W.; Countryman, S.; Couvares, P.; Coward, D. M.; Cowart, M. J.; Coyne, D. C.; Coyne, R.; Craig, K.; Creighton, J. D. E.; Creighton, T. D.; Cripe, J.; Crowder, S. G.; Cumming, A.; Cunningham, L.; Cutler, C.; Dahl, K.; Dal Canton, T.; Damjanic, M.; Danilishin, S. L.; Danzmann, K.; Dartez, L.; Dave, I.; Daveloza, H.; Davies, G. S.; Daw, E. J.; DeBra, D.; Del Pozzo, W.; Denker, T.; Dent, T.; Dergachev, V.; DeRosa, R. T.; DeSalvo, R.; Dhurandhar, S.; D´ıaz, M.; Di Palma, I.; Dojcinoski, G.; Dominguez, E.; Donovan, F.; Dooley, K. L.; Doravari, S.; Douglas, R.; Downes, T. P.; Driggers, J. C.; Du, Z.; Dwyer, S.; Eberle, T.; Edo, T.; Edwards, M.; Edwards, M.; Effler, A.; Eggenstein, H.-B.; Ehrens, P.; Eichholz, J.; Eikenberry, S. S.; Essick, R.; Etzel, T.; Evans, M.; Evans, T.; Factourovich, M.; Fairhurst, S.; Fan, X.; Fang, Q.; Farr, B.; Farr, W. M.; Favata, M.; Fays, M.; Fehrmann, H.; Fejer, M. M.; Feldbaum, D.; Ferreira, E. C.; Fisher, R. P.; Frei, Z.; Freise, A.; Frey, R.; Fricke, T. T.; Fritschel, P.; Frolov, V. V.; Fuentes-Tapia, S.; Fulda, P.; Fyffe, M.; Gair, J. R.; Gaonkar, S.; Gehrels, N.; Gergely, L. Á.; Giaime, J. A.; Giardina, K. D.; Gleason, J.; Goetz, E.; Goetz, R.; Gondan, L.; González, G.; Gordon, N.; Gorodetsky, M. L.; Gossan, S.; Goßler, S.; Gräf, C.; Graff, P. B.; Grant, A.; Gras, S.; Gray, C.; Greenhalgh, R. J. S.; Gretarsson, A. M.; Grote, H.; Grunewald, S.; Guido, C. J.; Guo, X.; Gushwa, K.; Gustafson, E. K.; Gustafson, R.; Hacker, J.; Hall, E. D.; Hammond, G.; Hanke, M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hanson, J.; Hardwick, T.; Harry, G. M.; Harry, I. W.; Hart, M.; Hartman, M. T.; Haster, C.-J.; Haughian, K.; Hee, S.; Heintze, M.; Heinzel, G.; Hendry, M.; Heng, I. S.; Heptonstall, A. W.; Heurs, M.; Hewitson, M.; Hild, S.; Hoak, D.; Hodge, K. A.; Hollitt, S. E.; Holt, K.; Hopkins, P.; Hosken, D. J.; Hough, J.; Houston, E.; Howell, E. J.; Hu, Y. M.; Huerta, E.; Hughey, B.; Husa, S.; Huttner, S. H.; Huynh, M.; Huynh-Dinh, T.; Idrisy, A.; Indik, N.; Ingram, D. R.; Inta, R.; Islas, G.; Isler, J. C.; Isogai, T.; Iyer, B. R.; Izumi, K.; Jacobson, M.; Jang, H.; Jawahar, S.; Ji, Y.; Jiménez-Forteza, F.; Johnson, W. W.; Jones, D. I.; Jones, R.; Ju, L.; Haris, K.; Kalogera, V.; Kandhasamy, S.; Kang, G.; Kanner, J. B.; Katsavounidis, E.; Katzman, W.; Kaufer, H.; Kaufer, S.; Kaur, T.; Kawabe, K.; Kawazoe, F.; Keiser, G. M.; Keitel, D.; Kelley, D. B.; Kells, W.; Keppel, D. G.; Key, J. S.; Khalaidovski, A.; Khalili, F. Y.; Khazanov, E. A.; Kim, C.; Kim, K.; Kim, N. G.; Kim, N.; Kim, Y.-M.; King, E. J.; King, P. J.; Kinzel, D. L.; Kissel, J. S.; Klimenko, S.; Kline, J.; Koehlenbeck, S.; Kokeyama, K.; Kondrashov, V.; Korobko, M.; Korth, W. Z.; Kozak, D. B.; Kringel, V.; Krishnan, B.; Krueger, C.; Kuehn, G.; Kumar, A.; Kumar, P.; Kuo, L.; Landry, M.; Lantz, B.; Larson, S.; Lasky, P. D.; Lazzarini, A.; Lazzaro, C.; Le, J.; Leaci, P.; Leavey, S.; Lebigot, E. O.; Lee, C. H.; Lee, H. K.; Lee, H. M.; Leong, J. R.; Levin, Y.; Levine, B.; Lewis, J.; Li, T. G. F.; Libbrecht, K.; Libson, A.; Lin, A. C.; Littenberg, T. B.; Lockerbie, N. A.; Lockett, V.; Logue, J.; Lombardi, A. L.; Lormand, M.; Lough, J.; Lubinski, M. J.; Lück, H.; Lundgren, A. P.; Lynch, R.; Ma, Y.; Macarthur, J.; MacDonald, T.; Machenschalk, B.; MacInnis, M.; Macleod, D. M.; Magaña-Sandoval, F.; Magee, R.; Mageswaran, M.; Maglione, C.; Mailand, K.; Mandel, I.; Mandic, V.; Mangano, V.; Mansell, G. L.; Márka, S.; Márka, Z.; Markosyan, A.; Maros, E.; Martin, I. W.; Martin, R. M.; Martynov, D.; Marx, J. N.; Mason, K.; Massinger, T. J.; Matichard, F.; Matone, L.; Mavalvala, N.; Mazumder, N.; Mazzolo, G.; McCarthy, R.; McClelland, D. E.; McCormick, S.; McGuire, S. C.; McIntyre, G.; McIver, J.; McLin, K.; McWilliams, S.; Meadors, G. D.; Meinders, M.; Melatos, A.; Mendell, G.; Mercer, R. A.; Meshkov, S.; Messenger, C.; Meyers, P. M.; Miao, H.; Middleton, H.; Mikhailov, E. E.; Miller, A.; Miller, J.; Millhouse, M.; Ming, J.; Mirshekari, S.; Mishra, C.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Moe, B.; Mohanty, S. D.; Mohapatra, S. R. P.; Moore, B.; Moraru, D.; Moreno, G.; Morriss, S. R.; Mossavi, K.; Mow-Lowry, C. M.; Mueller, C. L.; Mueller, G.; Mukherjee, S.; Mullavey, A.; Munch, J.; Murphy, D.; Murray, P. G.; Mytidis, A.; Nash, T.; Nayak, R. K.; Necula, V.; Nedkova, K.; Newton, G.; Nguyen, T.; Nielsen, A. B.; Nissanke, S.; Nitz, A. H.; Nolting, D.; Normandin, M. E. N.; Nuttall, L. K.; Ochsner, E.; O'Dell, J.; Oelker, E.; Ogin, G. H.; Oh, J. J.; Oh, S. H.; Ohme, F.; Oppermann, P.; Oram, R.; O'Reilly, B.; Ortega, W.; O'Shaughnessy, R.; Osthelder, C.; Ott, C. D.; Ottaway, D. J.; Ottens, R. S.; Overmier, H.; Owen, B. J.; Padilla, C.; Pai, A.; Pai, S.; Palashov, O.; Pal-Singh, A.; Pan, H.; Pankow, C.; Pannarale, F.; Pant, B. C.; Papa, M. A.; Paris, H.; Patrick, Z.; Pedraza, M.; Pekowsky, L.; Pele, A.; Penn, S.; Perreca, A.; Phelps, M.; Pierro, V.; Pinto, I. M.; Pitkin, M.; Poeld, J.; Post, A.; Poteomkin, A.; Powell, J.; Prasad, J.; Predoi, V.; Premachandra, S.; Prestegard, T.; Price, L. R.; Principe, M.; Privitera, S.; Prix, R.; Prokhorov, L.; Puncken, O.; Pürrer, M.; Qin, J.; Quetschke, V.; Quintero, E.; Quiroga, G.; Quitzow-James, R.; Raab, F. J.; Rabeling, D. S.; Radkins, H.; Raffai, P.; Raja, S.; Rajalakshmi, G.; Rakhmanov, M.; Ramirez, K.; Raymond, V.; Reed, C. M.; Reid, S.; Reitze, D. H.; Reula, O.; Riles, K.; Robertson, N. A.; Robie, R.; Rollins, J. G.; Roma, V.; Romano, J. D.; Romanov, G.; Romie, J. H.; Rowan, S.; Rüdiger, A.; Ryan, K.; Sachdev, S.; Sadecki, T.; Sadeghian, L.; Saleem, M.; Salemi, F.; Sammut, L.; Sandberg, V.; Sanders, J. R.; Sannibale, V.; Santiago-Prieto, I.; Sathyaprakash, B. S.; Saulson, P. R.; Savage, R.; Sawadsky, A.; Scheuer, J.; Schilling, R.; Schmidt, P.; Schnabel, R.; Schofield, R. M. S.; Schreiber, E.; Schuette, D.; Schutz, B. F.; Scott, J.; Scott, S. M.; Sellers, D.; Sengupta, A. S.; Sergeev, A.; Serna, G.; Sevigny, A.; Shaddock, D. A.; Shahriar, M. S.; Shaltev, M.; Shao, Z.; Shapiro, B.; Shawhan, P.; Shoemaker, D. H.; Sidery, T. L.; Siemens, X.; Sigg, D.; Silva, A. D.; Simakov, D.; Singer, A.; Singer, L.; Singh, R.; Sintes, A. M.; Slagmolen, B. J. J.; Smith, J. R.; Smith, M. R.; Smith, R. J. E.; Smith-Lefebvre, N. D.; Son, E. J.; Sorazu, B.; Souradeep, T.; Staley, A.; Stebbins, J.; Steinke, M.; Steinlechner, J.; Steinlechner, S.; Steinmeyer, D.; Stephens, B. C.; Steplewski, S.; Stevenson, S.; Stone, R.; Strain, K. A.; Strigin, S.; Sturani, R.; Stuver, A. L.; Summerscales, T. Z.; Sutton, P. J.; Szczepanczyk, M.; Szeifert, G.; Talukder, D.; Tanner, D. B.; Tápai, M.; Tarabrin, S. P.; Taracchini, A.; Taylor, R.; Tellez, G.; Theeg, T.; Thirugnanasambandam, M. P.; Thomas, M.; Thomas, P.; Thorne, K. A.; Thorne, K. S.; Thrane, E.; Tiwari, V.; Tomlinson, C.; Torres, C. V.; Torrie, C. I.; Traylor, G.; Tse, M.; Tshilumba, D.; Ugolini, D.; Unnikrishnan, C. S.; Urban, A. L.; Usman, S. A.; Vahlbruch, H.; Vajente, G.; Valdes, G.; Vallisneri, M.; van Veggel, A. A.; Vass, S.; Vaulin, R.; Vecchio, A.; Veitch, J.; Veitch, P. J.; Venkateswara, K.; Vincent-Finley, R.; Vitale, S.; Vo, T.; Vorvick, C.; Vousden, W. D.; Vyatchanin, S. P.; Wade, A. R.; Wade, L.; Wade, M.; Walker, M.; Wallace, L.; Walsh, S.; Wang, H.; Wang, M.; Wang, X.; Ward, R. L.; Warner, J.; Was, M.; Weaver, B.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Welborn, T.; Wen, L.; Wessels, P.; Westphal, T.; Wette, K.; Whelan, J. T.; Whitcomb, S. E.; White, D. J.; Whiting, B. F.; Wilkinson, C.; Williams, L.; Williams, R.; Williamson, A. R.; Willis, J. L.; Willke, B.; Wimmer, M.; Winkler, W.; Wipf, C. C.; Wittel, H.; Woan, G.; Worden, J.; Xie, S.; Yablon, J.; Yakushin, I.; Yam, W.; Yamamoto, H.; Yancey, C. C.; Yang, Q.; Zanolin, M.; Zhang, Fan; Zhang, L.; Zhang, M.; Zhang, Y.; Zhao, C.; Zhou, M.; Zhu, X. J.; Zucker, M. E.; Zuraw, S.; Zweizig, J.

    2015-04-01

    The Advanced LIGO gravitational wave detectors are second-generation instruments designed and built for the two LIGO observatories in Hanford, WA and Livingston, LA, USA. The two instruments are identical in design, and are specialized versions of a Michelson interferometer with 4 km long arms. As in Initial LIGO, Fabry-Perot cavities are used in the arms to increase the interaction time with a gravitational wave, and power recycling is used to increase the effective laser power. Signal recycling has been added in Advanced LIGO to improve the frequency response. In the most sensitive frequency region around 100 Hz, the design strain sensitivity is a factor of 10 better than Initial LIGO. In addition, the low frequency end of the sensitivity band is moved from 40 Hz down to 10 Hz. All interferometer components have been replaced with improved technologies to achieve this sensitivity gain. Much better seismic isolation and test mass suspensions are responsible for the gains at lower frequencies. Higher laser power, larger test masses and improved mirror coatings lead to the improved sensitivity at mid and high frequencies. Data collecting runs with these new instruments are planned to begin in mid-2015.

  1. Video on phone lines: technology and applications

    NASA Astrophysics Data System (ADS)

    Hsing, T. Russell

    1996-03-01

    Recent advances in communications signal processing and VLSI technology are fostering tremendous interest in transmitting high-speed digital data over ordinary telephone lines at bit rates substantially above the ISDN Basic Access rate (144 Kbit/s). Two new technologies, high-bit-rate digital subscriber lines and asymmetric digital subscriber lines promise transmission over most of the embedded loop plant at 1.544 Mbit/s and beyond. Stimulated by these research promises and rapid advances on video coding techniques and the standards activity, information networks around the globe are now exploring possible business opportunities of offering quality video services (such as distant learning, telemedicine, and telecommuting etc.) through this high-speed digital transport capability in the copper loop plant. Visual communications for residential customers have become more feasible than ever both technically and economically.

  2. Nuclear reactor overflow line

    DOEpatents

    Severson, Wayne J.

    1976-01-01

    The overflow line for the reactor vessel of a liquid-metal-cooled nuclear reactor includes means for establishing and maintaining a continuous bleed flow of coolant amounting to 5 to 10% of the total coolant flow through the overflow line to prevent thermal shock to the overflow line when the reactor is restarted following a trip. Preferably a tube is disposed concentrically just inside the overflow line extending from a point just inside the reactor vessel to an overflow tank and a suction line is provided opening into the body of liquid metal in the reactor vessel and into the annulus between the overflow line and the inner tube.

  3. Subsea completion technology needs advances

    SciTech Connect

    Ledbetter, R.

    1995-09-18

    Subsea technology needs further advances to reduce operational costs before operators will expand the use of subsea well completions in the Gulf of Mexico. They will continue to choose surface completion-oriented systems as long as these are more economical operationally than subsea system. Designs of subsea equipment such as trees, connectors, control pods, umbilicals, and flow lines, must bring about reductions in the cost of both installation and workover compatibility. Remote operated vehicle (ROV) manipulation is one avenue that should be exploited. The bottom line is that significant cooperation between equipment manufacturers and ROV companies is needed to develop advanced ROV technology, and operators should be involved to help guide operational strategies.

  4. Advanced Pacemaker

    NASA Technical Reports Server (NTRS)

    1990-01-01

    Synchrony, developed by St. Jude Medical's Cardiac Rhythm Management Division (formerly known as Pacesetter Systems, Inc.) is an advanced state-of-the-art implantable pacemaker that closely matches the natural rhythm of the heart. The companion element of the Synchrony Pacemaker System is the Programmer Analyzer APS-II which allows a doctor to reprogram and fine tune the pacemaker to each user's special requirements without surgery. The two-way communications capability that allows the physician to instruct and query the pacemaker is accomplished by bidirectional telemetry. APS-II features 28 pacing functions and thousands of programming combinations to accommodate diverse lifestyles. Microprocessor unit also records and stores pertinent patient data up to a year.

  5. Peripheral intravenous line (image)

    MedlinePlus

    A peripheral intravenous line is a small, short plastic catheter that is placed through the skin into a vein, ... or foot, but occasionally in the head. A peripheral intravenous line is used to give fluids and ...

  6. Peripheral arterial line (image)

    MedlinePlus

    A peripheral arterial line is a small, short plastic catheter placed through the skin into an artery of the arm or leg. The purpose of a peripheral arterial line is to allow continuous monitoring of ...

  7. Advanced laser image recorder.

    PubMed

    Gramenopoulos, N; Hartfield, E D

    1972-12-01

    A laser image recorder is described, which is unique because of its advanced design and the state-of-the-art components employed to achieve high performance and versatility. The critical components are the pyramidal mirror scanner and the beam focusing lens. The scanner has a six-facet, beryllium mirror accurate to 0.33 sec of arc and rotating at 0-50,000 rpm on air bearings. A rapid change in speed is an important feature of this scanner. The focusing lens is diffraction limited with a flat field of 54 degrees , allowing a 90% duty cycle and the use of photographic film transported by a cylindrical drum. The lens converts the constant angular velocity of the reflected beam to a constant scanning velocity of the focused spot with a linearity of 0.05%. Maximum number of picture elements per line is 36,800 over a format of 228.6 mm. PMID:20119408

  8. Pancreatic cancer: New hopes after first line treatment

    PubMed Central

    Aroldi, Francesca; Bertocchi, Paola; Savelli, Giordano; Rosso, Edoardo; Zaniboni, Alberto

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. Extensive research has yielded advances in first-line treatment strategies, but there is no standardized second-line therapy. In this review, we examine the literature trying to establish a possible therapeutic algorithm. PMID:27672426

  9. Pancreatic cancer: New hopes after first line treatment

    PubMed Central

    Aroldi, Francesca; Bertocchi, Paola; Savelli, Giordano; Rosso, Edoardo; Zaniboni, Alberto

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. Extensive research has yielded advances in first-line treatment strategies, but there is no standardized second-line therapy. In this review, we examine the literature trying to establish a possible therapeutic algorithm.

  10. Pancreatic cancer: New hopes after first line treatment.

    PubMed

    Aroldi, Francesca; Bertocchi, Paola; Savelli, Giordano; Rosso, Edoardo; Zaniboni, Alberto

    2016-09-15

    Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. Extensive research has yielded advances in first-line treatment strategies, but there is no standardized second-line therapy. In this review, we examine the literature trying to establish a possible therapeutic algorithm. PMID:27672426

  11. Exploring the Action Landscape via Trial World-Lines

    ERIC Educational Resources Information Center

    Joglekar, Yogesh N.; Tham, Weng Kian

    2011-01-01

    The Hamilton action principle, also known as the principle of least action, and Lagrange equations are an integral part of intermediate and advanced undergraduate mechanics. Although the Hamilton principle is oft stated as "the action for any nearby trial world-line is greater than the action for the classical world-line," the landscape of action…

  12. Scrubber lining betterment

    SciTech Connect

    Cmiel, R. )

    1990-01-01

    This article is intended to provide guidance in the selection, qualification, and application of corrosion-resistant coatings and linings in electrical generating plants with emphasis on flue gas desulfurization (FGD) scrubber maintenance. Guidance is included here especially for those facing a lining project. This article describes scrubber outlet duct vinyl ester lining installation at San Miguel Electric. This lining is also being used in scrubber waste slurry thickeners and in the scrubber absorber vessel to overcoat existing flakeglass linings providing useful life extension.

  13. Gamma ray line astronomy

    NASA Technical Reports Server (NTRS)

    Ramaty, R.

    1984-01-01

    The interpretations and implications of the astrophysical observations of gamma-ray lines are reviewed. At the Galactic Center e(+)-e(-) pairs from a compact object produce an annihilation line that shows no redshift, indicating an annihilation site far removed from this object. In the jets of SS433, gamma-ray lines are produced by inelastic excitations, probably in dust grains, although line emission from fusion reactions has also been considered. Observations of diffuse galactic line emission reveal recently synthesized radioactive aluminum in the interstellar medium. In gamma-ray bursts, redshifted pair annihilation lines are consistent with a neutron star origin for the bursts. In solar flares, gamma-ray line emission reveals the prompt acceleration of protons and nuclei, in close association with the flare energy release mechanism.

  14. Advanced capacitors

    NASA Astrophysics Data System (ADS)

    Parker, R. D.; Buritz, R. S.; Taylor, A. R.; Bullwinkel, E. P.

    1982-11-01

    An experimental development program was conducted to develop and test advanced dielectric materials for capacitors for airborne power systems. High rep rate and low rate capacitors for use in pulse-forming networks, high voltage filter capacitors, and high frequency ac capacitors for series resonant inverters were considered. The initial goal was to develop an improved polysulfone film. Initially, low breakdown strength was thought to be related to inclusions of conductive particles. The effect of filtration of the casting solution was investigated. These experiments showed that more filtration was not the entire solution to low breakdown. The film samples were found to contain dissolved ionic impurities that move through the dielectric when voltage is applied and cause enhancement of the electric field. These contaminants enter the film via the resin and solvent, and can be partially removed. However, these treatments did not significantly improve the breakdown characteristics. A new material, Ultem, was proposed for use in high energy density capacitors. This new polyetherimide resin has properties similar to polysulfone and polyimide, with improvement in breakdown characteristics and temperature capability. The technique of casting films on a roughened drum was demonstrated, and found useful in preparing textured films. this is the first step toward a replacement for kraft paper.

  15. Advanced capacitors

    NASA Astrophysics Data System (ADS)

    Ennis, J. B.; Buritz, R. S.

    1984-10-01

    This report describes an experimental program to develop and test advanced dielectric materials for capacitors for airborne power systems. Five classes of capacitors were considered: high rep rate and low rep rate pulse capacitors for use in pulse-forming networks, high voltage filter capacitors, high frequency AC capacitors for series resonant inverters, and AC filter capacitors. To meet these requirements, existing dielectric materials were modified, and new materials were developed. The initial goal was to develop an improved polysulfone film with fewer imperfections that could operate at significantly higher electrical stresses. It was shown that contaminants enter the film via the resin and solvent, and that they can be partially removed. As far as developed, however, these treatments did not significantly improved the breakdown characteristics. The technique of casting films on a roughened drum was demonstrated, and found useful in preparing textured films -- the first step toward a replacement for Kraft paper. A new material, Ultem, was proposed for use in high energy density capacitors. This new polyetherimide resin has properties similar to polysulfone and polyimide, with improvement in breakdown characteristics and temperature capability. This material was selected for further study in model capacitor designs.

