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Sample records for advanced intercross line

  1. Using advanced intercross lines for high-resolution mapping of HDL cholesterol quantitative trait loci.

    PubMed

    Wang, Xiaosong; Le Roy, Isabelle; Nicodeme, Edwige; Li, Renhua; Wagner, Richard; Petros, Christina; Churchill, Gary A; Harris, Stephen; Darvasi, Ariel; Kirilovsky, Jorge; Roubertoux, Pierre L; Paigen, Beverly

    2003-07-01

    Mapping quantitative trait loci (QTLs) with high resolution facilitates identification and positional cloning of the underlying genes. The novel approach of advanced intercross lines (AILs) generates many more recombination events and thus can potentially narrow QTLs significantly more than do conventional backcrosses and F2 intercrosses. In this study, we carried out QTL analyses in (C57BL/6J x NZB/BlNJ) x C57BL/6J backcross progeny fed either chow or an atherogenic diet to detect QTLs that regulate high-density lipoprotein cholesterol (HDL)concentrations, and in (C57BL/6J x NZB/BlNJ) F11 AIL progeny to confirm and narrow those QTLs. QTLs for HDL concentrations were found on chromosomes 1, 5, and 16. AIL not only narrowed the QTLs significantly more than did a conventional backcross but also resolved a chromosome 5 QTL identified in the backcross into two QTLs, the peaks of both being outside the backcross QTL region. We tested 27 candidate genes and found significant mRNA expression differences for 12 (Nr1i3, Apoa2, Sap, Tgfb2, Fgfbp1, Prom, Ppargc1, Tcf1, Ncor2, Srb1, App, and Ifnar). Some of these underlay the same QTL, indicating that expression differences are common and not sufficient to identify QTL genes. All the major HDL QTLs in our study had homologous counterparts in humans, implying that their underlying genes regulate HDL in humans. PMID:12805272

  2. Using Advanced Intercross Lines for High-Resolution Mapping of HDL Cholesterol Quantitative Trait Loci

    PubMed Central

    Wang, Xiaosong; Le Roy, Isabelle; Nicodeme, Edwige; Li, Renhua; Wagner, Richard; Petros, Christina; Churchill, Gary A.; Harris, Stephen; Darvasi, Ariel; Kirilovsky, Jorge; Roubertoux, Pierre L.; Paige, Beverly

    2003-01-01

    Mapping quantitative trait loci (QTLs)with high resolution facilitates identification and positional cloning of the underlying genes. The novel approach of advanced intercross lines (AILs) generates many more recombination events and thus can potentially narrow QTLs significantly more than do conventional backcrosses and F2 intercrosses. In this study, we carried out QTL analyses in (C57BL/6J × NZB/BlNJ)× C57BL/6J backcross progeny fed either chow or an atherogenic diet to detect QTLs that regulate high-density lipoprotein cholesterol (HDL)concentrations, and in (C57BL/6J × NZB/BlNJ)F11 AIL progeny to confirm and narrow those QTLs. QTLs for HDL concentrations were found on chromosomes 1, 5, and 16. AIL not only narrowed the QTLs significantly more than did a conventional backcross but also resolved a chromosome 5 QTL identified in the backcross into two QTLs, the peaks of both being outside the backcross QTL region. We tested 27 candidate genes and found significant mRNA expression differences for 12 (Nr1i3, Apoa2, Sap, Tgfb2, Fgfbp1, Prom, Ppargc1, Tcf1, Ncor2, Srb1, App, and Ifnar). Some of these underlay the same QTL, indicating that expression differences are common and not sufficient to identify QTL genes. All the major HDL QTLs in our study had homologous counterparts in humans, implying that their underlying genes regulate HDL in humans. PMID:12805272

  3. Genetic Control of Spontaneous Arthritis in a Four-Way Advanced Intercross Line

    PubMed Central

    Ranea, Laura Mellado; de Castro Marques, Andreia; Möller, Steffen; Gupta, Yask; Ibrahim, Saleh M.

    2013-01-01

    Identifying the genetic basis of complex diseases, such as rheumatoid arthritis, remains a challenge that requires experimental models to reduce the genetic and environmental variability. Numerous loci for arthritis have been identified in induced animal models; however, few spontaneous models have been genetically studied. Therefore, we generated a four-way advanced intercross line (AIL) from four inbred strains, including BXD2/TyJ which spontaneously develops autoimmune arthritis. A genome-wide scan for spontaneous arthritis was performed in a cohort of 366 mice of the fourth generation (G4) of this cross. Five loci contributing to clinical phenotypes were identified in chromosomes 3, 7, 13, 18, and X. Three of the loci found in this study, confirm previously identified loci; whereas two of them are novel loci. Interesting candidate genes for the loci are highlighted. This study provides a genetic overview of spontaneous arthritis in mice and aids to solve the genetic etiology of rheumatoid arthritis and to gain a better understanding of the disease. PMID:24146764

  4. 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

  5. Inferring Genome-Wide Recombination Landscapes from Advanced Intercross Lines: Application to Yeast Crosses

    PubMed Central

    Illingworth, Christopher J. R.; Parts, Leopold; Bergström, Anders; Liti, Gianni; Mustonen, Ville

    2013-01-01

    Accurate estimates of recombination rates are of great importance for understanding evolution. In an experimental genetic cross, recombination breaks apart and rejoins genetic material, such that the genomes of the resulting isolates are comprised of distinct blocks of differing parental origin. We here describe a method exploiting this fact to infer genome-wide recombination profiles from sequenced isolates from an advanced intercross line (AIL). We verified the accuracy of the method against simulated data. Next, we sequenced 192 isolates from a twelve-generation cross between West African and North American yeast Saccharomyces cerevisiae strains and inferred the underlying recombination landscape at a fine genomic resolution (mean segregating site distance 0.22 kb). Comparison was made with landscapes inferred for a similar cross between four yeast strains, and with a previous single-generation, intra-strain cross (Mancera et al., Nature 2008). Moderate congruence was identified between landscapes (correlation 0.58–0.77 at 5 kb resolution), albeit with variance between mean genome-wide recombination rates. The multiple generations of mating undergone in the AILs gave more precise inference of recombination rates than could be achieved from a single-generation cross, in particular in identifying recombination cold-spots. The recombination landscapes we describe have particular utility; both AILs are part of a resource to study complex yeast traits (see e.g. Parts et al., Genome Res 2011). Our results will enable future applications of this resource to take better account of local linkage structure heterogeneities. Our method has general applicability to other crossing experiments, including a variety of experimental designs. PMID:23658715

  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. 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

  8. Genome Reshuffling for Advanced Intercross Permutation (GRAIP): Simulation and permutation for advanced intercross population analysis

    SciTech Connect

    Pierce, Jeremy; Broman, Karl; Lu, Lu; Chesler, Elissa J; Zhou, Guomin; Airey, David; Birmingham, Amanda; Williams, Robert

    2008-04-01

    Background: Advanced intercross lines (AIL) are segregating populations created using a multi-generation breeding protocol for fine mapping complex trait loci (QTL) in mice and other organisms. Applying QTL mapping methods for intercross and backcross populations, often followed by na ve permutation of individuals and phenotypes, does not account for the effect of AIL family structure in which final generations have been expanded and leads to inappropriately low significance thresholds. The critical problem with na ve mapping approaches in AIL populations is that the individual is not an exchangeable unit. Methodology/Principal Findings: The effect of family structure has immediate implications for the optimal AIL creation (many crosses, few animals per cross, and population expansion before the final generation) and we discuss these and the utility of AIL populations for QTL fine mapping. We also describe Genome Reshuffling for Advanced Intercross Permutation, (GRAIP) a method for analyzing AIL data that accounts for family structure. GRAIP permutes a more interchangeable unit in the final generation crosses - the parental genome - and simulating regeneration of a permuted AIL population based on exchanged parental identities. GRAIP determines appropriate genome-wide significance thresholds and locus-specific Pvalues for AILs and other populations with similar family structures. We contrast GRAIP with na ve permutation using a large densely genotyped mouse AIL population (1333 individuals from 32 crosses). A na ve permutation using coat color as a model phenotype demonstrates high false-positive locus identification and uncertain significance levels, which are corrected using GRAIP. GRAIP also detects an established hippocampus weight locus and a new locus, Hipp9a. Conclusions and Significance: GRAIP determines appropriate genome-wide significance thresholds and locus-specific Pvalues for AILs and other populations with similar family structures. The effect of

  9. Genome Reshuffling for Advanced Intercross Permutation (GRAIP): Simulation and permutation for advanced intercross population analysis

    SciTech Connect

    Pierce, Jeremy; Broman, Karl; Chesler, Elissa J; Zhou, Guomin; Airey, David; Birmingham, Amanda; Williams, Robert

    2008-01-01

    Abstract Background Advanced intercross lines (AIL) are segregating populations created using a multigeneration breeding protocol for fine mapping complex traits in mice and other organisms. Applying quantitative trait locus (QTL) mapping methods for intercross and backcross populations, often followed by na ve permutation of individuals and phenotypes, does not account for the effect of family structure in AIL populations in which final generations have been expanded and leads to inappropriately low significance thresholds. The critical problem with a na ve mapping approach in such AIL populations is that the individual is not an exchangeable unit given the family structure. Methodology/Principal Findings The effect of family structure has immediate implications for the optimal AIL creation (many crosses, few animals per cross, and population expansion before the final generation) and we discuss these and the utility of AIL populations for QTL fine mapping. We also describe Genome Reshuffling for Advanced Intercross Permutation, (GRAIP) a method for analyzing AIL data that accounts for family structure. RAIP permutes a more interchangeable unit in the final generation crosses - the parental genome - and simulating regeneration of a permuted AIL population based on exchanged parental identities. GRAIP determines appropriate genome- ide significance thresholds and locus-specific P-values for AILs and other populations with similar family structures. We contrast GRAIP with na ve permutation using a large densely genotyped mouse AIL population (1333 individuals from 32 crosses). A na ve permutation using coat color as a model phenotype demonstrates high false-positive locus identification and uncertain significance levels in our AIL population, which are corrected by use of GRAIP. We also show that GRAIP detects an established hippocampus weight locus and a new locus, Hipp9a. Conclusions and Significance GRAIP determines appropriate genome-wide significance thresholds

  10. 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

  11. Discovery and refinement of muscle weight QTLs in B6 × D2 advanced intercross mice

    PubMed Central

    Carbonetto, P.; Cheng, R.; Gyekis, J. P.; Parker, C. C.; Blizard, D. A.; Palmer, A. A.

    2014-01-01

    The genes underlying variation in skeletal muscle mass are poorly understood. Although many quantitative trait loci (QTLs) have been mapped in crosses of mouse strains, the limited resolution inherent in these conventional studies has made it difficult to reliably pinpoint the causal genetic variants. The accumulated recombination events in an advanced intercross line (AIL), in which mice from two inbred strains are mated at random for several generations, can improve mapping resolution. We demonstrate these advancements in mapping QTLs for hindlimb muscle weights in an AIL (n = 832) of the C57BL/6J (B6) and DBA/2J (D2) strains, generations F8–F13. We mapped muscle weight QTLs using the high-density MegaMUGA SNP panel. The QTLs highlight the shared genetic architecture of four hindlimb muscles and suggest that the genetic contributions to muscle variation are substantially different in males and females, at least in the B6D2 lineage. Out of the 15 muscle weight QTLs identified in the AIL, nine overlapped the genomic regions discovered in an earlier B6D2 F2 intercross. Mapping resolution, however, was substantially improved in our study to a median QTL interval of 12.5 Mb. Subsequent sequence analysis of the QTL regions revealed 20 genes with nonsense or potentially damaging missense mutations. Further refinement of the muscle weight QTLs using additional functional information, such as gene expression differences between alleles, will be important for discerning the causal genes. PMID:24963006

  12. 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. ...

  13. Genetic variance and covariance patterns for body weight and energy balance characters in an advanced intercross population of mice

    PubMed Central

    Leamy, Larry J; Elo, Kari; Nielsen, Merlyn K; Van Vleck, L Dale; Pomp, Daniel

    2005-01-01

    We estimated heritabilities and genetic correlations for a suite of 15 characters in five functional groups in an advanced intercross population of over 2000 mice derived from a cross of inbred lines selected for high and low heat loss. Heritabilities averaged 0.56 for three body weights, 0.23 for two energy balance characters, 0.48 for three bone characters, 0.35 for four measures of adiposity, and 0.27 for three organ weights, all of which were generally consistent in magnitude with estimates derived in previous studies. Genetic correlations varied from -0.65 to +0.98, and were higher within these functional groups than between groups. These correlations generally conformed to a priori expectations, being positive in sign for energy expenditure and consumption (+0.24) and negative in sign for energy expenditure and adiposity (-0.17). The genetic correlations of adiposity with body weight at 3, 6, and 12 weeks of age (-0.29, -0.22, -0.26) all were negative in sign but not statistically significant. The independence of body weight and adiposity suggests that this advanced intercross population is ideal for a comprehensive discovery of genes controlling regulation of mammalian adiposity that are distinct from those for body weight. PMID:16194522

  14. 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

  15. 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

  16. High-Resolution Mapping of Complex Traits with a Four-Parent Advanced Intercross Yeast Population

    PubMed Central

    Cubillos, Francisco A.; Parts, Leopold; Salinas, Francisco; Bergström, Anders; Scovacricchi, Eugenio; Zia, Amin; Illingworth, Christopher J. R.; Mustonen, Ville; Ibstedt, Sebastian; Warringer, Jonas; Louis, Edward J.; Durbin, Richard; Liti, Gianni

    2013-01-01

    A large fraction of human complex trait heritability is due to a high number of variants with small marginal effects and their interactions with genotype and environment. Such alleles are more easily studied in model organisms, where environment, genetic makeup, and allele frequencies can be controlled. Here, we examine the effect of natural genetic variation on heritable traits in a very large pool of baker’s yeast from a multiparent 12th generation intercross. We selected four representative founder strains to produce the Saccharomyces Genome Resequencing Project (SGRP)-4X mapping population and sequenced 192 segregants to generate an accurate genetic map. Using these individuals, we mapped 25 loci linked to growth traits under heat stress, arsenite, and paraquat, the majority of which were best explained by a diverging phenotype caused by a single allele in one condition. By sequencing pooled DNA from millions of segregants grown under heat stress, we further identified 34 and 39 regions selected in haploid and diploid pools, respectively, with most of the selection against a single allele. While the most parsimonious model for the majority of loci mapped using either approach was the effect of an allele private to one founder, we could validate examples of pleiotropic effects and complex allelic series at a locus. SGRP-4X is a deeply characterized resource that provides a framework for powerful and high-resolution genetic analysis of yeast phenotypes and serves as a test bed for testing avenues to attack human complex traits. PMID:24037264

  17. 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. PMID:26041397

  18. Mapping QTL Affecting Resistance to Marek's Disease in an F6 Advanced Intercross Population of Commercial Layer Chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a T-cell lymphoma of chickens caused by the Marek’s disease virus (MDV), an oncogenic avian herpesvirus. MD is a major cause of economic loss to the poultry industry and the most serious and persistent infectious disease concern. A full-sib intercross population, consisting o...

  19. 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. PMID:25989359

  20. 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

  1. 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.

  2. NASDA's Advanced On-Line System (ADOLIS)

    NASA Technical Reports Server (NTRS)

    Yamamoto, Yoshikatsu; Hara, Hideo; Yamada, Shigeo; Hirata, Nobuyuki; Komatsu, Shigenori; Nishihata, Seiji; Oniyama, Akio

    1993-01-01

    Spacecraft operations including ground system operations are generally realized by various large or small scale group work which is done by operators, engineers, managers, users and so on, and their positions are geographically distributed in many cases. In face-to-face work environments, it is easy for them to understand each other. However, in distributed work environments which need communication media, if only using audio, they become estranged from each other and lose interest in and continuity of work. It is an obstacle to smooth operation of spacecraft. NASDA has developed an experimental model of a new real-time operation control system called 'ADOLIS' (ADvanced On-Line System) adopted to such a distributed environment using a multi-media system dealing with character, figure, image, handwriting, video and audio information which is accommodated to operation systems of a wide range including spacecraft and ground systems. This paper describes the results of the development of the experimental model.

  3. 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.

  4. 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

  5. Weak Epistasis Generally Stabilizes Phenotypes in a Mouse Intercross

    PubMed Central

    Tyler, Anna L.; Donahue, Leah Rae; Churchill, Gary A.; Carter, Gregory W.

    2016-01-01

    The extent and strength of epistasis is commonly unresolved in genetic studies, and observed epistasis is often difficult to interpret in terms of biological consequences or overall genetic architecture. We investigated the prevalence and consequences of epistasis by analyzing four body composition phenotypes—body weight, body fat percentage, femoral density, and femoral circumference—in a large F2 intercross of B6-lit/lit and C3.B6-lit/lit mice. We used Combined Analysis of Pleiotropy and Epistasis (CAPE) to examine interactions for the four phenotypes simultaneously, which revealed an extensive directed network of genetic loci interacting with each other, circulating IGF1, and sex to influence these phenotypes. The majority of epistatic interactions had small effects relative to additive effects of individual loci, and tended to stabilize phenotypes towards the mean of the population rather than extremes. Interactive effects of two alleles inherited from one parental strain commonly resulted in phenotypes closer to the population mean than the additive effects from the two loci, and often much closer to the mean than either single-locus model. Alternatively, combinations of alleles inherited from different parent strains contribute to more extreme phenotypes not observed in either parental strain. This class of phenotype-stabilizing interactions has effects that are close to additive and are thus difficult to detect except in very large intercrosses. Nevertheless, we found these interactions to be useful in generating hypotheses for functional relationships between genetic loci. Our findings suggest that while epistasis is often weak and unlikely to account for a large proportion of heritable variance, even small-effect genetic interactions can facilitate hypotheses of underlying biology in well-powered studies. PMID:26828925

  6. Exploring multiple quantitative trait loci models of hepatic fibrosis in a mouse intercross.

    PubMed

    Hall, Rabea A; Hillebrandt, Sonja; Lammert, Frank

    2016-02-01

    Most common diseases are attributed to multiple genetic variants, and the feasibility of identifying inherited risk factors is often restricted to the identification of alleles with high or intermediate effect sizes. In our previous studies, we identified single loci associated with hepatic fibrosis (Hfib1-Hfib4). Recent advances in analysis tools allowed us to model loci interactions for liver fibrosis. We analysed 322 F2 progeny from an intercross of the fibrosis-susceptible strain BALB/cJ and the resistant strain FVB/NJ. The mice were challenged with carbon tetrachloride (CCl4) for 6 weeks to induce chronic hepatic injury and fibrosis. Fibrosis progression was quantified by determining histological fibrosis stages and hepatic collagen contents. Phenotypic data were correlated to genome-wide markers to identify quantitative trait loci (QTL). Thirteen susceptibility loci were identified by single and composite interval mapping, and were included in the subsequent multiple QTL model (MQM) testing. Models provided evidence for susceptibility loci with strongest association to collagen contents (chromosomes 1, 2, 8 and 13) or fibrosis stages (chromosomes 1, 2, 12 and 14). These loci contained the known fibrosis risk genes Hc, Fasl and Foxa2 and were incorporated in a fibrosis network. Interestingly the hepatic fibrosis locus on chromosome 1 (Hfib5) connects both phenotype networks, strengthening its role as a potential modifier locus. Including multiple QTL mapping to association studies adds valuable information on gene-gene interactions in experimental crosses and human cohorts. This study presents an initial step towards a refined understanding of profibrogenic gene networks. PMID:26547557

  7. Tracking Spectral Noise Lines in Advanced LIGO Data

    NASA Astrophysics Data System (ADS)

    Beltz-Mohrmann, Gillian Dora; Weinstein, Alan J.; Kanner, Jonah

    2016-01-01

    The Advanced LIGO detectors are expected to make gravitational wave observations possible within the next few years. However, sharp spectral noise lines continue to obscure the data, and it is unknown if or how these lines wander over time. Therefore, we are developing a method that will track the frequencies of the various noise sources which appear in our data. Using Python for scripting, we utilize various signal processing techniques to identify the exact frequencies of the noise sources present in our time series. We then heterodyne to determine if and how a given spectral line wanders in frequency over time. This technique will provide beneficial insight for improving the quality of the data and the sensitivity to gravitational waves from spinning neutron stars and other astrophysical sources.

  8. Advanced coating lining systems for challenging chemical environments

    SciTech Connect

    Brupbacher, J.M.; Stiles, J.E.

    1997-08-01

    Advanced coatings and coating lining systems are being increasingly used by industry to protect process equipment in challenging chemical environments. This includes not only severe corrosive liquors encountered in many Chemical Process Industry streams, but also the high purity process liquors and rinse systems of the pharmaceutical and microelectronics industries. This paper discusses the design options for optimizing the performance of fluoropolymer-based coating systems for industry-specific applications such as these. Design factors discussed will include surface pre-treatment options, chemical and mechanical bonding systems, field-proven and advanced polymer barrier coatings, homogeneous and graded polymer barrier stacks, and imbedded permeation barriers. The processing techniques for applying engineered coatings will be discussed since processing also plays an important role in the design options available to individual coating applicators and ultimate performance of the coating system applied. Several case studies will be presented and discussed.

  9. 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.

  10. Advance of the Ground Relay of the Line Protection

    NASA Astrophysics Data System (ADS)

    Inukai, Michihiko; Nishida, Tadashi; Noro, Jun; Matsuda, Akihiro

    This paper describes the advance of the ground relay of the line protection. First of all, we examined the ground fault in a resistively grounded power system. The protective relay detects the ground fault by the zero phase current in the system. There are two methods for the current input to the relay. One uses the residual circuit of CT secondary winding, and the other uses the CT tertiary winding. When the ground current is insufficient in the residual circuit, the CT tertiary winding is used. In order to omit the CT tertiary winding and to get more reliability, we reviewed the full-scale of relay and evaluating the error of CT. As result, almost all transmission lines could omit the CT tertiary winding. Next, we examined the ground fault with high fault resistance in a solidly grounded power system. When that fault occurs in the system, the PCM current differential relay acts by fault current. So, this relay possibly mal-operates when the CT secondary circuit is disconnected. Therefore, it uses a special CT to raise the reliability. Nowadays GIS has become small and the CT installation space has been decreased, it is needed to reduce these CT cores. In order to omit the special CT, we utilized the combination of the power relay and the rate of change of relay current. As a result, there is a prospect that the relay would not need the special CT. These improvements are effective to reduce cost too.

  11. Genetic analysis of albuminuria in collaborative cross and multiple mouse intercross populations.

    PubMed

    Thaisz, Jill; Tsaih, Shirng-Wern; Feng, Minjie; Philip, Vivek M; Zhang, Yunyu; Yanas, Liane; Sheehan, Susan; Xu, Lingfei; Miller, Darla R; Paigen, Beverly; Chesler, Elissa J; Churchill, Gary A; Dipetrillo, Keith

    2012-10-01

    Albuminuria is an important marker of nephropathy that increases the risk of progressive renal and chronic cardiovascular diseases. The genetic basis of kidney disease is well-established in humans and rodent models, but the causal genes remain to be identified. We applied several genetic strategies to map and refine genetic loci affecting albuminuria in mice and translated the findings to human kidney disease. First, we measured albuminuria in mice from 33 inbred strains, used the data for haplotype association mapping (HAM), and detected 10 genomic regions associated with albuminuria. Second, we performed eight F(2) intercrosses between genetically diverse strains to identify six loci underlying albuminuria, each of which was concordant to kidney disease loci in humans. Third, we used the Oak Ridge National Laboratory incipient Collaborative Cross subpopulation to detect an additional novel quantitative trait loci (QTL) underlying albuminuria. We also performed a ninth intercross, between genetically similar strains, that substantially narrowed an albuminuria QTL on Chromosome 17 to a region containing four known genes. Finally, we measured renal gene expression in inbred mice to detect pathways highly correlated with albuminuria. Expression analysis also identified Glcci1, a gene known to affect podocyte structure and function in zebrafish, as a strong candidate gene for the albuminuria QTL on Chromosome 6. Overall, these findings greatly enhance our understanding of the genetic basis of albuminuria in mice and may guide future studies into the genetic basis of kidney disease in humans. PMID:22859403

  12. 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

  13. Advancements in application of thermoplastic powder coatings for railcar linings

    SciTech Connect

    Horton, D.; Loustaunau, P.J.

    1996-10-01

    Powder coatings offer many benefits for coating applications. These products offer zero VOC emissions and improved performance. Railcars have been largely excluded from these applications due to their physical size. With innovative coating materials and coating techniques, these parts may be economically lined with high performance polymer coatings.

  14. An introduction to the Advanced Testing Line for Actinide Separations (ATLAS)

    SciTech Connect

    Pope, N.G.; Yarbro, S.L.; Schreiber, S.B.; Day, R.S.

    1992-03-01

    The Advanced Testing Line for Actinide Separations (ATLAS) will evaluate promising plutonium recovery process modifications and new technologies. It combines advances in process chemistry, process control, process analytical chemistry, and process engineering. ATLAS has a processing capability equal to other recovery systems but without the pressure to achieve predetermined recovery quotas.

  15. 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...

  16. Line energy and the relation between advancing, receding, and young contact angles.

    PubMed

    Tadmor, Rafael

    2004-08-31

    The line energy associated with the triple phase contact line is a function of local surface defects (chemical and topographical); however, it can still be calculated from the advancing and receding contact angles to which those defects give rise. In this study an expression for the line energy associated with the triple phase contact line is developed. The expression relates the line energy to the drop volume, the interfacial energies, and the actual contact angle (be it advancing, receding, or in between). From the expression we can back calculate the equilibrium Young contact angle, theta0, as a function of the maximal advancing, thetaA, and minimal receding, thetaR, contact angles. To keep a certain maximal hysteresis between advancing and receding angles, different line energies are required depending on the three interfacial energies and the drop's volume V. We learn from the obtained expressions that the hysteresis is determined by some dimensionless parameter, K, which is some normalized line energy. The value of K required to keep a constant hysteresis (thetaA-thetaR) rises to infinity as we get closer to theta0 = 90 degrees. PMID:15323516

  17. 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

  18. Identification of quantitative trait loci affecting body composition in a mouse intercross

    PubMed Central

    Vitarius, James A.; Sehayek, Ephraim; Breslow, Jan L.

    2006-01-01

    Gravimetric analysis and dual energy x-ray absorptiometry densitometry were used to determine lean, fat, and bone tissue traits in a F2 mouse population from a C57BL/6J and CASA/Rk intercross (B6CASAF2). These traits were used in a linkage analysis to identify quantitative trait loci that affect body composition. Linkage mapping showed that body weight (BW) loci on proximal chromosome 2 occurred in the same region as body length, lean tissue mass, and bone mineral content and on chromosome 13 in the same region as lean tissue mass, bone mineral density, and bone mineral content. Fat-related loci occurring on mid-chromosome 2 near 60 cM, proximal chromosome 6, and mid-chromosome 10 were distinct from BW, lean tissue, and bone tissue loci. In B6CASAF2 females, heterozygotes and CASA/Rk homozygotes at the chromosome 6 locus marker had higher body fat percentages, and this locus was responsible for 11% of the variance for body fat percentage. Female heterozygotes and C57BL/6J homozygotes at the chromosome 15 locus marker had higher bone mineral densities, and this locus could explain 8% of that trait's variance. A survey of the literature did not reveal any previous reports of fat-specific loci in the chromosomal 10 region near 42 cM reported in this study. The results of this study indicate that BW and BMI have limited usefulness as phenotypes in linkage or association studies when used as obesity phenotypes. PMID:17179051

  19. Recent advances in nuclear physics through on-line isotope separation

    NASA Astrophysics Data System (ADS)

    Jenkins, David Gareth

    2014-12-01

    Nuclear physics is advancing rapidly at the precision frontier, where measurements of nuclear observables are challenging state-of-the-art nuclear models. A major contribution is associated with the increasing availability of accelerated beams of radioactive ions produced using the isotope separation on-line technique. These advances have come hand in hand with significant progress in the development of high-efficiency detector systems and improved target technologies which are invaluable in exploiting these beams to their full advantage. This article reviews some of the recent highlights in the field of nuclear structure profiting from these technological advances.

  20. 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...

  1. Disease evaluations and agronomic traits of advanced peanut breeding lines in 2013

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A total of 21 peanut cultivars and high-oleic advanced breeding lines were evaluated in small field plots in 2013 for agronomic traits (crop value, yield, seed grade, and characteristics) and resistance to diseases (Sclerotinia blight, southern blight, and Pythium and Rhizoctonia pod rot). Among th...

  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. 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.

  4. 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

  5. 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.

  6. 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…

  7. Which strategy after first-line therapy in advanced colorectal cancer?

    PubMed Central

    Andrea, Coinu; Fausto, Petrelli; Francesca, Borgonovo Karen; Mary, Cabiddu; Mara, Ghilardi; Veronica, Lonati; Sandro, Barni

    2014-01-01

    Second-line therapy for advanced colorectal cancer is an integral part of the treatment strategy that needs to be set from the beginning for each patient, bearing in mind the expected toxicities of chosen treatments, the patient's clinical condition, comorbidities, preferences, the aims of the treatment and the molecular status. Furthermore, the distinction between lines of therapy is no longer absolute. The perspective of “continuum of care” includes switching chemotherapy prior to disease progression, maintenance therapy, drug "holidays" if needed, surgical resection of metastases in selected patients, and seems to allow a tailored treatment, in which patients are more likely to benefit from exposure to all active agents, which is known to correlate with overall survival. The scenario of second-line treatment has changed dramatically over the years and could currently benefit from several options including chemotherapy with a single agent or in combination and the addition of molecular-targeted agents developed in the last decade, such as epidermal growth factor receptor antibodies (cetuximab, panitumumab) and vascular endothelial growth factor-targeting agents (bevacizumab, aflibercept), with the possibility of bevacizumab use even beyond first progression. The purpose of this review is to summarize the most important scientific data supporting the use of chemotherapy and the new biologic agents in the second-line setting in advanced colorectal cancer. PMID:25083064

  8. Advanced photoresist for high-throughput i-line stepper applications

    NASA Astrophysics Data System (ADS)

    Canize, Anthony; Spiess, Walter; Ficner, Stanley A.; Lu, Ping-Hung; Dammel, Ralph R.; Perez, Yvette M.

    1995-06-01

    The use of i-line photolithography is finding increased importance in generating today's advanced semiconductor devices. The requirements in this area have led to the recent development of wide field i-line steppers whose large field sizes permit higher device throughput. The introductions of these wide field i-line steppers generate additional demands on the photoresist used in the manufacturing process. This paper describes the development of an advanced i-line photoresist for use in high-throughput applications. The requirements of this photoresist are high photospeed of the order of 75 mJ/cm2 to achieve targeted throughput requirements at low lamp power densities, high resolution of approximately 0.80 micrometers at NA equals 0.24 to satisfy device critical dimension requirements, and high resistance to thermal flow to permit further processing stages. The photoresist's formulation and processing were optimized to produce the desired performance characteristics. Exposure, focus latitude, photosensitivity, and resistance to thermal flow were determined and correlated with resin dissolution characteristics, relative photosensitizer concentration, softbake and post exposure bake temperatures.

