Genotyping-by-sequencing provides the discriminating power to investigate the subspecies of Daucus carota (Apiaceae)

USDA-ARS?s Scientific Manuscript database

Premise of study: Premise of study: The taxonomic classification of the subspecies of Daucus carota is unresolved. Intercrosses among traditionally recognized subspecies has been well-documented, as have intercrosses with other Daucus species containing 2n = 18 chromosomes (D. sahariensis and D. syr...

The genetics of rhizosheath size in a multiparent mapping population of wheat.

PubMed

Delhaize, Emmanuel; Rathjen, Tina M; Cavanagh, Colin R

2015-08-01

Rhizosheaths comprise soil that adheres to plant roots and, in some species, are indicative of root hair length. In this study, the genetics of rhizosheath size in wheat was investigated by screening the progeny of multiparent advanced generation intercrosses (MAGIC). Two MAGIC populations were screened for rhizosheath size using a high throughput method. One MAGIC population was developed from intercrosses between four parents (4-way) and the other from intercrosses between eight parents (8-way). Transgressive segregation for rhizosheath size was observed in both the 4-way and 8-way MAGIC populations. A quantitative trait loci (QTL) analysis of the 4-way population identified six major loci located on chromosomes 2B, 4D, 5A, 5B, 6A, and 7A together accounting for 42% of the variation in rhizosheath size. Rhizosheath size was strongly correlated with root hair length and was robust across different soil types in the absence of chemical constraints. Rhizosheath size in the MAGIC populations was a reliable surrogate for root hair length and, therefore, the QTL identified probably control root hair elongation. Members of the basic helix-loop-helix family of transcription factors have previously been identified to regulate root hair length in Arabidopsis and rice. Since several wheat members of the basic helix-loop-helix family of genes are located within or near the QTL, these genes are candidates for controlling the long root hair trait. The QTL for rhizosheath size identified in this study provides the opportunity to implement marker-assisted selection to increase root hair length for improved phosphate acquisition in wheat. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Leapfrogging: primordial germ cell transplantation permits recovery of CRISPR/Cas9-induced mutations in essential genes

PubMed Central

Fish, Margaret B.; Cho, Ken W. Y.

2016-01-01

CRISPR/Cas9 genome editing is revolutionizing genetic loss-of-function analysis but technical limitations remain that slow progress when creating mutant lines. First, in conventional genetic breeding schemes, mosaic founder animals carrying mutant alleles are outcrossed to produce F1 heterozygotes. Phenotypic analysis occurs in the F2 generation following F1 intercrosses. Thus, mutant analyses will require multi-generational studies. Second, when targeting essential genes, efficient mutagenesis of founders is often lethal, preventing the acquisition of mature animals. Reducing mutagenesis levels may improve founder survival, but results in lower, more variable rates of germline transmission. Therefore, an efficient approach to study lethal mutations would be useful. To overcome these shortfalls, we introduce ‘leapfrogging’, a method combining efficient CRISPR mutagenesis with transplantation of mutated primordial germ cells into a wild-type host. Tested using Xenopus tropicalis, we show that founders containing transplants transmit mutant alleles with high efficiency. F1 offspring from intercrosses between F0 animals that carry embryonic lethal alleles recapitulate loss-of-function phenotypes, circumventing an entire generation of breeding. We anticipate that leapfrogging will be transferable to other species. PMID:27385011

Genetic architecture of natural variation in Drosophila melanogaster aggressive behavior

PubMed Central

Shorter, John; Couch, Charlene; Huang, Wen; Carbone, Mary Anna; Peiffer, Jason; Anholt, Robert R. H.; Mackay, Trudy F. C.

2015-01-01

Aggression is an evolutionarily conserved complex behavior essential for survival and the organization of social hierarchies. With the exception of genetic variants associated with bioamine signaling, which have been implicated in aggression in many species, the genetic basis of natural variation in aggression is largely unknown. Drosophila melanogaster is a favorable model system for exploring the genetic basis of natural variation in aggression. Here, we performed genome-wide association analyses using the inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and replicate advanced intercross populations derived from the most and least aggressive DGRP lines. We identified genes that have been previously implicated in aggressive behavior as well as many novel loci, including gustatory receptor 63a (Gr63a), which encodes a subunit of the receptor for CO2, and genes associated with development and function of the nervous system. Although genes from the two association analyses were largely nonoverlapping, they mapped onto a genetic interaction network inferred from an analysis of pairwise epistasis in the DGRP. We used mutations and RNAi knock-down alleles to functionally validate 79% of the candidate genes and 75% of the candidate epistatic interactions tested. Epistasis for aggressive behavior causes cryptic genetic variation in the DGRP that is revealed by changing allele frequencies in the outbred populations derived from extreme DGRP lines. This phenomenon may pertain to other fitness traits and species, with implications for evolution, applied breeding, and human genetics. PMID:26100892

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

PubMed

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

2013-01-01

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

Worse Renal Disease in Postmenopausal F2[Dahl S x R]-Intercross Rats: Detection of Novel QTLs Affecting Hypertensive Kidney Disease

PubMed Central

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

2013-01-01

The prevalence of hypertension increases after menopause with 75% of postmenopausal women developing hypertension in the United States, along with hypertensive end organ diseases. While human and animal model studies have indicated a protective role for estrogen against cardiovascular disease and glomerulosclerosis, clinical studies of hormone replacement therapy in postmenopausal women have shown polar results with some improvement in hypertension but worsening of hypertensive kidney disease, or no effect at all. These observations suggest that the pathogenesis of postmenopausal hypertension and its target organ complications is more complex than projected, and that loss of endogenous estrogens induces epigenetic changes that alter genetic susceptibility to end-organ complications per se resulting in pathogenetic mechanisms beyond correction by hormone replacement. We studied postmenopausal-induced changes in renal disease and performed a total genome scan for quantitative trait loci (QTLs) affecting kidney disease in postmenopausal 16m-old F2[Dahl S x R]-intercross female rats. We used glomerular injury score (GIS) as quantitative trait. We compared QTLs amongst premenopausal, ovariectomized and postmenopausal F2[Dahl S x R]-intercross rats using identical phenotype characterization. Postmenopausal F2[Dahl S x R]-intercross rats exhibited increased hypertensive glomerulosclerosis (P<0.01) and equivalent levels of kidney disease when compared to premenopausal and ovariectomized F2[Dahl S x R]-intercross rats respectively. We detected three significant to highly significant GIS-QTLs (GIS-pm1 on chromosome 4, LOD 3.54; GIS-pm2 on chromosome 3, LOD 2.72; GIS-pm3 on chromosome 5, LOD 2.37) and two suggestive GIS-QTLs (GIS-pm4 on chromosome 2, LOD 1.70; GIS-pm5 on chromosome 7, LOD 1.28), all of which were unique to this postmenopausal population. Detection of increased renal disease phenotype in postmenopausal and ovariectomized subjects suggests a protective role of ovarian hormones. Furthermore, the detection of distinct GIS-QTLs in postmenopausal intercross female rats suggests that distinct genetic mechanisms underlie hypertensive glomerulosclerosis in premenopausal and postmenopausal states. PMID:23393608

Exercise and diet affect quantitative trait loci for body weight and composition traits in an advanced intercross population of mice

PubMed Central

Kelly, Scott A.; Hua, Kunjie; Pomp, Daniel

2012-01-01

Driven by the recent obesity epidemic, interest in understanding the complex genetic and environmental basis of body weight and composition is great. We investigated this by searching for quantitative trait loci (QTLs) affecting a number of weight and adiposity traits in a G10 advanced intercross population produced from crosses of mice in inbred strain C57BL/6J with those in a strain selected for high voluntary wheel running. The mice in this population were fed either a high-fat or a control diet throughout the study and also measured for four exercise traits prior to death, allowing us to test for pre- and postexercise QTLs as well as QTL-by-diet and QTL-by-exercise interactions. Our genome scan uncovered a number of QTLs, of which 40% replicated QTLs previously found for similar traits in an earlier (G4) generation. For those replicated QTLs, the confidence intervals were reduced from an average of 19 Mb in the G4 to 8 Mb in the G10. Four QTLs on chromosomes 3, 8, 13, and 18 were especially prominent in affecting the percentage of fat in the mice. About of all QTLs showed interactions with diet, exercise, or both, their genotypic effects on the traits showing a variety of patterns depending on the diet or level of exercise. It was concluded that the indirect effects of these QTLs provide an underlying genetic basis for the considerable variability in weight or fat loss typically found among individuals on the same diet and/or exercise regimen. PMID:23048196

Water Deficit and Salinity Stress Reveal Many Specific QTL for Plant Growth and Fruit Quality Traits in Tomato

PubMed Central

Diouf, Isidore A.; Derivot, Laurent; Bitton, Frédérique; Pascual, Laura; Causse, Mathilde

2018-01-01

Quality is a key trait in plant breeding, especially for fruit and vegetables. Quality involves several polygenic components, often influenced by environmental conditions with variable levels of genotype × environment interaction that must be considered in breeding strategies aiming to improve quality. In order to assess the impact of water deficit and salinity on tomato fruit quality, we evaluated a multi-parent advanced generation intercross (MAGIC) tomato population in contrasted environmental conditions over 2 years, one year in control vs. drought condition and the other in control vs. salt condition. Overall 250 individual lines from the MAGIC population—derived from eight parental lines covering a large diversity in cultivated tomato—were used to identify QTL in both experiments for fruit quality and yield component traits (fruit weight, number of fruit, Soluble Solid Content, firmness), phenology traits (time to flower and ripe) and a vegetative trait, leaf length. All the traits showed a large genotype variation (33–86% of total phenotypic variation) in both experiments and high heritability whatever the year or treatment. Significant genotype × treatment interactions were detected for five of the seven traits over the 2 years of experiments. QTL were mapped using 1,345 SNP markers. A total of 54 QTL were found among which 15 revealed genotype × environment interactions and 65% (35 QTL) were treatment specific. Confidence intervals of the QTL were projected on the genome physical map and allowed identifying regions carrying QTL co-localizations, suggesting pleiotropic regulation. We then applied a strategy for candidate gene detection based on the high resolution mapping offered by the MAGIC population, the allelic effect of each parental line at the QTL and the sequence information of the eight parental lines. PMID:29559986

Achievements and prospects of genomics-assisted breeding in three legume crops of the semi-arid tropics.

PubMed

Varshney, Rajeev K; Mohan, S Murali; Gaur, Pooran M; Gangarao, N V P R; Pandey, Manish K; Bohra, Abhishek; Sawargaonkar, Shrikant L; Chitikineni, Annapurna; Kimurto, Paul K; Janila, Pasupuleti; Saxena, K B; Fikre, Asnake; Sharma, Mamta; Rathore, Abhishek; Pratap, Aditya; Tripathi, Shailesh; Datta, Subhojit; Chaturvedi, S K; Mallikarjuna, Nalini; Anuradha, G; Babbar, Anita; Choudhary, Arbind K; Mhase, M B; Bharadwaj, Ch; Mannur, D M; Harer, P N; Guo, Baozhu; Liang, Xuanqiang; Nadarajan, N; Gowda, C L L

2013-12-01

Advances in next-generation sequencing and genotyping technologies have enabled generation of large-scale genomic resources such as molecular markers, transcript reads and BAC-end sequences (BESs) in chickpea, pigeonpea and groundnut, three major legume crops of the semi-arid tropics. Comprehensive transcriptome assemblies and genome sequences have either been developed or underway in these crops. Based on these resources, dense genetic maps, QTL maps as well as physical maps for these legume species have also been developed. As a result, these crops have graduated from 'orphan' or 'less-studied' crops to 'genomic resources rich' crops. This article summarizes the above-mentioned advances in genomics and genomics-assisted breeding applications in the form of marker-assisted selection (MAS) for hybrid purity assessment in pigeonpea; marker-assisted backcrossing (MABC) for introgressing QTL region for drought-tolerance related traits, Fusarium wilt (FW) resistance and Ascochyta blight (AB) resistance in chickpea; late leaf spot (LLS), leaf rust and nematode resistance in groundnut. We critically present the case of use of other modern breeding approaches like marker-assisted recurrent selection (MARS) and genomic selection (GS) to utilize the full potential of genomics-assisted breeding for developing superior cultivars with enhanced tolerance to various environmental stresses. In addition, this article recommends the use of advanced-backcross (AB-backcross) breeding and development of specialized populations such as multi-parents advanced generation intercross (MAGIC) for creating new variations that will help in developing superior lines with broadened genetic base. In summary, we propose the use of integrated genomics and breeding approach in these legume crops to enhance crop productivity in marginal environments ensuring food security in developing countries. Copyright © 2012 Elsevier Inc. All rights reserved.

The genetic basis of flecking and its relationship to disease resistance in the IBM maize mapping population.

PubMed

Vontimitta, Vijay; Olukolu, Bode A; Penning, Bryan W; Johal, Gurmukh; Balint-Kurti, P J

2015-11-01

In this paper, we determine the genetic architecture controlling leaf flecking in maize and investigate its relationship to disease resistance and the defense response. Flecking is defined as a mild, often environmentally dependent lesion phenotype observed on the leaves of several commonly used maize inbred lines. Anecdotal evidence suggests a link between flecking and enhanced broad-spectrum disease resistance. Neither the genetic basis underlying flecking nor its possible relationship to disease resistance has been systematically evaluated. The commonly used maize inbred Mo17 has a mild flecking phenotype. The IBM-advanced intercross mapping population, derived from a cross between Mo17 and another commonly used inbred B73, has been used for mapping a number of traits in maize including several related to disease resistance. In this study, flecking was assessed in the IBM population over 6 environments. Several quantitative trait loci for flecking were identified, with the strongest one located on chromosome 6. Low but moderately significant correlations were observed between stronger flecking and higher disease resistance with respect to two diseases, southern leaf blight and northern leaf blight and between stronger flecking and a stronger defense response.

QGene 4.0, an extensible Java QTL-analysis platform.

PubMed

Joehanes, Roby; Nelson, James C

2008-12-01

Of many statistical methods developed to date for quantitative trait locus (QTL) analysis, only a limited subset are available in public software allowing their exploration, comparison and practical application by researchers. We have developed QGene 4.0, a plug-in platform that allows execution and comparison of a variety of modern QTL-mapping methods and supports third-party addition of new ones. The software accommodates line-cross mating designs consisting of any arbitrary sequence of selfing, backcrossing, intercrossing and haploid-doubling steps that includes map, population, and trait simulators; and is scriptable. Software and documentation are available at http://coding.plantpath.ksu.edu/qgene. Source code is available on request.

Exclusion of EDNRB and KIT as the basis for white spotting in Border Collies.

PubMed

Metallinos, D; Rine, J

2000-01-01

White spotting patterns in mammals can be caused by mutations in the genes for the endothelin B receptor and c-Kit, whose protein products are necessary for proper migration, differentiation or survival of the melanoblast population of cells. Although there are many different dog breeds that segregate white spotting patterns, no genes have been identified that are linked to these phenotypes. An intercross was generated from a female Newfoundland and a male Border Collie and the white spotting phenotypes of the intercross progeny were evaluated by measuring percentage surface area of white in the puppies. The Border Collie markings segregated as a simple autosomal recessive (7/25 intercross progeny had the phenotype). Two candidate genes, for the endothelin B receptor (EDNRB) and c-Kit (KIT), were evaluated for segregation with the white spotting pattern. Polymorphisms between the Border Collie and Newfoundland were identified for EDNRB using Southern analysis after a portion of the canine gene had been cloned. Polymorphisms for KIT were identified using a microsatellite developed from a bacterial artificial chromosome containing the canine gene. Both EDNRB and KIT were excluded as a cause of the white spotting pattern in at least two of the intercross progeny. Although these genes have been implicated in white spotting in other mammals, including horses, pigs, cows, mice and rats, they do not appear to be responsible for the white spotting pattern found in the Border Collie breed of dog.

Exclusion of EDNRB and KIT as the basis for white spotting in Border Collies

PubMed Central

Metallinos, Danika; Rine, Jasper

2000-01-01

Background: White spotting patterns in mammals can be caused by mutations in the genes for the endothelin B receptor and c-Kit, whose protein products are necessary for proper migration, differentiation or survival of the melanoblast population of cells. Although there are many different dog breeds that segregate white spotting patterns, no genes have been identified that are linked to these phenotypes. Results: An intercross was generated from a female Newfoundland and a male Border Collie and the white spotting phenotypes of the intercross progeny were evaluated by measuring percentage surface area of white in the puppies. The Border Collie markings segregated as a simple autosomal recessive (7/25 intercross progeny had the phenotype). Two candidate genes, for the endothelin B receptor (EDNRB) and c-Kit (KIT), were evaluated for segregation with the white spotting pattern. Polymorphisms between the Border Collie and Newfoundland were identified for EDNRB using Southern analysis after a portion of the canine gene had been cloned. Polymorphisms for KIT were identified using a microsatellite developed from a bacterial artificial chromosome containing the canine gene. Conclusions: Both EDNRB and KIT were excluded as a cause of the white spotting pattern in at least two of the intercross progeny. Although these genes have been implicated in white spotting in other mammals, including horses, pigs, cows, mice and rats, they do not appear to be responsible for the white spotting pattern found in the Border Collie breed of dog. PMID:11178229

Genetics and Genomics of Social Behavior in a Chicken Model.

PubMed

Johnsson, Martin; Henriksen, Rie; Fogelholm, Jesper; Höglund, Andrey; Jensen, Per; Wright, Dominic

2018-05-01

The identification of genes affecting sociality can give insights into the maintenance and development of sociality and personality. In this study, we used the combination of an advanced intercross between wild and domestic chickens with a combined QTL and eQTL genetical genomics approach to identify genes for social reinstatement, a social and anxiety-related behavior. A total of 24 social reinstatement QTL were identified and overlaid with over 600 eQTL obtained from the same birds using hypothalamic tissue. Correlations between overlapping QTL and eQTL indicated five strong candidate genes, with the gene TTRAP being strongly significantly correlated with multiple aspects of social reinstatement behavior, as well as possessing a highly significant eQTL. Copyright © 2018 by the Genetics Society of America.

Genetic architecture of adiposity and organ weight using combined generation QTL analysis.

PubMed

Fawcett, Gloria L; Roseman, Charles C; Jarvis, Joseph P; Wang, Bing; Wolf, Jason B; Cheverud, James M

2008-08-01

We present here a detailed study of the genetic contributions to adult body size and adiposity in the LG,SM advanced intercross line (AIL), an obesity model. This study represents a first step in fine-mapping obesity quantitative trait loci (QTLs) in an AIL. QTLs for adiposity in this model were previously isolated to chromosomes 1, 6, 7, 8, 9, 12, 13, and 18. This study focuses on heritable contributions and the genetic architecture of fatpad and organ weights. We analyzed both the F(2) and F(3) generations of the LG,SM AIL population single-nucleotide polymorphism (SNP) genotyped with a marker density of approximately 4 cM. We replicate 88% of the previously identified obesity QTLs and identify 13 new obesity QTLs. Nearly half of the single-trait QTLs were sex-specific. Several broad QTL regions were resolved into multiple, narrower peaks. The 113 single-trait QTLs for organs and body weight clustered into 27 pleiotropic loci. A large number of epistatic interactions are described which begin to elucidate potential interacting molecular networks. We present a relatively rapid means to obtain fine-mapping details from AILs using dense marker maps and consecutive generations. Analysis of the complex genetic architecture underlying fatpad and organ weights in this model may eventually help to elucidate not only heritable contributions to obesity but also common gene sets for obesity and its comorbidities.

Approaches in Characterizing Genetic Structure and Mapping in a Rice Multiparental Population.

PubMed

Raghavan, Chitra; Mauleon, Ramil; Lacorte, Vanica; Jubay, Monalisa; Zaw, Hein; Bonifacio, Justine; Singh, Rakesh Kumar; Huang, B Emma; Leung, Hei

2017-06-07

Multi-parent Advanced Generation Intercross (MAGIC) populations are fast becoming mainstream tools for research and breeding, along with the technology and tools for analysis. This paper demonstrates the analysis of a rice MAGIC population from data filtering to imputation and processing of genetic data to characterizing genomic structure, and finally quantitative trait loci (QTL) mapping. In this study, 1316 S6:8 indica MAGIC (MI) lines and the eight founders were sequenced using Genotyping by Sequencing (GBS). As the GBS approach often includes missing data, the first step was to impute the missing SNPs. The observable number of recombinations in the population was then explored. Based on this case study, a general outline of procedures for a MAGIC analysis workflow is provided, as well as for QTL mapping of agronomic traits and biotic and abiotic stress, using the results from both association and interval mapping approaches. QTL for agronomic traits (yield, flowering time, and plant height), physical (grain length and grain width) and cooking properties (amylose content) of the rice grain, abiotic stress (submergence tolerance), and biotic stress (brown spot disease) were mapped. Through presenting this extensive analysis in the MI population in rice, we highlight important considerations when choosing analytical approaches. The methods and results reported in this paper will provide a guide to future genetic analysis methods applied to multi-parent populations. Copyright © 2017 Raghavan et al.

Association between erythrocyte 2,3-diphosphoglycerate levels and reproduction capacity in Long-Evans rats.

PubMed

Noble, N A; Brewer, G J

1982-03-01

During genetic selection of rats for high and low levels of red cell 2,3-diphosphoglycerate (DPG) the decreased fertility in Low-DPG animals was due to significantly (P less than 0.01) fewer offspring born per litter. The rat lines were intercrossed and animals at the tails of the F2 2,3-diphosphoglycerate distribution were mated. Subsequent matings of F3 offspring were monitored. Low-DPG F3 pregnant females killed at 20 days of gestation showed significantly (P less than 0.05) fewer corpora lutea than High-DPG F3 females. There were also significantly (P less than 0.01) fewer corpora lutea in Low-DPG line rats compared to High-DPG rats. It is concluded that the relationship between 2,3-diphosphoglycerate levels and fertility is not due to inbreeding but to a possible genetic linkage, a shared biochemical determinant or a relationship through the effect of 2,3-diphosphoglycerate levels on oxygen delivery to tissue.

Inheritance of Hetero-Diploid Pollen S-Haplotype in Self-Compatible Tetraploid Chinese Cherry (Prunus pseudocerasus Lindl)

PubMed Central

Gu, Chao; Liu, Qing-Zhong; Yang, Ya-Nan; Zhang, Shu-Jun; Khan, Muhammad Awais; Wu, Jun; Zhang, Shao-Ling

2013-01-01

The breakdown of self-incompatibility, which could result from the accumulation of non-functional S-haplotypes or competitive interaction between two different functional S-haplotypes, has been studied extensively at the molecular level in tetraploid Rosaceae species. In this study, two tetraploid Chinese cherry (Prunus pseudocerasus) cultivars and one diploid sweet cherry (Prunus avium) cultivar were used to investigate the ploidy of pollen grains and inheritance of pollen-S alleles. Genetic analysis of the S-genotypes of two intercross-pollinated progenies showed that the pollen grains derived from Chinese cherry cultivars were hetero-diploid, and that the two S-haplotypes were made up of every combination of two of the four possible S-haplotypes. Moreover, the distributions of single S-haplotypes expressed in self- and intercross-pollinated progenies were in disequilibrium. The number of individuals of the two different S-haplotypes was unequal in two self-pollinated and two intercross-pollinated progenies. Notably, the number of individuals containing two different S-haplotypes (S1- and S5-, S5- and S8-, S1- and S4-haplotype) was larger than that of other individuals in the two self-pollinated progenies, indicating that some of these hetero-diploid pollen grains may have the capability to inactivate stylar S-RNase inside the pollen tube and grow better into the ovaries. PMID:23596519

QTL mapping of genome regions controlling temephos resistance in larvae of the mosquito Aedes aegypti.

PubMed

Reyes-Solis, Guadalupe Del Carmen; Saavedra-Rodriguez, Karla; Suarez, Adriana Flores; Black, William C

2014-10-01

The mosquito Aedes aegypti is the principal vector of dengue and yellow fever flaviviruses. Temephos is an organophosphate insecticide used globally to suppress Ae. aegypti larval populations but resistance has evolved in many locations. Quantitative Trait Loci (QTL) controlling temephos survival in Ae. aegypti larvae were mapped in a pair of F3 advanced intercross lines arising from temephos resistant parents from Solidaridad, México and temephos susceptible parents from Iquitos, Peru. Two sets of 200 F3 larvae were exposed to a discriminating dose of temephos and then dead larvae were collected and preserved for DNA isolation every two hours up to 16 hours. Larvae surviving longer than 16 hours were considered resistant. For QTL mapping, single nucleotide polymorphisms (SNPs) were identified at 23 single copy genes and 26 microsatellite loci of known physical positions in the Ae. aegypti genome. In both reciprocal crosses, Multiple Interval Mapping identified eleven QTL associated with time until death. In the Solidaridad×Iquitos (SLD×Iq) cross twelve were associated with survival but in the reciprocal IqxSLD cross, only six QTL were survival associated. Polymorphisms at acetylcholine esterase (AchE) loci 1 and 2 were not associated with either resistance phenotype suggesting that target site insensitivity is not an organophosphate resistance mechanism in this region of México. Temephos resistance is under the control of many metabolic genes of small effect and dispersed throughout the Ae. aegypti genome.

QTL Mapping of Genome Regions Controlling Temephos Resistance in Larvae of the Mosquito Aedes aegypti

PubMed Central

Reyes-Solis, Guadalupe del Carmen; Saavedra-Rodriguez, Karla; Suarez, Adriana Flores; Black, William C.

2014-01-01

Introduction The mosquito Aedes aegypti is the principal vector of dengue and yellow fever flaviviruses. Temephos is an organophosphate insecticide used globally to suppress Ae. aegypti larval populations but resistance has evolved in many locations. Methodology/Principal Findings Quantitative Trait Loci (QTL) controlling temephos survival in Ae. aegypti larvae were mapped in a pair of F3 advanced intercross lines arising from temephos resistant parents from Solidaridad, México and temephos susceptible parents from Iquitos, Peru. Two sets of 200 F3 larvae were exposed to a discriminating dose of temephos and then dead larvae were collected and preserved for DNA isolation every two hours up to 16 hours. Larvae surviving longer than 16 hours were considered resistant. For QTL mapping, single nucleotide polymorphisms (SNPs) were identified at 23 single copy genes and 26 microsatellite loci of known physical positions in the Ae. aegypti genome. In both reciprocal crosses, Multiple Interval Mapping identified eleven QTL associated with time until death. In the Solidaridad×Iquitos (SLD×Iq) cross twelve were associated with survival but in the reciprocal IqxSLD cross, only six QTL were survival associated. Polymorphisms at acetylcholine esterase (AchE) loci 1 and 2 were not associated with either resistance phenotype suggesting that target site insensitivity is not an organophosphate resistance mechanism in this region of México. Conclusions/Significance Temephos resistance is under the control of many metabolic genes of small effect and dispersed throughout the Ae. aegypti genome. PMID:25330200

Genomic Mapping of Direct and Correlated Responses to Long-Term Selection for Rapid Growth Rate in Mice

PubMed Central

Allan, Mark F.; Eisen, Eugene J.; Pomp, Daniel

2005-01-01

Understanding the genetic architecture of traits such as growth, body composition, and energy balance has become a primary focus for biomedical and agricultural research. The objective of this study was to map QTL in a large F2 (n = 1181) population resulting from an intercross between the M16 and ICR lines of mice. The M16 line, developed by long-term selection for 3- to 6-week weight gain, is larger, heavier, fatter, hyperphagic, and diabetic relative to its randomly selected control line of ICR origin. The F2 population was phenotyped for growth and energy intake at weekly intervals from 4 to 8 weeks of age and for body composition and plasma levels of insulin, leptin, TNFα, IL6, and glucose at 8 weeks and was genotyped for 80 microsatellite markers. Since the F2 was a cross between a selection line and its unselected control, the QTL identified likely represent genes that contributed to direct and correlated responses to long-term selection for rapid growth rate. Across all traits measured, 95 QTL were identified, likely representing 19 unique regions on 13 chromosomes. Four chromosomes (2, 6, 11, and 17) harbored loci contributing disproportionately to selection response. Several QTL demonstrating differential regulation of regional adipose deposition and age-dependent regulation of growth and energy consumption were identified. PMID:15944354

[Ultraviolet spectroscopic study on the fine structures in the solar polar hole].

PubMed

Zhang, Min; Wang, Dong; Liu, Guo-Hong

2014-07-01

Fine structures in the south solar polar coronal hole were observed by N IV line of SOHO/SUMER spectrograph. The scales of the fine structures range spatially range from 1 arcsec to several arcsecs, temporally from 1 min to several minutes, and parts of them are in strip shape along the slit direction. The line-of-sight velocity of them is up to tens of km x s(-1) with red and blue shift intercrossed occasionally, which appear periodically as long as 100 minutes in some regions. Part of the fine structures can be clearly observed at the Ne V III line with higher formation temperature in the same spectral window. The time and location of some fine structures with high velocity in the Ne V III spectrum are almost the same as that in N IV spectrum, but they are extended and diffused in the Ne V III spectrum. Some fine structures have non-Gaussian profiles with the line-of-sight Doppler velocities up to 150 km x s(-1) in the N IV blue/red wings, which is similar with the explosive events in the transition region. In the past, explosive events are small-scale dynamic phenomena often observed in the quiet-sun (QS) region, while their properties in coronal holes (CHs) remain unclear. Here, we find the EE-like events with strong dynamics in the south solar polar coronal hole by N IV line of SOHO/SUMER spectrograph.

Genetic Analysis of Ligation-Induced Neointima Formation in an F2 Intercross of C57BL/6 and FVB/N Inbred Mouse Strains

PubMed Central

Östergren, Caroline; Shim, Jeong; Larsen, Jens Vinther; Nielsen, Lars Bo; Bentzon, Jacob F.

2015-01-01

Objective Proliferation and migration of vascular smooth muscle cells (SMCs) are central for arterial diseases including atherosclerosis and restenosis. We hypothesized that the underlying mechanisms may be modeled by carotid ligation in mice. In FVB/N inbred mice, ligation leads to abundant neointima formation with proliferating media-derived SMCs, whereas in C57BL/6 mice hardly any neointima is formed. In the present study, we aimed to identify the chromosomal location of the causative gene variants in an F2 intercross between these two mouse strains. Methods and Results The neointimal cross-sectional area was significantly different between FVB/N, C57BL/6 and F1 female mice 4 weeks after ligation. Carotid artery ligation and a genome scan using 800 informative SNP markers were then performed in 157 female F2 mice. Using quantitative trait loci (QTL) analysis, we identified suggestive, but no genome-wide significant, QTLs on chromosomes 7 and 12 for neointimal cross-sectional area and on chromosome 14 for media area. Further analysis of the cross revealed 4 QTLs for plasma cholesterol, which combined explained 69% of the variation among F2 mice. Conclusions We identified suggestive QTLs for neointima and media area after carotid ligation in an intercross of FVB/N and C57BL/6 mice, but none that reached genome-wide significance indicating a complex genetic architecture of the traits. Genome-wide significant QTLs for total cholesterol levels were identified on chromosomes 1, 3, 9, and 12. PMID:25875831

Predicting the evolutionary dynamics of seasonal adaptation to novel climates in Arabidopsis thaliana

PubMed Central

Fournier-Level, Alexandre; Perry, Emily O.; Wang, Jonathan A.; Braun, Peter T.; Migneault, Andrew; Cooper, Martha D.; Metcalf, C. Jessica E.; Schmitt, Johanna

2016-01-01

Predicting whether and how populations will adapt to rapid climate change is a critical goal for evolutionary biology. To examine the genetic basis of fitness and predict adaptive evolution in novel climates with seasonal variation, we grew a diverse panel of the annual plant Arabidopsis thaliana (multiparent advanced generation intercross lines) in controlled conditions simulating four climates: a present-day reference climate, an increased-temperature climate, a winter-warming only climate, and a poleward-migration climate with increased photoperiod amplitude. In each climate, four successive seasonal cohorts experienced dynamic daily temperature and photoperiod variation over a year. We measured 12 traits and developed a genomic prediction model for fitness evolution in each seasonal environment. This model was used to simulate evolutionary trajectories of the base population over 50 y in each climate, as well as 100-y scenarios of gradual climate change following adaptation to a reference climate. Patterns of plastic and evolutionary fitness response varied across seasons and climates. The increased-temperature climate promoted genetic divergence of subpopulations across seasons, whereas in the winter-warming and poleward-migration climates, seasonal genetic differentiation was reduced. In silico “resurrection experiments” showed limited evolutionary rescue compared with the plastic response of fitness to seasonal climate change. The genetic basis of adaptation and, consequently, the dynamics of evolutionary change differed qualitatively among scenarios. Populations with fewer founding genotypes and populations with genetic diversity reduced by prior selection adapted less well to novel conditions, demonstrating that adaptation to rapid climate change requires the maintenance of sufficient standing variation. PMID:27140640

Predicting the evolutionary dynamics of seasonal adaptation to novel climates in Arabidopsis thaliana.

PubMed

Fournier-Level, Alexandre; Perry, Emily O; Wang, Jonathan A; Braun, Peter T; Migneault, Andrew; Cooper, Martha D; Metcalf, C Jessica E; Schmitt, Johanna

2016-05-17

Predicting whether and how populations will adapt to rapid climate change is a critical goal for evolutionary biology. To examine the genetic basis of fitness and predict adaptive evolution in novel climates with seasonal variation, we grew a diverse panel of the annual plant Arabidopsis thaliana (multiparent advanced generation intercross lines) in controlled conditions simulating four climates: a present-day reference climate, an increased-temperature climate, a winter-warming only climate, and a poleward-migration climate with increased photoperiod amplitude. In each climate, four successive seasonal cohorts experienced dynamic daily temperature and photoperiod variation over a year. We measured 12 traits and developed a genomic prediction model for fitness evolution in each seasonal environment. This model was used to simulate evolutionary trajectories of the base population over 50 y in each climate, as well as 100-y scenarios of gradual climate change following adaptation to a reference climate. Patterns of plastic and evolutionary fitness response varied across seasons and climates. The increased-temperature climate promoted genetic divergence of subpopulations across seasons, whereas in the winter-warming and poleward-migration climates, seasonal genetic differentiation was reduced. In silico "resurrection experiments" showed limited evolutionary rescue compared with the plastic response of fitness to seasonal climate change. The genetic basis of adaptation and, consequently, the dynamics of evolutionary change differed qualitatively among scenarios. Populations with fewer founding genotypes and populations with genetic diversity reduced by prior selection adapted less well to novel conditions, demonstrating that adaptation to rapid climate change requires the maintenance of sufficient standing variation.

Multiple Quantitative Trait Loci Influence the Shape of a Male-Specific Genital Structure in Drosophila melanogaster

PubMed Central

McNeil, Casey L.; Bain, Clint L.; Macdonald, Stuart J.

2011-01-01

The observation that male genitalia diverge more rapidly than other morphological traits during evolution is taxonomically widespread and likely due to some form of sexual selection. One way to elucidate the evolutionary forces acting on these traits is to detail the genetic architecture of variation both within and between species, a program of research that is considerably more tractable in a model system. Drosophila melanogaster and its sibling species, D. simulans, D. mauritiana, and D. sechellia, are morphologically distinguishable only by the shape of the posterior lobe, a male-specific elaboration of the genital arch. We extend earlier studies identifying quantitative trait loci (QTL) responsible for lobe divergence across species and report the first genetic dissection of lobe shape variation within a species. Using an advanced intercross mapping design, we identify three autosomal QTL contributing to the difference in lobe shape between a pair of D. melanogaster inbred lines. The QTL each contribute 4.6–10.7% to shape variation, and two show a significant epistatic interaction. Interestingly, these intraspecific QTL map to the same locations as interspecific lobe QTL, implying some shared genetic control of the trait within and between species. As a first step toward a mechanistic understanding of natural lobe shape variation, we find an association between our QTL data and a set of genes that show sex-biased expression in the developing genital imaginal disc (the precursor of the adult genitalia). These genes are good candidates to harbor naturally segregating polymorphisms contributing to posterior lobe shape. PMID:22384345

Combined Large-Scale Phenotyping and Transcriptomics in Maize Reveals a Robust Growth Regulatory Network1[OPEN

PubMed Central

Herman, Dorota; Slabbinck, Bram; Pè, Mario Enrico

2016-01-01

Leaves are vital organs for biomass and seed production because of their role in the generation of metabolic energy and organic compounds. A better understanding of the molecular networks underlying leaf development is crucial to sustain global requirements for food and renewable energy. Here, we combined transcriptome profiling of proliferative leaf tissue with in-depth phenotyping of the fourth leaf at later stages of development in 197 recombinant inbred lines of two different maize (Zea mays) populations. Previously, correlation analysis in a classical biparental mapping population identified 1,740 genes correlated with at least one of 14 traits. Here, we extended these results with data from a multiparent advanced generation intercross population. As expected, the phenotypic variability was found to be larger in the latter population than in the biparental population, although general conclusions on the correlations among the traits are comparable. Data integration from the two diverse populations allowed us to identify a set of 226 genes that are robustly associated with diverse leaf traits. This set of genes is enriched for transcriptional regulators and genes involved in protein synthesis and cell wall metabolism. In order to investigate the molecular network context of the candidate gene set, we integrated our data with publicly available functional genomics data and identified a growth regulatory network of 185 genes. Our results illustrate the power of combining in-depth phenotyping with transcriptomics in mapping populations to dissect the genetic control of complex traits and present a set of candidate genes for use in biomass improvement. PMID:26754667

Combined Large-Scale Phenotyping and Transcriptomics in Maize Reveals a Robust Growth Regulatory Network.

PubMed

Baute, Joke; Herman, Dorota; Coppens, Frederik; De Block, Jolien; Slabbinck, Bram; Dell'Acqua, Matteo; Pè, Mario Enrico; Maere, Steven; Nelissen, Hilde; Inzé, Dirk

2016-03-01

Leaves are vital organs for biomass and seed production because of their role in the generation of metabolic energy and organic compounds. A better understanding of the molecular networks underlying leaf development is crucial to sustain global requirements for food and renewable energy. Here, we combined transcriptome profiling of proliferative leaf tissue with in-depth phenotyping of the fourth leaf at later stages of development in 197 recombinant inbred lines of two different maize (Zea mays) populations. Previously, correlation analysis in a classical biparental mapping population identified 1,740 genes correlated with at least one of 14 traits. Here, we extended these results with data from a multiparent advanced generation intercross population. As expected, the phenotypic variability was found to be larger in the latter population than in the biparental population, although general conclusions on the correlations among the traits are comparable. Data integration from the two diverse populations allowed us to identify a set of 226 genes that are robustly associated with diverse leaf traits. This set of genes is enriched for transcriptional regulators and genes involved in protein synthesis and cell wall metabolism. In order to investigate the molecular network context of the candidate gene set, we integrated our data with publicly available functional genomics data and identified a growth regulatory network of 185 genes. Our results illustrate the power of combining in-depth phenotyping with transcriptomics in mapping populations to dissect the genetic control of complex traits and present a set of candidate genes for use in biomass improvement. © 2016 American Society of Plant Biologists. All Rights Reserved.

Quantifying selection in evolving populations using time-resolved genetic data

NASA Astrophysics Data System (ADS)

Illingworth, Christopher J. R.; Mustonen, Ville

2013-01-01

Methods which uncover the molecular basis of the adaptive evolution of a population address some important biological questions. For example, the problem of identifying genetic variants which underlie drug resistance, a question of importance for the treatment of pathogens, and of cancer, can be understood as a matter of inferring selection. One difficulty in the inference of variants under positive selection is the potential complexity of the underlying evolutionary dynamics, which may involve an interplay between several contributing processes, including mutation, recombination and genetic drift. A source of progress may be found in modern sequencing technologies, which confer an increasing ability to gather information about evolving populations, granting a window into these complex processes. One particularly interesting development is the ability to follow evolution as it happens, by whole-genome sequencing of an evolving population at multiple time points. We here discuss how to use time-resolved sequence data to draw inferences about the evolutionary dynamics of a population under study. We begin by reviewing our earlier analysis of a yeast selection experiment, in which we used a deterministic evolutionary framework to identify alleles under selection for heat tolerance, and to quantify the selection acting upon them. Considering further the use of advanced intercross lines to measure selection, we here extend this framework to cover scenarios of simultaneous recombination and selection, and of two driver alleles with multiple linked neutral, or passenger, alleles, where the driver pair evolves under an epistatic fitness landscape. We conclude by discussing the limitations of the approach presented and outlining future challenges for such methodologies.

Standing genetic variation as a major contributor to adaptation in the Virginia chicken lines selection experiment.

PubMed

Sheng, Zheya; Pettersson, Mats E; Honaker, Christa F; Siegel, Paul B; Carlborg, Örjan

2015-10-01

Artificial selection provides a powerful approach to study the genetics of adaptation. Using selective-sweep mapping, it is possible to identify genomic regions where allele-frequencies have diverged during selection. To avoid false positive signatures of selection, it is necessary to show that a sweep affects a selected trait before it can be considered adaptive. Here, we confirm candidate, genome-wide distributed selective sweeps originating from the standing genetic variation in a long-term selection experiment on high and low body weight of chickens. Using an intercross between the two divergent chicken lines, 16 adaptive selective sweeps were confirmed based on their association with the body weight at 56 days of age. Although individual additive effects were small, the fixation for alternative alleles across the loci contributed at least 40 % of the phenotypic difference for the selected trait between these lines. The sweeps contributed about half of the additive genetic variance present within and between the lines after 40 generations of selection, corresponding to a considerable portion of the additive genetic variance of the base population. Long-term, single-trait, bi-directional selection in the Virginia chicken lines has resulted in a gradual response to selection for extreme phenotypes without a drastic reduction in the genetic variation. We find that fixation of several standing genetic variants across a highly polygenic genetic architecture made a considerable contribution to long-term selection response. This provides new fundamental insights into the dynamics of standing genetic variation during long-term selection and adaptation.

Weeping dragon, a unique ornamenal citrus

USDA-ARS?s Scientific Manuscript database

‘Weeping Dragon’ is a new ornamental citrus cultivar developed by intercrossing of two unusual and unique citrus types, Poncirus trifoliata cultivated variety (cv.) Flying Dragon, and Citrus sinensis cv. ‘Cipo’. This new hybrid cultivar combines strongly contorted and weeping growth traits in a smal...

Facile fabrication of BiVO4 nanofilms with controlled pore size and their photoelectrochemical performances

NASA Astrophysics Data System (ADS)

Feng, Chenchen; Jiao, Zhengbo; Li, Shaopeng; Zhang, Yan; Bi, Yingpu

2015-12-01

We demonstrate a facile method for the rational fabrication of pore-size controlled nanoporous BiVO4 photoanodes, and confirmed that the optimum pore-size distributions could effectively absorb visible light through light diffraction and confinement functions. Furthermore, in situ X-ray photoelectron spectroscopy (XPS) reveals more efficient photoexcited electron-hole separation than conventional particle films, induced by light confinement and rapid charge transfer in the inter-crossed worm-like structures.We demonstrate a facile method for the rational fabrication of pore-size controlled nanoporous BiVO4 photoanodes, and confirmed that the optimum pore-size distributions could effectively absorb visible light through light diffraction and confinement functions. Furthermore, in situ X-ray photoelectron spectroscopy (XPS) reveals more efficient photoexcited electron-hole separation than conventional particle films, induced by light confinement and rapid charge transfer in the inter-crossed worm-like structures. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06584d

Updated estimates of HAL n and RN- effects on pork quality: fresh and processed loin and ham.

PubMed

Cherel, P; Glénisson, J; Figwer, P; Pires, J; Damon, M; Franck, M; Le Roy, P

2010-12-01

A 1000-pig F2 intercross QTL detection experimental population was generated using two commercial sire lines. Independent carriers of HAL n and RN- mutations (10% and 14%, respectively) were included in this population as control genotypes. The effects of HAL n and RN- heterozygous genotypes on fresh and transformed loins and hams were estimated using a mixed model methodology. The results document the unfavorable effects of both mutations on meat quality. Smaller effects of HAL Nn genotype compared to HAL nn or RN-rn+ genotypes were estimated. Interestingly, effects of HAL Nn genotype on meat pH and loin color could be insignificant at 24-h postmortem, but translate into higher water losses on storage and cooking, and result in tougher cooked loin. Using the same methodology, significant effects of the PRKAG3 (RN) I199 allele on ultimate pH values but not on glycolytic potential were observed. Copyright © 2010 The American Meat Science Association. Published by Elsevier Ltd. All rights reserved.

Natural reversal of left-right gut/gonad asymmetry in C. elegans males is independent of embryonic chirality.

PubMed

Callander, Davon C; Alcorn, Melissa R; Birsoy, Bilge; Rothman, Joel H

2014-06-01

Anatomical left-right (L/R) asymmetry in C. elegans is established in the four-cell embryo as a result of anteroposterior skewing of transverse mitotic spindles with a defined handedness. This event creates a chiral embryo and ultimately an adult body plan with fixed L/R positioning of internal organs and components of the nervous system. While this "dextral" configuration is invariant in hermaphrodites, it can be reversed by physical manipulation of the early embryo or by mutations that interfere with mitotic spindle orientation, which leads to viable, mirror-reversed (sinistral) animals. During normal development of the C. elegans male, the gonad develops on the right of the midline, with the gut bilaterally apposed on the left. However, we found that in males of the laboratory N2 strain and Hawaiian ("Hw") wild isolate, the gut/gonad asymmetry is frequently reversed in a temperature-dependent manner, independent of normal embryonic chirality. We also observed sporadic errors in gonad migration occurring naturally during early larval stages of these and other wild strains; however, the incidence of such errors does not correlate with the frequency of L/R gut/gonad reversals in these strains. Analysis of N2/Hw hybrids and recombinant inbred advanced intercross lines (RIAILs) indicate that the L/R organ reversals are likely to result from recessively acting variations in multiple genes. Thus, unlike the highly reproducible L/R asymmetries of most structures in hermaphrodites, the L/R asymmetry of the male C. elegans body plan is less rigidly determined and subject to natural variation that is influenced by a multiplicity of genes. © 2014 Wiley Periodicals, Inc.

Quantitative Trait Loci Mapping of Genome Regions Controlling Permethrin Resistance in the Mosquito Aedes aegypti

PubMed Central

Saavedra-Rodriguez, Karla; Strode, Clare; Flores Suarez, Adriana; Fernandez Salas, Ildefonso; Ranson, Hilary; Hemingway, Janet; Black, William C.

2008-01-01

The mosquito Aedes aegypti is the principal vector of dengue and yellow fever flaviviruses. Permethrin is an insecticide used to suppress Ae. aegypti adult populations but metabolic and target site resistance to pyrethroids has evolved in many locations worldwide. Quantitative trait loci (QTL) controlling permethrin survival in Ae. aegypti were mapped in an F3 advanced intercross line. Parents came from a collection of mosquitoes from Isla Mujeres, México, that had been selected for permethrin resistance for two generations and a reference permethrin-susceptible strain originally from New Orleans. Following a 1-hr permethrin exposure, 439 F3 adult mosquitoes were phenotyped as knockdown resistant, knocked down/recovered, or dead. For QTL mapping, single nucleotide polymorphisms (SNPs) were identified at 22 loci with potential antixenobiotic activity including genes encoding cytochrome P450s (CYP), esterases (EST), or glutathione transferases (GST) and at 12 previously mapped loci. Seven antixenobiotic genes mapped to chromosome I, six to chromosome II, and nine to chromosome III. Two QTL of major effect were detected on chromosome III. One corresponds with a SNP previously associated with permethrin resistance in the para sodium channel gene and the second with the CCEunk7o esterase marker. Additional QTL but of relatively minor effect were also found. These included two sex-linked QTL on chromosome I affecting knockdown and recovery and a QTL affecting survival and recovery. On chromosome II, one QTL affecting survival and a second affecting recovery were detected. The patterns confirm that mutations in the para gene cause target-site insensitivity and are the major source of permethrin resistance but that other genes dispersed throughout the genome contribute to recovery and survival of mosquitoes following permethrin exposure. PMID:18723882

The expression and genetics of resistance to stripe (yellow) rust in three European and four New Zealand wheat cultivars.