  16. Advanced Manufacture of Reflectors

    SciTech Connect

    Angel, Roger

    2014-12-17

    The main project objective has been to develop an advanced gravity sag method for molding large glass solar reflectors with either line or point focus, and with long or short focal length. The method involves taking standard sized squares of glass, 1.65 m x 1.65 m, and shaping them by gravity sag into precision steel molds. The method is designed for high volume manufacture when incorporated into a production line with separate pre-heating and cooling. The performance objectives for the self-supporting glass mirrors made by this project include mirror optical accuracy of 2 mrad root mean square (RMS), requiring surface slope errors less than 1 mrad rms, a target not met by current production of solar reflectors. Our objective also included development of new methods for rapidly shaping glass mirrors and coating them for higher reflectivity and soil resistance. Reflectivity of 95% for a glass mirror with anti-soil coating was targeted, compared to the present ~94% with no anti-soil coating. Our mirror cost objective is ~$20/m2 in 2020, a significant reduction compared to the present ~$35/m2 for solar trough mirrors produced for trough solar plants.

  17. Advances in cholangiocyte immunobiology

    PubMed Central

    Syal, Gaurav; Fausther, Michel

    2012-01-01

    Cholangiocytes, or bile duct epithelia, were once thought to be the simple lining of the conduit system comprising the intra- and extrahepatic bile ducts. Growing experimental evidence demonstrated that cholangiocytes are in fact the first line of defense of the biliary system against foreign substances. Experimental advances in recent years have unveiled previously unknown roles of cholangiocytes in both innate and adaptive immune responses. Cholangiocytes can release inflammatory modulators in a regulated fashion. Moreover, they express specialized pattern-recognizing molecules that identify microbial components and activate intracellular signaling cascades leading to a variety of downstream responses. The cytokines secreted by cholangiocytes, in conjunction with the adhesion molecules expressed on their surface, play a role in recruitment, localization, and modulation of immune responses in the liver and biliary tract. Cholangiocyte survival and function is further modulated by cytokines and inflammatory mediators secreted by immune cells and cholangiocytes themselves. Because cholangiocytes act as professional APCs via expression of major histocompatibility complex antigens and secrete antimicrobial peptides in bile, their role in response to biliary infection is critical. Finally, because cholangiocytes release mediators critical to myofibroblastic differentiation of portal fibroblasts and hepatic stellate cells, cholangiocytes may be essential in the pathogenesis of biliary cirrhosis. PMID:22961800

  18. Advances in Projection Technology for On-Line Instruction.

    ERIC Educational Resources Information Center

    Davis, H. Scott; Miller, Marsha

    This document consists of supplemental information designed to accompany a presentation on the application of projection technology, including video projectors and liquid crystal display (LCD) devices, in the online catalog library instruction program at the Indiana State University libraries. Following an introductory letter, the packet includes:…

  19. Advanced Turbofan Duct Liner Concepts

    NASA Technical Reports Server (NTRS)

    Bielak, Gerald W.; Premo, John W.; Hersh, Alan S.

    1999-01-01

    The Advanced Subsonic Technology Noise Reduction Program goal is to reduce aircraft noise by 10 EPNdB by the year 2000 relative, to 1992 technology. The improvement goal for nacelle attenuation is 25% relative to 1992 technology by 1997 and 50% by 2000. The Advanced Turbofan Duct Liner Concepts Task work by Boeing presented in this document was in support of these goals. The basis for the technical approach was a Boeing study conducted in 1993-94 under NASA/FAA contract NAS1-19349, Task 6, investigating broadband acoustic liner concepts. As a result of this work, it was recommended that linear double layer, linear and perforate triple layer, parallel element, and bulk absorber liners be further investigated to improve nacelle attenuations. NASA LaRC also suggested that "adaptive" liner concepts that would allow "in-situ" acoustic impedance control also be considered. As a result, bias flow and high-temperature liner concepts were also added to the investigation. The major conclusion from the above studies is that improvements in nacelle liner average acoustic impedance characteristics alone will not result in 25% increased nacelle noise reduction relative to 1992 technology. Nacelle design advancements currently being developed by Boeing are expected to add 20-40% more acoustic lining to hardwall regions in current inlets, which is predicted to result in and additional 40-80% attenuation improvement. Similar advancements are expected to allow 10-30% more acoustic lining in current fan ducts with 10-30% more attenuation expected. In addition, Boeing is currently developing a scarf inlet concept which is expected to give an additional 40-80% attenuation improvement for equivalent lining areas.

  20. High energy beam lines

    NASA Astrophysics Data System (ADS)

    Marchetto, M.; Laxdal, R. E.

    2014-01-01

    The ISAC post accelerator comprises an RFQ, DTL and SC-linac. The high energy beam lines connect the linear accelerators as well as deliver the accelerated beams to two different experimental areas. The medium energy beam transport (MEBT) line connects the RFQ to the DTL. The high energy beam transport (HEBT) line connects the DTL to the ISAC-I experimental stations (DRAGON, TUDA-I, GPS). The DTL to superconducting beam (DSB) transport line connects the ISAC-I and ISAC-II linacs. The superconducting energy beam transport (SEBT) line connects the SC linac to the ISAC-II experimental station (TUDA-II, HERACLES, TIGRESS, EMMA and GPS). All these lines have the function of transporting and matching the beams to the downstream sections by manipulating the transverse and longitudinal phase space. They also contain diagnostic devices to measure the beam properties.

  1. Series Transmission Line Transformer

    DOEpatents

    Buckles, Robert A.; Booth, Rex; Yen, Boris T.

    2004-06-29

    A series transmission line transformer is set forth which includes two or more of impedance matched sets of at least two transmissions lines such as shielded cables, connected in parallel at one end ans series at the other in a cascading fashion. The cables are wound about a magnetic core. The series transmission line transformer (STLT) which can provide for higher impedance ratios and bandwidths, which is scalable, and which is of simpler design and construction.

  2. Nematostatics of triple lines.

    PubMed

    Rey, Alejandro D

    2003-01-01

    The Landau-de Gennes model for nematic liquid crystal bulk and interfaces has been extended to nematic triple lines involving the intersection of two isotropic fluids and one nematic liquid crystalline phase. A complete set of bulk, interface, and triple line force and torque balance equations has been formulated. The triple line force and torque balance equations have linear, interfacial, and bulk contributions. The bulk contributions appear as junction integrals, the surface contributions as junctions sums, and the line contributions as gradients of stresses. Reduction of dimensionality from three to one dimensional creates the following effects: (a) bulk terms enter interfacial balances as surface jumps and line balances as junction integrals, and (b) surface terms enter linear balances as junction sums. Line stress and torque equations are derived using classical liquid crystal models. The correspondence between line stress and line torque and their surface and bulk analogs is established. The triple line force and torque balance equations are use to analyze the contact angle in a nematic lens lying at the interface between two isotropic fluids, when the preferred surface orientation is tangential. The effect of anisotropy and long range elasticity on triple line phases is established. Under weak anchoring the contact angle is shown to be a function of the anchoring energy at the nematic-isotropic interface, while under strong anchoring conditions the contact angle is a function of the Peach-Koehler force that originates from bulk long range elasticity and acts on the triple line. The use of the complete set of balance equations removes the classical inconsistency in force balances at a contact line by properly taking into account long range (bulk gradient elasticity) and anisotropic (interfacial anchoring elasticity) effects.

  3. Dental operatory water lines.

    PubMed

    Beierle, J W

    1993-02-01

    Water samples were collected from dental handpiece and air-water syringe lines at various times during the day and cultured for the presence and prevalence of various microbes. It was found that the longer a dental unit was out of use, the greater the microbial build-up in water lines. However, purging lines for two to three minutes at the start of the day and between patients significantly reduced microbial presence.

  4. Advanced Motors

    SciTech Connect

    Knoth, Edward A; Chelluri, Bhanumathi; Schumaker, Edward J

    2012-12-14

    vProject Summary Transportation energy usage is predicted to increase substantially by 2020. Hybrid vehicles and fuel cell powered vehicles are destined to become more prominent as fuel prices rise with the demand. Hybrid and fuel cell vehicle platforms are both dependent on high performance electric motors. Electric motors for transportation duty will require sizeable low-speed torque to accelerate the vehicle. As motor speed increases, the torque requirement decreases which results in a nearly constant power motor output. Interior permanent magnet synchronous motors (IPMSM) are well suited for this duty. , , These rotor geometries are configured in straight lines and semi circular arc shapes. These designs are of limited configurations because of the lack of availability of permanent magnets of any other shapes at present. We propose to fabricate rotors via a novel processing approach where we start with magnet powders and compact them into a net shape rotor in a single step. Using this approach, widely different rotor designs can be implemented for efficiency. The current limitation on magnet shape and thickness will be eliminated. This is accomplished by co-filling magnet and soft iron powders at specified locations in intricate shapes using specially designed dies and automatic powder filling station. The process fundamentals for accomplishing occurred under a previous Applied Technology Program titled, Motors and Generators for the 21st Century. New efficient motor designs that are not currently possible (or cost prohibitive) can be accomplished by this approach. Such an approach to motor fabrication opens up a new dimension in motor design. Feasibility Results We were able to optimize a IPMSM rotor to take advantage of the powder co-filling and DMC compaction processing methods. The minimum low speed torque requirement of 5 N-m can be met through an optimized design with magnet material having a Br capability of 0.2 T. This level of magnetic performance can

  5. SCIENCE BRIEF: ADVANCED CONCEPTS

    EPA Science Inventory

    Research on advanced concepts will evaluate and demonstrate the application of innovative infrastructure designs, management procedures and operational approaches. Advanced concepts go beyond simple asset management. The infusion of these advanced concepts into established wastew...

  6. Tangent Lines without Calculus

    ERIC Educational Resources Information Center

    Rabin, Jeffrey M.

    2008-01-01

    This article presents a problem that can help high school students develop the concept of instantaneous velocity and connect it with the slope of a tangent line to the graph of position versus time. It also gives a method for determining the tangent line to the graph of a polynomial function at any point without using calculus. (Contains 1 figure.)

  7. Airborne Fraunhofer Line Discriminator

    NASA Technical Reports Server (NTRS)

    Gabriel, F. C.; Markle, D. A.

    1969-01-01

    Airborne Fraunhofer Line Discriminator enables prospecting for fluorescent materials, hydrography with fluorescent dyes, and plant studies based on fluorescence of chlorophyll. Optical unit design is the coincidence of Fraunhofer lines in the solar spectrum occurring at the characteristic wavelengths of some fluorescent materials.

  8. Line of Contact.

    ERIC Educational Resources Information Center

    Miller, Sue Ellen

    1988-01-01

    Teachers and coaches can help tennis players develop accuracy in the forehand and backhand strokes by using the "straight line" or "flattened arc" concept. The four elements essential to proper execution of these strokes are explained, and drawings are provided which demonstrate the straight line concept. (IAH)

  9. Attachment Line Blockage Models

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Photographs shows the attachment-line experiment model with fairing and fence for supersonic attachment-line experiments. The fairing is intended to eliminate the wing/fuselage juncture shock and align the flow for the streamlined fence. The streamlined fence traps the turbulent fuselage boundary layer to prevent turbulent contamination of the leading edge flow.

  10. Transmission Line Security Monitor

    SciTech Connect

    2011-01-01

    The Transmission Line Security Monitor is a multi-sensor monitor that mounts directly on high-voltage transmission lines to detect, characterize and communicate terrorist activity, human tampering and threatening conditions around support towers. For more information about INL's critical infrastructure protection research, visit http://www.facebook.com/idahonationallaboratory.

  11. Transmission Line Security Monitor

    ScienceCinema

    None

    2016-07-12

    The Transmission Line Security Monitor is a multi-sensor monitor that mounts directly on high-voltage transmission lines to detect, characterize and communicate terrorist activity, human tampering and threatening conditions around support towers. For more information about INL's critical infrastructure protection research, visit http://www.facebook.com/idahonationallaboratory.

  12. Database of emission lines

    NASA Astrophysics Data System (ADS)

    Binette, L.; Ortiz, P.; Joguet, B.; Rola, C.

    1998-11-01

    A widely accessible data bank (available through Netscape) and consiting of all (or most) of the emission lines reported in the litterature is being built. It will comprise objects as diverse as HII regions, PN, AGN, HHO. One of its use will be to define/refine existing diagnostic emission line diagrams.

  13. A general modeling framework for genome ancestral origins in multiparental populations.

    PubMed

    Zheng, Chaozhi; P Boer, Martin; van Eeuwijk, Fred A

    2014-09-01

    The next generation of QTL (quantitative trait loci) mapping populations have been designed with multiple founders, where one to a number of generations of intercrossing are introduced prior to the inbreeding phase to increase accumulated recombinations and thus mapping resolution. Examples of such populations are Collaborative Cross (CC) in mice and Multiparent Advanced Generation Inter-Cross (MAGIC) lines in Arabidopsis. The genomes of the produced inbred lines are fine-grained random mosaics of the founder genomes. In this article, we present a novel framework for modeling ancestral origin processes along two homologous autosomal chromosomes from mapping populations, which is a major component in the reconstruction of the ancestral origins of each line for QTL mapping. We construct a general continuous time Markov model for ancestral origin processes, where the rate matrix is deduced from the expected densities of various types of junctions (recombination breakpoints). The model can be applied to monoecious populations with or without self-fertilizations and to dioecious populations with two separate sexes. The analytic expressions for map expansions and expected junction densities are obtained for mapping populations that have stage-wise constant mating schemes, such as CC and MAGIC. Our studies on the breeding design of MAGIC populations show that the intercross mating schemes do not matter much for large population size and that the overall expected junction density, and thus map resolution, are approximately proportional to the inverse of the number of founders.

  14. ADVANCED DEHYDRATOR DESIGN SAVES GAS AND REDUCES HAP EMISSIONS

    EPA Science Inventory

    Glycol dehydrators remove water from gas pipe lines. An advanced dehydrator by Engineered Concepts, Farmington, NM, saves a significant amount of gas, while reducing hazardous air pollutants, volatile organic compounds and CO2 air pollutants

  15. Marketing Potential of Advanced Breeding Clones

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The accumulation of reducing sugars during cold storage of potato tubers is a serious and costly problem for producers and processors. The degree to which cultivars accumulate reducing sugars during storage determines their processing and market potential. Cultivars or advanced breeding lines with...

  16. Marketing potential of advanced breeding clones

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The accumulation of reducing sugars during cold storage of potato tubers is a serious and costly problem for producers and processors. The degree to which cultivars accumulate reducing sugars during storage determines their processing and market potential. Cultivars or advanced breeding lines with...

  17. Hybrid mesh generation using advancing reduction technique

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study presents an extension of the application of the advancing reduction technique to the hybrid mesh generation. The proposed algorithm is based on a pre-generated rectangle mesh (RM) with a certain orientation. The intersection points between the two sets of perpendicular mesh lines in RM an...

  18. Advances in targeted genome editing.

    PubMed

    Perez-Pinera, Pablo; Ousterout, David G; Gersbach, Charles A

    2012-08-01

    New technologies have recently emerged that enable targeted editing of genomes in diverse systems. This includes precise manipulation of gene sequences in their natural chromosomal context and addition of transgenes to specific genomic loci. This progress has been facilitated by advances in engineering targeted nucleases with programmable, site-specific DNA-binding domains, including zinc finger proteins and transcription activator-like effectors (TALEs). Recent improvements have enhanced nuclease performance, accelerated nuclease assembly, and lowered the cost of genome editing. These advances are driving new approaches to many areas of biotechnology, including biopharmaceutical production, agriculture, creation of transgenic organisms and cell lines, and studies of genome structure, regulation, and function. Genome editing is also being investigated in preclinical and clinical gene therapies for many diseases.

  19. How Water Advances on Superhydrophobic Surfaces

    NASA Astrophysics Data System (ADS)

    Schellenberger, Frank; Encinas, Noemí; Vollmer, Doris; Butt, Hans-Jürgen

    2016-03-01

    Superliquid repellency can be achieved by nano- and microstructuring surfaces in such a way that protrusions entrap air underneath the liquid. It is still not known how the three-phase contact line advances on such structured surfaces. In contrast to a smooth surface, where the contact line can advance continuously, on a superliquid-repellent surface, the contact line has to overcome an air gap between protrusions. Here, we apply laser scanning confocal microscopy to get the first microscopic videos of water drops advancing on a superhydrophobic array of micropillars. In contrast to common belief, the liquid surface gradually bends down until it touches the top face of the next micropillars. The apparent advancing contact angle is 180°. On the receding side, pinning to the top faces of the micropillars determines the apparent receding contact angle. Based on these observations, we propose that the apparent receding contact angle should be used for characterizing superliquid-repellent surfaces rather than the apparent advancing contact angle and hysteresis.

  20. Coherent soliton communication lines

    SciTech Connect

    Yushko, O. V. Redyuk, A. A.; Fedoruk, M. P.; Turitsyn, S. K.

    2014-11-15

    The data transmission in coherent fiber-optical communication lines using solitons with a variable phase is studied. It is shown that nonlinear coherent structures (solitons) can be applied for effective signal transmission over a long distance using amplitude and optical-phase keying of information. The optimum ratio of the pulse width to the bit slot at which the spectral efficiency (transmitted bits per second and hertz) is maximal is determined. It is shown that soliton fiber-optical communication lines can ensure data transmission at a higher spectral efficiency as compared to traditional communication lines and at a high signal-to-noise ratio.

  1. Flow line sampler

    DOEpatents

    Nicholls, Colin I.

    1992-07-14

    An on-line product sampling apparatus and method for measuring product samples from a product stream (12) in a flow line (14) having a sampling aperture (11), includes a sampling tube (18) for containing product samples removed from flow line (14). A piston (22) removes product samples from the product stream (12) through the sampling aperture (11) and returns samples to product stream (12). A sensor (20) communicates with sample tube (18), and senses physical properties of samples while the samples are within sample tube (18). In one embodiment, sensor (20) comprises a hydrogen transient nuclear magnetic resonance sensor for measuring physical properties of hydrogen molecules.

  2. Enamel craze lines.

    PubMed

    Larson, Thomas D

    2014-01-01

    Enamel craze lines are a common clinical finding, especially in older patients and in patients who brux. These craze lines frequently are discolored and may present as clear in color, grey, or brown. The clinical question is, when do enamel craze lines need restoration and when should we leave them untreated? This review will look at enamel structure and the effects of occlusion, bruxing, temperature, and restorations on enamel structure. Recommendations will be made on how and when to deal with these cosmetic defects of enamel.

  3. Challenges of advanced hepatocellular carcinoma.

    PubMed

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-09-14

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

  4. Challenges of advanced hepatocellular carcinoma

    PubMed Central

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-01-01

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials.

  5. Challenges of advanced hepatocellular carcinoma

    PubMed Central

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-01-01

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

  6. Line, Shape, Color.

    ERIC Educational Resources Information Center

    Greenman, Geri

    2002-01-01

    Describes an art project used with beginning high school art students that teaches them about continuous line drawing. Explains that the students create portraits of themselves, or another student, using glue, black construction paper, and chalk. (CMK)

  7. Illustrating the Euler Line.

    ERIC Educational Resources Information Center

    Rubillo, James M.

    1987-01-01

    Euler's discovery about the centroid of a triangle trisecting the line segment joining its circumference to its orthocenter is discussed. An activity that will help students review fundamental concepts is included. (MNS)

  8. IRIS Spectrum Line Plot

    NASA Video Gallery

    This video shows a line plot of the spectrum. The spectra here are shown for various locations on the Sun. The changes in the movie are caused by differing physical conditions in the locations. Cre...

  9. Power line detection system

    DOEpatents

    Latorre, Victor R.; Watwood, Donald B.

    1994-01-01

    A short-range, radio frequency (RF) transmitting-receiving system that provides both visual and audio warnings to the pilot of a helicopter or light aircraft of an up-coming power transmission line complex. Small, milliwatt-level narrowband transmitters, powered by the transmission line itself, are installed on top of selected transmission line support towers or within existing warning balls, and provide a continuous RF signal to approaching aircraft. The on-board receiver can be either a separate unit or a portion of the existing avionics, and can also share an existing antenna with another airborne system. Upon receipt of a warning signal, the receiver will trigger a visual and an audio alarm to alert the pilot to the potential power line hazard.

  10. Power line detection system

    DOEpatents

    Latorre, V.R.; Watwood, D.B.

    1994-09-27

    A short-range, radio frequency (RF) transmitting-receiving system that provides both visual and audio warnings to the pilot of a helicopter or light aircraft of an up-coming power transmission line complex. Small, milliwatt-level narrowband transmitters, powered by the transmission line itself, are installed on top of selected transmission line support towers or within existing warning balls, and provide a continuous RF signal to approaching aircraft. The on-board receiver can be either a separate unit or a portion of the existing avionics, and can also share an existing antenna with another airborne system. Upon receipt of a warning signal, the receiver will trigger a visual and an audio alarm to alert the pilot to the potential power line hazard. 4 figs.

  11. Veterans Crisis Line

    MedlinePlus

    ... also access and download the Veterans Crisis Line Branding Guidelines for guidance on how to consistently apply ... Program ADMINISTRATION Veterans Health Administration Veterans Benefits Administration National Cemetery Administration U.S. Department of Veterans Affairs | 810 ...

  12. PORTION OF A LINE (AT LEFT) AND B LINE (AT ...

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

    PORTION OF A LINE (AT LEFT) AND B LINE (AT RIGHT) ON GENTLE TERRACE SLOPE. A LINE POLE 75A (LEFT FOREGROUND) HAS ORIGINAL GLASS PIN-TYPE INSULATORS AND INTACT COMMUNICATION LINE CROSS ARM. VIEW TO WEST-SOUTHWEST. - Mystic Lake Hydroelectric Facility, Electric Transmission A Line, Along West Rosebud Creek, Fishtail, Stillwater County, MT

  13. On-Line and Off-Line Assessment of Metacognition

    ERIC Educational Resources Information Center

    Saraç, Seda; Karakelle, Sema

    2012-01-01

    The study investigates the interrelationships between different on-line and off-line measures for assessing metacognition. The participants were 47 fifth grade elementary students. Metacognition was assessed through two off-line and two on-line measures. The off-line measures consisted of a teacher rating scale and a self-report questionnaire. The…

  14. The ECLSS Advanced Automation Project Evolution and Technology Assessment

    NASA Technical Reports Server (NTRS)

    Dewberry, Brandon S.; Carnes, James R.; Lukefahr, Brenda D.; Rogers, John S.; Rochowiak, Daniel M.; Mckee, James W.; Benson, Brian L.

    1990-01-01

    Viewgraphs on Environmental Control and Life Support System (ECLSS) advanced automation project evolution and technology assessment are presented. Topics covered include: the ECLSS advanced automation project; automatic fault diagnosis of ECLSS subsystems descriptions; in-line, real-time chemical and microbial fluid analysis; and object-oriented, distributed chemical and microbial modeling of regenerative environmental control systems description.

  15. CellLineNavigator: a workbench for cancer cell line analysis.

    PubMed

    Krupp, Markus; Itzel, Timo; Maass, Thorsten; Hildebrandt, Andreas; Galle, Peter R; Teufel, Andreas

    2013-01-01

    The CellLineNavigator database, freely available at http://www.medicalgenomics.org/celllinenavigator, is a web-based workbench for large scale comparisons of a large collection of diverse cell lines. It aims to support experimental design in the fields of genomics, systems biology and translational biomedical research. Currently, this compendium holds genome wide expression profiles of 317 different cancer cell lines, categorized into 57 different pathological states and 28 individual tissues. To enlarge the scope of CellLineNavigator, the database was furthermore closely linked to commonly used bioinformatics databases and knowledge repositories. To ensure easy data access and search ability, a simple data and an intuitive querying interface were implemented. It allows the user to explore and filter gene expression, focusing on pathological or physiological conditions. For a more complex search, the advanced query interface may be used to query for (i) differentially expressed genes; (ii) pathological or physiological conditions; or (iii) gene names or functional attributes, such as Kyoto Encyclopaedia of Genes and Genomes pathway maps. These queries may also be combined. Finally, CellLineNavigator allows additional advanced analysis of differentially regulated genes by a direct link to the Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resources.