  9. Clinical studies in the second line setting of advanced pancreatic cancer: are we making any progress?

    PubMed

    Ramfidis, Vassilios S; Strimpakos, Alexios S; Syrigos, Kostas N; Saif, Muhammad W

    2012-07-01

    Despite the enormous advances in clinical research in oncology, the prognosis of pancreatic carcinoma remains poor. The therapeutic options in this type of cancer are very limited, with modest results at present. In the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, four interesting trials on the second line treatment of pancreatic cancer were presented. The first study (Abstract #4017) with a phase II design suggested that maintenance therapy with sunitinib, after a complete course of standard first line treatment, was feasible and effective while the second phase I/II study (Abstract #4034) evaluated the role of trabedersen, an agent that inhibits TGF-β2 expression. Finally, the efficacy and toxicity of lapatinib combined with either FOLFOX (Abstract #e14533) or capecitabine (Abstract #e14569) were examined in the second line setting of pancreatic cancer. PMID:22797389

  10. Paclitaxel combined with capecitabine as first-line chemotherapy for advanced or recurrent gastric cancer.

    PubMed

    Yuan, Meiqin; Yang, Yunshan; Lv, Wangxia; Song, Zhengbo; Zhong, Haijun

    2014-07-01

    Chemotherapy is of crucial importance in advanced gastric cancer (AGC) patients, in order to obtain palliation of symptoms and improve survival. To date, no standard chemotherapy regimen has been established for AGC. The purpose of the present study was to evaluate the efficacy and toxicity of the combination regimen of paclitaxel and capecitabine (PX) as first-line chemotherapy in patients with advanced or recurrent gastric cancer. Patients with advanced or recurrent gastric cancer who were treated with PX as first-line chemotherapy between January 2001 and December 2012 at the Zhejiang Cancer Hospital (Hangzhou, China) were retrospectively investigated. Survival was evaluated using the Kaplan-Meier method. In total, 36 patients were enrolled, with a median age of 53.5 years and a Karnofsky performance status (KPS) score of ≥80. A median of 4 PX cycles were administered (range, 2-8 cycles). The median progression-free survival time was 3.7 months [95% confidence interval (CI), 2.9-4.5 months) and the median overall survival time was 12.0 months (95% CI, 9.8-14.1 months). From the 36 patients evaluated, one (2.8%) achieved a complete response, seven (19.4%) achieved a partial response, 24 (66.7%) exhibited stable disease and four (11.1%) exhibited progressive disease. The objective response rate was 22.2% (8/36), and the disease control rate was 88.9% (32/36). All 36 patients were assessed for treatment toxicity. Grade 3 or 4 adverse events included neutropenia (2.8% of patients), hand-foot syndrome (2.8%) and vomiting (2.8%). No neutropenic fever or treatment-related mortalities were observed. PX combination chemotherapy may be a valuable first-line therapy for advanced or recurrent gastric cancer. PMID:24959275

  11. Base Stock Policy in a Join-Type Production Line with Advanced Demand Information

    NASA Astrophysics Data System (ADS)

    Hiraiwa, Mikihiko; Tsubouchi, Satoshi; Nakade, Koichi

    Production control such as the base stock policy, the kanban policy and the constant work-in-process policy in a serial production line has been studied by many researchers. Production lines, however, usually have fork-type, join-type or network-type figures. In addition, in most previous studies on production control, a finished product is required at the same time as arrival of demand at the system. Demand information is, however, informed before due date in practice. In this paper a join-type (assembly) production line under base stock control with advanced demand information in discrete time is analyzed. The recursive equations for the work-in-process are derived. The heuristic algorithm for finding appropriate base stock levels of all machines at short time is proposed and the effect of advanced demand information is examined by simulation with the proposed algorithm. It is shown that the inventory cost can decreases with little backlogs by using the appropriate amount of demand information and setting appropriate base stock levels.

  12. 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

  13. Multiple obesity QTLs identified in an intercross between the NZO (New Zealand obese) and the SM (small) mouse strains.

    PubMed

    Taylor, B A; Wnek, C; Schroeder, D; Phillips, S J

    2001-02-01

    The inheritance of adiposity levels has been investigated in an intercross of the obese, diabetes-prone NZO and the small, lean SM mouse strains. Adiposity index (AI) was defined as the sum of four fat pad weights divided by body weight. DNA pools from fat and lean mice were analyzed with microsatellite variants to screen the genome for quantitative trait loci (QTLs) affecting AI. Ten significant QTLs affecting AI were identified on Chromosome (Chr) 1 (three loci), Chr 2, Chr 5 (two loci), Chr 6 (two loci), Chr 7, and Chr 17. Most of the QTLs appear to be novel. Several QTLs differentially affect specific fat depots. Thus, Chr 2 and Chr 7 QTLs affect gonadal more than inguinal fat, while the converse is true for the Chr 17 QTL. Gender influences the expression of several of the QTLs. For example, effects of the proximal Chr 1 QTL (Obq7) on AI appears to be primarily in males. The proximal AI QTL on Chr 6 (Obq13) maps near the neuropeptide Y (Npy) locus. Sequence analysis of the Npy gene revealed a 1-nucleotide deletion within a highly conserved portion of the 3' untranslated region in strain NZO. However, the deletion is polymorphic among mouse strains. Furthermore, lack of association between this same variant and AI in previously analyzed crosses raises doubt that it is the basis of Obq13. The present cross is the fourth in a series of intercrosses among 10 inbred strains arranged such that each strain is crossed with each adjacent strain within a circle. This design affords multiple opportunities to analyze each segregating QTL. PMID:11210195

  14. 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.

  15. The Advanced Light Source U8 beam line, 20--300 eV

    SciTech Connect

    Heimann, P.; Warwick, T.; Howells, M.; McKinney, W.; Digennaro, D.; Gee, B.; Yee, D.; Kincaid, B.

    1991-10-01

    The U8 is a beam line under construction at the Advanced Light Source (ALS). The beam line will be described along with calculations of its performance and its current status. An 8 cm period undulator is followed by two spherical collecting mirrors, an entrance slit, spherical gratings having a 15{degree} deviation angle, a moveable exit slit, and refocusing and branching mirrors. Internal water cooling is provided to the metal M1 and M2 mirrors as well as to the gratings. Calculations have been made of both the flux output and the resolution over its photon energy range of 20--300 eV. The design goal was to achieve high intensity, 10{sup 12} photons/sec, at a high resolving power of 10,000. The U8 Participating Research Team (PRT) is planning experiments involving the photoelectron spectroscopy of gaseous atoms and molecules, the spectroscopy of ions and actinide spectroscopy.

  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. 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.

  2. Beyond first-line chemotherapy for advanced pancreatic cancer: An expanding array of therapeutic options?

    PubMed Central

    Walker, Evan J; Ko, Andrew H

    2014-01-01

    While an increasing number of therapeutic options are now available for the first-line treatment of locally advanced or metastatic pancreatic cancer, the optimal choice for treatment in the second-line setting and beyond is less well defined. A variety of cytotoxic agents, either alone or in combination, have been evaluated, although primarily in the context of small single-arm or retrospective studies. Most regimens have been associated with median progression-free survival rates in the range of 2-4 mo and overall survival rates between 4-8 mo, highlighting the very poor prognosis of patients who are candidates for such treatment. Targeted therapies studied in this chemotherapy-refractory setting, meanwhile, have produced even worse efficacy results. In the current article, we review the clinical evidence for treatment of refractory disease, primarily in patients who have progressed on front-line gemcitabine-based chemotherapy. In the process, we highlight the limitations of the available data to date as well as some of the challenges in designing appropriate clinical trials in this salvage setting, including how to select an appropriate control arm given the absence of a well-established reference standard, and the importance of incorporating predictive biomarkers and quality of life measures whenever possible into study design. PMID:24605022

  3. Advanced biliary tract carcinomas: a retrospective multicenter analysis of first and second-line chemotherapy

    PubMed Central

    2014-01-01

    Background Gemcitabine/Cisplatin (Gem/CDDP) combination has demonstrated a clear survival advantage over gemcitabine alone and has become a new standard in advanced Biliary Tract Carcinoma (aBTC). However, Gemcitabine/Oxaliplatin (GEMOX) combination and Gemcitabine/Carboplatin (Gem/Carb) combination regimens have shown efficacy in phase II trials and there is no comparative study between different platinum salts. We assessed the efficacy and safety of different platinum-based chemotherapies at first line in aBTC patients. We also analysed the second-line chemotherapy. Methods Sixty-four consecutive patients with aBTC diagnosed between 1998 and 2010 were included for analysis. At first line chemotherapy, 44 patients received one day GEMOX regimen (gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 Day 1, every 2 weeks), and 20 patients received Gem/Carb regimen (gemcitabine at 1000 mg/m2 Days 1 and 8 with carboplatin delivered according to an area-under-the-curve (AUC) 5 at day 1, every 3 weeks). At second line, a total of 16 patients received a fluoropyrimidine-based chemotherapy. Results With GEMOX regimen, median progression-free survival (PFS) was 3.7 months (95%CI, 2.4 to 5) and median overall survival (OS) was 10.5 months (95%CI, 6.4 to14.7). The main toxicity was peripheral neuropathy (20% grade 2 and 7% grade 3). Grade 3/4 haematological toxicities were rare. With Gem/Carb regimen, PFS was 2.5 months (95%CI, 2.1 to 3.7) and OS was 4.8 months (95%CI, 3.7 to 5.8). The main grade 3/4 toxicities were haematological: anaemia (45%), thrombocytopenia (45%), and neutropenia (40%). At second-line, fluoropyrimidine-based chemotherapy was feasible in only a fourth of the patients. The median OS was 5.3 months (95%CI, 4.1 to 6.6), and median PFS was 4.0 months (95%CI, 2.6 to 5.5). Conclusions One day GEMOX regimen has a favourable toxicity profile and could be an alternative to standard Gem/CDDP regimen, in particular in unfit patients for CDDP. At second-line

  4. 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.

  5. 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.

  6. Shrub line advance in Arctic and alpine tundra of the Yukon Territory

    NASA Astrophysics Data System (ADS)

    Myers-Smith, I. H.; Hik, D.

    2010-12-01

    Growing evidence indicates an expansion of canopy-forming woody shrubs up mountain slopes and northward into Arctic tundra. The correlation between warming and greening has been used to link climate change with shrub expansion; however, the exact mechanisms driving observed increases in canopy-forming shrubs are probably more complex. Shrub expansion that results in a change in canopy cover may modify the ecology of tundra ecosystems by changing understory plant composition, soil thermal dynamics, surface albedo, nutrient turnover times and carbon storage. We surveyed the abundance of all tundra willow species (Salix spp.) growing at three sites in the Yukon Territory: the mountains of the Kluane Region, the Richardson Mountains, and on Qikiqtaruk - Herschel Island in the Beaufort Sea. At the two mountainous sites, we collected sections from the largest stem of willow shrubs at shrub line (the maximum elevation at which canopy-forming shrubs grow) and below shrub line (at approximately 50% shrub cover) in a total of 16 valleys. At the coastal site we collected samples from each of the 4 vegetation types: the alluvial fan, ridges, tussock tundra and disturbed terrain. Shrub stems were thin-sectioned using a microtome, photographed with a microscope and ring widths were measured from the digital images. We compared age distributions of willow individuals at and below shrub line and found younger populations at higher elevations, particularly on warm, south-facing aspects. Younger willows at shrub line and a lack of significant mortality in the field surveys indicate that shrubs have advanced up slope at the mountainous sites. Photographic and long-term plot data indicate increases in cover and height of willow shrub patches at the coastal site. We compared growth rings to regional weather data, and found positive correlations between annual growth and summer temperatures. Our results indicate that willows grew most in years with a warm June and July. This evidence of

  7. 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.

  8. 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.

  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. 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

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. Progression-free survival as a surrogate endpoint for overall survival in patients with third-line or later-line chemotherapy for advanced gastric cancer

    PubMed Central

    Liu, Liya; Yu, Hao; Huang, Lihong; Shao, Fang; Bai, Jianling; Lou, Donghua; Chen, Feng

    2015-01-01

    Background The correlation between overall survival (OS) and progression-free survival (PFS) has been evaluated in patients with metastatic or advanced gastric cancer who have received first-line and/or second-line chemotherapy. However, no corresponding analysis has been done for patients who have undergone third-line or later-line chemotherapy. Methods A total of 303 patients from the Phase II/III studies of apatinib were pooled (the Phase II study as a training data set, the Phase III study as a testing data set). Landmark analyses of PFS at 2 months from randomization were performed to minimize lead time bias. The Cox proportional hazard model was used to test for the significance effect of PFS rate at 2 months in predicting OS. Additionally, the PFS/OS correlations were evaluated by the normal induced copula (National Institute for Health and Care Excellence) estimation model. Results The median OS was 3.37 months (95% confidence interval 2.63–3.80) in patients who experienced progression at 2 months and 5.67 months in patients who did not (95% confidence interval 4.83–6.67; P<0.0001). Compared with patients who did not progress at 2 months, the adjusted hazard ratio for death was 3.39 (95% confidence interval 1.79–6.41; P<0.0001) for patients who experienced progression at 2 months. Moreover, the correlation of PFS/OS was 0.84 (95% confidence interval 0.74–0.90). Similar results were found in the testing data set. Conclusion These results indicate that PFS correlates strongly with OS, suggesting PFS may be a useful early endpoint for patients with advanced gastric cancer who have undergone third-line or later-line chemotherapy. These observations require prospective validation. PMID:25960663

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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…

  1. Docetaxel/S-1 Versus Docetaxel/Capecitabine as First-Line Treatment for Advanced Breast Cancer: A Retrospective Study.

    PubMed

    Li, Jinyu; You, Junhao; Si, Wen; Zhu, Yanyun; Chen, Yi; Yang, Bo; Han, Chun; Linghu, Ruixia; Zhang, Xingyang; Jiao, Shunchang; Yang, Junlan

    2015-10-01

    The treatment efficacy of advanced breast cancer is still not promising. This study aimed to compare the efficacy and safety of docetaxel/S-1 (DS1) versus docetaxel/capecitabine (DX) as the first-line treatment for advanced breast cancer.From June 2008 to June 2013, 22 patients with advanced breast cancer were treated with the DS1 regimen. Another 26 age- and disease status-matched patients treated with the DX regimen served as controls. The 2 groups were compared in terms of time to progression (TTP), objective response rate, disease control rate, clinical benefit rate, and safety profiles.Median TTP did not differ significantly between the DS1 group and the DX group (9.04 vs 10.94 months, P = 0.473). There were no significant differences in objective response rate, disease control rate, and clinical benefit rate between the 2 groups. Both the DS1 and the DX regimens showed good tolerability. The 2 regimens showed no significant difference in adverse events except degree III hand-foot syndrome (DS1 0 vs DX 23.1%, P = 0.025).For the first-line treatment of advanced breast cancer, the DS1 and the DX regimens showed similar efficacy and safety. The DS1 regimen had less severe hand-foot syndrome than the DX regimen. PMID:26469889

  2. Insertion device and beam line plans for the Advanced Photon Source: A report and recommendations by the Insertion Device and Beam Line Planning Committee

    SciTech Connect

    Not Available

    1988-02-01

    In the 7-GeV Advanced Photon Source (APS) Conceptual Design Report (CDR), fifteen complete experimental beam lines were specified in order to establish a representative technical and cost base for the components involved. In order to optimize the composition of the insertion devices and the beam line, these funds are considered a ''Trust Fund.'' The present report evaluates the optimization for the distribution of these funds so that the short- and long-term research programs will be most productive, making the facility more attractive from the user's point of view. It is recommended that part of the ''Trust Fund'' be used for the construction of the insertion devices, the front-end components, and the first-optics, minimizing the cost to potential users of completing a beam line. In addition, the possibility of cost savings resulting from replication and standardization of high multiplicity components (such as IDs, front ends, and first-optics instrumentation) is addressed. 2 refs., 5 tabs.

  3. Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer

    PubMed Central

    Shen, Yan-Wei; Zhang, Xiao-Man; Li, Shu-Ting; Lv, Meng; Yang, Jiao; Wang, Fan; Chen, Zhe-Ling; Wang, Bi-Yuan; Li, Pan; Chen, Ling; Yang, Jin

    2016-01-01

    Background and objective Several clinical trials have proven that icotinib hydrochloride, a novel epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. This study was performed to assess the efficacy and toxicity of icotinib as first-line therapy for patients with advanced pulmonary adenocarcinoma with EGFR-sensitive mutation. Patients and methods Thirty-five patients with advanced NSCLC with EGFR-sensitive mutation who were sequentially admitted to the First Affiliated Hospital of Xi’an Jiaotong University from March 2012 to March 2014 were enrolled into our retrospective research. All patients were administered icotinib as first-line treatment. The tumor responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Results Among the 35 patients, the tumor objective response rate (ORR) and disease control rate were 62.9% (22/35) and 88.6% (31/35), respectively. The median progression-free survival was 11.0 months (95% confidence interval [CI]: 10.2–11.8 months), and median overall survival was 21.0 months (95% CI: 20.1–21.9 months). The most common drug-related toxicities were rashes (eleven patients) and diarrhea (nine patients), but these were generally manageable and reversible. Conclusion Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation. PMID:26966381

  4. 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

  5. ZD9331 as second- or third-line therapy in patients with advanced colorectal cancer: a phase II multicenter trial.

    PubMed

    Schulz, J; Keller, A; Canfield, V; Parker, G; Douglass, E

    2004-08-01

    This study investigated the efficacy and tolerability of ZD9331 as second- or third-line treatment for patients with advanced colorectal cancer (aCRC). One hundred patients were recruited to the study: 45 in group 1 (failed first-line 5-FU-based regimen) and 55 in group 2 (failed first-line 5-FU-based regimen and second-line irinotecan). Patients received ZD9331 as a 30-minute intravenous infusion on days 1 and 8 of a 3-week cycle, and treatment continued until disease progression (PD) or withdrawal. After a median of 4 cycles of treatment, there were no objective responses in group 1 (N = 37), 25 (67.6%) patients had a best overall response of stable disease (SD), and 12 (32.4%) had PD. After a median of 3 cycles of treatment, there were 2 (4.5%) partial responses in group 2 (N = 44), 21 (47.7%) patients had a best overall response of SD, 20 (45.4%) had PD, and 1 (2.3%) had clinical progression. At data cut-off, 59.5% and 77.3% of patients in groups 1 and 2, respectively, had PD. The main adverse events were neutropenia (69%), fatigue (53%), nausea (46%), and diarrhea (40%), and most (72.3%) were grade I/II. ZD9331 demonstrated minimal antitumor activity, and manageable toxicity, in the second- or third-line treatment of aCRC. PMID:15289725

  6. Genome-wide study refines the quantitative trait locus for number of ribs in a Large White × Minzhu intercross pig population and reveals a new candidate gene.

    PubMed

    Zhang, Long-Chao; Yue, Jing-Wei; Pu, Lei; Wang, Li-Gang; Liu, Xin; Liang, Jing; Yan, Hua; Zhao, Ke-Bin; Li, Na; Shi, Hui-Bi; Zhang, Yue-Bo; Wang, Li-Xian

    2016-10-01

    In China, sparerib is one of the most valuable parts of the pork carcass. As a result, candidate gene mining for number of ribs has become an interesting study focus. To examine the genetic basis for this major trait, we genotyped 596 individuals from an F2 Large White × Minzhu intercross pig population using the PorcineSNP60 Genotyping BeadChip. The genome-wide association study identified a locus for number of ribs in a 2.38-Mb region on Sus scrofa chromosome 7 (SSC7 of Sus scrofa genome assembly, Sscrofa10.2). We identified the top significant SNP ASGA0035536, which explained 16.51 % of the phenotypic variance. A previously reported candidate causal mutation (g.19034 A>C) in vertebrae development-associated gene VRTN explained 8.79 % of the phenotypic variation on number of ribs and had a much lower effect than ASGA0035536. Haplotype sharing analysis in F1 boars localized the rib number QTL to a 951-kb interval on SSC7. This interval encompassed 17 annotated genes in Sscrofa10.2, including the previously reported VRTN candidate gene. Of the 17 candidate genes, LTBP2, which encodes a latent transforming growth factor beta binding protein, was previously reported to indirectly regulate the activity of growth differentiation factor Gdf11, which has been shown to increase the number of ribs in knock-out mice. Thus, we propose LTBP2 as a good new candidate gene for number of ribs in the pig population. This finding advances our understanding of the genetic architecture of rib number in pigs. PMID:27307002

  7. 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.

  8. 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

  9. Cytotoxic Chemotherapy as First-Line Therapy for Advanced Non-Small-Cell Lung Cancer in Taiwan: Daily Practice

    PubMed Central

    Liang, Yi-Hsin; Shao, Yu-Yun; Liao, Bin-Chi; Lee, Ho-Sheng; Yang, James Chih-Hsin; Chen, Ho-Min; Chiang, Chun-Ju; Cheng, Ann-Lii; Lai, Mei-Shu

    2016-01-01

    Aim: Cytotoxic chemotherapy is the standard first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) without specific gene alterations. This study examined the prescription pattern and the survival outcome of cytotoxic chemotherapy regimens in daily practice in Taiwan. Methods:We established a population-based cohort of patients diagnosed with advanced NSCLC between 2005 and 2009 using the databases of Taiwan Cancer Registry and National Health Insurance in Taiwan. We then analyzed chemotherapy prescriptions and the survival outcomes of patients. Results:A total of 25,008 patients with advanced NSCLC were identified, 17,443 (70.0%) of which received first-line chemotherapy and were therefore included in this study. Among them, 11,551 (66.2%) patients had adenocarcinoma and 3,292 (18.9%) patients had squamous cell carcinoma (SCC). Approximately 70% of the patients were diagnosed with NSCLC in medical centers. Platinum-based doublet chemotherapy was administered to 66.9% of the patients. Among all chemotherapy regimens, platinum with gemcitabine (33.8%) was the most common, irrespective of geographic region. The second and third most common regimens were vinorelbine alone (13.0%) and platinum with docetaxel (11.6%). The prevalence of platinum-based doublet chemotherapy regimens decreased from 71.4% in 2005 to 64.1% in 2009. Among patients with adenocarcinoma histology, those who received platinum with pemetrexed had longer OS than did patients who received other platinum-based regimens (p < 0.001). Conclusion: Our findings reaffirm that in real-world practice, treatment plans of advanced NSCLC should be drawn up according to histology type. PMID:27471567

  10. 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 Central

    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. PMID:26734004

  11. 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

  12. R and D advances in corrosion and crack monitoring for oil and gas lines

    SciTech Connect

    Atherton, D.L.; Czura, W.; Krause, T.W.; Laursen, P.; Mergelas, B.; Hauge, C.

    1996-12-31

    Magnetic Flux Leakage (MFL) inspection techniques for in-line corrosion monitoring of pipelines continue to evolve rapidly. Current R and D is aimed at improving the accuracy and reliability of defect sizing. Major issues are the variability and consequent need to characterize the magnetic properties of the pipes and the effects of line pressure, residual and bending stresses on MFL signals. Magnetic Barkhausen Noise (MBN) measurements are being used to study the stress-induced changes in magnetic anisotropy. Remote Field Eddy Current (RFEC) techniques are being investigated for detection and measurement of stress corrosion cracking in gas pipelines. Anomalous defect source models have improved the detailed explanation of crack defect interactions greatly.

  13. An advanced AFM sensor for high-aspect ratio pattern profile in-line measurement

    NASA Astrophysics Data System (ADS)

    Watanabe, Masahiro; Baba, Shuichi; Nakata, Toshihiko; Kurenuma, Toru; Kuroda, Hiroshi; Hiroki, Takenori

    2006-03-01

    Design rule shrinkage and the wider adoption of new device structures such as STI, copper damascene interconnects, and deep trench structures have increased the necessity of in-line process monitoring of step heights and profiles of device structures. For monitoring active device patterns, not test patterns as in OCD, AFM is the only non-destructive 3D monitoring tool. The barriers to using AFM in-line monitoring are its slow throughput and the accuracy degradation associated with probe tip wear and spike noise caused by unwanted oscillation on the steep slopes of high-aspect-ratio patterns. Our proprietary AFM scanning method, Step in mode®, is the method best suited to measuring high-aspect-ratio pattern profiles. Because the probe is not dragged on the sample surface as in conventional AFM, the profile trace fidelity across steep slopes is excellent. Because the probe does not oscillate and hit the sample at a high frequency as in AC scanning mode, this mode is free from unwanted spurious noises on steep sample slopes and incurs extremely little probe tip wear. To fully take advantage of the above properties, we have developed an AFM sensor optimized for in-line use, which produces accurate profile data at high speeds. The control scheme we have developed for the AFM sensor, which we call "Smart Step-in", elaborately analyses the contact force signal, enabling efficient probe tip scanning and a low and stable contact force. The mechanism of the AFM sensor has been optimized for the higher scanning rate and has improved the accuracy, such as the scanning planarity, position and height accuracy, and slope angle accuracy. Our prototype AFM sensor can scan high-aspect-ratio patterns while stabilizing the contact force at 3 nN. The step height measurement repeatability was 0.8 nm (3σ). A STI-like test pattern was scanned, and the steep sidewalls with angles of 84° were measured with high fidelity and without spurious noises.

  14. 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. PMID:26958507

  15. Economic evaluation of first-line and maintenance treatments for advanced non-small cell lung cancer: a systematic review

    PubMed Central

    Chouaïd, Christos; Crequit, Perinne; Borget, Isabelle; Vergnenegre, Alain

    2015-01-01

    During these last years, there have been an increased number of new drugs for non-small cell lung cancer (NSCLC), with a growing financial effect on patients and society. The purpose of this article was to review the economics of first-line and maintenance NSCLC treatments. We reviewed economic analyses of NSCLC therapies published between 2004 and 2014. In first-line settings, in unselected patients with advanced NSCLC, the cisplatin gemcitabine doublet appears to be cost-saving compared with other platinum doublets. In patients with nonsquamous NSCLC, the incremental cost-effectiveness ratios (ICERs) per life-year gained (LYG) were $83,537, $178,613, and more than $300,000 for cisplatin-pemetrexed compared with, respectively, cisplatin-gemcitabine, cisplatin-carboplatin-paclitaxel, and carboplatin-paclitaxel-bevacizumab. For all primary chemotherapy agents, use of carboplatin is associated with slightly higher costs than cisplatin. In all the analysis, bevacizumab had an ICER greater than $150,000 per quality-adjusted life-year (QALY). In epidermal growth factor receptor mutated advanced NSCLC, compared with carboplatin-paclitaxel doublet, targeted therapy based on testing available tissue yielded an ICER of $110,644 per QALY, and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Compared with the triplet carboplatin-paclitaxel-bevacizumab, testing and rebiopsy strategies had ICERs of $25,547 and $44,036 per QALY, respectively. In an indirect comparison, ICERs per LYG and QALY of erlotinib versus gefitinib were $39,431 and $62,419, respectively. In anaplastic lymphoma kinase-positive nonsquamous advanced NSCLC, the ICER of first-line crizotinib compared with that of chemotherapy was $255,970 per QALY. For maintenance therapy, gefitinib had an ICER of $19,214 per QALY, erlotinib had an ICER of $127,343 per LYG, and pemetrexed had an ICER varying between $183,589 and $205,597 per LYG. Most recent NSCLC strategies are based on apparently no cost

  16. A new bend magnet beam line for scanning transmission x-ray microscopy at the Advanced Light Source

    SciTech Connect

    Warwick, Tony; Ade, Harald; Kilcoyne, A.L. David; Kritscher, Michael; Tylisczcak, Tolek; Fakra, Sirine; Hitchcock, Adam P.; Hitchcock, Peter; Padmore, Howard A.

    2001-12-12

    The high brightness of the bend magnets at the Advanced Light Source has been exploited to illuminate a Scanning Transmission X-ray Microscope (STXM). This is the first diffraction-limited scanning x-ray microscope to operate with useful count rate on a synchrotron bend magnet source. A simple, dedicated beam line has been built covering the range of photon energy from 250 eV to 600 eV. Ease of use and operational availability are radically improved compared to previous installations using undulator beams. This facility provides radiation for C 1s, N 1s and O 1s near edge x-ray absorption spectro-microscopy with a spectral resolution up to about 1:5000 and with STXM count rates in excess of 1 MHz.

  17. Plutonium process control using an advanced on-line gamma monitor for uranium, plutonium, and americium

    SciTech Connect

    Marsh, S.F.; Miller, M.C.

    1987-05-01

    An on-line gamma monitor has been developed to profile uranium, plutonium, and americium in waste and product streams of the anion exchange process used to recover and purify plutonium at the Los Alamos Plutonium Facility. The gamma monitor employs passive gamma spectrometry to measure /sup 241/Am and /sup 239/Pu, based on their 59.5-keV and 129-keV gamma rays, respectively. Because natural and depleted uranium present in typical process streams have no gamma rays suitable for measurement by such passive methods, uranium measurement requires a novel and less direct technique. Plutonium-241, which is always present in plutonium processed at Los Alamos, decays primarily by beta emission to form /sup 241/Am. However, a small fraction of /sup 241/Pu decays by alpha emission to 6.8-day /sup 237/U. The short half-life and 208-keV gamma energy of /sup 237/U make it an ideal radiotracer to mark the position of macro amounts of uranium impurity in the separation process. The real-time data obtained from an operating process allow operators to optimize many process parameters. The gamma monitor also provides a permanent record of the daily performance of each ion exchange system. 2 refs., 12 figs.

  18. 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

  19. 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

  20. Sub-0.25-μm i-line photoresist: the role of advanced resin technology

    NASA Astrophysics Data System (ADS)

    Xu, Cheng-Bai; Zampini, Anthony; Sandford, Harold F.; Lachowski, Joseph; Carmody, Judy

    1999-06-01

    The use of di-functional monomers such as 2,6- Bis(hydroxymethyl)-p-cresol has allowed the design of novolak resins having alternating architecture with enhanced o,o'-bonding order, specific end-groups and narrow molecular weight distribution. When compared with a conventional m-/p- cresol formaldehyde novolak, the new resins have a lower molecular weight and molecular weight distribution with no p-cresol enriched oligomer fractions. Generally, these resins are used without further processing. With the proper monomer selection novolak resins can be made with the appropriate hydrophilic balance and dissolution characteristics essential for advanced resist development and optimization. By coupling the resin properties with the properties of diazonaphthoquinone sulfonate esters that have a high resolution potential, two advanced sub 0.25 micrometers i- line resist prototypes were developed. With annular illumination, Resist Prototype I demonstrated excellent linear resolution of 0.22 micrometers and an exceptional focus latitude of 1.4 micrometers and 1.7 micrometers for the 0.23 micrometers and 0.25 micrometers dense L/S, respectively; while Resist Prototype II showed linear resolution of 0.18 micrometers L/S and outstanding focus latitudes of 1.6 micrometers and 1.7 micrometers for the 0.21 micrometers L/S and the 0.23 micrometers L/S, respectively.

  1. Original Article A phase I study of imexon plus gemcitabine as first-line therapy for advanced pancreatic cancer

    PubMed Central

    Cohen, Steven J.; Zalupski, Mark M.; Modiano, Manuel R.; Conkling, Paul; Patt, Yehuda Z.; Davis, Peg; Dorr, Robert T.; Boytim, Michelle L.; Hersh, Evan M.