PubMed

Pathan, Amin K; Park, Robert F; Wellings, Colin R; Bariana, Harbans S

2007-01-01

Adult plant resistance (APR) to stripe rust in three European (Pegaso, Victo and Aztec) and four New Zealand cultivars (Weka, Kopara, Kokart and Takahe) was characterised using hybrid analysis and tests of allelism. In agreement with earlier work, the APR in most of these cultivars appeared to be controlled by two or more genes with additive effects. It was suggested that heavy selection pressure should be avoided in early generations in breeding programs utilising APR, because lines in which APR genes are heterozygous may display lower levels of resistance due to the incompletely dominant and interactive nature of many APRs. Such lines are capable of generating more resistant progenies following selfing. It was also demonstrated that it is possible to misclassify F2 plants as susceptible if APR genes are in a heterozygous condition, especially in the case of gene(s) conferring intermediate levels of resistance. The presence of a common APR gene in Kopara and Takahe, and perhaps Weka, was suggested because all shared a common parent in their pedigree and no susceptible plants were observed in F2 populations derived from intercrossing them. The difficulties inherent in conducting genetic studies on APRs and the need for large population sizes for such studies were emphasised.

Facile in situ synthesis of hierarchical porous Ni/Ni(OH)₂ hybrid sponges with excellent electrochemical energy-storage performances for supercapacitors.

PubMed

Wang, Wanren; Wang, Wenhua; Wang, Mengjiao; Guo, Xiaohui

2014-09-01

Herein, we report the in situ growth of single-crystalline Ni(OH)2 nanoflakes on a Ni support by using facile hydrothermal processes. The as-prepared Ni/Ni(OH)2 sponges were well-characterized by using X-ray diffraction (XRD), SEM, TEM, and X-ray photoelectron spectroscopy (XPS) techniques. The results revealed that the nickel-skeleton-supported Ni(OH)2 rope-like aggregates were composed of numerous intercrossed single-crystal Ni(OH)2 flake-like units. The Ni/Ni(OH)2 hybrid sponges served as electrodes and displayed ultrahigh specific capacitance (SC=3247 F g(-1)) and excellent rate-capability performance, likely owing to fast electron and ion transport, sufficient Faradic redox reaction, and robust structural integrity of the Ni/Ni(OH)2 hybrid electrode. These results support the promising application of Ni(OH)2 nanoflakes as advanced pseudocapacitor materials. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genetic sex separation in Anopheles arabiensis and the production of sterile hybrids.

PubMed

Curtis, C F

1978-01-01

The gene for dieldrin resistance has been artificially male-linked so that females can be selectively killed with dieldrin. By intercrossing different sibling species of the Anopheles gambiae complex, batches consisting of sterile males only can be reared. This seems to have potential for use in genetic control operations.

Genetic sex separation in Anopheles arabiensis and the production of sterile hybrids

PubMed Central

Curtis, C. F.

1978-01-01

The gene for dieldrin resistance has been artificially male-linked so that females can be selectively killed with dieldrin. By intercrossing different sibling species of the Anopheles gambiae complex, batches consisting of sterile males only can be reared. This seems to have potential for use in genetic control operations. PMID:308410

Intercrossed carbon nanorings with pure surface states as low-cost and environment-friendly phosphors for white-light-emitting diodes.

PubMed

Li, Xiaoming; Liu, Yanli; Song, Xiufeng; Wang, Hao; Gu, Haoshuang; Zeng, Haibo

2015-02-02

As an important energy-saving technique, white-light-emitting diodes (W-LEDs) have been seeking for low-cost and environment-friendly substitutes for rare-earth-based expensive phosphors or Pd(2+)/Cd(2+)-based toxic quantum dots (QDs). In this work, precursors and chemical processes were elaborately designed to synthesize intercrossed carbon nanorings (IC-CNRs) with relatively pure hydroxy surface states for the first time, which enable them to overcome the aggregation-induced quenching (AIQ) effect, and to emit stable yellow-orange luminescence in both colloidal and solid states. As a direct benefit of such scarce solid luminescence from carbon nanomaterials, W-LEDs with color coordinate at (0.28, 0.27), which is close to pure white light (0.33, 0.33), were achieved through using these low-temperature-synthesized and toxic ion-free IC-CNRs as solid phosphors on blue LED chips. This work demonstrates that the design of surface states plays a crucial role in exploring new functions of fluorescent carbon nanomaterials. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sex-specific genetic determinants for arterial stiffness in Dahl salt-sensitive hypertensive rats.

PubMed

Decano, Julius L; Pasion, Khristine A; Black, Nicole; Giordano, Nicholas J; Herrera, Victoria L; Ruiz-Opazo, Nelson

2016-01-11

Arterial stiffness is an independent predictor of cardiovascular outcomes in hypertensive patients including myocardial infarction, fatal stroke, cerebral micro-bleeds which predicts cerebral hemorrhage in hypertensive patients, as well as progression to hypertension in non-hypertensive subjects. The association between arterial stiffness and various cardiovascular outcomes (coronary heart disease, stroke) remains after adjusting for age, sex, blood pressure, body mass index and other known predictors of cardiovascular disease, suggesting that arterial stiffness, measured via carotid-femoral pulse wave velocity, has a better predictive value than each of these factors. Recent evidence shows that arterial stiffening precedes the onset of high blood pressure; however their molecular genetic relationship (s) and sex-specific determinants remain uncertain. We investigated whether distinct or shared genetic determinants might underlie susceptibility to arterial stiffening in male and female Dahl salt-sensitive rats. Thus, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting arterial stiffness in six-week old F2 (Dahl S x R)-intercross male and female rats characterized for abdominal aortic pulse wave velocity and aortic strain by high-resolution ultrasonography. We detected five highly significant QTLs affecting aortic stiffness: two interacting QTLs (AS-m1 on chromosome 4 and AS-m2 on chromosome16, LOD 8.8) in males and two distinct interacting QTLs (AS-f1 on chromosome 9 and AS-f2 on chromosome11, LOD 8.9) in females affecting pulse wave velocity. One QTL (AS-1 on chromosome 3, LOD 4.3) was found to influence aortic strain in a sex-independent manner. None of these arterial stiffness QTLs co-localized with previously reported blood pressure QTLs detected in equivalent genetic intercrosses. These data reveal sex-specific genetic determinants for aortic pulse wave velocity and suggest distinct polygenic susceptibility for arterial stiffness and salt-sensitive hypertension in Dahl rats based upon reported blood pressure QTLs in equivalent (Dahl S x R)-intercrosses.

Effects of stacked quantitative resistances to downy mildew in lettuce do not simply add up.

PubMed

den Boer, Erik; Pelgrom, Koen T B; Zhang, Ningwen W; Visser, Richard G F; Niks, Rients E; Jeuken, Marieke J W

2014-08-01

In a stacking study of eight resistance QTLs in lettuce against downy mildew, only three out of ten double combinations showed an increased resistance effect under field conditions. Complete race nonspecific resistance to lettuce downy mildew, as observed for the nonhost wild lettuce species Lactuca saligna, is desired in lettuce cultivation. Genetic dissection of L. saligna's complete resistance has revealed several quantitative loci (QTL) for resistance with field infection reductions of 30-50 %. To test the effect of stacking these QTL, we analyzed interactions between homozygous L. saligna CGN05271 chromosome segments introgressed into the genetic background of L. sativa cv. Olof. Eight different backcross inbred lines (BILs) with single introgressions of 30-70 cM and selected predominately for quantitative resistance in field situations were intercrossed. Ten developed homozygous lines with stacked introgression segments (double combinations) were evaluated for resistance in the field. Seven double combinations showed a similar infection as the individual most resistant parental BIL, revealing epistatic interactions with 'less-than-additive' effects. Three double combinations showed an increased resistance level compared to their parental BILs and their interactions were additive, 'less-than-additive' epistatic and 'more-than-additive' epistatic, respectively. The additive interaction reduced field infection by 73 %. The double combination with a 'more-than-additive' epistatic effect, derived from a combination between a susceptible and a resistant BIL with 0 and 30 % infection reduction, respectively, showed an average field infection reduction of 52 %. For the latter line, an attempt to genetically dissect its underlying epistatic loci by substitution mapping did not result in smaller mapping intervals as none of the 22 substitution lines reached a similar high resistance level. Implications for breeding and the inheritance of L. saligna's complete resistance are discussed.

GPRC6A regulates prostate cancer progression

PubMed Central

Pi, Min; Quarles, L. Darryl

2011-01-01

BACKGROUND GPRC6A is a nutrient sensing GPCR that is activated in vitro by a variety of ligands, including amino acids, calcium, zinc, osteocalcin (OC) and testosterone. The association between nutritional factors and risk of prostate cancer, the finding of increased expression of OC in prostate cancer cells and the association between GPRC6A and risk of prostate cancer in Japanese men implicates a role of GPRC6A in prostate cancer. METHODS We examined if GPRC6A is expressed in human prostate cancer cell lines and used siRNA-mediated knockdown GPRC6A expression in prostate cancer cells to explore the function of GPRC6A in vitro. To assess the role GPRC6A in prostate cancer progression in vivo we intercrossed Gprc6a−/− mice onto the TRAMP mouse prostate cancer model. RESULTS GPRC6A transcripts were markedly increased in prostate cancer cell lines 22Rv1, PC-3 and LNCaP, compared to the normal prostate RWPE-1 cell line. In addition, a panel of GPRC6A ligands, including calcium, OC, and arginine, exhibited in prostate cancer cell lines a dose-dependent stimulation of ERK activity, cell proliferation, chemotaxis, and prostate specific antigen and Runx 2 gene expression. These responses were inhibited by siRNA-mediated knockdown of GPRC6A. Finally, transfer of Gprc6a deficiency onto a TRAMP mouse model of prostate cancer significantly retarded prostate cancer progression and improved survival of compound Gprc6a−/−/TRAMP mice. CONCLUSIONS GPRC6A is a novel molecular target for regulating prostate growth and cancer progression. Increments in GPRC6A may augment the ability of prostate cancer cells to proliferate in response to dietary and bone derived ligands. PMID:21681779

Oxygen evolution from BF3/MnO4-.

PubMed

Yiu, Shek-Man; Man, Wai-Lun; Wang, Xin; Lam, William W Y; Ng, Siu-Mui; Kwong, Hoi-Ki; Lau, Kai-Chung; Lau, Tai-Chu

2011-04-14

MnO(4)(-) is activated by BF(3) to undergo intramolecular coupling of two oxo ligands to generate O(2). DFT calculations suggest that there should be a spin intercrossing between the singlet and triplet potential energy surfaces on going from the active intermediate [MnO(2)(OBF(3))(2)](-) to the O···O coupling transition state.

Production of haploids and doubled haploids in oil palm

PubMed Central

2010-01-01

Background Oil palm is the world's most productive oil-food crop despite yielding well below its theoretical maximum. This maximum could be approached with the introduction of elite F1 varieties. The development of such elite lines has thus far been prevented by difficulties in generating homozygous parental types for F1 generation. Results Here we present the first high-throughput screen to identify spontaneously-formed haploid (H) and doubled haploid (DH) palms. We secured over 1,000 Hs and one DH from genetically diverse material and derived further DH/mixoploid palms from Hs using colchicine. We demonstrated viability of pollen from H plants and expect to generate 100% homogeneous F1 seed from intercrosses between DH/mixoploids once they develop female inflorescences. Conclusions This study has generated genetically diverse H/DH palms from which parental clones can be selected in sufficient numbers to enable the commercial-scale breeding of F1 varieties. The anticipated step increase in productivity may help to relieve pressure to extend palm cultivation, and limit further expansion into biodiverse rainforest. PMID:20929530

Artificial Selection Response due to Polygenic Adaptation from a Multilocus, Multiallelic Genetic Architecture.

PubMed

Zan, Yanjun; Sheng, Zheya; Lillie, Mette; Rönnegård, Lars; Honaker, Christa F; Siegel, Paul B; Carlborg, Örjan

2017-10-01

The ability of a population to adapt to changes in their living conditions, whether in nature or captivity, often depends on polymorphisms in multiple genes across the genome. In-depth studies of such polygenic adaptations are difficult in natural populations, but can be approached using the resources provided by artificial selection experiments. Here, we dissect the genetic mechanisms involved in long-term selection responses of the Virginia chicken lines, populations that after 40 generations of divergent selection for 56-day body weight display a 9-fold difference in the selected trait. In the F15 generation of an intercross between the divergent lines, 20 loci explained >60% of the additive genetic variance for the selected trait. We focused particularly on fine-mapping seven major QTL that replicated in this population and found that only two fine-mapped to single, bi-allelic loci; the other five contained linked loci, multiple alleles or were epistatic. This detailed dissection of the polygenic adaptations in the Virginia lines provides a deeper understanding of the range of different genome-wide mechanisms that have been involved in these long-term selection responses. The results illustrate that the genetic architecture of a highly polygenic trait can involve a broad range of genetic mechanisms, and that this can be the case even in a small population bred from founders with limited genetic diversity. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Regional ecological construction and mission of landscape ecology].

PubMed

Xiao, Duning; Xie, Fuju; Wei, Jianbing

2004-10-01

The eco-construction on regional and landscape scale is the one which can be used to specific landscape and intercrossing ecosystem in specific region including performing scientific administration of ecosystem and optimizing environmental function. Recently, the government has taken a series of significant projects into action, such as national forest protection item, partly forest restoration, and adjustment of water, etc. Enforcing regional eco-construction and maintaining the ecology security of the nation have become the strategic requisition. In various regions, different eco-construction should be applied, for example, performing ecological safeguard measure in ecological sensitive zone, accommodating the ecological load in ecological fragile zone, etc., which can control the activities of human being, so that, sustainable development can be reached. Facing opportunity and challenge in the development of landscape ecology, we have some key topics: landscape pattern of ecological security, land use and ecological process, landscape changes under human activity stress, quantitative evaluation of the influence on human being activities, evaluation of zonal ecological security and advance warning of ecological risk, and planning and optimizing of model in landscape eco-construction.

A genome-wide association study of limb bone length using a Large White × Minzhu intercross population.

PubMed

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

2014-11-04

In pig, limb bone length influences ham yield and body height to a great extent and has important economic implications for pig industry. In this study, an intercross population was constructed between the indigenous Chinese Minzhu pig breed and the western commercial Large White pig breed to examine the genetic basis for variation in limb bone length. The aim of this study was to detect potential genetic variants associated with porcine limb bone length. A total of 571 F2 individuals from a Large White and Minzhu intercross population were genotyped using the Illumina PorcineSNP60K Beadchip, and phenotyped for femur length (FL), humerus length (HL), hipbone length (HIPL), scapula length (SL), tibia length (TL), and ulna length (UL). A genome-wide association study was performed by applying the previously reported approach of genome-wide rapid association using mixed model and regression. Statistical significance of the associations was based on Bonferroni-corrected P-values. A total of 39 significant SNPs were mapped to a 11.93 Mb long region on pig chromosome 7 (SSC7). Linkage analysis of these significant SNPs revealed three haplotype blocks of 495 kb, 376 kb and 492 kb, respectively, in the 11.93 Mb region. Annotation based on the pig reference genome identified 15 genes that were located near or contained the significant SNPs in these linkage disequilibrium intervals. Conditioned analysis revealed that four SNPs, one on SSC2 and three on SSC4, showed significant associations with SL and HL, respectively. Analysis of the 15 annotated genes that were identified in these three haplotype blocks indicated that HMGA1 and PPARD, which are expressed in limbs and influence chondrocyte cell growth and differentiation, could be considered as relevant biological candidates for limb bone length in pig, with potential applications in breeding programs. Our results may also be useful for the study of the mechanisms that underlie human limb length and body height.

Heritability of articular cartilage regeneration and its association with ear wound healing in mice.

PubMed

Rai, Muhammad Farooq; Hashimoto, Shingo; Johnson, Eric E; Janiszak, Kara L; Fitzgerald, Jamie; Heber-Katz, Ellen; Cheverud, James M; Sandell, Linda J

2012-07-01

Emerging evidence suggests that genetic components contribute significantly to cartilage degeneration in osteoarthritis pathophysiology, but little information is available on the genetics of cartilage regeneration. Therefore, this study was undertaken to investigate cartilage regeneration in genetic murine models using common inbred strains and a set of recombinant inbred (RI) lines generated from LG/J (healer of ear wounds) and SM/J (nonhealer) inbred mouse strains. An acute full-thickness cartilage injury was introduced in the trochlear groove of 8-week-old mice (n=265) through microsurgery. Mouse knee joints were sagittally sectioned and stained with toluidine blue to evaluate regeneration. For the ear wound phenotype, a bilateral 2-mm through-and-through puncture was created in 6-week-old mice (n=229), and healing outcomes were measured after 30 days. Broad-sense heritability and genetic correlations were calculated for both phenotypes. Time-course analysis of the RI mouse lines showed no significant regeneration until 16 weeks after surgery; at that time, the strains could be segregated into 3 categories: good, intermediate, and poor healers. Analysis of heritability (H2) showed that both cartilage regeneration (H2=26%; P=0.006) and ear wound closure (H2=53%; P<0.00001) were significantly heritable. The genetic correlations between the two healing phenotypes for common inbred mouse strains (r=0.92) and RI mouse lines (r=0.86) were found to be extremely high. Our findings indicate that articular cartilage regeneration in mice is heritable, the differences between the mouse lines are due to genetic differences, and a strong genetic correlation between the two phenotypes exists, indicating that they plausibly share a common genetic basis. We therefore surmise that LG/J by SM/J intercross mice can be used to dissect the genetic basis of variation in cartilage regeneration. Copyright © 2012 by the American College of Rheumatology.

Mapping a region within the 1RS.1BL translocation in common wheat affecting grain yield and canopy water status.

PubMed

Howell, Tyson; Hale, Iago; Jankuloski, Ljupcho; Bonafede, Marcos; Gilbert, Matthew; Dubcovsky, Jorge

2014-12-01

This study identifies a small distal region of the 1RS chromosome from rye that has a positive impact on wheat yield. The translocation of the short arm of rye (Secale cereale L.) chromosome one (1RS) onto wheat (Triticum aestivum L.) chromosome 1B (1RS.1BL) is used in wheat breeding programs worldwide due to its positive effect on yield, particularly under abiotic stress. Unfortunately, this translocation is associated with poor bread-making quality. To mitigate this problem, the 1RS arm was engineered by the removal and replacement of two interstitial rye segments with wheat chromatin: a distal segment to introduce the Glu-B3/Gli-B1 loci from wheat, and a proximal segment to remove the rye Sec-1 locus. We used this engineered 1RS chromosome (henceforth 1RS(WW)) to develop and evaluate two sets of 1RS/1RS(WW) near isogenic lines (NILs). Field trials showed that standard 1RS lines had significantly higher yield and better canopy water status than the 1RS(WW) NILs in both well-watered and water-stressed environments. We intercrossed the 1RS and 1RS(WW) lines and generated two additional NILs, one carrying the distal (1RS(RW)) and the other carrying the proximal (1RS(WR)) wheat segment. Lines not carrying the distal wheat region (1RS and 1RS(WR)) showed significant improvements in grain yield and canopy water status compared to NILs carrying the distal wheat segment (1RS(WW) and 1RS(RW)), indicating that the 1RS region replaced by the distal wheat segment carries the beneficial allele(s). NILs without the distal wheat segment also showed higher carbon isotope discrimination and increased stomatal conductance, suggesting that these plants had improved access to water. The 1RS(WW), 1RS(WR) and 1RS(RW) NILs have been deposited in the National Small Grains Collection.

Conditionally Immortal Slc4a11-/- Mouse Corneal Endothelial Cell Line Recapitulates Disrupted Glutaminolysis Seen in Slc4a11-/- Mouse Model.

PubMed

Zhang, Wenlin; Ogando, Diego G; Kim, Edward T; Choi, Moon-Jung; Li, Hongde; Tenessen, Jason M; Bonanno, Joseph A

2017-07-01

To establish conditionally immortal mouse corneal endothelial cell lines with genetically matched Slc4a11+/+ and Slc4a11-/- mice as a model for investigating pathology and therapies for SLC4A11 associated congenital hereditary endothelial dystrophy (CHED) and Fuchs' endothelial corneal dystrophy. We intercrossed H-2Kb-tsA58 mice (Immortomouse) expressing an IFN-γ dependent and temperature-sensitive mutant of the SV40 large T antigen (tsTAg) with Slc4a11+/+ and Slc4a11-/- C57BL/6 mice. The growth characteristics of the cell lines was assessed by doubling time. Ion transport activities (Na+/H+ exchange, bicarbonate, lactate, and Slc4a11 ammonia transport) were analyzed by intracellular pH measurement. The metabolic status of the cell lines was assessed by analyzing TCA cycle intermediates via gas chromatography mass spectrometry (GC-MS). The immortalized Slc4a11+/+ and Slc4a11-/- mouse corneal endothelial cells (MCECs) remained proliferative through passage 49 and maintained similar active ion transport activity. As expected, proliferation was temperature sensitive and IFN-γ dependent. Slc4a11-/- MCECs exhibited decreased proliferative capacity, reduced NH3:H+ transport, altered expression of glutaminolysis enzymes similar to the Slc4a11-/- mouse, and reduced proportion of TCA cycle intermediates derived from glutamine with compensatory increases in glucose flux compared with Slc4a11+/+ MCECs. This is the first report of the immortalization of MCECs. Ion transport of the immortalized endothelial cells remains active, except for NH3:H+ transporter activity in Slc4a11-/- MCECs. Furthermore, Slc4a11-/- MCECs recapitulate the glutaminolysis defects observed in Slc4a11-/- mouse corneal endothelium, providing an excellent tool to study the pathogenesis of SLC4A11 mutations associated with corneal endothelial dystrophies and to screen potential therapeutic agents.

Facile fabrication of BiVO4 nanofilms with controlled pore size and their photoelectrochemical performances.

PubMed

Feng, Chenchen; Jiao, Zhengbo; Li, Shaopeng; Zhang, Yan; Bi, Yingpu

2015-12-28

We demonstrate a facile method for the rational fabrication of pore-size controlled nanoporous BiVO(4) photoanodes, and confirmed that the optimum pore-size distributions could effectively absorb visible light through light diffraction and confinement functions. Furthermore, in situ X-ray photoelectron spectroscopy (XPS) reveals more efficient photoexcited electron-hole separation than conventional particle films, induced by light confinement and rapid charge transfer in the inter-crossed worm-like structures.

Joint Analysis of Strain and Parent-of-Origin Effects for Recombinant Inbred Intercrosses Generated from Multiparent Populations with the Collaborative Cross as an Example.

PubMed

Liu, Yanyan; Xiong, Sican; Sun, Wei; Zou, Fei

2018-02-02

Multiparent populations (MPP) have become popular resources for complex trait mapping because of their wider allelic diversity and larger population size compared with traditional two-way recombinant inbred (RI) strains. In mice, the collaborative cross (CC) is one of the most popular MPP and is derived from eight genetically diverse inbred founder strains. The strategy of generating RI intercrosses (RIX) from MPP in general and from the CC in particular can produce a large number of completely reproducible heterozygote genomes that better represent the (outbred) human population. Since both maternal and paternal haplotypes of each RIX are readily available, RIX is a powerful resource for studying both standing genetic and epigenetic variations of complex traits, in particular, the parent-of-origin (PoO) effects, which are important contributors to many complex traits. Furthermore, most complex traits are affected by >1 genes, where multiple quantitative trait locus mapping could be more advantageous. In this paper, for MPP-RIX data but taking CC-RIX as a working example, we propose a general Bayesian variable selection procedure to simultaneously search for multiple genes with founder allelic effects and PoO effects. The proposed model respects the complex relationship among RIX samples, and the performance of the proposed method is examined by extensive simulations. Copyright © 2018 Liu et al.

Genetics and evolution of hybrid male sterility in house mice.

PubMed

White, Michael A; Stubbings, Maria; Dumont, Beth L; Payseur, Bret A

2012-07-01

Comparative genetic mapping provides insights into the evolution of the reproductive barriers that separate closely related species. This approach has been used to document the accumulation of reproductive incompatibilities over time, but has only been applied to a few taxa. House mice offer a powerful system to reconstruct the evolution of reproductive isolation between multiple subspecies pairs. However, studies of the primary reproductive barrier in house mice-hybrid male sterility-have been restricted to a single subspecies pair: Mus musculus musculus and Mus musculus domesticus. To provide a more complete characterization of reproductive isolation in house mice, we conducted an F(2) intercross between wild-derived inbred strains from Mus musculus castaneus and M. m. domesticus. We identified autosomal and X-linked QTL associated with a range of hybrid male sterility phenotypes, including testis weight, sperm density, and sperm morphology. The pseudoautosomal region (PAR) was strongly associated with hybrid sterility phenotypes when heterozygous. We compared QTL found in this cross with QTL identified in a previous F(2) intercross between M. m. musculus and M. m. domesticus and found three shared autosomal QTL. Most QTL were not shared, demonstrating that the genetic basis of hybrid male sterility largely differs between these closely related subspecies pairs. These results lay the groundwork for identifying genes responsible for the early stages of speciation in house mice.

Genetics and Evolution of Hybrid Male Sterility in House Mice

PubMed Central

White, Michael A.; Stubbings, Maria; Dumont, Beth L.; Payseur, Bret A.

2012-01-01

Comparative genetic mapping provides insights into the evolution of the reproductive barriers that separate closely related species. This approach has been used to document the accumulation of reproductive incompatibilities over time, but has only been applied to a few taxa. House mice offer a powerful system to reconstruct the evolution of reproductive isolation between multiple subspecies pairs. However, studies of the primary reproductive barrier in house mice—hybrid male sterility—have been restricted to a single subspecies pair: Mus musculus musculus and Mus musculus domesticus. To provide a more complete characterization of reproductive isolation in house mice, we conducted an F2 intercross between wild-derived inbred strains from Mus musculus castaneus and M. m. domesticus. We identified autosomal and X-linked QTL associated with a range of hybrid male sterility phenotypes, including testis weight, sperm density, and sperm morphology. The pseudoautosomal region (PAR) was strongly associated with hybrid sterility phenotypes when heterozygous. We compared QTL found in this cross with QTL identified in a previous F2 intercross between M. m. musculus and M. m. domesticus and found three shared autosomal QTL. Most QTL were not shared, demonstrating that the genetic basis of hybrid male sterility largely differs between these closely related subspecies pairs. These results lay the groundwork for identifying genes responsible for the early stages of speciation in house mice. PMID:22554891

Hypertensive renal disease: susceptibility and resistance in inbred hypertensive rat lines.

PubMed

Braun, Michael C; Herring, Stacy M; Gokul, Nisha; Monita, Monique; Bell, Rebecca; Hicks, M John; Wenderfer, Scott E; Doris, Peter A

2013-10-01

Spontaneously hypertensive rat (SHR) lines differ in their susceptibility to hypertensive end-organ disease and may provide an informative model of genetic risk of disease. Lines derived from the original SHR-B and SHR-C clades are highly resistant to hypertensive end-organ disease, whereas lines derived from the SHR-A clade were selected for stroke susceptibility and experience hypertensive renal disease. Here we characterize the temporal development of progressive renal injury in SHR-A3 animals consuming 0.3% sodium in the diet and drinking water. SHR-A3 rats demonstrate albuminuria, glomerular damage, tubulointerstitial injury, and renal fibrosis that emerge at 18 weeks of age and progress. Mortality of SHR-A3 animals was 50% at 40 weeks of age, and animals surviving to this age had reduced renal function. In contrast SHR-B2, which are 87% genetically identical to SHR-A3, are substantially protected from renal injury and demonstrate only moderate changes in albuminuria and renal histological injury over this time period. At 40 weeks of age, electron microscopy of the renal glomerulus revealed severe podocyte effacement in SHR-A3, but slit diaphragm architecture in SHR-B2 at this age was well preserved. Renal injury traits in the F1 and F2 progeny of an intercross between SHR-A3 and SHR-B2 were measured to determine heritability of renal injury in this model. Heritability of albuminuria, glomerular injury, and tubulointerstitial injury were estimated at 48.9, 66.5 and 58.6%, respectively. We assessed the relationship between blood pressure and renal injury measures in the F2 animals and found some correlation between these variables that explain up to 26% of the trait variation. Quantitative trait locus (QTL) mapping was performed using over 200 single nucleotide polymorphism markers distributed across the 13% of the genome that differs between these two closely related lines. Mapping of albuminuria, tubulointerstitial injury, and renal fibrosis failed to identify loci linked with disease susceptibility, suggesting a complex inheritance of disease risk. We detected a single QTL conferring susceptibility to glomerular injury that was confined to a small haplotype block at chromosome 14:70-76Mb.

Disease management patterns for postmenopausal women in Europe with hormone-receptor-positive, human epidermal growth factor receptor-2 negative advanced breast cancer.

PubMed

André, Fabrice; Neven, Patrick; Marinsek, Nina; Zhang, Jie; Baladi, Jean-Francois; Degun, Ravi; Benelli, Giancarlo; Saletan, Stephen; Jerusalem, Guy

2014-06-01

International guidelines for hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2 negative (HER2(-)) advanced breast cancer (BC) recommend sequential lines of hormonal therapy (HT), and only recommend chemotherapy for patients with extensive visceral involvement or rapidly progressive disease. This study evaluated actual physician-reported treatments for advanced BC in Europe. We conducted a retrospective chart review of 355 postmenopausal women with HR(+), HER2(-) advanced BC who progressed on ≥1 line of HT (adjuvant or advanced) and completed ≥1 line of chemotherapy (advanced). Treatment choice was evaluated for each line of therapy. Of 355 patients, 111 (31%) received first-line chemotherapy, whereas 218 (61%) and 26 (7%) switched from HT to chemotherapy in second and third line, respectively. More patients receiving first-line HT had bone metastases (73% vs 27% chemotherapy). Patients treated with first-line chemotherapy had more brain (12% vs 3% HT) or extensive liver (13% vs 6% HT) metastases. Subgroup analysis of 188 patients who received first-line HT and had de novo advanced BC or relapsed/recurrent disease more than 1 year after adjuvant therapy found that the majority (89%; n = 167) of these patients switched to chemotherapy in second line. However, among these 167 patients, 27% had no significant changes in metastases between first and second line. Among the 73% of patients who had significant changes in metastases, 20% had no brain metastases or extensive visceral disease. Our study suggests that the guideline-recommended use of multiple HT lines is open to interpretation and that optimal treatment for European postmenopausal women with HR(+), HER2(-) advanced BC who responded to HT may not be achieved.

Development and characterization of a strawberry MAGIC population derived from crosses with six strawberry cultivars

PubMed Central

Wada, Takuya; Oku, Koichiro; Nagano, Soichiro; Isobe, Sachiko; Suzuki, Hideyuki; Mori, Miyuki; Takata, Kinuko; Hirata, Chiharu; Shimomura, Katsumi; Tsubone, Masao; Katayama, Takao; Hirashima, Keita; Uchimura, Yosuke; Ikegami, Hidetoshi; Sueyoshi, Takayuki; Obu, Ko-ichi; Hayashida, Tatsuya; Shibato, Yasushi

2017-01-01

A strawberry Multi-parent Advanced Generation Intercrosses (MAGIC) population, derived from crosses using six strawberry cultivars was successfully developed. The population was composed of 338 individuals; genome conformation was evaluated by expressed sequence tag-derived simple short repeat (EST-SSR) markers. Cluster analysis and principal component analysis (PCA) based on EST-SSR marker polymorphisms revealed that the MAGIC population was a mosaic of the six founder cultivars and covered the genomic regions of the six founders evenly. Fruit quality related traits, including days to flowering (DTF), fruit weight (FW), fruit firmness (FF), fruit color (FC), soluble solid content (SC), and titratable acidity (TA), of the MAGIC population were evaluated over two years. All traits showed normal transgressive segregation beyond the founder cultivars and most traits, except for DTF, distributed normally. FC exhibited the highest correlation coefficient overall and was distributed normally regardless of differences in DTF, FW, FF, SC, and TA. These facts were supported by PCA using fruit quality related values as explanatory variables, suggesting that major genetic factors, which are not influenced by fluctuations in other fruit traits, could control the distribution of FC. This MAGIC population is a promising resource for genome-wide association studies and genomic selection for efficient strawberry breeding. PMID:29085247

Conditionally Immortal Slc4a11−/− Mouse Corneal Endothelial Cell Line Recapitulates Disrupted Glutaminolysis Seen in Slc4a11−/− Mouse Model

PubMed Central

Zhang, Wenlin; Ogando, Diego G.; Kim, Edward T.; Choi, Moon-Jung; Li, Hongde; Tenessen, Jason M.; Bonanno, Joseph A.

2017-01-01

Purpose To establish conditionally immortal mouse corneal endothelial cell lines with genetically matched Slc4a11+/+ and Slc4a11−/− mice as a model for investigating pathology and therapies for SLC4A11 associated congenital hereditary endothelial dystrophy (CHED) and Fuchs' endothelial corneal dystrophy. Methods We intercrossed H-2Kb-tsA58 mice (Immortomouse) expressing an IFN-γ dependent and temperature-sensitive mutant of the SV40 large T antigen (tsTAg) with Slc4a11+/+ and Slc4a11−/− C57BL/6 mice. The growth characteristics of the cell lines was assessed by doubling time. Ion transport activities (Na+/H+ exchange, bicarbonate, lactate, and Slc4a11 ammonia transport) were analyzed by intracellular pH measurement. The metabolic status of the cell lines was assessed by analyzing TCA cycle intermediates via gas chromatography mass spectrometry (GC-MS). Results The immortalized Slc4a11+/+ and Slc4a11−/− mouse corneal endothelial cells (MCECs) remained proliferative through passage 49 and maintained similar active ion transport activity. As expected, proliferation was temperature sensitive and IFN-γ dependent. Slc4a11−/− MCECs exhibited decreased proliferative capacity, reduced NH3:H+ transport, altered expression of glutaminolysis enzymes similar to the Slc4a11−/− mouse, and reduced proportion of TCA cycle intermediates derived from glutamine with compensatory increases in glucose flux compared with Slc4a11+/+ MCECs. Conclusions This is the first report of the immortalization of MCECs. Ion transport of the immortalized endothelial cells remains active, except for NH3:H+ transporter activity in Slc4a11−/− MCECs. Furthermore, Slc4a11−/− MCECs recapitulate the glutaminolysis defects observed in Slc4a11−/− mouse corneal endothelium, providing an excellent tool to study the pathogenesis of SLC4A11 mutations associated with corneal endothelial dystrophies and to screen potential therapeutic agents. PMID:28738416

Defects-tolerant Co-Cr-Mo dental alloys prepared by selective laser melting.

PubMed

Qian, B; Saeidi, K; Kvetková, L; Lofaj, F; Xiao, C; Shen, Z

2015-12-01

CrCoMo alloy specimens were successfully fabricated using selective laser melting (SLM). The aim of this study was to carefully investigate microstructure of the SLM specimens in order to understand the influence of their structural features inter-grown on different length scales ranging from nano- to macro-levels on their mechanical properties. Two different sets of processing parameters developed for building the inner part (core) and the surface (skin) of dental prostheses were tested. Microstructures were characterized by SEM, EBSD and XRD analysis. The elemental distribution was assessed by EDS line profile analysis under TEM. The mechanical properties of the specimens were measured. The microstructures of both specimens were characterized showing formation of grains comprised of columnar sub-grains with Mo-enrichment at the sub-grain boundaries. Clusters of columnar sub-grains grew coherently along one common crystallographic direction forming much larger single crystal grains which are intercrossing in different directions forming an overall dendrite-like microstructure. Three types of microstructural defects were occasionally observed; small voids (<10 μm), fine cracks at grain boundaries (<10 μm) and cracks at weld line boundaries (>10 μm). Despite the presence of these defects, the yield and the ultimate tensile strength (UTS) were 870 and 430MPa and 1300MPa and 1160MPa, respectively, for the skin and core specimens which are higher than casted dental alloy. Although the formation of microstructural defects is hard to be avoided during the SLM process, the SLM CoCrMo alloys can achieve improved mechanical properties than their casted counterparts, implying they are "defect-tolerant". Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Genetic determinism of bone and mineral metabolism in meat-type chickens: A QTL mapping study.

PubMed

Mignon-Grasteau, Sandrine; Chantry-Darmon, Céline; Boscher, Marie-Yvonne; Sellier, Nadine; Chabault-Dhuit, Marie; Le Bihan-Duval, Elisabeth; Narcy, Agnès

2016-12-01

Skeletal integrity in meat-type chickens is affected by many factors including rapid growth rate, nutrition and genetics. To investigate the genetic basis of bone and mineral metabolism, a QTL detection study was conducted in an intercross between two lines of meat-type chickens divergently selected for their high (D +) or low (D -) digestive efficiency. Tibia size (length, diameter, volume) and ash content were determined at 3 weeks of age as well as phosphorus (P) retention and plasma concentration. Heritability of these traits and their genetic correlations with digestive efficiency were estimated. A QTL mapping study was performed using 3379 SNP markers. Tibia size, weight, ash content and breaking strength were highly heritable (0.42 to 0.61). Relative tibia diameter and volume as well as P retention were strongly and positively genetically correlated with digestive efficiency (0.57 to 0.80). A total of 35 QTL were identified (9 for tibia weight, 13 for tibia size, 5 for bone strength, 5 for bone mineralization, 2 for plasma P concentration and 1 for P retention). Six QTL were genome-wide significant, and 3 QTL for tibia relative volume, weight and ash weight on chromosome 6 were fixed, the positive allele coming from the D-line. For two QTL for ash content on chromosome 18 and relative tibia length on chromosome 26, the confidence intervals were small enough to identify potential candidate genes. These findings support the evidence of multiple genetic loci controlling bone and mineral metabolism. The identification of candidate genes may provide new perspectives in the understanding of bone regulation, even beyond avian species.

Quantitative Trait Loci for BMD in an SM/J by NZB/BlNJ Intercross Population and Identification of Trps1 as a Probable Candidate Gene

PubMed Central

Ishimori, Naoki; Stylianou, Ioannis M; Korstanje, Ron; Marion, Michael A; Li, Renhua; Donahue, Leah Rae; Rosen, Clifford J; Beamer, Wesley G; Paigen, Beverly; Churchill, Gary A

2008-01-01

Identification of genes that regulate BMD will enhance our understanding of osteoporosis and could provide novel molecular targets for treatment or prevention. We generated a mouse intercross population and carried out a quantitative trait locus (QTL) analysis of 143 female and 124 male F2 progeny from progenitor strains SM/J and NZB/BlNJ using whole body and vertebral areal BMD (aBMD) as measured by DXA. We found that both whole body and vertebral aBMD was affected by two loci on chromosome 9: one with a significant epistatic interaction on distal chromosome 8 and the other with a sex-specific effect. Two additional significant QTLs were identified on chromosome 12, and several suggestive ones were identified on chromosomes 5, 8, 15, and 19. The chromosome 9, 12, and 15 loci have been previously identified in other crosses. SNP-based haplotype analysis of the progenitor strains identified blocks within the QTL region that distinguish the low allele strains from the high allele strains, significantly narrowing the QTL region and reducing the possible candidate genes to 98 for chromosome 9, 31 for chromosome 12, and only 2 for chromosome 15. Trps1 is the most probable candidate gene for the chromosome 15 QTL. The sex-specific effects may help to elucidate the BMD differences between males and females. This study shows the power of statistical modeling to resolve linked QTLs and the use of haplotype analysis in narrowing the list of candidates. PMID:18442308

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

PubMed

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

2014-12-01

A high-density single nucleotide polymorphism (SNP) array containing 62 163 markers was employed for a genome-wide association study (GWAS) to identify variants associated with lean meat in ham (LMH, %) and lean meat percentage (LMP, %) within a porcine Large White×Minzhu intercross population. For each individual, LMH and LMP were measured after slaughter at the age of 240±7 days. A total of 557 F2 animals were genotyped. The GWAS revealed that 21 SNPs showed significant genome-wide or chromosome-wide associations with LMH and LMP by the Genome-wide Rapid Association using Mixed Model and Regression-Genomic Control approach. Nineteen significant genome-wide SNPs were mapped to the distal end of Sus Scrofa Chromosome (SSC) 2, where a major known gene responsible for muscle mass, IGF2 is located. A conditioned analysis, in which the genotype of the strongest associated SNP is included as a fixed effect in the model, showed that those significant SNPs on SSC2 were derived from a single quantitative trait locus. The two chromosome-wide association SNPs on SSC1 disappeared after conditioned analysis suggested the association signal is a false association derived from using a F2 population. The present result is expected to lead to novel insights into muscle mass in different pig breeds and lays a preliminary foundation for follow-up studies for identification of causal mutations for subsequent application in marker-assisted selection programs for improving muscle mass in pigs. © 2014 Japanese Society of Animal Science.

Distribution of Escherichia coli F4 adhesion phenotypes in pigs of 15 Chinese and Western breeds and a White DurocxErhualian intercross.

PubMed

Yan, Xueming; Huang, Xiang; Ren, Jun; Zou, Zhengzhi; Yang, Shujin; Ouyang, Jing; Zeng, Weihong; Yang, Bin; Xiao, Shijun; Huang, Lusheng

2009-08-01

Diarrhoea in newborn and weaned piglets is mainly caused by enterotoxigenic Escherichia coli (ETEC) with fimbriae F4. To investigate the prevalence of resistance to three fimbrial strains, F4ab, F4ac and F4ad, among Chinese indigenous pigs and Western commercial pigs introduced into China, we determined the ETEC F4 adhesion phenotypes in 292 pure-bred piglets from three Western commercial breeds and 12 Chinese indigenous breeds, and a total of 1093 adult pigs in a White DurocxErhualian intercross, by an in vitro microscopic adhesion assay. All the Tibet and Lantang pigs and a majority of the Erhualian and Rongchang pigs were resistant (nonadherent) to ETEC F4 whereas all the Laiwu pigs and most of the Jiangquhai and Tongcheng pigs were susceptible (adhesive) to at least one of the F4 strains. Yushan Black pigs were uniformly resistant to F4ab, and Jinhua pigs were predominantly resistant to F4ac. Susceptible and resistant animals were observed in the other breeds, indicating that diarrhoea caused by ETEC F4 could be prevalent in these breeds. This study confirmed the existence of eight previously reported F4 adhesion patterns, and supported the assumption that the three F4 receptors are encoded by distinct loci. Expression of the weakly adherent phenotype was observed in six pure-bred piglets and 90 adult F(2)/F(3) animals, and the inheritance of this phenotype and its correlation with susceptibility to disease are still not known.

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

DOT National Transportation Integrated Search

2013-01-01

SunLine Transit Agency provides public transit services to the Coachella Valley area of California. SunLine has demonstrated hydrogen and fuel cell bus technologies for more than 10 years. In May 2010, SunLine began demonstrating the advanced technol...

Combination Therapy with Capecitabine and Cisplatin as Second-Line Chemotherapy for Advanced Biliary Tract Cancer.

PubMed

Jung, Jang Han; Lee, Hee Seung; Jo, Jung Hyun; Cho, In Rae; Chung, Moon Jae; Bang, Seungmin; Park, Seung Woo; Song, Si Young; Park, Jeong Youp

2017-01-01

Palliative chemotherapy is the main treatment for advanced biliary tract cancer (BTC). However, there is a lack of established second-line chemotherapy to treat disease progression after first-line chemotherapy. We examined combination therapy with capecitabine and cisplatin for advanced BTC as a second-line regimen. We analyzed the medical records of 40 patients diagnosed with BTC who received palliative second-line chemotherapy with capecitabine and cisplatin. The median overall survival from the start of second-line chemotherapy was 6.3 months. The median overall survival from diagnosis was 17.9 months. The median progression-free survival during second-line chemotherapy was 2.3 months. Nine (30%) patients experienced adverse events of grade ≥3. Eastern Cooperative Oncology Group performance score was an independent predictor of adverse events. Combination therapy with capecitabine and cisplatin may be an option for second-line chemotherapy in some of patients with advanced BTC. © 2017 S. Karger AG, Basel.

The genetic architecture of resistance to virus infection in Drosophila.

PubMed

Cogni, Rodrigo; Cao, Chuan; Day, Jonathan P; Bridson, Calum; Jiggins, Francis M

2016-10-01

Variation in susceptibility to infection has a substantial genetic component in natural populations, and it has been argued that selection by pathogens may result in it having a simpler genetic architecture than many other quantitative traits. This is important as models of host-pathogen co-evolution typically assume resistance is controlled by a small number of genes. Using the Drosophila melanogaster multiparent advanced intercross, we investigated the genetic architecture of resistance to two naturally occurring viruses, the sigma virus and DCV (Drosophila C virus). We found extensive genetic variation in resistance to both viruses. For DCV resistance, this variation is largely caused by two major-effect loci. Sigma virus resistance involves more genes - we mapped five loci, and together these explained less than half the genetic variance. Nonetheless, several of these had a large effect on resistance. Models of co-evolution typically assume strong epistatic interactions between polymorphisms controlling resistance, but we were only able to detect one locus that altered the effect of the main effect loci we had mapped. Most of the loci we mapped were probably at an intermediate frequency in natural populations. Overall, our results are consistent with major-effect genes commonly affecting susceptibility to infectious diseases, with DCV resistance being a near-Mendelian trait. © 2016 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

Genetic Dissection of a Key Reproductive Barrier Between Nascent Species of House Mice

PubMed Central

White, Michael A.; Steffy, Brian; Wiltshire, Tim; Payseur, Bret A.

2011-01-01

Reproductive isolation between species is often caused by deleterious interactions among loci in hybrids. Finding the genes involved in these incompatibilities provides insight into the mechanisms of speciation. With recently diverged subspecies, house mice provide a powerful system for understanding the genetics of reproductive isolation early in the speciation process. Although previous studies have yielded important clues about the genetics of hybrid male sterility in house mice, they have been restricted to F1 sterility or incompatibilities involving the X chromosome. To provide a more complete characterization of this key reproductive barrier, we conducted an F2 intercross between wild-derived inbred strains from two subspecies of house mice, Mus musculus musculus and Mus musculus domesticus. We identified a suite of autosomal and X-linked QTL that underlie measures of hybrid male sterility, including testis weight, sperm density, and sperm morphology. In many cases, the autosomal loci were unique to a specific sterility trait and exhibited an effect only when homozygous, underscoring the importance of examining reproductive barriers beyond the F1 generation. We also found novel two-locus incompatibilities between the M. m. musculus X chromosome and M. m. domesticus autosomal alleles. Our results reveal a complex genetic architecture for hybrid male sterility and suggest a prominent role for reproductive barriers in advanced generations in maintaining subspecies integrity in house mice. PMID:21750261

Genetic dissection of a key reproductive barrier between nascent species of house mice.

PubMed

White, Michael A; Steffy, Brian; Wiltshire, Tim; Payseur, Bret A

2011-09-01

Reproductive isolation between species is often caused by deleterious interactions among loci in hybrids. Finding the genes involved in these incompatibilities provides insight into the mechanisms of speciation. With recently diverged subspecies, house mice provide a powerful system for understanding the genetics of reproductive isolation early in the speciation process. Although previous studies have yielded important clues about the genetics of hybrid male sterility in house mice, they have been restricted to F1 sterility or incompatibilities involving the X chromosome. To provide a more complete characterization of this key reproductive barrier, we conducted an F2 intercross between wild-derived inbred strains from two subspecies of house mice, Mus musculus musculus and Mus musculus domesticus. We identified a suite of autosomal and X-linked QTL that underlie measures of hybrid male sterility, including testis weight, sperm density, and sperm morphology. In many cases, the autosomal loci were unique to a specific sterility trait and exhibited an effect only when homozygous, underscoring the importance of examining reproductive barriers beyond the F1 generation. We also found novel two-locus incompatibilities between the M. m. musculus X chromosome and M. m. domesticus autosomal alleles. Our results reveal a complex genetic architecture for hybrid male sterility and suggest a prominent role for reproductive barriers in advanced generations in maintaining subspecies integrity in house mice.

Fine-scale maps of recombination rates and hotspots in the mouse genome.