  16. Line Lengths and Starch Scores.

    ERIC Educational Resources Information Center

    Moriarty, Sandra E.

    1986-01-01

    Investigates readability of different line lengths in advertising body copy, hypothesizing a normal curve with lower scores for shorter and longer lines, and scores above the mean for lines in the middle of the distribution. Finds support for lower scores for short lines and some evidence of two optimum line lengths rather than one. (SKC)

  17. Dynamics of the Molten Contact Line

    NASA Technical Reports Server (NTRS)

    Sonin, Ain A.; Schiaffino, Stefano

    1996-01-01

    In contrast to the ordinary contact line problem, virtually no information is available on the similar problem associated with a molten material spreading on a solid which is below the melt's fusion point. The latter is a more complex problem which heat transfer and solidification take place simultaneously with spreading, and requires answers not only for the hot melt's advance speed over the cold solid as a function of contact angle, but also for how one is to predict the point of the molten contact line's arrest by freezing. This issues are of importance in evolving methods of materials processing. The purpose of our work is to develop, based on both experiments and theory, an understanding of the dynamic processes that occur when a molten droplet touches a subcooled solid, spreads partly over it by capillary action, and freezes. We seek answers to the following basic questions. First, what is the relationship between the melt's contact line speed and the apparent (dynamic) contact angle? Secondly, at what point will the contact line modon be arrested by freezing? The talk will describe three components of our work: (1) deposition experiments with small molten droplets; (2) investigation of the dynamics of the molten contact line by means of a novel forced spreading method; and (3) an attempt to provide a theoretical framework for answering the basic questions posed above.

  18. Long line coupling models.

    SciTech Connect

    Warne, Larry Kevin; Chen, Kenneth C.

    2004-03-01

    This report assembles models for the response of a wire interacting with a conducting ground to an electromagnetic pulse excitation. The cases of an infinite wire above the ground as well as resting on the ground and buried beneath the ground are treated. The focus is on the characteristics and propagation of the transmission line mode. Approximations are used to simplify the description and formulas are obtained for the current. The semi-infinite case, where the short circuit current can be nearly twice that of the infinite line, is also examined.

  19. Pipe Line Control

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The array of tanks, pipes and valves in the photo below is a petroleum tank farm in Georgia, part of a petrochemical pipe line system that moves refined petroleum products from Texas and Louisiana to the mid-Eastern seaboard. The same pipes handle a number of different products, such as gasoline, kerosene, jet fuel or fuel oil. The fluids are temporarily stored in tanks, pumped into the pipes in turn and routed to other way stations along the pipe line. The complex job of controlling, measuring and monitoring fuel flow is accomplished automatically by a computerized control and communications system which incorporates multiple space technologies.

  20. Advanced Electrophysiologic Mapping Systems

    PubMed Central

    2006-01-01

    Executive Summary Objective To assess the effectiveness, cost-effectiveness, and demand in Ontario for catheter ablation of complex arrhythmias guided by advanced nonfluoroscopy mapping systems. Particular attention was paid to ablation for atrial fibrillation (AF). Clinical Need Tachycardia Tachycardia refers to a diverse group of arrhythmias characterized by heart rates that are greater than 100 beats per minute. It results from abnormal firing of electrical impulses from heart tissues or abnormal electrical pathways in the heart because of scars. Tachycardia may be asymptomatic, or it may adversely affect quality of life owing to symptoms such as palpitations, headaches, shortness of breath, weakness, dizziness, and syncope. Atrial fibrillation, the most common sustained arrhythmia, affects about 99,000 people in Ontario. It is associated with higher morbidity and mortality because of increased risk of stroke, embolism, and congestive heart failure. In atrial fibrillation, most of the abnormal arrhythmogenic foci are located inside the pulmonary veins, although the atrium may also be responsible for triggering or perpetuating atrial fibrillation. Ventricular tachycardia, often found in patients with ischemic heart disease and a history of myocardial infarction, is often life-threatening; it accounts for about 50% of sudden deaths. Treatment of Tachycardia The first line of treatment for tachycardia is antiarrhythmic drugs; for atrial fibrillation, anticoagulation drugs are also used to prevent stroke. For patients refractory to or unable to tolerate antiarrhythmic drugs, ablation of the arrhythmogenic heart tissues is the only option. Surgical ablation such as the Cox-Maze procedure is more invasive. Catheter ablation, involving the delivery of energy (most commonly radiofrequency) via a percutaneous catheter system guided by X-ray fluoroscopy, has been used in place of surgical ablation for many patients. However, this conventional approach in catheter ablation

  1. An Energy-Stabilized Varied-Line-Space-Monochromator UndulatorBeam Line for PEEM Illumination and Magnetic Circular Dichroism

    SciTech Connect

    Warwick, Tony; McKinney, Wayne; Domning, Ed; Doran, Andrew; Padmore, Howard

    2006-06-01

    A new undulator beam line has been built and commissioned at the Advanced Light Source for illumination of the PEEM3 microscope. The beam line delivers high flux beams over an energy range from C1s through the transition metals to include the M edges of the magnetic rare earth elements. We present details of the optical design, and data on the performance of the zero-order tracking of the photon energy.

  2. PORTION OF A LINE (LEFT) AND B LINE (RIGHT) ON ...

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

    PORTION OF A LINE (LEFT) AND B LINE (RIGHT) ON STEEP, ROCKY SLOPE. A LINE POLE 20 (LEFT BACKGROUND) HAS ORIGINAL GLASS PIN-TYPE INSULATORS. VIEW TO SOUTHEAST. - Mystic Lake Hydroelectric Facility, Electric Transmission A Line, Along West Rosebud Creek, Fishtail, Stillwater County, MT

  3. Microwave spectral line listing

    NASA Technical Reports Server (NTRS)

    White, W. F., Jr.

    1975-01-01

    The frequency, intensity, and identification of 9615 spectral lines belonging to 75 molecules are tabulated in order of increasing frequency. Measurements for all 75 molecules were made in the frequency range from 26500 to 40000 MHz by a computer controlled spectrometer. Measurements were also made in the 18000 to 26500 MHz range for some of the molecules.

  4. Line Replaceable Unit Analysis

    NASA Technical Reports Server (NTRS)

    Oepomo, T.; Prouty, T. V.

    1982-01-01

    Shuttle LRU (Line Replaceable Unit) Analysis Program (SLAP) aids in evaluation of LRU interface voltages in Shuttle orbiter electrical system. Slap includes reduced model of Shuttle LRU circuit. Although primarily intended for analysis of Shuttle LRU's SLAP could be adapted for voltage analysis in other situations.

  5. Straight Line Graphs

    ERIC Educational Resources Information Center

    Krueger, Tom

    2010-01-01

    In this article, the author shares one effective lesson idea on straight line graphs that he applied in his lower ability Y9 class. The author wanted something interesting for his class to do, something that was fun and engaging with direct feedback, and something that worked because someone else had tried it before. In a word, the author admits…

  6. Building with a Line

    ERIC Educational Resources Information Center

    Hubbert, Beth

    2011-01-01

    Architecture is a versatile, multifaceted area to study in the artroom with multiple age levels. It can easily stimulate a study of basic line, shape, and various other art elements and principles. It can then be extended into a more extensive study of architectural elements, styles, specific architects, architecture of different cultures, and…

  7. Control line sealing connection

    SciTech Connect

    Tohill, H.O.

    1984-07-10

    A sealing connection for the passage of a fluid control line through adjoining members is claimed. The connection comprises a metallic tubular sealing element provided with tapered end portions, each end having internal frusto-conical surfaces and external frusto-conical surfaces in coaxial alignment with the bore through the element. The external frusto-conical surfaceas provide metal-to-metal sealing with aligned frusto-conical seating surfaces in opposed pockets formed in aligned portions of the control line at their respective openings at the adjoining surfaces of the adjoined member. The tubular sealing element is subjected to axial compression between the frusto-conical pocket seating surfaces when the adjoined members are bolted tightly together which results in deformation of its tapered end portions to provide metal-to-metal sealing with the adjoined members which is effective to seal against both internal and external fluid pressurization of the control line and without internally obstructing or restricting the control line. Secondary sealing is provided by elastomeric O-ring seals mounted in circumferential annular grooves formed in the exterior of the tubular sealing element.

  8. The Front Line.

    ERIC Educational Resources Information Center

    Unks, Gerald

    1979-01-01

    The author draws an analogy between today's school system and an assembly line, deploring the notion that all children are taught the same thing at the same time, ending in humiliation, disgrace, and failure for some, and nonchallenging academic activities for others. (KC)

  9. On-Line Cataloging.

    ERIC Educational Resources Information Center

    OCLC Online Computer Library Center, Inc., Dublin, OH.

    The principal objective of the Ohio College Library Center is to lower the rate of rise of per-unit library costs while increasing the availability of library resources for use by patrons of participating libraries. A major procedural goal of the on-line cataloging system is to furnish cataloging personnel in individual libraries with…

  10. Columnar lined Barrett's oesophagus.

    PubMed

    Sharma, Neel; Ho, Khek Yu

    2015-12-01

    Over the past few years, the definition of Barrett's oesophagus has altered with no real agreement on histological understanding. This article highlights the increasing confusion regarding Barrett's oesophagus with a focus on the all-too-frequently ignored aspect of the columnar lined oesophagus.

  11. Advanced planetary studies

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Results of planetary advanced studies and planning support are summarized. The scope of analyses includes cost estimation research, planetary mission performance, penetrator advanced studies, Mercury mission transport requirements, definition of super solar electric propulsion/solar sail mission discriminators, and advanced planning activities.

  12. Advances in recombinant antibody manufacturing.

    PubMed

    Kunert, Renate; Reinhart, David

    2016-04-01

    Since the first use of Chinese hamster ovary (CHO) cells for recombinant protein expression, production processes have steadily improved through numerous advances. In this review, we have highlighted several key milestones that have contributed to the success of CHO cells from the beginning of their use for monoclonal antibody (mAb) expression until today. The main factors influencing the yield of a production process are the time to accumulate a desired amount of biomass, the process duration, and the specific productivity. By comparing maximum cell densities and specific growth rates of various expression systems, we have emphasized the limiting parameters of different cellular systems and comprehensively described scientific approaches and techniques to improve host cell lines. Besides the quantitative evaluation of current systems, the quality-determining properties of a host cell line, namely post-translational modifications, were analyzed and compared to naturally occurring polyclonal immunoglobulin fractions from human plasma. In summary, numerous different expression systems for mAbs are available and also under scientific investigation. However, CHO cells are the most frequently investigated cell lines and remain the workhorse for mAb production until today.

  13. Advanced midwifery practice or advancing midwifery practice?

    PubMed

    Smith, Rachel; Leap, Nicky; Homer, Caroline

    2010-09-01

    Advanced midwifery practice is a controversial notion in midwifery, particularly at present in Australia. The proposed changes in legislation around access to the publicly funded Medical Benefits Scheme (MBS) and the Pharmaceutical Benefits Scheme (PBS) in 2009-2010 have meant that the issue of advanced midwifery practice has again taken prominence. Linking midwifery access to MBS and PBS to a safety and quality framework that includes an 'advanced midwifery credentialling framework' is particularly challenging. The Haxton and Fahy paper in the December 2009 edition of Women and Birth is timely as it enables a reflection upon these issues and encourages debate and discussion about exactly what is midwifery, what are we educating our students for and is working to the full scope of practice practising at advanced level? This paper seeks to address some of these questions and open up the topic for further debate.

  14. The Bicycle Assembly Line Game

    ERIC Educational Resources Information Center

    Klotz, Dorothy

    2011-01-01

    "The Bicycle Assembly Line Game" is a team-based, in-class activity that helps students develop a basic understanding of continuously operating processes. Each team of 7-10 students selects one of seven prefigured bicycle assembly lines to operate. The lines are run in real-time, and the team that operates the line that yields the…

  15. A Quantitative Transmission Line Experiment

    ERIC Educational Resources Information Center

    Johnston, D. C.; Silbernagel, B. G.

    1969-01-01

    Describes modifications of a commercially available strip-type transmission line, which makes possible reproducible measurements of standing waves on the line. Experimental data yield values for the characteristic impedance, phase velocity and line wavelength of radiation in the transmission line, and the dielectric constant of material in the…

  16. New line of high efficiency turbochargers

    SciTech Connect

    Chellini, R,

    1994-11-01

    The French firm Hispano Suiza has recently introduced the first of a new family of high-efficiency turbochargers. The design objectives for these turbochargers is to combine the most advanced technology in both the compressor and turbine components. The HS 5800 New Generation Turbocharger is suited for diesel engines in the 1700-3000 kW power range for a single turbocharger unit. When the HS 4800 and HS 6800 sizes are introduced the line will cover a range of engines from 1200 to 9000 kW. 5 figs.

  17. The fault lines of academic medicine.

    PubMed

    Schafer, Andrew I

    2002-01-01

    Unprecedented advances in biomedical research and the upheaval in health care economics have converged to cause seismic changes in the traditional organization of medical schools and academic health centers. This process is particularly evident in departments of internal medicine. The activities and functions of academic medicine are in the midst of separation and realignment along lines that do not honor historical departmental and divisional boundaries. The organization of a successful medical school or department must be dynamic, constantly serving its constituents to accommodate progress and change and to promote optimal structure for academic productivity.

  18. Printed circuit dispersive transmission line

    DOEpatents

    Ikezi, H.; Lin-Liu, Y.R.; DeGrassie, J.S.

    1991-08-27

    A printed circuit dispersive transmission line structure is disclosed comprising an insulator, a ground plane formed on one surface of the insulator, a first transmission line formed on a second surface of the insulator, and a second transmission line also formed on the second surface of the insulator and of longer length than the first transmission line and periodically intersecting the first transmission line. In a preferred embodiment, the transmission line structure exhibits highly dispersive characteristics by designing the length of one of the transmission line between two adjacent periodic intersections to be longer than the other. 5 figures.

  19. Printed circuit dispersive transmission line

    DOEpatents

    Ikezi, Hiroyuki; Lin-Liu, Yuh-Ren; DeGrassie, John S.

    1991-01-01

    A printed circuit dispersive transmission line structure is disclosed comprising an insulator, a ground plane formed on one surface of the insulator, a first transmission line formed on a second surface of the insulator, and a second transmission line also formed on the second surface of the insulator and of longer length than the first transmission line and periodically intersecting the first transmission line. In a preferred embodiment, the transmission line structure exhibits highly dispersive characteristics by designing the length of one of the transmission line between two adjacent periodic intersections to be longer than the other.

  20. Coolant line hydrometer

    SciTech Connect

    Barber, M.D.; Kipp, W.G.

    1987-03-17

    This patent describes a hydrometer unit for connection in an automobile coolant flow line comprising: a tubular fitting adapted to be connected to the coolant flow line; a coolant receiving chamber means connected to the tubular fitting for receiving coolant from the tubular fitting; and indicating float elements contained within the coolant receiving chamber means and adapted to rise therein individually as a function of the specific gravity of the coolant. The coolant receiving chamber means includes a closure cap which when connected to the tubular fitting forms a coolant receiving chamber, retaining means for retaining the indicating float elements within the coolant receiving chamber, a viewing window member of a substantially clear material through which the float elements can be visually observed within the coolant receiving chamber means, and air venturi means located within the coolant receiving chamber means for automatically removing air which may collect within the coolant chamber means.

  1. CRUCIBLE LINING METHOD

    DOEpatents

    Bone, W.H.; Schmidt, W.W.

    1958-11-01

    A method is presented for forming refractory liners in cylindrical reaction vessels used for the reductlon of uranium tetrafluoride to metallic uranium. A preliminary form, having positioning lugs attached thereto, is inserted into the reaction vessel and the refractory powder, usually CaO, is put in the annular space between the form and the inner wall of the reaction vessel. A jolting table is used to compact this charge of liner material ln place, and after thls has been done, the preliminary form is removed and the flnal form or plug is lnserted without disturbing the partially completed lining. The remainder of the lining charge is then introduced and compacted by jolting, after which the form is removed.

  2. Drill string transmission line

    DOEpatents

    Hall, David R.; Hall, Jr., H. Tracy; Pixton, David S.; Bradford, Kline; Fox, Joe

    2006-03-28

    A transmission line assembly for transmitting information along a downhole tool comprising a pin end, a box end, and a central bore traveling between the pin end and the box end, is disclosed in one embodiment of the invention as including a protective conduit. A transmission line is routed through the protective conduit. The protective conduit is routed through the central bore and the ends of the protective conduit are routed through channels formed in the pin end and box end of the downhole tool. The protective conduit is elastically forced into a spiral or other non-linear path along the interior surface of the central bore by compressing the protective conduit to a length within the downhole tool shorter than the protective conduit.

  3. Approximate line shapes for hydrogen

    NASA Technical Reports Server (NTRS)

    Sutton, K.

    1978-01-01

    Two independent methods are presented for calculating radiative transport within hydrogen lines. In Method 1, a simple equation is proposed for calculating the line shape. In Method 2, the line shape is assumed to be a dispersion profile and an equation is presented for calculating the half half-width. The results obtained for the line shapes and curves of growth by the two approximate methods are compared with similar results using the detailed line shapes by Vidal et al.

  4. Line managers as marketers.

    PubMed

    Rynne, T J

    1986-09-01

    Many hospital administrators and boards of directors, having overcome their initial opposition to advertising and hired a marketing professional, are wondering why their marketing programs have not accomplished all that they had hoped. The answer lies in their perception of who is responsible for marketing. Marketing is not a specialty separate from the disciplines of management--it is a basic management skill. Its goal is to satisfy the customer by providing products and services that meet the customer's needs, wants, and preferences. Line managers must understand the hospital's customers and make the critical day-to-day differences in satisfying them. They are the hospital's front-line marketers, and the marketing department's role is to support them in this function. The marketing department should develop the line managers' marketing skills by furnishing them with the appropriate tools: formats, models, examples, and instructions. In addition, the marketing staff should provide such specialized services as marketing research, ad agency management, and development of communications. PMID:10277616

  5. Relativistic Iron Line Fits

    NASA Astrophysics Data System (ADS)

    Fink, M.; Dauser, T.; Beuchert, T.; Jeffreson, S.; Tawabutr, J.; Wilms, J.; García, J.; Walton, D. J.

    2016-08-01

    The 6.4 keV Iron reflection line possesses strong diagnostic potential for AGN-systems. In the rare case of unobscured AGN, this line receives a contribution from the very center of the accretion flow close to the event horizon that is subject to strong relativistic effects. The shape of this line distortion can be used infer important parameters of the central accretion region, especially the black hole spin parameter a* and the accretion disk inclination i. We analyze several (nine?) bare AGN spectra from the sample of Walton et al. 2012 using high resolution spectra from the XMM and NuStar archives. The relativistic reflection is modeled using the RELXILL code (Dauser 20XX). The newest iteration of the RELXILL model also supports a lamp post geometry for the irradiation of the accretion disk. By combining these detailed models with the wide spectral range of NuStar and XMM/NuStar joint observations we can put tight constraints on the aforementioned parameters and we can constrain the height of the source h in a possible lamp post geometry.

  6. Sleep, Off-Line Processing, and Vocal Learning

    ERIC Educational Resources Information Center

    Margoliash, Daniel; Schmidt, Marc F.

    2010-01-01

    The study of song learning and the neural song system has provided an important comparative model system for the study of speech and language acquisition. We describe some recent advances in the bird song system, focusing on the role of off-line processing including sleep in processing sensory information and in guiding developmental song…

  7. Humanities On (the) line: Classrooms, Space, and the Supplement.

    ERIC Educational Resources Information Center

    Nunes, Mark

    New technological advances, in particular the Internet, can alter the architectural limits that restrict education by providing "lines of flight" outside of traditional structures. For example, students can access a library catalogue using computers in class, rather than actually having to go as a class to the library. In a computer-assisted…

  8. Platte pipe line, built in 50s, exceeded founders' dreams

    SciTech Connect

    Not Available

    1984-05-01

    This is a short paper on the history and development of the Platte Pipe Line which stretches 1156 miles from Byron, Wyoming, to Wood River, Illinois. It discusses the development and significance of one of the most used crude oil pipelines in the United States. It also discusses its role in advanced pipeline control technology and the future of the system.

  9. ON-LINE TOXICITY MONITORS AND WATERSHED EARLY WARNING SYSTEMS

    EPA Science Inventory

    A Water Quality Early Warning System using On-line Toxicity Monitors (OTMs) has been deployed in the East Fork of the Little Miami River, Clermont County, OH. Living organisms have long been used to determine the toxicity of environmental samples. With advancements in electronic ...

  10. Coaching and Counseling: Where To Draw the Line.

    ERIC Educational Resources Information Center

    Colvert, Audra L.

    Examining the role of the forensics coach as counselor, this paper attempts to define the role more clearly and offers guidelines and suggestions concerning where to draw the line between coaching and counseling "forensicators." The paper advances the premise that coaches have many responsibilities which include significant dimensions of…

  11. Recent advancement of turbulent flow measurement techniques

    NASA Technical Reports Server (NTRS)

    Battle, T.; Wang, P.; Cheng, D. Y.

    1974-01-01

    Advancements of the fluctuating density gradient cross beam laser Schlieren technique, the fluctuating line-reversal temperature measurement and the development of the two-dimensional drag-sensing probe to a three-dimensional drag-sensing probe are discussed. The three-dimensionality of the instantaneous momentum vector can shed some light on the nature of turbulence especially with swirling flow. All three measured fluctuating quantities (density, temperature, and momentum) can provide valuable information for theoreticians.

  12. Advance care planning.

    PubMed

    Lo, Bernard

    2004-01-01

    Advance directives allow patients to have some control over decisions even when they are no longer able to make decisions themselves. All states authorize written advance directives, such as the appointment of a health care proxy, but commonly impose procedural requirements. Some states have restricted the use of oral advance directives, although they are frequently used in everyday practice. Advance directives are limited because they are infrequently used, may not be informed, and may conflict with the patient's current best interests. Moreover, surrogates often cannot state patients' preferences accurately. Furthermore, discussions among physicians and patients about advance directives are flawed. Physicians can improve discussions about advance directives by asking the patient who should serve as proxy and by ascertaining the patient's values and general preferences before discussing specific clinical situations. PMID:15538068

  13. 45. SELAH LINE, LOOKING NORTHEAST, SHOWING END OF LINE AT ...