    2010-01-01

    Purpose Imexon is an aziridine-derived iminopyrrolidone which has synergy with gemcitabine in pancreatic cancer cell lines. Gemcitabine is a standard therapy for pancreatic cancer. We performed a phase I trial of imexon and gemcitabine to evaluate safety, dose limiting toxicity (DLT), and maximum tolerated dose (MTD) in patients with advanced pancreatic cancer. Methods Patients with untreated locally advanced or metastatic pancreatic adenocarcinoma received therapy in sequential cohorts on regimen A (n=19; imexon 200 or 280 mg/m2 intravenously (IV) over 30 minutes days 1–5, 15–19 and gemcitabine 800 or 1,000 mg/m2 IV over 30 minutes on days 1,8,15 every 28 days) or regimen B (n=86; imexon 280–1,300 mg/m2 IV over 30–60 minutes days 1, 8, and 15 and gemcitabine 1,000 mg/m2 IV over 30 minutes on days 1, 8, and 15 every 28 days). Results One hundred-five patients received 340 treatment cycles (median 2, range 1–16). Patient characteristics: median age 63, 61% male, ECOG PS 0/1 50%/50%, 93% metastatic. DLT was abdominal cramping and pain, often with transient, acute diarrhea. Best response was confirmed partial response (PR) in 11.4%, 8.9% unconfirmed PR, and 48.1% with stable disease. There was a dose proportional increase in imexon AUC across the doses tested with terminal half-life 69 minutes at the MTD and no alteration of gemcitabine pharmacokinetics. Conclusions The recommended phase II dose of imexon is 875 mg/m2 with gemcitabine 1,000 mg/m2. DLT was acute abdominal pain and cramping. Encouraging antitumor responses support further evaluation of this combination in advanced pancreatic cancer. PMID:19855966

  2. First-generation HapMap in Cajanus spp. reveals untapped variations in parental lines of mapping populations.

    PubMed

    Kumar, Vinay; Khan, Aamir W; Saxena, Rachit K; Garg, Vanika; Varshney, Rajeev K

    2016-08-01

    Whole genome re-sequencing (WGRS) was conducted on a panel of 20 Cajanus spp. accessions (crossing parentals of recombinant inbred lines, introgression lines, multiparent advanced generation intercross and nested association mapping population) comprising of two wild species and 18 cultivated species accessions. A total of 791.77 million paired-end reads were generated with an effective mapping depth of ~12X per accession. Analysis of WGRS data provided 5 465 676 genome-wide variations including 4 686 422 SNPs and 779 254 InDels across the accessions. Large structural variations in the form of copy number variations (2598) and presence and absence variations (970) were also identified. Additionally, 2 630 904 accession-specific variations comprising of 2 278 571 SNPs (86.6%), 166 243 deletions (6.3%) and 186 090 insertions (7.1%) were also reported. Identified polymorphic sites in this study provide the first-generation HapMap in Cajanus spp. which will be useful in mapping the genomic regions responsible for important traits. PMID:26821983

  3. 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

  4. 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

  5. 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

  6. Fractionate analysis of the phytochemical composition and antioxidant activities in advanced breeding lines of high-lycopene tomatoes.

    PubMed

    Ilahy, Riadh; Piro, Gabriella; Tlili, Imen; Riahi, Anissa; Sihem, Rabaoui; Ouerghi, Imen; Hdider, Chafik; Lenucci, Marcello Salvatore

    2016-01-01

    This study investigates the antioxidant components [lycopene, total phenolics, total flavonoids, ascorbic acid (AsA) and dehydroascorbic acid (DHA)] as well as antioxidant activities of the hydrophilic and lipophilic fractions (AAHF and AALF) of peel, pulp and seed fractions isolated from red-ripe berries of the ordinary tomato cultivar Rio Grande and the two high-lycopene tomato breeding lines HLT-F61 and HLT-F62 simultaneously grown in an open-field of Northern Tunisia. Significant differences (p < 0.05) were found among cultivars for each trait studied. All fractions isolated from the red-ripe berries of HLT lines showed higher lycopene, total phenolics and total flavonoid contents, as well as higher AAHF and AALF, than those isolated from Rio Grande. Regardless of the fraction, HLT-F61 had the highest lycopene content (893.0 mg per kg fw, 280.0 mg per kg fw, and 47.5 mg per kg fw in peel, pulp and seed fractions, respectively) and total phenolics at least 2-fold and 3-fold higher than HLT-F62 and Rio Grande, respectively. Peel and seed fractions from HLT-F61 red-ripe tomato berries had the highest AsA content (345 mg per kg fw and 115 mg per kg fw, respectively), while no significant difference was found in the seed fraction between HLT-F62 and Rio Grande. The HLT-F62 pulp fraction showed the highest content of AsA (186 mg per kg fw) and DHA (151 mg per kg fw) among all the assayed cultivars. Except for the peel fraction, where HLT-F61 had similar AAHF values to HLT-F62, the high-lycopene line HLT-F61 showed higher AAHF values than HLT-F62 and Rio Grande. Regardless of the fraction, the highest AALF values were recorded in HLT-F61 berries. Thus, both HLT tomato lines are promising for the introduction, as advanced hybrids, in either fresh market or processing industry. PMID:26462607

  7. 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.

  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. Pharmacogenetic prediction of clinical outcome in advanced colorectal cancer patients receiving oxaliplatin/5-fluorouracil as first-line chemotherapy.

    PubMed

    Paré, L; Marcuello, E; Altés, A; del Río, E; Sedano, L; Salazar, J; Cortés, A; Barnadas, A; Baiget, M

    2008-10-01

    To determine whether molecular parameters could be partly responsible for resistance or sensitivity to oxaliplatin (OX)-based chemotherapy used as first-line treatment in advanced colorectal cancer (CRC). We studied the usefulness of the excision repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group D (XPD), XRCC1 and GSTP1 polymorphisms as predictors of clinical outcome in these patients. We treated 126 CRC patients with a first-line OX/5-fluorouracil chemotherapeutic regimen. Genetic polymorphisms were determined by real-time PCR on an ABI PRISM 7000, using DNA from peripheral blood. Clinical response (CR), progression-free survival (PFS) and overall survival (OS) were evaluated according to each genotype. In the univariate analysis for CR, ERCC1-118 and XPD 751 polymorphisms were significant (P=0.02 and P=0.05, respectively). After adjustment for the most relevant clinical variables, only ERCC1-118 retained significance (P=0.008). In the univariate analysis for PFS, ERCC1-118 and XPD 751 were significant (P=0.003 and P=0.009, respectively). In the multivariant analysis, only the XPD 751 was significant for PFS (P=0.02). Finally, ERCC1-118 and XPD 751 polymorphisms were significant in the univariate analysis for OS (P=0.006 and P=0.015, respectively). Both genetic variables remained significant in the multivariate Cox survival analysis (P=0.022 and P=0.03). Our data support the hypothesis that enhanced DNA repair diminishes the benefit of platinum-based treatments. PMID:18797464

  10. Pharmacogenetic prediction of clinical outcome in advanced colorectal cancer patients receiving oxaliplatin/5-fluorouracil as first-line chemotherapy

    PubMed Central

    Paré, L; Marcuello, E; Altés, A; Río, E del; Sedano, L; Salazar, J; Cortés, A; Barnadas, A; Baiget, M

    2008-01-01

    To determine whether molecular parameters could be partly responsible for resistance or sensitivity to oxaliplatin (OX)-based chemotherapy used as first-line treatment in advanced colorectal cancer (CRC). We studied the usefulness of the excision repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group D (XPD), XRCC1 and GSTP1 polymorphisms as predictors of clinical outcome in these patients. We treated 126 CRC patients with a first-line OX/5-fluorouracil chemotherapeutic regimen. Genetic polymorphisms were determined by real-time PCR on an ABI PRISM 7000, using DNA from peripheral blood. Clinical response (CR), progression-free survival (PFS) and overall survival (OS) were evaluated according to each genotype. In the univariate analysis for CR, ERCC1-118 and XPD 751 polymorphisms were significant (P=0.02 and P=0.05, respectively). After adjustment for the most relevant clinical variables, only ERCC1-118 retained significance (P=0.008). In the univariate analysis for PFS, ERCC1-118 and XPD 751 were significant (P=0.003 and P=0.009, respectively). In the multivariant analysis, only the XPD 751 was significant for PFS (P=0.02). Finally, ERCC1-118 and XPD 751 polymorphisms were significant in the univariate analysis for OS (P=0.006 and P=0.015, respectively). Both genetic variables remained significant in the multivariate Cox survival analysis (P=0.022 and P=0.03). Our data support the hypothesis that enhanced DNA repair diminishes the benefit of platinum-based treatments. PMID:18797464

  11. Second-line erlotinib in patients with advanced non-small-cell lung cancer: subgroup analyses from the TRUST study.

    PubMed

    Heigener, David F; Wu, Yi-Long; van Zandwijk, Nico; Mali, Pekka; Horwood, Keith; Reck, Martin

    2011-11-01

    Erlotinib is a highly potent inhibitor of epidermal growth factor receptor tyrosine-kinase activity that significantly prolongs overall survival in patients with non-small-cell lung cancer (NSCLC), and improves symptom control and quality of life compared with placebo. The safety and efficacy of erlotinib has been investigated in a large, international, phase IV, open-label study (TRUST) in patients (n=6665) with advanced stage IIIB/IV NSCLC. An analysis of efficacy and safety outcomes is reported for patients receiving erlotinib as second-line therapy in TRUST (n=3224). Best response data were available for all 3224 patients. Complete response, partial response and stable disease were achieved in 25 (<1%), 368 (14%) and 1444 (54%) patients, respectively, for a disease control rate of 68%. Median progression-free and overall survivals were 13.6 weeks and 8.6 months, respectively; 1-year survival was 39.4%. Safety data were available for all patients. Of these, 389 patients (12%) had an erlotinib-related adverse event (AE) other than pre-specified AEs defined in the protocol; only 96 patients (3%) had an erlotinib-related AE ≥ grade 3. Of 1376 patients (43%) with serious AEs (SAEs), only 122 (4%) had treatment-related SAEs and most were gastrointestinal disorders (mainly diarrhoea and nausea). No treatment-related SAE occurred in ≥ 1% of patients. Data on the incidence of erlotinib-related rash were collected for all patients, 2302 (71%) of whom experienced rash. Of these rash events, 83% were of grade 1/2. These data confirm the good efficacy and tolerability of second-line erlotinib in a broad range of patients with NSCLC. PMID:21439671

  12. High-Brightness Beam Generation and Characterization at the Advanced Photon Source Low-Energy Undulator Test Line Linac*

    NASA Astrophysics Data System (ADS)

    Lewellen, John; Biedron, Sandra; Borland, Michael; Hahne, Michael; Harkay, Katherine; Lumpkin, Alex; Milton, Stephen; Sereno, Nicholas; Travish, Gil

    2000-04-01

    Improvements to the Advanced Photon Source injector linac have been made to allow for the production and characterization of high-brightness beams in support of fourth-generation light source research. In particular, effort has been directed at generating beams suitable for use in the low-energy undulator test line (LEUTL) free-electron laser (FEL). We describe the enhancements to the linac operational and diagnostic capabilities that enabled self-amplified spontaneous emission (SASE) operation of the FEL at 530 nm. Electron beam measurement techniques and recent results will be discussed. Beam properties are measured under the same operational conditions as those used for FEL studies. The nominal FEL beam parameters are as follows: 217 MeV beam energy; less than 0.15 mm-mrad normalized emittance; 100 A peak current from a 0.7-nC charge at a 7-psec bunch. * Work supported by the U.S. Department of Energy, Office of Basic Energy Sciences, under Contract No. W-31-109-ENG-38

  13. Genetic mapping of quantitative trait loci affecting susceptibility to Marek's disease virus induced tumors in F2 intercross chickens.

    PubMed Central

    Vallejo, R L; Bacon, L D; Liu, H C; Witter, R L; Groenen, M A; Hillel, J; Cheng, H H

    1998-01-01

    Marek's disease (MD) is a lymphoproliferative disease caused by the MD virus (MDV), which costs the poultry industry nearly $1 billion annually. To identify quantitative trait loci (QTL) affecting MD susceptibility, the inbred lines 6(3) (MD resistant) and 7(2) (MD susceptible) were mated to create more than 300 F2 chickens. The F2 chickens were challenged with MDV JM strain, moderately virulent) at 1 wk of age and assessed for MD susceptibility. The QTL analysis was divided into three stages. In stage 1, 65 DNA markers selected from the chicken genetic maps were typed on the 40 most MD-susceptible and the 40 most MD-resistant F2 chickens, and 21 markers residing near suggestive QTL were revealed by analysis of variance (ANOVA). In stage 2, the suggestive markers plus available flanking markers were typed on 272 F2 chickens, and three suggestive QTL were identified by ANOVA. In stage 3, using the interval mapping program Map Manager and permutation tests, two significant and two suggestive MD QTL were identified on four chromosomal subregions. Three to five loci collected explained between 11 and 23% of the phenotypic MD variation, or 32-68% of the genetic variance. This study constitutes the first report in the domestic chicken on the mapping of non-major histocompatibility complex QTL affecting MD susceptibility. PMID:9475745

  14. Genome-Wide Association Study of Meat Quality Traits in a White Duroc×Erhualian F2 Intercross and Chinese Sutai Pigs

    PubMed Central

    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. PMID:23724019

  15. Advanced glycation endproducts increase proliferation, migration and invasion of the breast cancer cell line MDA-MB-231.

    PubMed

    Sharaf, Hana; Matou-Nasri, Sabine; Wang, Qiuyu; Rabhan, Zaki; Al-Eidi, Hamad; Al Abdulrahman, Abdulkareem; Ahmed, Nessar

    2015-03-01

    Diabetic patients have increased likelihood of developing breast cancer. Advanced glycation endproducts (AGEs) underlie the pathogenesis of diabetic complications but their impact on breast cancer cells is not understood. This study aims to determine the effects of methylglyoxal-derived bovine serum albumin AGEs (MG-BSA-AGEs) on the invasive MDA-MB-231 breast cancer cell line. By performing cell counting, using wound-healing assay, invasion assay and zymography analysis, we found that MG-BSA-AGEs increased MDA-MB-231 cell proliferation, migration and invasion through Matrigel™ associated with an enhancement of matrix metalloproteinase (MMP)-9 activities, in a dose-dependent manner. Using Western blot and flow cytometry analyses, we demonstrated that MG-BSA-AGEs increased expression of the receptor for AGEs (RAGE) and phosphorylation of key signaling protein extracellular signal-regulated kinase (ERK)-1/2. Furthermore, in MG-BSA-AGE-treated cells, phospho-protein micro-array analysis revealed enhancement of phosphorylation of the ribosomal protein 70 serine S6 kinase beta 1 (p70S6K1), which is known to be involved in protein synthesis, the signal transducer and activator of transcription (STAT)-3 and the mitogen-activated protein kinase (MAPK) p38, which are involved in cell survival. Blockade of MG-BSA-AGE/RAGE interactions using a neutralizing anti-RAGE antibody inhibited MG-BSA-AGE-induced MDA-MB-231 cell processes, including the activation of signaling pathways. Throughout the study, non-modified BSA had a negligible effect. In conclusion, AGEs might contribute to breast cancer development and progression partially through the regulation of MMP-9 activity and RAGE signal activation. The up-regulation of RAGE and the concomitant increased phosphorylation of p70S6K1 induced by AGEs may represent promising targets for drug therapy to treat diabetic patients with breast cancer. PMID:25514746

  16. First-line treatment with FOLFOXIRI for advanced pancreatic cancer in clinical practice: Patients' outcome and analysis of prognostic factors.

    PubMed

    Vivaldi, Caterina; Caparello, Chiara; Musettini, Gianna; Pasquini, Giulia; Catanese, Silvia; Fornaro, Lorenzo; Lencioni, Monica; Falcone, Alfredo; Vasile, Enrico

    2016-08-15

    FOLFIRINOX is a standard first-line treatment for advanced pancreatic cancer (aPC). The Gruppo Oncologico Nord Ovest (GONO) FOLFOXIRI regimen demonstrated efficacy in metastatic colorectal cancer. We aimed to evaluate activity and tolerability of FOLFOXIRI regimen in patients with aPC and to explore putative prognostic factors. One hundred thirty-seven consecutive aPC patients were treated with FOLFOXIRI in our institution between 2008 and 2014. Clinical, laboratory and pathological data were collected and their association with activity, progression free survival (PFS) and overall survival (OS) was investigated. After a median follow up of 30 months, median PFS and OS were 8.0 months (95% CI 6.19-9.81) and 12 months (95% CI 9.75-14.25), respectively. Response rate was 38.6%, while disease-control rate 72.2%. At multivariate analysis liver metastases (p = 0.019; Hazard Ratio, HR, 0.59, 95% Confidence Interval, CI, 0.380.96), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 1 (p = 0.001; HR 2.26, 95%CI 1.42-3.59) and neutrophil-lymphocyte ratio (NLR)> 4 (p= 0.002; HR: 2.42; 95% CI 1.38-4.25) were associated with poorer OS. We categorized 119 pts with complete available data as good-risk (0 factors, 38 pts), intermediate-risk (1 factor, 49 pts) and poor-risk (≥2 factors, 32 pts). Median OS for these three groups were 17.6, 11.1 and 7.4 months, respectively (p < 0.001). FOLFOXIRI is active and feasible in aPC. Prognosis of aPC pts treated with FOLFOXIRI is influenced by easily available factors: our analysis revealed ECOG PS, liver metastases and NLR as the most important predictors of survival. These factors could be helpful for treatment decision and clinical trial design. PMID:27038273

  17. P11: 18FDG-PET/CT for early prediction of response to first line platinum chemotherapy in advanced thymic epithelial tumors

    PubMed Central

    Palmieri, Giovannella; Ottaviano, Margaret; Del Vecchio, Silvana; Segreto, Sabrina; Tucci, Irene; Damiano, Vincenzo

    2015-01-01

    Background To investigate the value of the metabolic tumor response assessed with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), compared with clinicobiological markers, to predict the response disease to first line platinum based chemotherapy in advanced thymic epithelial tumors (TETs). Methods Twenty patients with diagnosis of TET and stage of disease III and IV sec, Masaoka-Koga, were retrospectively included in this monocentric study. Different pre-treatment clinical, biological and pathological parameters, including histotype sec, WHO 2004 and stage of disease sec, Masaoka-Koga were assessed. Tumor glucose metabolism at baseline and its change after the first line platinum based chemotherapy (from 4 to 6 cycles) were assessed using FDG-PET, moreover the response disease was assessed using total body CT scan for the evaluation of RECIST criteria 1.1. Results Twelve patients had an objective response to the first line platinum based chemotherapy according RECIST criteria 1.1 and all of them started with a SUVmax at baseline major than 5, indeed the other eight patients, non-responders to chemotherapy, had a SUVmax at baseline minor than 5. Conclusions It is important to define the chemosensitivity of advanced TETs early. Combining bio-pathological parameters with the metabolism at baseline assessed with FDG-PET can help the physician to early predict the probability of obtaining a disease response to first line platinum based chemotherapy. The SUVmax cut off of 5 at 18FDG-PET/CT performed at baseline treatment might be a new parameter for choosing the most powerful first line of chemotherapy. Given these results, further prospective studies are needed to establish a new first line therapy in advanced TETs with a low SUVmax at baseline, non-responders to conventional chemotherapy.

  18. Neutropenia as a prognostic factor and safety of second-line therapy with S-1 for advanced or recurrent pancreatic cancer

    PubMed Central

    Ikagawa, Makiko; Kimura, Michio; Iwai, Mina; Usami, Eiseki; Yoshimura, Tomoaki; Yasuda, Kimio

    2016-01-01

    The aim of this retrospective study was to investigate the safety of S-1 as second-line therapy and to evaluate the association between neutropenia occurring during first-line gemcitabine (GEM) therapy and survival for advanced or recurrent pancreatic cancer (APC). Between January, 2010 and December, 2014, 123 APC patients received chemotherapy at the Ogaki Municipal Hospital (Ogaki, Japan). Of those, 37 received GEM as first-line and S-1 as a second-line therapy (GEM→S-1 group). A further 60 patients received GEM as first-line therapy, but did not receive second-line therapy (GEM group). The median overall survival in the GEM→S-1 (n=37) and GEM (n=60) groups was 323 days [95% confidence interval (CI): 138–218.9 days] and 172 days (95% CI: 105–184.4 days), respectively (P=0.0004). The median overall survival in the mild (grade ≤2; n=63) and severe (grade ≥3; n=34) neutropenia groups was 178 days (95% CI: 182–275 days) and 330 days (95% CI: 297–514 days), respectively (log-rank test, P=0.0023). The severe non-haematological toxicities associated with S-1 as second-line therapy were nausea (2.7%) and hand-foot syndrome (2.7%). Second-line S-1 treatment was discontinued due to adverse events in 5.4% (2/37) of the cases. In conclusion, neutropenia occurring during GEM therapy administered as first-line treatment to APC patients was strongly associated with a better prognosis. S-1 therapy as second-line treatment was associated with a low incidence of severe adverse events and the patients were able to successfully continue treatment.

  19. Efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell-lung cancer: a systematic review and meta-analysis

    PubMed Central

    Xiao, Huai-Qing; Tian, Rong-Hua; Zhang, Zhi-Hao; Du, Kai-Qi; Ni, Yi-Ming

    2016-01-01

    Purpose To assess the efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell lung cancer (NSCLC) through a trial-level meta-analysis. Methods Trials published between 1990 and 2015 were identified by an electronic search of public databases (Medline, Embase, and Cochrane Library). All clinical studies were independently identified by two authors. Demographic data, treatment regimens, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were extracted and analyzed using comprehensive meta-analysis software (version 2.0). Results A total of 2,551 patients with advanced nonsquamous NSCLC from ten trials were included for analysis: 1,565 patients were treated with pemetrexed plus platinum doublet chemotherapy and 986 with platinum plus other first-line chemotherapy. Pooled ORR for pemetrexed plus platinum chemotherapy was 37.8% (95% confidence interval [CI]: 31.7%–44.3%), with median PFS and OS of 5.7 and 16.05 months, respectively. When compared to other platinum-based doublet chemotherapies, the use of pemetrexed plus platinum chemotherapy significantly improved OS (hazard ratio [HR] =0.86, 95% CI: 0.77–0.97, P=0.01) but not PFS (HR =0.90, 95% CI: 0.80–1.01, P=0.084) in advanced nonsquamous NSCLC patients. Conclusion Pemetrexed plus platinum doublet regimen is an efficacious treatment for advanced nonsquamous NSCLC patients. Our findings support the use of pemetrexed plus platinum doublet regimen as first-line treatment in advanced nonsquamous NSCLC patients because of its potential survival benefits. PMID:27042115

  20. 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.

  1. Establishment of a Cell Line (CNUH-HNSCC-1) Derived from an Advanced Laryngeal Squamous Cell Carcinoma

    PubMed Central

    Lee, Dong-Hoon

    2011-01-01

    Cancer cell lines are the basic material for various lines of cancer research. Diverse cancer cell lines derived from tissues of various head and neck regions are needed for biological research on head and neck cancer. However, cell lines derived from cancer of the head and neck are not common. Recently, we established and characterized a novel human squamous carcinoma cell line, CNUH-HNSCC-1. From six cases of head and neck cancer, we established one specimen that was maintained for over 50 passages. We characterized the cell line as follows: growth patterns and curve, morphology by use of phase-contrast microscopy, and tumorigenicity by implanting the cell line into nude mice and making morphological comparisons. CNUH-HNSCC-1 cells grew well in vitro even after passage 50. However, the cells failed to form tumors in nude mice. CNUH-HNSCC-1 cells could be used as a control cell line for studying the biology of head and neck cancer. PMID:22111066

  2. 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

  3. Exercise Capacity and Response to Training Quantitative Trait Loci in a NZW X 129S1 Intercross and Combined Cross Analysis of Inbred Mouse Strains

    PubMed Central

    Massett, Michael P.; Avila, Joshua J.; Kim, Seung Kyum

    2015-01-01

    Genetic factors determining exercise capacity and the magnitude of the response to exercise training are poorly understood. The aim of this study was to identify quantitative trait loci (QTL) associated with exercise training in mice. Based on marked differences in training responses in inbred NZW (-0.65 ± 1.73 min) and 129S1 (6.18 ± 3.81 min) mice, a reciprocal intercross breeding scheme was used to generate 285 F2 mice. All F2 mice completed an exercise performance test before and after a 4-week treadmill running program, resulting in an increase in exercise capacity of 1.54 ± 3.69 min (range = -10 to +12 min). Genome-wide linkage scans were performed for pre-training, post-training, and change in run time. For pre-training exercise time, suggestive QTL were identified on Chromosomes 5 (57.4 cM, 2.5 LOD) and 6 (47.8 cM, 2.9 LOD). A significant QTL for post-training exercise capacity was identified on Chromosome 5 (43.4 cM, 4.1 LOD) and a suggestive QTL on Chromosomes 1 (55.7 cM, 2.3 LOD) and 8 (66.1 cM, 2.2 LOD). A suggestive QTL for the change in run time was identified on Chromosome 6 (37.8 cM, 2.7 LOD). To identify shared QTL, this data set was combined with data from a previous F2 cross between B6 and FVB strains. In the combined cross analysis, significant novel QTL for pre-training exercise time and change in exercise time were identified on Chromosome 12 (54.0 cM, 3.6 LOD) and Chromosome 6 (28.0 cM, 3.7 LOD), respectively. Collectively, these data suggest that combined cross analysis can be used to identify novel QTL and narrow the confidence interval of QTL for exercise capacity and responses to training. Furthermore, these data support the use of larger and more diverse mapping populations to identify the genetic basis for exercise capacity and responses to training. PMID:26710100

  4. 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

  5. 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

  6. Advances in first-line treatment of chronic lymphocytic leukemia: current recommendations on management and first-line treatment by the German CLL Study Group (GCLLSG).

    PubMed

    Cramer, Paula; Langerbeins, Petra; Eichhorst, Barbara; Hallek, Michael

    2016-01-01

    The management of patients with CLL is undergoing significant changes; during the last decade, the outcome of first-line therapies has been markedly improved with the addition of anti-CD20 antibodies to chemotherapy. Today, chemoimmunotherapy for physically fit patients ≤ 65 years should consist of fludarabine, cyclophosphamide, and rituximab (FCR). The combination of bendamustine and rituximab (BR) should be considered in physically fit patients > 65 years and in patients with a higher risk of infections. Patients with reduced fitness and/or relevant comorbidity should receive chlorambucil with a CD20 antibody, preferably obinutuzumab. Regardless of their fitness, patients with CLL carrying genetic aberrations such as del(17p) and/or TP53 mutation poorly respond to chemoimmunotherapy and therefore require different therapeutic approaches. An increasing understanding of the disease biology has led to the development of targeted drugs for the treatment of CLL, such as the BTK inhibitor ibrutinib and PI3K inhibitor idelalisib. These agents have shown efficacy in high-risk and relapsed/refractory patients and are currently being evaluated in clinical trials for first-line therapy. It is anticipated that these compounds and further other novel agents will profoundly change the therapy of CLL. PMID:26332019

  7. 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

  8. 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

  9. Six-Month Progression-Free Survival as the Primary Endpoint to Evaluate the Activity of New Agents as Second-line Therapy for Advanced Urothelial Carcinoma

    PubMed Central

    Agarwal, Neeraj; Bellmunt, Joaquim; Maughan, Benjamin L.; Boucher, Kenneth M.; Choueiri, Toni K.; Qu, Angela Q.; Vogelzang, Nicholas J.; Fougeray, Ronan; Niegisch, Guenter; Albers, Peter; Wong, Yu-Ning; Ko, Yoo-Joung; Sridhar, Srikala S.; Tantravahi, Srinivas K.; Galsky, Matthew D.; Petrylak, Daniel P.; Vaishampayan, Ulka N.; Mehta, Amitkumar N.; Beer, Tomasz M.; Sternberg, Cora. N.; Rosenberg, Jonathan E.; Sonpavde, Guru

    2014-01-01

    This study examined the association of progression-free survival at 6 months with overall survival in the context of second-line therapy of advanced urothelial carcinoma in pooled patient-level data from 10 phase II trials and then externally validated in a large phase III trial. Progression-free survival at 6 months was significantly correlated with overall survival and is an innovative primary endpoint to evaluate new agents in this setting. Objective Second-line systemic therapy for advanced urothelial carcinoma (UC) has substantial unmet needs, and current agents show dismal activity. Second-line trials of metastatic UC have used response rate (RR) and median progression-free survival (PFS) as primary endpoints, which may not reflect durable benefits. A more robust endpoint to identify signals of durable benefits when investigating new agents in second-line trials may expedite drug development. PFS at 6 months (PFS6) is a candidate endpoint, which may correlate with overall survival (OS) at 12 months (OS12) and may be applicable across cytostatic and cytotoxic agents. Methods Ten second-line phase II trials with individual patient outcomes data evaluating chemotherapy or biologics were combined for discovery, followed by external validation in a phase III trial. The relationship between PFS6/RR and OS12 was assessed at the trial level using Pearson correlation and weighted linear regression, and at the individual level using Pearson chi-square test with Yates continuity correction. Results In the discovery dataset, a significant correlation was observed between PFS6 and OS12 at the trial (R2 = 0.55, Pearson correlation = 0.66) and individual levels (82%, Қ = 0.45). Response correlated with OS12 at the individual level less robustly (78%, Қ = 0.36), and the trial level association was not statistically significant (R2 = 0.16, Pearson correlation = 0.37). The correlation of PFS6 (81%, Қ = 0.44) appeared PMID:24220220

  10. Efficacy and safety of capecitabine-based first-line chemotherapy in advanced or metastatic breast cancer: a meta-analysis of randomised controlled trials

    PubMed Central

    Liu, Gang; Huang, Li; Gao, Shegan; Feng, Xiaoshan

    2015-01-01

    We sought to evaluate the efficacy and safety of capecitabine-based therapy as first-line chemotherapy in advanced breast cancer. Randomised controlled trials of capecitabine monotherapy or combined treatment were included in the meta-analysis. PubMed, EMBASE, the Cochrane Library database and important meeting summaries were searched systematically. Outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and grades 3–4 drug-related adverse events. Nine trials with 1798 patients were included. The results indicated a significant improvement with capecitabine-based chemotherapy compared with capecitabine-free chemotherapy in ORR (relative risk [RR] 1.14, 95% confidence interval [CI] 1.03 to 1.26, P = 0.013) and PFS (hazard ratio [HR] 0.77, 95% CI 0.69 to 0.87, P < 0.0001). Overall survival favoured capecitabine-based chemotherapy, but this was not significant. There were more incidences of neutropenia and neutropenic fever in the capecitabine-free chemotherapy group and more vomiting, diarrhoea and hand–foot syndrome in the capecitabine-based chemotherapy group. There were no significant differences in nausea, fatigue, cardiotoxicity or mucositis/stomatitis between the two treatment regimens. Capecitabine-based chemotherapy significantly improves ORR and PFS in patients with advanced breast cancer, but has no demonstrable impact on OS. Capecitabine-based regimens are suitable as first-line treatment for patients with advanced breast cancer. PMID:26420815

  11. Efficacy and safety of capecitabine-based first-line chemotherapy in advanced or metastatic breast cancer: a meta-analysis of randomised controlled trials.

    PubMed

    Yin, Weijiao; Pei, Guangsheng; Liu, Gang; Huang, Li; Gao, Shegan; Feng, Xiaoshan

    2015-11-17

    We sought to evaluate the efficacy and safety of capecitabine-based therapy as first-line chemotherapy in advanced breast cancer. Randomised controlled trials of capecitabine monotherapy or combined treatment were included in the meta-analysis. PubMed, EMBASE, the Cochrane Library database and important meeting summaries were searched systematically. Outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and grades 3-4 drug-related adverse events.Nine trials with 1798 patients were included. The results indicated a significant improvement with capecitabine-based chemotherapy compared with capecitabine-free chemotherapy in ORR (relative risk [RR] 1.14, 95% confidence interval [CI] 1.03 to 1.26, P = 0.013) and PFS (hazard ratio [HR] 0.77, 95% CI 0.69 to 0.87, P < 0.0001). Overall survival favoured capecitabine-based chemotherapy, but this was not significant. There were more incidences of neutropenia and neutropenic fever in the capecitabine-free chemotherapy group and more vomiting, diarrhoea and hand-foot syndrome in the capecitabine-based chemotherapy group. There were no significant differences in nausea, fatigue, cardiotoxicity or mucositis/stomatitis between the two treatment regimens.Capecitabine-based chemotherapy significantly improves ORR and PFS in patients with advanced breast cancer, but has no demonstrable impact on OS. Capecitabine-based regimens are suitable as first-line treatment for patients with advanced breast cancer. PMID:26420815

  12. 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.