PubMed

Brunschwig, Hadassa; Levi, Liat; Ben-David, Eyal; Williams, Robert W; Yakir, Benjamin; Shifman, Sagiv

2012-07-01

Recombination events are not uniformly distributed and often cluster in narrow regions known as recombination hotspots. Several studies using different approaches have dramatically advanced our understanding of recombination hotspot regulation. Population genetic data have been used to map and quantify hotspots in the human genome. Genetic variation in recombination rates and hotspots usage have been explored in human pedigrees, mouse intercrosses, and by sperm typing. These studies pointed to the central role of the PRDM9 gene in hotspot modulation. In this study, we used single nucleotide polymorphisms (SNPs) from whole-genome resequencing and genotyping studies of mouse inbred strains to estimate recombination rates across the mouse genome and identified 47,068 historical hotspots--an average of over 2477 per chromosome. We show by simulation that inbred mouse strains can be used to identify positions of historical hotspots. Recombination hotspots were found to be enriched for the predicted binding sequences for different alleles of the PRDM9 protein. Recombination rates were on average lower near transcription start sites (TSS). Comparing the inferred historical recombination hotspots with the recent genome-wide mapping of double-strand breaks (DSBs) in mouse sperm revealed a significant overlap, especially toward the telomeres. Our results suggest that inbred strains can be used to characterize and study the dynamics of historical recombination hotspots. They also strengthen previous findings on mouse recombination hotspots, and specifically the impact of sequence variants in Prdm9.

Efficiency of low dosage apatinib in post-first-line treatment of advanced lung adenocarcinoma.

PubMed

Zeng, Da-Xiong; Wang, Chang-Guo; Lei, Wei; Huang, Jian-An; Jiang, Jun-Hong

2017-09-12

Chemotherapy is the standard treatment of in advanced lung adenocarcinoma patients without driver mutation. However, few drugs could be selected when diseases progressed after second-line treatment. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), apatinib was suggested mainly using in advanced gastric cancer. In this study, we showed the results of apatinib as second-line to fourth-line treatment in EGFR wild-type advanced lung adenocarcinoma patients. 16 EGFR wild-type advanced lung adenocarcinoma patients were administrated apatinib (250-500 mg/d) orally. 3 patients showed partial response and 8 patients showed stable diseases response to apatinib, with a medium progression-free survival (PFS) of 4.4 month (2-10 months). The objective remission rate (ORR) was 18.75%(3/16). The total disease control rate (DCR) was 68.75% (11/16). The main toxicities were hypertension, hand-foot syndrome, proteinuria and thrombocytopenia which were tolerable and manageable. So, apatinib might be an optional choice for post-first-line treatment of EGFR wild-type advanced lung adenocarcinoma patients.

Identification of Aortic Arch-Specific Quantitative Trait Loci for Atherosclerosis by an Intercross of DBA/2J and 129S6 Apolipoprotein E-Deficient Mice

PubMed Central

Kayashima, Yukako; Makhanova, Natalia A.; Matsuki, Kota; Tomita, Hirofumi; Bennett, Brian J.; Maeda, Nobuyo

2015-01-01

The genetic background of apolipoprotein E (apoE) deficient mice influences atherosclerotic plaque development. We previously reported three quantitative trait loci (QTL), Aath1–Aath3, that affect aortic arch atherosclerosis independently of those in the aortic root in a cross between C57BL6 apoEKO mice (B6-apoE) and 129S6 apoEKO mice (129-apoE). To gain further insight into genetic factors that influence atherosclerosis at different vascular locations, we analyzed 335 F2 mice from an intercross between 129-apoE and apoEKO mice on a DBA/2J genetic background (DBA-apoE). The extent of atherosclerosis in the aortic arch was very similar in the two parental strains. Nevertheless, a genome-wide scan identified two significant QTL for plaque size in the aortic arch: Aath4 on Chromosome (Chr) 2 at 137 Mb and Aath5 on Chr 10 at 51 Mb. The DBA alleles of Aath4 and Aath5 respectively confer susceptibility and resistance to aortic arch atherosclerosis over 129 alleles. Both QTL are also independent of those affecting plaque size at the aortic root. Genome analysis suggests that athero-susceptibility of Aath4 in DBA may be contributed by multiple genes, including Mertk and Cd93, that play roles in phagocytosis of apoptotic cells and modulate inflammation. A candidate gene for Aath5 is Stab2, the DBA allele of which is associated with 10 times higher plasma hyaluronan than the 129 allele. Overall, our identification of two new QTL that affect atherosclerosis in an aortic arch-specific manner further supports the involvement of distinct pathological processes at different vascular locations. PMID:25689165

Hypothalamic expression of Peg3 gene is associated with maternal care differences between SM/J and LG/J mouse strains

PubMed Central

Chiavegatto, Silvana; Sauce, Bruno; Ambar, Guilherme; Cheverud, James M; Peripato, Andrea C

2012-01-01

Maternal care is essential in mammals, and variations in the environment provided by mothers may directly influence the viability of newborns and emotional behavior later in life. A previous study investigated genetic variations associated with maternal care in an intercross of LG/J and SM/J inbred mouse strains and identified two single-locus QTLs (quantitative trait loci). Here, we selected three candidate genes located within these QTLs intervals; Oxt on chromosome 2, and FosB and Peg3 on chromosome 7 and tested their association with maternal care. LG/J females showed impaired postpartum nest building and pup retrieval, a one-day delay in milk ejection, reduced exploratory activity, and higher anxiety-like behavior when compared to SM/J females. The nucleotide sequences of Oxt and FosB were similar between strains, as were their hypothalamic expression levels. Conversely, Peg3 nucleotide sequences showed four nonsynonymous replacement substitutions on LG/J dams, T11062G, G13744A, A13808G, and G13813A, and a 30 base pair (10 aa) in tandem repeat in the coding region with three copies in SM/J and five copies in LG/J. Maternal care impaired LG/J mothers express 37% lower Peg3 mRNA levels in the hypothalamus on the second postpartum day. We also found an association of the Peg3 repeat-variant and poor maternal care in F2 heterozygote females derived from a LG/J × SM/J intercross. These results may suggest that the maternally imprinted Peg3 gene is responsible for the single-locus QTL on chromosome 7 that has been shown to influence maternal care in these strains. Furthermore, these data provide additional support for an epigenetic regulation of maternal behavior. PMID:22950040

Differential Genetic Basis for Pre-Menopausal and Post-Menopausal Salt-Sensitive Hypertension

PubMed Central

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

2012-01-01

Essential hypertension affects 75% of post-menopausal women in the United States causing greater cardiovascular complications compared with age-matched men and pre-menopausal women. Hormone replacement and current anti-hypertensive therapies do not correct this post-menopausal increased risk suggesting a distinct pathogenic framework. We investigated the hypothesis that distinct genetic determinants might underlie susceptibility to salt sensitive hypertension in pre-menopausal and post-menopausal states. To determine whether distinct genetic loci contribute to post-menopausal salt-sensitive hypertension, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting blood pressure (BP) in 16-month old post-menopausal F2 (Dahl S×R)-intercross female rats characterized for blood pressure by radiotelemetry. Given identical environments and high salt challenge, post-menopausal BP levels were significantly higher than observed in pre-menopausal (post-menopausal versus pre-menopausal SBP, P<0.0001) and ovariectomized (post-menopausal versus ovariectomized SBP, P<0.001) F2-intercross female rats. We detected four significant to highly significant BP-QTLs (BP-pm1 on chromosome 13, LOD 3.78; BP-pm2 on chromosome 11, LOD 2.76; BP-pm3 on chromosome 2, LOD 2.61; BP-pm4 on chromosome 4, LOD 2.50) and two suggestive BP-QTLs (BP-pm5 on chromosome 15, LOD 2.37; BP-f1 on chromosome 5, LOD 1.65), four of which (BP-pm2, BP-pm3, BP-pm4, BP-pm5) were unique to this post-menopausal cohort. These data demonstrate distinct polygenic susceptibility underlying post-menopausal salt-sensitive hypertension providing a pathway towards the identification of mechanism-based therapy for post-menopausal hypertension and ensuing target-organ complications. PMID:22912817

Differential genetic basis for pre-menopausal and post-menopausal salt-sensitive hypertension.

PubMed

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

2012-01-01

Essential hypertension affects 75% of post-menopausal women in the United States causing greater cardiovascular complications compared with age-matched men and pre-menopausal women. Hormone replacement and current anti-hypertensive therapies do not correct this post-menopausal increased risk suggesting a distinct pathogenic framework. We investigated the hypothesis that distinct genetic determinants might underlie susceptibility to salt sensitive hypertension in pre-menopausal and post-menopausal states. To determine whether distinct genetic loci contribute to post-menopausal salt-sensitive hypertension, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting blood pressure (BP) in 16-month old post-menopausal F2 (Dahl S×R)-intercross female rats characterized for blood pressure by radiotelemetry. Given identical environments and high salt challenge, post-menopausal BP levels were significantly higher than observed in pre-menopausal (post-menopausal versus pre-menopausal SBP, P<0.0001) and ovariectomized (post-menopausal versus ovariectomized SBP, P<0.001) F2-intercross female rats. We detected four significant to highly significant BP-QTLs (BP-pm1 on chromosome 13, LOD 3.78; BP-pm2 on chromosome 11, LOD 2.76; BP-pm3 on chromosome 2, LOD 2.61; BP-pm4 on chromosome 4, LOD 2.50) and two suggestive BP-QTLs (BP-pm5 on chromosome 15, LOD 2.37; BP-f1 on chromosome 5, LOD 1.65), four of which (BP-pm2, BP-pm3, BP-pm4, BP-pm5) were unique to this post-menopausal cohort. These data demonstrate distinct polygenic susceptibility underlying post-menopausal salt-sensitive hypertension providing a pathway towards the identification of mechanism-based therapy for post-menopausal hypertension and ensuing target-organ complications.

Genetic basis of differences in myxospore count between whirling disease-resistant and -susceptible strains of rainbow trout

USGS Publications Warehouse

Fetherman, Eric R.; Winkelman, Dana L.; Schisler, George J.; Antolin, Michael F.

2012-01-01

We used a quantitative genetics approach and estimated broad sense heritability (h2b) of myxospore count and the number of genes involved in myxospore formation to gain a better understanding of how resistance to Myxobolus cerebralis, the parasite responsible for whirling disease, is inherited in rainbow trout Oncorhynchus mykiss. An M. cerebralis-resistant strain of rainbow trout, the German Rainbow (GR), and a wild, susceptible strain of rainbow trout, the Colorado River Rainbow (CRR), were spawned to create 3 intermediate crossed populations (an F1 cross, F2 intercross, and a B2 backcross between the F1 and the CRR). Within each strain or cross, h2b was estimated from the between-family variance of myxospore counts using full-sibling families. Estimates of h2b and average myxospore counts were lowest in the GR strain, F1 cross, and F2 intercross (h2b = 0.34, 0.42, and 0.34; myxospores fish−1 = 275, 9566, and 45780, respectively), and highest in the B2 backcross and CRR strain (h2b = 0.93 and 0.89; myxospores fish−1 = 97865 and 187595, respectively). Comparison of means and a joint-scaling test suggest that resistance alleles arising from the GR strain are dominant to susceptible alleles from the CRR strain. Resistance was retained in the intermediate crosses but decreased as filial generation number increased (F2) or backcrossing occurred (B2). The estimated number of segregating loci responsible for differences in myxospore count in the parental strains was 9 ± 5. Our results indicate that resistance to M. cerebralis is a heritable trait within these populations and would respond to either artificial selection in hatcheries or natural selection in the wild.

Molecular mapping of the tubby (tub) mutation on mouse chromosome 7

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, W.K.; Goldberg-Berman, J.; Power-Kehoe, L.

1996-03-01

Using 180 F2 progeny of a C57BL6/J x CAST/Ei tub/+F1 intersubspecific intercross, a map of 28 molecular markers (including eight genes) on chromosome 7 surrounding the tub locus was generated. Using 33 obese F2 progeny, tub was localized approximately 50-52 cM distal to the centromere on mouse chromosome 7 in the interval defined proximally by hemoglobin beta (Hbb), D7Mit38, D7Mit217, D7Mit37, D7Mit96, and D7Mit33 and distally by D7Mit 98. Using 39 obese F2 progeny from a similar intersubspecific intercross, a telomeric boundary of the interval defining tub was defined by D7Mit53; the order centromere-Hbb/tub-D7Mit53/D7Mit328/D7Mit220-parathyroid hormone (Pth)-calcitonin (Calc)-zona pellucida 2 (2p2)more » was established. By combining the data from the two crosses, the most likely gene order on mouse chromosome 7 is centromere-Hbb-tub-Pth-Calc, thus making it likely that the human homolog of tub resides on 11p15, where the gene order HBB-PTH-CALC is conserved. Assignment of the human tubby homolog to 11p15 allows selection and development of polymorphic molecular markers that can be used to examine segregation of a human homolog of tubby in pedigrees segregating for obesity. The gene sulfonylurea receptor was eliminated as a candidate gene for tubby on the basis of its map position, approximately 3.1 {plus_minus} 3.1 cM centromeric of tyrosinase and approximately 14.9 {plus_minus} 4.8 cM centromeric of Hbb. 47 refs., 2 figs., 2 tabs.« less

A novel humanized mouse model of Huntington disease for preclinical development of therapeutics targeting mutant huntingtin alleles.

PubMed

Southwell, Amber L; Skotte, Niels H; Villanueva, Erika B; Østergaard, Michael E; Gu, Xiaofeng; Kordasiewicz, Holly B; Kay, Chris; Cheung, Daphne; Xie, Yuanyun; Waltl, Sabine; Dal Cengio, Louisa; Findlay-Black, Hailey; Doty, Crystal N; Petoukhov, Eugenia; Iworima, Diepiriye; Slama, Ramy; Ooi, Jolene; Pouladi, Mahmoud A; Yang, X William; Swayze, Eric E; Seth, Punit P; Hayden, Michael R

2017-03-15

Huntington disease (HD) is a neurodegenerative disease caused by a mutation in the huntingtin (HTT) gene. HTT is a large protein, interacts with many partners and is involved in many cellular pathways, which are perturbed in HD. Therapies targeting HTT directly are likely to provide the most global benefit. Thus there is a need for preclinical models of HD recapitulating human HTT genetics. We previously generated a humanized mouse model of HD, Hu97/18, by intercrossing BACHD and YAC18 mice with knockout of the endogenous mouse HD homolog (Hdh). Hu97/18 mice recapitulate the genetics of HD, having two full-length, genomic human HTT transgenes heterozygous for the HD mutation and polymorphisms associated with HD in populations of Caucasian descent. We have now generated a companion model, Hu128/21, by intercrossing YAC128 and BAC21 mice on the Hdh-/- background. Hu128/21 mice have two full-length, genomic human HTT transgenes heterozygous for the HD mutation and polymorphisms associated with HD in populations of East Asian descent and in a minority of patients from other ethnic groups. Hu128/21 mice display a wide variety of HD-like phenotypes that are similar to YAC128 mice. Additionally, both transgenes in Hu128/21 mice match the human HTT exon 1 reference sequence. Conversely, the BACHD transgene carries a floxed, synthetic exon 1 sequence. Hu128/21 mice will be useful for investigations of human HTT that cannot be addressed in Hu97/18 mice, for developing therapies targeted to exon 1, and for preclinical screening of personalized HTT lowering therapies in HD patients of East Asian descent. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

New quantitative trait loci for carotid atherosclerosis identified in an intercross derived from apolipoprotein E-deficient mouse strains

PubMed Central

Rowlan, Jessica S.; Zhang, Zhimin; Wang, Qian; Fang, Yan

2013-01-01

Carotid atherosclerosis is the primary cause of ischemic stroke. To identify genetic factors contributing to carotid atherosclerosis, we performed quantitative trait locus (QTL) analysis using female mice derived from an intercross between C57BL/6J (B6) and BALB/cJ (BALB) apolipoprotein E (Apoe−/−) mice. We started 266 F2 mice on a Western diet at 6 wk of age and fed them the diet for 12 wk. Atherosclerotic lesions in the left carotid bifurcation and plasma lipid levels were measured. We genotyped 130 microsatellite markers across the entire genome. Three significant QTLs, Cath1 on chromosome (Chr) 12, Cath2 on Chr5, and Cath3 on Chr13, and four suggestive QTLs on Chr6, Chr9, Chr17, and Chr18 were identified for carotid lesions. The Chr6 locus replicated a suggestive QTL and was named Cath4. Six QTLs for HDL, three QTLs for non-HDL cholesterol, and three QTLs for triglyceride were found. Of these, a significant QTL for non-HDL on Chr1 at 60.3 cM, named Nhdl13, and a suggestive QTL for HDL on ChrX were new. A significant locus for HDL (Hdlq5) was overlapping with a suggestive locus for carotid lesions on Chr9. A significant correlation between carotid lesion sizes and HDL cholesterol levels was observed in the F2 population (R = −0.153, P = 0.0133). Thus, we have identified several new QTLs for carotid atherosclerosis and the locus on Chr9 may exert effect through interactions with HDL. PMID:23463770

[Prospect and Current Situation of Immune Checkpoint Inhibitors 
in First-line Treatment in Advanced Non-small Cell Lung Cancer Patients].

PubMed

Wang, Haiyang; Yu, Xiaoqing; Fan, Yun

2017-06-20

With the breakthroughs achieved of programmed death-1 (PD-1)/PD-L1 inhibitors monotherapy as first-line and second-line treatment in advanced non-small cell lung cancer (NSCLC), the treatment strategy is gradually evolving and optimizing. Immune combination therapy expands the benefit population and improves the curative effect. A series of randomized phase III trials are ongoing. In this review, we discuss the prospect and current situation of immune checkpoint inhibitors in first-line treatment in advanced NSCLC patients.

Antiangiogenic therapy for patients with aggressive or refractory advanced non-small cell lung cancer in the second-line setting.

PubMed

Reck, Martin; Garassino, Marina Chiara; Imbimbo, Martina; Shepherd, Frances A; Socinski, Mark A; Shih, Jin-Yuan; Tsao, Anne; Lee, Pablo; Winfree, Katherine B; Sashegyi, Andreas; Cheng, Rebecca; Varea, Rocio; Levy, Benjamin; Garon, Edward

2018-06-01

A majority of patients with advanced or metastatic non-small cell lung cancer (NSCLC) will experience disease progression after first-line therapy. Patients who have advanced NSCLC that is especially aggressive, which is defined as disease that rapidly progresses on first-line treatment or disease that is refractory to first-line treatment, have a critical unmet medical need. These patients have a poor prognosis in the second-line setting. Several studies have recently shown that treatment with an antiangiogenic therapy may benefit these patients. This review summarizes the approved antiangiogenic therapies for the treatment of patients with advanced NSCLC in the second-line setting, specifically focusing on the outcomes from subgroups of patients with rapidly progressing or refractory disease. Several antiangiogenic agents, as monotherapy or in combination with other treatments, have been or are currently being studied in patients with advanced NSCLC. Antiangiogenics that are approved for use in patients with advanced NSCLC are limited to bevacizumab in combination with chemotherapy (nonsquamous NSCLC), ramucirumab in combination with docetaxel (all histologies), and nintedanib in combination with docetaxel (adenocarcinoma histology). This review focuses on the efficacy, safety, and quality of life outcomes in the subpopulation of patients with rapidly progressing or refractory NSCLC treated with approved antiangiogenic therapies in the second-line setting. We also discuss the impact of newly approved immunotherapy agents on the outcomes of patients with aggressive or refractory disease. Studies in progress and planned future research will determine if combination treatment with antiangiogenics and immunotherapies will benefit patients with aggressive, advanced NSCLC. Copyright © 2018. Published by Elsevier B.V.

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…

Biological constraints limit the use of rapamycin-inducible FKBP12-Inp54p for depleting PIP2 in dorsal root ganglia neurons.

PubMed

Coutinho-Budd, Jaeda C; Snider, Samuel B; Fitzpatrick, Brendan J; Rittiner, Joseph E; Zylka, Mark J

2013-09-08

Rapamycin-induced translocation systems can be used to manipulate biological processes with precise temporal control. These systems are based on rapamycin-induced dimerization of FK506 Binding Protein 12 (FKBP12) with the FKBP Rapamycin Binding (FRB) domain of mammalian target of rapamycin (mTOR). Here, we sought to adapt a rapamycin-inducible phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phosphatase (Inp54p) system to deplete PIP2 in nociceptive dorsal root ganglia (DRG) neurons. We genetically targeted membrane-tethered CFP-FRBPLF (a destabilized FRB mutant) to the ubiquitously expressed Rosa26 locus, generating a Rosa26-FRBPLF knockin mouse. In a second knockin mouse line, we targeted Venus-FKBP12-Inp54p to the Calcitonin gene-related peptide-alpha (CGRPα) locus. We hypothesized that after intercrossing these mice, rapamycin treatment would induce translocation of Venus-FKBP12-Inp54p to the plasma membrane in CGRP+ DRG neurons. In control experiments with cell lines, rapamycin induced translocation of Venus-FKBP12-Inp54p to the plasma membrane, and subsequent depletion of PIP2, as measured with a PIP2 biosensor. However, rapamycin did not induce translocation of Venus-FKBP12-Inp54p to the plasma membrane in FRBPLF-expressing DRG neurons (in vitro or in vivo). Moreover, rapamycin treatment did not alter PIP2-dependent thermosensation in vivo. Instead, rapamycin treatment stabilized FRBPLF in cultured DRG neurons, suggesting that rapamycin promoted dimerization of FRBPLF with endogenous FKBP12. Taken together, our data indicate that these knockin mice cannot be used to inducibly deplete PIP2 in DRG neurons. Moreover, our data suggest that high levels of endogenous FKBP12 could compete for binding to FRBPLF, hence limiting the use of rapamycin-inducible systems to cells with low levels of endogenous FKBP12.

Apatinib in gastric carcinoma: A case report of partial response for first-line treatment in advanced disease.

PubMed

Wang, Yaping; Bi, Minghong; Zhang, Haoran; Gao, Zhenyuan; Zhou, Hairong; Chang, Shu

2017-10-01

Gastric cancer (GC) is the most common gastrointestinal malignant tumor, with a gradual increasing incidence throughout the world. Mostly GC is diagnosed in its late stage. To date, there is no usable standardized treatment regimen for patients with advanced GC. Apatinib mesylate, small-molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor (TKI), has been approved as third-line treatment for patients with advanced gastric adenocarcinoma in China, October, 2014. Till now, there is no case report about apatinib as first-line treatment for patients with advanced GC in literature. We present an 83-year-old Chinese man with advanced gastric adenocarcinoma, who received apatinib as first-line option and obtained clinical benefit within 2 weeks. The lung metastases disappeared completely and the liver metastases shrank significantly. The patient's progression-free survival was 163 days and overall survival was 201 days. This paper reviews and discusses apatinib as a new targeted drug for patients with advanced GC by comparison with other effective molecular-targeted therapy. © 2016 John Wiley & Sons Australia, Ltd.

Beyond landraces: developing improved germplasm resources for underutilized species - a case for Bambara groundnut.

PubMed

Aliyu, Siise; Massawe, Festo; Mayes, Sean

2014-10-01

The potential for underutilized crops (also known as minor, neglected or orphan crops) to improve food and nutrition security has been gaining prominence within the research community in recent years. This is due to their significance for diversified agricultural systems which is a necessary component of future agriculture to address food and nutritional security concerns posed by changing climate and a growing world population. Developing workable value chain systems for underutilized crop species, coupled with comparative trait studies with major crops, potentially allows us to identify suitable agricultural modalities for such species. Bambara groundnut (Vigna subterranea L. Verdc.), an underutilized leguminous species, is of interest for its reported high levels of drought tolerance in particular, which contributes to environmental resilience in semi-arid environments. Here, we present a synopsis of suitable strategies for the genetic improvement of Bambara groundnut as a guide to other underutilized crop species. Underutilized crops have often been adapted over thousands of years in particular regions by farmers and largely still exist as landraces with little or no genetic knowledge of key phenotypic traits. Breeding in these species is fundamentally different to breeding in major crops, where significant pedigree structures and history allow highly directed improvement. In this regard, deploying new integrated germplasm development approaches for variety development and genetic analysis, such as multi-parent advance generation inter-crosses (MAGIC), within breeding programmes of underutilized species will be important to be able to fully utilize such crops.

Genome Wide Analysis of Fatty Acid Desaturation and Its Response to Temperature1[OPEN

PubMed Central

Menard, Guillaume N.; Moreno, Jose Martin; Bryant, Fiona M.; Munoz-Azcarate, Olaya; Hassani-Pak, Keywan; Kurup, Smita

2017-01-01

Plants modify the polyunsaturated fatty acid content of their membrane and storage lipids in order to adapt to changes in temperature. In developing seeds, this response is largely controlled by the activities of the microsomal ω-6 and ω-3 fatty acid desaturases, FAD2 and FAD3. Although temperature regulation of desaturation has been studied at the molecular and biochemical levels, the genetic control of this trait is poorly understood. Here, we have characterized the response of Arabidopsis (Arabidopsis thaliana) seed lipids to variation in ambient temperature and found that heat inhibits both ω-6 and ω-3 desaturation in phosphatidylcholine, leading to a proportional change in triacylglycerol composition. Analysis of the 19 parental accessions of the multiparent advanced generation intercross (MAGIC) population showed that significant natural variation exists in the temperature responsiveness of ω-6 desaturation. A combination of quantitative trait locus (QTL) analysis and genome-wide association studies (GWAS) using the MAGIC population suggests that ω-6 desaturation is largely controlled by cis-acting sequence variants in the FAD2 5′ untranslated region intron that determine the expression level of the gene. However, the temperature responsiveness of ω-6 desaturation is controlled by a separate QTL on chromosome 2. The identity of this locus is unknown, but genome-wide association studies identified potentially causal sequence variants within ∼40 genes in an ∼450-kb region of the QTL. PMID:28108698

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

USDA-ARS?s Scientific Manuscript database

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...

Droplet sliding on inclined superhydrophobic surfaces: the effect of anisotropic contact line

NASA Astrophysics Data System (ADS)

Jiang, Youhua; Cao, Lile; Guo, Zongqi; Choi, Chang-Hwan

2017-11-01

Although the effects of solid structures on droplet retention on superhydrophobic surfaces have been studied extensively, the investigation has been restricted to the sessile droplets on horizontal surfaces where the contact line motions are axisymmetric or isotropic (either advancing or receding). In the droplet retention on inclined surfaces, the contact line motions are asymmetric or anisotropic; the advancing and receding motions coexist. In this study, we investigate the correlation between the droplet boundary pinning and the surface morphology on inclined superhydrophobic surfaces. The evolution of the droplet contact angle and width show contrary behaviors between pillar- and pore-structured surfaces due to the distinctive microscopic contact line motions. Therefore, the visualizations of the contact line motions at different locations of the boundary on inclined superhydrophobic surfaces are performed and the averaged contact line density of the boundary is quantified. The result shows that the droplet retentive force monotonously increase with the increase in contact line density, regardless of the surface morphological types, dimensions, or the direction of contact line motion (advancing, receding, or both). The result indicates that the droplet retentive force on superhydrophobic surfaces is mainly determined by the contact line density, regardless of the isotropy of the contact line.

Development and application of Human Genome Epidemiology

NASA Astrophysics Data System (ADS)

Xu, Jingwen

2017-12-01

Epidemiology is a science that studies distribution of diseases and health in population and its influencing factors, it also studies how to prevent and cure disease and promote health strategies and measures. Epidemiology has developed rapidly in recent years and it is an intercross subject with various other disciplines to form a series of branch disciplines such as Genetic epidemiology, molecular epidemiology, drug epidemiology and tumor epidemiology. With the implementation and completion of Human Genome Project (HGP), Human Genome Epidemiology (HuGE) has emerged at this historic moment. In this review, the development of Human Genome Epidemiology, research content, the construction and structure of relevant network, research standards, as well as the existing results and problems are briefly outlined.

Post-Progression Survival Associated with Overall Survival in Patients with Advanced Non-Small-Cell Lung Cancer Receiving Docetaxel Monotherapy as Second-Line Chemotherapy.

PubMed

Kotake, Mie; Miura, Yosuke; Imai, Hisao; Mori, Keita; Sakurai, Reiko; Kaira, Kyoichi; Tomizawa, Yoshio; Minato, Koichi; Saito, Ryusei; Hisada, Takeshi

2017-01-01

In patients with non-small-cell lung cancer (NSCLC), the effects of second-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies. Therefore, using individual-level data, we aimed to determine the relationships between progression-free survival (PFS) and post-progression survival (PPS) with OS in patients with advanced NSCLC treated with docetaxel monotherapy as second-line chemotherapy. Between April 2002 and December 2014, data from 86 patients with advanced NSCLC who underwent second-line docetaxel monotherapy following first-line treatment with platinum combination chemotherapy were analyzed. The relationships of PFS and PPS with OS were analyzed at the individual level. Spearman rank correlation and linear regression analyses showed that PPS was strongly associated with OS (r = 0.86, p < 0.05, R2 = 0.93), whereas PFS was moderately correlated with OS (r = 0.50, p < 0.05, R2 = 0.21). Performance status at the end of second-line treatment and the number of regimens after progression beyond second-line chemotherapy were significantly associated with PPS (p < 0.05). In patients with advanced NSCLC with unknown oncogenic driver mutations undergoing docetaxel monotherapy as second-line chemotherapy, when compared with PFS, PPS had a stronger association with OS. This finding suggests that subsequent treatment after disease progression following second-line docetaxel monotherapy has a significant influence on OS. © 2017 S. Karger AG, Basel.

Successful TS-1 monotherapy as the second-line treatment for advanced extramammary Paget's disease: A report of two cases.

PubMed

Kato, Junji; Hida, Tokimasa; Yamashita, Toshiharu; Kamiya, Shiori; Horimoto, Kohei; Sato, Sayuri; Takahashi, Hitomi; Sawada, Masahide; Yamada, Mao; Uhara, Hisashi

2018-01-01

There is no standard chemotherapeutic treatment for advanced extramammary Paget's disease, though the effectiveness of some chemotherapy regimens, including docetaxel, has been reported. In this report, we report that TS-1 monotherapy was effective in two patients with advanced extramammary Paget's disease after docetaxel treatment failure. TS-1 monotherapy may be useful as the second-line treatment for patients with advanced extramammary Paget's disease. © 2017 Japanese Dermatological Association.

Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience

PubMed Central

2012-01-01

Background Although first-line therapy for patients affected by advanced mesothelioma is well established, there is a lack of data regarding the impact of second-line treatment. Methods We retrospectively collected data of patients affected by advanced mesothelioma, already treated with first-line therapy based on pemetrexed and platin, with a response (partial response or stable disease) lasting at least 6 months, and re-treated with a pemetrexed-based therapy at progression. The primary objective was to describe time to progression and overall survival after re-treatment. Results Overall across several Italian oncological Institutions we found 30 patients affected by advanced mesothelioma, in progression after a 6-month lasting clinical benefit following a first-line treatment with cisplatin and pemetrexed, and re-challenged with a pemetrexed-based therapy. In these patients we found a disease control rate of 66%, with reduction of pain in 43% of patients. Overall time to progression and survival were promising for a second-line setting of patients with advanced mesothelioma, being 5.1 and 13.6 months, respectively. Conclusions In our opinion, when a patient has a long-lasting benefit from previous treatment with pemetrexed combined with a platin compound, the same treatment should be offered at progression. PMID:22943698

A splice mutation in the PHKG1 gene causes high glycogen content and low meat quality in pig skeletal muscle.

PubMed

Ma, Junwu; Yang, Jie; Zhou, Lisheng; Ren, Jun; Liu, Xianxian; Zhang, Hui; Yang, Bin; Zhang, Zhiyan; Ma, Huanban; Xie, Xianhua; Xing, Yuyun; Guo, Yuanmei; Huang, Lusheng

2014-10-01

Glycolytic potential (GP) in skeletal muscle is economically important in the pig industry because of its effect on pork processing yield. We have previously mapped a major quantitative trait loci (QTL) for GP on chromosome 3 in a White Duroc × Erhualian F2 intercross. We herein performed a systems genetic analysis to identify the causal variant underlying the phenotype QTL (pQTL). We first conducted genome-wide association analyses in the F2 intercross and an F19 Sutai pig population. The QTL was then refined to an 180-kb interval based on the 2-LOD drop method. We then performed expression QTL (eQTL) mapping using muscle transcriptome data from 497 F2 animals. Within the QTL interval, only one gene (PHKG1) has a cis-eQTL that was colocolizated with pQTL peaked at the same SNP. The PHKG1 gene encodes a catalytic subunit of the phosphorylase kinase (PhK), which functions in the cascade activation of glycogen breakdown. Deep sequencing of PHKG1 revealed a point mutation (C>A) in a splice acceptor site of intron 9, resulting in a 32-bp deletion in the open reading frame and generating a premature stop codon. The aberrant transcript induces nonsense-mediated decay, leading to lower protein level and weaker enzymatic activity in affected animals. The mutation causes an increase of 43% in GP and a decrease of>20% in water-holding capacity of pork. These effects were consistent across the F2 and Sutai populations, as well as Duroc × (Landrace × Yorkshire) hybrid pigs. The unfavorable allele exists predominantly in Duroc-derived pigs. The findings provide new insights into understanding risk factors affecting glucose metabolism, and would greatly contribute to the genetic improvement of meat quality in Duroc related pigs.

Polygenic Control of Carotid Atherosclerosis in a BALB/cJ × SM/J Intercross and a Combined Cross Involving Multiple Mouse Strains.

PubMed

Grainger, Andrew T; Jones, Michael B; Chen, Mei-Hua; Shi, Weibin

2017-02-09

Atherosclerosis in the carotid arteries is a major cause of ischemic stroke, which accounts for 85% of all stroke cases. Genetic factors contributing to carotid atherosclerosis remain poorly understood. The aim of this study was to identify chromosomal regions harboring genes contributing to carotid atherosclerosis in mice. From an intercross between BALB/cJ (BALB) and SM/J (SM) apolipoprotein E-deficient ( Apoe -/- ) mice, 228 female F2 mice were generated and fed a "Western" diet for 12 wk. Atherosclerotic lesion sizes in the left carotid artery were quantified. Across the entire genome, 149 genetic markers were genotyped. Quantitative trait locus (QTL) analysis revealed eight loci for carotid lesion sizes, located on chromosomes 1, 5, 12, 13, 15, 16, and 18. Combined cross-linkage analysis using data from this cross, and two previous F2 crosses derived from BALB, C57BL/6J and C3H/HeJ strains, identified five significant QTL on chromosomes 5, 9, 12, and 13, and nine suggestive QTL for carotid atherosclerosis. Of them, the QTL on chromosome 12 had a high LOD score of 9.95. Bioinformatic analysis prioritized Arhgap5 , Akap6 , Mipol1 , Clec14a , Fancm , Nin , Dact1 , Rtn1 , and Slc38a6 as probable candidate genes for this QTL. Atherosclerotic lesion sizes were significantly correlated with non-HDL cholesterol levels ( r = 0.254; p = 0.00016) but inversely correlated with HDL cholesterol levels ( r = -0.134; p = 0.049) in the current cross. Thus, we demonstrated the polygenic control of carotid atherosclerosis in mice. The correlations of carotid lesion sizes with non-HDL and HDL suggest that genetic factors exert effects on carotid atherosclerosis partially through modulation of lipoprotein homeostasis. Copyright © 2017 Grainger et al.

A link between thrifty phenotype and maternal care across two generations of intercrossed mice

PubMed Central

Goes, Carolina P.; Forti, Isabela; O. do Monte, Bruno Gabriel; Watanabe, Isabela M.; Cunha, Joao; Peripato, Andrea C.

2017-01-01

Maternal effects are causal influences from mother to offspring beyond genetic information, and have lifelong consequences for multiple traits. Previously, we reported that mice whose mothers did not nurse properly had low birth weight followed by rapid fat accumulation and disturbed development of some organs. That pattern resembles metabolic syndromes known collectively as the thrifty phenotype, which is believed to be an adaptation to a stressful environment which prepares offspring for reduced nutrient supply. The potential link between maternal care, stress reactivity, and the thrifty phenotype, however, has been poorly explored in the human and animal literature: only a couple of studies even mention (much less, test) these concepts under a cohesive framework. Here, we explored this link using mice of the parental inbred strains SM/J and LG/J–who differ dramatically in their maternal care–and the intercrossed generations F1 and F2. We measured individual differences in 15 phenotypes and used structural equation modeling to test our hypotheses. We found a remarkable relationship between thrifty phenotype and lower quality of maternal behaviors, including nest building, pup retrieval, grooming/licking, and nursing. To our knowledge, this is the first study to show, in any mammal, a clear connection between the natural variation in thrifty phenotype and maternal care. Both traits in the mother also had a substantial effect on survival rate in the F3 offspring. To our surprise, however, stress reactivity seemed to play no role in our models. Furthermore, the strain of maternal grandmother, but not of paternal grandmother, affected the variation of maternal care in F2 mice, and this effect was mediated by thrifty phenotype in F2. Since F1 animals were all genetically identical, this finding suggests that maternal effects pass down both maternal care and thrifty phenotype in these mice across generations via epigenetic transmission. PMID:28542485

Mapping quantitative trait loci for fear-like behaviors in mice.

PubMed

Gershenfeld, H K; Paul, S M

1997-11-15

Two mouse models developed for screening anxiolytic drugs were selected for genetic analysis, namely "wall-seeking" tendency in an open field ("thigmotaxis") and the light-to-dark transition (LD) paradigm, a conflict test. These tests measure differences in naturalistic tendencies of mice to explore a novel environment and to avoid a bright light or the center of an open field. In an F2 intercross of two strains of mice (A/J and C57BL/6J) that differ markedly in these behaviors, we estimated a broad sense heritability ranging from 0.3 to 0.59. With this intercross (n = 518), we have mapped several quantitative trait loci (QTL) for these behaviors by performing a genome-wide search. A significant QTL on chromosome 10 (near D10Mit237; LOD of 9.3) that affects LD behavior was identified, and suggestive QTL (LOD > 2.8) were mapped to chromosomes 6, 15, 19, and X. For center time behaviors, QTL were identified on chromosome 1 (LOD of 7.7 and 4.0 for the initial 5-min epoch and the first trial average of the next two 5-min epochs, respectively), and suggestive QTL (LOD > 2.8) were mapped to chromosomes 6 and 14. These QTL individually explain from 2.3 to 8.4% of the phenotypic variance. Collectively, the multiple independent QTL explain from 3.5 to 26.5% of the F2 population's phenotypic variance, depending on the trait. The complexity and heterogeneity of the genetic factors underlying these fear-like behaviors are illustrated by the lack of shared QTL between paradigms and by mapping different QTL for repeated trials of behavior. The identification of QTL affecting individual differences in fear-like behavior may lead to the identification of new gene products and pathways that modulate behavior, providing targets for rational drug design.

Next Generation Mapping of Enological Traits in an F2 Interspecific Grapevine Hybrid Family

PubMed Central

Sun, Qi; Manns, David C.; Sacks, Gavin L.; Mansfield, Anna Katharine; Luby, James J.; Londo, Jason P.; Reisch, Bruce I.; Cadle-Davidson, Lance E.; Fennell, Anne Y.

2016-01-01

In winegrapes (Vitis spp.), fruit quality traits such as berry color, total soluble solids content (SS), malic acid content (MA), and yeast assimilable nitrogen (YAN) affect fermentation or wine quality, and are important traits in selecting new hybrid winegrape cultivars. Given the high genetic diversity and heterozygosity of Vitis species and their tendency to exhibit inbreeding depression, linkage map construction and quantitative trait locus (QTL) mapping has relied on F1 families with the use of simple sequence repeat (SSR) and other markers. This study presents the construction of a genetic map by single nucleotide polymorphisms identified through genotyping-by-sequencing (GBS) technology in an F2 mapping family of 424 progeny derived from a cross between the wild species V. riparia Michx. and the interspecific hybrid winegrape cultivar, ‘Seyval’. The resulting map has 1449 markers spanning 2424 cM in genetic length across 19 linkage groups, covering 95% of the genome with an average distance between markers of 1.67 cM. Compared to an SSR map previously developed for this F2 family, these results represent an improved map covering a greater portion of the genome with higher marker density. The accuracy of the map was validated using the well-studied trait berry color. QTL affecting YAN, MA and SS related traits were detected. A joint MA and SS QTL spans a region with candidate genes involved in the malate metabolism pathway. We present an analytical pipeline for calling intercross GBS markers and a high-density linkage map for a large F2 family of the highly heterozygous Vitis genus. This study serves as a model for further genetic investigations of the molecular basis of additional unique characters of North American hybrid wine cultivars and to enhance the breeding process by marker-assisted selection. The GBS protocols for identifying intercross markers developed in this study can be adapted for other heterozygous species. PMID:26974672

Detection of expression quantitative trait Loci in complex mouse crosses: impact and alleviation of data quality and complex population substructure.

PubMed

Iancu, Ovidiu D; Darakjian, Priscila; Kawane, Sunita; Bottomly, Daniel; Hitzemann, Robert; McWeeney, Shannon

2012-01-01

Complex Mus musculus crosses, e.g., heterogeneous stock (HS), provide increased resolution for quantitative trait loci detection. However, increased genetic complexity challenges detection methods, with discordant results due to low data quality or complex genetic architecture. We quantified the impact of theses factors across three mouse crosses and two different detection methods, identifying procedures that greatly improve detection quality. Importantly, HS populations have complex genetic architectures not fully captured by the whole genome kinship matrix, calling for incorporating chromosome specific relatedness information. We analyze three increasingly complex crosses, using gene expression levels as quantitative traits. The three crosses were an F(2) intercross, a HS formed by crossing four inbred strains (HS4), and a HS (HS-CC) derived from the eight lines found in the collaborative cross. Brain (striatum) gene expression and genotype data were obtained using the Illumina platform. We found large disparities between methods, with concordance varying as genetic complexity increased; this problem was more acute for probes with distant regulatory elements (trans). A suite of data filtering steps resulted in substantial increases in reproducibility. Genetic relatedness between samples generated overabundance of detected eQTLs; an adjustment procedure that includes the kinship matrix attenuates this problem. However, we find that relatedness between individuals is not evenly distributed across the genome; information from distinct chromosomes results in relatedness structure different from the whole genome kinship matrix. Shared polymorphisms from distinct chromosomes collectively affect expression levels, confounding eQTL detection. We suggest that considering chromosome specific relatedness can result in improved eQTL detection.

Interleaving lattice for the Argonne Advanced Photon Source linac

NASA Astrophysics Data System (ADS)

Shin, S.; Sun, Y.; Dooling, J.; Borland, M.; Zholents, A.

2018-06-01

To realize and test advanced accelerator concepts and hardware, a beam line is being reconfigured in the linac extension area (LEA) of the Argonne Advanced Photon Source (APS) linac. A photocathode rf gun installed at the beginning of the APS linac will provide a low emittance electron beam into the LEA beam line. The thermionic rf gun beam for the APS storage ring and the photocathode rf gun beam for the LEA beam line will be accelerated through the linac in an interleaved fashion. In this paper, the design studies for interleaving lattice realization in the APS linac is described with the initial experiment result.

Erlotinib or best supportive care for third-line treatment of advanced non-small-cell lung cancer: a real-world cost-effectiveness analysis.

PubMed

Cromwell, Ian; van der Hoek, Kimberly; Malfair Taylor, Suzanne C; Melosky, Barbara; Peacock, Stuart

2012-06-01

Erlotinib has been approved as a third-line treatment for advanced non-small-cell lung cancer (NSCLC) in British Columbia (BC). A cost-effectiveness analysis was conducted to compare costs and effectiveness in patients who received third-line erlotinib to those in a historical patient cohort that would have been eligible had erlotinib been available. In a population of patients who have been treated with drugs for advanced NSCLC, overall survival (OS), progression-to-death survival (PTD) and probability of survival one year after end of second-line (1YS) were determined using a Kaplan-Meier survival analysis. Costs were collected retrospectively from the perspective of the BC health care system. Incremental mean OS was 90 days (0.25 LYG), and incremental mean cost was $11,102 (CDN 2009), resulting in a mean ICER of $36,838/LYG. Univariate sensitivity analysis yielded ICERs ranging from $21,300 to $51,700/LYG. Our analysis suggests that erlotinib may be an effective and cost-effective third-line treatment for advanced NSCLC compared to best supportive care. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[Automatic analysis of the interference EMG of the brachioradial muscle in neuropathy of the radial nerve].

PubMed

Popelianskiĭ, Ia Iu; Bogdanov, E I; Khamidullina, V Z

1988-01-01

In 8 patients with radial neuropathy the authors studied histograms of distribution of potentials of motor units (PMU) by their duration, as well as of the number of intercrossings (T) and the mean amplitude of interference EMG of the musculus brachioradialis. The findings included a decrease in the T value and T/M ratio in the presence of an insignificant shift of the histograms and of the mean duration of PMU. With regard to the diagnosis of early neuropathies a reduction in the average value of T and T/M in the presence of ungraded voluntary tension of the muscle is diagnostically more important than changes in the duration of individual PMU.

Economic Analysis of First-Line Treatment with Erlotinib in an EGFR-Mutated Population with Advanced NSCLC.

PubMed

Vergnenegre, Alain; Massuti, Bartomeu; de Marinis, Filippo; Carcereny, Enric; Felip, Enriqueta; Do, Pascal; Sanchez, Jose Miguel; Paz-Arez, Luis; Chouaid, Christos; Rosell, Rafael

2016-06-01

The cost-effectiveness of first-line tyrosine kinase inhibitor therapy in epidermal growth factor receptor gene (EGFR)-mutated advanced-stage non-small cell lung cancer (NSCLC) is poorly documented. We therefore conducted a cost-effectiveness analysis of first-line treatment with erlotinib versus standard chemotherapy in European patients with advanced-stage EGFR-mutated NSCLC who were enrolled in the European Erlotinib versus Chemotherapy trial. The European Erlotinib versus Chemotherapy study was a multicenter, open-label, randomized phase III trial performed mainly in Spain, France, and Italy. We based our economic analysis on clinical data and data on resource consumption (drugs, drug administration, adverse events, and second-line treatments) collected during this trial. Utility values were derived from the literature. Incremental cost-effectiveness ratios were calculated for the first-line treatment phase and for the overall strategy from the perspective of the three participating countries. Sensitivity analyses were performed by selecting the main cost drivers. Compared with standard first-line chemotherapy, the first-line treatment with erlotinib was cost saving (€7807, €17,311, and €19,364 for Spain, Italy and France, respectively) and yielded a gain of 0.117 quality-adjusted life-years. A probabilistic sensitivity analysis indicated that, given a willingness to pay at least €90,000 for 1 quality-adjusted life-year, the probability that a strategy of first-line erlotinib would be cost-effective was 100% in France, 100% in Italy, and 99.8% in Spain. This economic analysis shows that first-line treatment with erlotinib, versus standard chemotherapy, is a dominant strategy for EGFR-mutated advanced-stage NSCLC in three European countries. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Resources and Costs Associated with the Treatment of Advanced and Metastatic Gastric Cancer in the Mexican Public Sector: A Patient Chart Review.

PubMed

Quintana, Miguel; Toriz, José A; Novick, Diego; Jones, Kyla; Botello, Brenda S; Silva, Juan Alejandro

2018-06-01

Little evidence is available on the management and cost of treating patients with advanced or metastatic gastric cancer (GC). This study evaluates patient characteristics, treatment patterns, and resource utilization for these patients in Mexico. Data were collected from three centers of investigation (tertiary level). Patients were ≥18 years of age, diagnosed between 1 January 2009 and 1 January 2015, had advanced or metastatic GC, received first-line fluoropyrimidine/platinum, and had ≥3 months follow-up after discontinuing first-line treatment. Data were summarized using descriptive statistics. The study sample totaled 180. Patients' mean age was 57.2 years (±12.4) and 57.0% were male; 151 (83.9%) patients received second-line chemotherapy. A total of 16 and 19 regimens were identified in first- and second-line therapy. Of the sample, 51 (28.3%) received third-line therapy, and <10% received more than three lines of active chemotherapy. Supportive care received in first- and second-line chemotherapy, included pain interventions (12.2 and 7.9%), nutritional support (3.3 and 1.3%), radiotherapy (6.1 and 16.6%), and transfusions (13.3 and 10.6%), respectively. Using Mexican Institute of Social Security (IMSS) tariffs, the average total cost per patient-month in first- and second-line therapy was US$1230 [95% confidence interval (CI) 1034-1425] and US$1192 (95% CI 913-1471), respectively. Administration and acquisition of chemotherapy comprised the majority of costs. This study shows considerable variation in first- and second-line chemotherapy regimens of patients with advanced or metastatic GC. Understanding GC treatment patterns in Mexico will help address unmet needs.