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

    45. SELAH LINE, LOOKING NORTHEAST, SHOWING END OF LINE AT LARSON FRUIT COMPANY - Yakima Valley Transportation Company Interurban Railroad, Connecting towns of Yakima, Selah & Wiley City, Yakima, Yakima County, WA

  14. Aquila field: Advanced contracting strategies

    SciTech Connect

    1997-04-01

    Aquila oil field, in 2,800 ft of water, is in the middle of the Otranto Channel in the Mediterranean Sea, approximately 28 miles offshore southern Italy, and is subject to difficult sea and weather conditions. The many difficulties, caused mainly by water depth, requires the use of advanced technology that can be obtained only through the direct association with contractor companies. This solution safeguards the technological reliability and allows for maximum control of time and cost. The selection of a floating production, storage, and offloading (FPSO) system resulted from a feasibility study that indicated this solution was the only method that would provide economical exploitation of the Aquila field. The system includes flowlines and control lines. The ship, FPSO Agip Firenze, has been specially redesigned to manage the field development. Agip will provide the subsea production system, the Christmas tree, control system, and artificial lift.

  15. Advances in pipe prover technology

    SciTech Connect

    Jakubenas, P.P.

    1996-09-01

    The petroleum industry has used pipe provers for on line calibration of liquid flow meters for over 30 years. Recently a number of innovations have come to the forefront that enhance the reliability of pipe provers, reduce their size, make them more accurate, and increase their value to the end users. With the widespread use of turbine meters for custody transfer, accurate measurement is more dependent on frequent proving, thus the industry will continue to demand advanced provers and proving techniques. The author will discuss the aforementioned subject with regard to both bidirectional and unidirectional pipe provers. A description of the operational principles of pipe provers and the enhancements that are now available in terms of prover mechanical configuration and electronic instrumentation will be described in detail. In addition, information will be provided concerning integration of pipe provers into measurement systems and design and use of sophisticated computer control systems for automated proving.

  16. Hydromechanical Advanced Coal Excavator

    NASA Technical Reports Server (NTRS)

    Estus, Jay M.; Summers, David

    1990-01-01

    Water-jet cutting reduces coal dust and its hazards. Advanced mining system utilizes full-face, hydromechanical, continuous miner. Coal excavator uses high-pressure water-jet lances, one in each of cutting heads and one in movable lance, to make cuts across top, bottom and middle height, respectively, of coal face. Wedge-shaped cutting heads advance into lower and upper cuts in turn, thereby breaking coal toward middle cut. Thrust cylinders and walking pads advance excavator toward coal face.

  17. Read Between the Lines

    NASA Astrophysics Data System (ADS)

    Moore, Lynny

    2009-10-01

    When viewing it is best to have another person standing behind you reading the list of names of some of the women in the physical sciences that are placed ``between the lines''. It creates a profound contrast to the written words of the author of the letter, Robert A. Millikan. My mother-in-law, Dr. Isabelle Ganz, said she attended a physics conference during her freshman year of college at the University of Rochester and personally ``waited'' on Robert Oppenheimer. She noted that there were no women present. They were most likely in the lab.

  18. Diatomic predissociation line widths

    NASA Technical Reports Server (NTRS)

    Child, M. S.

    1973-01-01

    Predissociation by rotation and curve crossing in diatomic molecules is discussed. The pattern of predissociation line widths is seen as providing a highly sensitive yardstick for the determination of unknown potential curves. In addition, the computation of such a pattern for given potential curves is considered a matter of routine, unless the predissociation happens to occur from an adiabatic potential curve. Analytic formulas are used to provide physical insight into the details of the predissociation pattern, to the extent that a direct inversion procedure is developed for determination of the repulsive potential curves for Type 1 predissociations.

  19. Worldlines as Wilson Lines

    SciTech Connect

    Green, Daniel; /SLAC /Stanford U., Dept. Phys.

    2008-04-29

    Gravitational theories do not admit gauge invariant local operators. We study the limits under which there exists a quasi-local description for a class of non-local gravitational observables where a sum over worldlines plays the role of the Wilson line for gauge theory observables. We study non-local corrections to the local description and circumstances where these corrections become large. We find that these operators are quasi-local in at space and AdS, but fail to be quasi-local in de Sitter space.

  20. Vertical bloch line memory

    NASA Technical Reports Server (NTRS)

    Katti, R.; Wu, J.; Stadler, H.

    1990-01-01

    Vertical Bloch Line (VBL) memory is a recently conceived, integrated, solid-state, block-access, VLSI memory which offers the potential of 1Gbit/sq cm real storage density, gigabit per second data rates, and sub-millisecond average access times simultaneously at relatively low mass, volume, and power values when compared to alternative technologies. VBL's are micromagnetic structures within magnetic domain walls which can be manipulated using magnetic fields from integrated conductors. The presence or absence of VBL pairs are used to store binary information. At present, efforts are being directed at developing a single-chip memory using 25Mbit/sq cm technology in magnetic garnet material which integrates, at a single operating point, the writing, storage, reading, and amplification functions needed in a memory. This paper describes the current design architecture, functional elements, and supercomputer simulation results which are used to assist the design process. The current design architecture uses three metal layers, two ion implantation steps for modulating the thickness of the magnetic layer, one ion implantation step for assisting propagation in the major line track, one NiFe soft magnetic layer, one CoPt hard magnetic layer, and one reflective Cr layer for facilitating magneto-optic observation of magnetic structure. Data are stored in a series of elongated magnetic domains, called stripes, which serve as storage sites for arrays of VBL pairs. The ends of these stripes are placed near conductors which serve as VBL read/write gates. A major line track is present to provide a source and propagation path for magnetic bubbles. Writing and reading, respectively, are achieved by converting magnetic bubbles to VBL's and vice versa. The output function is effected by stretching a magnetic bubble and detecting it magnetoresistively. Experimental results from the past design cycle created four design goals for the current design cycle. First, the bias field ranges

  1. Advancing the educational agenda.

    PubMed

    Baker, Cynthia

    2010-12-01

    This timely paper provides a thought-provoking analysis of current advanced practice nursing education in Canada. It comes at a critical juncture in the evolution of Canadian healthcare services and the redefinition of nursing roles. Increasingly, multiple sectors of society are calling for more nurses with advanced practice preparation and for a wider range of advanced practice nursing specialties. Advanced practice nurses (APNs) are being proposed as a solution to a financially overburdened national healthcare system, the increasing complexity of healthcare services, and a crisis in access to primary healthcare. Thus, governments seeking greater fiscal efficiency, medical specialists needing sophisticated collaborative support, and healthcare consumers see APNs as the way forward.

  2. Beyond "Line by Line": Strategies for Performance and Learning Transfer

    ERIC Educational Resources Information Center

    Musco, Ann Marie

    2011-01-01

    A variety of excellent method books aim to help student musicians develop skills in music reading and instrumental technique, but sometimes the best approach is not simply to move ahead line by line through the book. Rather, teachers will find it beneficial to consider apposite strategies to be used before, during, and after rehearsing a line so…

  3. Advanced Technology Composite Fuselage - Manufacturing

    NASA Technical Reports Server (NTRS)

    Wilden, K. S.; Harris, C. G.; Flynn, B. W.; Gessel, M. G.; Scholz, D. B.; Stawski, S.; Winston, V.

    1997-01-01

    The goal of Boeing's Advanced Technology Composite Aircraft Structures (ATCAS) program is to develop the technology required for cost-and weight-efficient use of composite materials in transport fuselage structure. Carbon fiber reinforced epoxy was chosen for fuselage skins and stiffening elements, and for passenger and cargo floor structures. The automated fiber placement (AFP) process was selected for fabrication of stringer-stiffened and sandwich skin panels. Circumferential and window frames were braided and resin transfer molded (RTM'd). Pultrusion was selected for fabrication of floor beams and constant-section stiffening elements. Drape forming was chosen for stringers and other stiffening elements cocured to skin structures. Significant process development efforts included AFP, braiding, RTM, autoclave cure, and core blanket fabrication for both sandwich and stiffened-skin structure. Outer-mold-line and inner-mold-line tooling was developed for sandwich structures and stiffened-skin structure. The effect of design details, process control and tool design on repeatable, dimensionally stable, structure for low cost barrel assembly was assessed. Subcomponent panels representative of crown, keel, and side quadrant panels were fabricated to assess scale-up effects and manufacturing anomalies for full-scale structures. Manufacturing database including time studies, part quality, and manufacturing plans were generated to support the development of designs and analytical models to access cost, structural performance, and dimensional tolerance.

  4. The Median-Median Line

    ERIC Educational Resources Information Center

    Wilson, David C.

    2010-01-01

    Graphing bivariate data in a scatter plot and drawing an approximate line of best fit for the data have become commonly recommended activities for middle school and high school students. The graphing calculator has provided a mechanism for students both to approximate a best-fit line and to calculate the best-fit line using a built-in option. Two…

  5. Bee Line BR-1 Racer

    NASA Technical Reports Server (NTRS)

    1926-01-01

    Bee Line BR-1 Racer: The Bee Line BR-1 was a racing aircraft used to compete in the 1922 Pulitzer Air Race. The aircraft and its sister ship, the Bee Line BR-2, came to Langley and the NACA in 1926. The BR-1 is shown in the NACA hangar at Langley Field in early 1926.

  6. CORONAL EMISSION LINES AS THERMOMETERS

    SciTech Connect

    Judge, Philip G.

    2010-01-10

    Coronal emission-line intensities are commonly used to measure electron temperatures using emission measure and/or line ratio methods. In the presence of systematic errors in atomic excitation calculations and data noise, the information on underlying temperature distributions is fundamentally limited. Increasing the number of emission lines used does not necessarily improve the ability to discriminate between different kinds of temperature distributions.

  7. Advanced Manufacturing Technologies

    NASA Technical Reports Server (NTRS)

    Fikes, John

    2016-01-01

    Advanced Manufacturing Technologies (AMT) is developing and maturing innovative and advanced manufacturing technologies that will enable more capable and lower-cost spacecraft, launch vehicles and infrastructure to enable exploration missions. The technologies will utilize cutting edge materials and emerging capabilities including metallic processes, additive manufacturing, composites, and digital manufacturing. The AMT project supports the National Manufacturing Initiative involving collaboration with other government agencies.

  8. Drilling at Advanced Levels

    ERIC Educational Resources Information Center

    Case, Doug

    1977-01-01

    Instances where drilling is useful for advanced language are discussed. Several types of drills are recommended, with the philosophy that advanced level drills should have a lighter style and be regarded as a useful, occasional means of practicing individual new items. (CHK)

  9. ADVANCED PLACEMENT IN OHIO.

    ERIC Educational Resources Information Center

    Ohio Council on Advanced Placement, Columbus.

    THE DOCUMENT PRESENTS A DESCRIPTION OF THE ADVANCED PLACEMENT PROGRAM IN OHIO. ANSWERS ARE GIVEN TO KEY QUESTIONS ON THE FUNCTION OF ADVANCED PLACEMENT, ACADEMIC AREAS COVERED, PROGRAM ADMINISTRATION, COSTS, BENEFITS, VARIOUS ORGANIZATIONAL PATTERNS, STUDENT PARTICIPANTS, COLLEGES AND UNIVERSITIES IN OHIO AND REPRESENTATIVE NATIONAL INSTITUTIONS…

  10. Kansas Advanced Semiconductor Project

    SciTech Connect

    Baringer, P.; Bean, A.; Bolton, T.; Horton-Smith, G.; Maravin, Y.; Ratra, B.; Stanton, N.; von Toerne, E.; Wilson, G.

    2007-09-21

    KASP (Kansas Advanced Semiconductor Project) completed the new Layer 0 upgrade for D0, assumed key electronics projects for the US CMS project, finished important new physics measurements with the D0 experiment at Fermilab, made substantial contributions to detector studies for the proposed e+e- international linear collider (ILC), and advanced key initiatives in non-accelerator-based neutrino physics.

  11. Advanced cryo propulsion systems

    NASA Technical Reports Server (NTRS)

    Tabata, William K.

    1991-01-01

    The following topics are presented in viewgraph form: (1) advanced space engine (ASE) chronology; (2) an ASE description; (3) a single expander; (4) a dual expander; (5) split expander; (6) launch vehicle start; (7) space start; (8) chemical transfer propulsion; and (9) an advanced expander test bed.

  12. Advanced Engineering Fibers.

    ERIC Educational Resources Information Center

    Edie, Dan D.; Dunham, Michael G.

    1987-01-01

    Describes Clemson University's Advanced Engineered Fibers Laboratory, which was established to provide national leadership and expertise in developing the processing equipment and advance fibers necessary for the chemical, fiber, and textile industries to enter the composite materials market. Discusses some of the laboratory's activities in…

  13. Advanced Life Support

    NASA Technical Reports Server (NTRS)

    Chambliss, Joe

    2004-01-01

    Viewgraphs on Advanced Life Support (ALS) Systems are presented. The topics include: 1) Fundamental Need for Advanced Life Support; 2) ALS organization; 3) Requirements and Rationale; 4) Past Integrated tests; 5) The need for improvements in life support systems; 6) ALS approach to meet exploration goals; 7) ALS Projects showing promise to meet exploration goals; and 9) GRC involvement in ALS.

  14. Advanced Chemical Propulsion Study

    NASA Technical Reports Server (NTRS)

    Woodcock, Gordon; Byers, Dave; Alexander, Leslie A.; Krebsbach, Al

    2004-01-01

    A study was performed of advanced chemical propulsion technology application to space science (Code S) missions. The purpose was to begin the process of selecting chemical propulsion technology advancement activities that would provide greatest benefits to Code S missions. Several missions were selected from Code S planning data, and a range of advanced chemical propulsion options was analyzed to assess capabilities and benefits re these missions. Selected beneficial applications were found for higher-performing bipropellants, gelled propellants, and cryogenic propellants. Technology advancement recommendations included cryocoolers and small turbopump engines for cryogenic propellants; space storable propellants such as LOX-hydrazine; and advanced monopropellants. It was noted that fluorine-bearing oxidizers offer performance gains over more benign oxidizers. Potential benefits were observed for gelled propellants that could be allowed to freeze, then thawed for use.

  15. Unique features in the ARIES glovebox line

    SciTech Connect

    Martinez, H.E.; Brown, W.G.; Flamm, B.; James, C.A.; Laskie, R.; Nelson, T.O.; Wedman, D.E.

    1998-12-31

    A series of unique features have been incorporated into the Advanced Recovery and Integrated Extraction System (ARIES) at the Los Alamos National Laboratory, TA-55 Plutonium Facility. The features enhance the material handling in the process of the dismantlement of nuclear weapon primaries in the glovebox line. Incorporated into these features are the various plutonium process module`s different ventilation zone requirements that the material handling systems must meet. These features include a conveyor system that consists of a remotely controlled cart that transverses the length of the conveyor glovebox, can be operated from a remote location and can deliver process components to the entrance of any selected module glovebox. Within the modules there exists linear motion material handling systems with lifting hoist, which are controlled via an Allen Bradley control panel or local control panels. To remove the packaged products from the hot process line, the package is processed through an air lock/electrolytic decontamination process that removes the radioactive contamination from the outside of the package container and allows the package to be removed from the process line.

  16. Open field lines instabilities

    SciTech Connect

    Pozzoli, R. |

    1995-09-01

    The results of some recent theoretical papers dealing with flute-like instabilities in the scrape-off layer of a tokamak with limiter configuration, where the magnetic field intersects conducting walls, are briefly recalled. Attention is then paid to the instability driven by the electron temperature gradient across the field in conjunction with the formation of the Debye sheath at the boundary, and to the effects due to the inclination of the end walls with respect to the magnetic field. When a divertor configuration is considered, important modifications are found owing to the strong deformations of the flux tubes passing near the {ital x}-point, which contrast the onset of flute-like perturbations, and to the stochasticity of field lines that can be excited by magnetic field perturbations. {copyright} {ital 1995 American Institute of Physics.}

  17. Continuous gutter lining

    SciTech Connect

    Butler, R.W.

    1988-05-03

    An apparatus for lining a gutter having a downspout and horizontal support members is described comprising: a strip of waterproof, normally flat, resilient material of substantially uniform cross section having a drain hole therein; the strip being deformed out of its flat shape to a U-shaped transverse cross-section and being located within the gutter beneath the horizontal support members, having a width dimension sufficient to traverse a cross-section of the gutter underneath the horizontal members having a first edge of the strip contacting a back wall of the gutter, a second edge of the strip contacting a front wall of the gutter and forming a U-shaped cross section; and the drain hole being located above the gutter downspout to facilitate draining.

  18. On a front line.

    PubMed Central

    Jones, L.

    1995-01-01

    Like the patients, doctors in Sarajevo depend largely on humanitarian aid; everyone in the public sector has worked without pay for almost three years. The hospital is on a front line; yet the psychiatric department continues to function, even conducting large scale studies of psychosocial aspects of war in Bosnia-Hercegovina. The type of inpatient morbidity and treatment patterns have changed. A plethora of psychosocial rehabilitation programmes has emerged, including counselling, drop in centres, and attending to special needs of elderly people, schoolchildren, and women. The most prominent psychological symptoms were exhaustion at the prospect of a third winter of war and bewilderment at the Western stereotype of Bosnians as Muslim fundamentalists. Images p1052-a p1053-a PMID:7728062

  19. Understanding Slag Freeze Linings

    NASA Astrophysics Data System (ADS)

    Fallah-Mehrjardi, Ata; Hayes, Peter C.; Jak, Evgueni

    2014-09-01

    Slag freeze linings, the formation of protective deposit layers on the inner walls of furnaces and reactors, are increasingly used in industrial pyrometallurgical processes to ensure that furnace integrity is maintained in these aggressive, high-temperature environments. Most previous studies of freeze-linings have analyzed the formation of slag deposits based solely on heat transfer considerations. These thermal models have assumed that the interface between the stationary frozen layer and the agitated molten bath at steady-state deposit thickness consists of the primary phase, which stays in contact with the bulk liquid at the liquidus temperature. Recent experimental studies, however, have clearly demonstrated that the temperature of the deposit/liquid bath interface can be lower than the liquidus temperature of the bulk liquid. A conceptual framework has been proposed to explain the observations and the factors influencing the microstructure and the temperature of the interface at steady-state conditions. The observations are consistent with a dynamic steady state that is a balance between (I) the rate of nucleation and growth of solids on detached crystals in a subliquidus layer as this fluid material moves toward the stagnant deposit interface and (II) the dissolution of these detached crystals as they are transported away from the interface by turbulent eddies. It is argued that the assumption that the interface temperature is the liquidus of the bulk material represents only a limiting condition, and that the interface temperature can be between T liquidus and T solidus depending on the process conditions and bath chemistry. These findings have implications for the modeling approach and boundary conditions required to accurately describe these systems. They also indicate the opportunity to integrate considerations of heat and mass flows with the selection of melt chemistries in the design of future high temperature industrial reactors.

  20. SunLine Leads the Way in Demonstrating Hydrogen-Fueled Bus Technologies (Brochure)

    SciTech Connect

    Not Available

    2011-01-01

    This brochure describes SunLine Transit Agency's newest advanced technology fuel cell electric bus. SunLine is collaborating with the U.S. Department of Energy's Fuel Cell Technologies Program to evaluate the bus in revenue service. This bus represents the sixth generation of hydrogen-fueled buses that the agency has operated since 2000.

  1. The Role of Intelligent Agents in Advanced Information Systems

    NASA Technical Reports Server (NTRS)

    Kerschberg, Larry

    1999-01-01

    In this presentation we review the current ongoing research within George Mason University's (GMU) Center for Information Systems Integration and Evolution (CISE). We define characteristics of advanced information systems, discuss a family of agents for such systems, and show how GMU's Domain modeling tools and techniques can be used to define a product line Architecture for configuring NASA missions. These concepts can be used to define Advanced Engineering Environments such as those envisioned for NASA's new initiative for intelligent design and synthesis environments.

  2. Structure and form of grounding lines of modern ice sheets

    NASA Astrophysics Data System (ADS)

    Tinto, K. J.; Bell, R. E.; Cochran, J. R.; Boghosian, A.; Porter, D. F.

    2015-12-01

    The form of the bed at the grounding line of a glacier and the character of the underlying rock can be critical to the stability of the glacier. Aerogravity measurements offer a unique insight in to the character of the grounding line environment. By combining depth measurements from further onshore radar and geological information from magnetic surveys, gravity-based models can reveal both the depth and slope of the bed at the grounding line. Where bed elevation is known at the grounding line, gravity models can show the density structure of the underlying rock. Operation IceBridge has flown coincident radar, lidar, photography, gravity and magnetic airborne surveys along fjords and over ice shelves in both Greenland and Antarctica. Aerogravity measurements have been used extensively to model the bathymetry of the sea floor in front of the grounding line, and to identify the depth of the grounding line in areas where radar measurements have proven challenging. These models have also been used to reveal the range of conditions at present day grounding lines, as well as those experienced in the past and predicted for future grounding line positions. In some regions, we have identified low-density sediment accumulations, at both present day grounding lines and within fjords, that we interpret to be terminal moraines deposited by the glacier itself during hiatuses in retreat. In other regions, we find that the present day grounding line is stalled on a ridge of high-density rock. Ridges such as these remain in the same position through many cycles of advance and retreat of the glacier. Our synthesis of gravity data from a wide range of glacial environments can be used to identify likely drivers of change at the grounding line, whether this is the depth, the slope, or the geological character of the glacier bed.

  3. Sea-level line extraction based on piecewise line detection

    NASA Astrophysics Data System (ADS)

    Lei, Bo; Ren, Tingting; Liu, Yingbin; Yu, Jianwei

    2014-11-01

    In infrared image, sea-level line could be hard to distinguish because of noises caused by wave clutters and sunlight conditions.This paper proposed a fast sea-level line extraction method which could localize the sea-level line in complex infrared sea-sky scenes. First, a down sample operation was performed to obtain a low resolution image which could reduce the time consumption without blurring the sea-level line, and then the Canny edge detection was carried out to extract edges in the scene. Second, the intersecting edges were separated by removing the joints of edges according to a certain rule, and the bounding rectangle of every short edge was obtained which helped to select straight lines, and then a long edge segmentation operation was used to count in possible sea-level line. Third, a line concatenation method was performed by their slopes and intercepts comparison. Finally, for sea-level line verification, the second-order vertical grads are calculated in the two sides of possible sea-level line. Experiments show that the proposed method is fast and effective for various kinds of infrared sea-sky scenes, and it is feasible even for the scenes where the sea-level line is blurring and hard to distinguish.

  4. Orthopaedic service lines-revisited.

    PubMed

    Patterson, Cheryl

    2008-01-01

    This article revisits the application of orthopaedic service lines from early introduction and growth of this organizational approach in the 1980s, through the 1990s, and into the current decade. The author has experienced and worked in various service-line structures through these three decades, as well as the preservice-line era of 1970s orthopaedics. Past lessons learned during earlier phases and then current trends and analysis by industry experts are summarized briefly, with indication given of the future for service lines. Variation versus consistency of certain elements in service-line definitions and in operational models is discussed. Main components of service-line structures and typical processes are described briefly, along with a more detailed section on the service-line director/manager role. Current knowledge contained here will help guide the reader to more "out-of-the-box" thinking toward comprehensive orthopaedic centers of excellence.

  5. Advanced Safeguards Approaches for New Reprocessing Facilities

    SciTech Connect

    Durst, Philip C.; Therios, Ike; Bean, Robert; Dougan, A.; Boyer, Brian; Wallace, Richard; Ehinger, Michael H.; Kovacic, Don N.; Tolk, K.