  13. Second-line treatment in advanced non-small-cell lung cancer in the epidermal growth factor receptor wild-type population: review of patient profile.

    PubMed

    Vázquez, Sergio; Lázaro, Martín; Fírvida, José Luis; Santomé, Lucía; Afonso, Javier; Amenedo, Margarita; Casal, Joaquín

    2014-04-01

    After progression during first-line treatment in advanced non-small-cell lung cancer (NSCLC), a large percentage of patients are candidates for second-line treatment. The majority do not have epidermal growth factor receptor-activating mutations (EGFRwt). This article reviews the treatment options available for this subpopulation of patients, which includes essentially docetaxel, pemetrexed and erlotinib. These drugs all have similar efficacy, both in terms of objective response rates and overall survival, although with different toxicity profiles. In view of the similar efficacy of the three agents (docetaxel, pemetrexed and erlotinib) in the second-line treatment of NSCLC in the EGFRwt population, and although there are no prospective studies on predictive variables or new molecular markers available, selection of the treatment will depend on the histological type (pemetrexed); patient preference (oral as opposed to intravenous formulation); the presence of comorbid conditions; quality of life; previous or residual toxicities; the risk of neutropenia; response to and the duration of the first-line chemotherapy; and history of smoking. PMID:24384805

  14. A prognostic model for platinum-doublet as second-line chemotherapy in advanced non-small-cell lung cancer patients.

    PubMed

    Mo, Hongnan; Hao, Xuezhi; Liu, Yutao; Wang, Lin; Hu, Xingsheng; Xu, Jianping; Yang, Sheng; Xing, Puyuan; Shi, Youwu; Jia, Bo; Wang, Yan; Li, Junling; Wang, Hongyu; Wang, Ziping; Sun, Yan; Shi, Yuankai

    2016-06-01

    Poor prognosis of advanced non-small-cell lung cancer (NSCLC) patients and the promising therapeutic effect of platinum urge the oncologists to evaluate the role of platinum doublet as second-line chemotherapy and establish the definition of platinum sensitivity in NSCLC. We retrospectively analyzed 364 advanced NSCLC patients who received platinum-doublet regimens as second-line chemotherapy after platinum-based first-line treatment. Patients were divided into four groups by their time-to-progression (TTP) after first-line chemotherapy: 0-3, 4-6, 7-12, and >12-month group, respectively. Treatment efficacy of patients' overall survival (OS), progression-free survival (PFS), and response rate (RR), as well as treatment-related toxicity, were compared among the four groups. A prognosis score system and a nomogram were established by Cox proportional hazard model, and validated by concordance index (c-index). Median OS was 14.0, 16.0, 20.0, 25.0 months for patients in the 0-3, 4-6, 7-12, >12-month group, respectively. Age ≤60 years (P = 0.002), female (P = 0.019), and TTP>12 months (P = 0.003) were independent prognostic factors. Prognostic score was calculated by adding 1 point each for any of the above three indicators, with a c-index of 0.590 (95% confidential interval [CI], 0.552-0.627). Median OS were equal to 25.0, 16.0, and 11.0 months for best (2-3 points), intermediate (1 point) and worst (0 point) category, respectively (P < 0.0001). A nomogram that integrated patient's age, gender, and TTP for OS has a c-index of 0.623 (95% CI, 0.603-0.643). Female, younger than 60 years, and TTP greater than 12 months may indicate prolonged survival after platinum-doublet second-line chemotherapy in advanced NSCLCpatients. PMID:26993156

  15. Microstructure evaluation of nanocrystalline MgO powders using the advanced X-ray line profile analysis

    NASA Astrophysics Data System (ADS)

    Soleimanian, V.; Abedi, M.; Aghdaee, S. R.

    2015-02-01

    In this study the magnesium oxide nanoparticles were synthesized via the sol-gel method and annealed at different temperatures between 400 and 800 °C in air. In order to evaluate the microstructure of samples, the scanning electron microscopy technique as well as the advanced X-ray diffraction analysis (DIFFaX software and eCMWP fitting procedure) was used and the behavior of crystallite size, size distribution function, dislocation density, the fractions of edge/screw dislocation characters and the probability of planar defects were studied as a function of annealing temperature.

  16. MicroRNA Expression Profiling of Peripheral Blood Samples Predicts Resistance to First-line Sunitinib in Advanced Renal Cell Carcinoma Patients12

    PubMed Central

    Gámez-Pozo, Angelo; Antón-Aparicio, Luis M; Bayona, Cristina; Borrega, Pablo; Gallegos Sancho, María I; García-Domínguez, Rocío; de Portugal, Teresa; Ramos-Vázquez, Manuel; Pérez-Carrión, Ramón; Bolós, María V; Madero, Rosario; Sánchez-Navarro, Iker; Fresno Vara, Juan A; Arranz, Enrique Espinosa

    2012-01-01

    Anti-angiogenic therapy benefits many patients with advanced renal cell carcinoma (RCC), but there is still a need for predictive markers that help in selecting the best therapy for individual patients. MicroRNAs (miRNAs) regulate cancer cell behavior and may be attractive biomarkers for prognosis and prediction of response. Forty-four patients with RCC were recruited into this observational prospective study conducted in nine Spanish institutions. Peripheral blood samples were taken before initiation of therapy and 14 days later in patients receiving first-line therapy with sunitinib for advanced RCC. miRNA expression in peripheral blood was assessed using microarrays and L2 boosting was applied to filtered miRNA expression data. Several models predicting poor and prolonged response to sunitinib were constructed and evaluated by binary logistic regression. Blood samples from 38 patients and 287 miRNAs were evaluated. Twenty-eight miRNAs of the 287 were related to poor response and 23 of the 287 were related to prolonged response to sunitinib treatment. Predictive models identified populations with differences in the established end points. In the poor response group, median time to progression was 3.5 months and the overall survival was 8.5, whereas in the prolonged response group these values were 24 and 29.5 months, respectively. Ontology analyses pointed out to cancer-related pathways, such angiogenesis and apoptosis. miRNA expression signatures, measured in peripheral blood, may stratify patients with advanced RCC according to their response to first-line therapy with sunitinib, improving diagnostic accuracy. After proper validation, these signatures could be used to tailor therapy in this setting. PMID:23308047

  17. Randomized Phase III Placebo-Controlled Trial of Letrozole Plus Oral Temsirolimus As First-Line Endocrine Therapy in Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer

    PubMed Central

    Wolff, Antonio C.; Lazar, Ann A.; Bondarenko, Igor; Garin, August M.; Brincat, Stephen; Chow, Louis; Sun, Yan; Neskovic-Konstantinovic, Zora; Guimaraes, Rodrigo C.; Fumoleau, Pierre; Chan, Arlene; Hachemi, Soulef; Strahs, Andrew; Cincotta, Maria; Berkenblit, Anna; Krygowski, Mizue; Kang, Lih Lisa; Moore, Laurence; Hayes, Daniel F.

    2013-01-01

    Purpose Recent data showed improvement in progression-free survival (PFS) when adding everolimus to exemestane in patients with advanced breast cancer experiencing recurrence/progression after nonsteroidal aromatase inhibitor (AI) therapy. Here, we report clinical outcomes of combining the mammalian target of rapamycin (mTOR) inhibitor temsirolimus with letrozole in AI-naive patients. Patients and Methods This phase III randomized placebo-controlled study tested efficacy/safety of first-line oral letrozole 2.5 mg daily/temsirolimus 30 mg daily (5 days every 2 weeks) versus letrozole/placebo in 1,112 patients with AI-naive, hormone receptor–positive advanced disease. An independent data monitoring committee recommended study termination for futility at the second preplanned interim analysis (382 PFS events). Results Patients were balanced (median age, 63 years; 10% stage III, 40% had received adjuvant endocrine therapy). Those on letrozole/temsirolimus experienced more grade 3 to 4 events (37% v 24%). There was no overall improvement in primary end point PFS (median, 9 months; hazard ratio [HR], 0.90; 95% CI, 0.76 to 1.07; P = .25) nor in the 40% patient subset with prior adjuvant endocrine therapy. An exploratory analysis showed improved PFS favoring letrozole/temsirolimus in patients ≤ age 65 years (9.0 v 5.6 months; HR, 0.75; 95% CI, 0.60 to 0.93; P = .009), which was separately examined by an exploratory analysis of 5-month PFS using subpopulation treatment effect pattern plot methodology (P = .003). Conclusion Adding temsirolimus to letrozole did not improve PFS as first-line therapy in patients with AI-naive advanced breast cancer. Exploratory analyses of benefit in younger postmenopausal patients require external confirmation. PMID:23233719

  18. 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

  19. Everolimus as second- or third-line treatment of advanced endometrial cancer: ENDORAD, a phase II trial of GINECO

    PubMed Central

    Ray-Coquard, I; Favier, L; Weber, B; Roemer-Becuwe, C; Bougnoux, P; Fabbro, M; Floquet, A; Joly, F; Plantade, A; Paraiso, D; Pujade-Lauraine, E

    2013-01-01

    Background: Patients with recurrent/metastatic endometrial cancer that progresses after chemotherapy have limited treatment options and poor outcomes. Preclinical data suggest the oral mammalian target of rapamycin inhibitor everolimus may provide clinical benefit in these patients. Methods: In this multicenter, open-label, phase 2 study, patients with advanced or metastatic endometrial cancer refractory to one or two previous chemotherapy regimens received everolimus 10 mg per day until progression or unacceptable toxicity. Primary end point was the non-progressive disease rate at 3 months. Secondary end points included duration of response, progression-free, and overall survival (OS), and safety. Results: Forty-four patients were enrolled (median age, 65 years); 66% received one previous chemotherapy regimen. The 3-month non-progressive disease rate was 36% (95% confidence interval 22–52%), including two patients (5%) with partial response (PR). At 6 months, two additional patients experienced PR. Median duration of response was 3.1 months. Median progression-free and OS were 2.8 months and 8.1 months, respectively. The most common adverse events were anaemia (100%), fatigue (93%), hypercholesterolaemia (81%), and lymphopenia (81%). Conclusion: Everolimus demonstrated efficacy and acceptable tolerability in patients with chemotherapy-refractory advanced or metastatic endometrial cancer. These results support the further development of phosphatidylinositol 3-kinase-targeted therapies in endometrial cancer. PMID:23612453

  20. 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

  1. 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

  2. [A case of advanced breast cancer with multiple bone metastases responding to docetaxel and high-dose toremifene as fourth-line chemo-endocrine therapy].

    PubMed

    Minamoto, Kanji; Ikeda, Toshio

    2009-12-01

    A 55-year old woman, who underwent left mastectomy (Bt+Ax), was revealed to have sternum metastasis by postoperative 99mTc bone scanning(T1bN1M1). She received daily aromatase inhibitor (anastrozole), as a primary systemic endocrine therapy, and biweekly pamidronate for metastatic breast cancer. However, she depended on folk medicine a year later, at which time the primary treatment was discontinued. Another year later, the bone metastases developed with increased serum levels of tumor markers (CEA, CA19-9, and NCC-ST-439). Then, she underwent three different regimens of systemic chemo-endocrine therapy over the following three years, including CAF+MPA as the first-line, paclitaxel (PTX) + anastrozole as the second-line, and S-1+anastrozole as the third-line regimen. She recently completed 10 courses of the fourth-line regimen[tri-weekly docetaxel (DOC) and high-dose toremifene (TOR 120 mg/day)], which reduced levels of 99mTc accumulation in the multiple bone metastases and levels of the serum tumor markers to the normal range. No severe adverse events occurred except peripheral thrombovasculitis (grade 2) in her left anterior arm during the fourth regimen. She recently maintains the current status by taking a regular dose (40 mg/day) of toremifene for 5 months. Combination treatment with DOC and high-dose TOR can be one of the worthwhile regimens as systemic chemo-endocrine therapy for patients with advanced breast cancer who develop bone metastases. PMID:20009468

  3. Impact of Smoking and Brain Metastasis on Outcomes of Advanced EGFR Mutation Lung Adenocarcinoma Patients Treated with First Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

    PubMed Central

    Jain, Amit; Lim, Cindy; Gan, Eugene MingJin; Ng, David Zhihao; Ng, Quan Sing; Ang, Mei Kim; Takano, Angela; Chan, Kian Sing; Tan, Wu Meng; Kanesvaran, Ravindran; Toh, Chee Keong; Loo, Chian Min; Hsu, Anne Ann Ling; Devanand, Anantham; Lim, Chong Hee; Koong, Heng Nung; Koh, Tina; Fong, Kam Weng; Yap, Swee Peng; Kim, Su Woon; Chowbay, Balram; Oon, Lynette; Lim, Kiat Hon; Lim, Wan Teck; Tan, Eng Huat; Tan, Daniel Shao Weng

    2015-01-01

    Objectives This purpose of this study was to examine clinical-pathologic factors – particularly smoking and brain metastases – in EGFR mutation positive (M+) lung adenocarcinoma (ADC) to determine their impact on survival in patients treated with first line EGFR TKI. Methods A retrospective review of EGFR mutation reflex testing experience for all ADC diagnosed at a tertiary Asian cancer centre from January 2009 to April 2013. Amongst this cohort, patients with advanced EGFR M+ ADC treated with first line EGFR TKI were identified to determine factors that influence progression free and overall survival. Results 444/742 (59.8%) ADC reflex tested for EGFR mutations were EGFR M+. Amongst never-smokers (n=468), EGFR M+ were found in 74.5% of females and 76.3% of males, and amongst ever smokers (n=283), in 53.3% of females and 35.6% of males. Exon 20 mutations were found more commonly amongst heavy smokers (> 50 pack years and > 20 pack years, Pearson’s chi square p=0.044, and p=0.038 respectively). 211 patients treated with palliative first line TKI had a median PFS and OS of 9.2 and 19.6 months respectively. 26% of patients had brain metastasis at diagnosis. This was significantly detrimental to overall survival (HR 1.85, CI 1.09-3.16, p=0.024) on multivariate analysis. There was no evidence that smoking status had a significant impact on survival. Conclusions The high prevalence of EGFR M+ in our patient population warrants reflex testing regardless of gender and smoking status. Smoking status and dosage did not impact progression free or overall survival in patients treated with first line EGFR TKI. The presence of brain metastasis at diagnosis negatively impacts overall survival. PMID:25955322

  4. 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

  5. Specific siRNA Targeting Receptor for Advanced Glycation End Products (RAGE) Decreases Proliferation in Human Breast Cancer Cell Lines

    PubMed Central

    Radia, AL-Madhagi; Yaser, AL-Madhagi; Ma, Xiaoqian; Zhang, Juan; Yang, Cejun; Dong, Qiong; Rong, Pengfei; Ye, Bin; Liu, Sheng; Wang, Wei

    2013-01-01

    Receptor for Advanced Glycation End Products (RAGE) is an oncogenic trans-membranous receptor overexpressed in various human cancers. However, the role of RAGE in breast cancer development and proliferation is still unclear. In this study, we demonstrated that RAGE expression levels are correlated to the degree of severity of breast cancer. Furthermore, there is a decrease in the proliferation of all sub-types of breast cancer, MCF-7, SK-Br-3 and MDA-MB-231, as a result of the effect of RAGE siRNA. RAGE siRNA arrested cells in the G1 phase and inhibited DNA synthesis (p < 0.05). Moreover, qRT-PCR and Western Blot results demonstrated that RAGE siRNA decreases the expression of transcriptional factor NF-κB p65 as well as the expression of cell proliferation markers PCNA and cyclinD1. RAGE and RAGE ligands can thus be considered as possible targets for breast cancer management and therapy. PMID:23579957

  6. Specific siRNA targeting receptor for advanced glycation end products (RAGE) decreases proliferation in human breast cancer cell lines.

    PubMed

    Radia, Al-Madhagi; Yaser, Al-Madhagi; Ma, Xiaoqian; Zhang, Juan; Yang, Cejun; Dong, Qiong; Rong, Pengfei; Ye, Bin; Liu, Sheng; Wang, Wei

    2013-01-01

    Receptor for Advanced Glycation End Products (RAGE) is an oncogenic trans-membranous receptor overexpressed in various human cancers. However, the role of RAGE in breast cancer development and proliferation is still unclear. In this study, we demonstrated that RAGE expression levels are correlated to the degree of severity of breast cancer. Furthermore, there is a decrease in the proliferation of all sub-types of breast cancer, MCF-7, SK-Br-3 and MDA-MB-231, as a result of the effect of RAGE siRNA. RAGE siRNA arrested cells in the G1 phase and inhibited DNA synthesis (p < 0.05). Moreover, qRT-PCR and Western Blot results demonstrated that RAGE siRNA decreases the expression of transcriptional factor NF-κB p65 as well as the expression of cell proliferation markers PCNA and cyclinD1. RAGE and RAGE ligands can thus be considered as possible targets for breast cancer management and therapy. PMID:23579957

  7. 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.

  8. 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.

  9. Recent Advances in On-Line Methods Based on Extraction for Speciation Analysis of Chromium in Environmental Matrices.

    PubMed

    Trzonkowska, Laura; Leśniewska, Barbara; Godlewska-Żyłkiewicz, Beata

    2016-07-01

    The biological activity of Cr(III) and Cr(VI) species, their chemical behavior, and toxic effects are dissimilar. The speciation analysis of Cr(III) and Cr(VI) in environmental matrices is then of great importance and much research has been devoted to this area. This review presents recent developments in on-line speciation analysis of chromium in such samples. Flow systems have proved to be excellent tools for automation of sample pretreatment, separation/preconcentration of chromium species, and their detection by various instrumental techniques. Analytical strategies used in chromium speciation analysis discussed in this review are divided into categories based on selective extraction/separation of chromium species on solid sorbents and liquid-liquid extraction of chromium species. The most popular strategy is that based on solid-phase extraction. Therefore, this review shows the potential of novel materials designed and used for selective binding of chromium species. The progress in miniaturization of measurement systems is also presented. PMID:26186521

  10. Phase II study of necitumumab plus modified FOLFOX6 as first-line treatment in patients with locally advanced or metastatic colorectal cancer

    PubMed Central

    Elez, E; Hendlisz, A; Delaunoit, T; Sastre, J; Cervantes, A; Varea, R; Chao, G; Wallin, J; Tabernero, J

    2016-01-01

    Background: This single-arm phase II study investigated the EGFR monoclonal antibody necitumumab plus modified FOLFOX6 (mFOLFOX6) in first-line treatment of locally advanced or metastatic colorectal cancer (mCRC). Methods: Patients received 800-mg intravenous necitumumab (day 1; 2-week cycles), followed by oxaliplatin 85 mg m−2, folinic acid 400 mg m−2, and 5-fluorouracil (400 mg m−2 bolus then 2400 mg m−2 over 46 h). Radiographic evaluation was performed every 8 weeks until progression. Primary endpoint was objective response rate. Results: Forty-four patients were enrolled and treated. Objective response rate was 63.6% (95% confidence interval 47.8–77.6); complete response was observed in four patients; median duration of response was 10.0 months (7.0–16.0). Median overall survival (OS) and progression-free survival (PFS) were 22.5 (11.0–30.0) and 10.0 months (7.0–12.0), respectively. Clinical outcome was better in patients with KRAS exon 2 wild type (median OS 30.0 months (23.0–NA); median PFS 12.0 (8.0–20.0)), compared with KRAS exon 2 mutant tumours (median OS 7.0 months (5.0–37.0); median PFS 7.0 (4.0–18.0)). The most common grade ⩾3 adverse events were neutropenia (29.5%), asthenia (27.3%), and rash (20.5%). Conclusion: First-line necitumumab+mFOLFOX6 was active with manageable toxicity in locally advanced or mCRC; additional evaluation of the impact of tumour RAS mutation status is warranted. PMID:26766738

  11. Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China

    PubMed Central

    Zhang, Chunxiang; Zhang, Hongmei; Shi, Jinning; Wang, Dong; Zhang, Xiuwei; Yang, Jian; Zhai, Qizhi; Ma, Aixia

    2016-01-01

    Background Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC) from the perspective of the Chinese healthcare system. Methods Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs) and incremental cost-utility ratios (ICURs) were calculated. One-way and probabilistic sensitivity analyses (PSA) were performed. Results Our model suggested that the median progression-free survival (PFS) was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy. Conclusions The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market. PMID:27015267

  12. Fiber Optic Fourier Transform Infrared Spectroscopic Techniques for Advanced On-Line Chemical Analysis in Semiconductor Fabrication Tools

    NASA Astrophysics Data System (ADS)

    Kester, Michael; Trygstad, Marc; Chabot, Paul

    2003-09-01

    A unique analytical methodology has recently been developed to perform real-time, on-line chemical analysis of bath solutions in semiconductor fabrication tools. A novel, patented fiber optic sensor is used to transmit infrared light directly through the tube walls of the circulating bath solutions within the fabrication tool in a completely non-invasive, non-extractive way. The sensor simply "clips" onto the tubing, thus permitting immediate analysis of the bath composition by Fourier Transform infrared (FTIR) spectroscopy. The infrared spectrometer is capable of multiplexing up to eight "Clippir™" sensor heads to a single interferometer using fiber optic cables. The instrument can analyze almost any bath solution utilized today. The analysis is performed using the near-infrared (NIR) portion of the electromagnetic spectrum, where absorption bands related to molecular vibrations can be found. The Fourier Transform infrared spectrometer gives access to absorption bands over a wide range of frequencies (or wavelengths), and the absorptions are correlated to concentrations using a chemometric approach employing a partial least-squares algorithm. Models are generated from this approach for each chemistry to be analyzed. This paper will review the analytical technology necessary to make such measurements, and discuss the instrument performance criteria required to achieve accurate and precise measurements of bath chemistries. The ability to measure non-infrared absorbing compounds will be discussed, as will the nature of the influence of sample temperature on measurement. Issues critical to the development of robust models and their direct implementation on multiple channels and even different instruments will be considered.

  13. 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

  14. 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

  15. FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy.

    PubMed

    Kim, Geoffrey; Ison, Gwynn; McKee, Amy E; Zhang, Hui; Tang, Shenghui; Gwise, Thomas; Sridhara, Rajeshwari; Lee, Eunice; Tzou, Abraham; Philip, Reena; Chiu, Haw-Jyh; Ricks, Tiffany K; Palmby, Todd; Russell, Anne Marie; Ladouceur, Gaetan; Pfuma, Elimika; Li, Hongshan; Zhao, Liang; Liu, Qi; Venugopal, Rajesh; Ibrahim, Amna; Pazdur, Richard

    2015-10-01

    On December 19, 2014, the FDA approved olaparib capsules (Lynparza; AstraZeneca) for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. The BRACAnalysis CDx (Myriad Genetic Laboratories, Inc.) was approved concurrently. An international multicenter, single-arm trial enrolled 137 patients with measurable gBRCAm-associated ovarian cancer treated with three or more prior lines of chemotherapy. Patients received olaparib at a dose of 400 mg by mouth twice daily until disease progression or unacceptable toxicity. The objective response rate (ORR) was 34% with median response duration of 7.9 months in this cohort. The most common adverse reactions (≥20%) in patients treated with olaparib were anemia, nausea, fatigue (including asthenia), vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/upper respiratory infection, cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash, and abdominal pain/discomfort. Myelodysplatic syndrome and/or acute myeloid leukemia occurred in 2% of the patients enrolled on this trial. PMID:26187614

  16. 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.

  17. 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

  18. 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

  19. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial

    PubMed Central

    Maughan, Timothy S; Adams, Richard A; Smith, Christopher G; Meade, Angela M; Seymour, Matthew T; Wilson, Richard H; Idziaszczyk, Shelley; Harris, Rebecca; Fisher, David; Kenny, Sarah L; Kay, Edward; Mitchell, Jenna K; Madi, Ayman; Jasani, Bharat; James, Michelle D; Bridgewater, John; Kennedy, M John; Claes, Bart; Lambrechts, Diether; Kaplan, Richard; Cheadle, Jeremy P

    2011-01-01

    Summary Background In the Medical Research Council (MRC) COIN trial, the epidermal growth factor receptor (EGFR)-targeted antibody cetuximab was added to standard chemotherapy in first-line treatment of advanced colorectal cancer with the aim of assessing effect on overall survival. Methods In this randomised controlled trial, patients who were fit for but had not received previous chemotherapy for advanced colorectal cancer were randomly assigned to oxaliplatin and fluoropyrimidine chemotherapy (arm A), the same combination plus cetuximab (arm B), or intermittent chemotherapy (arm C). The choice of fluoropyrimidine therapy (capecitabine or infused fluouroracil plus leucovorin) was decided before randomisation. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and C is described in a companion paper. Here, we present the comparison of arm A and B, for which the primary outcome was overall survival in patients with KRAS wild-type tumours. Analysis was by intention to treat. Further analyses with respect to NRAS, BRAF, and EGFR status were done. The trial is registered, ISRCTN27286448. Findings 1630 patients were randomly assigned to treatment groups (815 to standard therapy and 815 to addition of cetuximab). Tumour samples from 1316 (81%) patients were used for somatic molecular analyses; 565 (43%) had KRAS mutations. In patients with KRAS wild-type tumours (arm A, n=367; arm B, n=362), overall survival did not differ between treatment groups (median survival 17·9 months [IQR 10·3–29·2] in the control group vs 17·0 months [9·4–30·1] in the cetuximab group; HR 1·04, 95% CI 0·87–1·23, p=0·67). Similarly, there was no effect on progression-free survival (8·6 months [IQR 5·0–12·5] in the control group vs 8·6 months [5·1–13·8] in the cetuximab group; HR 0·96, 0·82–1·12, p=0·60). Overall response rate increased from 57% (n=209

  20. A Phase II Biomarker-Embedded Study of Lapatinib plus Capecitabine as First-line Therapy in Patients with Advanced or Metastatic Gastric Cancer.

    PubMed

    LaBonte, Melissa J; Yang, Dongyun; Zhang, Wu; Wilson, Peter M; Nagarwala, Yasir M; Koch, Kevin M; Briner, Colleen; Kaneko, Tomomi; Rha, Sun-Young; Gladkov, Oleg; Urba, Susan G; Sakaeva, Dina; Pishvaian, Michael J; Hsieh, Ruey-Kuen; Lee, Wei-Ping; Lenz, Heinz-Josef

    2016-09-01

    An exploratory phase II biomarker-embedded trial (LPT109747; NCT00526669) designed to determine the association of lapatinib-induced fluoropyrimidine gene changes with efficacy of lapatinib plus capecitabine as first-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma independent of tumor HER2 status. Tumor biopsies obtained before and after 7-day lapatinib (1,250 mg) to analyze changes in gene expression, followed by a 14-day course of capecitabine (1,000 mg/m(2) twice daily, 14/21 days) plus lapatinib 1,250 mg daily. Blood samples were acquired for pharmacokinetic analysis. Primary clinical objectives were response rate (RR) and 5-month progression-free survival (PFS). Secondary objectives were overall survival (OS), PFS, time to response, duration of response, toxicity, and identification of associations between lapatinib pharmacokinetics and biomarker endpoints. Primary biomarker objectives were modulation of 5-FU-pathway genes by lapatinib, effects of germline SNPs on treatment outcome, and trough steady-state plasma lapatinib concentrations. Sixty-eight patients were enrolled; (75% gastric cancer, 25% gastroesophageal junction). Twelve patients (17.9%) had confirmed partial response, 31 (46.3%) had stable disease, and 16 (23.9%) had progressive disease. Median PFS and OS were 3.3 and 6.3 months, respectively. Frequent adverse events included diarrhea (45%), decreased appetite (39%), nausea (36%), and fatigue (36%). Lapatinib induced no changes in gene expression from baseline and no significant associations were found for SNPs analyzed. Elevated baseline HER3 mRNA expression was associated with a higher RR (33% vs. 0%; P = 0.008). Lapatinib plus capecitabine was well tolerated, demonstrating modest antitumor activity in patients with advanced gastric cancer. The association of elevated HER3 and RR warrants further investigation as an important player for HER-targeted regimens in combination with capecitabine. Mol Cancer Ther

  1. Mitomycin C plus S-1 as second-line therapy in patients with advanced gastric cancer: a noncomparative phase II study.

    PubMed

    Park, Se Hoon; Kim, Young Saing; Hong, Junshik; Park, Jinny; Nam, Eunmi; Cho, Eun Kyung; Shin, Dong Bok; Lee, Jae Hoon; Lee, Woon Kee; Chung, Min

    2008-03-01

    S-1 is an oral fluoropyrimidine consisting of the 5-fluorouracil prodrug tegafur combined with two modulating substances, gimeracil and potassium oxonate. On the basis of the potential additive effect between mitomycin C (MMC) and 5-fluorouracil as a continuous infusion, we conducted a phase II study to assess the efficacy and tolerability of the combination of S-1 and MMC as second-line chemotherapy for advanced gastric cancer (AGC). Patients with measurable AGC, progressive after one prior chemotherapy for metastatic disease, received MMC (7 mg/m2) on day 1 and S-1 (40 mg/m2) twice daily as an intermittent regimen of 4 weeks of treatment followed by a 2-week rest. Treatment was repeated every 6 weeks. The primary objective was the response rate. For 43 patients registered, 42 patients were treated with MMC plus S-1. A total of 121 chemotherapy cycles were delivered (median: 2; range: 1-6). The patients' median age was 53 years (range: 31-75) and nine (21%) had an Eastern Cooperative Oncology Group performance status of 2. In an intent-to-treat analysis, nine patients (21%) achieved an objective response, which was maintained for 4.1 months. The median progression-free and overall survivals were 3.4 months (95% confidence interval: 2.3-4.5) and 8.0 months (95% confidence interval: 6.1-9.9), respectively. Although fatigue was the most frequently encountered toxicity safety profiles were generally predictable and manageable. One patient developed hemolytic anemia, which was resolved spontaneously. Grade > or = 2 hand-foot syndrome was observed in only three patients. Second-line chemotherapy with MMC and S-1 is an active and tolerable regimen for AGC patients with good performance status. PMID:18510177

  2. 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

  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. 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

  5. Sunitinib Plus Paclitaxel Versus Bevacizumab Plus Paclitaxel for First-Line Treatment of Patients With Advanced Breast Cancer: A Phase III, Randomized, Open-Label Trial

    PubMed Central

    Robert, Nicholas J.; Saleh, Mansoor N.; Paul, Devchand; Generali, Daniele; Gressot, Laurent; Copur, Mehmet S.; Brufsky, Adam M.; Minton, Susan E.; Giguere, Jeffrey K.; Smith, John W.; Richards, Paul D.; Gernhardt, Diana; Huang, Xin; Liau, Katherine F.; Kern, Kenneth A.; Davis, John

    2015-01-01

    Introduction A multicenter, open-label phase III study was conducted to test whether sunitinib plus paclitaxel prolongs progression-free survival (PFS) compared with bevacizumab plus paclitaxel as first-line treatment for patients with HER2− advanced breast cancer. Patients and Methods Patients with HER2− advanced breast cancer who were disease free for ≥ 12 months after adjuvant taxane treatment were randomized (1:1; planned enrollment 740 patients) to receive intravenous (I.V.) paclitaxel 90 mg/m2 every week for 3 weeks in 4-week cycles plus either sunitinib 25 to 37.5 mg every day or bevacizumab 10 mg/kg I.V. every 2 weeks. Results The trial was terminated early because of futility in reaching the primary endpoint as determined by the independent data monitoring committee during an interim futility analysis. At data cutoff, 242 patients had been randomized to sunitinib-paclitaxel and 243 patients to bevacizumab-paclitaxel. Median PFS was shorter with sunitinib-paclitaxel (7.4 vs. 9.2 months; hazard ratio [HR] 1.63 [95% confidence interval (CI), 1.18–2.25]; 1-sided P = .999). At a median follow-up of 8.1 months, with 79% of sunitinib-paclitaxel and 87% of bevacizumab-paclitaxel patients alive, overall survival analysis favored bevacizumab-paclitaxel (HR 1.82 [95% CI, 1.16–2.86]; 1-sided P = .996). The objective response rate was 32% in both arms, but median duration of response was shorter with sunitinib-paclitaxel (6.3 vs. 14.8 months). Bevacizumab-paclitaxel was better tolerated than sunitinib-paclitaxel. This was primarily due to a high frequency of grade 3/4, treatment-related neutropenia with sunitinib-paclitaxel (52%) precluding delivery of the prescribed doses of both drugs. Conclusion The sunitinib-paclitaxel regimen evaluated in this study was clinically inferior to the bevacizumab-paclitaxel regimen and is not a recommended treatment option for patients with advanced breast cancer. PMID:21569994

  6. 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. PMID:26653337

  7. 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

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

    PubMed Central

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

    2016-01-01

    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 (r2 > 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 5 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

  9. 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

  10. Glucagon-like peptide-1 counteracts the detrimental effects of Advanced Glycation End-Products in the pancreatic beta cell line HIT-T 15

    SciTech Connect

    Puddu, A.; Storace, D.; Durante, A.; Odetti, P.; Viviani, G.L.