Extended X-ray Absorption Fine Structure Study of Bond Constraints in Ge-Sb-Te Alloys

DTIC Science & Technology

2011-02-07

Ray Absorption Spectroscopy, or EXAFS. Using the spectroscopic capabilities provided by the MCAT line at the Advanced Photon Source at Argonne...Absorption Spectroscopy, or EXAFS. Using the spectroscopic capabilities provided by the MCAT line at the Advanced Photon Source at Argonne National

Disease evaluations and agronomic traits of advanced peanut breeding lines in 2017

USDA-ARS?s Scientific Manuscript database

Disease evaluations of advanced peanut breeding lines are conducted annually to compare the agronomic traits (crop value, yield, seed grade and characteristics) and disease resistance in cultivars that are currently available or close to being released for the Southwest. In 2017, a total of 19 comm...

[Comparison of the Efficacy and Safety of Icotinib with Standard Second-line 
Chemotherapy in Previously Treated Advanced Non-small Cell Lung Cancer].

PubMed

Yao, Shuyang; Qian, Kun; Wang, Ruotian; Li, Yuanbo; Zhang, Yi

2015-06-01

This study compared the efficacy and safety of icotinib with standard second-line chemotherapy (single-agent docetaxel or pemetrexed) in previously treated advanced non-small cell lung cancer (NSCLC). Thirty-two consecutive patients treated with icotinib and 33 consecutive patients treated with standard second-line chemotherapy in Xuanwu Hospital from January 2012 to July 2013 were enrolled in our retrospective research. The Response Evaluation Criteria in Solid Tumors were used to evaluate the tumor responses, and the progression-free survival (PFS) was evaluated by Kaplan-Meier method. Icotinib was comparable with standard second-line chemotherapy for advanced NSCLC in terms of overall response rate (ORR) (28.1% vs 18.2%, P=0.341), disease control rate (DFS)(43.8% vs 45.5%, P=0.890), and PFS (4.3 months vs 3.8 months, P=0.506). In the icotinib group, the ORR of epidermal growth factor receptor (EGFR) mutant was significantly higher than that of EGFR unknown or wild type (P=0.017). In multivariate analysis, age, gender, histology, and the optimum first-line treatment response were dependent prognostic factors based on the PFS of the icotinib group. The incidence of adverse events was significantly fewer in the icotinib group than in the chemotherapy group (P=0.001). Compared with the standard second-line chemotherapy, icotinib is active in the treatment of advanced NSCLC patients, especially with EGFR unknown in the second line, with an acceptable adverse event profile.

Surrogate endpoints for overall survival in advanced non-small-cell lung cancer patients with mutations of the epidermal growth factor receptor gene.

PubMed

Yoshino, Reiko; Imai, Hisao; Mori, Keita; Takei, Kousuke; Tomizawa, Mai; Kaira, Kyoichi; Yoshii, Akihiro; Tomizawa, Yoshio; Saito, Ryusei; Yamada, Masanobu

2014-09-01

Subsequent therapies confound the ability to discern the effect of first-line chemotherapy on overall survival (OS). We investigated whether progression-free survival (PFS), post-progression survival (PPS) and tumor response were valid surrogate endpoints for OS following first-line chemotherapy in individual patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive epidermal growth factor receptor gene mutations. We retrospectively analyzed 35 patients with advanced NSCLC treated with first-line gefitinib. The associations of PFS, PPS and tumor response with OS were analyzed. PPS was found to be strongly correlated with OS, unlike PFS and tumor shrinkage. The factors significantly associated with PPS were performance status (PS) after first-line treatment, best response to second-line treatment and number of regimens used after disease progression. PPS may be a surrogate for OS in this patient population and further therapy after disease progression following first-line chemotherapy may significantly affect OS. However, a larger study is required to validate these results.

A retrospective analysis of efficacy and safety of adding bevacizumab to chemotherapy as first- and second-line therapy in advanced non-small-cell lung cancer (NSCLC).

PubMed

Quan, Rencui; Huang, Jiaxing; Chen, Nan; Fang, Wenfeng; Hu, Zhihuang; Zhan, Jianhua; Zhou, Ting; Zhang, Li; Zhang, Hongyu

2016-08-01

Several phase III clinical trials had authenticated that the addition of bevacizumab to paclitaxel plus carboplatin or gemcitabine plus cisplatin showed encouraging efficacy as first-line therapy for advanced NSCLC patients. However, the benefits of adding bevacizumab to other chemotherapy regimens in first- or second-line therapy have not been reported. To compare the clinical efficacy and safety of bevacizumab concomitant with chemotherapy regimens in patients with advanced NSCLC as first- or second-line therapy, we retrospectively reviewed the effects of adding bevacizumab to chemotherapy regimens in naive-chemotherapy and pre-chemotherapy patients with advanced non-squamous NSCLC. A total of 79 patients with advanced non-squamous NSCLC received at least two cycles of bevacizumab with chemotherapy between October 2010 and December 2013 were selected. Our primary end points were overall response rate (ORR) and disease control rate (DCR). The secondary objective was overall survival (OS) and safety. Seventy-nine patients were included in this study. Overall response rates at first evaluation (after 2 cycles) were 23.1 % (9/39) and 5.0 % (2/40) in first- and second-line therapy (P = 0.020), respectively. And disease control rates were 84.6 % (33/39) and 50 % (20/40), respectively (P = 0.001). The median OS were 27.2 months (95 % CI 13.3-41.1 months) and 29.6 months (95 % CI 6.7-52.5 months), respectively (P = 0.740). Grade 3-4 adverse events included leukopenia (2/39), and neutropenia (3/39) in first-line therapy versus neutropenia (1/40) and thrombocytopenia (2/40) in second-line treatment. In our experience, combination of bevacizumab and chemotherapy had encouraging anti-tumor efficacy as both first- and second-line therapy.

Multiple Genes Cause Postmating Prezygotic Reproductive Isolation in the Drosophila virilis Group.

PubMed

Ahmed-Braimah, Yasir H

2016-12-07

Understanding the genetic basis of speciation is a central problem in evolutionary biology. Studies of reproductive isolation have provided several insights into the genetic causes of speciation, especially in taxa that lend themselves to detailed genetic scrutiny. Reproductive barriers have usually been divided into those that occur before zygote formation (prezygotic) and after (postzygotic), with the latter receiving a great deal of attention over several decades. Reproductive barriers that occur after mating but before zygote formation [postmating prezygotic (PMPZ)] are especially understudied at the genetic level. Here, I present a phenotypic and genetic analysis of a PMPZ reproductive barrier between two species of the Drosophila virilis group: D. americana and D. virilis This species pair shows strong PMPZ isolation, especially when D. americana males mate with D. virilis females: ∼99% of eggs laid after these heterospecific copulations are not fertilized. Previous work has shown that the paternal loci contributing to this incompatibility reside on two chromosomes, one of which (chromosome 5) likely carries multiple factors. The other (chromosome 2) is fixed for a paracentric inversion that encompasses nearly half the chromosome. Here, I present two results. First, I show that PMPZ in this species cross is largely due to defective sperm storage in heterospecific copulations. Second, using advanced intercross and backcross mapping approaches, I identify genomic regions that carry genes capable of rescuing heterospecific fertilization. I conclude that paternal incompatibility between D. americana males and D. virilis females is underlain by four or more genes on chromosomes 2 and 5. Copyright © 2016 Ahmed-Braimah.

Atezolizumab: feasible second-line therapy for patients with non-small cell lung cancer? A review of efficacy, safety and place in therapy.

PubMed

Jean, Fanny; Tomasini, Pascale; Barlesi, Fabrice

2017-12-01

Advanced non-small cell lung cancer (NSCLC) prognosis is still poor and has recently been reformed by the development of immune checkpoint inhibitors and the approval of anti-PD-1 (programmed cell-death 1) treatments such as nivolumab and pembrolizumab in second line. More recently, atezolizumab (MDPL 3280A), a programmed cell-death-ligand 1 (PD-L1) inhibitor, was also studied in this setting. Here, we report a review of the literature assessing the efficacy, safety, and place of atezolizumab in the second-line treatment of advanced NSCLC. We performed a literature search of PubMed, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference on Lung Cancer meetings. Atezolizumab showed a good tolerance profile and efficacy in comparison with docetaxel for second-line treatment of advanced NSCLC. Potential predictive biomarkers also have to be assessed.

Atezolizumab: feasible second-line therapy for patients with non-small cell lung cancer? A review of efficacy, safety and place in therapy

PubMed Central

Jean, Fanny; Tomasini, Pascale; Barlesi, Fabrice

2017-01-01

Advanced non-small cell lung cancer (NSCLC) prognosis is still poor and has recently been reformed by the development of immune checkpoint inhibitors and the approval of anti-PD-1 (programmed cell-death 1) treatments such as nivolumab and pembrolizumab in second line. More recently, atezolizumab (MDPL 3280A), a programmed cell-death-ligand 1 (PD-L1) inhibitor, was also studied in this setting. Here, we report a review of the literature assessing the efficacy, safety, and place of atezolizumab in the second-line treatment of advanced NSCLC. We performed a literature search of PubMed, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference on Lung Cancer meetings. Atezolizumab showed a good tolerance profile and efficacy in comparison with docetaxel for second-line treatment of advanced NSCLC. Potential predictive biomarkers also have to be assessed. PMID:29449897

Sequential treatment of icotinib after first-line pemetrexed in advanced lung adenocarcinoma with unknown EGFR gene status.

PubMed

Zheng, Yulong; Fang, Weijia; Deng, Jing; Zhao, Peng; Xu, Nong; Zhou, Jianying

2014-07-01

In non-small cell lung cancer (NSCLC), the well-developed epidermal growth factor receptor (EGFR) is an important therapeutic target. EGFR activating gene mutations have been proved strongly predictive of response to EGFR-tyrosine kinase inhibitors (TKI) in NSCLC. However, both in daily clinical practice and clinical trials, patients with unknown EGFR gene status (UN-EGFR-GS) are very common. In this study, we assessed efficacy and tolerability of sequential treatment of first-line pemetrexed followed by icotinib in Chinese advanced lung adenocarcinoma with UN-EGFR-GS. We analyzed 38 patients with advanced lung adenocarcinoma with UN-EGFR-GS treated with first-line pemetrexed-based chemotherapy followed by icotinib as maintenance or second-line therapy. The response rates to pemetrexed and icotinib were 21.1% and 42.1%, respectively. The median overall survival was 27.0 months (95% CI, 19.7-34.2 months). The 12-month overall survival probability was 68.4%. The most common toxicities observed in icotinib phase were rashes, diarrheas, and elevated aminotransferase. Subgroup analysis indicated that the overall survival is correlated with response to icotinib. The sequence of first-line pemetrexed-based chemotherapy followed by icotinib treatment is a promising option for advanced lung adenocarcinoma with UN-EGFR-GS in China.

Zone lines

Treesearch

Kevin T. Smith

2001-01-01

Zone lines are narrow, usually dark markings formed in decaying wood. Zone lines are found most frequently in advanced white rot of hardwoods, although they occasionally are associated both with brown rot and with softwoods.

[Clinical Analysis of Icotinib on Beneficiary of 
Advanced Non-small Cell Lung Cancer with EGFR Common Mutation].

PubMed

Jiang, Xiaowen; Wang, Wenxian; Zhang, Yiping

2016-04-20

Targeted therapy has become an indispensable therapy method in advanced non-small cell lung cancer (NSCLC) treatment. Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) can significantly prolong the survival of patients harboring EGFR gene mutation. Icotinb is China's first EGFR-TKI with independent intellectual property rights. The aim of this study is to investigate the clinical characteristics about the beneficiary of advanced NSCLC patients with EGFR Common mutation who were treated with Icotinib. Retrospectively collect the data about beneficiary [progression-free survival (PFS)≥6 months] and analysis of the related risk factors for prognosis. From September 1, 2011 to September 30, 2015, 231 cases of advanced NSCLC beneficiary with EGFR common mutation were enrolled for treatment with icotinib in Zhejiang Cancer Hospital. The one year benefit rate was 67.9% in the group treated with Icotinib as first line, and in the groupas second line or above was 53.6%, which is statisticallysignificant. The two years benefit rate was 18.7% and 9.3%, respectively. The median PFS of first line group and the second line or above was 16.7 and 12.4 months, respectively. The presence of brain metastasis (P=0.010), Prior chemotherapy (P=0.001), Eastern Cooperative Oncology Group (ECOG) score (P=0.001) were the main factors influencing the prognosis. The most common adverse were skin rashes (51 cases, 22.1%) and diarrhea (27 cases, 11.7%). Icotinib offers long-term clinical benefit and good tolerance for advanced NSCLC harboring EGFR gene mutation. Its advantage groups in addition to the patients with brain metastases and better ECOG score, the curative effect of patients with the first-line treatment is superior to second or further line. 
.

Efficacy of chemotherapy after first-line gefitinib therapy in EGFR mutation-positive advanced non-small cell lung cancer-data from a randomized Phase III study comparing gefitinib with carboplatin plus paclitaxel (NEJ002).

PubMed

Miyauchi, Eisaku; Inoue, Akira; Kobayashi, Kunihiko; Maemondo, Makoto; Sugawara, Shunichi; Oizumi, Satoshi; Isobe, Hiroshi; Gemma, Akihiko; Saijo, Yasuo; Yoshizawa, Hirohisa; Hagiwara, Koichi; Nukiwa, Toshihiro

2015-07-01

Epidermal growth factor receptor tyrosine kinase inhibitors are effective as first-line therapy for advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations. However, it is unknown whether second-line platinum-based chemotherapy after epidermal growth factor receptor tyrosine kinase inhibitor therapy could lead to better outcomes. We evaluated the efficacy of second-line platinum-based chemotherapy after gefitinib for advanced non-small cell lung cancers harboring epidermal growth factor receptor mutations (the NEJ002 study). Seventy-one non-small cell lung cancers, treated with gefitinib as first-line therapy and then receiving platinum-based chemotherapy as second-line therapy were evaluated in NEJ002. Patients were evaluated for antitumor response to second-line chemotherapy by computed tomography according to the criteria of the Response Evaluation Criteria in Solid Tumors group (version 1.0). Of the 71 patients receiving platinum-based chemotherapy after first-line gefitinib, a partial response was documented in 25.4% (18/71), stable disease in 43.7% (31/71) and progression of disease in 21.1% (15/71). The objective response and disease control rates were 25.4% (18/71) and 69% (49/71), respectively. There was no significant difference between first- and second-line chemotherapy in objective response and disease control rates for advanced non-small cell lung cancer harboring activating epidermal growth factor receptor mutations. In the analysis of epidermal growth factor receptor mutation types, the objective responses of deletions in exon 19 and a point mutation in exon 21 (L858R) were 27.3% (9/33) and 28.1% (9/32), respectively, but these differences between objective response rates were not significant. The efficacy of second-line platinum-based chemotherapy followed at progression by gefitinib was similar to first-line platinum-based chemotherapy, and epidermal growth factor receptor mutation types did not influence the efficacy of second-line platinum-based chemotherapy. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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…

Characterization of mature maize (Zea mays L.) root system architecture and complexity in a diverse set of Ex-PVP inbreds and hybrids.

PubMed

Hauck, Andrew L; Novais, Joana; Grift, Tony E; Bohn, Martin O

2015-01-01

The mature root system is a vital plant organ, which is critical to plant performance. Commercial maize (Zea mays L.) breeding has resulted in a steady increase in plant performance over time, along with noticeable changes in above ground vegetative traits, but the corresponding changes in the root system are not presently known. In this study, roughly 2500 core root systems from field trials of a set of 10 diverse elite inbreds formerly protected by Plant Variety Protection plus B73 and Mo17 and the 66 diallel intercrosses among them were evaluated for root traits using high throughput image-based phenotyping. Overall root architecture was modeled by root angle (RA) and stem diameter (SD), while root complexity, the amount of root branching, was quantified using fractal analysis to obtain values for fractal dimension (FD) and fractal abundance (FA). For each trait, per se line effects were highly significant and the most important contributor to trait performance. Mid-parent heterosis and specific combining ability was also highly significant for FD, FA, and RA, while none of the traits showed significant general combining ability. The interaction between the environment and the additive line effect was also significant for all traits. Within the inbred and hybrid generations, FD and FA were highly correlated (rp ≥ 0.74), SD was moderately correlated to FD and FA (0.69 ≥ rp ≥ 0.48), while the correlation between RA and other traits was low (0.13 ≥ rp ≥ -0.40). Inbreds with contrasting effects on complexity and architecture traits were observed, suggesting that root complexity and architecture traits are inherited independently. A more comprehensive understanding of the maize root system and the way it interacts with the environment will be useful for defining adaptation to nutrient acquisition and tolerance to stress from drought and high plant densities, critical factors in the yield gains of modern hybrids.

Superadiabatic driving of a three-level quantum system

NASA Astrophysics Data System (ADS)

Theisen, M.; Petiziol, F.; Carretta, S.; Santini, P.; Wimberger, S.

2017-07-01

We study superadiabatic quantum control of a three-level quantum system whose energy spectrum exhibits multiple avoided crossings. In particular, we investigate the possibility of treating the full control task in terms of independent two-level Landau-Zener problems. We first show that the time profiles of the elements of the full control Hamiltonian are characterized by peaks centered around the crossing times. These peaks decay algebraically for large times. In principle, such a power-law scaling invalidates the hypothesis of perfect separability. Nonetheless, we address the problem from a pragmatic point of view by studying the fidelity obtained through separate control as a function of the intercrossing separation. This procedure may be a good approach to achieve approximate adiabatic driving of a specific instantaneous eigenstate in realistic implementations.

Efficacy of tegafur-uracil in advanced urothelial cancer patients after the treatment failure of platinum-based chemotherapy.

PubMed

Maolake, Aerken; Izumi, Kouji; Takahashi, Rie; Itai, Shingo; Machioka, Kazuaki; Yaegashi, Hiroshi; Nohara, Takahiro; Kitagawa, Yasuhide; Kadono, Yoshifumi; Konaka, Hiroyuki; Mizokami, Atsushi; Namiki, Mikio

2015-03-01

Platinum-based chemotherapy is the first-line treatment for advanced urinary tract urothelial cancers. However, the optimal second-line treatment is unclear. Although tegafur-uracil is sometimes used for advanced urothelial cancer patients after the treatment failure of platinum-based chemotherapy, there is little evidence regarding its use as a second-line treatment. Advanced urothelial cancer patients previously treated with platinum-based chemotherapy were retrospectively analyzed. Overall survival (OS) was compared between patients with and without tegafur-uracil treatment. Thirty-one patients (27 and 4 patients with and without tegafur-uracil treatment, respectively) were analyzed. OS from the last day of the final chemotherapy course was better in patients with tegafur-uracil treatment than in those without (p<0.001, 358 and 66.5 days of the median survival time, respectively). Tegafur-uracil may be a candidate for the secondary treatment of advanced urothelial cancer patients after the treatment failure of platinum-based chemotherapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer?

PubMed

Salati, Massimiliano; Di Emidio, Katia; Tarantino, Vittoria; Cascinu, Stefano

2017-01-01

Gastric cancer is the third leading cause of cancer-related death globally with approximately 723 000 deaths every year. Most patients present with advanced unresectable or metastatic disease, only amenable to palliative systemic treatment and a median survival uncommonly exceeding 12 months. Over the last years, the efficacy of chemotherapy combination has plateaued and the introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has resulted in a limited survival gain in the upfront setting. After this positive experience, first-line treatment with new targeted therapies failed to improve the outcome of advanced gastric cancer. On the contrary, second-line options, including monochemotherapy with taxanes or irinotecan and the anti-vascular endothelial growth factor receptor 2 ramucirumab, either alone or combined with paclitaxel, opened new therapeutic rooms for an ever-increasing number of patients who maintain an acceptable performance status across multiple lines. This article provides an updated overview on the current management of advanced gastric cancer and discusses how the different treatment options available may be best combined to favourably impact the outcome of patients following the logic of a treatment strategy.

Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer?

PubMed Central

Salati, Massimiliano; Di Emidio, Katia; Tarantino, Vittoria; Cascinu, Stefano

2017-01-01

Gastric cancer is the third leading cause of cancer-related death globally with approximately 723 000 deaths every year. Most patients present with advanced unresectable or metastatic disease, only amenable to palliative systemic treatment and a median survival uncommonly exceeding 12 months. Over the last years, the efficacy of chemotherapy combination has plateaued and the introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has resulted in a limited survival gain in the upfront setting. After this positive experience, first-line treatment with new targeted therapies failed to improve the outcome of advanced gastric cancer. On the contrary, second-line options, including monochemotherapy with taxanes or irinotecan and the anti-vascular endothelial growth factor receptor 2 ramucirumab, either alone or combined with paclitaxel, opened new therapeutic rooms for an ever-increasing number of patients who maintain an acceptable performance status across multiple lines. This article provides an updated overview on the current management of advanced gastric cancer and discusses how the different treatment options available may be best combined to favourably impact the outcome of patients following the logic of a treatment strategy. PMID:29209523

Fluoropyrimidines plus cisplatin versus gemcitabine/gemcitabine plus cisplatin in locally advanced and metastatic biliary tract carcinoma - a retrospective study.

PubMed

Croitoru, Adina; Gramaticu, Iulia; Dinu, Ioana; Gheorghe, Liana; Alexandrescu, Sorin; Buica, Florina; Luca, Ioana; Becheanu, Gabriel; Herlea, Vlad; Simionov, Iulia; Hrehoret, Doina; Lupescu, Ioana; Popescu, Irinel; Diculescu, Mircea

2012-09-01

This is a retrospective study of patients with advanced biliary tract carcinoma (BTC), who were treated with different regimens of chemotherapy. We studied patients with advanced BTC registered at the Department of Oncology at the Fundeni Clinical Institute between 2004 and 2008. The following data were analyzed: rate of response, progression free survival (PFS) to first and second line of chemotherapy, overall survival (OS) and drug toxicity. Ninety-six patients were eligible having either advanced intra or extrahepatic cholangiocarcinoma, or gallbladder cancer with no prior chemotherapy. Out of 96 patients, 57 (59.4%) received fluoropyrimidines (FP)+cisplatin and 39 (40.6%) gemcitabine (Gem)+/-cisplatin. The median PFS for FP+cisplatin was 5.9 months (95%CI 5-6.9) and for Gem+/-cisplatin 6.3 months (95%CI 5.4-7.1), p=0.661. Median OS for FP+cisplatin was 10.3 months (95%CI 7.5-13.1) and for Gem+/-cisplatin 9.1 months (95%CI 7.0-11.2), p=0.098. On disease progression, 46 patients received second line CT (Gem or FP+/-platinum compounds). Median OS for patients with FP based first line and Gem+/-cisplatin in second line was 19 months (95%CI 8.9-29) higher than for the reverse sequence: 13.2 months (95%CI 12-14.4), but not statistically significant (p=0.830). All patients were evaluated for toxicities. Most patients (75.5%) reported at least one adverse event. Our results through direct comparison of FP+cisplatin with Gem+/-cisplatin as first line treatment did not show any statistical differences in terms of rate of response, PFS and OS. However, our study showed that FP+cisplatin as first line and Gem based second line therapy gave a better OS rate.

SunLine Transit Agency Advanced Technology Fuel Cell Bus Evaluation : Third Results Report

DOT National Transportation Integrated Search

2012-05-01

SunLine Transit Agency provides public transit services to the Coachella Valley area of California. SunLine has demonstrated hydrogen and fuel cell bus technologies for more than 10 years. This report describes operations at SunLine for a prototype f...

Management of advanced pancreatic cancer in daily clinical practice.

PubMed

Giuliani, Jacopo; Piacentini, Paolo; Bonetti, Andrea

2016-01-01

The aim of this outcome study was to evaluate the management of advanced pancreatic cancer in a real-world clinical practice; few such experiences have been reported in the literature. A retrospective analysis was performed of all consecutive patients with advanced pancreatic ductal adenocarcinoma followed at our medical oncology unit between January 2003 and December 2013. We evaluated 78 patients, mostly with metastatic disease (64.1%). Median follow-up was 10.77 months, by which time 74 patients (94.9%) had died. Median overall survival was 8.29 months. Median age was 67 years. In univariate analysis, pain at onset (p = 0.020), ECOG performance status (p<0.001), stage (p = 0.047), first-line chemotherapy (p<0.001), second-line chemotherapy (p<0.001) and weight loss at diagnosis (p = 0.029) were factors that had an impact on overall survival. In multivariate analysis, the presence of pain at onset (p = 0.043), stage (p = 0.003) and second-line chemotherapy (p = 0.004) were confirmed as independent prognostic factors. Our data, derived from daily clinical practice, confirmed advanced pancreatic cancer as an aggressive malignant disease with a very short expected survival. Second-line treatment seems to provide an advantage in terms of overall survival in patients who showed a partial response as their best response to first-line treatment.

Targeted therapies in non-small cell lung cancer: a focus on ALK/ROS1 tyrosine kinase inhibitors.

PubMed

Sgambato, Assunta; Casaluce, Francesca; Maione, Paolo; Gridelli, Cesare

2018-01-01

Anaplastic lymphoma kinase (ALK) and ROS1 rearrangements define important molecular subgroups of advanced non-small cell lung cancer (NSCLC). The identification of these genetic driver alterations created new potential for highly active therapeutic interventions. After discovery of ALK rearrangements in NSCLC, it was recognized that these confer sensitivity to ALK inhibition. Areas covered: Crizotinib, the first-in-class ALK/ROS1/MET inhibitor, was initially approved as second-line treatment of ALK-positive advanced NSCLC but after this, it was firmly established as the standard first-line therapy for advanced ALK-positive NSCLC. After initial response to crizotinib, tumors inevitably relapse. Next-generation ALK inhibitors, more potent and brain-penetrable than crizotinib, may be effective in re-inducing remissions when cancers are still addicted to ALK. Ceritinib and alectinib are approved for metastatic ALK positive NSCLC patients, while brigatinib received granted accelerated approval by the United States Food and Drug Administration. Regarding ROS1 rearrangement, to date crizotinib is the only ALK-tyrosine kinase inhibitor receiving indication as treatment of ROS1 positive advanced NSCLC. Expert commentary: Although novel ALK-inhibitors are under clinical investigation compared to crizotinib as front-line treatment for ALK-positive NSCLC, nowadays the current standard first-line therapy for these patients is crizotinib. Further research will clarify the best management of ALK-positive NSCLC, above all who progress on first-line crizotinib.

EMK protein kinase-null mice: dwarfism and hypofertility associated with alterations in the somatotrope and prolactin pathways.

PubMed

Bessone, S; Vidal, F; Le Bouc, Y; Epelbaum, J; Bluet-Pajot, M T; Darmon, M

1999-10-01

Gene trapping was used in embryonic stem (ES) cells in an attempt to inactivate genes involved in development. The Emk (ELKL motif kinase) gene has been disrupted and a mutant mouse line derived. Previous work had shown that EMK kinases, called MARK in the rat, exert a major control on microtubule stability by phosphorylating microtubule-associated proteins and that genes homologous to Emk in yeast or Caenorhabditis elegans are essential for cell and embryonic polarity. Although we found the Emk gene to be active in the preimplantation mouse embryo and then to show a widespread expression, Emk-null mice had no embryonic defect and were viable. They show an overall proportionate dwarfism and a peculiar hypofertility: homozygotes are not fertile when intercrossed, but are fertile in other types of crosses. Insulin-like growth factor I (IGF I) and IGF-binding protein 3 (IGFBP3) were reduced in the plasma of homozygotes of both sexes. A direct implication of the EMK kinase in IGF I plasmatic production is unlikely because the Emk gene does not seem to be expressed in hepatocytes. Nevertheless, GH assayed at arbitrary times in plasma did not show differences between genotypes and GH concentrations in pituitary extracts were not found to be altered in homozygotes. Our results, though, do not exclude the possibility that in the mutants the overall quantity of GH secreted daily is reduced. Our observation of a smaller size of the pituitaries of the mutants is in favor of this hypothesis. The prolactin concentration in the pituitaries was much lowered in homozygous females, but it was normal in males. The possible involvement of EMK protein kinase in hormone secretion in the pituitary and/or the hypothalamus, via the microtubule network, is discussed. Copyright 1999 Academic Press.

Bayesian QTL mapping using genome-wide SSR markers and segregating population derived from a cross of two commercial F1 hybrids of tomato.

PubMed

Ohyama, Akio; Shirasawa, Kenta; Matsunaga, Hiroshi; Negoro, Satomi; Miyatake, Koji; Yamaguchi, Hirotaka; Nunome, Tsukasa; Iwata, Hiroyoshi; Fukuoka, Hiroyuki; Hayashi, Takeshi

2017-08-01

Using newly developed euchromatin-derived genomic SSR markers and a flexible Bayesian mapping method, 13 significant agricultural QTLs were identified in a segregating population derived from a four-way cross of tomato. So far, many QTL mapping studies in tomato have been performed for progeny obtained from crosses between two genetically distant parents, e.g., domesticated tomatoes and wild relatives. However, QTL information of quantitative traits related to yield (e.g., flower or fruit number, and total or average weight of fruits) in such intercross populations would be of limited use for breeding commercial tomato cultivars because individuals in the populations have specific genetic backgrounds underlying extremely different phenotypes between the parents such as large fruit in domesticated tomatoes and small fruit in wild relatives, which may not be reflective of the genetic variation in tomato breeding populations. In this study, we constructed F 2 population derived from a cross between two commercial F 1 cultivars in tomato to extract QTL information practical for tomato breeding. This cross corresponded to a four-way cross, because the four parental lines of the two F 1 cultivars were considered to be the founders. We developed 2510 new expressed sequence tag (EST)-based (euchromatin-derived) genomic SSR markers and selected 262 markers from these new SSR markers and publicly available SSR markers to construct a linkage map. QTL analysis for ten agricultural traits of tomato was performed based on the phenotypes and marker genotypes of F 2 plants using a flexible Bayesian method. As results, 13 QTL regions were detected for six traits by the Bayesian method developed in this study.

Iddm30 controls pancreatic expression of Ccl11 (Eotaxin) and the Th1/Th2 balance within the insulitic lesions.

PubMed

Chao, Gary Y C; Wallis, Robert H; Marandi, Leili; Ning, Terri; Sarmiento, Janice; Paterson, Andrew D; Poussier, Philippe

2014-04-15

The autoimmune diabetic syndrome of the BioBreeding diabetes-prone (BBDP) rat is a polygenic disease that resembles in many aspects human type 1 diabetes (T1D). A successful approach to gain insight into the mechanisms underlying genetic associations in autoimmune diseases has been to identify and map disease-related subphenotypes that are under simpler genetic control than the full-blown disease. In this study, we focused on the β cell overexpression of Ccl11 (Eotaxin), previously postulated to be diabetogenic in BBDR rats, a BBDP-related strain. We tested the hypothesis that this trait is genetically determined and contributes to the regulation of diabetes in BBDP rats. Similar to the BBDR strain, we observed a time-dependent, insulitis-independent pancreatic upregulation of Ccl11 in BBDP rats when compared with T1D-resistant ACI.1u.lyp animals. Through linkage analysis of a cross-intercross of these two parental strains, this trait was mapped to a region on chromosome 12 that overlaps Iddm30. Linkage results were confirmed by phenotypic assessment of a novel inbred BBDP.ACI-Iddm30 congenic line. As expected, the Iddm30 BBDP allele is associated with a significantly higher pancreatic expression of Ccl11; however, the same allele confers resistance to T1D. Analysis of islet-infiltrating T cells in Iddm30 congenic BBDP animals revealed that overexpression of pancreatic Ccl11, a prototypical Th2 chemokine, is associated with an enrichment in Th2 CD4+ T cells within the insulitic lesions. These results indicate that, in the BBDP rat, Iddm30 controls T1D susceptibility through both the regulation of Ccl11 expression in β cells and the subsequent Th1/Th2 balance within islet-infiltrating T lymphocytes.

Effects of selection for ethanol preference on gene expression in the nucleus accumbens of HS-CC mice

PubMed Central

Colville, A. M.; Iancu, O. D.; Oberbeck, D. L.; Darakjian, P.; Zheng, C. L.; Walter, N. A. R.; Harrington, C. A.; Searles, R. P.; McWeeney, S.; Hitzemann, R. J.

2017-01-01

Previous studies on changes in murine brain gene expression associated with the selection for ethanol preference have used F2 intercross or heterogeneous stock (HS) founders, derived from standard laboratory strains. However, these populations represent only a small proportion of the genetic variance available in Mus musculus. To investigate a wider range of genetic diversity, we selected mice for ethanol preference using an HS derived from the eight strains of the collaborative cross. These HS mice were selectively bred (four generations) for high and low ethanol preference. The nucleus accumbens shell of naive S4 mice was interrogated using RNA sequencing (RNA-Seq). Gene networks were constructed using the weighted gene coexpression network analysis assessing both coexpression and cosplicing. Selection targeted one of the network coexpression modules (greenyellow) that was significantly enriched in genes associated with receptor signaling activity including Chrna7, Grin2a, Htr2a and Oprd1. Connectivity in the module as measured by changes in the hub nodes was significantly reduced in the low preference line. Of particular interest was the observation that selection had marked effects on a large number of cell adhesion molecules, including cadherins and protocadherins. In addition, the coexpression data showed that selection had marked effects on long non-coding RNA hub nodes. Analysis of the cosplicing network data showed a significant effect of selection on a large cluster of Ras GTPase-binding genes including Cdkl5, Cyfip1, Ndrg1, Sod1 and Stxbp5. These data in part support the earlier observation that preference is linked to Ras/Mapk pathways. PMID:28058793

Genetic Components of Heterosis for Seedling Traits in an Elite Rice Hybrid Analyzed Using an Immortalized F2 Population.

PubMed

Zhu, Dan; Zhou, Gang; Xu, Caiguo; Zhang, Qifa

2016-02-20

Utilization of heterosis has greatly contributed to rice productivity in China and many Asian countries. Superior hybrids usually show heterosis at two stages: canopy development at vegetative stage and panicle development at reproductive stage resulting in heterosis in yield. Although the genetic basis of heterosis in rice has been extensively investigated, all the previous studies focused on yield traits at maturity stage. In this study, we analyzed the genetic basis of heterosis at seedling stage making use of an "immortalized F2" population composed of 105 hybrids produced by intercrossing recombinant inbred lines (RILs) from a cross between Zhenshan 97 and Minghui 63, the parents of Shanyou 63, which is an elite hybrid widely grown in China. Eight seedling traits, seedling height, tiller number, leaf number, root number, maximum root length, root dry weight, shoot dry weight and total dry weight, were investigated using hydroponic culture. We analyzed single-locus and digenic genetic effects at the whole genome level using an ultrahigh-density SNP bin map obtained by population re-sequencing. The analysis revealed large numbers of heterotic effects for seedling traits including dominance, overdominance and digenic dominance (epistasis) in both positive and negative directions. Overdominance effects were prevalent for all the traits, and digenic dominance effects also accounted for a large portion of the genetic effects. The results suggested that cumulative small advantages of the single-locus effects and two-locus interactions, most of which could not be detected statistically, could explain the genetic basis of seedling heterosis of the F1 hybrid. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

A novel approach for the generation of genetically modified mammary epithelial cell cultures yields new insights into TGFβ signaling in the mammary gland

PubMed Central

2010-01-01

Introduction Molecular dissection of the signaling pathways that underlie complex biological responses in the mammary epithelium is limited by the difficulty of propagating large numbers of mouse mammary epithelial cells, and by the inability of ribonucleic acid interference-based knockdown approaches to fully ablate gene function. Here we describe a method for the generation of conditionally immortalized mammary epithelial cells with defined genetic defects, and we show how such cells can be used to investigate complex signal transduction processes using the transforming growth factor beta (TGFβ)/Smad pathway as an example. Methods We intercrossed the previously described H-2Kb-tsA58 transgenic mouse (Immortomouse), which expresses a temperature-sensitive mutant of the simian virus-40 large T-antigen (tsTAg), with mice of differing Smad genotypes. Conditionally immortalized mammary epithelial cell cultures were derived from the virgin mammary glands of offspring of these crosses and were used to assess the Smad dependency of different biological responses to TGFβ. Results IMECs could be propagated indefinitely at permissive temperatures and had a stable epithelial phenotype, resembling primary mammary epithelial cells with respect to several criteria, including responsiveness to TGFβ. Using this panel of cells, we demonstrated that Smad3, but not Smad2, is necessary for TGFβ-induced apoptotic, growth inhibitory and epithelial-to-mesenchymal transition responses, whereas either Smad2 or Smad3 can support TGFβ-induced invasion as long as a threshold level of total Smad is exceeded. Conclusions The present work demonstrates the practicality and utility of generating conditionally immortalized mammary epithelial cell lines from genetically modified Immortomice for detailed investigation of complex signaling pathways in the mammary epithelium. PMID:20942910

Four out of eight genes in a mouse chromosome 7 congenic donor region are candidate obesity genes.

PubMed

Sarahan, Kari A; Fisler, Janis S; Warden, Craig H

2011-09-22

We previously identified a region of mouse chromosome 7 that influences body fat mass in F2 littermates of congenic × background intercrosses. Current analyses revealed that alleles in the donor region of the subcongenic B6.C-D7Mit318 (318) promoted a twofold increase in adiposity in homozygous lines of 318 compared with background C57BL/6ByJ (B6By) mice. Parent-of-origin effects were discounted through cross-fostering studies and an F1 reciprocal cross. Mapping of the donor region revealed that it has a maximal size of 2.8 Mb (minimum 1.8 Mb) and contains a maximum of eight protein coding genes. Quantitative PCR in whole brain, liver, and gonadal white adipose tissue (GWAT) revealed differential expression between genotypes for three genes in females and two genes in males. Alpha-2,8-sialyltransferase 8B (St8sia2) showed reduced 318 mRNA levels in brain for females and males and in GWAT for females only. Both sexes of 318 mice had reduced Repulsive guidance molecule-a (Rgma) expression in GWAT. In brain, Family with sequence similarity 174 member b (Fam174b) had increased expression in 318 females, whereas Chromodomain helicase DNA binding protein 2 (Chd2-2) had reduced expression in 318 males. No donor region genes were differentially expressed in liver. Sequence analysis of coding exons for all genes in the 318 donor region revealed only one single nucleotide polymorphism that produced a nonsynonymous missense mutation, Gln7Pro, in Fam174b. Our findings highlight the difficulty of using expression and sequence to identify quantitative trait genes underlying obesity even in small genomic regions.

Potential role for mammalian target of rapamycin inhibitors as first-line therapy in hormone receptor–positive advanced breast cancer

PubMed Central

Beck, J Thaddeus

2015-01-01

Despite advances in cytotoxic chemotherapy and targeted therapies, 5-year survival rates remain low for patients with advanced breast cancer at diagnosis. This highlights the limited effectiveness of current treatment options. An improved understanding of cellular functions associated with the development and progression of breast cancer has resulted in the creation of a number of novel targeted molecular therapies. However, more work is needed to improve outcomes, particularly in the first-line recurrent or metastatic hormone receptor–positive breast cancer setting. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) pathway is a major intracellular signaling pathway that is often upregulated in breast cancer, and overactivation of this pathway has been associated with primary or developed resistance to endocrine treatment. Clinical data from the Phase III Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study of the mTOR inhibitor everolimus combined with exemestane in hormone receptor–positive advanced breast cancer were very promising, highlighting the potential role of mTOR inhibitors in combination with endocrine therapies as a first-line treatment option for these patients. It is hoped that the use of mTOR inhibitors combined with current standard-of-care endocrine therapies, such as aromatase inhibitors, in the first-line advanced breast cancer setting may result in greater antitumor effects and also delay or reverse treatment resistance. PMID:26675495

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

PubMed

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

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. 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). 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. Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation.

[Current standards in the treatment of gastric cancer].

PubMed

Hacker, Ulrich; Lordick, Florian

2015-08-01

Endoscopic resection is established in the treatment of early gastric cancer. More advanced gastric cancer requires gastrectomy and D2 lymphadenectomy. Perioperative chemotherapy improves overall survival in locally advanced gastric cancer representing a standard of care. Locally advanced adenocarcinomas of the esophago-gastric junction can alternatively be treated with concurrent radiochemotherapy. In metastatic disease, systemic chemotherapy improves survival, quality of life and symptom control. Trastuzumab plus chemotherapy should be used together with first-line chemotherapy in HER2 positive gastric cancer patients. Second- and third-line therapy is now well established. The anti-VEGFR2 antibody Ramucirumab improves survival in second line treatment both as a monotherapy and in combination with paclitaxel and represents a novel treatment option. © Georg Thieme Verlag KG Stuttgart · New York.

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

Code of Federal Regulations, 2010 CFR

2010-01-01

..., 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 or...

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

Code of Federal Regulations, 2011 CFR

2011-01-01

..., 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 or...

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 or...

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 or...

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 or...

Meta-analysis of first-line therapies with maintenance regimens for advanced non-small-cell lung cancer (NSCLC) in molecularly and clinically selected populations.

PubMed

Tan, Pui San; Bilger, Marcel; de Lima Lopes, Gilberto; Acharyya, Sanchalika; Haaland, Benjamin

2017-08-01

Evidence has suggested survival benefits of maintenance for advanced NSCLC patients not progressing after first-line chemotherapy. Additionally, particular first-line targeted therapies have shown survival improvements in selected populations. Optimal first-line and maintenance therapies remain unclear. Here, currently available evidence was synthesized to elucidate optimal first-line and maintenance therapy within patient groups. Literature was searched for randomized trials evaluating first-line and maintenance regimens in advanced NSCLC patients. Bayesian network meta-analysis was performed within molecularly and clinically selected groups. The primary outcome was combined clinically meaningful OS and PFS benefits. A total of 87 records on 56 trials evaluating first-line treatments with maintenance were included. Results showed combined clinically meaningful OS and PFS benefits with particular first-line with maintenance treatments, (1) first-line intercalated chemotherapy+erlotinib, maintenance erlotinib in patients with EGFR mutations, (2) first-line afatinib, maintenance afatinib in patients with EGFR deletion 19, (3) first-line chemotherapy + bevacizumab, maintenance bevacizumab in EGFR wild-type patients, (4) chemotherapy+conatumumab, maintenance conatumumab in patients with squamous histology, (5) chemotherapy+cetuximab, maintenance cetuximab or chemotherapy + necitumumab, maintenance necitumumab in EGFR FISH-positive patients with squamous histology, and (6) first-line chemotherapy+bevacizumab, maintenance bevacizumab or first-line sequential chemotherapy+gefitinib, maintenance gefitinib in patients clinically enriched for EGFR mutations with nonsquamous histology. No treatment showed combined clinically meaningful OS and PFS benefits in patients with EGFR L858R or nonsquamous histology. Particular first-line with maintenance treatments show meaningful OS and PFS benefits in patients selected by EGFR mutation or histology. Further research is needed to achieve effective therapy for patients with EGFR mutation L858R or nonsquamous histology. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

First-line therapy for advanced non-small cell lung cancer with activating EGFR mutation: is combined EGFR-TKIs and chemotherapy a better choice?

PubMed

Wang, Shuyun; Gao, Aiqin; Liu, Jie; Sun, Yuping

2018-03-01

As the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutation, EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved the median progression-free survival (PFS) up to 18.9 months. However, almost all patients eventually develop acquired resistance to EGFR-TKIs, which limits the first-line PFS. To overcome the resistance and improve overall survival, researchers have tried to identify the resistance mechanisms and develop new treatment strategies, among which a combination of EGFR-TKIs and cytotoxic chemotherapy is one of the hotspots. The data from preclinical and clinical studies on combined EGFR-TKIs and chemotherapy have shown very interesting results. Here, we reviewed the available preclinical and clinical studies on first-line EGFR-TKIs-chemotherapy combination in patients with advanced NSCLC harboring activating EGFR mutation, aiming to provide evidences for more potential choices and shed light on clinical treatment.

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.

The Changing Treatment Landscape for Metastatic Urothelial Carcinoma.

PubMed

Flaig, Thomas W

2018-05-01

Urothelial carcinoma is the predominant histologic type of bladder cancer. After 30 years of minimal progress in the treatment of advanced-stage disease, recent advances in the genomic characterization of urothelial cancer and breakthroughs in bladder cancer therapeutics have rejuvenated the field. Nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab are among the exciting recent novel therapeutic advances gaining approvals by the FDA for treatment of advanced-stage urothelial carcinoma. Yet the challenge for clinicians is to determine the optimal choice of agents as first-line or second-line therapy and which offers the best chance for overall survival for the individual patient in this rapidly changing field. Copyright © 2018 by the National Comprehensive Cancer Network.

Comparative study of smile analysis by subjective and computerized methods.

PubMed

Basting, Roberta Tarkany; da Trindade, Rita de Cássia Silva; Flório, Flávia Martão

2006-01-01

This study compared: 1) the subjective analyses of a smile done by specialists with advanced training and by general dentists; 2) the subjective analysis of a smile, or that associated with the face, by specialists with advanced training and general dentists; 3) subjective analysis using a computerized analysis of the smile by specialists with advanced training, verifying the midline, labial line, smile line, the line between commissures and the golden proportion. The sample consisted of 100 adults with natural dentition; 200 photographs were taken (100 of the smile and 100 of the entire face). Computerized analysis using AutoCAD software was performed, together with the subjective analyses of 2 groups of professionals (3 general dentists and 3 specialists with advanced training), using the following assessment factors: the midline, labial line, smile line, line between the commissures and the golden proportion. The smile itself and the smile associated with the entire face were recorded as being agreeable or not agreeable by the professionals. The McNemar test showed a highly significant difference (p=0.0000) among the subjective analyses performed by specialists compared to general dentists. Between the 2 groups of dental professionals, there were highly significant differences (p=0.0000) found between the subjective analyses of the smile and that of the face. The McNemar test showed statistical differences in all factors assessed, with the exception of the midline (p=0.1951), when the computerized analysis and subjective analysis of the specialists were compared. In order to establish harmony of the smile, it was not possible to establish a greater or lesser relevance among the factors analyzed.

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

GOES-R Advanced Base Line Imager Installation

NASA Image and Video Library

2016-08-30

Team members prepare the Advanced Base Line Imager, the primary optical instrument, for installation on the Geostationary Operational Environmental Satellite (GOES-R) inside the Astrotech payload processing facility in Titusville, Florida near NASA’s Kennedy Space Center. GOES-R will be the first satellite in a series of next-generation NOAA GOES Satellites. The spacecraft is to launch aboard a United Launch Alliance Atlas V rocket in November.

GOES-R Advanced Base Line Imager Installation

NASA Image and Video Library

2016-08-30

Team members install the Advanced Base Line Imager, the primary optical instrument, on the Geostationary Operational Environmental Satellite (GOES-R) inside the Astrotech payload processing facility in Titusville, Florida near NASA’s Kennedy Space Center. GOES-R will be the first satellite in a series of next-generation NOAA GOES Satellites. The spacecraft is to launch aboard a United Launch Alliance Atlas V rocket in November.

GOES-R Advanced Base Line Imager Installation

NASA Image and Video Library

2016-08-30

The Advanced Base Line Imager, the primary optical instrument, has been installed on the Geostationary Operational Environmental Satellite (GOES-R) inside the Astrotech payload processing facility in Titusville, Florida near NASA’s Kennedy Space Center. GOES-R will be the first satellite in a series of next-generation NOAA GOES Satellites. The spacecraft is to launch aboard a United Launch Alliance Atlas V rocket in November.