    2007-06-24

    U.S. efforts to promote the international expansion of nuclear energy through the Global Nuclear Energy Partnership (GNEP) will result in a dramatic expansion of nuclear fuel cycle facilities in the United States. New demonstration facilities, such as the Advanced Fuel Cycle Facility (AFCF), the Advanced Burner Reactor (ABR), and the Consolidated Fuel Treatment Center (CFTC) will use advanced nuclear and chemical process technologies that must incorporate increased proliferation resistance to enhance nuclear safeguards. The ASA-100 Project, “Advanced Safeguards Approaches for New Nuclear Fuel Cycle Facilities,” commissioned by the NA-243 Office of NNSA, has been tasked with reviewing and developing advanced safeguards approaches for these demonstration facilities. Because one goal of GNEP is developing and sharing proliferation-resistant nuclear technology and services with partner nations, the safeguards approaches considered are consistent with international safeguards as currently implemented by the International Atomic Energy Agency (IAEA). This first report reviews possible safeguards approaches for the new fuel reprocessing processes to be deployed at the AFCF and CFTC facilities. Similar analyses addressing the ABR and transuranic (TRU) fuel fabrication lines at AFCF and CFTC will be presented in subsequent reports.

  6. Advanced electron microscopy for advanced materials.

    PubMed

    Van Tendeloo, Gustaaf; Bals, Sara; Van Aert, Sandra; Verbeeck, Jo; Van Dyck, Dirk

    2012-11-01

    The idea of this Review is to introduce newly developed possibilities of advanced electron microscopy to the materials science community. Over the last decade, electron microscopy has evolved into a full analytical tool, able to provide atomic scale information on the position, nature, and even the valency atoms. This information is classically obtained in two dimensions (2D), but can now also be obtained in 3D. We show examples of applications in the field of nanoparticles and interfaces.

  7. Advanced biostack experiment

    NASA Technical Reports Server (NTRS)

    Buecker, H.

    1981-01-01

    The Advanced Biostack Experiment is described. The objectives are: (1) to confirm, complement, and enlarge the information obtained from the previous experiments by applying improved and advanced methods of localization and physical and biological evaluation, performing advanced experiments based on these data, and including additional biological specimens and additional radiation detectors; (2) to determine the biological importance of nuclear disintegration stars; (3) to determine the interference of HZE particle induced effects with those of other space flight factors (e.g., weightlessness); and (4) to determine the distribution of HZE particles and of disintegration stars at different locations inside the module and on the pallet.

  8. The ADvanced SEParation (ADSEP)

    NASA Technical Reports Server (NTRS)

    1998-01-01

    The ADvanced SEParation (ADSEP) commercial payload is making use of major advances in separation technology: The Phase Partitioning Experiment (PPE); the Micorencapsulation experiment; and the Hemoglobin Separation Experiment (HSE). Using ADSEP, commercial researchers will attempt to determine the partition coefficients for model particles in a two-phase system. With this information, researchers can develop a higher resolution, more effective cell isolation procedure that can be used for many different types of research and for improved health care. The advanced separation technology is already being made available for use in ground-based laboratories.

  9. Advanced information society(7)

    NASA Astrophysics Data System (ADS)

    Chiba, Toshihiro

    Various threats are hiding in advanced informationalized society. As we see car accident problems in motorization society light aspects necessarily accompy shady ones. Under the changing circumstances of advanced informationalization added values of information has become much higher. It causes computer crime, hacker, computer virus to come to the surface. In addition it can be said that infringement of intellectual property and privacy are threats brought by advanced information. Against these threats legal, institutional and insurance measures have been progressed, and newly security industry has been established. However, they are not adequate individually or totally. The future vision should be clarified, and countermeasures according to the visions have to be considered.

  10. Optimization of line configuration and balancing for flexible machining lines

    NASA Astrophysics Data System (ADS)

    Liu, Xuemei; Li, Aiping; Chen, Zurui

    2016-05-01

    Line configuration and balancing is to select the type of line and allot a given set of operations as well as machines to a sequence of workstations to realize high-efficiency production. Most of the current researches for machining line configuration and balancing problems are related to dedicated transfer lines with dedicated machine workstations. With growing trends towards great product variety and fluctuations in market demand, dedicated transfer lines are being replaced with flexible machining line composed of identical CNC machines. This paper deals with the line configuration and balancing problem for flexible machining lines. The objective is to assign operations to workstations and find the sequence of execution, specify the number of machines in each workstation while minimizing the line cycle time and total number of machines. This problem is subject to precedence, clustering, accessibility and capacity constraints among the features, operations, setups and workstations. The mathematical model and heuristic algorithm based on feature group strategy and polychromatic sets theory are presented to find an optimal solution. The feature group strategy and polychromatic sets theory are used to establish constraint model. A heuristic operations sequencing and assignment algorithm is given. An industrial case study is carried out, and multiple optimal solutions in different line configurations are obtained. The case studying results show that the solutions with shorter cycle time and higher line balancing rate demonstrate the feasibility and effectiveness of the proposed algorithm. This research proposes a heuristic line configuration and balancing algorithm based on feature group strategy and polychromatic sets theory which is able to provide better solutions while achieving an improvement in computing time.

  11. Bottom-line empowerment: lessons from the firing line

    NASA Astrophysics Data System (ADS)

    Miller, J. P.

    1993-03-01

    Empowering employees on the firing-line to actively participate in solving business problems can have a significant positive impact on bottom-line performance. Lessons from a number of companies and thousands of people from the firing-line have demonstrated this. Unfortunately, there is no simple, step-by-step method that can be guaranteed to succeed. Getting business results by successfully empowering the firing-line is as much art as science. Yet, as with any art, there are principles that, if rigorously followed, can go a long way to ensuring success. These principles are outlined in this paper as 18 critical success factors to empowerment.

  12. Bipolar pulse forming line

    DOEpatents

    Rhodes, Mark A.

    2008-10-21

    A bipolar pulse forming transmission line module for linear induction accelerators having first, second, third, fourth, and fifth planar conductors which form an interleaved stack with dielectric layers between the conductors. Each conductor has a first end, and a second end adjacent an acceleration axis. The first and second planar conductors are connected to each other at the second ends, the fourth and fifth planar conductors are connected to each other at the second ends, and the first and fifth planar conductors are connected to each other at the first ends via a shorting plate adjacent the first ends. The third planar conductor is electrically connectable to a high voltage source, and an internal switch functions to short a high voltage from the first end of the third planar conductor to the first end of the fourth planar conductor to produce a bipolar pulse at the acceleration axis with a zero net time integral. Improved access to the switch is enabled by an aperture through the shorting plate and the proximity of the aperture to the switch.

  13. EC Transmission Line Materials

    SciTech Connect

    Bigelow, Tim S

    2012-05-01

    The purpose of this document is to identify materials acceptable for use in the US ITER Project Office (USIPO)-supplied components for the ITER Electron cyclotron Heating and Current Drive (ECH&CD) transmission lines (TL), PBS-52. The source of material property information for design analysis shall be either the applicable structural code or the ITER Material Properties Handbook. In the case of conflict, the ITER Material Properties Handbook shall take precedence. Materials selection, and use, shall follow the guidelines established in the Materials Assessment Report (MAR). Materials exposed to vacuum shall conform to the ITER Vacuum Handbook. [Ref. 2] Commercial materials shall conform to the applicable standard (e.g., ASTM, JIS, DIN) for the definition of their grade, physical, chemical and electrical properties and related testing. All materials for which a suitable certification from the supplier is not available shall be tested to determine the relevant properties, as part of the procurement. A complete traceability of all the materials including welding materials shall be provided. Halogenated materials (example: insulating materials) shall be forbidden in areas served by the detritiation systems. Exceptions must be approved by the Tritium System and Safety Section Responsible Officers.

  14. Advances in cancer control

    SciTech Connect

    Anderson, P.N. ); Engstrom, P.F. ); Mortenson, L.E. )

    1989-01-01

    This book contains the proceedings of the sixth annual meeting on Advances in Cancer Control. Included are the following articles: Barriers and facilitators to compliance with routine mammographic screening, Preliminary report of an intervention to improve mammography skills of radiologists.

  15. Descendants and advance directives.

    PubMed

    Buford, Christopher

    2014-01-01

    Some of the concerns that have been raised in connection to the use of advance directives are of the epistemic variety. Such concerns highlight the possibility that adhering to an advance directive may conflict with what the author of the directive actually wants (or would want) at the time of treatment. However, at least one objection to the employment of advance directives is metaphysical in nature. The objection to be discussed here, first formulated by Rebecca Dresser and labeled by Allen Buchanan as the slavery argument and David DeGrazia the someone else problem, aims to undermine the legitimacy of certain uses of advance directives by concluding that such uses rest upon an incorrect assumption about the identity over time of those ostensibly governed by the directives. There have been numerous attempts to respond to this objection. This paper aims to assess two strategies that have been pursued to cope with the problem.

  16. Advances in Process Control.

    ERIC Educational Resources Information Center

    Morrison, David L.; And Others

    1982-01-01

    Advances in electronics and computer science have enabled industries (pulp/paper, iron/steel, petroleum/chemical) to attain better control of their processes with resulting increases in quality, productivity, profitability, and compliance with government regulations. (JN)

  17. Advances in cell culture

    SciTech Connect

    Maramorosch, K. )

    1987-01-01

    This book presents papers on advances in cell culture. Topics covered include: Genetic changes in the influenza viruses during growth in cultured cells; The biochemistry and genetics of mosquito cells in culture; and Tree tissue culture applications.

  18. Advanced Process Control Experiments.

    ERIC Educational Resources Information Center

    Deshpande, Pradeep B.; And Others

    1980-01-01

    Describes laboratory experiments of a chemistry course on advanced process control. The equipment for the process around which these experiments were developed by the University of Louisville was constructed from data provided by Exxon Oil Company. (HM)

  19. Recent Advances in Vibroacoustics

    NASA Technical Reports Server (NTRS)

    Hughes, William O.; McNelis, Mark E.

    2002-01-01

    Numerous vibroacoustics advances and impacts in the aerospace industry have occurred over the last 15 years. This article addresses some of these that developed from engineering programmatic task-work at the NASA Glenn Research Center at Lewis Field.

  20. Advanced information society(2)

    NASA Astrophysics Data System (ADS)

    Masuyama, Keiichi

    Our modern life is full of information and information infiltrates into our daily life. Networking of the telecommunication is extended to society, company, and individual level. Although we have just entered the advanced information society, business world and our daily life have been steadily transformed by the advancement of information network. This advancement of information brings a big influence on economy, and will play they the main role in the expansion of domestic demands. This paper tries to view the image of coming advanced information society, focusing on the transforming businessman's life and the situation of our daily life, which became wealthy by the spread of daily life information and the visual information by satellite system, in the development of the intelligent city.

  1. Advanced General Dentistry Program.

    ERIC Educational Resources Information Center

    Barnes, Douglas M.; And Others

    1988-01-01

    A description of the University of Maryland at Baltimore's one-year postdoctoral program in advanced general dentistry focuses on its goals and objectives, curriculum design, patient population, faculty and staff, finances, and program evaluation measures. (MSE)

  2. Advanced Welding Concepts

    NASA Technical Reports Server (NTRS)

    Ding, Robert J.

    2010-01-01

    Four advanced welding techniques and their use in NASA are briefly reviewed in this poster presentation. The welding techniques reviewed are: Solid State Welding, Friction Stir Welding (FSW), Thermal Stir Welding (TSW) and Ultrasonic Stir Welding.

  3. Descendants and advance directives.

    PubMed

    Buford, Christopher

    2014-01-01

    Some of the concerns that have been raised in connection to the use of advance directives are of the epistemic variety. Such concerns highlight the possibility that adhering to an advance directive may conflict with what the author of the directive actually wants (or would want) at the time of treatment. However, at least one objection to the employment of advance directives is metaphysical in nature. The objection to be discussed here, first formulated by Rebecca Dresser and labeled by Allen Buchanan as the slavery argument and David DeGrazia the someone else problem, aims to undermine the legitimacy of certain uses of advance directives by concluding that such uses rest upon an incorrect assumption about the identity over time of those ostensibly governed by the directives. There have been numerous attempts to respond to this objection. This paper aims to assess two strategies that have been pursued to cope with the problem. PMID:25743056

  4. Advanced space propulsion concepts

    NASA Technical Reports Server (NTRS)

    Lapointe, Michael R.

    1993-01-01

    The NASA Lewis Research Center has been actively involved in the evaluation and development of advanced spacecraft propulsion. Recent program elements have included high energy density propellants, electrode less plasma thruster concepts, and low power laser propulsion technology. A robust advanced technology program is necessary to develop new, cost-effective methods of spacecraft propulsion, and to continue to push the boundaries of human knowledge and technology.

  5. Advanced planetary studies

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Results of planetary advanced studies and planning support provided by Science Applications, Inc. staff members to Earth and Planetary Exploration Division, OSSA/NASA, for the period 1 February 1981 to 30 April 1982 are summarized. The scope of analyses includes cost estimation, planetary missions performance, solar system exploration committee support, Mars program planning, Galilean satellite mission concepts, and advanced propulsion data base. The work covers 80 man-months of research. Study reports and related publications are included in a bibliography section.

  6. [Advances in hormonal contraception].

    PubMed

    Villanueva Egan, Luis Alberto; Pichardo Cuevas, Mauricio

    2007-01-01

    This review provides an update regarding newer options in hormonal contraception that include the progestin-releasing intrauterine system, the contraceptive patch and ring, the single rod progestin-releasing implant, extended and emergency oral contraception and recent advances in hormonal male contraception. These methods represent a major advancement in this field, allowing for the development of more acceptable, safety and effective birth control regimens.

  7. Advanced drilling systems study

    SciTech Connect

    Pierce, K.G.; Livesay, B.J.

    1995-03-01

    This work was initiated as part of the National Advanced Drilling and Excavation Technologies (NADET) Program. It is being performed through joint finding from the Department of Energy Geothermal Division and the Natural Gas Technology Branch, Morgantown Energy Technology Center. Interest in advanced drilling systems is high. The Geothermal Division of the Department of Energy has initiated a multi-year effort in the development of advanced drilling systems; the National Research Council completed a study of drilling and excavation technologies last year; and the MIT Energy Laboratory recently submitted a proposal for a national initiative in advanced drilling and excavation research. The primary reasons for this interest are financial. Worldwide expenditures on oil and gas drilling approach $75 billion per year. Also, drilling and well completion account for 25% to 50% of the cost of producing electricity from geothermal energy. There is incentive to search for methods to reduce the cost of drilling. Work on ideas to improve or replace rotary drilling technology dates back at least to the 1930`s. There was a significant amount of work in this area in the 1960`s and 1970`s; and there has been some continued effort through the 1980`s. Undoubtedly there are concepts for advanced drilling systems that have yet to be studied; however, it is almost certain that new efforts to initiate work on advanced drilling systems will build on an idea or a variation of an idea that has already been investigated. Therefore, a review of previous efforts coupled with a characterization of viable advanced drilling systems and the current state of technology as it applies to those systems provide the basis for the current study of advanced drilling.

  8. Advanced Welding Applications

    NASA Technical Reports Server (NTRS)

    Ding, Robert J.

    2010-01-01

    Some of the applications of advanced welding techniques are shown in this poster presentation. Included are brief explanations of the use on the Ares I and Ares V launch vehicle and on the Space Shuttle Launch vehicle. Also included are microstructural views from four advanced welding techniques: Variable Polarity Plasma Arc (VPPA) weld (fusion), self-reacting friction stir welding (SR-FSW), conventional FSW, and Tube Socket Weld (TSW) on aluminum.

  9. Simulation of Assembly Line Balancing in Automotive Component Manufacturing

    NASA Astrophysics Data System (ADS)

    Jamil, Muthanna; Mohd Razali, Noraini

    2016-02-01

    This study focuses on the simulation of assembly line balancing in an automotive component in a vendor manufacturing company. A mixed-model assembly line of charcoal canister product that is used in an engine system as fuel's vapour filter was observed and found that the current production rate of the line does not achieve customer demand even though the company practices buffer stock for two days in advance. This study was carried out by performing detailed process flow and time studies along the line. To set up a model of the line by simulation, real data was taken from a factory floor and tested for distribution fit. The data gathered was then transformed into a simulation model. After verification of the model by comparing it with the actual system, it was found that the current line efficiency is not at its optimum condition due to blockage and idle time. Various what-if analysis were applied to eliminate the cause. Proposed layout shows that the line is balanced by adding buffer to avoid the blockage. Whereas, manpower is added the stations to reduce process time therefore reducing idling time. The simulation study was carried out using ProModel software.

  10. ADVANCED CUTTINGS TRANSPORT STUDY

    SciTech Connect

    Stefan Miska; Troy Reed; Ergun Kuru

    2004-09-30

    The Advanced Cuttings Transport Study (ACTS) was a 5-year JIP project undertaken at the University of Tulsa (TU). The project was sponsored by the U.S. Department of Energy (DOE) and JIP member companies. The objectives of the project were: (1) to develop and construct a new research facility that would allow three-phase (gas, liquid and cuttings) flow experiments under ambient and EPET (elevated pressure and temperature) conditions, and at different angle of inclinations and drill pipe rotation speeds; (2) to conduct experiments and develop a data base for the industry and academia; and (3) to develop mechanistic models for optimization of drilling hydraulics and cuttings transport. This project consisted of research studies, flow loop construction and instrumentation development. Following a one-year period for basic flow loop construction, a proposal was submitted by TU to the DOE for a five-year project that was organized in such a manner as to provide a logical progression of research experiments as well as additions to the basic flow loop. The flow loop additions and improvements included: (1) elevated temperature capability; (2) two-phase (gas and liquid, foam etc.) capability; (3) cuttings injection and removal system; (4) drill pipe rotation system; and (5) drilling section elevation system. In parallel with the flow loop construction, hydraulics and cuttings transport studies were preformed using drilling foams and aerated muds. In addition, hydraulics and rheology of synthetic drilling fluids were investigated. The studies were performed under ambient and EPET conditions. The effects of temperature and pressure on the hydraulics and cuttings transport were investigated. Mechanistic models were developed to predict frictional pressure loss and cuttings transport in horizontal and near-horizontal configurations. Model predictions were compared with the measured data. Predominantly, model predictions show satisfactory agreements with the measured data. As a

  11. Advanced Microturbine Systems

    SciTech Connect

    Rosfjord, T; Tredway, W; Chen, A; Mulugeta, J; Bhatia, T

    2008-12-31

    In July 2000, the United Technologies Research Center (UTRC) was one of five recipients of a US Department of Energy contract under the Advanced Microturbine System (AMS) program managed by the Office of Distributed Energy (DE). The AMS program resulted from several government-industry workshops that recognized that microturbine systems could play an important role in improving customer choice and value for electrical power. That is, the group believed that electrical power could be delivered to customers more efficiently and reliably than the grid if an effective distributed energy strategy was followed. Further, the production of this distributed power would be accomplished with less undesirable pollutants of nitric oxides (NOx) unburned hydrocarbons (UHC), and carbon monoxide (CO). In 2000, the electrical grid delivered energy to US customers at a national average of approximately 32% efficiency. This value reflects a wide range of powerplants, but is dominated by older, coal burning stations that provide approximately 50% of US electrical power. The grid efficiency is also affected by transmission and distribution (T&D) line losses that can be significant during peak power usage. In some locations this loss is estimated to be 15%. Load pockets can also be so constrained that sufficient power cannot be transmitted without requiring the installation of new wires. New T&D can be very expensive and challenging as it is often required in populated regions that do not want above ground wires. While historically grid reliability has satisfied most customers, increasing electronic transactions and the computer-controlled processes of the 'digital economy' demand higher reliability. For them, power outages can be very costly because of transaction, work-in-progress, or perishable commodity losses. Powerplants that produce the grid electrical power emit significant levels of undesirable NOx, UHC, and CO pollutants. The level of emission is quoted as either a technology

  12. Ramucirumab: A Review in Advanced Gastric Cancer.

    PubMed

    Greig, Sarah L; Keating, Gillian M

    2015-10-01

    Ramucirumab (Cyramza(®)), an intravenously administered, monoclonal antibody against vascular endothelial growth factor receptor-2, is approved in the USA, EU and Japan (either as a single agent or in combination with paclitaxel) as second-line treatment in adults with advanced gastric or gastro-oesophageal junction adenocarcinoma. In two phase III trials (REGARD and RAINBOW) in this indication, overall survival and progression-free survival were significantly prolonged with ramucirumab 8 mg/kg every 2 weeks compared with placebo, and with ramucirumab 8 mg/kg every 2 weeks plus weekly paclitaxel compared with placebo plus paclitaxel. Ramucirumab had a generally acceptable tolerability profile in phase III trials; hypertension was the most common non-haematological adverse event of grade 3 or higher with ramucirumab (either alone or with paclitaxel). As the first antiangiogenic agent to provide significant survival benefit in patients with advanced gastric cancer, ramucirumab is a valuable option in the second-line treatment of advanced gastric or gastro-oesophageal junction adenocarcinoma.

  13. Structure of magnetic field lines

    NASA Astrophysics Data System (ADS)

    Golmankhaneh, Ali Khalili; Golmankhaneh, Alireza Khalili; Jazayeri, Seyed Masud; Baleanu, Dumitru

    2012-02-01

    In this paper the Hamiltonian structure of magnetic lines is studied in many ways. First it is used vector analysis for defining the Poisson bracket and Casimir variable for this system. Second it is derived Pfaffian equations for magnetic field lines. Third, Lie derivative and derivative of Poisson bracket is used to show structure of this system. Finally, it is shown Nambu structure of the magnetic field lines.

  14. ALFA: Automated Line Fitting Algorithm

    NASA Astrophysics Data System (ADS)

    Wesson, R.

    2015-12-01

    ALFA fits emission line spectra of arbitrary wavelength coverage and resolution, fully automatically. It uses a catalog of lines which may be present to construct synthetic spectra, the parameters of which are then optimized by means of a genetic algorithm. Uncertainties are estimated using the noise structure of the residuals. An emission line spectrum containing several hundred lines can be fitted in a few seconds using a single processor of a typical contemporary desktop or laptop PC. Data cubes in FITS format can be analysed using multiple processors, and an analysis of tens of thousands of deep spectra obtained with instruments such as MUSE will take a few hours.

  15. A proposed neutral line signature

    NASA Technical Reports Server (NTRS)

    Doxas, I.; Speiser, T. W.; Dusenbery, P. B.; Horton, W.

    1992-01-01

    An identifying signature is proposed for the existence and location of the neutral line in the magnetotail. The signature, abrupt density, and temperature changes in the Earthtail direction, was first discovered in test particle simulations. Such temperature variations have been observed in ISEE data (Huang et. al. 1992), but their connection to the possible existence of a neutral line in the tail has not yet been established. The proposed signature develops earlier than the ion velocity space ridge of Martin and Speiser (1988), but can only be seen by spacecraft in the vicinity of the neutral line, while the latter can locate a neutral line remotely.

  16. Lines of Best Fit by Graphics and the Wald Line.

    ERIC Educational Resources Information Center

    Henriksen, Melvin, Ed.; Wagon, Stan, Ed.