    2010-07-30

    Research highlights: {yields} GLP-1 prevents AGEs-induced cell death. {yields} GLP-1 prevents AGEs-induced oxidative stress. {yields} GLP-1 ameliorated AGEs-induced cell dysfunction. {yields} GLP-1 attenuates AGEs-induced RAGE increment. {yields} GLP-1 counteracts AGEs-induced pancreatic cell death and dysfunction. -- Abstract: Advanced Glycation End-Products (AGEs), a group of compounds resulting from the non-enzymatic reaction of reducing sugars with the free amino group of proteins, are implicated in diabetic complications. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T 15 to high concentrations of AGEs significantly decreases cell proliferation and insulin secretion, and affects transcription factors regulating insulin gene transcription. The glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases proinsulin biosynthesis, stimulates insulin secretion, and improves pancreatic beta-cell viability. The aim of this work was to investigate the effects of GLP-1 on the function and viability of HIT-T 15 cells cultured with AGEs. HIT-T 15 cells were cultured for 5 days in presence of AGEs alone, or supplemented with 10 nmol/l GLP-1. Cell viability, insulin secretion, redox balance, and expression of the AGEs receptor (RAGE) were then determined. The results showed that GLP-1 protected beta cell against AGEs-induced cell death preventing both apoptosis and necrosis. Moreover, addition of GLP-1 to the AGEs culture medium restored the redox balance, improved the responsiveness to glucose, and attenuated AGEs-induced RAGE expression. These findings provide evidence that GLP-1 protects beta cells from the dangerous effects of AGEs.

  11. Everolimus for the second-line treatment of advanced and/or metastatic renal cell cancer: a critique of the submission from Novartis.

    PubMed

    Pitt, M; Crathorne, L; Moxham, T; Bond, M; Hyde, C

    2010-10-01

    This paper represents a summary of the evidence review group (ERG) report into the clinical efficacy, safety and cost-effectiveness of everolimus plus best supportive care (BSC) for the treatment of advanced renal cell carcinoma (RCC) which has progressed following or on vascular endothelial growth factor-targeted therapy (sunitinib, sorafenib, bevacizumab), compared to BSC alone. The submitting manufacturer's case for clinical effectiveness and cost-effectiveness was mainly based on a well-conducted randomised controlled trial (RCT), Renal Cell Cancer Treatment with Oral RAD001 Given Daily-1 (RECORD-1), comparing BSC plus everolimus with BSC plus placebo and a de novo economic model. The RCT indicated a marked statistically significant effect on progression-free survival. The base-case incremental cost-effectiveness ratio (ICER) estimate was 52,000 pounds per quality-adjusted life-year (this included a reduction in drug cost associated with an approved patient access scheme). The ERG undertook a critical appraisal of the submission. The ERG was generally in agreement with the submitting manufacturer concerning its estimates of effectiveness; however, there was greater concern surrounding the estimates of cost-effectiveness. The ERG judged that if potential errors in the model were corrected, the ICERs offered by the submitting manufacturer would overstate the cost-effectiveness of everolimus for the second-line treatment of metastatic RCC (that this ICER would be a higher value). Concerning the estimates of cost-effectiveness in RCC, the observations in the ERG report provide strong further support for research collecting rigorous estimates of utilities associated with the main health states likely to be experienced by patients with renal cell cancer. At the time of writing, NICE was yet to issue the Appraisal Consultation Document for this appraisal. PMID:21047490

  12. Phase II study of weekly vinorelbine and 24-h infusion of high-dose 5-fluorouracil plus leucovorin as first-line treatment of advanced breast cancer

    PubMed Central

    Yeh, K H; Lu, Y S; Hsu, C H; Lin, J F; Chao, H J; Huang, T C; Chung, C Y; Chang, C S; Yang, C H; Cheng, A L

    2005-01-01

    We prospectively investigated the efficacy and safety of combining weekly vinorelbine (VNB) with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV) in the treatment of patients with advanced breast cancer (ABC). Vinorelbine 25 mg m−2 30-min intravenous infusion, and high-dose 5-FU 2600 mg m−2 plus LV 300 mg m−2 24-h intravenous infusion (HDFL regimen) were given on days 1 and 8 every 3 weeks. Between June 1999 and April 2003, 40 patients with histologically confirmed recurrent or metastatic breast cancer were enrolled with a median age of 49 years (range: 36–68). A total of 25 patients had recurrent ABC, and 15 patients had primary metastatic diseases. The overall response rate for the intent-to-treat group was 70.0% (95% CI: 54–84%) with eight complete responses and 20 partial responses. All 40 patients were evaluated for survival and toxicities. Among a total of 316 cycles of VNB–HDFL given (average: 7.9: range: 4–14 cycles per patient), the main toxicity was Gr3/4 leucopenia and Gr3/4 neutropenia in 57 (18.0%) and 120 (38.0%) cycles, respectively. Gr1/2 infection and Gr1/2 stomatitis were noted in five (1.6%) and 59 (18.7%) cycles, respectively. None of the patients developed Gr3/4 stomatitis or Gr3/4 infection. Gr2/3 and Gr1 hand–foot syndrome was noted in two (5.0%) and 23 (57.5%) patients, respectively. Gr1 sensory neuropathy developed in three patients. The median time to progression was 8.0 months (range: 3–25.5 months), and the median overall survival was 25.0 months with a follow-up of 5.5 to 45+ months. This VNB–HDFL regimen is a highly active yet well-tolerated first-line treatment for ABC. PMID:15770209

  13. Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT)

    PubMed Central

    De Grève, Jacques; Van Meerbeeck, Jan; Vansteenkiste, Johan F.; Decoster, Lore; Meert, Anne-Pascale; Vuylsteke, Peter; Focan, Christian; Canon, Jean-Luc; Humblet, Yves; Berchem, Guy; Colinet, Benoit; Galdermans, Danny; Bosquée, Lionel; Vermeij, Joanna; Dewaele, Alex; Geers, Caroline; Schallier, Denis; Teugels, Erik

    2016-01-01

    Introduction Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibition is the preferred first-line treatment of advanced adenocarcinoma of the lung that harbors EGFR activating tyrosine kinase domain mutations. Most data available pertain to Asian populations in which such mutations are more prevalent. We report on the long-term results of first-line treatment with erlotinib in Caucasian patients with advanced adenocarcinoma of the lung that have a somatic EGFR mutation in their tumor. Methods Multicenter academic prospective phase II study with erlotinib in patients with an activating EGFR tyrosine kinase (TK) domain somatic mutation (any exon encoding the kinase domain) in the tumor and no prior treatment for their advanced disease. Results Phenotypic preselecting of 229 patients led to a high EGFR mutation detection rate of 24% of which 46 patients were included in the phase II study. With a progression free survival (PFS) of 81% at three months the study met its primary endpoint for presumed superiority over chemotherapy. With an overall median PFS of 11 months and a median overall survival (OS) of 23 months, the results compare favorably with results obtained in randomized studies using TKI in first line in EGFR mutation positive adenocarcinoma of the lung. Conclusion The present study reinforces the use of EGFR tyrosine kinase inhibition (TKI) as a first line treatment of choice for advanced adenocarcinoma of the lung carrying an activating EGFR mutation. The mutation rate in preselected Caucasian patients is higher than previously reported. Issues relevant for clinical practice are discussed. Trial Registration ClinicalTrials.gov NCT00339586 PMID:27032107

  14. 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

  15. 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…

  16. 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

  17. The potential predictive role of nuclear NHERF1 expression in advanced gastric cancer patients treated with epirubicin/oxaliplatin/capecitabine first line chemotherapy.

    PubMed

    Mangia, Anita; Caldarola, Lucia; Dell'Endice, Stefania; Scarpi, Emanuela; Saragoni, Luca; Monti, Manlio; Santini, Daniele; Brunetti, Oronzo; Simone, Giovanni; Silvestris, Nicola

    2015-01-01

    Cellular resistance in advanced gastric cancer (GC) might be related to function of multidrug resistance (MDR) proteins. The adaptor protein NHERF1 (Na(+)/H(+) exchanger regulatory factor) is an important player in cancer progression for a number of solid malignancies, even if its role to develop drug resistance remains uncertain. Herein, we aimed to analyze the potential association between NHERF1 expression and P-gp, sorcin and HIF-1α MDR-related proteins in advanced GC patients treated with epirubicin/oxaliplatin/capecitabine (EOX) chemotherapy regimen, and its relation to response. Total number of 28 untreated patients were included into the study. Expression and subcellular localization of all proteins were assessed by immunohistochemistry on formalin-fixed paraffin embedded tumor samples. We did not found significant association between NHERF1 expression and the MDR-related proteins. A trend was observed between positive cytoplasmic NHERF1 (cNHERF1) expression and negative nuclear HIF-1α (nHIF-1α) expression (68.8% versus 31.3% respectively, P = 0.054). However, cytoplasmic P-gp (cP-gp) expression was positively correlated with both cHIF-1α and sorcin expression (P = 0.011; P = 0.002, respectively). Interestingly, nuclear NHERF1 (nNHERF1) staining was statistically associated with clinical response. In detail, 66.7% of patients with high nNHERF1 expression had a disease control rate, while 84.6% of subjects with negative nuclear expression of the protein showed progressive disease (P = 0.009). Multivariate analysis confirmed a significant correlation between nNHERF1 and clinical response (OR 0.06, P = 0.019). These results suggest that nuclear NHERF1 could be related to resistance to the EOX regimen in advanced GC patients, identifying this marker as a possible independent predictive factor. PMID:26126066

  18. The potential predictive role of nuclear NHERF1 expression in advanced gastric cancer patients treated with epirubicin/oxaliplatin/capecitabine first line chemotherapy

    PubMed Central

    Mangia, Anita; Caldarola, Lucia; Dell'Endice, Stefania; Scarpi, Emanuela; Saragoni, Luca; Monti, Manlio; Santini, Daniele; Brunetti, Oronzo; Simone, Giovanni; Silvestris, Nicola

    2015-01-01

    Cellular resistance in advanced gastric cancer (GC) might be related to function of multidrug resistance (MDR) proteins. The adaptor protein NHERF1 (Na+/H+ exchanger regulatory factor) is an important player in cancer progression for a number of solid malignancies, even if its role to develop drug resistance remains uncertain. Herein, we aimed to analyze the potential association between NHERF1 expression and P-gp, sorcin and HIF-1α MDR-related proteins in advanced GC patients treated with epirubicin/oxaliplatin/capecitabine (EOX) chemotherapy regimen, and its relation to response. Total number of 28 untreated patients were included into the study. Expression and subcellular localization of all proteins were assessed by immunohistochemistry on formalin-fixed paraffin embedded tumor samples. We did not found significant association between NHERF1 expression and the MDR-related proteins. A trend was observed between positive cytoplasmic NHERF1 (cNHERF1) expression and negative nuclear HIF-1α (nHIF-1α) expression (68.8% versus 31.3% respectively, P = 0.054). However, cytoplasmic P-gp (cP-gp) expression was positively correlated with both cHIF-1α and sorcin expression (P = 0.011; P = 0.002, respectively). Interestingly, nuclear NHERF1 (nNHERF1) staining was statistically associated with clinical response. In detail, 66.7% of patients with high nNHERF1 expression had a disease control rate, while 84.6% of subjects with negative nuclear expression of the protein showed progressive disease (P = 0.009). Multivariate analysis confirmed a significant correlation between nNHERF1 and clinical response (OR 0.06, P = 0.019). These results suggest that nuclear NHERF1 could be related to resistance to the EOX regimen in advanced GC patients, identifying this marker as a possible independent predictive factor. PMID:26126066

  19. 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

  20. Patients with Exon 19 Deletion Were Associated with Longer Progression-Free Survival Compared to Those with L858R Mutation after First-Line EGFR-TKIs for Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

    PubMed Central

    Fang, Wenfeng; Yan, Yue; Hu, Zhihuang; Hong, Shaodong; Wu, Xuan; Qin, Tao; Liang, Wenhua; Zhang, Li

    2014-01-01

    Backgrounds It has been extensively proved that the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is superior to that of cytotoxic chemotherapy in advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, the question of whether the efficacy of EGFR-TKIs differs between exon 19 deletion and exon 21 L858R mutation has not been yet statistically answered. Methods Subgroup data on hazard ratio (HR) for progression-free survival (PFS) of correlative studies were extracted and synthesized based on random-effect model. Comparison of outcomes between specific mutations was estimated through indirect and direct methods, respectively. Results A total of 13 studies of advanced NSCLC patients with either 19 or 21 exon alteration receiving first-line EGFR-TKIs were included. Based on the data from six clinical trials for indirect meta-analysis, the pooled HRTKI/chemotherapy for PFS were 0.28 (95% CI 0.20–0.38, P<0.001) in patients with 19 exon deletion and 0.47 (95% CI 0.35–0.64, P<0.001) in those with exon 21 L858R mutation. Indirect comparison revealed that the patients with exon 19 deletion had longer PFS than those with exon 21 L858R mutation (HR19 exon deletion/exon 21 L858R mutation  = 0.59, 95% CI 0.38–0.92; P = 0.019). Additionally, direct meta-analysis showed similar result (HR19 exon deletion/exon 21 L858R mutation  = 0.75, 95% CI 0.65 to 0.85; P<0.001) by incorporating another seven studies. Conclusions For advanced NSCLC patients, exon 19 deletion might be associated with longer PFS compared to L858 mutation at exon 21 after first-line EGFR-TKIs. PMID:25222496

  1. A phase II, multicenter, single-arm trial of eribulin as first-line chemotherapy for HER2-negative locally advanced or metastatic breast cancer.

    PubMed

    Takashima, Tsutomu; Tokunaga, Shinya; Tei, Seika; Nishimura, Shigehiko; Kawajiri, Hidemi; Kashiwagi, Shinichiro; Yamagata, Shigehito; Noda, Satoru; Nishimori, Takeo; Mizuyama, Yoko; Sunami, Takeshi; Tezuka, Kenji; Ikeda, Katsumi; Ogawa, Yoshinari; Onoda, Naoyoshi; Ishikawa, Tetsuro; Kudoh, Shinzoh; Takada, Minoru; Hirakawa, Kosei

    2016-01-01

    The treatment goals for metastatic breast cancer (MBC) are prolonging survival and improving the quality of life. Eribulin, a non-taxane tubulin inhibitor, demonstrated improved survival in previous studies and also showed mild toxicity when used in late-line therapy for MBC. We conducted a phase II study to investigate the efficacy of eribulin mesylate as the first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative MBC. This was a phase II, open-label, single-arm, multicenter trial conducted in Japan. Patients with HER2-negative MBC received intravenous eribulin (1.4 mg/m(2) on days 1 and 8 of each 21-day cycle). The primary efficacy outcome was overall response rate (ORR). Secondary outcomes included time to treatment failure, progression-free survival (PFS), overall survival (OS), and safety. A total of 35 patients were enrolled and received a median of 8 (range 1-21) cycles of eribulin therapy. ORR and clinical benefit rate were 54.3 and 62.9 %, respectively. Median PFS was 5.8 months and median OS was 35.9 months. Grade 3 or 4 neutropenia was observed in 63 % of patients. The majority of non-hematological adverse events were mild in severity. The present trial demonstrated that eribulin has antitumor activity comparable with other key established cytotoxic agents with acceptable safety and tolerability. Thus, eribulin as first-line chemotherapy might be beneficial for patients with HER2-negative MBC. PMID:27026861

  2. Can EGFR-TKIs be used in first line treatment for advanced non-small cell lung cancer based on selection according to clinical factors ? -- A literature-based meta-analysis

    PubMed Central

    2012-01-01

    Background In the first line treatment of non-small cell lung cancer (NSCLC), several clinical trials have shown that not all NSCLC patients can benefit from treatment with tyrosine kinase inhibitors (TKIs) than receiving chemotherapy. Some trials treated patients with TKI according to their clinical characteristics. A few studies only chose patients with an epidermal grouth factor receptor (EGFR) mutation for TKI therapy. We aimed to determine whether patients could be treated with TKIs based on clinical factors in the first-line setting. Methods We performed a meta-analysis of randomized trials involving patients with advanced NSCLC treated with chemotherapy or TKIs by different selections. Efficacy outcomes of interest were the objective response rate (ORR), progression-free survival (PFS) and the overall survival (OS) of each treatment arm. Results Four trials enrolled unselected patients, and two trials selected East Asian patients using the clinical factors of gender and smoking history. Five trials chose patients with an EGFR mutation who were randomized for treatment with TKI or chemotherapy. For unselected patients, the risk ratio (RR) of the ORR was 3.52, the hazard ratio (HR) of the PFS was 1.29 and the HR of the OS was 1.35. For the clinically selected patients, the RR of the ORR was 0.64. The HRs of the PFS and OS were 0.83 and 0.92, respectively. The ORR and PFS were better for TKIs than for chemotherapy in patients with an EGFR mutation. The ORR was 0.47, and the HRs of the PFS and OS were 0.36 and 1.00, respectively. Conclusions Advanced NSCLC patients with an EGFR mutation benefit most from TKIs. EGFR-TKI treatment is justified for patients with unknown EGFR status,and those who cannot tolerate chemotherapy owing to age, poor performance status (PS) or other medical conditions, when selected according to clinical factors in the first-line setting. PMID:23050865

  3. 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

  4. 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

  5. Carboplatin and gemcitabine in first-line treatment of elderly patients with advanced non-small cell lung cancer: data from a retrospective study.

    PubMed

    Genestreti, G; Giovannini, N; Frizziero, M; Maglie, M; Sanna, S; Cingarlini, S; Molino, A M; Piciucchi, S; Cetto, G L; Santo, A

    2011-08-01

    We retrospectively evaluated elderly patients with advanced non-small cell lung cancer (NSCLC) treated with carboplatin (AUC 4-5) and gemcitabine (1,000-1,200 mg/m²). Thirty-six patients with performance Status (pS) 0-1 and median age 73 (range 70-78 years) were considered. Histology was squamous cell carcinoma (8 patients), adenocarcinoma (22) and NSCLC not otherwise specified (6). 149 cycles of chemotherapy were administered with a median of 3 per patient (range 3-6). Grade 3 non-hematologic toxicities were dyspnea (1 patient) and fever (1). Grade 3/4 hematologic toxicities were anemia (6), neutropenia (6) and thrombocytopenia (10), with dose reduction required in 13 patients. The overall disease control rate was 44.4%. We recorded no complete response, 8 partial response, 8 stable disease and 20 progressive disease. After a medium follow-up of 11 months, median progression- free survival and median survival were 5 and 11 months, respectively. Carboplatin and gemcitabine is a safe and active regimen in elderly advanced NSCLC patients with good PS. PMID:21803702

  6. 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.

  7. 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

  8. 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

  9. Impact of Young Age on Treatment Efficacy and Safety in Advanced Colorectal Cancer: A Pooled Analysis of Patients From Nine First-Line Phase III Chemotherapy Trials

    PubMed Central

    Blanke, Charles D.; Bot, Brian M.; Thomas, David M.; Bleyer, Archie; Kohne, Claus-Henning; Seymour, Matthew T.; de Gramont, Aimery; Goldberg, Richard M.; Sargent, Daniel J.

    2011-01-01

    Purpose Colorectal cancer predominantly occurs in the elderly, but approximately 5% of patients are 50 years old or younger. We sought to determine whether young age is prognostic, or whether it influences efficacy/toxicity of chemotherapy, in patients with advanced disease. Methods We analyzed individual data on 6,284 patients from nine phase III trials of advanced colorectal cancer (aCRC) that used fluorouracil-based single-agent and combination chemotherapy. End points included progression-free survival (PFS), overall survival (OS), response rate (RR), and grade 3 or worse adverse events. Stratified Cox and adjusted logistic-regression models were used to test for age effects and age-treatment interactions. Results A total of 793 patients (13%) were younger than 50 years old; 188 of these patients (3% of total patients) were younger than 40 years old. Grade 3 or worse nausea (10% v 7%; P = .01) was more common, and severe diarrhea (11% v 14%; P = .001) and neutropenia (23% v 26%; P < .001) were less common in young (younger than 50 years) than in older (older than 50 years) patients. Age was prognostic for PFS, with poorer outcomes occurring in those younger than 50 years (median, 6.0 v 7.5 months; hazard ratio, 1.10; P = .02), but it did not affect RR or OS. In the subset of monotherapy versus combination chemotherapy trials, the relative benefits of multiagent chemotherapy were similar for young and older patients. Results were comparable when utilizing an age cut point of 40 years. Conclusion Young age is modestly associated with poorer PFS but not OS or RR in treated patients with aCRC, and young patients have more nausea but less diarrhea and neutropenia with chemotherapy in general. Young versus older patients derive the same benefits from combination chemotherapy. Absent results of a clinical trial, standard combination chemotherapy approaches are appropriate for young patients with aCRC. PMID:21646604

  10. 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

  11. EGFR biomarkers predict benefit from vandetanib in combination with docetaxel in a randomized phase III study of second-line treatment of patients with advanced non-small cell lung cancer

    PubMed Central

    Heymach, J. V.; Lockwood, S. J.; Herbst, R. S.; Johnson, B. E.; Ryan, A. J.

    2014-01-01

    Background ZODIAC was a randomized phase III study of second-line treatment in patients with advanced non-small cell lung cancer (NSCLC) that evaluated the addition of vandetanib to docetaxel. The study showed a statistically significant improvement in progression-free survival and objective response rate, but not in overall survival for unselected patients. This study evaluated epidermal growth factor receptor (EGFR) gene mutation, copy number gain, and protein expression, and KRAS gene mutation, in pretreatment tumor samples as potential biomarkers predicting benefit from vandetanib as second-line treatment of NSCLC. Patients and methods After progression following first-line chemotherapy, 1391 patients with locally advanced or metastatic (stage IIIB/IV) NSCLC were randomized 1 : 1 to receive vandetanib (100 mg/day) plus docetaxel (75 mg/m2 every 21 days) or placebo plus docetaxel in the ZODIAC study. Archival tumor samples (n = 570) were collected from consenting patients (n = 958) for predefined, prospective biomarker analyses. Results Of evaluable samples, 14% were EGFR mutation positive, 35% were EGFR FISH positive, 88% were EGFR protein expression positive, and 13% were KRAS mutation positive. Compared with the overall study population, in which progression-free survival (PFS) [hazard ratio (HR) = 0.79] but not OS (HR = 0.91) were significantly improved with vandetanib, there was greater relative clinical benefit for patients with EGFR mutation-positive tumors [PFS HR 0.51, confidence interval (CI) 0.25–1.06 and OS HR 0.46, CI 0.14–1.57] and EGFR FISH-positive tumors (PFS HR 0.61, CI 0.39–0.94 and OS HR 0.48, CI 0.28–0.84). Similarly, patients with EGFR mutation or FISH-positive tumor samples who received vandetanib had an increased chance of objective tumor response (odds ratios 3.34, CI 0.8–13.89, and 3.90, CI 1.02–14.82, respectively). There did not appear to be benefit for vandetanib in patients with KRAS mutation-positive tumors. Conclusions

  12. Metabolic profiling for the identification of Huntington biomarkers by on-line solid-phase extraction capillary electrophoresis mass spectrometry combined with advanced data analysis tools.

    PubMed

    Pont, Laura; Benavente, Fernando; Jaumot, Joaquim; Tauler, Romà; Alberch, Jordi; Ginés, Silvia; Barbosa, José; Sanz-Nebot, Victoria

    2016-03-01

    In this work, an untargeted metabolomic approach based on sensitive analysis by on-line solid-phase extraction capillary electrophoresis mass spectrometry (SPE-CE-MS) in combination with multivariate data analysis is proposed as an efficient method for the identification of biomarkers of Huntington's disease (HD) progression in plasma. For this purpose, plasma samples from wild-type (wt) and HD (R6/1) mice of different ages (8, 12, and 30 weeks), were analyzed by C18 -SPE-CE-MS in order to obtain the characteristic electrophoretic profiles of low molecular mass compounds. Then, multivariate curve resolution alternating least squares (MCR-ALS) was applied to the multiple full scan MS datasets. This strategy permitted the resolution of a large number of metabolites being characterized by their electrophoretic peaks and their corresponding mass spectra. A total number of 29 compounds were relevant to discriminate between wt and HD plasma samples, as well as to follow-up the HD progression. The intracellular signaling was found to be the most affected metabolic pathway in HD mice after 12 weeks of birth, when mice already showed motor coordination deficiencies and cognitive decline. This fact agreed with the atrophy and dysfunction of specific neurons, loss of several types of receptors, and changed expression of neurotransmitters. PMID:26685060

  13. Cell Lines

    PubMed Central

    Cherbas, Lucy; Gong, Lei

    2014-01-01

    We review the properties and uses of cell lines in Drosophila research, emphasizing the variety of lines, the large body of genomic and transcriptional data available for many of the lines, and the variety of ways the lines have been used to provide tools for and insights into the developmental, molecular, and cell biology of Drosophila and mammals. PMID:24434506

  14. Cost-effectiveness of first-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy

    PubMed Central

    Khan, Iftekhar; Morris, Stephen; Hackshaw, Allan; Lee, Siow-Ming

    2015-01-01

    Objective To assess the cost-effectiveness of erlotinib versus supportive care (placebo) overall and within a predefined rash subgroup in elderly patients with advanced non-small-cell lung cancer who are unfit for chemotherapy and receive only active supportive care due to their poor performance status or presence of comorbidities. Setting Between 2005 and 2009, a total of 670 patients with non-small cell lung cancer (NSCLC) were randomised across 78 hospital sites (centres) in the UK. Participants 670 patients with pathologically confirmed stage IIIb-IV NSCLC, unfit for chemotherapy, predominantly poor performance status (>2 on Eastern Cooperative Oncology Group, ECOG) and estimated life expectancy of at least 8 weeks. Patients were followed until disease progression or death, including a subgroup of patients who developed first cycle rash. Interventions Patients were randomised (1:1) to receive best supportive care plus oral placebo or erlotinib (150 mg/day) until disease progression, toxicity or death. Primary outcome Overall survival (OS). Secondary outcomes Progression-free survival (PFS), tumour response and quality adjusted life years (QALY), including within prespecified subgroups. Results The mean incremental cost per QALY in all patients was £202 571/QALY. The probability of cost-effectiveness of erlotinib in all patients was <10% at thresholds up to £100 000. However, within the rash subgroup, the incremental cost/QALY was £56 770/QALY with a probability of cost-effectiveness of about 80% for cost-effectiveness thresholds between £50 000 to £60 000. Conclusions Erlotinib has about 80% chance of being cost-effective at thresholds between £50 000–£60 000 in a subset of elderly poor performance patients with NSCLC unfit for chemotherapy who develop first cycle (28 days) rash. Erlotinib is potentially cost-effective for this population, for which few treatment options apart from best supportive care are available. Trial

  15. Economic evaluation of nivolumab for the treatment of second-line advanced squamous NSCLC in Canada: a comparison of modeling approaches to estimate and extrapolate survival outcomes.

    PubMed

    Goeree, Ron; Villeneuve, Julie; Goeree, Jeff; Penrod, John R; Orsini, Lucinda; Tahami Monfared, Amir Abbas

    2016-06-01

    Background Lung cancer is the most common type of cancer in the world and is associated with significant mortality. Nivolumab demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with advanced squamous non-small cell lung cancer (NSCLC) who were previously treated. The cost-effectiveness of nivolumab has not been assessed in Canada. A contentious component of projecting long-term cost and outcomes in cancer relates to the modeling approach adopted, with the two most common approaches being partitioned survival (PS) and Markov models. The objectives of this analysis were to estimate the cost-utility of nivolumab and to compare the results using these alternative modeling approaches. Methods Both PS and Markov models were developed using docetaxel and erlotinib as comparators. A three-health state model was used consisting of progression-free, progressed disease, and death. Disease progression and time to progression were estimated by identifying best-fitting survival curves from the clinical trial data for PFS and OS. Expected costs and health outcomes were calculated by combining health-state occupancy with medical resource use and quality-of-life assigned to each of the three health states. The health outcomes included in the model were survival and quality-adjusted-life-years (QALYs). Results Nivolumab was found to have the highest expected per-patient cost, but also improved per-patient life years (LYs) and QALYs. Nivolumab cost an additional $151,560 and $140,601 per QALY gained compared to docetaxel and erlotinib, respectively, using a PS model approach. The cost-utility estimates using a Markov model were very similar ($152,229 and $141,838, respectively, per QALY gained). Conclusions Nivolumab was found to involve a trade-off between improved patient survival and QALYs, and increased cost. It was found that the use of a PS or Markov model produced very similar estimates of expected cost

  16. Phase II trial of carboplatin, S-1, and gefitinib as first-line triplet chemotherapy for advanced non-small cell lung cancer patients with activating epidermal growth factor receptor mutations.