Genomic Correlates of Relationship QTL Involved in Fore- versus Hind Limb Divergence in Mice

PubMed Central

Pavlicev, Mihaela; Wagner, Günter P.; Noonan, James P.; Hallgrímsson, Benedikt; Cheverud, James M.

2013-01-01

Divergence of serially homologous elements of organisms is a common evolutionary pattern contributing to increased phenotypic complexity. Here, we study the genomic intervals affecting the variational independence of fore- and hind limb traits within an experimental mouse population. We use an advanced intercross of inbred mouse strains to map the loci associated with the degree of autonomy between fore- and hind limb long bone lengths (loci affecting the relationship between traits, relationship quantitative trait loci [rQTL]). These loci have been proposed to interact locally with the products of pleiotropic genes, thereby freeing the local trait from the variational constraint due to pleiotropic mutations. Using the known polymorphisms (single nucleotide polymorphisms [SNPs]) between the parental strains, we characterized and compared the genomic regions in which the rQTL, as well as their interaction partners (intQTL), reside. We find that these two classes of QTL intervals harbor different kinds of molecular variation. SNPs in rQTL intervals more frequently reside in limb-specific cis-regulatory regions than SNPs in intQTL intervals. The intQTL loci modified by the rQTL, in contrast, show the signature of protein-coding variation. This result is consistent with the widely accepted view that protein-coding mutations have broader pleiotropic effects than cis-regulatory polymorphisms. For both types of QTL intervals, the underlying candidate genes are enriched for genes involved in protein binding. This finding suggests that rQTL effects are caused by local interactions among the products of the causal genes harbored in rQTL and intQTL intervals. This is the first study to systematically document the population-level molecular variation underlying the evolution of character individuation. PMID:24065733

Exploring Relationships between Canopy Architecture, Light Distribution, and Photosynthesis in Contrasting Rice Genotypes Using 3D Canopy Reconstruction

PubMed Central

Burgess, Alexandra J.; Retkute, Renata; Herman, Tiara; Murchie, Erik H.

2017-01-01

The arrangement of leaf material is critical in determining the light environment, and subsequently the photosynthetic productivity of complex crop canopies. However, links between specific canopy architectural traits and photosynthetic productivity across a wide genetic background are poorly understood for field grown crops. The architecture of five genetically diverse rice varieties—four parental founders of a multi-parent advanced generation intercross (MAGIC) population plus a high yielding Philippine variety (IR64)—was captured at two different growth stages using a method for digital plant reconstruction based on stereocameras. Ray tracing was employed to explore the effects of canopy architecture on the resulting light environment in high-resolution, whilst gas exchange measurements were combined with an empirical model of photosynthesis to calculate an estimated carbon gain and total light interception. To further test the impact of different dynamic light patterns on photosynthetic properties, an empirical model of photosynthetic acclimation was employed to predict the optimal light-saturated photosynthesis rate (Pmax) throughout canopy depth, hypothesizing that light is the sole determinant of productivity in these conditions. First, we show that a plant type with steeper leaf angles allows more efficient penetration of light into lower canopy layers and this, in turn, leads to a greater photosynthetic potential. Second the predicted optimal Pmax responds in a manner that is consistent with fractional interception and leaf area index across this germplasm. However, measured Pmax, especially in lower layers, was consistently higher than the optimal Pmax indicating factors other than light determine photosynthesis profiles. Lastly, varieties with more upright architecture exhibit higher maximum quantum yield of photosynthesis indicating a canopy-level impact on photosynthetic efficiency. PMID:28567045

Genetic regulation of bone metabolism in the chicken: similarities and differences to Mammalian systems.

PubMed

Johnsson, Martin; Jonsson, Kenneth B; Andersson, Leif; Jensen, Per; Wright, Dominic

2015-05-01

Birds have a unique bone physiology, due to the demands placed on them through egg production. In particular their medullary bone serves as a source of calcium for eggshell production during lay and undergoes continuous and rapid remodelling. We take advantage of the fact that bone traits have diverged massively during chicken domestication to map the genetic basis of bone metabolism in the chicken. We performed a quantitative trait locus (QTL) and expression QTL (eQTL) mapping study in an advanced intercross based on Red Junglefowl (the wild progenitor of the modern domestic chicken) and White Leghorn chickens. We measured femoral bone traits in 456 chickens by peripheral computerised tomography and femoral gene expression in a subset of 125 females from the cross with microarrays. This resulted in 25 loci for female bone traits, 26 loci for male bone traits and 6318 local eQTL loci. We then overlapped bone and gene expression loci, before checking for an association between gene expression and trait values to identify candidate quantitative trait genes for bone traits. A handful of our candidates have been previously associated with bone traits in mice, but our results also implicate unexpected and largely unknown genes in bone metabolism. In summary, by utilising the unique bone metabolism of an avian species, we have identified a number of candidate genes affecting bone allocation and metabolism. These findings can have ramifications not only for the understanding of bone metabolism genetics in general, but could also be used as a potential model for osteoporosis as well as revealing new aspects of vertebrate bone regulation or features that distinguish avian and mammalian bone.

Advanced optical delay line demonstrator

NASA Astrophysics Data System (ADS)

van den Dool, Teun; Kamphues, Fred; Fouss, B.; Henrioulle, K.; Hogenhuis, Harm

2004-09-01

TNO TPD, in cooperation with Micromega-Dynamics and Dutch Space, has designed an advanced Optical Delay Line (ODL) for use in future ground based and space interferometry missions. The work is performed under NIVR contract in preparation for GENIE and DARWIN. Using the ESO PRIMA DDL requirements as a baseline, the delay line can be used for PRIMA and GENIE without any modifications. The delay line design is modular and flexible, which makes scaling for other applications a relatively easy task. The ODL has a single linear motor actuator for Optical Path Difference (OPD) control, driving a two-mirror cat"s eye with SiC mirrors and CFRP structure. Magnetic bearings provide frictionless and wear free operation with zerohysteresis. The delay line is currently being assembled and will be subjected to a comprehensive test program in the second half of 2004.

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

PubMed

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

2016-11-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheftman, D., E-mail: dsheftman@trialphaenergy.com; Gupta, D.; Roche, T.

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

Taking charge: front-line nurse leadership development.

PubMed

Schwarzkopf, Ruth; Sherman, Rose O; Kiger, Anna J

2012-04-01

The recent Institute of Medicine (2010) report, The Future of Nursing: Leading Change, Advancing Health, included a recommendation that nurses at all levels should be prepared and enabled to lead change to advance health care in the United States. Historically, in most organizations, nursing leadership development programs have focused on nurses in management or executive roles rather than those working in front-line leadership roles. This article describes a front-line leadership development initiative developed by Tenet Healthcare Corporation and attended by 400 charge nurses. Program development, evaluation, and lessons learned that can be applied in other organizations are discussed. Copyright 2012, SLACK Incorporated.

The Effects of Ultra Thin Films on Dynamic Wetting

NASA Astrophysics Data System (ADS)

Chen, Xia; Garoff, Stephen; Rame, Enrique

2002-11-01

Dynamic wetting, the displacement of one fluid by another immiscible fluid on a surface, controls many natural and technological phenomena, such as coating, printing, spray painting and lubricating. Particularly in coating and spraying applications, contact lines advance across pre-existing fluid films. Most previous work has focused on contact lines advancing across films sufficiently thick that they behave as simple Newtonian fluids. Ultrathin films, where the film thickness may impinge on fundamental length scales in the fluid, have received less attention. In this talk, we will discuss the effects of ultrathin polymer films on dynamic wetting. We measure the interface shape within microns of moving contact lines advancing across preexisting films and compare the measurements to existing models of viscous bending for interfaces advancing across dry surfaces and 'thick' (in the sense that they behave as liquids) films. In the experiments, we advance a contact line of 10-poise and 1-poise polydimethylsiloxane (silicone oil) across pre-coated films of the same fluid with thickness from a single chain thickness (approx. 10 A) through a couple of radii of gyration (100-200 A) to films so thick they are likely bulk in behavior (103 A). All films are physisorbed, i.e. they readily rinse from the surface. Thus, molecules in the film are not anchored to the surface and can move within the film if the hydrodynamics dictate such motion. For films of the thickness of a single chain (approx. 10 A), our experiments indicate that the advancing fluid behaves just as it would if it advanced over a dry surface. For the thicker films (103 A), we find behavior indicating that the molecules in the film are acting as a fluid with the bulk properties. In this regime, results for the two different fluids are identical when the experiments are performed at the same pre-existing film thickness and advancing capillary number, Ca. For film of thickness of a few radii of gyration (approx. 100-200 A), the behavior depends on Ca of the advancing meniscus. At low Ca, the viscous bending of the interface near the contact line does not behave as it would on a dry surface. It has a lower curvature than expected. However, at higher Ca, the viscous bending is described by the model for spreading over a dry surface. These results show that the fluid flow in the film does behave differently than bulk as the film thickness becomes comparable to molecular length scale. But even more intriguing is the unusual velocity dependence of that behavior where the film behaves more solid-like at higher contact line speeds. We will discuss these results in terms of the properties of confined polymer melts.

The Effects of Ultra Thin Films on Dynamic Wetting

NASA Technical Reports Server (NTRS)

Chen, Xia; Garoff, Stephen; Rame, Enrique

2002-01-01

Dynamic wetting, the displacement of one fluid by another immiscible fluid on a surface, controls many natural and technological phenomena, such as coating, printing, spray painting and lubricating. Particularly in coating and spraying applications, contact lines advance across pre-existing fluid films. Most previous work has focused on contact lines advancing across films sufficiently thick that they behave as simple Newtonian fluids. Ultrathin films, where the film thickness may impinge on fundamental length scales in the fluid, have received less attention. In this talk, we will discuss the effects of ultrathin polymer films on dynamic wetting. We measure the interface shape within microns of moving contact lines advancing across preexisting films and compare the measurements to existing models of viscous bending for interfaces advancing across dry surfaces and 'thick' (in the sense that they behave as liquids) films. In the experiments, we advance a contact line of 10-poise and 1-poise polydimethylsiloxane (silicone oil) across pre-coated films of the same fluid with thickness from a single chain thickness (approx. 10 A) through a couple of radii of gyration (100-200 A) to films so thick they are likely bulk in behavior (10(exp 3) A). All films are physisorbed, i.e. they readily rinse from the surface. Thus, molecules in the film are not anchored to the surface and can move within the film if the hydrodynamics dictate such motion. For films of the thickness of a single chain (approx. 10 A), our experiments indicate that the advancing fluid behaves just as it would if it advanced over a dry surface. For the thicker films (10(exp 3) A), we find behavior indicating that the molecules in the film are acting as a fluid with the bulk properties. In this regime, results for the two different fluids are identical when the experiments are performed at the same pre-existing film thickness and advancing capillary number, Ca. For film of thickness of a few radii of gyration (approx. 100-200 A), the behavior depends on Ca of the advancing meniscus. At low Ca, the viscous bending of the interface near the contact line does not behave as it would on a dry surface. It has a lower curvature than expected. However, at higher Ca, the viscous bending is described by the model for spreading over a dry surface. These results show that the fluid flow in the film does behave differently than bulk as the film thickness becomes comparable to molecular length scale. But even more intriguing is the unusual velocity dependence of that behavior where the film behaves more solid-like at higher contact line speeds. We will discuss these results in terms of the properties of confined polymer melts.

Basic and Advanced Numerical Performances Relate to Mathematical Expertise but Are Fully Mediated by Visuospatial Skills

PubMed Central

2016-01-01

Recent studies have highlighted the potential role of basic numerical processing in the acquisition of numerical and mathematical competences. However, it is debated whether high-level numerical skills and mathematics depends specifically on basic numerical representations. In this study mathematicians and nonmathematicians performed a basic number line task, which required mapping positive and negative numbers on a physical horizontal line, and has been shown to correlate with more advanced numerical abilities and mathematical achievement. We found that mathematicians were more accurate compared with nonmathematicians when mapping positive, but not negative numbers, which are considered numerical primitives and cultural artifacts, respectively. Moreover, performance on positive number mapping could predict whether one is a mathematician or not, and was mediated by more advanced mathematical skills. This finding might suggest a link between basic and advanced mathematical skills. However, when we included visuospatial skills, as measured by block design subtest, the mediation analysis revealed that the relation between the performance in the number line task and the group membership was explained by non-numerical visuospatial skills. These results demonstrate that relation between basic, even specific, numerical skills and advanced mathematical achievement can be artifactual and explained by visuospatial processing. PMID:26913930

GOES-R Advanced Base Line Imager Installation

NASA Image and Video Library

2016-08-30

Team members assist as a crane lifts the Advanced Base Line Imager, the primary optical instrument, for installation on the Geostationary Operational Environmental Satellite (GOES-R) inside the Astrotech payload processing facility in Titusville, Florida near NASA’s Kennedy Space Center. GOES-R will be the first satellite in a series of next-generation NOAA GOES Satellites. The spacecraft is to launch aboard a United Launch Alliance Atlas V rocket in November.

GOES-R Advanced Base Line Imager Installation

NASA Image and Video Library

2016-08-30

Team members assist as a crane moves the Advanced Base Line Imager, the primary optical instruments, for installation on the Geostationary Operational Environmental Satellite (GOES-R) inside the Astrotech payload processing facility in Titusville, Florida near NASA’s Kennedy Space Center. GOES-R will be the first satellite in a series of next-generation NOAA GOES Satellites. The spacecraft is to launch aboard a United Launch Alliance Atlas V rocket in November.

Supply and Financial Systems Training for the Line Officer Afloat.

DTIC Science & Technology

1977-09-01

Structural training is a most efficient and recognized method to obtain basic knowledge of shipboard life . The line officer’s first contact with...resources in order to support the ship’s mission. For example, when he signs requests for leave, early liberty, advancement , or any other request...Naval War College, Naval Postgraduate School, and Department Head School (formerly Destroyer School). These provide advanced training in a great

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

Implementation status and explanatory analysis of early advance care planning for Stage IV non-small cell lung cancer patients.

PubMed

Tokito, Takaaki; Murakami, Haruyasu; Mori, Keita; Osaka, Iwao; Takahashi, Toshiaki

2015-03-01

The American Society of Clinical Oncology published the goals of individualized care including advance care planning for advanced cancer patients in 2011. However, no data are available on the implementation status of advance care planning. We retrospectively reviewed the electronic medical records and informed consent forms of consecutive Stage IV non-small cell lung cancer patients treated with chemotherapy between January 2010 and December 2012 at our institution. Two outcomes were defined to investigate the advance care planning implementation status: C-D, the duration from the last day of chemotherapy to death and D-D, that from the day of confirmed do-not-attempt-resuscitation order to death. The study included 136 eligible patients. The advance care planning implementation status in participating patients was as follows: 96 (70%) patients received information on 'incurable disease before first-line chemotherapy', 69 (50%) were informed about 'supportive care before first-line chemotherapy', whereas 43 (32%) learned about their prognosis. The do-not-attempt-resuscitation decision was reflected in 29 patients' will (21%). The median C-D was 64 days. Receipt of ≤2 chemotherapy regimens and provision of prognosis information to patients were significantly associated with long C-D in multivariate analysis. The median D-D was 25 days. Provision of information on supportive care before first-line chemotherapy and provision of prognosis information to patients were significantly associated with long D-D in multivariate analysis. Our results suggest that there is possible benefit from providing information on supportive care before first-line chemotherapy and informing patients about their prognosis in prolonging the duration of supportive care. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Number Line Is a Critical Spatial-Numerical Representation: Evidence from a Fraction Intervention

ERIC Educational Resources Information Center

Hamdan, Noora; Gunderson, Elizabeth A.

2017-01-01

Children's ability to place fractions on a number line strongly correlates with math achievement. But does the number line play a causal role in fraction learning or does it simply index more advanced fraction knowledge? The number line may be a particularly effective representation for fraction learning because its properties align with the…

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…

Measurement of pattern roughness and local size variation using CD-SEM: current status

NASA Astrophysics Data System (ADS)

Fukuda, Hiroshi; Kawasaki, Takahiro; Kawada, Hiroki; Sakai, Kei; Kato, Takashi; Yamaguchi, Satoru; Ikota, Masami; Momonoi, Yoshinori

2018-03-01

Measurement of line edge roughness (LER) is discussed from four aspects: edge detection, PSD prediction, sampling strategy, and noise mitigation, and general guidelines and practical solutions for LER measurement today are introduced. Advanced edge detection algorithms such as wave-matching method are shown effective for robustly detecting edges from low SNR images, while conventional algorithm with weak filtering is still effective in suppressing SEM noise and aliasing. Advanced PSD prediction method such as multi-taper method is effective in suppressing sampling noise within a line edge to analyze, while number of lines is still required for suppressing line to line variation. Two types of SEM noise mitigation methods, "apparent noise floor" subtraction method and LER-noise decomposition using regression analysis are verified to successfully mitigate SEM noise from PSD curves. These results are extended to LCDU measurement to clarify the impact of SEM noise and sampling noise on LCDU.

Understanding chemotherapy treatment pathways of advanced colorectal cancer patients to inform an economic evaluation in the United Kingdom

PubMed Central

Shabaruddin, F H; Elliott, R A; Valle, J W; Newman, W G; Payne, K

2010-01-01

Background: Accurate description of current practice within advanced colorectal cancer (CRC) specialties were needed to inform an economic evaluation of the UGT1A1 pharmacogenetic test for irinotecan in the United Kingdom. Methods: The study was based on a literature review and elicitation of expert opinion. The expert panel comprised 44 consultant oncologists in NHS Hospital Trusts across England. Results: Ten first-line, 10 second-line and 12 third-line chemotherapy regimens were reported, reflecting wide variations in treatment pathways. Predominant pathways emerged with: first-line treatment with oxaliplatin-based regimens, second-line treatment with irinotecan-based regimens and third-line treatment with mitomycin-based regimens. Experts estimated the frequency of febrile neutropaenia 8.4% (95% CI: 6.7–10.0), septic neutropaenia 4.7% (95% CI: 3.4–6.0) and severe diarrhoea 13.1% (95% CI: 10.8–15.5). Approaches for the clinical management of neutropaenia within the NHS were described. Conclusions: This study identified wide variations in the clinical management of advanced CRC patients. Descriptions of current treatment pathways are necessary for economic evaluations. Variations in clinical practice must be reflected in the model to ensure the findings from an economic evaluation of UGT1A1 testing are sufficient to inform policy regarding the cost-effective use of NHS resources. PMID:20661248

Advanced scatter search approach and its application in a sequencing problem of mixed-model assembly lines in a case company

NASA Astrophysics Data System (ADS)

Liu, Qiong; Wang, Wen-xi; Zhu, Ke-ren; Zhang, Chao-yong; Rao, Yun-qing

2014-11-01

Mixed-model assembly line sequencing is significant in reducing the production time and overall cost of production. To improve production efficiency, a mathematical model aiming simultaneously to minimize overtime, idle time and total set-up costs is developed. To obtain high-quality and stable solutions, an advanced scatter search approach is proposed. In the proposed algorithm, a new diversification generation method based on a genetic algorithm is presented to generate a set of potentially diverse and high-quality initial solutions. Many methods, including reference set update, subset generation, solution combination and improvement methods, are designed to maintain the diversification of populations and to obtain high-quality ideal solutions. The proposed model and algorithm are applied and validated in a case company. The results indicate that the proposed advanced scatter search approach is significant for mixed-model assembly line sequencing in this company.

An Advanced Actuator Line Method for Wind Energy Applications and Beyond

DOE Office of Scientific and Technical Information (OSTI.GOV)

Churchfield, Matthew J.; Schreck, Scott; Martinez-Tossas, Luis A.

The actuator line method to represent rotor aerodynamics within computational fluid dynamics has been in use for over a decade. This method applies a body force to the flow field along rotating lines corresponding to the individual rotor blades and employs tabular airfoil data to compute the force distribution. The actuator line method is attractive because compared to blade-resolved simulations, the required mesh is much simpler and the computational cost is lower. This work proposes a higher fidelity variant of the actuator line method meant to fill the space between current actuator line and blade-resolved simulations. It contains modifications inmore » two key areas. The first is that of freestream velocity vector estimation along the line, which is necessary to compute the lift and drag along the line using tabular airfoil data. Most current methods rely on point sampling in which the location of sampling is ambiguous. Here we test a velocity sampling method that uses a properly weighted integral over space, removing this ambiguity. The second area of improvement is the function used to project the one-dimensional actuator line force onto the three-dimensional fluid mesh as a body force. We propose and test a projection function that spreads the force over a region that looks something like a real blade with the hope that it will produce the blade local and near wake flow features with more accuracy and higher fidelity. Our goal is that between these two improvements, not only will the flow field predictions be enhanced, but also the spanwise loading will be made more accurate. We refer to this combination of improvements as the advanced actuator line method. We apply these improvements to two different wind turbine cases. Although there is a strong wind energy motivation in our work, there is no reason these advanced actuator line ideas cannot be used in other applications, such as helicopter rotors.« less

An Advanced Actuator Line Method for Wind Energy Applications and Beyond: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Churchfield, Matthew; Schreck, Scott; Martinez-Tossas, Luis A.

The actuator line method to represent rotor aerodynamics within computational fluid dynamics has been in use for over a decade. This method applies a body force to the flow field along rotating lines corresponding to the individual rotor blades and employs tabular airfoil data to compute the force distribution. The actuator line method is attractive because compared to blade-resolved simulations, the required mesh is much simpler and the computational cost is lower. This work proposes a higher fidelity variant of the actuator line method meant to fill the space between current actuator line and blade-resolved simulations. It contains modifications inmore » two key areas. The first is that of freestream velocity vector estimation along the line, which is necessary to compute the lift and drag along the line using tabular airfoil data. Most current methods rely on point sampling in which the location of sampling is ambiguous. Here we test a velocity sampling method that uses a properly weighted integral over space, removing this ambiguity. The second area of improvement is the function used to project the one-dimensional actuator line force onto the three-dimensional fluid mesh as a body force. We propose and test a projection function that spreads the force over a region that looks something like a real blade with the hope that it will produce the blade local and near wake flow features with more accuracy and higher fidelity. Our goal is that between these two improvements, not only will the flow field predictions be enhanced, but also the spanwise loading will be made more accurate. We refer to this combination of improvements as the advanced actuator line method. We apply these improvements to two different wind turbine cases. Although there is a strong wind energy motivation in our work, there is no reason these advanced actuator line ideas cannot be used in other applications, such as helicopter rotors.« less

Immune Checkpoint Inhibitors for Patients With Advanced Non-Small-Cell Lung Cancer: A Systematic Review.

PubMed

Ellis, Peter M; Vella, Emily T; Ung, Yee C

2017-09-01

Second-line treatment options are limited for patients with advanced non-small-cell lung cancer (NSCLC). Standard therapy includes the cytotoxic agents docetaxel and pemetrexed, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib. Immune checkpoint inhibitors are a new class of treatment that have shown durable overall radiologic response rates and have been well tolerated. The objective of this systematic review was to investigate the efficacy of immune checkpoint inhibitors compared with other chemotherapies in patients with advanced NSCLC. Medline, Embase, and PubMed were searched for randomized controlled trials comparing treatment with immune checkpoint inhibitors against treatment with chemotherapy in patients with stage IIIB or IV NSCLC. Nine randomized controlled trials with 15 publications were included. A significant overall survival benefit of second-line nivolumab (nonsquamous: hazard ratio [HR] = 0.72, 95% confidence interval [CI], 0.60-0.77; P < .001; squamous: HR = 0.59, 95% CI, 0.44-0.79; P < .001) or second-line atezolizumab (HR = 0.73, 95% CI, 0.62-0.87; P = .0003) or second-line pembrolizumab (in patients with programmed cell death ligand 1 [PD-L1]-positive tumors) (pembrolizumab 2 mg/kg HR = 0.71, 95% CI, 0.58-0.88; P = .0008; pembrolizumab 10 mg/kg HR = 0.61, 95% CI, 0.49-0.75; P < .0001) or first-line pembrolizumab (HR = 0.60, 95% CI, 0.41-0.89; P = .005) compared with chemotherapy was found. The adverse effects were mainly higher in the chemotherapy arms. For patients with advanced stage IIIB/IV NSCLC, the improvement in overall survival outweighed the harms and supported the use of first-line pembrolizumab (in patients with ≥ 50% PD-L1-positive tumors) or second-line nivolumab, atezolizumab, or pembrolizumab (in patients with PD-L1-positive tumors). Copyright © 2017 Elsevier Inc. All rights reserved.

Gemcitabine and capecitabine as third- or later-line therapy for refractory advanced colorectal cancer: a retrospective study.

PubMed

Salgado, Mercedes; Reboredo, Margarita; Mendez, Juan Carlos; Quintero, Guillermo; Pellón, María Luz; Romero, Carlos; Jorge, Mónica; Montes, Ana Fernández; Valladares-Ayerbes, Manuel; Ramos, Manuel; Varela, Silvia; Alonso, Miguel Ángel

2013-09-01

To evaluate gemcitabine plus capecitabine as third-line or later-line therapy in patients with refractory advanced colorectal cancer (CRC) who maintain a good performance status (PS). We retrospectively evaluated patients who had failed at least two lines of therapy or had contraindication to standard therapy and received gemcitabine (1,000 mg/m(2), d1 biweekly) plus capecitabine (1,700 mg/m(2)/day, d1-7 every two weeks) in a compassionate use program. Thirty-nine patients were enrolled. The majority (85%) had ECOG PS 1. Gemcitabine plus capecitabine was administered as third- and fourth-line in 49% and 23% of patients, respectively; and as fifth-line or later-line in 28%. A clinical benefit of 21% was found. The median progression-free survival and overall survival were 3.0 and 7.3 months, respectively. Toxicity was mild to moderate, with no reported grade 4 toxicities. Gemcitabine plus capecitabine was safe and well-tolerated. While the efficacy of this regimen was modest in terms of response, the survival data were acceptable and consistent with previous publications on this setting.

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.

Update on Advanced LIGO: the second observing run

NASA Astrophysics Data System (ADS)

Barsotti, Lisa; LIGO Scientific Collaboration Collaboration

2017-01-01

After several months of detector improvements, the two Advanced LIGO gravitational wave detectors are coming back on-line by the end of 2016 for their second Observing run, O2. In this talk I will discuss the status of Advanced LIGO and its observing plan.

Advanced Diesel Oil Fuel Processor Development

DTIC Science & Technology

1986-06-01

water exit 29 sample quencher: gas sample line inlet 30 sample quencher: gas sample line exit 31 sample quencher: cooling water inlet 32 desulfuriser ...exit line 33, 34 desulfurimer 35 heat exchanger: process gas exit (to desulfuriser ) 38 shift reactor inlet (top) 37 shift reactor: cooling air exit

Pest Resistance and agronomic performance of advanced BARBREN lines compared to commercial cultivars and the germplasm line BARBREN 713

USDA-ARS?s Scientific Manuscript database

The germplasm line BARBREN 713, which has resistance to both root-knot and reniform nematodes was released in 2012. Its major resistance to reniform nematodes is due to the Ren2 gene derived from Gossypium barbadense GB 713 and located near the DNA marker BNL 3279_105 on chromosome 21. Other lines...

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…

Basic and advanced numerical performances relate to mathematical expertise but are fully mediated by visuospatial skills.

PubMed

Sella, Francesco; Sader, Elie; Lolliot, Simon; Cohen Kadosh, Roi

2016-09-01

Recent studies have highlighted the potential role of basic numerical processing in the acquisition of numerical and mathematical competences. However, it is debated whether high-level numerical skills and mathematics depends specifically on basic numerical representations. In this study mathematicians and nonmathematicians performed a basic number line task, which required mapping positive and negative numbers on a physical horizontal line, and has been shown to correlate with more advanced numerical abilities and mathematical achievement. We found that mathematicians were more accurate compared with nonmathematicians when mapping positive, but not negative numbers, which are considered numerical primitives and cultural artifacts, respectively. Moreover, performance on positive number mapping could predict whether one is a mathematician or not, and was mediated by more advanced mathematical skills. This finding might suggest a link between basic and advanced mathematical skills. However, when we included visuospatial skills, as measured by block design subtest, the mediation analysis revealed that the relation between the performance in the number line task and the group membership was explained by non-numerical visuospatial skills. These results demonstrate that relation between basic, even specific, numerical skills and advanced mathematical achievement can be artifactual and explained by visuospatial processing. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Anomalous contact angle hysteresis of a captive bubble: advancing contact line pinning.

PubMed

Hong, Siang-Jie; Chang, Feng-Ming; Chou, Tung-He; Chan, Seong Heng; Sheng, Yu-Jane; Tsao, Heng-Kwong

2011-06-07

Contact angle hysteresis of a sessile drop on a substrate consists of continuous invasion of liquid phase with the advancing angle (θ(a)) and contact line pinning of liquid phase retreat until the receding angle (θ(r)) is reached. Receding pinning is generally attributed to localized defects that are more wettable than the rest of the surface. However, the defect model cannot explain advancing pinning of liquid phase invasion driven by a deflating bubble and continuous retreat of liquid phase driven by the inflating bubble. A simple thermodynamic model based on adhesion hysteresis is proposed to explain anomalous contact angle hysteresis of a captive bubble quantitatively. The adhesion model involves two solid–liquid interfacial tensions (γ(sl) > γ(sl)′). Young’s equation with γ(sl) gives the advancing angle θ(a) while that with γ(sl)′ due to surface rearrangement yields the receding angle θ(r). Our analytical analysis indicates that contact line pinning represents frustration in surface free energy, and the equilibrium shape corresponds to a nondifferential minimum instead of a local minimum. On the basis of our thermodynamic model, Surface Evolver simulations are performed to reproduce both advancing and receding behavior associated with a captive bubble on the acrylic glass.

Bevacizumab plus chemotherapy for patients with advanced pulmonary adenocarcinoma harboring EGFR mutations.

PubMed

Chen, R-L; Chen, H-J; Jiang, B-Y; Zhang, X-C; Zhou, Q; Tu, H-Y; Zhong, W-Z; Wu, Y-L; Yang, J-J

2018-02-01

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and bevacizumab plus chemotherapy were effective for EGFR-mutant patients. However, the appropriated treatment orders remained controvertible. We investigated the efficacy of treatment orders between bevacizumab plus chemotherapy and EGFR-TKIs for EGFR-mutant patients with advanced pulmonary adenocarcinoma. This study involved 40 EGFR-mutant patients with advanced pulmonary adenocarcinoma who were treated with bevacizumab plus carboplatin and paclitaxel (Bev + CP) and EGFR-TKIs in different treatment orders or gemcitabine plus cisplatin (GP) in first-line setting. Seventeen patients were treated with Bev + CP and 10 cases with GP in first-line treatment. Thirteen patients received EGFR-TKIs after first-line Bev + CP regimen, while 13 patients were treated with first-line EGFR-TKIs. Progression-free survival (PFS), the response rate (ORR) and overall survival (OS) were evaluated. Median PFS of Bev + CP treatment was significantly longer in first-line than non-first-line settings (11.7 vs. 5.6 months, P = 0.003). Median OS was 37.8 months for EGFR-mutant patients with first-line Bev + CP followed by second-line EGFR-TKIs and 31.0 months for those with first-line EGFR-TKIs and non-first-line Bev + CP, respectively (P = 0.509). Median PFS was 11.7 (95% CI 10.6-12.8) months for Bev + CP group and 4.7 (95% CI 4.4-5.0) months for GP group with the hazard ratio of 0.17 (P = 0.001). ORR was 70.6 and 50.0% in the two groups, respectively (P = 0.415). However, there was no significant difference in median OS (33.7 vs 27.8 months, P = 0.293). First-line Bev + CP followed by EGFR-TKIs might possibly provide favorable prognosis for EGFR-mutant patients. Bev + CP regimen significantly prolonged PFS in first-line than non-first-line settings. These findings warrant further investigations.

Health care resource use among patients with advanced non-small cell lung cancer: the PIvOTAL retrospective observational study.

PubMed

Lee, Dae Ho; Isobe, Hiroshi; Wirtz, Hubert; Aleixo, Sabina Bandeira; Parente, Phillip; de Marinis, Filippo; Huang, Min; Arunachalam, Ashwini; Kothari, Smita; Cao, Xiting; Donnini, Nello; Woodgate, Ann-Marie; de Castro, Javier

2018-03-01

Data are scarce regarding real-world health care resource use (HCRU) for non-small cell lung cancer (NSCLC). An understanding of current clinical practices and HCRU is needed to provide a benchmark for rapidly evolving NSCLC management recommendations and therapeutic options. The objective of this study was to describe real-world HCRU for patients with advanced NSCLC. This multinational, retrospective chart review study was conducted at academic and community oncology sites in Italy, Spain, Germany, Australia, Japan, South Korea, Taiwan, and Brazil. Deidentified data were drawn from medical records of 1440 adults (≥18 years old) who initiated systemic therapy (2011 to mid-2013) for a new, confirmed diagnosis of advanced or metastatic (stage IIIB or IV) NSCLC. We summarized HCRU associated with first and subsequent lines of systemic therapy for advanced/metastatic NSCLC. The proportion of patients who were hospitalized at least once varied by country from 24% in Italy to 81% in Japan during first-line therapy and from 22% in Italy to 84% in Japan during second-line therapy; overall hospitalization frequency was 2.5-11.1 per 100 patient-weeks, depending on country. Emergency visit frequency also varied among countries (overall from 0.3-5.9 per 100 patient-weeks), increasing consistently from first- through third-line therapy in each country. The outpatient setting was the most common setting of resource use. Most patients in the study had multiple outpatient visits in association with each line of therapy (overall from 21.1 to 59.0 outpatient visits per 100 patient-weeks, depending on country). The use of health care resources showed no regular pattern associated with results of tests for activating mutations of the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) gene rearrangements. HCRU varied across countries. These findings suggest differing approaches to the clinical management of advanced NSCLC among the eight countries. Comparative findings and an understanding of country-specific clinical practices can help to identify areas of need and guide future resource allocation for patients with advanced NSCLC. Further studies evaluating the costs associated with resource use are warranted.

77 FR 40586 - Draft NIST Interagency Report (NISTIR) 7823, Advanced Metering Infrastructure Smart Meter...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-10

...-01] Draft NIST Interagency Report (NISTIR) 7823, Advanced Metering Infrastructure Smart Meter... Technology (NIST) seeks comments on Draft NISTIR 7823, Advanced Metering Infrastructure Smart Meter.... Electronic comments should be sent to: Michaela Iorga at [email protected]nist.gov , with a Subject line...

Pembrolizumab Utilization and Outcomes for Advanced Melanoma in US Community Oncology Practices

PubMed Central

Liu, Frank Xiaoqing; Black-Shinn, Jenny; Stevinson, Kendall; Boyd, Marley; Frytak, Jennifer R.; Ebbinghaus, Scot W.

2018-01-01

The programmed death-1 inhibitor pembrolizumab has demonstrated efficacy and safety in clinical trials for treating advanced (unresectable/metastatic) melanoma. We investigated the real-world utilization of pembrolizumab and associated patient outcomes for advanced melanoma in US community oncology practices. This retrospective, observational study used deidentified data from electronic health records for adult patients with advanced melanoma who received pembrolizumab at The US Oncology Network sites from September 2014 through December 2015, with follow-up through September 2016. Patients enrolled in clinical trials were excluded. Overall survival (OS) and physician-stated progression-free survival (PFS) were analyzed from pembrolizumab initiation using Kaplan-Meier, and associations between pembrolizumab therapy and OS/PFS, using multivariable Cox regression. Of 168 patients studied, 110 (65%) were male; the median age was 66 years (range, 26–over 90). Pembrolizumab was prescribed as first-line, second-line, and third-line/later for 39 (23%), 87 (52%), and 42 (25%) patients, respectively. In total, 41 patients (24%) had brain metastases. At pembrolizumab initiation, 21/129 (16%) had Eastern Cooperative Oncology Group performance status (ECOG PS) >1; 51/116 (44%) had elevated lactate dehydrogenase. Median follow-up was 10.5 months (range, 0–25.1); median OS was 19.4 months (95% confidence interval, 14.0–not reached); median PFS was 4.2 months (95% confidence interval, 2.9–5.3). Brain metastases, ECOG PS>1, elevated lactate dehydrogenase, and third-line/later (vs. first-line) pembrolizumab were significant predictors (P<0.01) of decreased survival. Treatment-related toxicity was a discontinuation reason for 25% (29/117) of patients, and for 10 of these 29 patients (6% of the full-study cohort) treatment-related toxicity was the only reported reason. The real-world effectiveness and safety of pembrolizumab for advanced melanoma are consistent with clinical trial findings. PMID:29252916

[Efficacy of icotinib for advanced non-small cell lung cancer patients with EGFR status identified].

PubMed

Song, Zhengbo; Yu, Xinmin; Cai, Jufen; Shao, Lan; Lin, Baochai; He, Chunxiao; Zhang, Beibei; Zhang, Yiping

2013-03-01

As the first epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in China, icotinib shows promising anticancer activity in vitro and vivo. The phase III clinical study (ICOGEN) showed that icotinib has a good efficacy and tolerability in Chinese patients with advanced non-small cell lung cancer (NSCLC) compared with gefitinib. This retrospective study aims to evaluate the efficacy and tolerability of icotinib monotherapy for advanced NSCLC patients with EGFR mutation and wild-type patients in our hospital. Patients with advanced NSCLC who were treated with icotinib in Zhejiang Cancer Hospital were retrospectively analyzed from August, 2011 to August, 2012. Survival was estimated using Kaplan-Meier analysis and Log-rank tests. The clinical data of 49 patients (13 with wild-type and 36 with EGFR mutation) with NSCLC were enrolled in the current study. The patients' overall objective response rate (ORR) was 58.3% and the disease control rate (DCR) in 36 EGFR mutation patients was 88.9%. The ORR was 7.7% and DCR was 53.8% in the wild-type patients. Median progression-free survival (PFS) with icotinib treatment in EGFR mutation patients was 9.5 months and 2.2 months in wild-type patients (P<0.001). Nineteen patients with EGFR mutation received icotinib as first-line and 17 in further-line treatment. The PFS was 9.5 months in the first-line and 8.5 months for second-line or further-line patients (P=0.41). Median overall survival (OS) in EGFR mutation patients was not reached, but was 12.6 months in wild-type patients. Most of the drug-related adverse events were mild (grade I or II) and reversible with no grade IV toxicity. Icotinib monotherapy showed significant antitumor activity in advanced NSCLC EGFR mutation patients. The toxicity was well tolerated and acceptable.

Using whole mount in situ hybridization to link molecular and organismal biology.

PubMed

Jacobs, Nicole L; Albertson, R Craig; Wiles, Jason R

2011-03-31

Whole mount in situ hybridization (WISH) is a common technique in molecular biology laboratories used to study gene expression through the localization of specific mRNA transcripts within whole mount specimen. This technique (adapted from Albertson and Yelick, 2005) was used in an upper level undergraduate Comparative Vertebrate Biology laboratory classroom at Syracuse University. The first two thirds of the Comparative Vertebrate Biology lab course gave students the opportunity to study the embryology and gross anatomy of several organisms representing various chordate taxa primarily via traditional dissections and the use of models. The final portion of the course involved an innovative approach to teaching anatomy through observation of vertebrate development employing molecular techniques in which WISH was performed on zebrafish embryos. A heterozygous fibroblast growth factor 8 a (fgf8a) mutant line, ace, was used. Due to Mendelian inheritance, ace intercrosses produced wild type, heterozygous, and homozygous ace/fgf8a mutants in a 1:2:1 ratio. RNA probes with known expression patterns in the midline and in developing anatomical structures such as the heart, somites, tailbud, myotome, and brain were used. WISH was performed using zebrafish at the 13 somite and prim-6 stages, with students performing the staining reaction in class. The study of zebrafish embryos at different stages of development gave students the ability to observe how these anatomical structures changed over ontogeny. In addition, some ace/fgf8a mutants displayed improper heart looping, and defects in somite and brain development. The students in this lab observed the normal development of various organ systems using both external anatomy as well as gene expression patterns. They also identified and described embryos displaying improper anatomical development and gene expression (i.e., putative mutants). For instructors at institutions that do not already own the necessary equipment or where funds for lab and curricular innovation are limited, the financial cost of the reagents and apparatus may be a factor to consider, as will the time and effort required on the part of the instructor regardless of the setting. Nevertheless, we contend that the use of WISH in this type of classroom laboratory setting can provide an important link between developmental genetics and anatomy. As technology advances and the ability to study organismal development at the molecular level becomes easier, cheaper, and increasingly popular, many evolutionary biologists, ecologists, and physiologists are turning to research strategies in the field of molecular biology. Using WISH in a Comparative Vertebrate Biology laboratory classroom is one example of how molecules and anatomy can converge within a single course. This gives upper level college students the opportunity to practice modern biological research techniques, leading to a more diversified education and the promotion of future interdisciplinary scientific research.

Genomics meets ethology: a new route to understanding domestication, behavior, and sustainability in animal breeding.

PubMed

Jensen, Per; Andersson, Leif

2005-06-01

Animal behavior is a central part of animal welfare, a keystone in sustainable animal breeding. During domestication, animals have adapted with respect to behavior and an array of other traits. We compared the behavior of junglefowl and White Leghorn layers, selected for egg production (and indirectly for growth). Jungle-fowl had a more active behavior in social, exploratory, anti-predatory, and feeding tests. A genome scan for Quantitative Trait Loci (QTLs) in a junglefowl x White Leghorn intercross revealed several significant or suggestive QTLs for different traits. Some production QTLs coincided with QTLs for behavior, suggesting that pleiotropic effects may be important for the development of domestication phenotypes. One gene has been located, which has a strong effect on the risk of being a victim of feather pecking, a detrimental behavior disorder. Modern genomics paired with analysis of behavior may help in designing more sustainable and robust breeding in the future.

Smad3 mutant mice develop colon cancer with overexpression of COX-2

PubMed Central

Zhu, Yu-Ping; Liu, Zhuo; Fu, Zhi-Xuan; Li, De-Chuan

2017-01-01

Colon cancer is the second most common cause of cancer-associated mortality in human populations. The aim of the present study was to identify the role of cyclooxygenase-2 (COX-2) in Smad3 mutant mice, which are known to develop colon cancer. Homozygous Smad3 (−/−) mutant mice were generated from inbred and hybrid Smad3 mouse strains by intercrossing the appropriate heterozygotes. Immunohistochemistry with COX-2 antibody was performed throughout this experiment and the data was validated and cross-checked with reverse transcription-polymerase chain reaction (RT-PCR). Homozygous mutant Smad3 mice were generated and the overexpression pattern of COX-2 was identified by immunohistochemistry and validated with RT-PCR. The results of the present study demonstrated a link between the Smad3 mutant mice, colon cancer and COX-2. In addition, the overexpression pattern of COX-2 in Smad3 mutant mice that develop colon cancer was identified. PMID:28454287

A Sexual Ornament in Chickens Is Affected by Pleiotropic Alleles at HAO1 and BMP2, Selected during Domestication

PubMed Central

Johnsson, Martin; Gustafson, Ida; Rubin, Carl-Johan; Sahlqvist, Anna-Stina; Jonsson, Kenneth B.; Kerje, Susanne; Ekwall, Olov; Kämpe, Olle; Andersson, Leif; Jensen, Per; Wright, Dominic

2012-01-01

Domestication is one of the strongest forms of short-term, directional selection. Although selection is typically only exerted on one or a few target traits, domestication can lead to numerous changes in many seemingly unrelated phenotypes. It is unknown whether such correlated responses are due to pleiotropy or linkage between separate genetic architectures. Using three separate intercrosses between wild and domestic chickens, a locus affecting comb mass (a sexual ornament in the chicken) and several fitness traits (primarily medullary bone allocation and fecundity) was identified. This locus contains two tightly-linked genes, BMP2 and HAO1, which together produce the range of pleiotropic effects seen. This study demonstrates the importance of pleiotropy (or extremely close linkage) in domestication. The nature of this pleiotropy also provides insights into how this sexual ornament could be maintained in wild populations. PMID:22956912

What's the Bottom Line

EPA Science Inventory

Advances in analytical instrumentation have not only increased the number and types of chemicals measured, but reduced the quantitation limits, allowing these chemicals to be detected at progressively lower concentrations in various environmental matrices. Such analytical advanc...

Apatinib in the treatment of advanced lung adenocarcinoma with KRAS mutation.

PubMed

Zeng, Da-Xiong; Wang, Chang-Guo; Huang, Jian-An; Jiang, Jun-Hong

2017-01-01

Activating KRAS mutations in lung adenocarcinoma are characterized with treatment resistance and poor prognosis. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase, apatinib has been proven successful in advanced gastric cancer and breast cancer. In this study, we show the result of apatinib as salvage treatment in lung adenocarcinoma patients with KRAS mutation. Four advanced lung adenocarcinoma patients with KRAS mutation were orally administered apatinib (250 mg/d) after second-line treatment. One patient showed progressive disease, while 3 patients showed stable disease response to apatinib, with a median progression-free survival (PFS) of 3.8 months (1.5-5.5 months). The main toxicities were hoarseness and hemoptysis, which were manageable. Therefore, apatinib might be an optional choice for advanced lung adenocarcinoma patients with KRAS mutation in post second-line treatment.

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…

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 helpmore » 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.« less

CellLineNavigator: a workbench for cancer cell line analysis

PubMed Central

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

2013-01-01

The CellLineNavigator database, freely available at http://www.medicalgenomics.org/celllinenavigator, is a web-based workbench for large scale comparisons of a large collection of diverse cell lines. It aims to support experimental design in the fields of genomics, systems biology and translational biomedical research. Currently, this compendium holds genome wide expression profiles of 317 different cancer cell lines, categorized into 57 different pathological states and 28 individual tissues. To enlarge the scope of CellLineNavigator, the database was furthermore closely linked to commonly used bioinformatics databases and knowledge repositories. To ensure easy data access and search ability, a simple data and an intuitive querying interface were implemented. It allows the user to explore and filter gene expression, focusing on pathological or physiological conditions. For a more complex search, the advanced query interface may be used to query for (i) differentially expressed genes; (ii) pathological or physiological conditions; or (iii) gene names or functional attributes, such as Kyoto Encyclopaedia of Genes and Genomes pathway maps. These queries may also be combined. Finally, CellLineNavigator allows additional advanced analysis of differentially regulated genes by a direct link to the Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resources. PMID:23118487

Modifier locus mapping of a transgenic F2 mouse population identifies CCDC115 as a novel aggressive prostate cancer modifier gene in humans.

PubMed

Winter, Jean M; Curry, Natasha L; Gildea, Derek M; Williams, Kendra A; Lee, Minnkyong; Hu, Ying; Crawford, Nigel P S

2018-06-11

It is well known that development of prostate cancer (PC) can be attributed to somatic mutations of the genome, acquired within proto-oncogenes or tumor-suppressor genes. What is less well understood is how germline variation contributes to disease aggressiveness in PC patients. To map germline modifiers of aggressive neuroendocrine PC, we generated a genetically diverse F2 intercross population using the transgenic TRAMP mouse model and the wild-derived WSB/EiJ (WSB) strain. The relevance of germline modifiers of aggressive PC identified in these mice was extensively correlated in human PC datasets and functionally validated in cell lines. Aggressive PC traits were quantified in a population of 30 week old (TRAMP x WSB) F2 mice (n = 307). Correlation of germline genotype with aggressive disease phenotype revealed seven modifier loci that were significantly associated with aggressive disease. RNA-seq were analyzed using cis-eQTL and trait correlation analyses to identify candidate genes within each of these loci. Analysis of 92 (TRAMP x WSB) F2 prostates revealed 25 candidate genes that harbored both a significant cis-eQTL and mRNA expression correlations with an aggressive PC trait. We further delineated these candidate genes based on their clinical relevance, by interrogating human PC GWAS and PC tumor gene expression datasets. We identified four genes (CCDC115, DNAJC10, RNF149, and STYXL1), which encompassed all of the following characteristics: 1) one or more germline variants associated with aggressive PC traits; 2) differential mRNA levels associated with aggressive PC traits; and 3) differential mRNA expression between normal and tumor tissue. Functional validation studies of these four genes using the human LNCaP prostate adenocarcinoma cell line revealed ectopic overexpression of CCDC115 can significantly impede cell growth in vitro and tumor growth in vivo. Furthermore, CCDC115 human prostate tumor expression was associated with better survival outcomes. We have demonstrated how modifier locus mapping in mouse models of PC, coupled with in silico analyses of human PC datasets, can reveal novel germline modifier genes of aggressive PC. We have also characterized CCDC115 as being associated with less aggressive PC in humans, placing it as a potential prognostic marker of aggressive PC.