    1991-01-01

    Using a graphical analysis of the linear best fit for a set of Cartesian data points, the drawbacks of the least-squares method for determining this best fit are discussed. The Wald Line, which utilizes a variation of the geometric mean, is proposed as the best alternative to the least-squares regression line particularly when the data contain…

  17. The Assembly Line Enzymology of Polyketide Biosynthesis.

    PubMed

    Till, Marisa; Race, Paul R

    2016-01-01

    Polyketides are a structurally and functionally diverse family of bioactive natural products that have found widespread application as pharmaceuticals, agrochemicals, and veterinary medicines. In bacteria complex polyketides are biosynthesized by giant multifunctional megaenzymes, termed modular polyketide synthases (PKSs), which construct their products in a highly coordinated assembly line-like fashion from a pool of simple precursor substrates. Not only is the multifaceted enzymology of PKSs a fascinating target for study, but it also presents considerable opportunities for the reengineering of these systems affording access to functionally optimized unnatural natural products. Here we provide an introductory primer to modular polyketide synthase structure and function, and highlight recent advances in the characterization and exploitation of these systems.

  18. The Assembly Line Enzymology of Polyketide Biosynthesis.

    PubMed

    Till, Marisa; Race, Paul R

    2016-01-01

    Polyketides are a structurally and functionally diverse family of bioactive natural products that have found widespread application as pharmaceuticals, agrochemicals, and veterinary medicines. In bacteria complex polyketides are biosynthesized by giant multifunctional megaenzymes, termed modular polyketide synthases (PKSs), which construct their products in a highly coordinated assembly line-like fashion from a pool of simple precursor substrates. Not only is the multifaceted enzymology of PKSs a fascinating target for study, but it also presents considerable opportunities for the reengineering of these systems affording access to functionally optimized unnatural natural products. Here we provide an introductory primer to modular polyketide synthase structure and function, and highlight recent advances in the characterization and exploitation of these systems. PMID:26831699

  19. Ultra-Efficient Engine Technology (UEET), Proof of Concept Compressor, Advanced Compressor Casing T

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Ultra-Efficient Engine Technology (UEET), Proof of Concept Compressor, Advanced Compressor Casing Treatment testing; close up - throttle valve -wide open; oil and air lines plus instrumentation between collector and gearbox.

  20. PHENIX on-line and off-line computing

    NASA Astrophysics Data System (ADS)

    Adler, S. S.; Chujo, T.; Desmond, E. J.; Ewell, L.; Ghosh, T. K.; Haggerty, J. S.; Ichihara, T.; Jacak, B. V.; Johnson, S. C.; Kehayias, H.-J.; Lauret, J.; Maguire, C. F.; Messer, M.; Mioduszewski, S.; Mitchell, J. T.; Morrison, D. P.; Ojha, I. D.; Pinkenburg, C. H.; Pollack, M.; Pope, K.; Purschke, M. L.; Sorensen, S.; Sourikova, I.; Thomas, T. L.; Velkovsky, M.; Watanabe, Y.; Witzig, C.; Yokkaichi, S.; Zajc, W. A.; PHEN. I. X. Collaboration

    2003-03-01

    Data handling in PHENIX is carried out by the On-Line Computing System (ONCS) and Off-Line Computing System (Off-Line). ONCS provides the overall control and monitoring of the front-end electronics, trigger and data acquisition system and detector ancillary systems. It configures and initializes the on-line system, monitors and controls the data flow, coordinates calibration processes, interlocks the data acquisition process with the slow control subsystems and performs a number of other functions. ONCS uses CORBA software to monitor and control the hardware. Off-Line provides all aspects of data handling not directly connected to the collection of data and monitoring, such as event simulation and reconstruction, data analysis and information management. The impact of the unprecedented data volumes on the design is presented, along with a detailed discussion of the tasks and methods of simulating, obtaining and monitoring the data.

  1. Service-line management/bottom-line management.

    PubMed

    Longshore, G F

    1998-01-01

    To survive in the sturm und drang of health care administration, hospitals and health care systems will have to restructure themselves in ways that emphasize their specific clinical strengths, control their costs, and manage the delivery and outcomes of care. Structuring the organization along clinical lines of service (e.g., oncology, cardiology, rehabilitation) cedes total bottom-line authority for all aspects of that service to the service, or product, line manager. This article discusses the qualifications, compensation, and responsibilities of service-line managers in well-integrated health care systems and describes how they and managed care organizations view each other. It also suggests which organizations will, and will not, benefit from restructuring along service lines.

  2. A direct advance on advance directives.

    PubMed

    Shaw, David

    2012-06-01

    Advance directives (ADs), which are also sometimes referred to as 'living wills', are statements made by a person that indicate what treatment she should not be given in the event that she is not competent to consent or refuse at the future moment in question. As such, ADs provide a way for patients to make decisions in advance about what treatments they do not want to receive, without doctors having to find proxy decision-makers or having recourse to the doctrine of necessity. While patients can request particular treatments in an AD, only refusals are binding. This paper will examine whether ADs safeguard the autonomy and best interests of the incompetent patient, and whether legislating for the use of ADs is justified, using the specific context of the legal situation in the United Kingdom to illustrate the debate. The issue of whether the law should permit ADs is itself dependent on the issue of whether ADs are ethically justified; thus we must answer a normative question in order to answer the legislative one. It emerges that ADs suffer from two major problems, one related to autonomy and one to consent. First, ADs' emphasis on precedent autonomy effectively sentences some people who want to live to death. Second, many ADs might not meet the standard criteria for informed refusal of treatment, because they fail on the crucial criterion of sufficient information. Ultimately, it transpires that ADs are typically only appropriate for patients who temporarily lose physical or mental capacity.

  3. Recruit and ADVANCE

    NASA Astrophysics Data System (ADS)

    Rosser, Sue V.

    2007-04-01

    Beginning in 2001, the National Science Foundation launched the ADVANCE Initiative, which has now awarded more than 70 million to some thirty institutions for transformations to advance women. Results of studies on how to attract and retain women students and faculty underpinned our ADVANCE Institutional Transformation grant funded by the NSF for 3.7 million for five years, beginning in 2001. As co-principal investigator on this grant, I insured that this research informed the five major threads of the grant: 1) Four termed ADVANCE professors to mentor junior women faculty in each college; 2) Collection of MIT-Report-like data indicators to assess whether advancement of women really occurs during and after the institutional transformation undertaken through ADVANCE; 3) Family-friendly policies and practices to stop the tenure clock and provide active service, modified duties, lactation stations and day care; 4) Mini-retreats to facilitate access for tenure-track women faculty to male decision-makers and administrators for informal conversations and discussion on topics important to women faculty; 5) Removal of subtle gender, racial, and other biases in promotion and tenure. The dynamic changes resulting from the grant in quality of mentoring, new understanding of promotion and tenure, numbers of women retained and given endowed chairs, and emergence of new family friendly policies gave me hope for genuine diversification of leadership in science and technology. As the grant funding ends, the absence of NSF prestige and monitoring, coupled with a change in academic leadership at the top, provide new challenges for institutionalization, recruitment, and advancement of women into leadership positions in science and engineering.

  4. Advanced uncooled sensor product development

    NASA Astrophysics Data System (ADS)

    Kennedy, A.; Masini, P.; Lamb, M.; Hamers, J.; Kocian, T.; Gordon, E.; Parrish, W.; Williams, R.; LeBeau, T.

    2015-06-01

    The partnership between RVS, Seek Thermal and Freescale Semiconductor continues on the path to bring the latest technology and innovation to both military and commercial customers. The partnership has matured the 17μm pixel for volume production on the Thermal Weapon Sight (TWS) program in efforts to bring advanced production capability to produce a low cost, high performance product. The partnership has developed the 12μm pixel and has demonstrated performance across a family of detector sizes ranging from formats as small as 206 x 156 to full high definition formats. Detector pixel sensitivities have been achieved using the RVS double level advanced pixel structure. Transition of the packaging of microbolometers from a traditional die level package to a wafer level package (WLP) in a high volume commercial environment is complete. Innovations in wafer fabrication techniques have been incorporated into this product line to assist in the high yield required for volume production. The WLP seal yield is currently > 95%. Simulated package vacuum lives >> 20 years have been demonstrated through accelerated life testing where the package has been shown to have no degradation after 2,500 hours at 150°C. Additionally the rugged assembly has shown no degradation after mechanical shock and vibration and thermal shock testing. The transition to production effort was successfully completed in 2014 and the WLP design has been integrated into multiple new production products including the TWS and the innovative Seek Thermal commercial product that interfaces directly to an iPhone or android device.

  5. 76 FR 51367 - China Shipping Container Lines Co., Ltd.; COSCO Container Lines Company Limited; Evergreen Line A...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-18

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION China Shipping Container Lines Co., Ltd.; COSCO Container Lines Company Limited; Evergreen Line A Joint... Container Lines Co., Ltd.; COSCO Container Lines Company Limited; Evergreen Line A Joint Service...

  6. Advanced potato breeding clones: storage and processing evaluation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The accumulation of reducing sugars during cold storage of potato tubers is a serious and costly problem for producers and processors. The degree to which cultivars accumulate reducing sugars during storage determines their processing and market potential. Cultivars or advanced breeding lines with...

  7. Sleep, off-line processing, and vocal learning.

    PubMed

    Margoliash, Daniel; Schmidt, Marc F

    2010-10-01

    The study of song learning and the neural song system has provided an important comparative model system for the study of speech and language acquisition. We describe some recent advances in the bird song system, focusing on the role of off-line processing including sleep in processing sensory information and in guiding developmental song learning. These observations motivate a new model of the organization and role of the sensory memories in vocal learning. PMID:19906416

  8. On-line monitoring: Improving hydro maintenance and operations

    SciTech Connect

    Byers, W.

    1996-02-01

    Expert monitoring systems provide plant owners and operators with a means of judging the condition of hydropower equipment before problems arise. The systems also produce information that can be used to maximize efficiency and output and minimize costs. This article is a discussion of such on-line systems. Technical advances providing the basis for these systems and general applications of these systems are reviewed. Specific applications at the Hausling pumped storage project and the Itaipu hydroelectric project are discussed.

  9. On-line fluorometric microbiological analysis for life support systems

    NASA Astrophysics Data System (ADS)

    Schlager, Kenneth J.

    1992-07-01

    Fluorometric data, both spectral and time-resolved, are characterized by background luminescence and interfering, overlapping spectra from various living and nonliving fluorometric sources. Sophisticated pattern recognition techniques are used to identify and quantify microbial species of interest in the complex measurement environment. It is concluded that advanced pattern recognition methods based on neural networks supervised by genetic algorithms have been quite successful in identifying and quantifying bacteria and fungi in continuous on-line monitoring applications.

  10. CCD Base Line Subtraction Algorithms

    SciTech Connect

    Kotov, I.V.; OConnor, P.; Kotov, A.; Frank, J.; Perevoztchikov, V.; Takacs, P.

    2010-06-28

    High statistics astronomical surveys require photometric accuracy on a few percent level. The accuracy of sensor calibration procedures should match this goal. The first step in calibration procedures is the base line subtraction. The accuracy and robustness of different base line subtraction techniques used for Charge Coupled Device (CCD) sensors are discussed.

  11. Characteristic impedance of microstrip lines

    NASA Technical Reports Server (NTRS)

    Bailey, M. C.; Deshpande, M. D.

    1989-01-01

    The dyadic Green's function for a current embedded in a grounded dielectric slab is used to analyze microstrip lines at millimeter wave frequencies. The dyadic Green's function accounts accurately for fringing fields and dielectric cover over the microstrip line. Using Rumsey's reaction concept, an expression for the characteristic impedance is obtained. The numerical results are compared with other reported results.

  12. Line Manager Involvement in Careers.

    ERIC Educational Resources Information Center

    Renwick, Douglas; MacNeil, Christina M.

    2002-01-01

    Human resource functions have "devolved" to line managers, raising issues related to supervisors' ability and willingness to develop employees and the benefits and costs to the organization. Devolution of this work also has implications for the career development of human resource managers and line managers themselves. (Contains 39 references.)…

  13. relline: Relativistic line profiles calculation

    NASA Astrophysics Data System (ADS)

    Dauser, Thomas

    2015-05-01

    relline calculates relativistic line profiles; it is compatible with the common X-ray data analysis software XSPEC (ascl:9910.005) and ISIS (ascl:1302.002). The two basic forms are an additive line model (RELLINE) and a convolution model to calculate relativistic smearing (RELCONV).

  14. Biology of SNU Cell Lines

    PubMed Central

    Ku, Ja-Lok

    2005-01-01

    SNU (Seoul National University) cell lines have been established from Korean cancer patients since 1982. Of these 109 cell lines have been characterized and reported, i.e., 17 colorectal carcinoma, 12 hepatocellular carcinoma, 11 gastric carcinoma, 12 uterine cervical carcinoma, 17 B-lymphoblastoid cell lines derived from cancer patients, 5 ovarian carcinoma, 3 malignant mixed Mllerian tumor, 6 laryngeal squamous cell carcinoma, 7 renal cell carcinoma, 9 brain tumor, 6 biliary tract, and 4 pancreatic carcinoma cell lines. These SNU cell lines have been distributed to biomedical researchers domestic and worldwide through the KCLB (Korean Cell Line Bank), and have proven to be of value in various scientific research fields. The characteristics of these cell lines have been reported in over 180 international journals by our laboratory and by many other researchers from 1987. In this paper, the cellular and molecular characteristics of SNU human cancer cell lines are summarized according to their genetic and epigenetic alterations and functional analysis. PMID:19956504

  15. Where Should We Go With Advanced Placement?

    NASA Astrophysics Data System (ADS)

    Lichten, William

    2001-04-01

    This is a review of the Advanced Placement (AP)Program. In disagreement with claims of the College Board, there is firm evidence that the average test performance level has dropped. The College Board's scale and claims for AP qualification disagree seriously with college standards. A majority of tests taken do not qualify. It appears that "advanced placement" is coming closer to "placement." This paper recommends that the College Board's policy, which previously has concentrated on the numbers of participants, should include an emphasis on student performance and program quality. AP could accomplish its goal of reaching a wider range of students by changing along the lines followed in college introductory physics courses: multiple tracks.

  16. Advances in Primary Central Nervous System Lymphoma.

    PubMed

    Patrick, Lauren B; Mohile, Nimish A

    2015-12-01

    Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that is limited to the CNS. Although novel imaging techniques aid in discriminating lymphoma from other brain tumors, definitive diagnosis requires brain biopsy, vitreoretinal biopsy, or cerebrospinal fluid analysis. Survival rates in clinical studies have improved over the past 20 years due to the addition of high-dose methotrexate-based chemotherapy regimens to whole-brain radiotherapy. Long-term survival, however, is complicated by clinically devastating delayed neurotoxicity. Newer regimens are attempting to reduce or eliminate radiotherapy from first-line treatment with chemotherapy dose intensification. Significant advances have also been made in the fields of pathobiology and treatment, with more targeted treatments on the horizon. The rarity of the disease makes conducting of prospective clinical trials challenging, requiring collaborative efforts between institutions. This review highlights recent advances in the biology, detection, and treatment of PCNSL in immunocompetent patients.

  17. Advanced Rotorcraft Transmission (ART) Program summary

    NASA Astrophysics Data System (ADS)

    Krantz, T. L.; Kish, J. G.

    1992-07-01

    The Advanced Rotorcraft Transmission (ART) Program was initiated to advance the state of the art for rotorcraft transmissions. The goal of the ART Program was to develop and demonstrate the technologies needed to reduce transmission weight by 25 pct and reduce noise by 10 dB while obtaining a 5000 hr 'mean time between failure'. The research done under the ART Program is summarized. A split path design was selected as best able to meet the program goals. Key part technologies needed for this design were identified, studied, and developed. Two of these technologies are discussed in detail: the load sharing of split path designs including the use of a compliant elastomeric torque splitter and the application of a high ratio, low pitch line velocity gear mesh. Development of an angular contact spherical roller bearing, transmission error analysis, and fretting fatigue testing are discussed. The technologies for a light weight, quiet, and reliable rotorcraft transmission were demonstrated.

  18. Advanced Rotorcraft Transmission (ART) program summary

    NASA Technical Reports Server (NTRS)

    Krantz, T. L.; Kish, J. G.

    1992-01-01

    The Advanced Rotorcraft Transmission (ART) Program was initiated to advance the state of the art for rotorcraft transmissions. The goal of the ART Program was to develop and demonstrate the technologies needed to reduce transmission weight by 25 pct. and reduce noise by 10 dB while obtaining a 5000 hr 'mean time between failure'. The research done under the ART Program is summarized. A split path design was selected as best able to meet the program goals. Key part technologies needed for this design were identified, studied, and developed. Two of these technologies are discussed in detail: the load sharing of split path designs including the use of a compliant elastomeric torque splitter and the application of a high ratio, low pitch line velocity gear mesh. Development of an angular contact spherical roller bearing, transmission error analysis, and fretting fatigue testing are discussed. The technologies for a light weight, quiet, and reliable rotorcraft transmission were demonstrated.

  19. Advances in Primary Central Nervous System Lymphoma.

    PubMed

    Patrick, Lauren B; Mohile, Nimish A

    2015-12-01

    Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that is limited to the CNS. Although novel imaging techniques aid in discriminating lymphoma from other brain tumors, definitive diagnosis requires brain biopsy, vitreoretinal biopsy, or cerebrospinal fluid analysis. Survival rates in clinical studies have improved over the past 20 years due to the addition of high-dose methotrexate-based chemotherapy regimens to whole-brain radiotherapy. Long-term survival, however, is complicated by clinically devastating delayed neurotoxicity. Newer regimens are attempting to reduce or eliminate radiotherapy from first-line treatment with chemotherapy dose intensification. Significant advances have also been made in the fields of pathobiology and treatment, with more targeted treatments on the horizon. The rarity of the disease makes conducting of prospective clinical trials challenging, requiring collaborative efforts between institutions. This review highlights recent advances in the biology, detection, and treatment of PCNSL in immunocompetent patients. PMID:26475775

  20. US line-ups outperform UK line-ups

    PubMed Central

    Seale-Carlisle, Travis M.

    2016-01-01

    In the USA and the UK, many thousands of police suspects are identified by eyewitnesses every year. Unfortunately, many of those suspects are innocent, which becomes evident when they are exonerated by DNA testing, often after having been imprisoned for years. It is, therefore, imperative to use identification procedures that best enable eyewitnesses to discriminate innocent from guilty suspects. Although police investigators in both countries often administer line-up procedures, the details of how line-ups are presented are quite different and an important direct comparison has yet to be conducted. We investigated whether these two line-up procedures differ in terms of (i) discriminability (using receiver operating characteristic analysis) and (ii) reliability (using confidence–accuracy characteristic analysis). A total of 2249 participants watched a video of a crime and were later tested using either a six-person simultaneous photo line-up procedure (USA) or a nine-person sequential video line-up procedure (UK). US line-up procedure yielded significantly higher discriminability and significantly higher reliability. The results do not pinpoint the reason for the observed difference between the two procedures, but they do suggest that there is much room for improvement with the UK line-up. PMID:27703695

  1. Recent advances in chemotherapy for advanced gastric cancer.

    PubMed

    Kim, Jong Gwang; Chung, Ho Young; Yu, Wansik

    2010-07-15

    Although medical treatment has been shown to improve quality of life and prolong survival, no significant progress has been made in the treatment of advanced gastric cancer (AGC) within the last two decades. Thus, the choice of optimum standard first-line chemotherapy regimen for AGC remains debatable, and most responses to chemotherapy are partial and of short duration, with a median survival of approximately 7-11 mo and survival at 2 years rarely more than 10%. Recently, remarkable progress in tumor biology has led to the development of new agents that target critical aspects of oncogenic pathways. For AGC, several molecular targeting agents are now under evaluation in international randomized studies, and trastuzumab, an anti-HER2 monoclonal antibody, has shown antitumor activity against HER-2 positive AGC. However, this benefit is limited to only about 20% of patients with AGC (patients with HER-2 positive AGC). Therefore, there remains a critical need for both the development of more effective agents and the identification of predictive and prognostic molecular markers to select those patients who will benefit most from specific chemotherapeutic regimens and targeted therapies.

  2. Advanced transmission studies

    NASA Technical Reports Server (NTRS)

    Coy, John J.; Bill, Robert C.

    1988-01-01

    The NASA Lewis Research Center and the U.S. Army Aviation Systems Command share an interest in advancing the technology for helicopter propulsion systems. In particular, this paper presents highlights from that portion of the program in drive train technology and the related mechanical components. The major goals of the program are to increase the life, reliability, and maintainability; reduce the weight, noise, and vibration; and maintain the relatively high mechanical efficiency of the gear train. The current activity emphasizes noise reduction technology and analytical code development followed by experimental verification. Selected significant advances in technology for transmissions are reviewed, including advanced configurations and new analytical tools. Finally, the plan for future transmission research is presented.

  3. Advanced Hydrogen Turbine Development

    SciTech Connect

    Marra, John

    2015-09-30

    Under the sponsorship of the U.S. Department of Energy (DOE) National Energy Technology Laboratories, Siemens has completed the Advanced Hydrogen Turbine Development Program to develop an advanced gas turbine for incorporation into future coal-based Integrated Gasification Combined Cycle (IGCC) plants. All the scheduled DOE Milestones were completed and significant technical progress was made in the development of new technologies and concepts. Advanced computer simulations and modeling, as well as subscale, full scale laboratory, rig and engine testing were utilized to evaluate and select concepts for further development. Program Requirements of: A 3 to 5 percentage point improvement in overall plant combined cycle efficiency when compared to the reference baseline plant; 20 to 30 percent reduction in overall plant capital cost when compared to the reference baseline plant; and NOx emissions of 2 PPM out of the stack. were all met. The program was completed on schedule and within the allotted budget

  4. Advances in craniofacial surgery.

    PubMed

    Tatum, Sherard A; Losquadro, William D

    2008-01-01

    The past 10 years have witnessed many advances in craniofacial surgery. Advances in surgical techniques, such as distraction osteogenesis and endoscopic procedures, combined with refinements in surgical equipment, such as resorbable plating and distractors, have improved surgical outcomes, while minimizing morbidity. Technological advances in 3-dimensional imaging, computer simulation, and intraoperative navigation facilitate diagnosis, preoperative planning, and surgical execution. Rising cases of deformational plagiocephaly owing to increased supine infant sleep positioning necessitated the development of appropriate diagnosis and treatment and the avoidance of unnecessary surgery. A greater understanding of the genetic basis of craniofacial disorders has allowed better preoperative assessment and counseling. Finally, efforts to develop better bone graft substitutes with gene therapy and nanotechnology are ongoing. PMID:19018057

  5. Advanced thermionic energy conversion

    NASA Technical Reports Server (NTRS)

    Britt, E. J.; Fitzpatrick, G. D.; Hansen, L. K.; Rasor, N. S.

    1974-01-01

    Basic analytical and experimental exploration was conducted on several types of advanced thermionic energy converters, and preliminary analysis was performed on systems utilizing advanced converter performance. The Pt--Nb cylindrical diode which exhibited a suppressed arc drop, as described in the preceding report, was reassembled and the existence of the postulated hydrid mode of operation was tentatively confirmed. Initial data obtained on ignited and unignited triode operation in the demountable cesium vapor system essentially confirmed the design principles developed in earlier work, with a few exceptions. Three specific advanced converter concepts were selected as candidates for concentrated basic study and for practical evaluation in fixed-configuration converters. Test vehicles and test stands for these converters and a unique controlled-atmosphere station for converter assembly and processing were designed, and procurement was initiated.