    PubMed

    Tamiya, Akihiro; Tamiya, Motohiro; Shiroyama, Takayuki; Saijo, Nobuhiko; Nakatani, Takeshi; Minomo, Shojiro; Tsuji, Taisuke; Takeuchi, Naoko; Omachi, Naoki; Kurata, Kanako; Suzuki, Hidekazu; Okamoto, Norio; Okishio, Kyoichi; Hirashima, Tomonori; Atagi, Shinji

    2015-03-01

    Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is an effective treatment for advanced non-small cell lung cancer (NSCLC) in patients with activating EGFR mutations. However, there have been little evidence-based studies of gefitinib in combination with platinum-doublet therapy in these patients. We performed a phase II trial to determine the efficacy and safety of triplet chemotherapy with gefitinib, carboplatin, and S-1 as a first-line treatment. This was a multicentre, single-arm, phase II trial of carboplatin, S-1, and gefitinib in advanced NSCLC patients with activating EGFR mutations. Patients received four courses of these drugs in 3-4 week cycles. In each cycle, carboplatin (area under curve = 5) was administered on day 1, S-1 (80 mg/m(2)) on days 1-14, and gefitinib (250 mg) every day. Subsequently, the same regimen without carboplatin was administered until disease progression or unacceptable toxicity occurred. The 1-year progression-free survival (PFS) was the primary endpoint, while response rate (RR), PFS, overall survival (OS), and safety were secondary endpoints. Thirty-five patients were enrolled into this study. The 1-year PFS was 74.3% and the overall RR was 85.7%. The median PFS for all patients was 17.6 months (95% confidence interval 15.5-∞), but the median OS was not reached, because 28 patients were still alive after a median follow-up time of 21.4 months. Haematological adverse events (grade 3 or higher) included neutropaenia (17.1%), thrombocytopenia (14.3%), and anaemia (5.7%), while non-haematological adverse events (grade 3 or higher) included elevated aminotransferase (20.0%), diarrhoea (14.3%), and febrile neutropaenia (2.9%). No interstitial lung disease or treatment-related deaths occurred. Combination chemotherapy with carboplatin, S-1, and gefitinib is efficacious and well tolerated as a first-line treatment in advanced NSCLC patients with activating EGFR mutations. PMID:25616723

  17. 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

  18. 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…

  19. 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. PMID:23764674

  20. 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

  1. Real-world hospital costs for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer in Chinese patients: a retrospective cohort study

    PubMed Central

    Chen, Jianhua; Wu, Shengqi; Hu, Chenping; Yang, Yicheng; Rajan, Narayan; Chen, Yun; Yang, Canjuan; Li, Jianfeng; Chen, Wendong

    2016-01-01

    Objective The objective of this study was to compare hospital costs per treatment cycle (HCTC) for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer (AdvNS-NSCLC) in Chinese patients. Methods Patients receiving platinum-based doublets in the first-line setting for AdvNS-NSCLC from 2010 to 2012 in two Chinese tertiary hospitals were identified to create the retrospective study cohort. Propensity score methods were used to create matched treatment groups for head-to-head comparisons on HCTC between pemetrexed–platinum and other platinum-based doublets. Multiple linear regression analyses were performed to rank studied platinum-based doublets for their associations with the log10 scale of HCTC for nonchemotherapy drugs and nondrug care. Results Propensity score methods created matched treatment groups for pemetrexed–platinum versus docetaxel–platinum (61 pairs), paclitaxel–platinum (39 pairs), gemcitabine–platinum (93 pairs), and vinorelbine–platinum (73 pairs), respectively. Even though the log10 scale of HCTC for nonchemotherapy drugs and nondrug care associated with pemetrexed–platinum was ranked lowest in all patients (coefficient −0.174, P=0.015), which included patients experiencing any hematological adverse events (coefficient −0.199, P=0.013), neutropenia (coefficient −0.426, P=0.021), or leukopenia (coefficient −0.406, P=0.001), pemetrexed–platinum had the highest total HCTC (median difference from RMB 1,692 to RMB 7,400, P<0.001) among platinum-based doublets because of its higher drug acquisition costs (median difference from RMB 4,636 to RMB 7,332, P<0.001). Conclusion Among Chinese patients receiving platinum-based doublets in the first-line setting for AdvNS-NSCLC, the higher acquisition costs for nonplatinum cytotoxic drugs associated with pemetrexed–platinum could be partially offset by its significantly lower hospital

  2. 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

  3. 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. PMID:16751589

  4. Intensified dose of cyclophosphamide with G-CSF support versus standard dose combined with platinum in first-line treatment of advanced ovarian cancer a randomised study from the GINECO group

    PubMed Central

    Ray-Coquard, I; Paraiso, D; Guastalla, J-P; Leduc, B; Guichard, F; Martin, C; Chauvenet, L; Haddad-Guichard, Z; Lepillé, D; Orfeuvre, H; Gautier, H; Castera, D; Pujade-Lauraine, É

    2007-01-01

    ICON3 trial results have suggested that CAP and carboplatin–taxol regimens as first-line treatment of advanced ovarian cancer (AOC) yield similar survival. We explored the impact of increased dose of cyclophosphamide in a modified CAP regimen on the disease-free survival (DFS) and overall survival (OS) of AOC patients. From February 1994 to June 1997, 164 patients were randomised to receive six cycles every 3 weeks of either standard CEP (S) combining cyclophosphamide (C), 500 mg m−2, epirubicin (E) 50 mg m−2, and cisplatin (P) 75 mg m−2 or intensive CEP (I) with E and P at the same doses, but with (C) 1800 mg m−2 and filgrastim 5 μg kg−1 per day × 10 days. Response was evaluated at second-look surgery. Patient characteristics were well balanced. Except for grade 3–4 neutropaenia (S: 54%, I: 38% of cycles), Arm1 presented a significantly more important toxicity: infection requiring antibiotics, grade 3–4 thrombocytopaenia, anaemia, nausea-vomiting, diarrhoea, mucositis. Median follow-up was 84 months. DFS (15.9 vs 14.8 months) and OS (33 vs 30 months) were not significantly different between S and I (P>0.05). Increasing cyclophosphamide dose by more than 3 times with filgrastim support in the modified CAP regimen CEP induces more toxicity but not better efficacy in AOC. PMID:17923867

  5. High-mobility group box 1 protein is implicated in advanced glycation end products–induced vascular endothelial growth factor A production in the rat retinal ganglion cell line RGC-5

    PubMed Central

    Lee, Jong-Jer; Hsiao, Chang-Chun; Yang, I-Hui; Chou, Ming-Huei; Wu, Chia-Lin; Wei, Yin-Chu; Chen, Chih-Hsin

    2012-01-01

    Purpose High-mobility group box 1 protein (HMGB1) has been reported to be a potent proangiogenic factor induced by inflammatory stress. In this study, we explore the role of HMGB1 in advanced glycation end products (AGEs)–induced vascular endothelial growth factor A (VEGF-A) production in rat retinal ganglion cell line 5 (RGC-5) cells. Methods The VEGF-A protein and mRNA levels in conditioned medium of RGC-5 cells incubated with AGE-modified BSA (AGE-BSA) were examined with real-time PCR and enzyme-linked immunosorbent assay (ELISA), and BSA-treated cells were used as controls. The expression of HMGB1, c-Jun N-terminal kinase (JNK), extracellular-signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase (p38 MAPK) was assessed with immunofluorescence and western blot analysis. Reactive oxidative species (ROS) were detected with flow cytometry measurements of peroxide-dependent oxidation of 2′-7′-dichlorofluorescein-diacetate (DCFH-DA). N-Acetyl-L-cysteine (NAC), glycyrrhizin (GZ), and SP600125 were used to block ROS, HMGB1, and JNK, respectively. Results Compared with the BSA controls, the RGC-5 cells incubated with AGE-BSA showed a dose- and time-dependent increase in VEGF-A mRNA and VEGF-A protein secretion in the supernatant, with the highest levels achieved at 24 h. AGE-BSA stimulated a significant release of HMGB1 in the supernatant and a significant increase of intracellular ROS production at 3 h. NAC blocked HMGB1 production in a dose-dependent manner. Blocking with GZ, NAC, and JNK significantly suppressed AGE-induced VEGF-A production. Conclusions HMGB1 is implicated in the production of VEGF-A in retinal ganglion cell line-5 (RGC-5). Blocking HMGB1, ROS, or the JNK pathway may attenuate VEGF-A production, suggesting HMGB1 and related signaling molecules play a role in diabetic retinopathy. PMID:22511847

  6. Capecitabine and bevacizumab with or without vinorelbine in first-line treatment of HER2/neu-negative metastatic or locally advanced breast cancer: final efficacy and safety data of the randomised, open-label superiority phase 3 CARIN trial.

    PubMed

    Welt, A; Marschner, N; Lerchenmueller, C; Decker, T; Steffens, C-C; Koehler, A; Depenbusch, R; Busies, S; Hegewisch-Becker, S

    2016-02-01

    The study was designed to evaluate efficacy and superiority of capecitabine/bevacizumab + vinorelbine (CAP/BEV/VIN) compared to CAP/BEV alone. Main purpose was to introduce a taxane-/anthracycline-free first-line treatment in advanced breast cancer (ABC), in order to avoid long-term toxicities. In this open-label, superiority, phase 3 trial, patients with HER2-negative ABC were randomized 1:1 to receive either oral CAP at 1000 mg/m(2) [twice daily, days 1-14, q3w] plus intravenous BEV at 15 mg/kg [day 1, q3w] (arm A) or in addition to this protocol intravenous VIN at 25 mg/m(2) [days 1 + 8, q3w] (arm B) until disease progression, unacceptable toxicity or withdrawal of consent. Between 26 February 2009 and 26 October 2012, we randomised 600 patients (arm A N = 300; arm B N = 300) from 57 German outpatient-centres and 2 university hospitals. Median progression-free survival (PFS) (primary endpoint) was not improved with VIN (CAP/BEV, 8.8 months; CAP/BEV/VIN, 9.6 months; HR 0.84 [95 % CI 0.70-1.01], P = 0.058). Median overall survival (OS) (secondary endpoint) was 25.1 and 27.2 months for CAP/BEV and CAP/BEV/VIN, respectively, average HR 0.85 [95 % CI 0.70-1.03], P = 0.104). The 1- and 2-year OS rates appeared to be similar (78.0 and 77.0 %; 53.0 and 54.0 %). Toxicity profiles were generally mild and manageable. Adverse events occurred more frequently in arm B. Regarding the balance between clinical efficacy (PFS, OS) and toxicity, the CAP/BEV combination provides a favourable treatment option in first-line ABC avoiding taxane- and/or anthracycline-induced long-term toxicity. Superiority of CAP/BEV/VIN was not met, and side effects were even enhanced. Nevertheless, no safety issues occurred. PMID:26927446

  7. 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

  8. 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

  9. Line-by-line pulse shaping control for optical arbitrary waveform generation.

    PubMed

    Jiang, Z; Leaird, D E; Weiner, A M

    2005-12-12

    We demonstrate a fundamental operation for generating complex waveforms in the optical domain - line-by-line pulse shaping control for optical arbitrary waveform generation (O-AWG). Independent manipulation of the spectral amplitude and phase of individual lines from a mode-locked frequency comb, or spectral line-by-line pulse shaping, leads to synthesis of user-specified ultrafast optical waveforms with unprecedented control. Coupled with recent advances in frequency stabilized mode-locked lasers, line-by-line pulse shaping control should have significant impact to fields drawing upon developments in the field of ultrafast science. PMID:19503258

  10. 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)

  11. Power Line Technician's Training. Instructional Units.

    ERIC Educational Resources Information Center

    Smith, Earle L.

    These instructional units, developed in Oklahoma, are designed for training power line technicians for rural electric cooperatives. Planned to help current employees advance in knowledge and skill, the instructional materials are divided into seven areas of training: Laborer; Groundworker or Equipment Operator; Power Line Technician, Step 1; Power…

  12. Advance directives

    PubMed Central

    O’Sullivan, Rory; Mailo, Kevin; Angeles, Ricardo; Agarwal, Gina

    2015-01-01

    Abstract Objective To establish the prevalence of patients with advance directives in a family practice, and to describe patients’ perspectives on a family doctor’s role in initiating discussions about advance directives. Design A self-administered patient questionnaire. Setting A busy urban family medicine teaching clinic in Hamilton, Ont. Participants A convenience sample of adult patients attending the clinic over the course of a typical business week. Main outcome measures The prevalence of advance directives in the patient population was determined, and the patients’ expectations regarding the role of their family doctors were elucidated. Results The survey population consisted of 800 participants (a response rate of 72.5%) well distributed across age groups; 19.7% had written advance directives and 43.8% had previously discussed the topic of advance directives, but only 4.3% of these discussions had occurred with family doctors. In 5.7% of cases, a family physician had raised the issue; 72.3% of respondents believed patients should initiate the discussion. Patients who considered advance directives extremely important were significantly more likely to want their family doctors to start the conversation (odds ratio 3.98; P < .05). Conclusion Advance directives were not routinely addressed in the family practice. Most patients preferred to initiate the discussion of advance directives. However, patients who considered the subject extremely important wanted their family doctors to initiate the discussion. PMID:25873704

  13. Outcome of advanced chronic lymphocytic leukemia following different first-line and relapse therapies: a meta-analysis of five prospective trials by the German CLL Study Group (GCLLSG)

    PubMed Central

    Cramer, Paula; Isfort, Susanne; Bahlo, Jasmin; Stilgenbauer, Stephan; Döhner, Hartmut; Bergmann, Manuela; Stauch, Martina; Kneba, Michael; Lange, Elisabeth; Langerbeins, Petra; Pflug, Natali; Kovacs, Gabor; Goede, Valentin; Fink, Anna-Maria; Elter, Thomas; Fischer, Kirsten; Wendtner, Clemens-Martin; Hallek, Michael; Eichhorst, Barbara

    2015-01-01

    To evaluate the effect of first-line and subsequent therapies, the outcome of 1,558 patients with chronic lymphocytic leukemia from five prospective phase II/III trials conducted between 1999 and 2010 was analyzed. The 3-year overall survival rate was higher after first-line treatment with chemoimmunotherapies such as fludarabine/cyclophosphamide/rituximab (87.9%) or bendamustine/rituximab (90.7%) compared to chemotherapies without an antibody (fludarabine/cyclophosphamide: 84.6%; fludarabine: 77.5%; chlorambucil: 77.4%). Furthermore, the median overall survival was longer in patients receiving at least one antibody-containing regimen in any treatment line (94.4 months) compared to the survival in patients who never received an antibody (84.3 months, P<0.0001). Univariate Cox regression analysis demonstrated that patients who did receive antibody treatment had a 1.42-fold higher risk of death (hazard ratio, 1.42; 95% confidence interval: 1.185–1.694). Therapies administered at relapse were very heterogeneous. Only 55 of 368 patients (14.9%) who started second-line treatment >24 months after first-line therapy repeated the first-line regimen. Among 315 patients requiring treatment ≤24 months after first-line therapy, cyclophosphamide/doxorubicin/vincristine/prednisone with or without rituximab as well as alemtuzumab were the most commonly used therapies. In these early relapsing patients, the median overall survival was shorter following therapies containing an anthracycline and/or three or more cytotoxic agents (e.g. cyclophosphamide/doxorubicin/vincristine/prednisone or fludarabine/cyclophosphamide/mitoxantrone, 30.0 months) compared to single agent chemotherapy (e.g. fludarabine; 39.6 months) and standard chemoimmunotherapy (e.g. fludarabine/cyclophosphamide/rituximab: 61.6 months). In conclusion, the analysis confirms the superior efficacy of chemoimmunotherapies in patients with chronic lymphocytic leukemia. Moreover, the use of aggressive chemo

  14. 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

  15. 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 ...

  16. 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

  17. Advanced Vapor-Supply Manifold

    NASA Technical Reports Server (NTRS)

    Clark, I. O.; Debnam, William J., Jr.; Fripp, Archibald L., Jr.; Crouch, R. K.

    1986-01-01

    Advanced vapor-supply manifold solves problem of manifold purging. Design virtually eliminates dead gas volumes in manifold system. System incorporates special valve into manifold in way that leaks and contamination problems of previous systems, which use tees and three-port valves, are minimized or eliminated in both main manifold line and in supply line. Of considerable use in gas manifold systems where even small amounts of gaseous impurities constitute problem or where more than one gaseous material used in single system.

  18. 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.

  19. 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

  20. Impact of palbociclib plus letrozole on pain severity and pain interference with daily activities in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer as first-line treatment.

    PubMed

    Bell, T; Crown, J P; Lang, I; Bhattacharyya, H; Zanotti, G; Randolph, S; Kim, S; Huang, X; Huang Bartlett, C; Finn, R S; Slamon, D

    2016-05-01

    Background Palbociclib is a recently approved drug for use in combination with letrozole as initial endocrine-based therapy for the treatment of postmenopausal women with advanced estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer. This report assesses the impact of palbociclib in combination with letrozole versus letrozole alone on patient-reported outcomes of pain. Methods Palbociclib was evaluated in an open-label, randomized, phase II study (PALOMA-1/TRIO-18) among postmenopausal women with advanced ER+/HER2- breast cancer who had not received prior systemic treatment for their advanced disease. Patients received continuous oral letrozole 2.5 mg daily alone or the same letrozole dose and schedule plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over repeated 28-day cycles. The primary study endpoint was investigator-assessed progression-free survival in the intent-to-treat population, and these results have recently been published (Finn et al., Lancet Oncol 2015;16:25-35). One of the key secondary endpoints was the evaluation of pain, as measured using the Brief Pain Inventory (BPI) patient-reported outcome tool. The BPI was administered at baseline and on day 1 of every cycle thereafter until disease progression and/or treatment discontinuation. Clinical trial registration This study is registered with ClinicalTrials.gov (NCT00721409). Results There were no statistically significant differences in Pain Severity or Pain Interference scores of the BPI between the two treatment groups for the overall population or among those with any bone disease at baseline. A limitation of the study is that results were not adjusted for the concomitant use of opioids or other medications used to control pain. Conclusions The addition of palbociclib to letrozole was associated with increased efficacy without negatively impacting pain severity or pain interference with daily activities

  1. 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.

  2. 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…

  3. 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…

  4. Technical advances power neuroscience

    SciTech Connect

    Barinaga, M.

    1991-01-01

    New techniques are helping researchers study the development of nerve cells in cell cultures and in vivo. These new methods are offering insights into the brain that were not available even a couple of years ago. Among the new advances discussed are imaging technology for evaluating the thinking human brain. One area in which researchers have made recent progress is the quest for ways to create immortal cell lines from specific types of nerve cells. Other projects using genetically engineered retroviruses and tumor-inducing genes, as well as gene regulation are discussed. Recent advances in neuroscience techniques apply not only to neurons, but also to whole brains as well. One example is a high-resulution electroencephalogram (EEG). Although the EEG cannot pin down the actual sites of activity as precisely as static brain imaging methods, it complements them with real-time recording that can keep up with the very rapid pace of brain activity.

  5. A retrospective analysis of safety and efficacy of weekly nab-paclitaxel as second-line chemotherapy in elderly patients with advanced squamous non-small-cell lung carcinoma

    PubMed Central

    Jin, Feng; Zhu, Hui; Shi, Fang; Kong, Li; Yu, Jinming

    2016-01-01

    Purpose The aim of this retrospective study was to investigate the anticancer effect and toxicity of weekly administered nab-paclitaxel as a second-line chemotherapy in elderly patients with relapsed squamous non-small-cell lung cancer (NSCLC). Patients and methods We retrospectively reviewed the treatment of 42 elderly patients with relapsed squamous NSCLC, who received nab-paclitaxel monotherapy as a second-line treatment from January 2010 to March 2014. A dose of 100 mg/m2 nab-paclitaxel was administered weekly on days 1, 8, and 15, followed by 1 week of rest. The protocol was maintained for at least two cycles. Results The overall response rate (ORR) and the disease control rate (DCR) were 21.43% (9/42) and 47.62% (20/42), respectively. The median progression-free survival (PFS) and overall survival (OS) were 6.6 and 10.9 months, respectively. In the subgroup analysis, there was no significant difference in ORR, DCR, PFS, and OS, accounting for the first-line therapy factors (taxane agent, radiotherapy, or surgery). There was a statistically significant difference in DCR for stages III and IV (62.96% vs 20%, P=0.008), but there was no such difference in either PFS or OS. The ORR of 29 patients receiving more than three cycles of treatment was higher than that of those receiving less than three cycles of treatment (31.03% vs 0%, P=0.038), and there was a significant difference in PFS (7.6 vs 4.9 months, P=0.004) and OS (11.7 vs 8.9 months, P=0.002). No hypersensitivity reactions or treatment-related grade 4 adverse events were reported. Conclusion Nab-paclitaxel monotherapy administered weekly at a dose of 100 mg/m2 is shown to be an effective and safe regimen for elderly patients with relapsed squamous NSCLC, especially for patients with stage III disease or good performance status. PMID:26929611

  6. A genotype-directed phase I–IV dose-finding study of irinotecan in combination with fluorouracil/leucovorin as first-line treatment in advanced colorectal cancer

    PubMed Central

    Marcuello, E; Páez, D; Paré, L; Salazar, J; Sebio, A; del Rio, E; Baiget, M

    2011-01-01

    Background: Infusional fluorouracil/leucovorin (FU/LV) plus irinotecan (FOLFIRI) is one of the standard first-line options for patients with metastatic colorectal cancer (mCRC). Irinotecan is converted into 7-ethyl-10-hydroxycamptothecin (SN-38) by a carboxylsterase and metabolised through uridine diphosphate glucuronosyl transferase (UGT1A1). The UGT1A1*28 allele has been associated with the risk of developing severe toxicities. The present trial was designed to define the maximum tolerated dose according to UGT1A1 genotype. This report focuses on the results of tolerance to different escalated doses of FOLFIRI first-line of chemotherapy. Patients and methods: Patients undergoing first-line treatment for mCRC and eligible for treatment with FOLFIRI were classified according to UGT1A1 genotype. A total of 94 patients were eligible for dose escalation of irinotecan. The starting dose of biweekly irinotecan was 180 mg m−2 for the *1/*1, 110 mg m−2 for the *1/*28 and 90 mg m−2 for the *28/*28 genotypes. Results: The dose of irinotecan was escalated to 450 mg m−2 in patients with the *1/*1 genotype, to 390 mg m−2 in those with the *1/*28 genotype and to 150 mg m−2 in those with the *28/*28 genotype. Neutropenia and diarrhoea were the most common grade 3 or 4 toxicities. Conclusions: Our results demonstrated that the recommended dose of 180 mg m−2 for irinotecan in FOLFIRI is considerably lower than the dose that can be tolerated for patients with the UGT1A1 *1/*1 and *1/*28 genotypes. The maximum tolerable dose (MTD) in patients with a high-risk UGT1A1 *28/*28 genotype is 30% lower than the standard dose of 180 mg m−2. PMID:21654688

  7. 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

  8. 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…

  9. 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…

  10. 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.

  11. 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.

  12. 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

  13. Electric Field Lines

    NASA Astrophysics Data System (ADS)

    Arribas, E.; Gallardo, C.; Molina, M.; Sanjosé, V.

    We present the computer program called LINES which is able to calculate and visualize the electric field lines due to seven different discrete configurations of electric point charges. Also we show two examples of the graphic screens generated by LINES.

  14. Analysis of potential predictive markers of cetuximab benefit in BMS099, a phase III study of cetuximab and first-line taxane/carboplatin in advanced non-small-cell lung cancer.

    PubMed

    Khambata-Ford, Shirin; Harbison, Christopher T; Hart, Lowell L; Awad, Melissa; Xu, Li-An; Horak, Christine E; Dakhil, Shaker; Hermann, Robert C; Lynch, Thomas J; Weber, Martin R

    2010-02-20

    PURPOSE The anti-epidermal growth factor receptor (EGFR) antibody cetuximab is efficacious in multiple tumor types. Patient selection with markers predictive of benefit may enhance its therapeutic index. This retrospective, correlative analysis of the phase III trial BMS099 of cetuximab in advanced non-small-cell lung cancer (NSCLC) was conducted to identify molecular markers for the selection of patients most likely to benefit from cetuximab. METHODS In BMS099, 676 chemotherapy-naïve patients with stage IIIB (pleural effusion) or stage IV NSCLC of any histology or EGFR expression status were randomly assigned to taxane/carboplatin (T/C) with or without cetuximab. Biomarkers analyzed included K-Ras and EGFR mutations by direct sequencing, EGFR protein expression by immunohistochemistry (IHC), and EGFR gene copy number by fluorescent in situ hybridization (FISH). Relationships between biomarker status and progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) were assessed by log-rank tests per treatment arm for treatment-specific effects and across the total evaluable population. Results Tumor samples were available from 225 randomly assigned patients. K-Ras mutations were found in 17% of evaluable patients (35 of 202 patients), EGFR mutations were found in 10% (17 of 166 patients), EGFR positivity by IHC was found in 89% (131 of 148 patients), and FISH positivity was found in 52% (54 of 104 patients). No significant associations were found between biomarker status and PFS, OS, and ORR in the treatment-specific analyses. CONCLUSION In contrast with colorectal cancer, and within the limitations of the data set, efficacy parameters did not appear to correlate with K-Ras mutation status or with any of the EGFR-related biomarkers evaluated. Additional exploratory analyses are essential to identify predictive markers and to optimize patient selection for cetuximab therapy in NSCLC. PMID:20100958

  15. 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).

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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…

  1. The Language of Lines.

    ERIC Educational Resources Information Center

    Breig-Allen, Cheryl; Hill, Janet; Geismar-Ryan, Lori; Cadwell, Louise Boyd

    1998-01-01

    Describes a project about lines in the environment used with 2- and 3-year olds and based on the Reggio Emilia approach. Activities included making tracks with riding toys, drawing lines on papers, seeing cloud lines, and making lines with yarn and Cuisenaire rods. Shows how young children's observations and ongoing discoveries can uncover their…

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Reconnection of vorticity lines and magnetic lines

    NASA Technical Reports Server (NTRS)

    Greene, John M.

    1993-01-01

    Magnetic field and fluid vorticity share many features. First, as divergence-free vector fields they are conveniently visualized in terms of their field lines, curves that are everywhere tangent to the field. The lines indicate direction and their density indicates field strength. The question arises of the extent to which the evolution of the fields can be treated in terms of the evolution of their field lines. Newcomb (1958) derived the general conditions on the evolution of vector fields that permit the identification of field lines from one instant to the next. The equations of evolution of the vorticity field and the magnetic field fall within Newcomb's analysis. The dynamics of the flows differ between these two systems, so that geometrically similar phenomena happen in different ways in the two systems. In this paper the geometrical similarities are emphasized. Reconnection will be defined here as evolution in which it is not possible to preserve the global identification of some field lines. There is a close relation between reconnection and the topology of the vector field lines. Nontrivial topology occurs where the field has null points or there are field lines that are closed loops.

  8. 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.

  9. 11 CFR 100.83 - Brokerage loans and lines of credit to candidates.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., credit card, home equity line of credit, or other line of credit available to the candidate, including an... making such loan makes loans derived from an advance on a candidate's brokerage account, credit card... card, home equity line of credit, or other line of credit available to the candidate, for which he...

  10. 11 CFR 100.83 - Brokerage loans and lines of credit to candidates.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., credit card, home equity line of credit, or other line of credit available to the candidate, including an... making such loan makes loans derived from an advance on a candidate's brokerage account, credit card... card, home equity line of credit, or other line of credit available to the candidate, for which he...

  11. 11 CFR 100.83 - Brokerage loans and lines of credit to candidates.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., credit card, home equity line of credit, or other line of credit available to the candidate, including an... making such loan makes loans derived from an advance on a candidate's brokerage account, credit card... card, home equity line of credit, or other line of credit available to the candidate, for which he...

  12. Peripheral arterial line - infants

    MedlinePlus

    PAL - infants; Art line - infants ... an "art line." This article addresses PALs in babies. Why is a PAL used? Doctors and nurses use a PAL to watch your baby's blood pressure. A PAL can also be use ...

  13. 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.

  14. 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.

  15. Future advances.

    PubMed

    Celesia, Gastone G; Hickok, Gregory

    2015-01-01

    Future advances in the auditory systems are difficult to predict, and only educated guesses are possible. It is expected that innovative technologies in the field of neuroscience will be applied to the auditory system. Optogenetics, Brainbow, and CLARITY will improve our knowledge of the working of neural auditory networks and the relationship between sound and language, providing a dynamic picture of the brain in action. CLARITY makes brain tissue transparent and offers a three-dimensional view of neural networks, which, combined with genetically labeling neurons with multiple, distinct colors (Optogenetics), will provide detailed information of the complex brain system. Molecular functional magnetic resonance imaging (MRI) will allow the study of neurotransmitters detectable by MRI and their function in the auditory pathways. The Human Connectome project will study the patterns of distributed brain activity that underlie virtually all aspects of cognition and behavior and determine if abnormalities in the distributed patterns of activity may result in hearing and behavior disorders. Similarly, the programs of Big Brain and ENIGMA will improve our understanding of auditory disorders. New stem-cell therapy and gene therapies therapy may bring about a partial restoration of hearing for impaired patients by inducing regeneration of cochlear hair cells. PMID:25726297

  16. An approach to dyspnea in advanced disease.

    PubMed Central

    Gallagher, Romayne

    2003-01-01

    INTRODUCTION: To describe an approach to assessment and treatment of dyspnea. SOURCES OF INFORMATION: New level I evidence can guide management of dyspnea in advanced illness. Assessment and use of adjuvant medications and oxygen relies on level II and III evidence. MAIN MESSAGE: Opioids are first-line therapy for managing dyspnea in advanced illness. They are safe and effective in reducing shortness of breath. Neuroleptics are useful adjuvant medications. Evidence does not support use of oxygen for every patient experiencing dyspnea; it should be tried for patients who do not benefit from first-line medications and nonmedicinal therapies. CONCLUSION: Opioids relieve dyspnea and are indicated as first-line treatment for dyspnea arising from advanced disease of any cause. PMID:14708926

  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 cholangiocyte immunobiology.

    PubMed

    Syal, Gaurav; Fausther, Michel; Dranoff, Jonathan A

    2012-11-15

    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

  19. Harnessing natural product assembly lines: structure, promiscuity, and engineering.

    PubMed

    Ladner, Christopher C; Williams, Gavin J

    2016-03-01

    Many therapeutically relevant natural products are biosynthesized by the action of giant mega-enzyme assembly lines. By leveraging the specificity, promiscuity, and modularity of assembly lines, a variety of strategies has been developed that enables the biosynthesis of modified natural products. This review briefly summarizes recent structural advances related to natural product assembly lines, discusses chemical approaches to probing assembly line structures in the absence of traditional biophysical data, and surveys efforts that harness the inherent or engineered promiscuity of assembly lines for the synthesis of non-natural polyketides and non-ribosomal peptide analogues. PMID:26527577

  20. 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…

  1. 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:…

  2. 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.

  3. Germ-line genetic enhancement and Rawlsian primary goods.

    PubMed

    Allhoff, Fritz

    2005-03-01

    Genetic interventions raise a host of moral issues and, of its various species, germ-line genetic enhancement is the most morally contentious. This paper surveys various arguments against germ-line enhancement and attempts to demonstrate their inadequacies. A positive argument is advanced in favor of certain forms of germ-line enhancements, which holds that they are morally permissible if and only if they augment Rawlsian primary goods, either directly or by facilitating their acquisition. PMID:15881795

  4. The Advanced Light Source: Technical Design

    SciTech Connect

    Authors, Various

    1984-05-01

    The Advanced Light Source (ALS) is a synchrotron radiation source consisting of a 50-MeV linear accelerator, a 1.3-GeV 'booster' synchrotron, a 1.3-GeV electron storage ring, and a number of photon beam lines, as shown in Figure 1. As an introduction to a detailed description of the Advanced Light Source, this section provides brief discussions on the characteristics of synchrotron radiation and on the theory of storage rings. Appendix A contents: Introduction to Synchrotron-Radiation Sources; Storage Ring; Injection System; Control System; Insertion Devices; Photon Beam Lines; and References.

  5. 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.