Consomic mouse strain selection based on effect size measurement, statistical significance testing and integrated behavioral z-scoring: focus on anxiety-related behavior and locomotion.

PubMed

Labots, M; Laarakker, M C; Ohl, F; van Lith, H A

2016-06-29

Selecting chromosome substitution strains (CSSs, also called consomic strains/lines) used in the search for quantitative trait loci (QTLs) consistently requires the identification of the respective phenotypic trait of interest and is simply based on a significant difference between a consomic and host strain. However, statistical significance as represented by P values does not necessarily predicate practical importance. We therefore propose a method that pays attention to both the statistical significance and the actual size of the observed effect. The present paper extends on this approach and describes in more detail the use of effect size measures (Cohen's d, partial eta squared - η p (2) ) together with the P value as statistical selection parameters for the chromosomal assignment of QTLs influencing anxiety-related behavior and locomotion in laboratory mice. The effect size measures were based on integrated behavioral z-scoring and were calculated in three experiments: (A) a complete consomic male mouse panel with A/J as the donor strain and C57BL/6J as the host strain. This panel, including host and donor strains, was analyzed in the modified Hole Board (mHB). The consomic line with chromosome 19 from A/J (CSS-19A) was selected since it showed increased anxiety-related behavior, but similar locomotion compared to its host. (B) Following experiment A, female CSS-19A mice were compared with their C57BL/6J counterparts; however no significant differences and effect sizes close to zero were found. (C) A different consomic mouse strain (CSS-19PWD), with chromosome 19 from PWD/PhJ transferred on the genetic background of C57BL/6J, was compared with its host strain. Here, in contrast with CSS-19A, there was a decreased overall anxiety in CSS-19PWD compared to C57BL/6J males, but not locomotion. This new method shows an improved way to identify CSSs for QTL analysis for anxiety-related behavior using a combination of statistical significance testing and effect sizes. In addition, an intercross between CSS-19A and CSS-19PWD may be of interest for future studies on the genetic background of anxiety-related behavior.

Phase III randomized trial comparing 5-fluorouracil and oxaliplatin with or without docetaxel in first-line advanced gastric cancer chemotherapy (GASTFOX study).

PubMed

Zaanan, Aziz; Samalin, Emmanuelle; Aparicio, Thomas; Bouche, Olivier; Laurent-Puig, Pierre; Manfredi, Sylvain; Michel, Pierre; Monterymard, Carole; Moreau, Marie; Rougier, Philippe; Tougeron, David; Taieb, Julien; Louvet, Christophe

2018-04-01

In advanced gastric cancer, doublet regimen including platinum salts and fluoropyrimidine is considered as a standard first-line treatment. The addition of docetaxel (75 mg/m 2  q3w) to cisplatin (75 mg/m 2  q3w) and 5-fluorouracil has been shown to improve efficacy. However, this regimen (DCF) was associated with frequent severe toxicities (including more complicated neutropenia), limiting its use in clinical practice. Interesting alternative docetaxel-based regimens have been developed that need to be validated. GASTFOX study is a randomized phase III trial comparing FOLFOX alone or with docetaxel at 50 mg/m 2 (TFOX regimen) in first-line treatment for advanced gastric cancer. In both arms, cycle is repeated every 2 weeks until disease progression or unacceptable toxicity. Main eligibility criteria: histologically proven locally advanced or metastatic gastric or esogastric junction adenocarcinoma, HER negative status, measurable disease, ECOG performance status 0 or 1, and adequate renal, hepatic and bone marrow functions. The primary endpoint is radiological/clinical progression-free survival (PFS). A difference of 2 months for the median PFS in favor of TFOX is expected (HR = 0.73) Based on a two-sided α risk of 5% and a power of 90%, 454 events are required to show this difference. Secondary endpoints included overall survival, overall response rate, safety, quality of life and the therapeutic index. This study is planned to include 506 patients to demonstrate the superiority of TFOX over FOLFOX in first-line advanced gastric cancer treatment (NCT03006432). Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction.

PubMed

Li, Jin; Qin, Shukui; Xu, Jianming; Xiong, Jianping; Wu, Changping; Bai, Yuxian; Liu, Wei; Tong, Jiandong; Liu, Yunpeng; Xu, Ruihua; Wang, Zhehai; Wang, Qiong; Ouyang, Xuenong; Yang, Yan; Ba, Yi; Liang, Jun; Lin, Xiaoyan; Luo, Deyun; Zheng, Rongsheng; Wang, Xin; Sun, Guoping; Wang, Liwei; Zheng, Leizhen; Guo, Hong; Wu, Jingbo; Xu, Nong; Yang, Jianwei; Zhang, Honggang; Cheng, Ying; Wang, Ningju; Chen, Lei; Fan, Zhining; Sun, Piaoyang; Yu, Hao

2016-05-01

There is currently no standard treatment strategy for patients with advanced metastatic gastric cancer experiencing progression after two or more lines of chemotherapy. We assessed the efficacy and safety of apatinib, a novel vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, in patients with advanced gastric or gastroesophageal junction adenocarcinoma for whom at least two lines of prior chemotherapy had failed. This was a randomized, double-blind, placebo-controlled phase III trial. Patients from 32 centers in China with advanced gastric or gastroesophageal junction adenocarcinoma, for whom two or more prior lines of chemotherapy had failed, were enrolled. Patients were randomly assigned to oral apatinib 850 mg or placebo once daily. The primary end points were overall (OS) and progression-free survival (PFS). Between January 2011 and November 2012, 267 patients were enrolled. Median OS was significantly improved in the apatinib group compared with the placebo group (6.5 months; 95% CI, 4.8 to 7.6 v 4.7 months; 95% CI, 3.6 to 5.4; P = .0149; hazard ratio, 0.709; 95% CI, 0.537 to 0.937; P = .0156). Similarly, apatinib significantly prolonged median PFS compared with placebo (2.6 months; 95% CI, 2.0 to 2.9 v 1.8 months; 95% CI, 1.4 to 1.9; P < .001; hazard ratio, 0.444; 95% CI, 0.331 to 0.595; P < .001). The most common grade 3 to 4 nonhematologic adverse events were hand-foot syndrome, proteinuria, and hypertension. These data show that apatinib treatment significantly improved OS and PFS with an acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy. © 2016 by American Society of Clinical Oncology.

Clinical features and response to systemic therapy in a historical cohort of advanced or unresectable mucosal melanoma.

PubMed

Shoushtari, Alexander N; Bluth, Mark J; Goldman, Debra A; Bitas, Christiana; Lefkowitz, Robert A; Postow, Michael A; Munhoz, Rodrigo R; Buchar, Gauri; Hester, Robert H; Romero, Jacqueline A; Fitzpatrick, Laura J; Weiser, Martin R; Panageas, Katherine S; Wolchok, Jedd D; Chapman, Paul B; Carvajal, Richard D

2017-02-01

There are very few data available regarding the pattern of first metastases in resected mucosal melanomas (MMs) as well as the response of advanced MM to cytotoxic therapy. A retrospective, single-institution cohort was assembled of all patients with advanced/unresectable MM between 1995 and 2012 who had received systemic therapy with available imaging (N=81). Responses to first-line and second-line systemic therapy were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The relationship between response, overall survival, and clinical covariates was investigated using Cox proportional hazards regression. Primary sites included anorectal (N=31, 38%), vulvovaginal (N=28, 35%), head and neck (N=21, 26%), and gallbladder (N=1, 1%) mucosa. Seven percent of patients had their first relapse in the brain. Cytotoxic therapy represented 82 and 51% of first-line and second-line regimens. The best response achieved in the first-line setting was similar for single-agent [10%; 95% confidence interval (CI): 1-32%] and combination alkylator therapy (8%; 95% CI: 2-21%). Median overall survival from first-line treatment was 10.3 months (95% CI: 8.7-13.9 months). Patients with elevated lactic dehydrogenase [hazard ratio (HR): 1.87, 95% CI: 1.10-3.19, P=0.020] and Eastern Cooperative Oncology Group performance status 1-2 (HR: 1.69, 95% CI: 1.05-2.72, P=0.030) had a higher risk of death, whereas patients with 12-week objective responses had a lower risk of death (HR: 0.12, 95% CI: 0.04-0.41, P<0.001). Cytotoxic systemic therapy has modest activity in advanced/unresectable MM, belying its adjuvant benefit. Patients whose tumors have an objective response to therapy have a lower probability of death. Brain imaging should be considered in routine surveillance.

Palliative systemic therapy and overall survival of 1,395 patients with advanced breast cancer - Results from the prospective German TMK cohort study.

PubMed

Fietz, Thomas; Tesch, Hans; Rauh, Jacqueline; Boller, Emil; Kruggel, Lisa; Jänicke, Martina; Marschner, Norbert

2017-08-01

Data on treatment and outcome of advanced breast cancer in routine practice are rare, especially concerning recurrent disease, but important to complement the results from clinical trials and to improve the standard of care. We present data on choice of systemic first-line treatment, number of treatment lines, and survival of patients treated by medical oncologists in Germany. 1395 patients recruited by 124 sites at start of first-line therapy into the ongoing, prospective German clinical cohort study TMK (Tumour Registry Breast Cancer) between February 2007 and October 2015 were analysed. The median OS was 33.8 months (95% CI 30.2-40.2) for HR-positive/HER2-negative, 38.2 months (95% CI 31.3-43.0) for HER2-positive and 16.8 months (95% CI 11.5-22.0) for triple negative breast cancer. Patients with triple negative tumours more often died before start of a third-line therapy than patients with HR-positive or HER2-positive tumours (44% vs. 25%). Use of taxane-based chemotherapies has increased since 2007, with 65% of all first-line chemotherapy-treatments containing taxanes in 2013-15 (60% HR-positive/HER2-negative, 75% HER2-positive, 56% triple negative). 52% of the patients with HR-positive/HER2-negative tumours received first-line endocrine therapy in 2013-15; when restricted to patients with only non-visceral metastases this percentage increased to 63%. To our knowledge, this is the first cohort study showing systemic first-line therapy for all subtypes of advanced breast cancer. Overall survival in the TMK is comparable to that reported by clinical trials despite the inclusion of older and comorbid patients. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Daratumumab resistance is frequent in advanced-stage multiple myeloma patients irrespective of CD38 expression and is related to dismal prognosis.

PubMed

Pick, Marjorie; Vainstein, Vladimir; Goldschmidt, Neta; Lavie, David; Libster, Diana; Gural, Alexander; Grisariu, Sigal; Avni, Batia; Ben Yehuda, Dina; Gatt, Moshe E

2018-05-01

Daratumumab is a promising new antimyeloma agent. We report a single center "real-world" series of multiple myeloma (MM) and amyloidosis (AL) patients treated with daratumumab. Forty-one patients were included: 7 second-line MM, 30 heavily pretreated (median number of therapies of 5) advanced MM, and 4 with AL. Second-line patients and advanced AL showed high rate of durable overall responses. However, advanced MM patients had a dismal prognosis with an overall response rate (ORR) of 36%, and a short median progression-free and overall survival of 2.3 and 6.6 months, respectively. Responses were particularly poor in patients with extramedullary plasmacytomas. Neither the addition of another agent to daratumumab nor changing to the next line of therapy produced significant durable responses in this patient population. Flow cytometry analysis demonstrated that CD38 expression level was not predictive of response. We show that CD38 expression dynamics by a commercially available anti-CD38 antibody after daratumumab administration was hindered by competitive binding of daratumumab. Responses to daratumumab and combinations in patients with advanced MM, particularly with extramedullary disease, are low and short-lived, stressing the administration of this agent should be early in the course of the disease. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Docetaxel/S-1 Versus Docetaxel/Capecitabine as First-Line Treatment for Advanced Breast Cancer

PubMed Central

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

2015-01-01

Abstract 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

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.

Factors associated with prolonged time to treatment failure with fulvestrant 500 mg in patients with post-menopausal estrogen receptor-positive advanced breast cancer: a sub-group analysis of the JBCRG-C06 Safari study.

PubMed

Kawaguchi, Hidetoshi; Masuda, Norikazu; Nakayama, Takahiro; Aogi, Kenjiro; Anan, Keisei; Ito, Yoshinori; Ohtani, Shoichiro; Sato, Nobuaki; Saji, Shigehira; Takano, Toshimi; Tokunaga, Eriko; Nakamura, Seigo; Hasegawa, Yoshie; Hattori, Masaya; Fujisawa, Tomomi; Morita, Satoshi; Yamaguchi, Miki; Yamashita, Hiroko; Yamashita, Toshinari; Yamamoto, Yutaka; Yotsumoto, Daisuke; Toi, Masakazu; Ohno, Shinji

2018-01-01

The JBCRG-C06 Safari study showed that earlier fulvestrant 500 mg (F500) use, a longer time from diagnosis to F500 use, and no prior palliative chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with estrogen receptor-positive (ER+) advanced breast cancer (ABC). The objective of this sub-group analysis was to further examine data from the Safari study, focusing on ER + and human epidermal growth factor receptor-negative (HER2-) cases. The Safari study (UMIN000015168) was a retrospective, multi-center cohort study, conducted in 1,072 patients in Japan taking F500 for ER + ABC. The sub-analysis included only patients administered F500 as second-line or later therapy (n = 960). Of these, 828 patients were HER2-. Results Multivariate analysis showed that advanced age (≥65 years; p = .035), longer time (≥3 years) from ABC diagnosis to F500 use (p < .001), no prior chemotherapy (p < .001), and F500 treatment line (p < .001) were correlated with prolonged TTF (median = 5.39 months). In ER+/HER2- patients receiving F500 as a second-line or later therapy, treatment line, advanced age, no prior palliative chemotherapy use, and a longer period from ABC diagnosis to F500 use were associated with longer TTF.

VICTOR: Vinflunine in advanced metastatic transitional cell carcinoma of the urothelium: A retrospective analysis of the use of vinflunine in multi-centre real life setting as second line chemotherapy through Free of Charge Programme for patients in the UK and Ireland.

PubMed

Hussain, Syed A; Ansari, Jawaher; Huddart, Robert; Power, Derek G; Lyons, Jeanette; Wylie, James; Vilarino-Varlela, Maria; Elander, Nils O; McMenemin, Rhona; Pickering, Lisa M; Faust, Guy; Chauhan, Seema; Jackson, Richard J

2017-03-01

There is no standard of care in the UK or Ireland for second-line chemotherapy for patients with advanced transitional cell carcinoma (TCCU). Vinflunine is approved for TCCU patients who have failed a platinum-based regimen, and is standard of care in Europe but is not routinely available in the UK. Data were collected retrospectively on patients who received vinfluine as a second-line treatment. The aims were to document the toxicity and efficacy in a real life setting. Data were collected on 49 patients from 9 sites across the UK and Ireland [median age, 64 (IQR, 57-70) years, 33 males]. All patients had advanced metastatic TCCU. Thirteen patients had bone or liver metastases, 4 patients had PS 2 and 11 patients had HB <10. Median vinflunine administration was 3.5 cycles (range 1-18). Most common grade 3-4 toxicities were constipation (4 patients) and fatigue (3 patients). Partial response rate was 29% (14 PR, 11 SD, 19 PD, 4 NE, 1 not available). Median OS was 9.1 (6.0, 12.7) months. Results are consistent with real life data from Europe. Toxicity is further reduced with prophylactic laxative and oral antibiotics. Vinflunine is an efficient and tolerable second line treatment in advanced TCCU.

Second-line chemotherapy in advanced biliary cancer progressed to first-line platinum-gemcitabine combination: a multicenter survey and pooled analysis with published data.

PubMed

Fornaro, Lorenzo; Vivaldi, Caterina; Cereda, Stefano; Leone, Francesco; Aprile, Giuseppe; Lonardi, Sara; Silvestris, Nicola; Santini, Daniele; Milella, Michele; Caparello, Chiara; Musettini, Gianna; Pasquini, Giulia; Falcone, Alfredo; Brandi, Giovanni; Sperduti, Isabella; Vasile, Enrico

2015-12-23

After progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers (aBTC). Indeed, literature data suggest limited activity of most second-line agents evaluated so far. We collected a large retrospective series of aBTC patients treated with second-line chemotherapy after progression to a first-line GP regimen at different Italian institutions. We then pooled the data with those reported in previous studies, which were identified with a Medline search and the on-line abstract datasets of major international oncology meetings. A total of 174 patients were included in the multicenter survey: response rate (RR) with second-line chemotherapy was low (3.4 %), with median PFS and OS of 3.0 months and 6.6 months, respectively. At multivariate analysis, preserved performance status, low CA19.9 levels and absence of distant metastases were favorable prognostic factors. Data from other five presented or published series were identified, for a total of 499 patients included in the pooled analysis. The results confirmed marginal activity of second-line chemotherapy (RR: 10.2 %), with limited efficacy in unselected patient populations (median PFS: 3.1 months; median OS: 6.3 months). The current analysis highlights the limited value of second-line chemotherapy after a first-line GP combination in aBTC. While waiting for effective biologic agents in this setting, ongoing randomized trials will identify the optimal second-line chemotherapy regimen and validate prognostic factors for individual patient management.

26 CFR 1.36B-4 - Reconciling the premium tax credit with advance credit payments.

Code of Federal Regulations, 2014 CFR

2014-04-01

... taxpayer whose household income is less than 400 percent of the Federal poverty line is limited to the... tax limitation table. Household income percentage of Federal poverty line Limitation amount for... projects A's 2014 household income to be $27,925 (250 percent of the Federal poverty line for a family of...

26 CFR 1.36B-4 - Reconciling the premium tax credit with advance credit payments.

Code of Federal Regulations, 2013 CFR

2013-04-01

... taxpayer whose household income is less than 400 percent of the Federal poverty line is limited to the... tax limitation table. Household income percentage of Federal poverty line Limitation amount for... projects A's 2014 household income to be $27,925 (250 percent of the Federal poverty line for a family of...

Brake Lining for Transit Buses - Bonded vs. Bolted

DOT National Transportation Integrated Search

1985-06-01

This report points out an often cited complaint from urban transit agencies concerning the Advanced Design Bus: the relatively short brake lining life. Despite design improvements made by the equipment supply industry since the introduction of the AD...

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.

Evaluation of bike boxes at signalized intersections.

DOT National Transportation Integrated Search

2011-01-01

This report presents a before-after study of bike boxes at 10 signalized intersections in Portland, Oregon. The bike boxes, also known as advanced stop lines or advanced stop boxes, were installed to increase visibility of cyclists and reduce conflic...

Cost-Effectiveness of Immune Checkpoint Inhibition in BRAF Wild-Type Advanced Melanoma

PubMed Central

Zeichner, Simon B.; Chen, Qiushi; Montero, Alberto J.; Goldstein, Daniel A.; Flowers, Christopher R.

2017-01-01

Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17%. Randomized controlled trials of recent US Food and Drug Administration–approved immune checkpoint inhibitors—pembrolizumab (PEM), nivolumab (NIVO), and ipilumumab (IPI)—demonstrate improved patient outcomes, but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear. To inform policy makers about the value of these treatments, we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma. Materials and Methods We developed Markov models by using a US-payer perspective and lifetime horizon to estimate costs (2016 US$) and quality-adjusted life years (QALYs) for treatment sequences with first-line NIVO, IPI, NIVO + IPI, PEM every 2 weeks, and PEM every 3 weeks. Health states were defined for initial treatment, first and second progression, and death. Rates for drug discontinuation, frequency of adverse events, disease progression, and death obtained from randomized phase III trials were used to determine the likelihood of transition between states. Deterministic and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. Results PEM every 3 weeks followed by second-line IPI was both more effective and less costly than dacarbazine followed by IPI then NIVO, or IPI followed by NIVO. Compared with the first-line dacarbazine treatment strategy, NIVO followed by IPI produced an incremental cost effectiveness ratio of $90,871/QALY, and first-line NIVO + IPI followed by carboplatin plus paclitaxel chemotherapy produced an incremental cost effectiveness ratio of $198,867/QALY. Conclusion For patients with treatment-naive BRAF wild-type advanced melanoma, first-line PEM every 3 weeks followed by second-line IPI or first-line NIVO followed by second-line IPI are the most cost-effective, immune-based treatment strategies for metastatic melanoma. PMID:28221865

Pacific Pediatric Advanced Care Initiative

DTIC Science & Technology

2009-10-01

Prepare IV ports:  Identify IV ports (UVC, Femoral venous line, other central venous lines, or PIV) for easy access to push meds or administer volume...Supply Department CVL central venous line CXR chest xray DC discontinue DI Diagnostic Imaging DIC disseminated intravascular coagulation diff...programs at KMCWC. These include the blood bank, blood utilization committee, clinical laboratories, operating room, central supply, pharmacy

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

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

PubMed Central

Trojan, Jörg; Waidmann, Oliver

2016-01-01

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

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

PubMed

Trojan, Jörg; Waidmann, Oliver

2016-01-01

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

Patient Comprehension and Attitudes toward Maintenance Chemotherapy for Lung Cancer

PubMed Central

Gerber, David E.; Hamann, Heidi A.; Rasco, Drew W.; Woodruff, Sharon; Craddock Lee, Simon J.

2012-01-01

Objective Maintenance chemotherapy is a recently approved approach to the treatment of advanced non-small cell lung cancer (NSCLC). We sought to gain insight into patients’ perceptions of maintenance chemotherapy using qualitative methods. Methods We conducted thematic content analysis of focus groups at a freestanding cancer center and at an associated safety-net county hospital. Patients with advanced NSCLC who had started but not yet completed first-line platinum doublet chemotherapy were provided visual and written explanations of maintenance chemotherapy before being guided in group discussion. Results Key themes to emerge for consideration of maintenance chemotherapy included (1) survival benefits, disease control, and “buying time”; (2) the importance of “doing something”; (3) quality of life concerns; (4) the role of provider opinion/preference; and (5) the importance of logistics. Conclusions Patients undergoing first-line chemotherapy for advanced NSCLC were able to understand the concept of maintenance chemotherapy, distinguish it from traditional treatment paradigms, identify pros and cons of this approach, and convey reasons for considering it. Practice Implications Advances in oncology care that alter therapy modalities and delivery may significantly impact patient perceptions and treatment experiences. Clinical team members may wish to elicit treatment preferences of first-line patients through clinical discussions that anticipate these considerations. PMID:22632736

Efficacy of icotinib versus traditional chemotherapy as first-line treatment for preventing brain metastasis from advanced lung adenocarcinoma in patients with epidermal growth factor receptor-sensitive mutation.

PubMed

Zhao, Xiao; Zhu, Guangqin; Chen, Huoming; Yang, Ping; Li, Fang; Du, Nan

2016-01-01

This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma. This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment. The therapeutic efficacy was compared among patients with advanced. (stages IIIB and IV) lung adenocarcinoma with epidermal growth factor receptor (EGFR)-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas, the secondary endpoint was overall survival(OS). Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance was determined using the log-rank test. The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups. Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR.sensitive mutation.

Efficacy of icotinib versus traditional chemotherapy as first-line treatment for preventing brain metastasis from advanced lung adenocarcinoma in patients with epidermal growth factor receptor-sensitive mutation.

PubMed

Zhao, Xiao; Zhu, Guangqin; Chen, Huoming; Yang, Ping; Li, Fang; Du, Nan

2014-11-01

This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma. This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment. The therapeutic efficacy was compared among patients with advanced (stages IIIB and IV) lung adenocarcinoma with epidermal growth factor receptor (EGFR)-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas the secondary endpoint was overall survival (OS). Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance were determined using the log-rank test. The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups. Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR-sensitive mutation.

In-line height profiling metrology sensor for zero defect production control

NASA Astrophysics Data System (ADS)

Snel, Rob; Winters, Jasper; Liebig, Thomas; Jonker, Wouter

2017-06-01

Contemporary production systems of mechanical precision parts show challenges as increased complexity, tolerances shrinking to sub-microns and yield losses that must be mastered to the extreme. More advanced automation and process control is required to accomplish this task. Often a solution based on feedforward/feedback control is chosen requiring innovative and more advanced in line metrology. This article concentrates first on the context of in line metrology for process control and then on the development of a specific in line height profiling sensor. The novel sensor technology is based on full field time domain white light interferometry which is well know from the quality lab. The novel metrology system is to be mounted close to the production equipment, as required to minimize time delay in the control loop, and is thereby fully exposed to vibrations. This sensor is innovated to perform in line with an orders of magnitude faster throughput than laboratory instruments; it's robust to withstand the rigors of workshops and has a height resolution that is in the nanometer range.

Advanced propeller aerodynamic analysis

NASA Technical Reports Server (NTRS)

Bober, L. J.

1980-01-01

The analytical approaches as well as the capabilities of three advanced analyses for predicting propeller aerodynamic performance are presented. It is shown that two of these analyses use a lifting line representation for the propeller blades, and the third uses a lifting surface representation.

Marketing potential of advanced breeding clones

USDA-ARS?s Scientific Manuscript database

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...

Cyclophosphamide-hydroxycamptothecin as second-line chemotherapy for advanced Ewing's sarcoma: experience of a single institution.

PubMed

Han, Kun; Sun, Yuanjue; Zhang, Jianjun; He, Aina; Zheng, Shui'er; Shen, Zan; Yao, Yang

2014-06-01

To investigate the feasibility and efficacy of cyclophosphamide (CTX)-hydroxycamptothecin (HCPT) as second-line chemotherapy on advanced Ewing's sarcoma. From April 2009 to November 2010, 27 patients with advanced Ewing's sarcoma who had progressive disease after the first-line chemotherapy regimen of vincristine, dactinomycin and cyclophosphamide and ifosfamide and etoposide were retrospectively reviewed in this analysis. CTX was given (0.6 g/m(2), i.v. push day 1) and HCPT (6 mg/m(2), i.v. drip days 1-5) as second-line chemotherapy every 3 weeks. The primary end-point was overall response rate, the secondary end-point included progression-free, overall survival, disease control rate and toxicities. A total of 134 cycles were given, median four cycles per patient (range 2-6). Overall response rate was 30% and disease control rate was 82%, with two complete response (8%), six partial remission (22%) and 14 stable disease (52%). The median time to progression and overall survival time were 7 months (95% CI 3-10) and 11 months (95% CI 5-18), respectively. Major severe toxicities (grade 3 and 4) were: nausea/vomiting (17%), alopecia (17%); leukopenia (27%) in total cycles. Mild toxicities (grade 1 or 2) were leukopenia (73%), nausea/vomiting (83%), hepatic lesion (14%) and anemia (44%). A CTX-HCPT regimen can control disease progression effectively and the side effects can be tolerable for Chinese advanced Ewing's sarcoma patients. Further assessment is necessary to confirm the safety and efficacy of this treatment. © 2012 Wiley Publishing Asia Pty Ltd.

Three-gradient regular solution model for simple liquids wetting complex surface topologies

PubMed Central

Akerboom, Sabine; Kamperman, Marleen

2016-01-01

Summary We use regular solution theory and implement a three-gradient model for a liquid/vapour system in contact with a complex surface topology to study the shape of a liquid drop in advancing and receding wetting scenarios. More specifically, we study droplets on an inverse opal: spherical cavities in a hexagonal pattern. In line with experimental data, we find that the surface may switch from hydrophilic (contact angle on a smooth surface θY < 90°) to hydrophobic (effective advancing contact angle θ > 90°). Both the Wenzel wetting state, that is cavities under the liquid are filled, as well as the Cassie–Baxter wetting state, that is air entrapment in the cavities under the liquid, were observed using our approach, without a discontinuity in the water front shape or in the water advancing contact angle θ. Therefore, air entrapment cannot be the main reason why the contact angle θ for an advancing water front varies. Rather, the contact line is pinned and curved due to the surface structures, inducing curvature perpendicular to the plane in which the contact angle θ is observed, and the contact line does not move in a continuous way, but via depinning transitions. The pinning is not limited to kinks in the surface with angles θkink smaller than the angle θY. Even for θkink > θY, contact line pinning is found. Therefore, the full 3D-structure of the inverse opal, rather than a simple parameter such as the wetting state or θkink, determines the final observed contact angle. PMID:27826512

Advanced training of specialists in area of fiber-optic communication lines maintenance

NASA Astrophysics Data System (ADS)

Andreev, Vladimir A.; Voronkov, Andrey A.; Bukashkin, Sergey A.; Buzova, Maria A.

2017-04-01

The paper considers the concept of fiber-optic communication lines (FOCL) maintenance. Performance criterion of FOCL technical maintenance was proposed. For the first time the algorithm for evaluation of the FOCL maintenance efficiency at telecommunication specialists training was applied.

Ectopic Expression of Nolz-1 in Neural Progenitors Promotes Cell Cycle Exit/Premature Neuronal Differentiation Accompanying with Abnormal Apoptosis in the Developing Mouse Telencephalon

PubMed Central

Chang, Sunny Li-Yun; Chen, Shih-Yun; Huang, Huai-Huei; Ko, Hsin-An; Liu, Pei-Tsen; Liu, Ya-Chi; Chen, Ping-Hau; Liu, Fu-Chin

2013-01-01

Nolz-1, as a murine member of the NET zinc-finger protein family, is expressed in post-mitotic differentiating neurons of striatum during development. To explore the function of Nolz-1 in regulating the neurogenesis of forebrain, we studied the effects of ectopic expression of Nolz-1 in neural progenitors. We generated the Cre-loxP dependent conditional transgenic mice in which Nolz-1 was ectopically expressed in proliferative neural progenitors. Ectopic expression of Nolz-1 in neural progenitors by intercrossing the Nolz-1 conditional transgenic mice with the nestin-Cre mice resulted in hypoplasia of telencephalon in double transgenic mice. Decreased proliferation of neural progenitor cells were found in the telencephalon, as evidenced by the reduction of BrdU−, Ki67− and phospho-histone 3-positive cells in E11.5–12.5 germinal zone of telencephalon. Transgenic Nolz-1 also promoted cell cycle exit and as a consequence might facilitate premature differentiation of progenitors, because TuJ1-positive neurons were ectopically found in the ventricular zone and there was a general increase of TuJ1 immunoreactivity in the telencephalon. Moreover, clusters of strong TuJ1-expressing neurons were present in E12.5 germinal zone. Some of these strong TuJ1-positive clusters, however, contained apoptotic condensed DNA, suggesting that inappropriate premature differentiation may lead to abnormal apoptosis in some progenitor cells. Consistent with the transgenic mouse analysis in vivo, similar effects of Nozl-1 over-expression in induction of apoptosis, inhibition of cell proliferation and promotion of neuronal differentiation were also observed in three different N18, ST14A and N2A neural cell lines in vitro. Taken together, our study indicates that ectopic expression of Nolz-1 in neural progenitors promotes cell cycle exit/premature neuronal differentiation and induces abnormal apoptosis in the developing telencephalon. PMID:24073229

Ectopic expression of nolz-1 in neural progenitors promotes cell cycle exit/premature neuronal differentiation accompanying with abnormal apoptosis in the developing mouse telencephalon.

PubMed

Chang, Sunny Li-Yun; Chen, Shih-Yun; Huang, Huai-Huei; Ko, Hsin-An; Liu, Pei-Tsen; Liu, Ya-Chi; Chen, Ping-Hau; Liu, Fu-Chin

2013-01-01

Nolz-1, as a murine member of the NET zinc-finger protein family, is expressed in post-mitotic differentiating neurons of striatum during development. To explore the function of Nolz-1 in regulating the neurogenesis of forebrain, we studied the effects of ectopic expression of Nolz-1 in neural progenitors. We generated the Cre-loxP dependent conditional transgenic mice in which Nolz-1 was ectopically expressed in proliferative neural progenitors. Ectopic expression of Nolz-1 in neural progenitors by intercrossing the Nolz-1 conditional transgenic mice with the nestin-Cre mice resulted in hypoplasia of telencephalon in double transgenic mice. Decreased proliferation of neural progenitor cells were found in the telencephalon, as evidenced by the reduction of BrdU-, Ki67- and phospho-histone 3-positive cells in E11.5-12.5 germinal zone of telencephalon. Transgenic Nolz-1 also promoted cell cycle exit and as a consequence might facilitate premature differentiation of progenitors, because TuJ1-positive neurons were ectopically found in the ventricular zone and there was a general increase of TuJ1 immunoreactivity in the telencephalon. Moreover, clusters of strong TuJ1-expressing neurons were present in E12.5 germinal zone. Some of these strong TuJ1-positive clusters, however, contained apoptotic condensed DNA, suggesting that inappropriate premature differentiation may lead to abnormal apoptosis in some progenitor cells. Consistent with the transgenic mouse analysis in vivo, similar effects of Nozl-1 over-expression in induction of apoptosis, inhibition of cell proliferation and promotion of neuronal differentiation were also observed in three different N18, ST14A and N2A neural cell lines in vitro. Taken together, our study indicates that ectopic expression of Nolz-1 in neural progenitors promotes cell cycle exit/premature neuronal differentiation and induces abnormal apoptosis in the developing telencephalon.

Using the Animal Model to Accelerate Response to Selection in a Self-Pollinating Crop

PubMed Central

Cowling, Wallace A.; Stefanova, Katia T.; Beeck, Cameron P.; Nelson, Matthew N.; Hargreaves, Bonnie L. W.; Sass, Olaf; Gilmour, Arthur R.; Siddique, Kadambot H. M.

2015-01-01

We used the animal model in S0 (F1) recurrent selection in a self-pollinating crop including, for the first time, phenotypic and relationship records from self progeny, in addition to cross progeny, in the pedigree. We tested the model in Pisum sativum, the autogamous annual species used by Mendel to demonstrate the particulate nature of inheritance. Resistance to ascochyta blight (Didymella pinodes complex) in segregating S0 cross progeny was assessed by best linear unbiased prediction over two cycles of selection. Genotypic concurrence across cycles was provided by pure-line ancestors. From cycle 1, 102/959 S0 plants were selected, and their S1 self progeny were intercrossed and selfed to produce 430 S0 and 575 S2 individuals that were evaluated in cycle 2. The analysis was improved by including all genetic relationships (with crossing and selfing in the pedigree), additive and nonadditive genetic covariances between cycles, fixed effects (cycles and spatial linear trends), and other random effects. Narrow-sense heritability for ascochyta blight resistance was 0.305 and 0.352 in cycles 1 and 2, respectively, calculated from variance components in the full model. The fitted correlation of predicted breeding values across cycles was 0.82. Average accuracy of predicted breeding values was 0.851 for S2 progeny of S1 parent plants and 0.805 for S0 progeny tested in cycle 2, and 0.878 for S1 parent plants for which no records were available. The forecasted response to selection was 11.2% in the next cycle with 20% S0 selection proportion. This is the first application of the animal model to cyclic selection in heterozygous populations of selfing plants. The method can be used in genomic selection, and for traits measured on S0-derived bulks such as grain yield. PMID:25943522

Safety behavior of in-line skaters

PubMed Central

Osberg, J; Stiles, S.

2000-01-01

Objectives and setting—Injuries from in-line skating have risen sharply in many cities around the world. To understand risk taking behavior and safety practices associated with urban in-line skating, 2210 outdoor skaters were observed in Boston, Massachusetts. Methods—Estimated age, gender, use of helmets, wrist guards, elbow and kneepads were recorded. Skaters were coded as beginner, average, or advanced, and skating locations were classified as street, sidewalk, or bicycle path. Results—About 60% of skaters wore wrist guards, but only 5.7% wore helmets. Males wore less protective equipment than females, and were more likely to skate on streets. Beginners and advanced skaters wore more protective gear than average skaters. Surprisingly, street skaters wore less protective gear than skaters on sidewalks or paths. Conclusions—Renewed focus on the importance of wearing helmets is needed. Given the higher injury risks for males, clinicians and public health experts need to target male skaters in prevention efforts. In addition, average and advanced skaters need to be convinced that even though they have improved, it is still important to wear protective gear. PMID:11003191

Compact advanced extreme-ultraviolet imaging spectrometer for spatiotemporally varying tungsten spectra from fusion plasmas.

PubMed

Song, Inwoo; Seon, C R; Hong, Joohwan; An, Y H; Barnsley, R; Guirlet, R; Choe, Wonho

2017-09-01

A compact advanced extreme-ultraviolet (EUV) spectrometer operating in the EUV wavelength range of a few nanometers to measure spatially resolved line emissions from tungsten (W) was developed for studying W transport in fusion plasmas. This system consists of two perpendicularly crossed slits-an entrance aperture and a space-resolved slit-inside a chamber operating as a pinhole, which enables the system to obtain a spatial distribution of line emissions. Moreover, a so-called v-shaped slit was devised to manage the aperture size for measuring the spatial resolution of the system caused by the finite width of the pinhole. A back-illuminated charge-coupled device was used as a detector with 2048 × 512 active pixels, each with dimensions of 13.5 × 13.5 μm 2 . After the alignment and installation on Korea superconducting tokamak advanced research, the preliminary results were obtained during the 2016 campaign. Several well-known carbon atomic lines in the 2-7 nm range originating from intrinsic carbon impurities were observed and used for wavelength calibration. Further, the time behavior of their spatial distributions is presented.

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.

Calculation of stresses in a rock mass and lining in stagewise face drivage

NASA Astrophysics Data System (ADS)

Seryakov, VM; Zhamalova, BR

2018-03-01

Using the method of calculating mechanical state of a rock mass for the conditions of stagewise drivage of a production face in large cross-section excavations, the specific features of stress redistribution in lining of excavations are found. The zones of tensile stresses in the lining are detected. The authors discuss the influence of the initial stress state of rocks on the tension stress zones induced in the lining in course of the heading advance

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 ...

Cost-effectiveness of Paclitaxel + Ramucirumab Combination Therapy for Advanced Gastric Cancer Progressing After First-line Chemotherapy in Japan.

PubMed

Saito, Shota; Muneoka, Yusuke; Ishikawa, Takashi; Akazawa, Kouhei

2017-12-01

The combination of paclitaxel + ramucirumab is a standard second-line treatment in patients with advanced gastric cancer. This therapy has been associated with increased median overall survival and progression-free survival compared with those with paclitaxel monotherapy. We evaluated the cost-effectiveness of paclitaxel + ramucirumab combination therapy in patients with advanced gastric cancer, from the perspective of health care payers in Japan. We constructed a Markov model to compare, over a time horizon of 3 years, the costs and effectiveness of the combination of paclitaxel + ramucirumab and paclitaxel alone as second-line therapies for advanced gastric cancer in Japan. Health outcomes were measured in life-years (LYs) and quality-adjusted (QA) LYs gained. Costs were calculated using year-2016 Japanese yen (¥1 = US $17.79) according to the social insurance reimbursement schedule and drug tariff of the fee-for-service system in Japan. Model robustness was addressed through 1-way and probabilistic sensitivity analyses. The costs and QALYs were discounted at a rate of 2% per year. The willingness-to-pay threshold was set at the World Health Organization's criterion of ¥12 million, because no consensus exists regarding the threshold for acceptable cost per QALY ratios in Japan's health policy. Paclitaxel + ramucirumab combination therapy was estimated to provide an additional 0.09 QALYs (0.10 LYs) at a cost of ¥3,870,077, resulting in an incremental cost-effectiveness ratio of ¥43,010,248/QALY. The incremental cost-effectiveness ratio for the combination therapy was >¥12 million/QALY in all of the 1-way and probabilistic sensitivity analyses. Adding ramucirumab to a regimen of paclitaxel in the second-line treatment of advanced gastric cancer is expected to provide a minimal incremental benefit at a high incremental cost per QALY. Based on our findings, adjustments in the price of ramucirumab, as well as improves in other clinical parameters such as survival time and adverse event in advanced gastric cancer therapy, are needed. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

A Study to Assess the Efficacy of IMAB362 Plus mFOLFOX6 Compared With Placebo Plus mFOLFOX6 as First-line Treatment of Subjects With Claudin (CLDN) 18.2 Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

ClinicalTrials.gov

2018-05-30

Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or Cancer; Locally Advanced Unresectable Gastric Adenocarcinoma or Cancer; Metastatic Gastric Adenocarcinoma or Cancer; Metastatic Gastroesophageal Junction (GEJ) Adenocarcinoma

Advanced X-ray Imaging Crystal Spectrometer for Magnetic Fusion Tokamak Devices

NASA Astrophysics Data System (ADS)

Lee, S. G.; Bak, J. G.; Bog, M. G.; Nam, U. W.; Moon, M. K.; Cheon, J. K.

2008-03-01

An advanced X-ray imaging crystal spectrometer is currently under development using a segmented position sensitive detector and time-to-digital converter (TDC) based delay-line readout electronics for burning plasma diagnostics. The proposed advanced XICS utilizes an eight-segmented position sensitive multi-wire proportional counter and supporting electronics to increase the spectrometer performance includes the photon count-rate capability and spatial resolution.

Physiologic and Genetic Evidence Links Hemopexin to Triglycerides in Mice and Humans

PubMed Central

Lawson, Heather A; Zayed, Mohamed; Wayhart, Jessica P; Fabbrini, Elisa; Love-Gregory, Latisha; Klein, Samuel; Semenkovich, Clay F

2017-01-01

Background/Objectives Elevated triglycerides predict insulin resistance and vascular disease in obesity, but how the inert triglyceride molecule is related to development of metabolic disease is unknown. To pursue novel potential mediators of triglyceride-associated metabolic disease, we used a forward genetics approach involving inbred mice and translated our findings to human subjects. Subjects/Methods Hemopexin was identified as a differentially expressed gene within a quantitative trait locus associated with serum triglycerides in an F16 advanced intercross between the LG/J and SM/J strains of mice. Hpx expression was evaluated in both reproductive fatpads and livers of mice representing three strains, LG/J (n = 25), SM/J (n = 27) and C57Bl/6J (n = 19), on high- and low-fat diets. The effect of altered Hpx expression on adipogenesis was studied in 3T3-L1 cells. Circulating HPX protein along with HPX expression were characterized in subcutaneous white adipose tissue samples obtained from a cohort of metabolically abnormal (n = 18) and of metabolically normal (n = 24) obese human subjects. We further examined the relationship between HPX and triglycerides in human atherosclerotic plaques (n = 18). Results Hemopexin expression in mouse adipose tissue, but not liver, was regulated by dietary fat regardless of genetic background. Hemopexin increased in concert with adipogenesis in 3T3-L1 cells, and disruption of its expression impaired adipocyte differentiation. RNAseq data from the adipose tissue of obese humans showed differential expression of hemopexin based on metabolic disease status (p < 0.05), and circulating hemopexin levels were correlated with serum triglycerides in these subjects (r = 0.33; p = 0.03). Hemopexin was also found in an unbiased proteomic screen of human atherosclerotic plaques, and shown to display differential abundance based on extent of disease and triglyceride content (p < 0.05). Conclusions Our findings suggest that hemopexin is associated with triglycerides and provide a framework for understanding mechanisms underlying lipid metabolism and metabolic disease. PMID:28119529

Physiologic and genetic evidence links hemopexin to triglycerides in mice and humans.

PubMed

Lawson, H A; Zayed, M; Wayhart, J P; Fabbrini, E; Love-Gregory, L; Klein, S; Semenkovich, C F

2017-04-01

Elevated triglycerides predict insulin resistance and vascular disease in obesity, but how the inert triglyceride molecule is related to development of metabolic disease is unknown. To pursue novel potential mediators of triglyceride-associated metabolic disease, we used a forward genetics approach involving inbred mice and translated our findings to human subjects. Hemopexin (HPX) was identified as a differentially expressed gene within a quantitative trait locus associated with serum triglycerides in an F 16 advanced intercross between the LG/J and SM/J strains of mice. Hpx expression was evaluated in both the reproductive fat pads and livers of mice representing three strains, LG/J (n=25), SM/J (n=27) and C57Bl/6J (n=19), on high- and low-fat diets. The effect of altered Hpx expression on adipogenesis was studied in 3T3-L1 cells. Circulating HPX protein along with HPX expression were characterized in subcutaneous white adipose tissue samples obtained from a cohort of metabolically abnormal (n=18) and of metabolically normal (n=24) obese human subjects. We further examined the relationship between HPX and triglycerides in human atherosclerotic plaques (n=18). HPX expression in mouse adipose tissue, but not in liver, was regulated by dietary fat regardless of genetic background. HPX increased in concert with adipogenesis in 3T3-L1 cells, and disruption of its expression impaired adipocyte differentiation. RNAseq data from the adipose tissue of obese humans showed differential expression of HPX based on metabolic disease status (P<0.05), and circulating HPX levels were correlated with serum triglycerides in these subjects (r=0.33; P=0.03). HPX was also found in an unbiased proteomic screen of human atherosclerotic plaques and shown to display differential abundance based on the extent of disease and triglyceride content (P<0.05). Our findings suggest that HPX is associated with triglycerides and provide a framework for understanding mechanisms underlying lipid metabolism and metabolic disease.

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.

Apatinib: A Review in Advanced Gastric Cancer and Other Advanced Cancers.

PubMed

Scott, Lesley J

2018-05-01

Apatinib [Aitan ® (brand name in China)], also known as rivoceranib, is a novel, small molecule, selective vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor and is the second anti-angiogenic drug to be approved in China for the treatment of advanced or metastatic gastric cancer. This article summarizes the pharmacological properties of apatinib and reviews its clinical use in chemotherapy-experienced patients with advanced gastric adenocarcinoma, including gastroesophageal adenocarcinoma (GEA), or with other advanced cancers such as non-small cell lung cancer (NSCLC), breast cancer, gynaecological cancers, hepatocellular carcinoma (HCC), thyroid cancer and sarcomas. As third- or subsequent-line therapy, oral apatinib significantly prolonged median progression-free survival (PFS) and overall survival (OS) compared with placebo and had a manageable safety profile in Chinese patients with advanced or metastatic gastric cancer or GEA participating in randomized, double-blind, multicentre, phase 2 and 3 trials. More limited evidence also supports it use as subsequent-line treatment in Chinese patients with other advanced or metastatic solid tumours, including NSCLC, breast cancer and HCC. Further clinical experience and long-term pharmacovigilance data are required to more definitively establish the efficacy and safety profile of apatinib, including its use in combination with other chemotherapy agents and its role in the management of other types of advanced or metastatic solid tumours. In the meantime, given its convenient administration regimen and the limited treatment options and poor prognosis for patients with advanced or metastatic solid tumours, apatinib is an important, emerging treatment option for adult patients with advanced gastric adenocarcinoma or GEA who have progressed or relapsed after chemotherapy.

Inducible expression of photoacoustic reporter gene tyrosinase in cells using a single plasmid

NASA Astrophysics Data System (ADS)

Paproski, Robert J.; Zemp, Roger J.

2012-02-01

We have previously demonstrated that tyrosinase is a reporter gene for photoacoustic imaging since tyrosinase is the rate-limiting step in the synthesis of melanin, a pigment capable of producing strong photoacoustic signals. We previously created a cell line capable of inducible tyrosinase expression (important due to toxicity of melanin) by stably transfecting tyrosinase in MCF-7 Tet-OnR cell line (Clontech) which expresses a doxycycline-controlled transactivator. Unfortunately, Clontech provides few Tet-On Advanced cell lines making it difficult to have inducible tyrosinase expression in cell lines not provided by Clontech. In order to simplify the creation of cell lines with inducible expression of tyrosinase, we created a single plasmid that encodes both the transactivator as well as tyrosinase. PCR was used to amplify both the transactivator and tyrosinase from the Tet-OnR Advanced and pTRE-Tight-TYR plasmids, respectively. Both PCR products were cloned into the pEGFP-N1 plasmid and the newly created plasmid was transfected into ZR-75-1, MCF-7, and MIA PaCa-1 cells using lipofectamine. After several days, brown melanin was only observed in cells incubated with doxycycline, suggesting that the newly created single plasmid allowed inducible tyrosinase expression in many different cells lines.