  6. Advanced servomanipulator development

    SciTech Connect

    Kuban, D.P.

    1985-01-01

    The Advanced Servomanipulator (ASM) System consists of three major components: the ASM slave, the dual arm master controller (DAMC) or master, and the control system. The ASM is remotely maintainable force-reflecting servomanipulator developed at the Oak Ridge National Laboratory (ORNL) as part of the Consolidated Fuel Reprocessing Program. This new manipulator addresses requirements of advanced nuclear fuel reprocessing with emphasis on force reflection, remote maintainability, reliability, radiation tolerance, and corrosion resistance. The advanced servomanipulator is uniquely subdivided into remotely replaceable modules which will permit in situ manipulator repair by spare module replacement. Manipulator modularization and increased reliability are accomplished through a force transmission system that uses gears and torque tubes. Digital control algorithms and mechanical precision are used to offset the increased backlash, friction, and inertia resulting from the gear drives. This results in the first remotely maintainable force-reflecting servomanipulator in the world.

  7. Advanced ramjet concepts program

    NASA Technical Reports Server (NTRS)

    Leingang, J. L.

    1992-01-01

    Uniquely advantageous features, on both the performance and weight sides of the ledger, can be achieved through synergistic design integration of airbreathing and rocket technologies in the development of advanced orbital space transport propulsion systems of the combined cycle type. In the context of well understood advanced airbreathing and liquid rocket propulsion principles and practices, this precept of synergism is advanced mainly through six rather specific examples. These range from the detailed component level to the overall vehicle system level as follows: using jet compression; achieving a high area ratio rocket nozzle; ameliorating gas generator cycle rocket system deficiencies; using the in-duct special rocket thrust chamber assembly as the principal scramjet fuel injection operation; using the unstowed, covered fan as a duct closure for effecting high area ratio rocket mode operation; and creating a unique airbreathing rocket system via the onboard, cryogenic hydrogen induced air liquefaction process.

  8. CONDOR Advanced Visionics System

    NASA Astrophysics Data System (ADS)

    Kanahele, David L.; Buckanin, Robert M.

    1996-06-01

    The Covert Night/Day Operations for Rotorcraft (CONDOR) program is a collaborative research and development program between the governments of the United States and the United Kingdom of Great Britain and Northern Ireland to develop and demonstrate an advanced visionics concept coupled with an advanced flight control system to improve rotorcraft mission effectiveness during day, night, and adverse weather conditions in the Nap- of-the-Earth environment. The Advanced Visionics System for CONDOR is the flight- ruggedized head mounted display and computer graphics generator with the intended use of exploring, developing, and evaluating proposed visionic concepts for rotorcraft including; the application of color displays, wide field-of-view, enhanced imagery, virtual displays, mission symbology, stereo imagery, and other graphical interfaces.

  9. Advanced quantum noise correlations

    NASA Astrophysics Data System (ADS)

    Vogl, Ulrich; Glasser, Ryan T.; Clark, Jeremy B.; Glorieux, Quentin; Li, Tian; Corzo, Neil V.; Lett, Paul D.

    2014-01-01

    We use the quantum correlations of twin beams of light to investigate the fundamental addition of noise when one of the beams propagates through a fast-light medium based on phase-insensitive gain. The experiment is based on two successive four-wave mixing processes in rubidium vapor, which allow for the generation of bright two-mode-squeezed twin beams followed by a controlled advancement while maintaining the shared quantum correlations between the beams. The demonstrated effect allows the study of irreversible decoherence in a medium exhibiting anomalous dispersion, and for the first time shows the advancement of a bright nonclassical state of light. The advancement and corresponding degradation of the quantum correlations are found to be operating near the fundamental quantum limit imposed by using a phase-insensitive amplifier.

  10. Advanced Aerodynamic Control Effectors

    NASA Technical Reports Server (NTRS)

    Wood, Richard M.; Bauer, Steven X. S.

    1999-01-01

    A 1990 research program that focused on the development of advanced aerodynamic control effectors (AACE) for military aircraft has been reviewed and summarized. Data are presented for advanced planform, flow control, and surface contouring technologies. The data show significant increases in lift, reductions in drag, and increased control power, compared to typical aerodynamic designs. The results presented also highlighted the importance of planform selection in the design of a control effector suite. Planform data showed that dramatic increases in lift (greater than 25%) can be achieved with multiple wings and a sawtooth forebody. Passive porosity and micro drag generator control effector data showed control power levels exceeding that available from typical effectors (moving surfaces). Application of an advanced planform to a tailless concept showed benefits of similar magnitude as those observed in the generic studies.

  11. Cyclotron Line Measurements with INTEGRAL

    NASA Technical Reports Server (NTRS)

    Pottschmidt, K.; Kreykenbohm, I.; Caballero, I.; Fritz, S.; Schoenherr, G.; Kretschmar, P.; Wilms, J.; McBride, V. A.; Suchy, S.; Rothschild, R. E.

    2008-01-01

    Due to its broadband energy coverage, INTEGRAL has made important contributions to observing and interpreting cyclotron lines, which are present in the 10-100 keV range of a sample of accreting pulsars. In these systems photons with energies fulfilling the resonance condition inelastically Compton scatter off electrons quantized in the accretion column above the neutron star's magnetic pole(s). This process gives rise to the broad, absorption-like lines or 'cyclotron resonant scattering features' (CRSF). The observed lines allow to directly measure the B-fields of these sources, resulting in values of a few times 1E12G. In this overview I will present recent highlights regarding CRSF observations as well as discuss current ideas and models for the physical conditions in the accretion column. Among the former are the stability of the spectrum of Vela X-1 during giant flares in 2003, the observation of three cyclotron lines during the 2004 outburst of V0332+53, the confirmation of the fundamental line at approximately 45 keV during a 2005 normal outburst of A0535-26, and the simultaneous detection of the two lines in the dipping source 4U 1907+09 (for which also a torque reversal was detected for the first time). Through these and other observations it has become increasingly apparent that two types of observations can potentially be used to constrain the accretion column geometry: the determination of energy ratios for multiple harmonic lines (only two sources with greater than 2 lines are known), was well as the evolution of the fundamental line centroid, which, for different sources, may or may not be correlated with flux. Furthermore, first steps have been taken away from the usual phenomenological description of the lines, towards a physical approach based on self-consistent CRSF modeling. Initial applications are presented.

  12. Advanced fuel chemistry for advanced engines.

    SciTech Connect

    Taatjes, Craig A.; Jusinski, Leonard E.; Zador, Judit; Fernandes, Ravi X.; Miller, James A.

    2009-09-01

    Autoignition chemistry is central to predictive modeling of many advanced engine designs that combine high efficiency and low inherent pollutant emissions. This chemistry, and especially its pressure dependence, is poorly known for fuels derived from heavy petroleum and for biofuels, both of which are becoming increasingly prominent in the nation's fuel stream. We have investigated the pressure dependence of key ignition reactions for a series of molecules representative of non-traditional and alternative fuels. These investigations combined experimental characterization of hydroxyl radical production in well-controlled photolytically initiated oxidation and a hybrid modeling strategy that linked detailed quantum chemistry and computational kinetics of critical reactions with rate-equation models of the global chemical system. Comprehensive mechanisms for autoignition generally ignore the pressure dependence of branching fractions in the important alkyl + O{sub 2} reaction systems; however we have demonstrated that pressure-dependent 'formally direct' pathways persist at in-cylinder pressures.

  13. Advances in the Treatment of Neuropathic Pain.

    PubMed

    Xu, Li; Zhang, Yuguan; Huang, Yuguang

    2016-01-01

    Neuropathic pain is pain that arises as a direct consequence of a lesion or diseases affecting the somatosensory system. Treatments for neuropathic pain include pharmacological, nonpharmacological, and interventional therapies. Currently recommended first-line pharmacological treatments include antidepressants and anticonvulsants (gabapentin and pregabalin). However, in some cases, pharmacological therapy alone fails to give adequate control of the chronic pain. New techniques have been invented and have been proved effective on neuropathic pain, such as behavioral, cognitive, integrative, and physical therapies. In this review, we focused on the advances in the treatment of central neuropathic pain, diabetic peripheral neuropathy, postherpetic neuralgia, and cancer pain. PMID:26900067

  14. 46 CFR 45.31 - Deck line.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Deck line. 45.31 Section 45.31 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES GREAT LAKES LOAD LINES Load Line Marks § 45.31 Deck line. (a) Each vessel must be marked with a deck line on the outer surface of the shell on each side...

  15. 46 CFR 45.31 - Deck line.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Deck line. 45.31 Section 45.31 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES GREAT LAKES LOAD LINES Load Line Marks § 45.31 Deck line. (a) Each vessel must be marked with a deck line on the outer surface of the shell on each side...

  16. Teaching Braille Line Tracking Using Stimulus Fading

    ERIC Educational Resources Information Center

    Scheithauer, Mindy C.; Tiger, Jeffrey H.

    2014-01-01

    Line tracking is a prerequisite skill for braille literacy that involves moving one's finger horizontally across a line of braille text and identifying when a line ends so the reader may reset his or her finger on the subsequent line. Current procedures for teaching line tracking are incomplete, because they focus on tracking lines with only…

  17. Advanced solar dynamic technology program

    NASA Technical Reports Server (NTRS)

    Calogeras, James

    1990-01-01

    Viewgraphs and discussion on Advanced Solar Dynamic Technology Program are presented. Topics covered include: advanced solar dynamic technology program; advanced concentrators; advanced heat receivers; power conversion systems; dished all metal honeycomb sandwich panels; Stirling cavity heat pipe receiver; Brayton solar receiver; and thermal energy storage technology.

  18. Parachute systems technology: Fundamentals, concepts, and applications: Advanced parachute design

    SciTech Connect

    Peterson, C.W.; Johnson, D.W.

    1987-01-01

    Advances in high-performance parachute systems and the technologies needed to design them are presented in this paper. New parachute design and performance prediction codes are being developed to assist the designer in meeting parachute system performance requirements after a minimum number of flight tests. The status of advanced design codes under development at Sandia National Laboratories is summarized. An integral part of parachute performance prediction is the rational use of existing test data. The development of a data base for parachute design has been initiated to illustrate the effects of inflated diameter, geometric porosity, reefing line length, suspension line length, number of gores, and number of ribbons on parachute drag. Examples of advancements in parachute materials are presented, and recent problems with Mil-Spec broadgoods are reviewed. Finally, recent parachute systems tested at Sandia are summarized to illustrate new uses of old parachutes, new parachute configurations, and underwater recovery of payloads.

  19. MR Neurography: Advances

    PubMed Central

    Chhabra, Avneesh; Zhao, Lianxin; Carrino, John A.; Trueblood, Eo; Koceski, Saso; Shteriev, Filip; Lenkinski, Lionel; Sinclair, Christopher D. J.; Andreisek, Gustav

    2013-01-01

    High resolution and high field magnetic resonance neurography (MR neurography, MRN) is shown to have excellent anatomic capability. There have been considerable advances in the technology in the last few years leading to various feasibility studies using different structural and functional imaging approaches in both clinical and research settings. This paper is intended to be a useful seminar for readers who want to gain knowledge of the advancements in the MRN pulse sequences currently used in clinical practice as well as learn about the other techniques on the horizon aimed at better depiction of nerve anatomy, pathology, and potential noninvasive evaluation of nerve degeneration or regeneration. PMID:23589774

  20. Advances in attosecond science

    NASA Astrophysics Data System (ADS)

    Calegari, Francesca; Sansone, Giuseppe; Stagira, Salvatore; Vozzi, Caterina; Nisoli, Mauro

    2016-03-01

    Attosecond science offers formidable tools for the investigation of electronic processes at the heart of important physical processes in atomic, molecular and solid-state physics. In the last 15 years impressive advances have been obtained from both the experimental and theoretical points of view. Attosecond pulses, in the form of isolated pulses or of trains of pulses, are now routinely available in various laboratories. In this review recent advances in attosecond science are reported and important applications are discussed. After a brief presentation of various techniques that can be employed for the generation and diagnosis of sub-femtosecond pulses, various applications are reported in atomic, molecular and condensed-matter physics.

  1. Advancing cardiovascular tissue engineering

    PubMed Central

    Truskey, George A.

    2016-01-01

    Cardiovascular tissue engineering offers the promise of biologically based repair of injured and damaged blood vessels, valves, and cardiac tissue. Major advances in cardiovascular tissue engineering over the past few years involve improved methods to promote the establishment and differentiation of induced pluripotent stem cells (iPSCs), scaffolds from decellularized tissue that may produce more highly differentiated tissues and advance clinical translation, improved methods to promote vascularization, and novel in vitro microphysiological systems to model normal and diseased tissue function. iPSC technology holds great promise, but robust methods are needed to further promote differentiation. Differentiation can be further enhanced with chemical, electrical, or mechanical stimuli. PMID:27303643

  2. Advanced engine study program

    NASA Astrophysics Data System (ADS)

    Masters, A. I.; Galler, D. E.; Denman, T. F.; Shied, R. A.; Black, J. R.; Fierstein, A. R.; Clark, G. L.; Branstrom, B. R.

    1993-06-01

    A design and analysis study was conducted to provide advanced engine descriptions and parametric data for space transfer vehicles. The study was based on an advanced oxygen/hydrogen engine in the 7,500 to 50,000 lbf thrust range. Emphasis was placed on defining requirements for high-performance engines capable of achieving reliable and versatile operation in a space environment. Four variations on the expander cycle were compared, and the advantages and disadvantages of each were assessed. Parametric weight, envelope, and performance data were generated over a range of 7,500 to 50,000 lb thrust and a wide range of chamber pressure and nozzle expansion ratio.

  3. Advanced engine study program

    NASA Technical Reports Server (NTRS)

    Masters, A. I.; Galler, D. E.; Denman, T. F.; Shied, R. A.; Black, J. R.; Fierstein, A. R.; Clark, G. L.; Branstrom, B. R.

    1993-01-01

    A design and analysis study was conducted to provide advanced engine descriptions and parametric data for space transfer vehicles. The study was based on an advanced oxygen/hydrogen engine in the 7,500 to 50,000 lbf thrust range. Emphasis was placed on defining requirements for high-performance engines capable of achieving reliable and versatile operation in a space environment. Four variations on the expander cycle were compared, and the advantages and disadvantages of each were assessed. Parametric weight, envelope, and performance data were generated over a range of 7,500 to 50,000 lb thrust and a wide range of chamber pressure and nozzle expansion ratio.

  4. Avionics advanced development strategy

    NASA Technical Reports Server (NTRS)

    Dyer, D.

    1990-01-01

    Discussed here is the problem of how to put together an integrated, phased, and affordable avionics advanced development program that links and applies to operational, evolving, and developing programs/vehicles, as well as those in the planning phases. Collecting technology needs from individual programs/vehicles and proposed technology items from individual developers usually results in a mismatch and something that is unaffordable. A strategy to address this problem is outlined with task definitions which will lead to avionics advanced development items that will fit within an overall framework, prioritized to support budgeting, and support the scope of NASA space transportations needs.

  5. Advanced Monitoring systems initiative

    SciTech Connect

    R.J. Venedam; E.O. Hohman; C.F. Lohrstorfer; S.J. Weeks; J.B. Jones; W.J. Haas

    2004-09-30

    The Advanced Monitoring Systems Initiative (AMSI) actively searches for promising technologies and aggressively moves them from the research bench into DOE/NNSA end-user applications. There is a large unfulfilled need for an active element that reaches out to identify and recruit emerging sensor technologies into the test and evaluation function. Sensor research is ubiquitous, with the seeds of many novel concepts originating in the university systems, but at present these novel concepts do not move quickly and efficiently into real test environments. AMSI is a widely recognized, self-sustaining ''business'' accelerating the selection, development, testing, evaluation, and deployment of advanced monitoring systems and components.

  6. Advanced sensors technology survey

    NASA Technical Reports Server (NTRS)

    Cooper, Tommy G.; Costello, David J.; Davis, Jerry G.; Horst, Richard L.; Lessard, Charles S.; Peel, H. Herbert; Tolliver, Robert

    1992-01-01

    This project assesses the state-of-the-art in advanced or 'smart' sensors technology for NASA Life Sciences research applications with an emphasis on those sensors with potential applications on the space station freedom (SSF). The objectives are: (1) to conduct literature reviews on relevant advanced sensor technology; (2) to interview various scientists and engineers in industry, academia, and government who are knowledgeable on this topic; (3) to provide viewpoints and opinions regarding the potential applications of this technology on the SSF; and (4) to provide summary charts of relevant technologies and centers where these technologies are being developed.

  7. Advanced Neuroimaging of Tinnitus.

    PubMed

    Raghavan, Prashant; Steven, Andrew; Rath, Tanya; Gandhi, Dheeraj

    2016-05-01

    Although tinnitus may originate in damage to the peripheral auditory apparatus, its perception and distressing symptomatology are consequences of alterations to auditory, sensory, and limbic neural networks. This has been described in several studies, some using advanced structural MR imaging techniques such as diffusion tensor imaging. An understanding of these complex changes could enable development of targeted treatment. New MR imaging techniques enabling detailed depiction of the labyrinth may be useful when diagnosis of Meniere disease is equivocal. Advances in computed tomography and MR imaging have enabled noninvasive diagnosis of dural arteriovenous fistulae. PMID:27154611

  8. Advanced Solar Power Systems

    NASA Technical Reports Server (NTRS)

    Atkinson, J. H.; Hobgood, J. M.

    1984-01-01

    The Advanced Solar Power System (ASPS) concentrator uses a technically sophisticated design and extensive tooling to produce very efficient (80 to 90%) and versatile energy supply equipment which is inexpensive to manufacture and requires little maintenance. The advanced optical design has two 10th order, generalized aspheric surfaces in a Cassegrainian configuration which gives outstanding performance and is relatively insensitive to temperature changes and wind loading. Manufacturing tolerances also have been achieved. The key to the ASPS is the direct absorption of concentrated sunlight in the working fluid by radiative transfers in a black body cavity. The basic ASPS design concepts, efficiency, optical system, and tracking and focusing controls are described.

  9. Advanced subsonic transport propulsion

    NASA Technical Reports Server (NTRS)

    Nored, D. L.; Ciepluch, C. C.; Chamberlain, R.; Meleason, E. T.; Kraft, G. A.

    1981-01-01

    A brief review of the current NASA Energy Efficient Engine (E(3)) Project is presented. Included in this review are the factors that influenced the design of these turbofan engines and the advanced technology incorporated in them to reduce fuel consumption and improve environmental characteristics. In addition, factors such as the continuing spiral in fuel cost, that could influence future aircraft propulsion systems beyond those represented by the E(3) engines, are also discussed. Advanced technologies that will address these influencing factors and provide viable future propulsion systems are described. The potential importance of other propulsion system types, such as geared fans and turboshaft engines, is presented.

  10. Advances in surgery.

    PubMed

    Weder, W

    2012-09-01

    In the last decade, technological advances, new staging tools, better understanding the role of surgery within multimodal treatment concepts in advanced stages and progress in the functional assessment of surgical candidates improved the quality of surgery in the management of patients with lung cancer. Lung resection with video-assisted thoracoscopic access gained wide acceptance, the indication for lobectomy or sublobar resection in early stages was applied based on new data and selection for multimodal treatment in stage III is better understood based on the data. a major impact on the outcome of patients with lung cancer has the treatment in specialized high-volume centers.

  11. Reliability Testing of Advanced Interconnect Materials

    NASA Astrophysics Data System (ADS)

    Keller, R. R.; Strus, M. C.; Chiaramonti, A. N.; Kim, Y. L.; Jung, Y. J.; Read, D. T.

    2011-11-01

    We describe the development of electrical test methods to evaluate damage that determines reliability in advanced, small-scale conductors, including damascene copper and aligned carbon nanotube networks. Rapid thermal cycling induced during high-current AC stressing provides a means for measuring lifetimes associated with cyclic plasticity and/or diffusive damage in damascene copper. The specific type of damage that develops depends on the line geometry and the nature of the stress state induced within the lines during cycling. Voids form in both fully passivated and partially passivated lines under high levels of hydrostatic tension. Dislocation activity takes place in partially passivated lines in the presence of high shears. High-current DC stressing provides a means for evaluating the fabrication quality of aligned carbon nanotube (CNT) networks, in what we believe to be the first lifetime degradation tests of such materials. While classic electromigration is unlikely in nanocarbon, we observed through resistance changes two forms of degradation that we believe are tied to the nanotube packing and resulting conduction path density through the network: a gradual build-up of damage, and a more abrupt, unpredictable form of damage accumulation, which may be linked to sudden changes in network morphology due to stressing.

  12. Start up testing for the secure automated fabrication line

    SciTech Connect

    Gerber, E.W.; Benson, E.M.; Dahl, R.E.

    1986-10-21

    The Secure Automated Fabrication (SAF) Line has been designed and built by Westinghouse Hanford Company for the Department of Energy at the Hanford Site near Richland, Washington. The SAF Line will provide the capability for remote manufacture of fuel for Liquid Metal Reactors, and will supply fuel for the Fast Flux Test Facility (FFTF). The SAF process is highly automated and represents a major advancement in nuclear fuel manufacturing, offering significant improvements in product quality, productivity, safety, and accountability of Special Nuclear Materials. The construction phase of the project is complete, and testing has been initiated to accomplish start up of the plant for manufacture of FFTF fuel. This paper describes the test methodology used for SAF Line start up.

  13. Advanced infrared astronomy

    NASA Technical Reports Server (NTRS)

    Kostiuk, Theodor

    1991-01-01

    This task supports the application of infrared heterodyne spectroscopy and other high resolution techniques, as well as infrared arrays to ultra-high resolution studies of molecular constituents of planetary atmospheres. High spectral and spatial resolution measurement and analysis of individual spectral lines permits the retrieval of distributions of atmospheric molecular abundances and temperatures and thus, information on local photochemical processes. Determination of absolute line positions to better than 10(exp -8) permits direct measurement of gas velocities to a few m/sec and thus, the study of dynamics. Observations are made from ground based observatories.

  14. Advanced proteomic liquid chromatography

    SciTech Connect

    Xie, Fang; Smith, Richard D.; Shen, Yufeng

    2012-10-26

    Liquid chromatography coupled with mass spectrometry is the predominant platform used to analyze proteomics samples consisting of large numbers of proteins and their proteolytic products (e.g., truncated polypeptides) and spanning a wide range of relative concentrations. This review provides an overview of advanced capillary liquid chromatography techniques and methodologies that greatly improve separation resolving power and proteomics analysis coverage, sensitivity, and throughput.

  15. Advanced geometries and regimes

    SciTech Connect

    Bulanov, S. S.; Bulanov, S. V.; Turchetti, G.; Limpouch, J.; Klimo, O.; Psikal, J.; Margarone, D.; Korn, G.

    2013-07-26

    We review and discuss different schemes of laser ion acceleration as well as advanced target geometries in connection with the development of the laser-driven proton source for hadron therapy of oncological diseases, which is a part of the ELIMED project.