  6. Investigation of native fluorescence spectral difference among prostate cancer cell lines with different risk levels

    NASA Astrophysics Data System (ADS)

    Pu, Yang; Xue, Jianpeng; Xu, Baogang; Wang, Wubao; Gu, Yueqing; Tang, Rui; Achilefu, S.; Ackerstaff, Ellen; Koutcher, Jason A.; Alfano, R. R.

    2013-03-01

    The alteration of native fluorophores among different types of cancer cell lines was investigated by the fluorescence spectroscopy. Different types of cancer cell lines with different risk levels, such as moderate metastatic (DU-145) and advanced metastatic (PC-3) cell lines as well as normal cell line (Fibroblast), were excited by the selective excitation wavelength of 300 nm to explore changes of the relative contents of tryptophan and NADH using principal component analysis (PCA). The higher relative content of tryptophan was observed in the advanced metastatic cancer cell lines in comparison with the moderate metastatic and non aggressive cell lines.

  7. Firing up the front line.

    PubMed

    Katzenbach, J R; Santamaria, J A

    1999-01-01

    For many organizations, achieving competitive advantage means eliciting superior performance from employees on the front line--the burger flippers, hotel room cleaners, and baggage handlers whose work has an enormous effect on customers. That's no easy task. Front line workers are paid low wages, have scant hope of advancement, and--not surprisingly--often care little about the company's performance. But then how do some companies succeed in engaging the emotional energy of rank-and-file workers? A team of researchers at McKinsey & Company and the Conference Board recently explored that question and discovered that one highly effective route is demonstrated by the U.S. Marine Corps. The Marines' approach to motivation follows the "mission, values, and pride" path, which researchers say is practical and relevant for the business world. More specifically, the authors say the Marines follow five practices: they over-invest in cultivating core value; prepare every person to lead, including front line supervisors; learn when to create teams and when to create single-leader work groups; attend to all employees, not just the top half; and encourage self-discipline as a way of building pride. The authors admit there are critical differences between the Marines and most businesses. But using vivid examples from companies such as KFC and Marriott International, the authors illustrate how the Marines' approach can be translated for corporate use. Sometimes, the authors maintain, minor changes in a company's standard operating procedure can have a powerful effect on front line pride and can result in substantial payoffs in company performance. PMID:10387573

  8. 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

  9. 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.

  10. 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.

  11. 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...

  12. Birds on power lines

    NASA Astrophysics Data System (ADS)

    Arnaldo Redinz, José

    2014-07-01

    Why can a bird safely rest on a high-voltage power line? We discuss three effects that can lead to the development of voltages and currents in the bird's body. To explain the absence of electric shocks, we give numerical estimates of these voltages and currents obtained from the standard solution for the voltage along a two-wire transmission line.

  13. Structuring a service line.

    PubMed

    Zablocki, E

    1997-05-01

    In 1993, Community Hospitals Indianapolis created 10 service lines--each unique to the needs of the patients it serves. Two service line leaders talk about the factors critical to successful restructuring, the working relationships established, and the importance of clear communication to ensure understanding and get buy-in to the process. PMID:10167712

  14. 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.)

  15. 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.

  16. Transmission Line Security Monitor

    ScienceCinema

    None

    2013-05-28

    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.

  17. 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.

  18. 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.

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. How Water Advances on Superhydrophobic Surfaces.

    PubMed

    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. PMID:26991185

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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)

  11. 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...

  12. Central line infections - hospitals

    MedlinePlus

    ... risk is higher if you: Are in the intensive care unit (ICU) Have a weakened immune system or serious ... unless you have washed your hands. Tell your nurse if your central line: Gets dirty Is coming ...

  13. 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 ...

  14. 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…

  15. 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

  16. Nasca Lines, Peru

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Nasca Lines are located in the Pampa region of Peru, the desolate plain of the Peruvian coast 400 km south of Lima. The Lines were first spotted when commercial airlines began flying across the Peruvian desert in the 1920's. Passengers reported seeing 'primitive landing strips' on the ground below. The Lines were made by removing the iron-oxide coated pebbles which cover the surface of the desert. When the gravel is removed, they contrast with the light color underneath. In this way the lines were drawn as furrows of a lighter color. On the pampa, south of the Nasca Lines, archaeologists have now uncovered the lost city of the line-builders, Cahuachi. It was built nearly two thousand years ago and was mysteriously abandoned 500 years later. This ASTER sub-image covers an area of 14 x 18 km, was acquired on December 22, 2000, and is located at 14.7 degrees south latitude and 75.1 degrees west longitude.

    The U.S. science team is located at NASA's Jet Propulsion Laboratory, Pasadena, Calif. The Terra mission is part of NASA's Science Mission Directorate.

  17. 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)

  18. 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.

  19. The hydrodynamics of a moving fluid-liquid contact line

    NASA Astrophysics Data System (ADS)

    Vanderzanden, Antonius Johannus J.

    The hydrodynamics associated with an advancing contact line, where a viscous liquid displaces a fluid with a negligible viscosity, is examined. A model is proposed which approximates the shape of an advancing meniscus in a tube or between parallel plates. Comparison of the predictions of the model with available numerical and experimental results provides an indication of its reliability. This model is applied to receding contact lines, where a viscous liquid is displaced by a fluid of negligible viscosity. The model is extended to examine moving liquid-liquid contact lines where the viscosity of neither fluid can be neglected. Experiments concerning the macroscopic shape of a meniscus in a tube and experiments which lay claim to be able to peep into the microscopic region close to the contact line not accessible with the naked eye are presented.

  20. Integrated survey and design for transmission lines

    SciTech Connect

    Miller, M.A.; Simpson, K.D.

    1994-12-31

    Gathering and compiling information on the features and uses of the land within a proposed corridor provides the basis for selecting a route, obtaining easements, and designing and constructing a transmission line. Traditionally, gathering this information involved searches of existing maps and records to obtain the available information, which would then be supplemented with aerial photography to record current conditions. Ground surveys were performed to collect topographic data for design purposes. This information was manually transferred to drawings and other documents to show the terrain, environmentally sensitive areas, property ownership, and existing facilities. These drawing served as the base to which the transmission line right-of-way, structures, and other design information were added. As the design was completed, these drawings became the source of information for constructing the line and ultimately, the record of the facility. New technologies and the every growing need for instantly accessible information have resulted in changes in almost every step of gathering, storing and using information. Electronic data collection, global positioning systems (GPS), digitized terrain models, computerized design techniques, development of drawings using CAD, and graphical information systems (GIS) have individually resulted in significant advancements in this process. Combining these components into an integrated system, however, is truly revolutionizing transmission line engineering. This paper gives an overview of the survey and mapping information that is required for transmission line projects, review the traditional techniques that have been employed to obtain and utilize this information, and discuss the recent advances in the technology. Additionally, a system is presented that integrates the components in this process to achieve efficiency, minimize chances of errors, and provide improved access to project information.

  1. Advance Care Planning

    MedlinePlus

    ... Division of Geriatrics and Clinical Gerontology Division of Neuroscience FAQs Funding Opportunities Intramural Research Program Office of ... Is Advance Care Planning? Advance care planning involves learning about the types of decisions that might need ...

  2. 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

  3. Blasted Cell Line Names

    PubMed Central

    Wang, Jing; Byers, Lauren A.; Yordy, John S.; Liu, Wenbin; Shen, Li; Baggerly, Keith A.; Giri, Uma; Myers, Jeffrey N.; Ang, K. Kian; Story, Michael D.; Girard, Luc; Minna, John D.; Heymach, John V.; Coombes, Kevin R.

    2010-01-01

    Background: While trying to integrate multiple data sets collected by different researchers, we noticed that the sample names were frequently entered inconsistently. Most of the variations appeared to involve punctuation, white space, or their absence, at the juncture between alphabetic and numeric portions of the cell line name. Results: Reasoning that the variant names could be described in terms of mutations or deletions of character strings, we implemented a simple version of the Needleman-Wunsch global sequence alignment algorithm and applied it to the cell line names. All correct matches were found by this procedure. Incorrect matches only occured when a cell line was present in one data set but not in the other. The raw match scores tended to be substantially worse for the incorrect matches. Conclusions: A simple application of the Needleman-Wunsch global sequence alignment algorithm provides a useful first pass at matching sample names from different data sets. PMID:21082038

  4. Circumstellar radio molecular lines

    NASA Technical Reports Server (NTRS)

    NGUYEN-QUANG-RIEU

    1987-01-01

    Radio molecular lines appear to be useful probes into the stellar environment. Silicon oxide masers provide information on the physical conditions in the immediate vicinity of the stellar photosphere. Valuable information on the physics operating in the envelope of IRC + 10216 was recently obtained by high sensitivity observations and detailed theoretical analyses. Infrared speckle interferometry in the molecular lines and in the continuum is helpful in the investigation of the inner region of the envelope. These techniques are discussed in terms of late-type star mass loss.

  5. 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.

  6. Rewards and advancements for clinical pharmacists.

    PubMed

    Goodwin, S Diane; Kane-Gill, Sandra L; Ng, Tien M H; Melroy, Joel T; Hess, Mary M; Tallian, Kimberly; Trujillo, Toby C; Vermeulen, Lee C

    2010-01-01

    The American College of Clinical Pharmacy charged the Clinical Practice Affairs Committee to review and update the College's 1995 White Paper, "Rewards and Advancements for Clinical Pharmacy Practitioners." Because of the limited data on the present state of rewards and advancements for clinical pharmacists, an online survey of "front-line" clinical pharmacists and pharmacy managers was conducted (1126 total respondents, 14% response rate). The resulting White Paper discusses motivators and existing systems of rewards and advancements for clinical pharmacists, as well as perceived barriers to implementation of these systems. Clinical pharmacists reported work-life balance, a challenging position, and opportunities for professional advancement as the most important factors for career success. At the time of the survey, financial rewards appeared not to be a major motivator for clinical pharmacists. Managers underestimated the importance that clinical pharmacists place on work-life balance and favorable work schedules. Although almost two thirds of the clinical pharmacists surveyed had not developed a professional development plan, 84% indicated an interest in career planning. Both clinical pharmacists and managers rated the lack of a clear reward and advancement structure as the most important barrier to effective systems of rewards and advancements. Pharmacy managers and administrators are encouraged to develop effective systems of rewards and advancements for clinical pharmacists that positively impact patient care and the institution's mission; these systems will benefit the clinical pharmacist, the health care institution, and the patient. PMID:20030483

  7. 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. PMID:26936774

  8. 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.

  9. 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. PMID:20018582

  10. 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.

  11. 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…

  12. Cracks and Lines

    NASA Technical Reports Server (NTRS)

    2004-01-01

    6 June 2004 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) picture shows an odd area of the south polar region that has sets of fine, nearly parallel lines running from the northeast (upper right) toward southwest (lower left) and a darker, wider set of cracks with a major trend running almost perpendicular to the finer lines. The appearance of these features is enhanced by seasonal frost. Dark areas have no frost, bright areas still have frozen carbon dioxide ice. In summer, the ice would be gone and the cracks and lines less obvious when viewed from orbit. Although unknown, wind might be responsible for forming the fine set of lines, and perhaps freeze-thaw cycles of ground ice or structural deformation would have contributed to formation of the wider cracks. The image is located near 85.0oS, 324.0oW, and covers an area about 1.5 km (nearly 1 mi) across. The scene is illuminated by sunlight from the upper left.

  13. 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.

  14. 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…

  15. 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)

  16. Advanced information society (12)

    NASA Astrophysics Data System (ADS)

    Komatsuzaki, Seisuke

    In this paper, the original Japanese idea of "advanced information society" was reviewed at the first step. Thus, advancement of information/communication technology, advancement of information/communication needs and tendency of industrialization of information" were examined. Next, by comparing studies on advanced information society in various countries, the Japanese characteristics of consensus building was reviewed. Finally, in pursuit of prospect and tasks for the society, advancement of innovation and convergence information/communication technology, information/communication needs, institutional environment for utilization of information/communication and countermeasures against information pollution. Matching of information/communication technology and needs, besides with countermeasures against information pollution were discussed.

  17. 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…

  18. 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…

  19. 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.

  20. 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.

  1. Linear induction accelerator approach for advanced radiography

    SciTech Connect

    Caporaso, G.J.

    1997-05-01

    Recent advances in induction accelerator technology make it possible to envision a single accelerator that can serve as an intense, precision multiple pulse x-ray source for advanced radiography. Through the use of solid-state modulator technology repetition rates on the order of 1 MHz can be achieved with beam pulse lengths ranging from 200 ns to 2 {micro}secs. By using fast kickers, these pulses may be sectioned into pieces which are directed to different beam lines so as to interrogate the object under study from multiple lines of sight. The ultimate aim is to do a time dependent tomographic reconstruction of a dynamic object. The technology to accomplish these objectives along with a brief discussion of the experimental plans to verify it will be presented.

  2. 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.

  3. 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.

  4. Cryoresistive gas insulated line

    NASA Astrophysics Data System (ADS)

    Hidaka, K.; Matsumoto, S.; Kouno, T.

    An insulation strength of more than 16 kV mm -1 has been realized using nitrogen gas at 133 K and 0.4 MPa with the application of a.c. and impulse voltages. A cryoresistive gas insulated line (CRGIL) using nitrogen gas is proposed on the basis of the measured insulation strength. An efficient method for use of the cooling heat of liquefied natural gas is also proposed so that no refrigerator is required and the cost of cooling is reduced. The CRGIL has the advantages of having a large current carrying capacity, small power loss and small capacitance. Moreover, a given transmission capacity is achieved by a CRGIL whose rated voltage is about half that in a conventional gas insulated line.

  5. 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.

  6. A comparison of fluoropolymer linings

    SciTech Connect

    Khaladkar, P.R. )

    1994-02-01

    Five established methods of applying fluoropolymer to metallic and fiber-reinforced plastic (FRP) substrates of barrier or lining applications include: (1) loose linings; (2) rotolining; (3) adhesively bonded linings; (4) spray and baked linings; and (5) dual laminate with FRP linings. With their low strength and high creep rates, fluoropolymers most often are used as barriers on substrates. The article offers some guidelines on the selection of suitable options for given applications.

  7. An Improved Optical Spectral Line List for RR Telescopii

    NASA Technical Reports Server (NTRS)

    Crawford, F. L.; McKenna, F. C.; Keenan, F. P.; Allen, L. H.; Feibelman, W. A.; Ryan, S. G.

    1999-01-01

    The symbiotic nova RR Telescopli has been observed with the 3.9m telescope of the Anglo-Australian Observatory (AAO), using the University College London Echelle Spectrograph in conjunction with a Tek CCD. It displays a rich emission line spectrum, ranging in excitation from N I to [Ni VIII]. We present a list of 824 measured lines, with their suggested identifications and absolute line intensities, covering a wavelength range from 3180 A to 9455 A. The absolute line intensities have been derived by comparing the high resolution data with a flux-calibrated low resolution spectrum taken with the Australian National University 2.3 m telescope. All of the lines have been successfully identified. Comparing our results with those of previous studies indicates that the RR Tel system is advancing towards higher degrees of ionization.

  8. 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…

  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. 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…

  11. Systematic Spacing of Townsites along Eastern South Dakota's Rail Lines.

    ERIC Educational Resources Information Center

    Lockwood, Catherine M.

    1990-01-01

    Investigates townsite distribution in South Dakota's land settlement pattern. Reviews past theories explaining eastern South Dakota's systematic spacing of towns along rail lines. Indicates a correlation between railroad functions and town development, advancing the theory that nineteenth-century railroad technology, involving traffic control and…

  12. 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.

  13. Vertical bloch line memory

    NASA Technical Reports Server (NTRS)

    Katti, Romney R. (Inventor); Stadler, Henry L. (Inventor); Wu, Jiin-chuan (Inventor)

    1995-01-01

    A new read gate design for the vertical Bloch line (VBL) memory is disclosed which offers larger operating margin than the existing read gate designs. In the existing read gate designs, a current is applied to all the stripes. The stripes that contain a VBL pair are chopped, while the stripes that do not contain a VBL pair are not chopped. The information is then detected by inspecting the presence or absence of the bubble. The margin of the chopping current amplitude is very small, and sometimes non-existent. A new method of reading Vertical Bloch Line memory is also disclosed. Instead of using the wall chirality to separate the two binary states, the spatial deflection of the stripe head is used. Also disclosed herein is a compact memory which uses vertical Bloch line (VBL) memory technology for providing data storage. A three-dimensional arrangement in the form of stacks of VBL memory layers is used to achieve high volumetric storage density. High data transfer rate is achieved by operating all the layers in parallel. Using Hall effect sensing, and optical sensing via the Faraday effect to access the data from within the three-dimensional packages, an even higher data transfer rate can be achieved due to parallel operation within each layer.

  14. 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

  15. 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.

  16. Advance Care Planning.

    PubMed

    Stallworthy, Elizabeth J

    2013-04-16

    Advance care planning should be available to all patients with chronic kidney disease, including end-stage kidney disease on renal replacement therapy. Advance care planning is a process of patient-centred discussion, ideally involving family/significant others, to assist the patient to understand how their illness might affect them, identify their goals and establish how medical treatment might help them to achieve these. An Advance Care Plan is only one useful outcome from the Advance Care Planning process, the education of patient and family around prognosis and treatment options is likely to be beneficial whether or not a plan is written or the individual loses decision making capacity at the end of life. Facilitating Advance Care Planning discussions requires an understanding of their purpose and communication skills which need to be taught. Advance Care Planning needs to be supported by effective systems to enable the discussions and any resulting Plans to be used to aid subsequent decision making. PMID:23586906

  17. 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.

  18. Comparison of inoculation strategies to assess biological interactions between sorghum lines and fungi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Comparison of inoculation strategies to assess biological interactions between sorghum lines and fungi Bioassays were assessed for utility to characterize fungal species associated with sorghum or to screen germplasm for advancement in breeding programs. Isolates of Alternaria alternata, Fusarium e...

  19. On the front lines.

    PubMed

    Lipley, Nick

    2016-06-10

    Why did you become an emergency nurse? After qualifying as a registered adult nurse in 2003, I started my nursing career as a theatre nurse, which I enjoyed for six years. Here I developed my anaesthetic and recovery nursing skills which gave me great grounding for my career in ED. I had the opportunity to complete an advanced standing children's nursing programme from which I qualified in 2010 as a dual trained adult/paediatric nurse. I then consolidated my knowledge on an acute paediatric ward, before moving to emergency care where I could use my dual training best. PMID:27286031

  20. 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

  1. Insights into the chemical logic and enzymatic machinery of NRPS assembly lines.

    PubMed

    Walsh, Christopher T

    2016-02-01

    Appreciation that some cyclic peptide antibiotics such as gramicidin S and tyrocidine were nonribosomally synthesized has been known for 50 years. The past two decades of research including advances in bacterial genetics, genomics, protein biochemistry and mass spectrometry have codified the principles of assembly line enzymology for hundreds of nonribosomal peptides and in parallel for thousands of polyketides. The advances in understanding the strategies used for chain initiation, elongation and termination from these assembly lines have revitalized natural product biosynthetic communities. PMID:26175103

  2. 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 <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. During the first year a custom batch furnace was built to develop the method with high power radiative heating to simulate transfer of glass into a hot slumping zone in a production line. To preserve the original high polish of the float glass on both front and back surfaces, as required for a second surface mirror, the mold surface is machined to the required shape as grooves which intersect the glass at cusps, reducing the mold contact area to significantly less than 1%. The mold surface is gold-plated to reflect thermal radiation. Optical metrology of glass replicas made with the system has been carried out with a novel, custom-built test system. This test provides collimated, vertically-oriented parallel beams from a linear array of co-aligned lasers translated in a perpendicular direction across the reflector. Deviations of

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. A short line segment squirms along a zigzag line.

    PubMed

    Ito, Hiroyuki; Yang, Xie

    2013-01-01

    When a short straight line segment moves across a zigzag line and is viewed in one's peripheral vision, it appears to exhibit nonrigid squirming motion (the squirm effect). This phenomenon demonstrates that the form, orientation, and motion direction of a short line are influenced by those of a longer one when they are viewed in one's peripheral vision. PMID:23755359

  8. Advanced Airspace Concept

    NASA Technical Reports Server (NTRS)

    Erzberger, Heinz

    2002-01-01

    A general overview of the Advanced Airspace Concept (AAC) is presented. The topics include: 1) Limitations of the existing system; 2) The Advanced Airspace Concept; 3) Candidate architecture for the AAC; 4) Separation assurance and conflict avoidance system (TSAFE); and 5) Ground-Air Interactions. This paper is in viewgraph form.

  9. 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.

  10. 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…

  11. 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.

  12. 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.

  13. 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)

  14. 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.

  15. 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.

  16. Iron Line Diagnostics of Narrow Emission Line Galaxies

    NASA Astrophysics Data System (ADS)

    Nousek, John A.

    1996-05-01

    This report describes the activities at Penn State University supported by NASA Grant NAG5-2528, 'Iron Line Diagnostics of Narrow Emission Line Galaxies'. The aim of this investigation was to accurately measure the iron (Fe K) line emission in two X-ray selected Seyfert 2 galaxies (NGC 2992 and MCG-5-23-16). The astrophysics being probed was to determine whether the Fe line was narrow, broad or both. The broad line component is very important as a probe of the nature of the innermost accretion onto the central engine in AGN's.

  17. TIGER/LINE FILES, 1998

    EPA Science Inventory

    TIGER, TIGER/Line, and Census TIGER are registered trademarks of the Bureau of the Census. The 1998 TIGER/Line files are an extract of selected geographic and cartographic information from the Census TIGER data base. The geographic coverage for a single TIGER/Line file is a cou...

  18. Atlas of Infrared Absorption Lines

    NASA Technical Reports Server (NTRS)

    Park, J. H.

    1977-01-01

    This atlas of infrared absorption line contains absorption line parameters (line strength vs. wavenumber) from 500 to 7000 cm(exp-1) for 15 gases: H2O, CO2, O3, N2O, CO, CH4, O2, SO2, NO, NO2, NH3, HCl, HF, HNO3 and CH3Cl.

  19. 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.

  20. 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.

  1. Conservation with underground power lines

    SciTech Connect

    Graneau, P.

    1980-01-01

    The following aspects of underground power transmission lines are discussed: their contribution to area beautification; line losses and their causes; the energy conservation potential of large-conductor underground cables; reliability and outage advantages as compared with overhead lines; the history of underground systems; problems with polyethylene insulation; and the development and performance of sodium conductors for underground cables. (LCL)

  2. 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.

  3. 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.

  4. 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.}

  5. 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.

  6. 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.

  7. 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.

  8. Stripe rust resistance and genes in Chinese wheat cultivars and breeding lines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most important diseases on wheat in China. To assess resistance in wheat cultivars and breeding lines in China, 330 leading cultivars and 164 advanced breeding lines were evaluated with stripe rust. In the greenhouse tes...

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Advanced launch system

    NASA Technical Reports Server (NTRS)

    Monk, Jan C.

    1991-01-01

    The Advanced Launch System (ALS) is presented. The costs, reliability, capabilities, infrastructure are briefly described. Quality approach, failure modes, structural design, technology benefits, and key facilities are outlined. This presentation is represented by viewgraphs.

  15. Advanced camera for surveys

    NASA Astrophysics Data System (ADS)

    Clampin, Mark; Ford, Holland C.; Bartko, Frank; Bely, Pierre Y.; Broadhurst, Tom; Burrows, Christopher J.; Cheng, Edward S.; Crocker, James H.; Franx, Marijn; Feldman, Paul D.; Golimowski, David A.; Hartig, George F.; Illingworth, Garth; Kimble, Randy A.; Lesser, Michael P.; Miley, George H.; Postman, Marc; Rafal, Marc D.; Rosati, Piero; Sparks, William B.; Tsvetanov, Zlatan; White, Richard L.; Sullivan, Pamela; Volmer, Paul; LaJeunesse, Tom

    2000-07-01

    The Advanced Camera for Surveys (ACS) is a third generation instrument for the Hubble Space Telescope (HST). It is currently planned for installation in HST during the fourth servicing mission in Summer 2001. The ACS will have three cameras.

  16. The Advanced Energy Initiative

    NASA Astrophysics Data System (ADS)

    Milliken, JoAnn; Joseck, Fred; Wang, Michael; Yuzugullu, Elvin

    The President's Advanced Energy Initiative (AEI), launched in 2006, addresses the challenges of energy supply and demand facing our Nation by supporting research and development of advanced technologies for transportation and stationary power generation. The AEI portfolio includes clean coal, nuclear and renewable energy technologies (solar and wind) for stationary power generation and advanced battery technologies, cellulosic ethanol as a fuel and hydrogen fuel cells for transportation. These research and development programs are underpinned by comprehensive life-cycle analysis efforts using models such as Hydrogen Analysis (H2A) and Greenhouse Gases, Regulated Emissions and Energy Use in Transportation (GREET) to enable a better understanding of the characteristics and trade-offs associated with advanced energy options and to help decision makers choose viable pathways for clean, reliable and affordable energy.

  17. 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)

  18. 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.

  19. 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.

  20. Advanced Lab Consortium ``Conspiracy''

    NASA Astrophysics Data System (ADS)

    Reichert, Jonathan F.

    2006-03-01

    Advanced Laboratory instruction is a time-honored and essential element of an undergraduate physics education. But, from my vantage point, it has been neglected by the two major professional societies, APS and AAPT. At some schools, it has been replaced by ``research experiences,'' but I contend that very few of these experiences in the research lab, particularly in the junior year, deliver what they promise. It is time to focus the attention of APS, AAPT, and the NSF on the advanced lab. We need to create an Advanced Lab Consortium (ALC) of faculty and staff to share experiments, suppliers, materials, pedagogy, ideas, in short to build a professional network for those committed to advanced lab instruction. The AAPT is currently in serious discussions on this topic and my company stands ready with both financial and personnel resources to support the effort. This talk is a plea for co-conspirators.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. Optimization of line configuration and balancing for flexible machining lines

    NASA Astrophysics Data System (ADS)

    Liu, Xuemei; Li, Aiping; Chen, Zurui

    2016-04-01

    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.

  9. 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.

  10. Electrowetting films on parallel line electrodes.

    PubMed

    Yeo, Leslie Y; Chang, Hsueh-Chia

    2006-01-01

    A lubrication analysis is presented for the spreading dynamics of a high permittivity polar dielectric liquid drop due to an electric field sustained by parallel line electrode pairs separated by a distance R(e). The normal Maxwell stress, concentrated at the tip region near the apparent three-phase contact line, produces a negative capillary pressure that is responsible for pulling out a thin finger of liquid film ahead of the macroscopic drop, analogous to that obtained in self-similar gravity spreading. This front-running electrowetting film maintains a constant contact angle and volume as its front position advances in time t by the universal law 0.43R(e)(t/T(cap))1/3, independent of the drop dimension, surface tension, and wettability. T(cap)=pi(2)mu(l)R(e)/8(epsilon0epsilonl)V2 is the electrocapillary time scale where mu(l) is the liquid viscosity, epsilon0epsilonl the liquid permittivity, and V the applied voltage. This spreading dynamics for the electrowetting film is much faster than the rest of the drop; after a short transient, the latter spreads over the electrowetting film by draining into it. By employing matched asymptotics, we are able to elucidate this unique mechanism, justified by the reasonable agreement with numerical and experimental results. Unlike the usual electrowetting-on-dielectric configuration where the field singularity at the contact line produces a static change in the contact angle consistent with the Lippmann equation, we show that the parallel electrode configuration produces a bulk negative Maxwell pressure within the drop. This Maxwell pressure increases in magnitude toward the contact line due to field confinement and is responsible for a bulk pressure gradient that gives rise to a front-running spontaneous electrowetting film. PMID:16486159

  11. 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.

  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. Reliable in vitro studies require appropriate ovarian cancer cell lines.

    PubMed

    Jacob, Francis; Nixdorf, Sheri; Hacker, Neville F; Heinzelmann-Schwarz, Viola A

    2014-01-01

    Ovarian cancer is the fifth most common cause of cancer death in women and the leading cause of death from gynaecological malignancies. Of the 75% women diagnosed with locally advanced or disseminated disease, only 30% will survive five years following treatment. This poor prognosis is due to the following reasons: limited understanding of the tumor origin, unclear initiating events and early developmental stages of ovarian cancer, lack of reliable ovarian cancer-specific biomarkers, and drug resistance in advanced cases. In the past, in vitro studies using cell line models have been an invaluable tool for basic, discovery-driven cancer research. However, numerous issues including misidentification and cross-contamination of cell lines have hindered research efforts. In this study we examined all ovarian cancer cell lines available from cell banks. Hereby, we identified inconsistencies in the reporting, difficulties in the identification of cell origin or clinical data of the donor patients, restricted ethnic and histological type representation, and a lack of tubal and peritoneal cancer cell lines. We recommend that all cell lines should be distributed via official cell banks only with strict guidelines regarding the minimal available information required to improve the quality of ovarian cancer research in future. PMID:24936210

  14. Reliable in vitro studies require appropriate ovarian cancer cell lines

    PubMed Central

    2014-01-01

    Ovarian cancer is the fifth most common cause of cancer death in women and the leading cause of death from gynaecological malignancies. Of the 75% women diagnosed with locally advanced or disseminated disease, only 30% will survive five years following treatment. This poor prognosis is due to the following reasons: limited understanding of the tumor origin, unclear initiating events and early developmental stages of ovarian cancer, lack of reliable ovarian cancer-specific biomarkers, and drug resistance in advanced cases. In the past, in vitro studies using cell line models have been an invaluable tool for basic, discovery-driven cancer research. However, numerous issues including misidentification and cross-contamination of cell lines have hindered research efforts. In this study we examined all ovarian cancer cell lines available from cell banks. Hereby, we identified inconsistencies in the reporting, difficulties in the identification of cell origin or clinical data of the donor patients, restricted ethnic and histological type representation, and a lack of tubal and peritoneal cancer cell lines. We recommend that all cell lines should be distributed via official cell banks only with strict guidelines regarding the minimal available information required to improve the quality of ovarian cancer research in future. PMID:24936210

  15. 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.

  16. 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. PMID:21133977

  17. Synthetic CA II Triplet Lines

    NASA Astrophysics Data System (ADS)

    Erdelyi, M. M.; Barbuy, B.

    1990-11-01

    RESUMEN. Se hicieron calculos de sintesis del espectro en el ititervalo de longitud de onda - 8700 A, ara ? oder verificar el comporta- mien to de diferentes lineas moleculares y at5micas como funci5n de los parametros esteldres de temperatura, gravedad y metalicidad. El espec- tro sintetico ha sido generado para:(a) todas las , (b) solamente de CN, (c) solamente de TiO, y (d) solamente lineas at6micas. Abstract. Spectrum synthesis calculations are carried out in the wavelength interval X 8300 - 8700 A, in order to verify the behaviour of different molecular and atomic lines as a function of the stellar para meters temperature, gravity and metallicity. Synthetic spectra were ge nerated for: (a) all lines, (b) only CN lines, (c) only TiO lines, and (d) only atomic lines Key `td6: LINE-PROFILE - ST S-AThOSPHERES

  18. 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.

  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. 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.

  1. 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.

  2. 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.

  3. LINE-ABOVE-GROUND ATTENUATOR

    DOEpatents

    Wilds, R.B.; Ames, J.R.

    1957-09-24

    The line-above-ground attenuator provides a continuously variable microwave attenuator for a coaxial line that is capable of high attenuation and low insertion loss. The device consists of a short section of the line-above- ground plane type transmission lime, a pair of identical rectangular slabs of lossy material like polytron, whose longitudinal axes are parallel to and indentically spaced away from either side of the line, and a geared mechanism to adjust amd maintain this spaced relationship. This device permits optimum fineness and accuracy of attenuator control which heretofore has been difficult to achieve.