Prognostic Factors for Survival in Patients with Advanced Intrahepatic Cholangiocarcinoma Treated with Gemcitabine plus Cisplatin as First-Line Treatment.

PubMed

Ishimoto, Utako; Kondo, Shunsuke; Ohba, Akihiro; Sasaki, Mitsuhito; Sakamoto, Yasunari; Morizane, Chigusa; Ueno, Hideki; Okusaka, Takuji

2018-01-01

Intrahepatic cholangiocarcinoma (ICC) is a rare type of liver cancer. No clinically useful prognostic factors have been reported for patients with advanced ICC. In the present study, we aimed to evaluate the clinical prognostic factors of patients with advanced ICC receiving gemcitabine plus cisplatin combination therapy (GC) as standard first-line chemotherapy. A retrospective analysis was performed of the data of patients with ICC treated at our institution from March 2011 to January 2016. We used the Cox regression model and estimated the hazard ratios of potential prognostic factors for survival. Of 216 patients with biliary tract cancer receiving GC as first-line chemotherapy, we extracted data for 77 patients who were diagnosed with ICC and received GC as first-line chemotherapy. The median overall survival was 13.8 months (95% CI, 8.9-18.6). In multivariate analysis, pretreatment serum lactate dehydrogenase (hazard ratio [HR]: 2.53, p = 0.005), C-reactive protein (HR: 3.06, p = 0.001), and carcinoembryonic antigen (HR: 2.39, p = 0.03) levels were significantly associated with overall survival. Readily available clinical laboratory values reliably predicted the prognosis of ICC patients receiving GC therapy. If validated in other studies, these results may provide a useful tool for individual patient-risk evaluation and the design and interpretation of future trials. © 2017 S. Karger AG, Basel.

First-line treatment of advanced ALK-positive non-small-cell lung cancer

PubMed Central

Gandhi, Shipra; Chen, Hongbin; Zhao, Yujie; Dy, Grace K

2015-01-01

Non-small-cell lung cancer (NSCLC) is one of the leading causes of cancer deaths, both within the US and worldwide. There have been major treatment advances in NSCLC over the past decade with the discovery of molecular drivers of NSCLC, which has ushered in an era of personalized medicine. There are several actionable genetic aberrations in NSCLC, such as epidermal growth factor receptor and anaplastic lymphoma kinase (ALK). In 3%–7% of NSCLC, a chromosomal inversion event in chromosome 2 leads to fusion of a portion of the ALK gene with the echinoderm microtubule–associated protein-like 4 (EML4) gene. The constitutive activation of the ALK fusion oncogene renders it vulnerable to therapeutic intervention. This review focuses on the first-line treatment of advanced ALK-positive NSCLC using ALK inhibitors. Crizotinib was the first agent proven to be efficacious as first-line treatment for ALK-positive NSCLC. However, acquired resistance inevitably develops. The central nervous system is a sanctuary site that represents a common site for disease progression as well. Hence, more potent, selective next-generation ALK inhibitors that are able to cross the blood–brain barrier have been developed for treatment against crizotinib-resistant ALK-positive NSCLC and are also currently being evaluated for first-line therapy as well. In this review, we provide summary of the clinical experience with these drugs in the treatment of ALK-positive NSCLC. PMID:28210152

Advanced Prop-fan Engine Technology (APET) single- and counter-rotation gearbox/pitch change mechanism

NASA Technical Reports Server (NTRS)

Reynolds, C. N.

1985-01-01

The preliminary design of advanced technology (1992) turboprop engines for single-rotation prop-fans and conceptual designs of pitch change mechanisms for single- and counter-rotation prop-fan application are discussed. The single-rotation gearbox is a split path, in-line configuration. The counter-rotation gearbox is an in-line, differential planetary design. The pitch change mechanisms for both the single- and counter-rotation arrangements are rotary/hydraulic. The advanced technology single-rotation gearbox yields a 2.4 percent improvement in aircraft fuel burn and a one percent improvement in operating cost relative to a current technology gearbox. The 1992 counter-rotation gearbox is 15 percent lighter, 15 percent more reliable, 5 percent lower in cost, and 45 percent lower in maintenance cost than the 1992 single-rotation gearbox. The pitch controls are modular, accessible, and external.

Promoting advanced traveler information systems among cellular and land-line phone users : SmarTraveler experience in Boston

DOT National Transportation Integrated Search

1997-01-01

In 1993 the SmarTraveler advanced traveler information system (ATIS) was introduced to travelers in the greater Boston area as part of an operational test jointly funded by FHWA and the Massachusetts Executive Office of Transportation and Constructio...

The emerging role of histology in the choice of first-line treatment of advanced non-small cell lung cancer: implication in the clinical decision-making.

PubMed

Rossi, Antonio; Maione, Paolo; Bareschino, Maria Anna; Schettino, Clorinda; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Castaldo, Vincenzo; Gridelli, Cesare

2010-01-01

Lung cancer is the leading cause of cancer mortality worldwide. Non-small cell lung cancer (NSCLC), accounting for about 85% of all lung cancers, includes squamous carcinoma, adenocarcinoma and undifferentiated large cell carcinoma. The majority of patients have advanced disease at diagnosis, and medical treatment is the cornerstone of management. Several randomized trials comparing third-generation platinum-based doublets concluded that all such combinations are comparable in their clinical efficacy, failing to document a difference based on histology. However, recent evidences, arising from the availability of pemetrexed, have shown that histology represents an important variable in the decision making. The major progresses in the understanding cancer biology and mechanism of oncogenesis have allowed the development of several potential molecular targets for cancer treatment such as vascular growth factor and its receptors and epidermal growth factor receptor. Targeted drugs seem to be safer or more effective in a specific histology subtype. All of these data have led to choose the optimal first-line treatment of advanced NSCLC based on histologic diagnosis. However, this scenario raises a diagnostic issue: a specific diagnosis of NSCLC histologic subtype is mandatory. This review will discuss these new evidences in the first-line treatment of advanced NSCLC and their implication in the current clinical decision-making.

Bevacizumab, Carboplatin and Paclitaxel Combination Treatment in Advanced Stage Ovarian Cancer: The First Experience in Thammasat University Hospital, Thailand: A Case Report.

PubMed

Suwannarurk, Komsun; Thaweekul, Yudthadej; Mairaing, Karicha; Poomtavorn, Yenrudee; Tangtiang, Kaan; Piyawang, Wichet; Bhamarapravatana, Kornkarn

2015-04-01

Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growthfactor (VEGF), has been approvedfor concurrent treatment with first line chemotherapy in advanced epithelial ovarian cancer. A case of an advanced stage epithelial ovarian cancer (EOC) receiving a combination of bevacizumab, carboplatin andpaclitaxel chemotherapy was reported. A 44-year-old woman was presented with abdominal discomfort and distention for 4 months. Bilateral 12 cm diameter ovarian tumors were diagnosed as FIGO stage IIIc after surgical staging operation. Histopathology report showed the mixed type of serous and endometriod adenocarcinoma. The patient was then started on carboplatin/paclitaxel combination chemotherapy for 6 cycles after surgery every 3 weeks. Bevacizumab (7.5 mg/ m2) was concurrently administered with chemotherapy every 3 weeks startingfrom the 2nd cycle. A complete remission was achieved after the end of the chemotherapy treatment. Bevacizumab was continued for one year after the completion of the standard chemotherapy. Bone marrow suppression, hypertension and proteinuria were not found during Bevacizumab treatment. At bevacizumab treatment completion, a platinum-sensitive recurrent ovarian cancer was diagnosed at the two weeks postprogram routine check-up. The patient was counseled to start second line chemotherapy treatment and has yet to come back with her decision. Combination of bevacizumab, carboplatin and paclitaxelfor first line chemotherapy in advanced EOC in this case had no serious side effects and need further study.

Extensive retreat and re-advance of the West Antarctic Ice Sheet during the Holocene.

PubMed

Kingslake, J; Scherer, R P; Albrecht, T; Coenen, J; Powell, R D; Reese, R; Stansell, N D; Tulaczyk, S; Wearing, M G; Whitehouse, P L

2018-06-01

To predict the future contributions of the Antarctic ice sheets to sea-level rise, numerical models use reconstructions of past ice-sheet retreat after the Last Glacial Maximum to tune model parameters 1 . Reconstructions of the West Antarctic Ice Sheet have assumed that it retreated progressively throughout the Holocene epoch (the past 11,500 years or so) 2-4 . Here we show, however, that over this period the grounding line of the West Antarctic Ice Sheet (which marks the point at which it is no longer in contact with the ground and becomes a floating ice shelf) retreated several hundred kilometres inland of today's grounding line, before isostatic rebound caused it to re-advance to its present position. Our evidence includes, first, radiocarbon dating of sediment cores recovered from beneath the ice streams of the Ross Sea sector, indicating widespread Holocene marine exposure; and second, ice-penetrating radar observations of englacial structure in the Weddell Sea sector, indicating ice-shelf grounding. We explore the implications of these findings with an ice-sheet model. Modelled re-advance of the grounding line in the Holocene requires ice-shelf grounding caused by isostatic rebound. Our findings overturn the assumption of progressive retreat of the grounding line during the Holocene in West Antarctica, and corroborate previous suggestions of ice-sheet re-advance 5 . Rebound-driven stabilizing processes were apparently able to halt and reverse climate-initiated ice loss. Whether these processes can reverse present-day ice loss 6 on millennial timescales will depend on bedrock topography and mantle viscosity-parameters that are difficult to measure and to incorporate into ice-sheet models.

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.

Identification of multiple genetic loci in the mouse controlling immobility time in the tail suspension and forced swimming tests.

PubMed

Abou-Elnaga, Ahmed F; Torigoe, Daisuke; Fouda, Mohamed M; Darwish, Ragab A; Abou-Ismail, Usama A; Morimatsu, Masami; Agui, Takashi

2015-05-01

Depression is one of the most famous psychiatric disorders in humans in all over the countries and considered a complex neurobehavioral trait and difficult to identify causal genes. Tail suspension test (TST) and forced swimming test (FST) are widely used for assessing depression-like behavior and antidepressant activity in mice. A variety of antidepressant agents are known to reduce immobility time in both TST and FST. To identify genetic determinants of immobility duration in both tests, we analyzed 101 F2 mice from an intercross between C57BL/6 and DBA/2 strains. Quantitative trait locus (QTL) mapping using 106 microsatellite markers revealed three loci (two significant and one suggestive) and five suggestive loci controlling immobility time in the TST and FST, respectively. Results of QTL analysis suggest a broad description of the genetic architecture underlying depression, providing underpinnings for identifying novel molecular targets for antidepressants to clear the complex genetic mechanisms of depressive disorders.

Genetic Architecture of Nest Building in Mice LG/J × SM/J

PubMed Central

Sauce, Bruno; de Brito, Reinaldo Alves; Peripato, Andrea Cristina

2012-01-01

Maternal care is critical to offspring growth and survival, which is greatly improved by building an effective nest. Some suggest that genetic variation and underlying genetic effects differ between fitness-related traits and other phenotypes. We investigated the genetic architecture of a fitness-related trait, nest building, in F2 female mice intercrossed from inbred strains SM/J and LG/J using a QTL analysis for six related nest phenotypes (Presence and Structure pre- and postpartum, prepartum Material Used and postpartum Temperature). We found 15 direct-effect QTLs explaining from 4 to 13% of the phenotypic variation in nest building, mostly with non-additive effect. Epistatic analyses revealed 71 significant epistatic interactions which together explain from 28.4 to 75.5% of the variation, indicating an important role for epistasis in the adaptive process of nest building behavior in mice. Our results suggest a genetic architecture with small direct effects and a larger number of epistatic interactions as expected for fitness-related phenotypes. PMID:22654894

Dahl (S × R) rat congenic strain analysis confirms and defines a chromosome 17 spatial navigation quantitative trait locus to <10 Mbp.

PubMed

Herrera, Victoria L; Pasion, Khristine A; Tan, Glaiza A; Ruiz-Opazo, Nelson

2013-01-01

A quantitative trait locus (QTL) linked with ability to find a platform in the Morris Water Maze (MWM) was located on chromosome 17 (Nav-5 QTL) using intercross between Dahl S and Dahl R rats. We developed two congenic strains, S.R17A and S.R17B introgressing Dahl R-chromosome 17 segments into Dahl S chromosome 17 region spanning putative Nav-5 QTL. Performance analysis of S.R17A, S.R17B and Dahl S rats in the Morris water maze (MWM) task showed a significantly decreased spatial navigation performance in S.R17B congenic rats when compared with Dahl S controls (P = 0.02). The S.R17A congenic segment did not affect MWM performance delimiting Nav-5 to the chromosome 17 65.02-74.66 Mbp region. Additional fine mapping is necessary to identify the specific gene variant accounting for Nav-5 effect on spatial learning and memory in Dahl rats.

Chemometric dissimilarity in nutritive value of popularly consumed Nigerian brown and white common beans.

PubMed

Moyib, Oluwasayo Kehinde; Alashiri, Ganiyy Olasunkanmi; Adejoye, Oluseyi Damilola

2015-01-01

Brown beans are the preferred varieties over the white beans in Nigeria due to their assumed richer nutrients. This study was aimed at assessing and characterising some popular Nigerian common beans for their nutritive value based on seed coat colour. Three varieties, each, of Nigerian brown and white beans, and one, each, of French bean and soybean were analysed for 19 nutrients. Z-statistics test showed that Nigerian beans are nutritionally analogous to French bean and soybean. Analysis of variance showed that seed coat colour varied with proximate nutrients, Ca, Fe, and Vit C. Chemometric analysis methods revealed superior beans for macro and micro nutrients and presented clearer groupings among the beans for seed coat colour. The study estimated a moderate genetic distance (GD) that will facilitate transfer of useful genes and intercrossing among the beans. It also offers an opportunity to integrate French bean and soybean into genetic improvement programs in Nigerian common beans. Copyright © 2014 Elsevier Ltd. All rights reserved.

A de novo mutation in KIT causes white spotting in a subpopulation of German Shepherd dogs.

PubMed

Wong, A K; Ruhe, A L; Robertson, K R; Loew, E R; Williams, D C; Neff, M W

2013-06-01

Although variation in the KIT gene is a common cause of white spotting among domesticated animals, KIT has not been implicated in the diverse white spotting observed in the dog. Here, we show that a loss-of-function mutation in KIT recapitulates the coat color phenotypes observed in other species. A spontaneous white spotting observed in a pedigree of German Shepherd dogs was mapped by linkage analysis to a single locus on CFA13 containing KIT (pairwise LOD = 15). DNA sequence analysis identified a novel 1-bp insertion in the second exon that co-segregated with the phenotype. The expected frameshift and resulting premature stop codons predicted a severely truncated c-Kit receptor with presumably abolished activity. No dogs homozygous for the mutation were recovered from multiple intercrosses (P = 0.01), suggesting the mutation is recessively embryonic lethal. These observations are consistent with the effects of null alleles of KIT in other species. © 2012 The Authors, Animal Genetics © 2012 Stichting International Foundation for Animal Genetics.

Cathepsin B is a novel gender-dependent determinant of cholesterol absorption from the intestine[S

PubMed Central

Wong, Winifred P. S.; Altemus, Jessica B.; Hester, James F.; Chan, Ernest R.; Côté, Jean-François; Serre, David; Sehayek, Ephraim

2013-01-01

We used a mouse C57BL/6J×CASA/Rk intercross to map a locus on chromosome 14 that displayed a gender-dependent effect on cholesterol absorption from the intestine. Studies in congenic animals revealed a complex locus with multiple operating genetic determinants resulting in alternating gender-dependent phenotypic effects. Fine-mapping narrowed the locus to a critical 6.3 Mb interval. Female subcongenics, but not males, of the critical interval displayed a decrease of 33% in cholesterol absorption. RNA-Seq analysis of female subcongenic jejunum revealed that cysteine protease cathepsin B (Ctsb) is a candidate to explain the interval effect. Consistent with the phenotype in critical interval subcongenics, female Ctsb knockout mice, but not males, displayed a decrease of 31% in cholesterol absorption. Although studies in Ctsb knockouts revealed a gender-dependent effect on cholesterol absorption, further fine-mapping dismissed a role for Ctsb in determining the effect of the critical 6.3 Mb interval on cholesterol absorption. PMID:23248330

The Calcitonin Receptor Gene Is a Candidate for Regulation of Susceptibility to Herpes simplex Type 1 Neuronal Infection Leading to Encephalitis in Rat

PubMed Central

Abdelmagid, Nada; Bereczky-Veress, Biborka; Guerreiro-Cacais, André Ortlieb; Bergman, Petra; Luhr, Katarina M.; Bergström, Tomas; Sköldenberg, Birgit; Piehl, Fredrik

2012-01-01

Herpes simplex encephalitis (HSE) is a fatal infection of the central nervous system (CNS) predominantly caused by Herpes simplex virus type 1. Factors regulating the susceptibility to HSE are still largely unknown. To identify host gene(s) regulating HSE susceptibility we performed a genome-wide linkage scan in an intercross between the susceptible DA and the resistant PVG rat. We found one major quantitative trait locus (QTL), Hse1, on rat chromosome 4 (confidence interval 24.3–31 Mb; LOD score 29.5) governing disease susceptibility. Fine mapping of Hse1 using recombinants, haplotype mapping and sequencing, as well as expression analysis of all genes in the interval identified the calcitonin receptor gene (Calcr) as the main candidate, which also is supported by functional studies. Thus, using unbiased genetic approach variability in Calcr was identified as potentially critical for infection and viral spread to the CNS and subsequent HSE development. PMID:22761571

Dynamics of in vivo ASC speck formation

PubMed Central

2017-01-01

Activated danger or pathogen sensors trigger assembly of the inflammasome adaptor ASC into specks, large signaling platforms considered hallmarks of inflammasome activation. Because a lack of in vivo tools has prevented the study of endogenous ASC dynamics, we generated a live ASC reporter through CRISPR/Cas9 tagging of the endogenous gene in zebrafish. We see strong ASC expression in the skin and other epithelia that act as barriers to insult. A toxic stimulus triggered speck formation and rapid pyroptosis in keratinocytes in vivo. Macrophages engulfed and digested that speck-containing, pyroptotic debris. A three-dimensional, ultrastructural reconstruction, based on correlative light and electron microscopy of the in vivo assembled specks revealed a compact network of highly intercrossed filaments, whereas pyrin domain (PYD) or caspase activation and recruitment domain alone formed filamentous aggregates. The effector caspase is recruited through PYD, whose overexpression induced pyroptosis but only after substantial delay. Therefore, formation of a single, compact speck and rapid cell-death induction in vivo requires a full-length ASC. PMID:28701426

Exploring the power of rice (O. sativa x O. rufipogon) chromosome segment substitution line libraries

USDA-ARS?s Scientific Manuscript database

Transgressive variation was reported as an increase in grain yield for several rice (Oryza sativa x O. rufipogon) advanced backcross mapping populations. The objective of this study was to develop chromosome segment substitution line (CSSL) libraries to further dissect the reported transgressive var...

Line-scan hyperspectral imaging platform for agro-food safety and quality evaluation: System enhancement and characterization

USDA-ARS?s Scientific Manuscript database

Line-scan-based hyperspectral imaging techniques have often served as a research tool to develop rapid multispectral methods based on only a few spectral bands for rapid online applications. With continuing technological advances and greater accessibility to and availability of optoelectronic imagin...

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

ERIC Educational Resources Information Center

Nunes, Mark

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

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…

Two Dimensional Positioning and Heading Solution for Flying Vehicles using a Line-Scanning Laser Radar (LADAR)

DTIC Science & Technology

2011-03-24

6 2.4.1 Reference Frames . . . . . . . . . . . . . . . . . 6 2.4.2 Line and Feature Extraction . . . . . . . . . . . 7 2.4.3 SLAM ...Positioning System . . . . . . . . . . . . . . . . . . 1 LADAR Laser Radar . . . . . . . . . . . . . . . . . . . . . . . . . . 1 LiDAR Light Detection and...Ranging . . . . . . . . . . . . . . . . 2 SLAM Simultaneous Localization and Mapping . . . . . . . . . . 2 ANT Advanced Navigation Technology

Response to oxalic acid as a resistance assay for Sclerotinia minor in peanut

USDA-ARS?s Scientific Manuscript database

Response to oxalic acid was evaluated as a potential assay for screening peanut breeding lines for resistance to Sclerotinia blight caused by Sclerotinia minor. Detached stems of seven Spanish- and six runner-type peanut cultivars and advanced breeding lines, varying in resistance to Sclerotinia bl...

Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application

PubMed Central

Li, Kaichun; Li, Jin

2016-01-01

Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2), can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab), VEGF targeting monoclonal antibodies (bevacizumab), mTOR inhibitor (everolimus), or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer. PMID:26880889

Equity, Status and Freedom: A Note on Higher Education

ERIC Educational Resources Information Center

Marginson, Simon

2011-01-01

Strategies to enhance socio-economic equity in higher education embody one or both of two objectives. The first strategy is to advance "fairness" by changing the composition of participation, bringing higher education into line with the ideal model of a socially representative system. The second strategy advances "inclusion" by…

The evaluation of advanced traveler information services (ATIS) impacts on truck travel time reliability : using the simulated yoked study concept

DOT National Transportation Integrated Search

2004-03-01

The ability of Advanced Traveler Information Systems (ATIS) to improve the on-time reliability of urban truck movements is evaluated through the application of the Heuristic On-Line Web- : Linked Arrival Time Estimation (HOWLATE) methodology. In HOWL...

Development of cost effective fenceline monitoring approaches to support advanced leak detection and repair strategies

EPA Science Inventory

Cost-effective fence line and process monitoring systems to support advanced leak detection and repair (LDAR) strategies can enhance protection of public health, facilitate worker safety, and help companies realize cost savings by reducing lost product. The U.S. EPA Office of Re...

School Integration Matters: Research-Based Strategies to Advance Equity

ERIC Educational Resources Information Center

Frankenberg, Erica, Ed.; Garces, Liliana M., Ed.; Hopkins, Megan, Ed.

2016-01-01

More than 60 years after the "Brown v. Board of Education" decision declared segregated schooling inherently unequal, this timely book sheds light on how and why U.S. schools are experiencing increasing segregation along racial, socioeconomic, and linguistic lines. It offers policy and programmatic alternatives for advancing equity and…

Computer aided statistical process control for on-line instrumentation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meils, D.E.

1995-01-01

On-line chemical process instrumentation historically has been used for trending. Recent technological advances in on-line instrumentation have improved the accuracy and reliability of on-line instrumentation. However, little attention has been given to validating and verifying on-line instrumentation. This paper presents two practical approaches for validating instrument performance by comparison of on-line instrument response to either another portable instrument or another bench instrument. Because the comparison of two instruments` performance to each other requires somewhat complex statistical calculations, a computer code (Lab Stats Pack{reg_sign}) is used to simplify the calculations. Lab Stats Pack{reg_sign} also develops control charts that may be usedmore » for continuous verification of on-line instrument performance.« less

Paclitaxel: a pharmacoeconomic review of its use in the treatment of ovarian cancer.

PubMed

Young, M; Plosker, G L

2001-01-01

Paclitaxel belongs to the group of antitumour agents called the taxanes. Its efficacy in advanced ovarian cancer has been established in large, randomised phase III clinical trials. When used in combination with cisplatin for first-line treatment of advanced ovarian cancer, it is superior to cyclophosphamide/cisplatin, with gains in median survival of around 1 year. Paclitaxel plus carboplatin has similar efficacy to paclitaxel plus cisplatin. There is now consensus that paclitaxel plus either carboplatin or cisplatin is the recommended first-line therapy for patients with advanced ovarian cancer. The particular combination employed may vary between institutions and geographical regions, although paclitaxel plus carboplatin is generally better tolerated (i.e. lower incidence of non-haematological adverse events) than paclitaxel plus cisplatin and is widely used in many countries. Paclitaxel is also used as monotherapy in second-line (salvage) treatment of ovarian cancer. Pharmacoeconomic analyses performed to date have primarily focused on first-line therapy comparing the combination of paclitaxel/cisplatin with cyclophosphamide/cisplatin. All studies incorporated clinical outcomes data, most commonly from the Gynecologic Oncology Group (GOG) 111 trial, showing a survival advantage for paclitaxel/cisplatin. These studies report incremental cost-effectiveness ratios (ICERs) ranging from $US 6395 per additional life-year gained (LYG) in Spain (1995/96 values) to $US 44,690 per additional progression-free LYG in France (year of costs not reported). Five studies were based in the US and Canada and these reported very similar ICERs of $US 13,135 (year of costs not reported) to $US 25,131 (1993 costs) per additional LYG. In all of these studies the incremental costs of paclitaxel/cisplatin therapy fall well within the commonly cited threshold limit of $US 50,000 for new therapies and compare well with incremental costs reported for other oncological and life-saving therapies. Patient preferences and quality of life are important issues due to the short survival of patients with advanced ovarian cancer. Two cost-utility studies reported similar incremental cost-utility ratios (ICURs). In the study based on US costs, the ICUR of paclitaxel/cisplatin treatment was US $18,200 per additional quality-adjusted life-year (QALY) [1995 drug costs]. In a Canadian study the ICUR ranged from 11,600 Canadian dollars ($Can) to $Can 24,200 (1996 costs) per additional progression-free QALY depending on the choice of second-line treatment. Paclitaxel used in combination with cisplatin offers survival and utility gains versus cyclophosphamide plus cisplatin, when used as first-line treatment in patients with stage III or IV ovarian cancer. The incremental cost for these gains is within the accepted range for healthcare interventions. However, pharmacoeconomic analyses of paclitaxel plus carboplatin--a combination widely accepted for use in women with advanced ovarian cancer and with clinical advantages over paclitaxel plus cisplatin in terms of ease of administration and tolerability profile--are currently lacking. Nevertheless, results of available pharmacoeconomic data support the clinical use of paclitaxel/platinum combinations, particularly paclitaxel plus cisplatin, as a first-line chemotherapy treatment option in patients with advanced ovarian cancer.

Efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with non-small-cell lung cancer harboring sensitive EGFR mutations.

PubMed

Imai, Hisao; Minemura, Hiroyuki; Sugiyama, Tomohide; Yamada, Yutaka; Kaira, Kyoichi; Kanazawa, Kenya; Kasai, Takashi; Kaburagi, Takayuki; Minato, Koichi

2018-05-08

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is effective as first-line chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive EGFR mutations. However, whether the efficacy of second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment is similar to that of first-line cytotoxic drug chemotherapy in elderly patients aged ≥ 75 years harboring sensitive EGFR mutations is unclear. Therefore, we aimed to investigate the efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations. We retrospectively evaluated the clinical effects and safety profiles of second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations (exon 19 deletion/exon 21 L858R mutation). Between April 2008 and December 2015, 78 elderly patients with advanced NSCLC harboring sensitive EGFR mutations received first-line EGFR-TKI at four Japanese institutions. Baseline characteristics, regimens, responses to first- and second-line treatments, whether or not patients received subsequent treatment, and if not, the reasons for non-administration were recorded. Overall, 20 patients with a median age of 79.5 years (range 75-85 years) were included in our analysis. The overall response, disease control, median progression-free survival, and overall survival rates were 15.0, 60.0%, 2.4, and 13.2 months, respectively. Common adverse events included leukopenia, neutropenia, anemia, thrombocytopenia, malaise, and anorexia. Major grade 3 or 4 toxicities included leukopenia (25.0%) and neutropenia (45.0%). No treatment-related deaths were noted. Second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment among elderly patients with NSCLC harboring sensitive EGFR mutations was effective and safe and showed equivalent outcomes to first-line cytotoxic drug chemotherapy.

Laparoscopic resection of locally advanced gastrointestinal stromal tumour (GIST) of the stomach following neoadjuvant imatinib chemoreduction.

PubMed

Berney, Christophe R

2015-01-01

Laparoscopic resection of locally advanced gastrointestinal stromal tumours (GISTs) is rarely offered to patients as a first line of treatment. We present two cases of locally advanced gastric GISTs successfully treated with neoadjuvant imatinib and followed up by complete laparoscopic excision of the residual tumour mass. There was no evidence of local recurrence or distant metastases after a mean follow up of more than 40 months. Over the last decade, the development of imatinib has totally revolutionized management of metastatic GISTs and it is now possible to achieve primary tumour downstaging of more than 80%. Unfortunately, current literature on laparoscopic excision of locally advanced gastric GISTs following neoadjuvant treatment of imatinib remains scarce. The present cases strongly suggest that this new therapeutic approach might become the preferred medical option in such clinical situation. Patients with locally advanced non-metastatic gastric GISTs should be offered first-line neoadjuvant. Imatinib-based cytoreductive chemotherapy as an alternative to radical debulking surgery, as a substantial proportion of them will experience significant tumour shrinkage and therefore benefit from a much less invasive laparoscopic approach. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Advanced RF Sources Based on Novel Nonlinear Transmission Lines

DTIC Science & Technology

2015-01-26

microwave (HPM) sources. It is also critical to thin film devices and integrated circuits, carbon nanotube based cathodes and interconnects, field emitters ... line model (TLM) in Fig. 6b. Our model is compared with TLM, shown in Fig. 7a. When the interface resistance rc is small, TLM becomes inaccurate...due to current crowding. Fig. 6. (a) Electrical contact including specific interfacial resistivity ρc, and (b) its transmission line model

Systemic Treatment Patterns With Advanced or Recurrent Non-small Cell Lung Cancer in Japan: A Retrospective Hospital Administrative Database Study.

PubMed

Wang, Feng; Mishina, Sari; Takai, Shinji; Le, T Kim; Ochi, Kenya; Funato, Kotaro; Matsuoka, Shozo; Ohe, Yuichiro

2017-06-01

Data on the treatment of non-small cell lung cancer (NSCLC) in real-world clinical practice in Japan are limited. This large-scale, retrospective cohort study examined data on patients' characteristics and systemic therapies for advanced or recurrent NSCLC in routine practice in Japan. This study used an electronic health records-based database of health claims and Diagnosis Procedure Combination data from 215 consenting hospitals in Japan. Records from April 2008 to September 2015 were analyzed. Regimens were examined by histology, age, sex, and therapeutic line. Logistic regression analysis was performed to predict which clinical and demographic factors affected patients' probability of receiving first- or second-line therapy or completing first-line platinum-based chemotherapy. Among 16,413 patients, 67.9%, 39.2%, and 22.3% received first-, second-, and third-line systemic treatment, respectively. Treatment was more common in patients aged <75 versus ≥75 years (76.0% vs 51.6%), in female versus male patients (71.6% vs 65.4%), and in patients with nonsquamous versus squamous disease (75.6% vs 61.9%). More than 30 systemic regimens were administered. The most common first-line therapy was platinum-based chemotherapy (nonsquamous, 53.6%; squamous, 73.7%). Non-platinum-based chemotherapy use increased in the second-line setting, but platinum-based chemotherapy use remained high (nonsquamous, 33.9%; squamous, 38.6%). Tyrosine kinase inhibitors were used in 32.0% and 29.4% of patients with nonsquamous NSCLC in the first- and second-line settings, respectively. Switches from first- to second-line platinum-based chemotherapy and from first- to second-line tyrosine kinase inhibitors occurred. Forty-two percent of the patients died during hospitalization. In the logistic regression analysis, factors associated with a decreased likelihood of receiving first-line therapy were male sex, squamous histology, age >75 years, treatment at a general (vs cancer-specific) hospital, worse scores on certain activities of daily living, presence of chronic pulmonary disease, worse Hugh-Jones classification, and positive smoking status. The likelihood of completing first-line platinum-based chemotherapy was increased with greater body mass index, better activities of daily living scores, absence of chronic pulmonary disease, and better Hugh-Jones classification. The likelihood of continuing with second-line therapy was decreased with older age and recurrence of NSCLC. Systemic treatment patterns for advanced or recurrent NSCLC in Japan were varied. Nearly 30% of all patients and approximately half of elderly patients did not receive systemic treatment. Treatment rates declined with subsequent therapeutic lines. Generally, guidelines were followed with first-line treatment administration, but not with second-line administration. These results underscore the need for better guideline adherence and more optimal treatment in and elderly patients and in those receiving later-line treatment in Japan. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Recent advances at NASA in calculating the electronic spectra of diatomic molecules

NASA Technical Reports Server (NTRS)

Whiting, Ellis E.; Paterson, John A.

1988-01-01

Advanced entry vehicles, such as the proposed Aero-assisted Orbital Transfer Vehicle, provide new and challenging problems for spectroscopy. Large portions of the flow field about such vehicles will be characterized by chemical and thermal nonequilibrium. Only by considering the actual overlap of the atomic and rotational lines emitted by the species present can the impact of radiative transport within the flow field be assessed correctly. To help make such an assessment, a new computer program is described that can generate high-resolution, line-by-line spectra for any spin-allowed transitions in diatomic molecules. The program includes the matrix elements for the rotational energy and distortion to the fourth order; the spin-orbit, spin-spin, and spin-rotation interactions to first order; and the lambda splitting by a perturbation calculation. An overview of the Computational Chemistry Branch at Ames Research Center is also presented.

Broadband, high-resolution investigation of advanced absorption line shapes at high temperature

NASA Astrophysics Data System (ADS)

Schroeder, Paul J.; Cich, Matthew J.; Yang, Jinyu; Swann, William C.; Coddington, Ian; Newbury, Nathan R.; Drouin, Brian J.; Rieker, Gregory B.

2017-08-01

Spectroscopic studies of planetary atmospheres and high-temperature processes (e.g., combustion) require absorption line-shape models that are accurate over extended temperature ranges. To date, advanced line shapes, like the speed-dependent Voigt and Rautian profiles, have not been tested above room temperature with broadband spectrometers. We investigate pure water vapor spectra from 296 to 1305 K acquired with a dual-frequency comb spectrometer spanning from 6800 to 7200 c m-1 at a point spacing of 0.0033 c m-1 and absolute frequency accuracy of <3.3 ×10-6c m-1 . Using a multispectral fitting analysis, we show that only the speed-dependent Voigt accurately models this temperature range with a single power-law temperature-scaling exponent for the broadening coefficients. Only the data from the analysis using this profile fall within theoretical predictions, suggesting that this mechanism captures the dominant narrowing physics for these high-temperature conditions.

Genetic architecture of atherosclerosis dissected by QTL analyses in three F2 intercrosses of apolipoprotein E-null mice on C57BL6/J, DBA/2J and 129S6/SvEvTac backgrounds

PubMed Central

Makhanova, Natalia; Morgan, Andrew P.; Kayashima, Yukako; Makhanov, Andrei; Hiller, Sylvia; Zhilicheva, Svetlana; Xu, Longquan; Pardo-Manuel de Villena, Fernando; Maeda, Nobuyo

2017-01-01

Quantitative trait locus (QTL) analyses of intercross populations between widely used mouse inbred strains provide a powerful approach for uncovering genetic factors that influence susceptibility to atherosclerosis. Epistatic interactions are common in complex phenotypes and depend on genetic backgrounds. To dissect genetic architecture of atherosclerosis, we analyzed F2 progeny from a cross between apolipoprotein E-null mice on DBA/2J (DBA-apoE) and C57BL/6J (B6-apoE) genetic backgrounds and compared the results with those from two previous F2 crosses of apolipoprotein E-null mice on 129S6/SvEvTac (129-apoE) and DBA-apoE backgrounds, and B6-apoE and 129-apoE backgrounds. In these round-robin crosses, in which each parental strain was crossed with two others, large-effect QTLs are expected to be detectable at least in two crosses. On the other hand, observation of QTLs in one cross only may indicate epistasis and/or absence of statistical power. For atherosclerosis at the aortic arch, Aath4 on chromosome (Chr)2:66 cM follows the first pattern, with significant QTL peaks in (DBAx129)F2 and (B6xDBA)F2 mice but not in (B6x129)F2 mice. We conclude that genetic variants unique to DBA/2J at Aath4 confer susceptibility to atherosclerosis at the aortic arch. A similar pattern was observed for Aath5 on chr10:35 cM, verifying that the variants unique to DBA/2J at this locus protect against arch plaque development. However, multiple loci, including Aath1 (Chr1:49 cM), and Aath2 (Chr1:70 cM) follow the second type of pattern, showing significant peaks in only one of the three crosses (B6-apoE x 129-apoE). As for atherosclerosis at aortic root, the majority of QTLs, including Ath29 (Chr9:33 cM), Ath44 (Chr1:68 cM) and Ath45 (Chr2:83 cM), was also inconsistent, being significant in only one of the three crosses. Only the QTL on Chr7:37 cM was consistently suggestive in two of the three crosses. Thus QTL analysis of round-robin crosses revealed the genetic architecture of atherosclerosis. PMID:28837567

The Manifestation of Chromosome Rearrangements in Unordered Asci of Neurospora

PubMed Central

Perkins, David D.

1974-01-01

Rapid, effective techniques have been developed for detecting and characterizing chromosome aberrations in Neurospora by visual inspection of ascospores and asci. Rearrangements that are detectable by the presence of deficient, nonblack ascospores in test crosses make up 5 to 10% of survivors after UV doses giving 10-55% survival. Over 135 rearrangements have been diagnosed by classifying unordered asci according to numbers of defective spores. (These include 15 originally identified or analyzed by other workers.) About 100 reciprocal translocations (RT's) have been confirmed and mapped genetically, involving all combinations of the seven chromosomes. Thirty-three other rearrangements generate viable nontandem duplications in meiosis. These consist of insertional translocations (IT's) (15 confirmed), and of rearrangements that involve a chromosome tip (10 translocations and 3 pericentric inversions). No inversion has been found that does not include the centromere. A reciprocal translocation was found within one population in nature. When pairs of RT's that involve the same two chromosome arms were intercrossed, viable duplications were produced if the breakpoints overlapped in such a way that pairing resembled that of insertional translocations (27 combinations).—The rapid analytical technique depends on the following. Deficiency ascospores are usually nonblack (W: "white") and inviable, while nondeficient ascospores, even those that include duplications, are black (B) and viable. Thus RT's typically produce 50% black spores, and IT's 75% black. Asci are shot spontaneously from ripe perithecia, and can be collected in large numbers as groups of eight ascospores representing unordered tetrads, which fall into five classes: 8B:0W; 6B:2W, 4B:4W, 2B:6B, 0B:8W. In isosequential crosses, 90-95% of tetrads are 8:0. When a rearrangement is heterozygous, the frequencies of tetrad classes are diagnostic of the type of rearrangement, and provide information also on the positions of break points. With RT's, 8:0 (alternate centromere segregation) = 0:8 (adjacent-1), 4:4's require interstitial crossing over in a centromere-break point interval, and no 6:2's or 2:6's are expected. With IT's, duplications are viable, 8:0 = 4:4, 6:2's are from interstitial crossing over, 0:8's or 2:6's are rare. Tetrads from RT's that involve a chromosome tip resemble those from IT's, as do tetrads from intercrosses between partially overlapping RT's that involve identical chromosome arms.—Because viable duplications and other aneuploid derivatives regularly occur among the offspring of rearrangements such as insertional translocations, care must be taken in selecting stocks, and original strains should be kept for reference. PMID:4416353

Development of a Design Technology for Ground Support for Tunnels in Soil : Vol. II. Three Dimensional Finite Element Analysis of Advanced and Conventional Shield Tunneling

DOT National Transportation Integrated Search

1983-11-01

The report presents design recommendations for concrete tunnel linings for transportation tunnels. The recommendations developed as a result of in-depth analysis and model testing of the behavior of concrete tunnel linings. The research addressed pro...

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…

Equity and Excellence in Education Reform: An Unfinished Agenda.

ERIC Educational Resources Information Center

Sadker, Myra; Sadker, David

This paper argues that the recent wave of school reform literature has neglected females, thereby threatening to close already narrowing windows of opportunity for their advanced education beyond high school. A line-by-line content analysis of 138 articles on educational reform published in nine influential professional journals between 1983 and…

78 FR 13100 - Models for Plant-Specific Adoption of Technical Specifications Task Force Traveler TSTF-535...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-26

... Definition To Address Advanced Fuel Designs,'' Using the Consolidated Line Item Improvement Process AGENCY...-specific adoption using the Consolidated Line Item Improvement Process (CLIIP). Additionally, the NRC staff..., which may be more reactive at shutdown temperatures above 68[emsp14][deg]F. This STS improvement is part...

Interarea Oscillation Damping Control Using High Voltage DC Transmission: a Survey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elizondo, Marcelo Anibal; Fan, Rui; Kirkham, Harold

High-voltage, direct current (HVDC) transmission lines are increasingly being installed in power systems around the world, and this trend is expected to continue with advancements in power electronics technology. These advancements are also bringing multi-terminal direct current (MTDC) systems closer to practical application. In addition, the continued deployment of phasor measurement units (PMUs) makes dynamic information about a large power system readily available for highly controllable components, such as HVDC lines. All these trends have increased the appeal of modulating HVDC lines and MTDC systems to provide grid services in addition to bulk power transfers. This paper provides a literaturemore » survey of HVDC and MTDC damping controllers for interarea oscillations in large interconnected power systems. The literature shows a progression from theoretical research to practical applications. Finally, there are already practical implementations of HVDC modulation for lines in point-to-point configuration, although the modulation of MTDC systems is still in the research stage. As a conclusion, this paper identifies and summarizes open questions that remain to be tackled by researchers and engineers.« less

Interarea Oscillation Damping Control Using High Voltage DC Transmission: a Survey

DOE PAGES

Elizondo, Marcelo Anibal; Fan, Rui; Kirkham, Harold; ...

2018-05-02

High-voltage, direct current (HVDC) transmission lines are increasingly being installed in power systems around the world, and this trend is expected to continue with advancements in power electronics technology. These advancements are also bringing multi-terminal direct current (MTDC) systems closer to practical application. In addition, the continued deployment of phasor measurement units (PMUs) makes dynamic information about a large power system readily available for highly controllable components, such as HVDC lines. All these trends have increased the appeal of modulating HVDC lines and MTDC systems to provide grid services in addition to bulk power transfers. This paper provides a literaturemore » survey of HVDC and MTDC damping controllers for interarea oscillations in large interconnected power systems. The literature shows a progression from theoretical research to practical applications. Finally, there are already practical implementations of HVDC modulation for lines in point-to-point configuration, although the modulation of MTDC systems is still in the research stage. As a conclusion, this paper identifies and summarizes open questions that remain to be tackled by researchers and engineers.« less

Systemic treatment in advanced biliary cancers: A multicenter Australian analysis and review.

PubMed

Brungs, Daniel; Aghmesheh, Morteza; Sjoquist, Katrin; Goldstein, David

2017-10-01

While first-line palliative chemotherapy (CT1) improves survival and quality of life in advanced biliary cancer (ABC), there is no randomized evidence to support second-line chemotherapy (CT2) in ABC. We aim to explore to role of CT2 in ABC. We performed a retrospective review of all patients who received one or more lines of chemotherapy for ABC at four Australian cancer centers between 2008 and 2011. A Cox proportional hazard model was developed to determine the impact of clinicopathologic variables on overall survival (OS) from time of progression on CT1. We identified 73 patients who received palliative chemotherapy for ABC. Twenty-five patients (34%) received two or more lines of chemotherapy. Patients with a preserved performance status on progression on first-line chemotherapy (CT1) were more likely to receive second-line chemotherapy (CT2) (P < 0.001). Disease control rate with CT2 was 36%, and mean progression-free survival was 3.2 months (95% confidence interval 1.5-4.9 months). The following variables were significant in the univariate analysis of OS from time of progression on CT1: lines of chemotherapy (P = 0.0001), Eastern Cooperative Oncology Group performance status at progression on CT1 (P < 0.0001) and disease control with CT1 (P = 0.027). Lines of chemotherapy received and performance status remained significant in the multivariate analysis for OS from progression on CT1. Second-line chemotherapy is feasible in a subset of patients with ABC. Even after accounting for confounding variables, CT2 appears to increase OS in ABC, although we are unable to exclude other unmeasured factors such as tumor biology. These findings warrant further evaluation with prospective trials. © 2016 John Wiley & Sons Australia, Ltd.

When Prior Knowledge Interferes, Inhibitory Control Matters for Learning: The Case of Numerical Magnitude Representations

ERIC Educational Resources Information Center

Laski, Elida V.; Dulaney, Alana

2015-01-01

The present study tested the "interference hypothesis"-that learning and using more advanced representations and strategies requires the inhibition of prior, less advanced ones. Specifically, it examined the relation between inhibitory control and number line estimation performance. Experiment 1 compared the accuracy of adults' (N = 53)…

Blurring the Lines: Leveraging Internet Technology for Successful Blending of Secondary/Post-Secondary Technical Education

ERIC Educational Resources Information Center

Ryan, Kenneth; Kopischke, Kevin

2008-01-01

The Remote Automation Management Platform (RAMP) is a real-time, interactive teaching tool which leverages common off-the-shelf internet technologies to provide high school learners extraordinary access to advanced technical education opportunities. This outreach paradigm is applicable to a broad range of advanced technical skills from automation…

Efficacy of Capecitabine Plus Oxaliplatin Combination Chemotherapy for Advanced Pancreatic Cancer after Failure of First-Line Gemcitabine-Based Therapy.

PubMed

Chung, Kwang Hyun; Ryu, Ji Kon; Son, Jun Hyuk; Lee, Jae Woo; Jang, Dong Kee; Lee, Sang Hyub; Kim, Yong-Tae

2017-03-15

Second-line chemotherapy in patients with advanced pancreatic ductal adenocarcinoma (PDAC) that progresses following gemcitabine-based treatment has not been established. This study aimed to investigate the efficacy and safety of second-line combination chemotherapy with capecitabine and oxaliplatin (XELOX) in these patients. Between August 2011 and May 2014, all patients who received at least one cycle of XELOX (capecitabine, 1,000 mg/m 2 twice daily for 14 days; oxaliplatin, 130 mg/m 2 on day 1 of a 3-week cycle) combination chemotherapy for unresectable or recurrent PDAC were retrospectively recruited. The response was evaluated every 9 weeks, and the tumor response rate, progression-free survival and overall survival, and adverse events were assessed. Sixty-two patients were included; seven patients (11.3%) had a partial tumor response, and 20 patients (32.3%) had stable disease. The median progression-free and overall survival were 88 days (range, 35.1 to 140.9 days) and 158 days (range, 118.1 to 197.9 days), respectively. Patients who remained stable longer with frontline therapy (≥120 days) exhibited significantly longer progression-free and overall survival. The most common grade 3 to 4 adverse events in patients were vomiting (8.1%) and anorexia (6.5%). There was one treatment-related mortality caused by severe neutropenia and typhlitis. Second-line XELOX combination chemotherapy demonstrated an acceptable response and survival rate in patients with advanced PDAC who had failed gemcitabine-based chemotherapy.

Modeling contact angle hysteresis of a liquid droplet sitting on a cosine wave-like pattern surface.

PubMed

Promraksa, Arwut; Chen, Li-Jen

2012-10-15

A liquid droplet sitting on a hydrophobic surface with a cosine wave-like square-array pattern in the Wenzel state is simulated by using the Surface Evolver to determine the contact angle. For a fixed drop volume, multiple metastable states are obtained at two different surface roughnesses. Unusual and non-circular shape of the three-phase contact line of a liquid droplet sitting on the model surface is observed due to corrugation and distortion of the contact line by structure of the roughness. The contact angle varies along the contact line for each metastable state. The maximum and minimum contact angles among the multiple metastable states at a fixed viewing angle correspond to the advancing and the receding contact angles, respectively. It is interesting to observe that the advancing/receding contact angles (and contact angle hysteresis) are a function of viewing angle. In addition, the receding (or advancing) contact angles at different viewing angles are determined at different metastable states. The contact angle of minimum energy among the multiple metastable states is defined as the most stable (equilibrium) contact angle. The Wenzel model is not able to describe the contact angle along the three-phase contact line. The contact angle hysteresis at different drop volumes is determined. The number of the metastable states increases with increasing drop volume. Drop volume effect on the contact angles is also discussed. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma].