  16. Advanced Cell Technology, Inc.

    PubMed

    Caldwell, William M

    2007-03-01

    Advanced Cell Technology, Inc. (OTCBB: ACTC) is a biotechnology company applying novel human embryonic stem cell technologies in the emerging field of regenerative medicine. We believe that regenerative medicine has the potential to revolutionize the field by enabling scientists to produce human cells of any kind for use in a wide array of therapies.

  17. Advanced Combustion Engineering.

    ERIC Educational Resources Information Center

    Bartholomew, Calvin H.

    1987-01-01

    Describes the development of the Advanced Combustion Engineering Research Center (ACERC), which is a cooperative project of Brigham Young University, the University of Utah, and 25 governmental and industrial research laboratories. Discusses the research objectives, the academic program, the industrial relations and technology transfer program,…

  18. Advanced Plant Habitat (APH)

    NASA Technical Reports Server (NTRS)

    Richards, Stephanie E. (Compiler); Levine, Howard G.; Reed, David W.

    2016-01-01

    The Advanced Plant Habitat (APH) hardware will be a large growth volume plant habitat, capable of hosting multigenerational studies, in which environmental variables (e.g., temperature, relative humidity, carbon dioxide level light intensity and spectral quality) can be tracked and controlled in support of whole plant physiological testing and Bio-regenerative Life Support System investigations.

  19. Oklahoma's Advanced School Funding.

    ERIC Educational Resources Information Center

    Green, Gary

    A new means of funding school operations known as advanced school funding allows Oklahoma schools financing during the temporary cash shortfalls. The program consists of the Oklahoma Development Authority issuing revenue bonds purchased by E. F. Hutton and Company, Inc., which then sells the tax free bonds to investors throughout the country. A…

  20. Advanced Distribution Management System

    NASA Astrophysics Data System (ADS)

    Avazov, Artur R.; Sobinova, Liubov A.

    2016-02-01

    This article describes the advisability of using advanced distribution management systems in the electricity distribution networks area and considers premises of implementing ADMS within the Smart Grid era. Also, it gives the big picture of ADMS and discusses the ADMS advantages and functionalities.

  1. Advances in Distance Learning.

    ERIC Educational Resources Information Center

    1999

    This document contains three symposium papers on advances in distance learning. "The Adoption of Computer Technology and Telecommunications: A Case Study" (Larry M. Dooley, Teri Metcalf, Ann Martinez) reports on a study of the possible applications of two theoretical models (Rogers' Diffusion of Innovations model and the Concerns-Based Adoption…

  2. Advanced fossil energy utilization

    SciTech Connect

    Shekhawat, D.; Berry, D.; Spivey, J.; Pennline, H.; Granite, E.

    2010-01-01

    This special issue of Fuel is a selection of papers presented at the symposium ‘Advanced Fossil Energy Utilization’ co-sponsored by the Fuels and Petrochemicals Division and Research and New Technology Committee in the 2009 American Institute of Chemical Engineers (AIChE) Spring National Meeting Tampa, FL, on April 26–30, 2009.

  3. Advances in Helium Cryogenics

    NASA Astrophysics Data System (ADS)

    Sciver, S. W. Van

    This review provides a survey of major advances that have occurred in recent years in the area of helium cryogenics. Helium-temperature cryogenics is the enabling technology for a substantial and growing number of low-temperature systems from superconducting magnets to space-based experimental facilities. In recent years there have been many advances in the technology of low-temperature helium, driven mostly by new applications. However, to keep the review from being too broad, this presentation focuses mainly on three of the most significant advances. These are: (1) the development of large-scale recuperative refrigeration systems mainly for superconducting magnet applications in accelerators and other research facilities; (2) the use of stored superfluid helium (He II) as a coolant for spacebased astrophysics experiments; and (3) the application of regenerative cryocoolers operating at liquid helium temperatures primarily for cooling superconducting devices. In each case, the reader should observe that critical technologies were developed to facilitate these applications. In addition to these three primary advances, other significant helium cryogenic technologies are briefly reviewed at the end of this chapter, along with some vision for future developments in these areas.

  4. Advancing beyond AP Courses

    ERIC Educational Resources Information Center

    Hammond, Bruce G.

    2009-01-01

    A quiet revolution is picking up steam in the nation's private secondary schools, with broad implications for college admissions and for teaching and learning on both sides of the transition from high school to college. About 50 of the nation's leading college-preparatory schools have opted out of the College Board's Advanced Placement (AP)…

  5. The Advancement Checkup.

    ERIC Educational Resources Information Center

    Sanders, Joseph

    1993-01-01

    It is proposed that an external audit of a college advancement program is analogous to a periodic physical examination that offers objectivity and expertise. Audits are appropriate at the time of administrative transitions, performance difficulties, and even periods of sustained success. Guidelines and expectations are discussed. (MSE)

  6. Advanced intrarenal ureteroscopic procedures.

    PubMed

    Monga, Manoj; Beeman, William W

    2004-02-01

    The role of flexible ureteroscopy in the management of intrarenal pathology has undergone a dramatic evolution, powered by improvements in flexible ureteroscope design; deflection and image quality; diversification of small, disposable instrumentation; and the use of holmium laser lithotripsy. This article reviews the application of flexible ureteroscopy for advanced intrarenal procedures.

  7. Advanced Heart Failure

    MedlinePlus

    ... High Blood Pressure Tools & Resources Stroke More Advanced Heart Failure Updated:Oct 8,2015 When heart failure (HF) ... content was last reviewed on 04/06/2015. Heart Failure • Home • About Heart Failure • Causes and Risks for ...

  8. Advanced Chemical Propulsion

    NASA Technical Reports Server (NTRS)

    Alexander, Leslie, Jr.

    2006-01-01

    Advanced Chemical Propulsion (ACP) provides near-term incremental improvements in propulsion system performance and/or cost. It is an evolutionary approach to technology development that produces useful products along the way to meet increasingly more demanding mission requirements while focusing on improving payload mass fraction to yield greater science capability. Current activities are focused on two areas: chemical propulsion component, subsystem, and manufacturing technologies that offer measurable system level benefits; and the evaluation of high-energy storable propellants with enhanced performance for in-space application. To prioritize candidate propulsion technology alternatives, a variety of propulsion/mission analyses and trades have been conducted for SMD missions to yield sufficient data for investment planning. They include: the Advanced Chemical Propulsion Assessment; an Advanced Chemical Propulsion System Model; a LOx-LH2 small pumps conceptual design; a space storables propellant study; a spacecraft cryogenic propulsion study; an advanced pressurization and mixture ratio control study; and a pump-fed vs. pressure-fed study.

  9. Advanced Concept Modeling

    NASA Technical Reports Server (NTRS)

    Chaput, Armand; Johns, Zachary; Hodges, Todd; Selfridge, Justin; Bevirt, Joeben; Ahuja, Vivek

    2015-01-01

    Advanced Concepts Modeling software validation, analysis, and design. This was a National Institute of Aerospace contract with a lot of pieces. Efforts ranged from software development and validation for structures and aerodynamics, through flight control development, and aeropropulsive analysis, to UAV piloting services.

  10. Advanced Cardiac Life Support.

    ERIC Educational Resources Information Center

    Kirkwood Community Coll., Cedar Rapids, IA.

    This document contains materials for an advanced college course in cardiac life support developed for the State of Iowa. The course syllabus lists the course title, hours, number, description, prerequisites, learning activities, instructional units, required text, six references, evaluation criteria, course objectives by units, course…

  11. Advanced Test Reactor Tour

    SciTech Connect

    Miley, Don

    2011-01-01

    The Advanced Test Reactor at Idaho National Laboratory is the foremost nuclear materials test reactor in the world. This virtual tour describes the reactor, how experiments are conducted, and how spent nuclear fuel is handled and stored. For more information about INL research, visit http://www.facebook.com/idahonationallaboratory.

  12. The Teacher Advancement Program.

    ERIC Educational Resources Information Center

    Schiff, Tamara W.

    2002-01-01

    This publication contains two essays discussing the Teacher Advancement Program (TAP) and a criticism of merit pay for teachers. Today's schools are larger, often overcrowded, and frequently staffed by temporary or inexperienced teachers. TAP was created in response to the need for teacher-quality reform. It addresses challenges of teacher quality…

  13. Interfaces for Advanced Computing.

    ERIC Educational Resources Information Center

    Foley, James D.

    1987-01-01

    Discusses the coming generation of supercomputers that will have the power to make elaborate "artificial realities" that facilitate user-computer communication. Illustrates these technological advancements with examples of the use of head-mounted monitors which are connected to position and orientation sensors, and gloves that track finger and…

  14. Advancement's Sticky Issues

    ERIC Educational Resources Information Center

    Jackson, Patricia

    2011-01-01

    The author did not expect to be surprised or disturbed by the data from the latest Council for Advancement and Support of Education (CASE) salary survey; however, she was. CASE has been conducting the survey since 1982, so she assumed the findings would mirror her own salary history and those of her peers. While she suspected that older women…

  15. Advanced Gas Turbine (AGT)

    NASA Technical Reports Server (NTRS)

    1983-01-01

    The development and progress of the Advanced Gas Turbine engine program is examined. An analysis of the role of ceramics in the design and major engine components is included. Projected fuel economy, emissions and performance standards, and versatility in fuel use are also discussed.

  16. Advances in Planetary Geology

    NASA Technical Reports Server (NTRS)

    Woronow, A. (Editor)

    1982-01-01

    Advances in Planetary Geology is a new series intended to serve the planetary geology community with a form for quick and thorough communications. There are no set lists of acceptable topics or formats, and submitted manuscripts will not undergo a formal review. All submissions should be in a camera ready form, preferably spaced, and submitted to the editor.

  17. Advanced turbine systems program

    SciTech Connect

    Wilkes, C.; Mukavetz, D.W.; Knickerbocker, T.K.; Ali, S.A.

    1992-01-01

    In accordance with the goals of the DOE program, improvements in the gas turbine are the primary focus of Allison activity during Phase I. To this end Allison conducted a survey of potentially applicable gas turbine cycles and selected the advanced combined cycle as reference system. Extensive analysis of two versions of the advanced combined cycle was performed against the requirement for a 60% thermal efficiency (LHV) utility-sized, natural gas fired system. This analysis resulted in technology requirements for this system. Additional analysis determined emissions potential for the system, established a coal-fueled derivative system and a commercialization plan. This report deals with the technical requirements for a system that meets the thermal efficiency goal. Allison initially investigated four basic thermodynamic cycles: Humid air turbine, intercalate-recuperated systems, advanced combined cycle, chemically recuperated cycle. Our survey and cycle analysis indicated that au had the potential of reaching 60% thermal efficiency. We also concluded that engine hot section technology would be a critical technology regardless of which cycle was chosen. Based on this result Allison chose to concentrate on the advanced combined cycle. This cycle is well known and understood by the utility turbine user community and is therefore likely to be acceptable to users.

  18. Advanced turbine systems program

    SciTech Connect

    Wilkes, C.; Mukavetz, D.W.; Knickerbocker, T.K.; Ali, S.A.

    1992-12-31

    In accordance with the goals of the DOE program, improvements in the gas turbine are the primary focus of Allison activity during Phase I. To this end Allison conducted a survey of potentially applicable gas turbine cycles and selected the advanced combined cycle as reference system. Extensive analysis of two versions of the advanced combined cycle was performed against the requirement for a 60% thermal efficiency (LHV) utility-sized, natural gas fired system. This analysis resulted in technology requirements for this system. Additional analysis determined emissions potential for the system, established a coal-fueled derivative system and a commercialization plan. This report deals with the technical requirements for a system that meets the thermal efficiency goal. Allison initially investigated four basic thermodynamic cycles: Humid air turbine, intercalate-recuperated systems, advanced combined cycle, chemically recuperated cycle. Our survey and cycle analysis indicated that au had the potential of reaching 60% thermal efficiency. We also concluded that engine hot section technology would be a critical technology regardless of which cycle was chosen. Based on this result Allison chose to concentrate on the advanced combined cycle. This cycle is well known and understood by the utility turbine user community and is therefore likely to be acceptable to users.

  19. Infant Development: Recent Advances.

    ERIC Educational Resources Information Center

    Bremner, Gavin, Ed.; Slater, Alan, Ed.; Butterworth, George, Ed.

    Noting that the last 30 years have seen enormous increases in the understanding of infancy, this book examines the current state of knowledge regarding infant development. The book's contents stem from meetings of the British Infancy Research Group. Although the book was intended for advanced undergraduates, it would also be useful for advanced…

  20. Advanced Civilian Aeronautical Concepts

    NASA Technical Reports Server (NTRS)

    Bushnell, Dennis M.

    1996-01-01

    Paper discusses alternatives to currently deployed systems which could provide revolutionary improvements in metrics applicable to civilian aeronautics. Specific missions addressed include subsonic transports, supersonic transports and personal aircraft. These alternative systems and concepts are enabled by recent and envisaged advancements in electronics, communications, computing and Designer Fluid Mechanics in conjunction with a design approach employing extensive synergistic interactions between propulsion, aerodynamics and structures.

  1. Advances in fetal surgery

    PubMed Central

    Pedreira, Denise Araujo Lapa

    2016-01-01

    ABSTRACT This paper discusses the main advances in fetal surgical therapy aiming to inform health care professionals about the state-of-the-art techniques and future challenges in this field. We discuss the necessary steps of technical evolution from the initial open fetal surgery approach until the development of minimally invasive techniques of fetal endoscopic surgery (fetoscopy). PMID:27074241

  2. Advanced Test Reactor Tour

    ScienceCinema

    Miley, Don

    2016-07-12

    The Advanced Test Reactor at Idaho National Laboratory is the foremost nuclear materials test reactor in the world. This virtual tour describes the reactor, how experiments are conducted, and how spent nuclear fuel is handled and stored. For more information about INL research, visit http://www.facebook.com/idahonationallaboratory.

  3. Advanced radiator concepts

    NASA Technical Reports Server (NTRS)

    Diem-Kirsop, P. S.

    1985-01-01

    The liquid droplet radiator and the liquid belt radiator currently under study by the NASA LeRC are discussed. These advanced concepts offer benefits in reduced mass, compact stowage, and ease of deployment. Operation and components of the radiators are described, heat transfer characteristics are discussed, and critical technologies are identified. The impact of the radiators on large power systems is also assessed.

  4. Pulse shaping with transmission lines

    DOEpatents

    Wilcox, R.B.

    1985-08-15

    A method and apparatus for forming shaped voltage pulses uses passive reflection from a transmission line with nonuniform impedance. The impedance of the reflecting line varies with length in accordance with the desired pulse shape. A high voltage input pulse is transmitted to the reflecting line. A reflected pulse is produced having the desired shape and is transmitted by pulse removal means to a load. Light activated photoconductive switches made of silicon can be utilized. The pulse shaper can be used to drive a Pockels cell to produce shaped optical pulses.

  5. Pulse shaping with transmission lines

    DOEpatents

    Wilcox, Russell B.

    1987-01-01

    A method and apparatus for forming shaped voltage pulses uses passive reflection from a transmission line with nonuniform impedance. The impedance of the reflecting line varies with length in accordance with the desired pulse shape. A high voltage input pulse is transmitted to the reflecting line. A reflected pulse is produced having the desired shape and is transmitted by pulse removal means to a load. Light activated photoconductive switches made of silicon can be utilized. The pulse shaper can be used to drive a Pockels cell to produce shaped optical pulses.

  6. Illusory movement of dotted lines

    PubMed Central

    Ito, Hiroyuki; Anstis, Stuart; Cavanagh, Patrick

    2013-01-01

    When oblique rows of black and white dots drifted horizontally across a mid-grey surround, the perceived direction of motion was shifted to be almost parallel to the dotted lines and was often nearly orthogonal to the real motion. The reason is that the black/white contrast signals between adjacent dots along the length of the line are stronger than black/grey or white/grey contrast signals across the line, and the motion is computed as a vector sum of local contrast-weighted motion signals. PMID:19911636

  7. Overview of plasma line broadening

    NASA Astrophysics Data System (ADS)

    Alexiou, S.

    2009-12-01

    We review the basics of line broadening, its relation to fluctuations and disorder, what causes broadening, the memory loss mechanism and the Standard Theory of line broadening developed by H.R. Griem and others from a modern viewpoint. This modern view benefits from many years of progress and includes a coherent theoretical perspective without the need for a conceptually different view of electrons and ions. Both electrons and ions are described in terms of their random fields. This modern and unified view allows, among other things, extending the range of validity of line profile calculations to complex situations.

  8. Electrical transmission line diametrical retainer

    DOEpatents

    Hall, David R.; Hall, Jr., H. Tracy; Pixton, David; Dahlgren, Scott; Sneddon, Cameron; Briscoe, Michael; Fox, Joe

    2004-12-14

    The invention is a mechanism for retaining an electrical transmission line. In one embodiment of the invention it is a system for retaining an electrical transmission line within down hole components. In accordance with one aspect of the invention, the system includes a plurality of downhole components, such as sections of pipe in a drill string. The system also includes a coaxial cable running between the first and second end of a drill pipe, the coaxial cable having a conductive tube and a conductive core within it. The invention allows the electrical transmission line to with stand the tension and compression of drill pipe during routine drilling cycles.

  9. Solving the "Hidden Line" Problem

    NASA Technical Reports Server (NTRS)

    1984-01-01

    David Hedgley Jr., a mathematician at Dryden Flight Research Center, has developed an accurate computer program that considers whether a line in a graphic model of a three dimensional object should or should not be visible. The Hidden Line Computer Code, program automatically removes superfluous lines and permits the computer to display an object from specific viewpoints, just as the human eye would see it. Users include Rowland Institute for Science in Cambridge, MA, several departments of Lockheed Georgia Co., and Nebraska Public Power District (NPPD).

  10. The Emission-Line Universe

    NASA Astrophysics Data System (ADS)

    Cepa, Jordi

    2012-02-01

    Preface; 1. What can emission lines tell us? G. Stasińska; 2. The observer's perspective: emission-line surveys M. Giavalisco; 3. The astrophysics of early galaxy formation P. Madau; 4. Primeval galaxies D. Schaerer; 5. Active galactic nuclei B. M. Peterson; 6. Chemical evolution F. Matteucci; 7. Galactic sources of emission lines S. Eikenberry; 8. Narrow band imaging S. Pascual and B. Cedrés; 9. Long-slit spectroscopy M. Sánchez and A. M. García; 10. Basic principles of tunable filters H. Castañeda and A. Bongiovanni.

  11. The Emission-Line Universe

    NASA Astrophysics Data System (ADS)

    Cepa, Jordi

    2008-11-01

    Preface; 1. What can emission lines tell us? G. Stasińska; 2. The observer's perspective: emission-line surveys M. Giavalisco; 3. The astrophysics of early galaxy formation P. Madau; 4. Primeval galaxies D. Schaerer; 5. Active galactic nuclei B. M. Peterson; 6. Chemical evolution F. Matteucci; 7. Galactic sources of emission lines S. Eikenberry; 8. Narrow band imaging S. Pascual and B. Cedrés; 9. Long-slit spectroscopy M. Sánchez and A. M. García; 10. Basic principles of tunable filters H. Castañeda and A. Bongiovanni.

  12. An Exploration of Learners' Conceptions of Language, Culture, and Learning in Advanced-Level Spanish Courses

    ERIC Educational Resources Information Center

    Drewelow, Isabelle; Mitchell, Claire

    2015-01-01

    This article reports on an exploratory study, which examines learners' rating of culture in relation to other concepts in advanced Spanish courses and their justification of the ratings attributed. Open-ended responses, elicited from a questionnaire completed by 179 respondents, were analysed line by line using an interpretive approach. Data…

  13. Vibrational averages along thermal lines

    NASA Astrophysics Data System (ADS)

    Monserrat, Bartomeu

    2016-01-01

    A method is proposed for the calculation of vibrational quantum and thermal expectation values of physical properties from first principles. Thermal lines are introduced: these are lines in configuration space parametrized by temperature, such that the value of any physical property along them is approximately equal to the vibrational average of that property. The number of sampling points needed to explore the vibrational phase space is reduced by up to an order of magnitude when the full vibrational density is replaced by thermal lines. Calculations of the vibrational averages of several properties and systems are reported, namely, the internal energy and the electronic band gap of diamond and silicon, and the chemical shielding tensor of L-alanine. Thermal lines pave the way for complex calculations of vibrational averages, including large systems and methods beyond semilocal density functional theory.

  14. Drawing with a Single Line.

    ERIC Educational Resources Information Center

    Johnson, Carole Austen; Anderson, Lorraine

    1979-01-01

    Described is a method of tapping students' creative potential in art: the Spontaneous Response Drawing. SRD consists of drawing with a single line, usually with crayons or colored felt tip pens on a large sheet of paper. (KC)

  15. Double space with double line

    SciTech Connect

    Cheltsov, I A

    2004-10-31

    For a singular double cover of P{sup 3} ramified in a sextic with double line, its birational maps into Fano 3-folds with canonical singularities, elliptic fibrations, and fibrations on surfaces of Kodaira dimension zero are described.

  16. Double space with double line

    NASA Astrophysics Data System (ADS)

    Cheltsov, I. A.

    2004-10-01

    For a singular double cover of \\mathbb P^3 ramified in a sextic with double line, its birational maps into Fano 3-folds with canonical singularities, elliptic fibrations, and fibrations on surfaces of Kodaira dimension zero are described.

  17. Horizontal and Vertical Line Designs.

    ERIC Educational Resources Information Center

    Johns, Pat

    2003-01-01

    Presents an art lesson in which students learn about the artist Piet Mondrian and create their own abstract artworks. Focuses on geometric shapes using horizontal and vertical lines. Includes background information about the artist. (CMK)

  18. Front-line ownership: imagine.

    PubMed

    Matlow, Anne

    2013-01-01

    When used in a military context, the term front line refers to the interface between enemies in action on the battlefield. In a non-military context, the front line is the site where the core activity defining a particular industry takes place, and those working there are key to successful operations. In healthcare, the need to improve patient safety has become a global imperative, and an armamentarium of strategies, tools and technological approaches have been adapted or developed for this context. Often neglected, however, have been strategies to engage the healthcare workers, those at the front line, in the cause.In order for healthcare to function error free, we must assume the characteristics of high-reliability organizations. In particular, the ability to bounce back, to be resilient in the face of a catastrophe, is of paramount importance. Those working at the front line may have the answers. We need to create an opportunity for them to be heard.`

  19. Equatorial Wave Line, Pacific Ocean

    NASA Technical Reports Server (NTRS)

    1993-01-01

    This Equatorial Wave Line (2.0 N, 102.5W) seen in the Pacific Ocean is of great interest to oceanographers because of the twice annual upwelling of the oceans nutrients. As a result of nearly constant easterly winds, cool nutrient rich water wells up at the equator. The long narrow line is an equatorial front or boundry between warm surface equatorial water and cool recently upwelled water as the intermix of nutrients takes place.

  20. Fin-line horn antenna

    DOEpatents

    Reindel, John

    1990-01-01

    A fin line circuit card containing a fin line slot feeds a dipole antenna ich extends a quarterwave outside the waveguide and provides an energy beam focal point at or near the open end of the waveguide. The dipole antenna thus maintains a wide and nearly constant beamwidth, low VSWR and a circular symmetric radiation pattern for use in electronic warfare direction finding and surveillance applications.