  4. 132. FORKS DIVERSION, HIGH LINE AND LOW LINE CANALS, TWIN ...

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

    132. FORKS DIVERSION, HIGH LINE AND LOW LINE CANALS, TWIN FALLS COUNTY, SOUTH OF HANSEN, IDAHO; POWER GATES FOR HYDRO-ELECTRIC. - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

  5. Advanced access appointments

    PubMed Central

    Hudec, John C.; MacDougall, Steven; Rankin, Elaine

    2010-01-01

    ABSTRACT OBJECTIVE To examine the effects of advanced access (same-day physician appointments) on patient and provider satisfaction and to determine its association with other variables such as physician income and patient emergency department use. DESIGN Patient satisfaction survey and semistructured interviews with physicians and support staff; analysis of physician medical insurance billings and patient emergency department visits. SETTING Cape Breton, NS. PARTICIPANTS Patients, physicians, and support staff of 3 comparable family physician practices that had not implemented advanced access and an established advanced access practice. MAIN OUTCOME MEASURES Self-reported provider and patient satisfaction, physician office income, and patients’ emergency department use. RESULTS The key benefits of implementation of advanced access were an increase in provider and patient satisfaction levels, same or greater physician office income, and fewer less urgent (triage level 4) and nonurgent (triage level 5) emergency department visits by patients. CONCLUSION Currently within the Central Cape Breton Region, 33% of patients wait 4 or more days for urgent appointments. Findings from this study can be used to enhance primary care physician practice redesign. This research supports many benefits of transitioning to an advanced access model of patient booking. PMID:20944024

  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. 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.

  8. 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

  9. Pessary use in advanced pelvic organ prolapse.

    PubMed

    Powers, Kenneth; Lazarou, George; Wang, Andrea; LaCombe, Julie; Bensinger, Giti; Greston, Wilma M; Mikhail, Magdy S

    2006-02-01

    The objective of this study was to review our experience with pessary use for advanced pelvic organ prolapse. Charts of patients treated for Stage III and IV prolapse were reviewed. Comparisons were made between patients who tried or refused pessary use. A successful trial of pessary was defined by continued use; a failed trial was defined by a patient's discontinued use. Thirty-two patients tried a pessary; 45 refused. Patients who refused a pessary were younger, had lesser degree of prolapse, and more often had urinary incontinence. Most patients (62.5%) continued pessary use and avoided surgery. Unsuccessful trial of pessary resorting to surgery included four patients (33%) with unwillingness to maintain, three patients (25%) with inability to retain and two patients (17%) with vaginal erosion and/or discharge. Our findings suggest that pessary use is an acceptable first-line option for treatment of advanced pelvic organ prolapse. PMID:15883856

  10. 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

  11. 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.

  12. 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.

  13. Advanced rocket propulsion

    NASA Technical Reports Server (NTRS)

    Obrien, Charles J.

    1993-01-01

    Existing NASA research contracts are supporting development of advanced reinforced polymer and metal matrix composites for use in liquid rocket engines of the future. Advanced rocket propulsion concepts, such as modular platelet engines, dual-fuel dual-expander engines, and variable mixture ratio engines, require advanced materials and structures to reduce overall vehicle weight as well as address specific propulsion system problems related to elevated operating temperatures, new engine components, and unique operating processes. High performance propulsion systems with improved manufacturability and maintainability are needed for single stage to orbit vehicles and other high performance mission applications. One way to satisfy these needs is to develop a small engine which can be clustered in modules to provide required levels of total thrust. This approach should reduce development schedule and cost requirements by lowering hardware lead times and permitting the use of existing test facilities. Modular engines should also reduce operational costs associated with maintenance and parts inventories.

  14. 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.

  15. Advanced rocket propulsion

    NASA Astrophysics Data System (ADS)

    Obrien, Charles J.

    1993-02-01

    Existing NASA research contracts are supporting development of advanced reinforced polymer and metal matrix composites for use in liquid rocket engines of the future. Advanced rocket propulsion concepts, such as modular platelet engines, dual-fuel dual-expander engines, and variable mixture ratio engines, require advanced materials and structures to reduce overall vehicle weight as well as address specific propulsion system problems related to elevated operating temperatures, new engine components, and unique operating processes. High performance propulsion systems with improved manufacturability and maintainability are needed for single stage to orbit vehicles and other high performance mission applications. One way to satisfy these needs is to develop a small engine which can be clustered in modules to provide required levels of total thrust. This approach should reduce development schedule and cost requirements by lowering hardware lead times and permitting the use of existing test facilities. Modular engines should also reduce operational costs associated with maintenance and parts inventories.

  16. Cascaded humidified advanced turbine

    SciTech Connect

    Nakhamkin, M.; Swenson, E.C.; Cohn, A.; Bradshaw, D.; Taylor, R.; Wilson, J.M.; Gaul, G.; Jahnke, F.; Polsky, M.

    1995-05-01

    This article describes how, by combining the best features of simple- and combined-cycle gas turbine power plants, the CHAT cycle concept offers power producers a clean, more efficient and less expensive alternative to both. The patented cascaded advanced turbine and its cascaded humidified advanced turbine (CHAT) derivative offer utilities and other power producers a practical advanced gas turbine power plant by combining commercially-available gas turbine and industrial compressor technologies in a unique way. Compared to combined-cycle plants, a CHAT power plant has lower emissions and specific capital costs-approximately 20 percent lower than what is presently available. Further, CHAT`s operating characteristics are especially well-suited to load following quick start-up scenarios and they are less susceptible to power degradation from higher ambient air temperature conditions.

  17. Advanced Worker Protection System

    SciTech Connect

    1996-04-01

    The Advanced Worker Protection System (AWPS) is a liquid-air-based, self-contained breathing and cooling system with a duration of 2 hrs. AWPS employs a patented system developed by Oceaneering Space Systems (OSS), and was demonstrated at their facility in Houston, TX as well as at Kansas State University, Manhattan. The heart of the system is the life-support backpack that uses liquid air to provide cooling as well as breathing gas to the worker. The backpack is combined with advanced protective garments, an advanced liquid cooling garment (LCG), a respirator, and communications and support equipment. The prototype unit development and testing under Phase 1 has demonstrated that AWPS has the ability to meet performance criteria. These criteria were developed with an understanding of both the AWPS capabilities and the DOE decontamination and decommissioning (D and D) activities protection needs.

  18. 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.

  19. Commercialization of advanced batteries

    SciTech Connect

    Mader, J.

    1996-11-01

    Mader and Associates has been working as a contractor for the South Coast Air Quality Management District (District) for the past several years. During this period it has performed various assessments of advanced battery technology as well as established the Advanced Battery Task Force. The following paper is Mader`s view of the status of battery technologies that are competing for the electric vehicle (EV) market being established by the California Air Resources Board`s Zero Emission Vehicle (ZEV) Mandate. The ZEV market is being competed for by various advanced battery technologies. And, given the likelihood of modifications to the Mandate, the most promising technologies should capture the following market share during the initial 10 years: Lead-Acid--8.4%, Nickel Metal Hydride--50.8%, Sodium Sulfur--7.8%, Lithium Ion 33.0%.

  20. The Advanced LIGO Detectors

    NASA Astrophysics Data System (ADS)

    Fritschel, Peter

    2016-03-01

    After decades of development, the Advanced LIGO gravitational wave detectors are now operating, and they completed their first observational run in early 2016. Advanced LIGO consists of two 4-km scale interferometric detectors located at separate sites in the US. The first year of detector commissioning that led to the first observation run produced instruments that have several times better sensitivity to gravitational-wave strain than previous instruments. At their final design sensitivity, the detectors will be another factor of 2-3x more sensitive than current performance. This talk will cover the design of Advanced LIGO, explain how the sensitivity improvements have been achieved, and lay out the path to reaching final design sensitivity.

  1. [Advanced Composites Technology Initiatives

    NASA Technical Reports Server (NTRS)

    Julian, Mark R.

    2002-01-01

    This final report closes out the W02 NASA Grant #NCC5-646. The FY02 grant for advanced technology initiatives through the Advanced Composites Technology Institute in Bridgeport, WV, at the Robert C. Byrd Institute (RCBI) Bridgeport Manufacturing Technology Center, is complete; all funding has been expended. RCBI continued to expand access to technology; develop and implement a workforce-training curriculum; improve material development; and provide prototyping and demonstrations of new and advanced composites technologies for West Virginia composites firms. The FY 02 efforts supported workforce development, technical training and the HST development effort of a super-lightweight composite carrier prototype and expanded the existing technical capabilities of the growing aerospace industry across West Virginia to provide additional support for NASA missions. Additionally, the Composites Technology and Training Center was awarded IS0 9001 - 2000 certification and Cleanroom Class 1000 certification during this report period.

  2. 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.

  3. Identification of Genes and Networks Driving Cardiovascular and Metabolic Phenotypes in a Mouse F2 Intercross

    PubMed Central

    Derry, Jonathan M. J.; Zhong, Hua; Molony, Cliona; MacNeil, Doug; Guhathakurta, Debraj; Zhang, Bin; Mudgett, John; Small, Kersten; El Fertak, Lahcen; Guimond, Alain; Selloum, Mohammed; Zhao, Wenqing; Champy, Marie France; Monassier, Laurent; Vogt, Tom; Cully, Doris; Kasarskis, Andrew; Schadt, Eric E.

    2010-01-01

    To identify the genes and pathways that underlie cardiovascular and metabolic phenotypes we performed an integrated analysis of a mouse C57BL/6J x A/J F2 (B6AF2) cross by relating genome-wide gene expression data from adipose, kidney, and liver tissues to physiological endpoints measured in the population. We have identified a large number of trait QTLs including loci driving variation in cardiac function on chromosomes 2 and 6 and a hotspot for adiposity, energy metabolism, and glucose traits on chromosome 8. Integration of adipose gene expression data identified a core set of genes that drive the chromosome 8 adiposity QTL. This chromosome 8 trans eQTL signature contains genes associated with mitochondrial function and oxidative phosphorylation and maps to a subnetwork with conserved function in humans that was previously implicated in human obesity. In addition, human eSNPs corresponding to orthologous genes from the signature show enrichment for association to type II diabetes in the DIAGRAM cohort, supporting the idea that the chromosome 8 locus perturbs a molecular network that in humans senses variations in DNA and in turn affects metabolic disease risk. We functionally validate predictions from this approach by demonstrating metabolic phenotypes in knockout mice for three genes from the trans eQTL signature, Akr1b8, Emr1, and Rgs2. In addition we show that the transcriptional signatures for knockout of two of these genes, Akr1b8 and Rgs2, map to the F2 network modules associated with the chromosome 8 trans eQTL signature and that these modules are in turn very significantly correlated with adiposity in the F2 population. Overall this study demonstrates how integrating gene expression data with QTL analysis in a network-based framework can aid in the elucidation of the molecular drivers of disease that can be translated from mice to humans. PMID:21179467

  4. Growth performance comparison of intercross-triploid, induced triploid, and diploid rainbow trout

    Technology Transfer Automated Retrieval System (TEKTRAN)

    All-female triploid fish are advantageous in rainbow trout (Oncorhynchus mykiss) aquaculture due to sterility and the consequent superior fillet quality, growth, and feed conversion achieved at reproductive size. Triploid fish are commonly produced by pressure or temperature shock of the zygote (in...

  5. Advanced Light Source beam position monitor

    SciTech Connect

    Hinkson, J.

    1991-10-28

    The Advanced Light Source (ALS) is a synchrotron radiation facility nearing completion at LBL. As a third-generation machine, the ALS is designed to produce intense light from bend magnets, wigglers, and undulators (insertion devices). The facility will include a 50 MeV electron linear accelerator, a 1.5 GeV booster synchrotron, beam transport lines, a 1--2 GeV storage ring, insertion devices, and photon beam lines. Currently, the beam injection systems are being commissioned, and the storage ring is being installed. Electron beam position monitors (BPM) are installed throughout the accelerator and constitute the major part of accelerator beam diagnostics. The design of the BPM instruments is complete, and 50 units have been constructed for use in the injector systems. We are currently fabricating 100 additional instruments for the storage ring. In this paper I discuss engineering fabrication, testing and performance of the beam pickup electrodes and the BPM electronics.

  6. 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.

  7. Advanced Containment System

    DOEpatents

    Kostelnik, Kevin M.; Kawamura, Hideki; Richardson, John G.; Noda, Masaru

    2005-02-08

    An advanced containment system for containing buried waste and associated leachate. The advanced containment system comprises a plurality of casing sections with each casing section interlocked to an adjacent casing section. Each casing section includes a complementary interlocking structure that interlocks with the complementary interlocking structure on an adjacent casing section. A barrier filler substantially fills the casing sections and may substantially fill the spaces of the complementary interlocking structure to form a substantially impermeable barrier. Some of the casing sections may include sensors so that the casing sections and the zone of interest may be remotely monitored after the casing sections are emplaced in the ground.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. Technological advances in teleradiology.

    PubMed

    Orphanoudakis, S C; Kaldoudi, E; Tsiknakis, M

    1996-06-01

    Teleradiology consists of a set of added-value telematic services, implemented over an advanced telecommunications infrastructure and supported by different information technologies and related applications. The main goal of teleradiology is to provide different levels of support for remote diagnostic imaging procedures. This paper considers technological advances in this important area, including a discussion of the various added-value telematic services, applications supporting these services, and the required information technology and telecommunications infrastructure. Teleradiology is also considered in the general context of an integrated regional health telematics network, emphasizing its role and its interaction with other information and networking services. PMID:8832235

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. Magnet costs for the Advanced Light Source

    SciTech Connect

    Tanabe, J.; Krupnick, J.; Hoyer, E.; Paterson, A.

    1993-05-01

    The Advanced Light Source (ALS) accelerator is now completed. The numerous conventional magnets required for the booster ring, the storage ring and the low and high energy transfer lines were installed during the last two years. This paper summarizes the various costs associated with the quantity fabrication of selected magnet families. These costs include the costs of prototypes, tooling, coil and core fabrication, assembly and magnetic measurements. Brief descriptions of the magnets and specialized requirements for magnetic measurements are included in order to associate the costs with the relative complexities of the various magnet systems.

  18. 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

  19. Uncooled thermal imaging sensor and application advances

    NASA Astrophysics Data System (ADS)

    Norton, Peter W.; Cox, Stephen; Murphy, Bob; Grealish, Kevin; Joswick, Mike; Denley, Brian; Feda, Frank; Elmali, Loriann; Kohin, Margaret

    2006-05-01

    BAE Systems continues to advance the technology and performance of microbolometer-based thermal imaging modules and systems. 640x480 digital uncooled infrared focal plane arrays are in full production, illustrated by recent production line test data for two thousand focal plane arrays. This paper presents a snapshot of microbolometer technology at BAE Systems and an overview of two of the most important thermal imaging sensor programs currently in production: a family of thermal weapons sights for the United States Army and a thermal imager for the remote weapons station on the Stryker vehicle.

  20. 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.

  1. Off-Line Catalog Production.

    ERIC Educational Resources Information Center

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

    The Ohio College Library Center's off-line catalog system is a limited technique for production of card catalogs. Unlike the on-line system, it cannotmake the resources of a region available to users in an individual institution, and it does not have the potential for significantly reducing rate of rise of library per-unit costs. In short, it is…

  2. Wiswesser Line Notation: An Introduction.

    ERIC Educational Resources Information Center

    Vollmer, John J.

    1983-01-01

    Wiswesser Line Notation, a system for representing structural formulas by a single line of common symbols (numerals, capital letters, and three punctuation marks), is gaining acceptance as an effective indexing tool. The resulting notations, denoting specific structural fragments of a molecule, can be retrieved by humans or computer. (Author/JN)

  3. 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).

  4. 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.

  5. On-line and Mobil Learning Activities

    NASA Astrophysics Data System (ADS)

    Ackerman, S. A.; Whittaker, T. M.; Jasmin, T.; Mooney, M. E.

    2012-12-01

    Introductory college-level science courses for non-majors are critical gateways to imparting not only discipline-specific information, but also the basics of the scientific method and how science influences society. They are also indispensable for student success to degree. On-line, web-based homework (whether on computers or mobile devices) is a rapidly growing use of the Internet and is becoming a major component of instruction in science, replacing delayed feedback from a few major exams. Web delivery and grading of traditional textbook-type questions is equally effective as having students write them out for hand grading, as measured by student performance on conceptual and problem solving exams. During this presentation we will demonstrate some of the interactive on-line activities used to teach concepts and how scientists approach problem solving, and how these activities have impacted student learning. Evaluation of the activities, including formative and summative, will be discussed and provide evidence that these interactive activities significantly enhance understanding of introductory meteorological concepts in a college-level science course. More advanced interactive activities are also used in our courses for department majors, some of these will be discussed and demonstrated. Bring your mobile devices to play along! Here is an example on teaching contouring: http://profhorn.aos.wisc.edu/wxwise/contour/index.html

  6. [Recent advances in transmissible tumors].

    PubMed

    Tingting, Yin; Lu, Wang; Guodong, Wang

    2015-11-01

    Transmissible tumors are a class of tumor that can be transmitted between individuals through living cells. So far, four types of transmissible tumors including canine transmissible venereal tumor (CTVT),Tasmanian devil facial tumor disease (DFTD), soft-shell clams leukemia (SSCL), and hamsters reticulum cell sarcoma (HRCS)have been discovered and identified. In the last decades, these transmissible tumors have been proved to be transmitted through living cells by cytological, histological and genetic studies. CTVT, the oldest mammalian somatic cell line, and DFTD originated from Schwann cell have been reported to avoid immunological recognition by down-regulating MHC expression, while a high copy number of Steamer retrotransposon is commonly exist in SSCL. In recent years, the whole-genome sequencing of CTVT and DFTD have been completed which facilitates studies on the mechanisms of tumorigenesis, transmission and evolution of transmissible tumors at the whole-genome level. In this review, we summarize the recent advances in transmissible tumors and discuss the research focus in next decade. PMID:26582522

  7. Advances in managing hepatocellular carcinoma.

    PubMed

    Reataza, Marielle; Imagawa, David K

    2014-06-01

    Multiple modalities for treatment of hepatocellular carcinoma are available, depending on tumor size and number. Surgical resection remains the gold standard, so long as the residual liver function reserve is sufficient. In patients with advanced cirrhosis, liver transplantation is the preferred option, as these patients may not have adequate hepatic reserve after resection. Salvage liver transplantation has also become an option for a select few patients who recur after surgical resection. Ablative techniques have been used for palliation as well as to either completely destroy the tumor, act as an adjunct to resection, or downstage the tumor to meet Milan criteria such that a patient may be a candidate for liver transplantation. Radiofrequency ablation, microwave ablation, chemoembolization, radioembolization, and irreversible electroporation have all been used in this capacity. Currently, sorafenib is the only US Food and Drug Administration-approved chemotherapeutic for hepatocellular carcinoma. The efficacy of sorafenib, in combination with other agents, transarterial chemoembolization, and surgical resection is currently being investigated. Sunitinib and brivanib, tyrosine kinase inhibitors, have failed as potential first- or second-line options for chemotherapy. Bevacizumab in combination with erlotinib is also currently being studied. Final analysis for ramucirumab and axitinib are pending. Tivantinib, a selective mesenchymal-epithelial transition factor (MET) inhibitor, is also undergoing clinical trials for efficacy in MET-high tumors. This review serves to emphasize the current and new technologies emerging in the treatment of hepatocellular carcinoma. PMID:24810646

  8. 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.

  9. 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.

  10. 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…

  11. Advanced Test Reactor Tour

    ScienceCinema

    Miley, Don

    2013-05-28

    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. Technological advances transforming rheumatology

    PubMed Central

    Robinson, William H.; Mao, Rong

    2016-01-01

    Technological advances over the past decade have revolutionized many areas of rheumatology, ranging from diagnosis, prognosis and therapeutic development to the mechanistic understanding of rheumatic diseases. This overview highlights key technological innovations and discusses the major impact that these developments are having on research and clinical practice. PMID:26439404

  13. 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.

  14. Advances in photoprotection.

    PubMed

    Baron, Elma D; Kirkland, Eugene B; Domingo, Diana Santo

    2008-08-01

    Major advancements in the realm of photoprotection have occurred over the last decade providing potential means to reduce the prevalence of ultraviolet radiation-related skin problems. This review elucidates current photoprotective methods and recent developments that may hold future promise. PMID:18819220

  15. 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…

  16. Skimming & Scanning. Advanced Level.

    ERIC Educational Resources Information Center

    Fry, Edward B.

    Part of a series intended to develop essential specialized reading skills, this text/workbook is designed to provide instruction and practice in skimming and scanning for students reading at the seventh through tenth grade reading levels, considered the advanced level. Part 1 of the book deals with skimming. A lesson defines skimming (the rapid…

  17. 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)…

  18. Impedance cardiography: recent advancements.

    PubMed

    Cybulski, Gerard; Strasz, Anna; Niewiadomski, Wiktor; Gąsiorowska, Anna

    2012-01-01

    The aim of this paper is the presentation of recent advancements in impedance cardiography regarding methodical approach, applied equipment and clinical or research implementations. The review is limited to the papers which were published over last 17 months (dated 2011 and 2012) in well recognised scientific journals. PMID:23042327

  19. 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

  20. NIST ADVANCED TECHNOLOGY PROGRAM

    EPA Science Inventory

    Not-yet-possible technologies are the domain of the National Institute of Standards and Technology (NIST) Advanced Technology Program. The ATP is a unique partnership between government and private industry to accelerate the development of high-risk technologies that promise sign...

  1. 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…

  2. 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.

  3. 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.

  4. 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.

  5. Management of advanced melanoma

    SciTech Connect

    Nathanson, L. )

    1986-01-01

    This book presents papers on the subject of management of advanced melanoma. The topics covered are: non-investigational cytotoxic agents; high-dosage chemotherapy in antologous bone marrow transplantation; Radiotherapy of melanomas; hyperthermia; ureal melanoma; surgical treatment of recurrent a metastatic melanoma; role of interferons in management of melanoma and molecular genetics of melanoma.

  6. Advancing Student Achievement

    ERIC Educational Resources Information Center

    Walberg, Herbert J.

    2010-01-01

    For the last half century, higher spending and many modern reforms have failed to raise the achievement of students in the United States to the levels of other economically advanced countries. A possible explanation, says Herbert Walberg, is that much current education theory is ill informed about scientific psychology, often drawing on fads and…

  7. 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…

  8. 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.

  9. Advances in satellite oceanography

    NASA Technical Reports Server (NTRS)

    Brown, O. B.; Cheney, R. E.

    1983-01-01

    Technical advances and recent applications of active and passive satellite remote sensing techniques to the study of oceanic processes are summarized. The general themes include infrared and visible radiometry, active and passive microwave sensors, and buoy location systems. The surface parameters of sea surface temperature, windstream, sea state, altimetry, color, and ice are treated as applicable under each of the general methods.

  10. 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.

  11. 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)

  12. 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.

  13. 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 ...

  14. Cartoons as Advance Organizers

    ERIC Educational Resources Information Center

    Kovalik, Cindy L.; Williams, Matthew A.

    2011-01-01

    This exploratory study investigated student reaction to the use of cartoons as advance organizers for online discussions in an online course. A convenience sample of 15 students participated in the study by contributing cartoons, participating in online discussions, and completing a survey. Overall, survey results indicated student reaction to the…

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  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 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.

  1. Advanced planetary studies

    NASA Technical Reports Server (NTRS)

    1978-01-01

    Eleven study tasks are described and key results are discussed for the following: advanced planning activity; cost estimation research; planetary missions performance handbooks-revisions; multiple discipline science assessment; asteroid workshop; galilean lander mission strategies; asteroid exploration study; ion drive transport capabilities; Mars strategy study; Venus surface sample return; and ion drive/solar sail assessment study.

  2. Advanced electric vehicle

    SciTech Connect

    O'Connell, L.G.

    1980-07-01

    The Advanced Electric Vehicle is defined as an automobile which can fulfill the general-purpose role of today's internal-combustion-engine-powered car without utilizing petroleum fuels directly. It relies principally on the utilization of electricity. A number of candidate systems are described. The present status of each is discussed as are the problems to be overcome before implementation can proceed.

  3. 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.

  4. Where Advancement Fails.

    ERIC Educational Resources Information Center

    Trachtman, Leon E.

    1987-01-01

    Faculty members and advancement officers tend to come from different environments and to inhabit different worlds. The failure of the two to understand one another and work together in the interest of their institutions is discussed. The central administration must serve as a bridge between the two. (MLW)

  5. 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…

  6. Horizontal drilling technology advances

    SciTech Connect

    Not Available

    1991-03-04

    Horizontal drilling technology is making further advances in the Texas Austin chalk play as such drilling continues to spread in many U.S. land areas. One company has completed a Cretaceous Austin chalk oil well with the longest horizontal well bore in Texas and what at 1 1/6 miles is believed to be the world's longest medium radius horizontal displacement.

  7. Advanced Chemical Propulsion

    NASA Astrophysics Data System (ADS)

    Alexander, L.

    2004-11-01

    Improving the performance and reliability characteristics of chemical propulsion systems requires research and testing of higher-performance propellants, higher efficiency thrusters, cryogenics technology, lightweight components and advancements in propulsion system design and assessment. Propellants are being investigated to identify practical combinations with higher efficiencies and better thermal properties to reduce thermal control requirements. This includes combinations with modest increases, such as LOX-hydrazine, as well as a new evaluation of major improvements available from fluorine-bearing oxidizers. Practical ways of implementing cryogenic propulsion to further increase efficiency are also being studied. Some potential advances include small pump-fed engines, and improvements in cryocooler technology and tank pressure control. Gelled propellants will be tested to determine the practicality of letting propellants freeze at low environmental temperatures and thawing them only when required for use. The propellant tank is typically the single highest non-expendable mass in a chemical propulsion system. Lightweight tank designs, materials and methods of fabrication are being investigated. These are projected to offer a 45-50 percent decrease in tank mass, representing the potential inert system mass savings. Mission and systems analyses are being conducted to guide the technology research and set priorities for technology investment, based on estimated gains in payload and mission capabilities. This includes development of advanced assessment tools and analyses of specific missions selected from Science Missions' Directorate. The goal is to mature a suite of reliable advanced propulsion technologies that will promote more cost efficient missions through the reduction of interplanetary trip time, increased scientific payload mass fraction and longer on-station operations. This talk will review the Advanced Chemical technology development roadmap, current

  8. 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.

  9. 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…

  10. Advances in neuroblastoma research

    SciTech Connect

    Evans, A.E.; D'Angio, G.J.; Seeger, R.C.

    1985-01-01

    This book contains over 50 papers. Some of the titles are: Studies on the expression of the amplified domain in human neuroblastoma cells; Comparison studies of oncogenes in retinoblastoma and neuroblastoma; Chromosome abnormalities, gene amplification and tumor progression; and Peripheral neuroepithelioma: Genetic analysis of tumor derived cell lines.

  11. 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.

  12. 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.

  13. 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.

  14. Advanced Space Propulsion

    NASA Technical Reports Server (NTRS)

    Frisbee, Robert H.

    1996-01-01

    This presentation describes a number of advanced space propulsion technologies with the potential for meeting the need for dramatic reductions in the cost of access to space, and the need for new propulsion capabilities to enable bold new space exploration (and, ultimately, space exploitation) missions of the 21st century. For example, current Earth-to-orbit (e.g., low Earth orbit, LEO) launch costs are extremely high (ca. $10,000/kg); a factor 25 reduction (to ca. $400/kg) will be needed to produce the dramatic increases in space activities in both the civilian and government sectors identified in the Commercial Space Transportation Study (CSTS). Similarly, in the area of space exploration, all of the relatively 'easy' missions (e.g., robotic flybys, inner solar system orbiters and landers; and piloted short-duration Lunar missions) have been done. Ambitious missions of the next century (e.g., robotic outer-planet orbiters/probes, landers, rovers, sample returns; and piloted long-duration Lunar and Mars missions) will require major improvements in propulsion capability. In some cases, advanced propulsion can enable a mission by making it faster or more affordable, and in some cases, by directly enabling the mission (e.g., interstellar missions). As a general rule, advanced propulsion systems are attractive because of their low operating costs (e.g., higher specific impulse, ISD) and typically show the most benefit for relatively 'big' missions (i.e., missions with large payloads or AV, or a large overall mission model). In part, this is due to the intrinsic size of the advanced systems as compared to state-of-the-art (SOTA) chemical propulsion systems. Also, advanced systems often have a large 'infrastructure' cost, either in the form of initial R&D costs or in facilities hardware costs (e.g., laser or microwave transmission ground stations for beamed energy propulsion). These costs must then be amortized over a large mission to be cost-competitive with a SOTA

  15. In-line hydraulic dashpot

    NASA Astrophysics Data System (ADS)

    Moody, Paul E.

    1992-10-01

    An in-line hydraulic dashpot is disclosed that effectively decelerates the piston of a power cylinder by controllably choking off the oil which is providing pressure to the piston. The in-line hydraulic dashpot of the invention includes a valve spool member movable between an open and closed position along a fluid flow path that supplies oil to the power cylinder. An actuator rod is cooperative with the valve spool member and the piston shaft of the power cylinder to move tile valve spool member between its open and closed positions. The in-line hydraulic dashpot eliminates the clashing of mechanical parts and therewith eliminates the noise that would otherwise be generated thereby. The in-line hydraulic dashpot of the present invention makes possible the adaptation of a fixed stroke power cylinder to applications that call for a variable stroke length.

  16. Coplanar Waveguide Radial Line Stub

    NASA Technical Reports Server (NTRS)

    Simons, R. N.; Taub, S. R.

    1993-01-01

    A coplanar waveguide radial line stub resonator is experimentally characterized with respect to stub radius, sectoral angle, substrate thickness, and relative dielectric constant. A simple closed-form design equation which predicts the resonance radius of the stub is presented.

  17. Winslow Homer: "The Life Line."

    ERIC Educational Resources Information Center

    Brigham, Diane

    1986-01-01

    Using a color print of Winslow Homer's oil painting, "The Life Line," the goal of this senior high school art lesson is to have students debate the importance of dramatic effect in a work of art. (JDH)

  18. Umbilic Lines in Orientational Order

    NASA Astrophysics Data System (ADS)

    Machon, Thomas; Alexander, Gareth P.

    2016-01-01

    Three-dimensional orientational order in systems whose ground states possess nonzero gradients typically exhibits linelike structures or defects: λ lines in cholesterics or Skyrmion tubes in ferromagnets, for example. Here, we show that such lines can be identified as a set of natural geometric singularities in a unit vector field, the generalization of the umbilic points of a surface. We characterize these lines in terms of the natural vector bundles that the order defines and show that they give a way to localize and identify Skyrmion distortions in chiral materials—in particular, that they supply a natural representative of the Poincaré dual of the cocycle describing the topology. Their global structure leads to the definition of a self-linking number and helicity integral which relates the linking of umbilic lines to the Hopf invariant of the texture.

  19. Line competition in gas lasers

    SciTech Connect

    Pikulev, A A

    2000-08-31

    Simultaneous lasing on two lines having a common upper level is analysed. Within the framework of the two-level model, a formula for the gain in each line is obtained. Two possible types of line competition are found: symbiosis and quenching. It is shown that competition in the quenching regime can be used to study the rates of population of the lower levels. The results are illustrated by competition diagrams for the 2.65-{mu}m and 2.03-{mu}m of the Xe atom in the Ar-Xe mixture and the 703.2-nm and 724.5-nm lines of the Ne atom in the Ne-Ar mixture. (active media)

  20. 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)