PubMed

Bernard-Tessier, Alice; Bonnet, Clément; Lavaud, Pernelle; Gizzi, Marco; Loriot, Yohann; Massard, Christophe

2018-02-01

Treatments for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin are currently limited. Atezolizumab (Tecentriq ® ) is a monoclonal antibody targeting PD-L1. The first of IMVIGOR 210 phase II trial (NCT02951767) investigated atezolizumab as front line treatment among 119 patients with metastatic urothelial cancer unfit for cisplatin. Response rate was 23% and median overall survival 15.9 months. The second cohort (NCT02108652) included 310 patients whose tumors were progressing after first line platinum-based chemotherapy. Response rate was 15% and median overall survival 7.9 months. Among patients with high PD-L1 expression on infiltrating immune cells (ICs), response rate was 26% and median overall survival 11 months. Atezolizumab was well-tolerated in both cohorts with 66% of treatment-related toxicities including 12% (cohort 1) and 7% (cohort 2) of grade 3-4 adverse events. These results led to an approval by the FDA in United States and the EMA in Europe. In France, atezolizumab was available through an early access agreement by the French National Agency for Medicines and Health Products (ANSM) for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin. So far, its avaibility in France within the EMA approval is pending its pricing. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Everolimus plus exemestane as first-line therapy in HR⁺, HER2⁻ advanced breast cancer in BOLERO-2.

PubMed

Beck, J Thaddeus; Hortobagyi, Gabriel N; Campone, Mario; Lebrun, Fabienne; Deleu, Ines; Rugo, Hope S; Pistilli, Barbara; Masuda, Norikazu; Hart, Lowell; Melichar, Bohuslav; Dakhil, Shaker; Geberth, Matthias; Nunzi, Martina; Heng, Daniel Y C; Brechenmacher, Thomas; El-Hashimy, Mona; Douma, Shyanne; Ringeisen, Francois; Piccart, Martine

2014-02-01

The present exploratory analysis examined the efficacy, safety, and quality-of-life effects of everolimus (EVE) + exemestane (EXE) in the subgroup of patients in BOLERO-2 whose last treatment before study entry was in the (neo)adjuvant setting. In BOLERO-2, patients with hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2-negative (HER2(-)) advanced breast cancer recurring/progressing after a nonsteroidal aromatase inhibitor (NSAI) were randomly assigned (2:1) to receive EVE (10 mg/day) + EXE (25 mg/day) or placebo (PBO) + EXE. The primary endpoint was progression-free survival (PFS) by local assessment. Overall, 137 patients received first-line EVE + EXE (n = 100) or PBO + EXE (n = 37). Median PFS by local investigator assessment nearly tripled to 11.5 months with EVE + EXE from 4.1 months with PBO + EXE (hazard ratio = 0.39; 95 % CI 0.25-0.62), while maintaining quality of life. This was confirmed by central assessment (15.2 vs 4.2 months; hazard ratio = 0.32; 95 % CI 0.18-0.57). The marked PFS improvement in patients receiving EVE + EXE as first-line therapy for disease recurrence during or after (neo)adjuvant NSAI therapy supports the efficacy of this combination in the first-line setting. Furthermore, the results highlight the potential benefit of early introduction of EVE + EXE in the management of HR(+), HER2(-) advanced breast cancer in postmenopausal patients.

Immune Checkpoint Inhibition in Hepatocellular Carcinoma: Basics and Ongoing Clinical Trials.

PubMed

Kudo, Masatoshi

2017-01-01

Clinical trials of antibodies targeting the immune checkpoint inhibitors programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) for the treatment of advanced hepatocellular carcinoma (HCC) are ongoing. Expansion cohorts of a phase I/II trial of the anti-PD-1 antibody nivolumab in advanced HCC showed favorable results. Two phase III studies are currently ongoing: a comparison of nivolumab and sorafenib in the first-line setting for advanced HCC, and a comparison of the anti-PD-1 antibody pembrolizumab and a placebo in the second-line setting for patients with advanced HCC who progressed on sorafenib therapy. The combination of anti-PD-1/PD-L1 and anti-CTLA-4 antibodies is being evaluated in other phase I/II trials, and the results suggest that an anti-PD-1 antibody combined with locoregional therapy or other molecular targeted agents is an effective treatment strategy for HCC. Immune checkpoint inhibitors may therefore open new doors to the treatment of HCC. © 2017 S. Karger AG, Basel.

Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1-Selected Advanced Non-Small-Cell Lung Cancer (BIRCH).

PubMed

Peters, Solange; Gettinger, Scott; Johnson, Melissa L; Jänne, Pasi A; Garassino, Marina C; Christoph, Daniel; Toh, Chee Keong; Rizvi, Naiyer A; Chaft, Jamie E; Carcereny Costa, Enric; Patel, Jyoti D; Chow, Laura Q M; Koczywas, Marianna; Ho, Cheryl; Früh, Martin; van den Heuvel, Michel; Rothenstein, Jeffrey; Reck, Martin; Paz-Ares, Luis; Shepherd, Frances A; Kurata, Takayasu; Li, Zhengrong; Qiu, Jiaheng; Kowanetz, Marcin; Mocci, Simonetta; Shankar, Geetha; Sandler, Alan; Felip, Enriqueta

2017-08-20

Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC). Patients and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, and zero to two or more lines of prior chemotherapy. Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on ≥ 5% of TC or IC (TC2/3 or IC2/3 [TC or IC ≥ 5% PD-L1-expressing cells, respectively]) were enrolled. Atezolizumab 1,200 mg was administered intravenously every 3 weeks. Efficacy-evaluable patients (N = 659) comprised three cohorts: first line (cohort 1; n = 139); second line (cohort 2; n = 268); and third line or higher (cohort 3; n = 252). The primary end point was independent review facility-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Secondary end points included median duration of response, progression-free survival, and overall survival (OS). Results BIRCH met its primary objective of demonstrating a significant ORR versus historical controls. With a minimum of 12 months of follow-up, the independent review facility-assessed ORR was 18% to 22% for the three cohorts, and 26% to 31% for the TC3 or IC3 subgroup; most responses are ongoing. Responses occurred regardless of EGFR or KRAS mutation status. The median OS from an updated survival analysis (minimum of 20 month follow up) for cohort 1 was 23.5 months (26.9 months for TC3 or IC3 patients); the median OS in cohorts 2 and 3 was 15.5 and 13.2 months, respectively. The safety profile was similar across cohorts and consistent with previous atezolizumab monotherapy trials. Conclusion BIRCH demonstrated responses with atezolizumab monotherapy in patients with PD-L1-selected advanced NSCLC, with good tolerability. PD-L1 status may serve as a predictive biomarker for identifying patients most likely to benefit from atezolizumab.

Everolimus for Previously Treated Advanced Gastric Cancer: Results of the Randomized, Double-Blind, Phase III GRANITE-1 Study

PubMed Central

Ohtsu, Atsushi; Ajani, Jaffer A.; Bai, Yu-Xian; Bang, Yung-Jue; Chung, Hyun-Cheol; Pan, Hong-Ming; Sahmoud, Tarek; Shen, Lin; Yeh, Kun-Huei; Chin, Keisho; Muro, Kei; Kim, Yeul Hong; Ferry, David; Tebbutt, Niall C.; Al-Batran, Salah-Eddin; Smith, Heind; Costantini, Chiara; Rizvi, Syed; Lebwohl, David; Van Cutsem, Eric

2013-01-01

Purpose The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer. Patients and Methods Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC. Randomization was stratified by previous chemotherapy lines (one v two) and region (Asia v rest of the world [ROW]). Treatment continued until disease progression or intolerable toxicity. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate, and safety. Results Six hundred fifty-six patients (median age, 62.0 years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and 4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124). Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms, respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse events included anemia, decreased appetite, and fatigue. The safety profile was similar in patients enrolled in Asia versus ROW. Conclusion Compared with BSC, everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy. The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers. PMID:24043745

Silicon photonics plasma-modulators with advanced transmission line design.

PubMed

Merget, Florian; Azadeh, Saeed Sharif; Mueller, Juliana; Shen, Bin; Nezhad, Maziar P; Hauck, Johannes; Witzens, Jeremy

2013-08-26

We have investigated two novel concepts for the design of transmission lines in travelling wave Mach-Zehnder interferometer based Silicon Photonics depletion modulators overcoming the analog bandwidth limitations arising from cross-talk between signal lines in push-pull modulators and reducing the linear losses of the transmission lines. We experimentally validate the concepts and demonstrate an E/O -3 dBe bandwidth of 16 GHz with a 4V drive voltage (in dual drive configuration) and 8.8 dB on-chip insertion losses. Significant bandwidth improvements result from suppression of cross-talk. An additional bandwidth enhancement of ~11% results from a reduction of resistive transmission line losses. Frequency dependent loss models for loaded transmission lines and E/O bandwidth modeling are fully verified.

A real-world study of treatment patterns and survival outcome in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer.

PubMed

Jin, Ying; Chen, Yamei; Yu, Xinmin; Shi, Xun

2018-06-01

Crizotinib is an anti-cancer drug with a substantial beneficial effect in advanced non-small-cell lung cancer (NSCLC) patients harboring anaplastic lymphoma kinase (ALK) rearrangement. However, the real-world data currently available on this drug are limited. Thus, the present study aimed to retrospectively examine the treatment patterns and survival outcome of 83 advanced NSCLC patients with ALK rearrangement in a single center in China. Of the 83 patients enrolled, 33 (39.8%) patients received crizotinib and the remaining 50 (60.2%) patients received chemotherapy as the initial therapy. The first-line use of crizotinib prolonged the PFS1 (progression-free survival to the first detection of subsequent disease progression) compared with chemotherapy (median, 18.5 vs. 4.9 months; P<0.001), however, it did not prolong the overall survival (OS; P=0.802). At the last follow up, 71 (85.5%) patients had received crizotinib and 12 (14.5%) patients were crizotinib-naive. Patients who had received crizotinib exhibited a significantly longer OS as compared with those who were crizotinib-naive [hazard ratio (HR) for mortality, 0.279; 95% confidence interval, 0.107-0.727; P<0.05). Among the 71 patients who had received crizotinib, this was administered as a first-line therapy in 33 (46.5%) cases, as a second-line therapy in 22 (31.0%) cases and after the second-line therapy in 16 (22.5%) cases. No significant difference in the OS among the three groups was observed (P=0.577). The Cox multivariate analysis identified the following independent negative prognostic factors for OS: Smoking history (HR=4.565), liver invasion at diagnosis (HR=4.294) and bone invasion at diagnosis (HR=2.587). In addition, the use of crizotinib (HR=0.319) was identified as a positive prognostic factor for OS. In conclusion, the present real-world study revealed that the use of crizotinib improved the long-term survival of patients with ALK-positive advanced NSCLC. There was no difference in survival outcome between patients with initial use of crizotinib and those with subsequent use of crizotinib after first-line therapy.

A stepwise algorithm using an at-a-glance first-line test for the non-invasive diagnosis of advanced liver fibrosis and cirrhosis.

PubMed

Boursier, Jérôme; de Ledinghen, Victor; Leroy, Vincent; Anty, Rodolphe; Francque, Sven; Salmon, Dominique; Lannes, Adrien; Bertrais, Sandrine; Oberti, Frederic; Fouchard-Hubert, Isabelle; Calès, Paul

2017-06-01

Chronic liver diseases (CLD) are common, and are therefore mainly managed by non-hepatologists. These physicians lack access to the best non-invasive tests of liver fibrosis, and consequently cannot accurately determine the disease severity. Referral to a hepatologist is then needed. We aimed to implement an algorithm, comprising a new first-line test usable by all physicians, for the detection of advanced liver fibrosis in all CLD patients. Diagnostic study: 3754 CLD patients with liver biopsy were 2:1 randomized into derivation and validation sets. Prognostic study: longitudinal follow-up of 1275 CLD patients with baseline fibrosis tests. Diagnostic study: the easy liver fibrosis test (eLIFT), an "at-a-glance" sum of points attributed to age, gender, gamma-glutamyl transferase, aspartate aminotransferase (AST), platelets and prothrombin time, was developed for the diagnosis of advanced fibrosis. In the validation set, eLIFT and fibrosis-4 (FIB4) had the same sensitivity (78.0% vs. 76.6%, p=0.470) but eLIFT gave fewer false positive results, especially in patients ≥60years old (53.8% vs. 82.0%, p<0.001), and was thus more suitable as screening test. FibroMeter with vibration controlled transient elastography (VCTE) was the most accurate among the eight fibrosis tests evaluated. The sensitivity of the eLIFT-FM VCTE algorithm (first-line eLIFT, second-line FibroMeter VCTE ) was 76.1% for advanced fibrosis and 92.1% for cirrhosis. Prognostic study: patients diagnosed as having "no/mild fibrosis" by the algorithm had excellent liver-related prognosis with thus no need for referral to a hepatologist. The eLIFT-FM VCTE algorithm extends the detection of advanced liver fibrosis to all CLD patients and reduces unnecessary referrals of patients without significant CLD to hepatologists. Blood fibrosis tests and transient elastography accurately diagnose advanced liver fibrosis in the large population of patients having chronic liver disease, but these non-invasive tests are only currently available in specialized centers. We have developed an algorithm including the easy liver fibrosis test (eLIFT), a new simple and widely available blood test. It is used as a first-line procedure that selects at-risk patients who need further evaluation with the FibroMeter VCTE , an accurate fibrosis test combining blood markers and transient elastography result. This new algorithm, called the eLIFT-FM VCTE , accurately identifies the patients with advanced chronic liver disease who need referral to a specialist, and those with no or mild liver lesions who can remain under the care of their usual physician. No registration (analysis of pooled data from previously published diagnostic studies). Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Advances in Social Circles Detection

DTIC Science & Technology

2015-07-01

Acknowledgements En primer lugar , agradecer a Roberto Paredes y Paolo Rosso la oportunidad de trabajar en el centro de investigación PRHLT, gracias a...Politècnica De València Technology Transfer Office_CTT UNIVERSITAT POLITÈCNICA DE VALÈNCIA - ABSTRACT Advances in Social Circles Detection Report Title...Our work opens the door to several lines of future work. Universitat Politècnica de València Trabajo de Fin de Máster Advances in Social Circles

Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review

PubMed Central

Chen, Li-Tzong; Oh, Do-Youn; Ryu, Min-Hee; Yeh, Kun-Huei; Yeo, Winnie; Carlesi, Roberto; Cheng, Rebecca; Kim, Jongseok; Orlando, Mauro; Kang, Yoon-Koo

2017-01-01

Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors. PMID:28052652

Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review.

PubMed

Chen, Li-Tzong; Oh, Do-Youn; Ryu, Min-Hee; Yeh, Kun-Huei; Yeo, Winnie; Carlesi, Roberto; Cheng, Rebecca; Kim, Jongseok; Orlando, Mauro; Kang, Yoon-Koo

2017-10-01

Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.

Real world study of regimen containing bevacizumab as first-line therapy in Chinese patients with advanced non-small cell lung cancer.

PubMed

Xing, Puyuan; Mu, Yuxin; Wang, Yan; Hao, Xuezhi; Zhu, Yixiang; Hu, Xingsheng; Wang, Hongyu; Liu, Peng; Lin, Lin; Wang, Zhijie; Li, Junling

2018-05-16

Large scale randomized controlled trials have demonstrated that the use of bevacizumab in addition to chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) conveys significant survival benefits. We explored the clinical impact of a first-line regimen containing bevacizumab (B+) versus a non-bevacizumab regimen (non-B) in advanced non-squamous NSCLC (NS-NSCLC) patients in a real world setting. The medical records of patients with advanced NS-NSCLC who received first-line therapy with or without bevacizumab were retrospectively collected. The primary outcome was progression-free survival (PFS), with secondary objectives of objective response rate (ORR), disease control rate (DCR), and safety. Exploratory analysis of EGFR and ALK status was conducted in subgroup. One hundred and forty-nine patients met the selection criteria: 62 in the B+ and 87 in the non-B group. The baseline characteristics were well balanced. In the overall population, the median PFS was significantly longer in the B+ than in the non-B group (9.7 vs. 7.0 months, hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.30-0.91; P = 0.0184). Improved trends in both ORR and DCR were observed in the B+ group. In wild-type patients, the median PFS of the B+ was 11.3 compared to 5.5 months in the non-B group (HR 0.43, 95% CI 0.20-0.91; P = 0.0234). In wild type and unknown populations, the median PFS was 11.3 (B+) compared to 6.0 months (non-B) (HR 0.53; 95% CI 0.28-1.02; P = 0.0520). The safety profile was acceptable in both groups and no unexpected findings were observed. Our analysis confirmed that a first-line regimen containing bevacizumab showed superior clinical benefits over a non-bevacizumab regimen in Chinese patients with advanced NS-NSCLC in a real world setting. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Life on the Number Line: Routes to Understanding Fraction Magnitude for Students With Difficulties Learning Mathematics.

PubMed

Gersten, Russell; Schumacher, Robin F; Jordan, Nancy C

Magnitude understanding is critical for students to develop a deep understanding of fractions and more advanced mathematics curriculum. The research reports in this special issue underscore magnitude understanding for fractions and emphasize number lines as both an assessment and an instructional tool. In this commentary, we discuss how number lines broaden the concept of fractions for students who are tied to the more general part-whole representations of area models. We also discuss how number lines, compared to other representations, are a superior and more mathematically correct way to explain fraction concepts.

Mouse cloning and somatic cell reprogramming using electrofused blastomeres.

PubMed

Riaz, Amjad; Zhao, Xiaoyang; Dai, Xiangpeng; Li, Wei; Liu, Lei; Wan, Haifeng; Yu, Yang; Wang, Liu; Zhou, Qi

2011-05-01

Mouse cloning from fertilized eggs can assist development of approaches for the production of "genetically tailored" human embryonic stem (ES) cell lines that are not constrained by the limitations of oocyte availability. However, to date only zygotes have been successfully used as recipients of nuclei from terminally differentiated somatic cell donors leading to ES cell lines. In fertility clinics, embryos of advanced embryonic stages are usually stored for future use, but their ability to support the derivation of ES cell lines via somatic nuclear transfer has not yet been proved. Here, we report that two-cell stage electrofused mouse embryos, arrested in mitosis, can support developmental reprogramming of nuclei from donor cells ranging from blastomeres to somatic cells. Live, full-term cloned pups from embryonic donors, as well as pluripotent ES cell lines from embryonic or somatic donors, were successfully generated from these reconstructed embryos. Advanced stage pre-implantation embryos were unable to develop normally to term after electrofusion and transfer of a somatic cell nucleus, indicating that discarded pre-implantation human embryos could be an important resource for research that minimizes the ethical concerns for human therapeutic cloning. Our approach provides an attractive and practical alternative to therapeutic cloning using donated oocytes for the generation of patient-specific human ES cell lines.

Manufacturing of Protected Lithium Electrodes for Advanced Lithium-Air, Lithium-Water & Lithium-Sulfur Batteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Visco, Steven J

The global demand for rechargeable batteries is large and growing rapidly. Assuming the adoption of electric vehicles continues to increase, the need for smaller, lighter, and less expensive batteries will become even more pressing. In this vein, PolyPlus Battery Company has developed ultra-light high performance batteries based on its proprietary protected lithium electrode (PLE) technology. The Company’s Lithium-Air and Lithium-Seawater batteries have already demonstrated world record performance (verified by third party testing), and we are developing advanced lithium-sulfur batteries which have the potential deliver high performance at low cost. In this program PolyPlus Battery Company teamed with Corning Incorporated tomore » transition the PLE technology from bench top fabrication using manual tooling to a pre- commercial semi-automated pilot line. At the inception of this program PolyPlus worked with a Tier 1 battery manufacturing engineering firm to design and build the first-of-its-kind pilot line for PLE production. The pilot line was shipped and installed in Berkeley, California several months after the start of the program. PolyPlus spent the next two years working with and optimizing the pilot line and now produces all of its PLEs on this line. The optimization process successfully increased the yield, throughput, and quality of PLEs produced on the pilot line. The Corning team focused on fabrication and scale-up of the ceramic membranes that are key to the PLE technology. PolyPlus next demonstrated that it could take Corning membranes through the pilot line process to produce state-of-the-art protected lithium electrodes. In the latter part of the program the Corning team developed alternative membranes targeted for the large rechargeable battery market. PolyPlus is now in discussions with several potential customers for its advanced PLE-enabled batteries, and is building relationships and infrastructure for the transition into manufacturing. It is likely that the next step will be accomplished through a combination of joint venture partnering and licensing of the technology.« less

Impact of the incorporation of tyrosine kinase inhibitor agents on the treatment of patients with a diagnosis of advanced renal cell carcinoma: study based on experience at the Hospital Universitario Central de Asturias.

PubMed

Muriel, Carolina; Esteban, Emilio; Corral, Norberto; Fonseca, Paula J; Luque, María; Berros, José Pablo; Fernández, Yolanda; Blay, Pilar; Fra, Joaquín; Villanueva, Noemí; Sanmamed, Miguel; Pardo, Pablo; Izquierdo, Marta; Vieitez, José María; Estrada, Enrique; Lacave, Ángel J

2010-08-01

For nearly the past two decades, cytokines (CKs) have been the only systemic treatment option available for advanced renal cell carcinoma (RCC). In recent years, tyrosine kinase inhibitors (TKIs) have demonstrated clinical activity on this tumour. Our purpose is to describe one centre's experience with the use of CKs and TKIs in the treatment of patients with advanced RCC. This study was designed as a retrospective chart review of RCC patients who were treated with CKs and/or TKIs in our department between July 1996 and June 2008. Efficacy and toxicity were assessed using World Health Organization (WHO) criteria. The Kaplan-Meier method was used to estimate progression-free (PFS) and overall (OS) survival. Ninety-four patients were classified into three groups depending on the modality of treatment administered: 46 were treated with CKs alone and/or chemotherapy (27 with immunotherapy, one with chemotherapy and 18 with both), 28 with TKIs alone (25 with sunitinib and 13 with sorafenib) and 20 with TKIs in second-line treatment following failure with CKs (17 with sunitinib, eight with sorafenib, four with bevacizumab and one with lapatinib). The median age was 60 years in the CK group and 65 and 62, respectively, in TKI in first and second-line treatment groups. Eighty-five percent of patients treated with CKs and 75% in the TKI group in first-line treatment and 80% in second-line treatment were men. Overall, 89% of patients had favourable risk, and 11% had intermediate risk. All patients were considered evaluable for toxicity. The main grade 3-4 (%) toxicity was asthenia for both groups, (ten in TKIs and 15 in CKs). Other grade 1-2 toxicities were mucositis (39), bleeding (8), hypertension (19), skin toxicity (33) and hypothyroidism (12.5) associated with TKIs; and anaemia (33), cough (29), asthenia (39) and emesis (14) associated with CKs. The objective response rate among 80 patients evaluable for activity was 10.6% with CKs and 46.5% and 35%, respectively, with TKIs in first- and second-line treatments. Disease stabilisation with CKs was recorded at 59% of patients and with TKIs 25% and 50% in first- and second-line treatment groups, respectively. The median progression-free survival (PFS) with CKs was 122 days [95% confidence interval (CI) 82-162] and with TKIs 201 days (65-337) in the first and 346 days (256-436) in second-line treatment groups. The median overall survival (OS) was 229 days (142-316) and 2,074 days (1,152-2,996) for patients treated with CKs and TKIs. Our results are in line with the activity and survival rates previously reported in the literature regarding the use of TKIs for patients with advanced RCC in first- and second-line treatment, which has demonstrated an acceptable toxicity level.

Clinical management and outcome of patients with advanced NSCLC carrying EGFR mutations in Spain.

PubMed

Arriola, Edurne; García Gómez, Ramón; Diz, Pilar; Majem, Margarita; Martínez Aguillo, Maite; Valdivia, Javier; Paredes, Alfredo; Sánchez-Torres, José Miguel; Peralta Muñoz, Sergio; Barneto, Isidoro; Gutierrez, Vanesa; Andrade Santiago, Jesús Manuel; Aparisi, Francisco; Isla, Dolores; Ponce, Santiago; Vicente Baz, David; Artal, Angel; Amador, Mariluz; Provencio, Mariano

2018-01-30

Although the benefit of first-line epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) over chemotherapy has been demonstrated in several clinical trials, data from clinical practice is lacking and the optimal EGFR TKI to be used remains unclear. This study aims to assess the real-life diagnostic and clinical management and outcome of patients with advanced non-small-cell lung cancer (NSCLC) carrying EGFR mutations in Spain. All consecutive patients recently diagnosed with advanced or metastatic NSCLC from April 2010 to December 2011 in 18 Spanish hospitals and carrying EGFR mutations were retrospectively evaluated. Between March and November 2013, a total of 187 patients were enrolled (98.3% Caucasian, 61.9% female, 54.9% never-smokers, 89.0% adenocarcinoma). Mutation testing was mainly performed on biopsy tumour tissue specimens (69.0%) using a qPCR-based test (90%) (47.0% Therascreen EGFR PCR Kit). Common sensitising mutations were detected in 79.8% of patients: 57.1% had exon 19 deletions and 22.6% exon 21 L858R point mutations. The vast majority of patients received first-line therapy (n = 168; 92.8%). EGFR TKIs were the most commonly used first-line treatment (81.5%), while chemotherapy was more frequently administered as a second- and third-line option (51.9% and 56.0%, respectively). Of 141 patients who experienced disease progression, 79 (56.0%) received second-line treatment. After disease progression on first-line TKIs (n = 112), 33.9% received chemotherapy, 8.9% chemotherapy and a TKI, and 9.8% continued TKI therapy. Most patients received first-line gefitinib (83.0%), while erlotinib was more frequently used in the second-line setting (83.0%). Progression-free survival (PFS) and overall survival (OS) in patients harbouring common mutations were 11.1 months and 20.1 months respectively (exon 19 deletions: 12.4 and 21.4 months; L858R: 8.3 and 14.5 months), and 3.9 months and 11.1 months respectively for those with rare mutations. EGFR TKIs (gefitinib and erlotinib) are used as the preferred first-line treatment while chemotherapy is more frequently administered as a second- and third-line option in routine clinical practice in Spain. In addition, efficacy data obtained in the real-life setting seem to concur with data from EGFR TKI phase III pivotal studies in NSCLC.

Life on the Number Line: Routes to Understanding Fraction Magnitude for Students with Difficulties Learning Mathematics

ERIC Educational Resources Information Center

Gersten, Russell; Schumacher, Robin F.; Jordan, Nancy C.

2017-01-01

Magnitude understanding is critical for students to develop a deep understanding of fractions and more advanced mathematics curriculum. The research reports in this special issue underscore magnitude understanding for fractions and emphasize number lines as both an assessment and an instructional tool. In this commentary, we discuss how number…

Online Programs to Stop Sexual Harassment: Easy to Use but Not Always Enough

ERIC Educational Resources Information Center

June, Audrey Williams

2009-01-01

A college's first line of defense against employees' making insinuating remarks, unwanted sexual advances, or requests for sexual favors is often about an hour of online sensitivity training. Some people, however, wonder if that line is strong enough. According to a 2006 survey of undergraduate students by the American Association of University…

Advanced Spectral Modeling Development

DTIC Science & Technology

1992-09-14

above, the AFGL line-by-line code already possesses many of the attributes desired of a generally applicable transmittance/radiance simulation code, it...transmittance calculations, (b) perform generalized multiple scattering calculations, (c) calculate both heating and dissociative fluxes, (d) provide...This report is subdivided into task specific subsections. The following section describes our general approach to address these technical issues (Section

Portable Technology: Media a la Cart

ERIC Educational Resources Information Center

Villano, Matt

2006-01-01

There was a time when being a teacher at Lenawee Intermediate School District (MI) meant getting in line--a long line--if a teacher wished to get hold of audiovisual equipment for the class. Teachers had to reserve the equipment weeks in advance. Next, once the time came to use it, representatives from the district's A/V department had to quite…

30 CFR 75.1507 - Emergency Response Plan; refuge alternatives.

Code of Federal Regulations, 2010 CFR

2010-07-01

... affirmative statement that the locations are— (i) Not within direct line of sight of the working face; and (ii... direct line of sight of the working face. (12) The maximum mine air temperature at each of the locations... 48 hours, the ERP shall detail advanced arrangements that have been made to assure that persons who...

76 FR 16715 - Drawbridge Operation Regulation; Raritan River, Arthur Kill and Their Tributaries, Staten Island...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-25

... would like to know that they reached the Facility, please enclose a stamped, self-addressed postcard or... dedicated telephone hot line for vessel operators to call the bridge in advance to coordinate anticipated bridge closures. The telephone hot line number shall be posted on signs at the bridge clearly visible...

Japan's advanced medicine.

PubMed

Sho, Ri; Narimatsu, Hiroto; Murakami, Masayasu

2013-10-01

Like health care systems in other developed countries, Japan's health care system faces significant challenges due to aging of the population and economic stagnation. Advanced medicine (Senshin Iryou) is a unique system of medical care in Japan offering highly technology-driven medical care that is not covered by public health insurance. Advanced medicine has recently developed and expanded as part of health care reform. Will it work? To answer this question, we briefly trace the historical development of advanced medicine and describe the characteristics and current state of advanced medical care in Japan. We then offer our opinions on the future of advanced medicine with careful consideration of its pros and cons. We believe that developing advanced medicine is an attempt to bring health care reform in line rather than the goal of health care reform.

Factors for Development of Learning Content and Task for MOOCs in an Asian Context

ERIC Educational Resources Information Center

Nordin, Norazah; Norman, Helmi; Embi, Mohamed Amin; Mansor, Ahmad Zamri; Idris, Fazilah

2016-01-01

The rapid advancement of emergent learning technologies has led to the introduction of massive open online courses (MOOCs) which offer open-based online learning courses to a large number of students. In line with the advancement, the Malaysia Ministry of Education has recently initiated Malaysia MOOCs via collaboration with four public…

Bourdieu's "Misrecognition": Why Educational Leadership Standards Will Not Reform Schools or Leadership

ERIC Educational Resources Information Center

English, Fenwick W.

2012-01-01

This article examines the concept of misrecognition as advanced by Pierre Bourdieu in the development and implementation of educational leadership standards in the USA and in England. The line of argument advanced is that leadership standards were promulgated as an agenda to control and dominate a contested field in both countries by certain…

Distance Learning in Advanced Military Education: Analysis of Joint Operations Course in the Taiwan Military

ERIC Educational Resources Information Center

Tung, Ming-Chih; Huang, Jiung-yao; Keh, Huan-Chao; Wai, Shu-shen

2009-01-01

High-ranking officers require advanced military education in war tactics for future combat. However, line officers rarely have time to take such courses on campus. The conventional solution to this problem used to take the inefficient correspondence courses. Whereas Internet technologies progress, online course is the current trend for military…

Equilibrium-line altitude during the Antarctic Cold Reversal at Río Tranquilo glacier (47°S), Central Patagonia

NASA Astrophysics Data System (ADS)

Sagredo, E. A.; Ward, D.; Gonzalez, M. A.; Lowell, T. V.; Kelly, M. A.; Aravena, J. C.

2013-12-01

Documenting the magnitude of former glacial fluctuations is critical for understanding the mechanisms and climate signals underlying these glacial events. Here, we estimate the equilibrium line altitudes (ELA) associated with the most prominent glacial advance occurred during the Last Glacial Termination (T1) at Tranquilo glacier (47°S). Geomorphic evidence suggest that, following the Last Glacial Maximum, several small glaciers, which today occupy the headwalls of Río Tranquilo valley, expanded and coalesced, forming the extended version of the Tranquilo glacier at least three different times. 10Be ages suggest that the most prominent of these glacial advances occurred ~13 kyr BP, at the end of the Antarctic Cold Reversal (ACR). Based on glacial geomorphic mapping and the application of a glaciological model (GC2D), we reconstruct the former glacial surface at Tranquilo glacier and estimate the ELA for this major glacial advance. Preliminary data show that the equilibrium line altitude at Tranquilo glacier during the ACR could have been up to 500 m lower than the present. This study represents the first effort to quantify the ELA during the Antarctic Cold Reversal in Patagonia, and provides a baseline to decipher the climatic signals driving this glacial event.

On-Line Thermal Barrier Coating Monitoring for Real-Time Failure Protection and Life Maximization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dennis H. LeMieux

2004-10-01

Under the sponsorship of the U. S. Department of Energy's National Energy Laboratory, Siemens Westinghouse Power Corporation proposes a four year program titled, ''On-Line Thermal Barrier Coating (TBC) Monitor for Real-Time Failure Protection and Life Maximization'', to develop, build and install the first generation of an on-line TBC monitoring system for use on land -based advanced gas turbines (AGT). Federal deregulation in electric power generation has accelerated power plant owner's demand for improved reliability availability maintainability (RAM) of the land-based advanced gas turbines. As a result, firing temperatures have been increased substantially in the advanced turbine engines, and the TBCsmore » have been developed for maximum protection and life of all critical engine components operating at these higher temperatures. Losing TBC protection can therefore accelerate the degradation of substrate components materials and eventually lead to a premature failure of critical component and costly unscheduled power outages. This program seeks to substantially improve the operating life of high cost gas turbine components using TBC; thereby, lowering the cost of maintenance leading to lower cost of electricity. Siemens Westinghouse Power Corporation has teamed with Indigo Systems; a supplier of state-of-the-art infrared camera systems, and Wayne State University, a leading research organization.« less

Warthog: A MOOSE-Based Application for the Direct Code Coupling of BISON and PROTEUS

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCaskey, Alexander J.; Slattery, Stuart; Billings, Jay Jay

The Nuclear Energy Advanced Modeling and Simulation (NEAMS) program from the Department of Energy's Office of Nuclear Energy provides a robust toolkit for the modeling and simulation of current and future advanced nuclear reactor designs. This toolkit provides these technologies organized across product lines: two divisions targeted at fuels and end-to-end reactor modeling, and a third for integration, coupling, and high-level workflow management. The Fuels Product Line and the Reactor Product line provide advanced computational technologies that serve each respective field well, however, their current lack of integration presents a major impediment to future improvements of simulation solution fidelity. Theremore » is a desire for the capability to mix and match tools across Product Lines in an effort to utilize the best from both to improve NEAMS modeling and simulation technologies. This report details a new effort to provide this Product Line interoperability through the development of a new application called Warthog. This application couples the BISON Fuel Performance application from the Fuels Product Line and the PROTEUS Core Neutronics application from the Reactors Product Line in an effort to utilize the best from all parts of the NEAMS toolkit and improve overall solution fidelity of nuclear fuel simulations. To achieve this, Warthog leverages as much prior work from the NEAMS program as possible, and in doing so, enables interoperability between the disparate MOOSE and SHARP frameworks, and the libMesh and MOAB mesh data formats. This report describes this work in full. We begin with a detailed look at the individual NEAMS framework technologies used and developed in the various Product Lines, and the current status of their interoperability. We then introduce the Warthog application: its overall architecture and the ways it leverages the best existing tools from across the NEAMS toolkit to enable BISON-PROTEUS integration. Furthermore, we show how Warthog leverages a tool known as DataTransferKit to seamlessly enable the transfer for solution data between disparate frameworks and mesh formats. To end, we demonstrate tests for the direct software coupling of BISON and PROTEUS using Warthog, and discuss current impediments and solutions to the construction of physically realistic input models for this coupled BISON-PROTEUS system.« less

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.

Safety and efficacy of first-line bevacizumab with chemotherapy in Asian patients with advanced nonsquamous NSCLC: results from the phase IV MO19390 (SAiL) study.

PubMed

Tsai, Chun-Ming; Au, Joseph Siu-kie; Chang, Gee-Chen; Cheng, Ashley Chi-kin; Zhou, Caicun; Wu, Yi-long

2011-06-01

First-line treatment with bevacizumab combined with chemotherapy has been shown to improve outcomes in patients with advanced, nonsquamous non-small cell lung cancer (NSNSCLC) in phase III clinical trials. SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a preplanned subanalysis of Asian patients enrolled in SAiL. Patients with untreated, locally advanced, metastatic or recurrent NSNSCLC received bevacizumab 7.5 or 15 mg/kg every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Eligibility criteria for SAiL permitted enrolment of a broad patient population. The primary end point was safety; secondary end points included time to disease progression and overall survival. The Asian intent-to-treat population comprised 314 of the 2212 patients enrolled in the SAiL trial. In the Asian subanalysis, patients received a median of nine cycles of bevacizumab, and the median follow-up was 16.4 months. The incidence of clinically significant adverse events (grade ≥3) of special interest was relatively low in this population (15.6% overall); proteinuria (7.6%), hypertension (4.8%), and bleeding (2.5%) were the most common. A total of five adverse events related to bevacizumab were reported as grade 5. Disease control rate was 94.1%, median time to disease progression was 8.3 months, and median overall survival was 18.9 months. The safety and efficacy of first-line bevacizumab-based treatment in Asian patients with advanced NSNSCLC is consistent with that demonstrated in phase III studies and in the overall SAiL population. There were no new safety signals.

Safety and efficacy of first-line bevacizumab combination therapy in Chinese population with advanced non-squamous NSCLC: data of subgroup analyses from MO19390 (SAiL) study.

PubMed

Zhou, C C; Bai, C X; Guan, Z Z; Jiang, G L; Shi, Y K; Wang, M Z; Wu, Y L; Zhang, Y P; Zhu, Y Z

2014-05-01

Bevacizumab is a monoclonal antibody with high antitumor activity against malignant diseases. Previous studies have demonstrated the efficacy of first-line bevacizumab combination therapy in advanced, non-squamous non-small cell lung cancer (NS-NSCLC). SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a subgroup analysis of Chinese patients enrolled in SAiL. Chemo-naive Chinese patients with locally advanced, metastatic or recurrent NSCLC were randomized to receive Bev 15 mg/kg every 3 weeks plus carboplatin + paclitaxel for maximum of six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety. Secondary endpoints included time to progression and overall survival. The Chinese intent-to-treat (ITT) population consists of 198 Chinese patients, among whom 107 (54 %) were non-smokers and 90 (45.5 %) were female. The median cycle of bevacizumab administration was 10 and median duration of bevacizumab treatment was 29.5 weeks. Only eight cases of severe adverse events were observed in the study, which were deemed to be related to bevacizumab. The incidence of AEs over grade 3 in Chinese ITT patients was generally low (<9 %). No new safety signals were reported. Objective response rate in 195 evaluable Chinese patients was 68.8 %, including four complete responses (2.1 %). Time to disease progression (TTP) and overall survival were 8.8 and 18.5 months, respectively. The safety and efficacy of first-line bevacizumab-based treatment in Chinese population with advanced NS-NSCLC are consistent with those in previous studies as well as in Asian subgroup population from SAiL study. No new safety signals were reported.

Erlotinib as single agent first line treatment in locally advanced or metastatic activating EGFR mutation-positive lung adenocarcinoma (CEETAC): an open-label, non-randomized, multicenter, phase IV clinical trial.

PubMed

Markóczy, Zsolt; Sárosi, Veronika; Kudaba, Iveta; Gálffy, Gabriella; Turay, Ülkü Yilmaz; Demirkazik, Ahmet; Purkalne, Gunta; Somfay, Attila; Pápai-Székely, Zsolt; Rásó, Erzsébet; Ostoros, Gyula

2018-05-25

Erlotinib is approved for the first line treatment of epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer. Since the number of prospective studies in Caucasian patients treated in routine clinical setting is limited we conducted a multicenter, phase IV clinical trial to determine the efficacy and safety of erlotinib and to demonstrate the feasibility of the validated standardized companion diagnostic method of EGFR mutation detection. 651 chemonaive, cytologically or histologically verified advanced stage lung adenocarcinoma patients from Hungary, Turkey and Latvia were screened for exon19 microdeletions and exon21 L858R EGFR mutations using the companion diagnostic EGFR test. EGFR mutation-positive, locally advanced or metastatic lung adenocarcinoma patients received as first line treatment erlotinib at 150 mg/day. The primary endpoint was progression-free survival (PFS). 62 EGFR mutation-positive patients (9.5% of screened) were included in the safety/intent-to-treat cohort. Median PFS was 12.8 months (95%CI, 9.9-15.8), objective response rate and one-year survival was 66.1% and 82.5%, respectively. Most frequent treatment related adverse events were diarrhoea and rash. Eastern Oncology Cooperative Group Performance Status (ECOG PS), smoking status and M1a/M1b disease stage were significant prognosticators of PFS (p = 0.017, p = 0.045 and p = 0.002, respectively). There was no significant difference in PFS between the subgroups stratified by gender, age or exon19 vs exon21 mutation. Our study confirmed the efficacy and safety of first line erlotinib monotherapy in Caucasian patients with locally advanced or metastatic lung adenocarcinoma carrying activating EGFR mutations based on the screening with the approved companion diagnostic procedure. ClinicalTrials.gov Identifier: NCT01609543.

Nivolumab Monotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer

PubMed Central

Rizvi, Naiyer A.; Chow, Laura Q.; Borghaei, Hossein; Brahmer, Julie; Ready, Neal; Gerber, David E.; Shepherd, Frances A.; Antonia, Scott; Goldman, Jonathan W.; Juergens, Rosalyn A.; Laurie, Scott A.; Nathan, Faith E.; Shen, Yun; Harbison, Christopher T.; Hellmann, Matthew D.

2016-01-01

Purpose Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non–small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial. Methods Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment was permitted per protocol. The primary objective was to assess safety; secondary objectives included objective response rate (ORR) and 24-week progression-free survival (PFS) rate; overall survival (OS) was an exploratory end point. Results Any-grade treatment-related adverse events (AEs) occurred in 71% of patients, most commonly: fatigue (29%), rash (19%), nausea (14%), diarrhea (12%), pruritus (12%), and arthralgia (10%). Ten patients (19%) reported grade 3 to 4 treatment-related AEs; grade 3 rash was the only grade 3 to 4 event occurring in more than one patient (n = 2; 4%). Six patients (12%) discontinued because of a treatment-related AE. The confirmed ORR was 23% (12 of 52), including four ongoing complete responses. Nine of 12 responses (75%) occurred by first tumor assessment (week 11); eight (67%) were ongoing (range, 5.3+ to 25.8+ months) at the time of data lock. ORR was 28% (nine of 32) in patients with any degree of tumor PD–ligand 1 expression and 14% (two of 14) in patients with no PD–ligand 1 expression. Median PFS was 3.6 months, and the 24-week PFS rate was 41% (95% CI, 27 to 54). Median OS was 19.4 months, and the 1-year and 18-month OS rates were 73% (95% CI, 59 to 83) and 57% (95% CI, 42 to 70), respectively. Conclusion First-line nivolumab monotherapy demonstrated a tolerable safety profile and durable responses in first-line advanced NSCLC. PMID:27354485

Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer.

PubMed

Gettinger, Scott; Rizvi, Naiyer A; Chow, Laura Q; Borghaei, Hossein; Brahmer, Julie; Ready, Neal; Gerber, David E; Shepherd, Frances A; Antonia, Scott; Goldman, Jonathan W; Juergens, Rosalyn A; Laurie, Scott A; Nathan, Faith E; Shen, Yun; Harbison, Christopher T; Hellmann, Matthew D

2016-09-01

Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non-small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial. Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment was permitted per protocol. The primary objective was to assess safety; secondary objectives included objective response rate (ORR) and 24-week progression-free survival (PFS) rate; overall survival (OS) was an exploratory end point. Any-grade treatment-related adverse events (AEs) occurred in 71% of patients, most commonly: fatigue (29%), rash (19%), nausea (14%), diarrhea (12%), pruritus (12%), and arthralgia (10%). Ten patients (19%) reported grade 3 to 4 treatment-related AEs; grade 3 rash was the only grade 3 to 4 event occurring in more than one patient (n = 2; 4%). Six patients (12%) discontinued because of a treatment-related AE. The confirmed ORR was 23% (12 of 52), including four ongoing complete responses. Nine of 12 responses (75%) occurred by first tumor assessment (week 11); eight (67%) were ongoing (range, 5.3+ to 25.8+ months) at the time of data lock. ORR was 28% (nine of 32) in patients with any degree of tumor PD-ligand 1 expression and 14% (two of 14) in patients with no PD-ligand 1 expression. Median PFS was 3.6 months, and the 24-week PFS rate was 41% (95% CI, 27 to 54). Median OS was 19.4 months, and the 1-year and 18-month OS rates were 73% (95% CI, 59 to 83) and 57% (95% CI, 42 to 70), respectively. First-line nivolumab monotherapy demonstrated a tolerable safety profile and durable responses in first-line advanced NSCLC. © 2016 by American Society of Clinical Oncology.

Decision aids for second-line palliative chemotherapy: a randomised phase II multicentre trial.

PubMed

Oostendorp, Linda J M; Ottevanger, Petronella B; Donders, A Rogier T; van de Wouw, Agnes J; Schoenaker, Ivonne J H; Smilde, Tineke J; van der Graaf, Winette T A; Stalmeier, Peep F M

2017-08-31

There is increasing recognition of the delicate balance between the modest benefits of palliative chemotherapy and the burden of treatment. Decision aids (DAs) can potentially help patients with advanced cancer with these difficult treatment decisions, but providing detailed information could have an adverse impact on patients' well-being. The objective of this randomised phase II study was to evaluate the safety and efficacy of DAs for patients with advanced cancer considering second-line chemotherapy. Patients with advanced breast or colorectal cancer considering second-line treatment were randomly assigned to usual care (control group) or usual care plus a DA (intervention group) in a 1:2 ratio. A nurse offered a DA with information on adverse events, tumour response and survival. Outcome measures included patient-reported well-being (primary outcome: anxiety) and quality of the decision-making process and the resulting choice. Of 128 patients randomised, 45 were assigned to the control group and 83 to the intervention group. Median age was 62 years (range 32-81), 63% were female, and 73% had colorectal cancer. The large majority of patients preferred treatment with chemotherapy (87%) and subsequently commenced treatment with chemotherapy (86%). No adverse impact on patients' well-being was found and nurses reported that consultations in which the DAs were offered went well. Being offered the DA was associated with stronger treatment preferences (3.0 vs. 2.5; p=0.030) and increased subjective knowledge (6.7 vs. 6.3; p=0.022). Objective knowledge, risk perception and perceived involvement were comparable between the groups. DAs containing detailed risk information on second-line palliative treatment could be delivered to patients with advanced cancer without having an adverse impact on patient well-being. Surprisingly, the DAs only marginally improved the quality of the decision-making process. The effectiveness of DAs for palliative treatment decisions needs further exploration. Netherlands Trial Registry (NTR): NTR1113 (registered on 2 November 2007).

Cost-effectiveness of Pembrolizumab in Second-line Advanced Bladder Cancer.

PubMed

Sarfaty, Michal; Hall, Peter S; Chan, Kelvin K W; Virik, Kiran; Leshno, Moshe; Gordon, Noa; Moore, Assaf; Neiman, Victoria; Rosenbaum, Eli; Goldstein, Daniel A

2018-03-22

Immune-modulating drugs have recently been introduced to the second-line setting of advanced bladder cancer. Pembrolizumab increases overall survival and is associated with less toxicity compared with chemotherapy in this setting based on the Keynote 045 study. The high cost of immunotherapy necessitates an assessment of its value by considering both efficacy and cost. To estimate the cost-effectiveness of pembrolizumab for the second-line treatment of advanced bladder cancer from the perspective of payers in multiple countries. We developed a Markov model to compare the cost and effectiveness of pembrolizumab with those of chemotherapy in the second-line treatment of advanced bladder cancer based on the Keynote 045 study. Drug costs were acquired for the United States (US), United Kingdom (UK), Canada, and Australia. All costs were converted from local currency to US dollars at the exchange rates in September 2017. Health outcomes were measured in quality-adjusted life-years (QALYs). Pembrolizumab generated a gain of 0.36-0.37 QALYs compared with chemotherapy. Our analysis established the following incremental cost-effectiveness ratios (ICERs) for pembrolizumab versus chemotherapy in second-line advanced bladder cancer treatment: US $122 557/QALY; UK $91 995/QALY; Canada $90 099/QALY; and Australia $99 966/QALY. The willingness-to-pay (WTP) thresholds per QALY are considered to be around 100 000-150 000 US dollars for the US, 20 000-50 000 pounds for the UK (US$25 000-65 000), 20 000 -100 000 CAD for Canada (US$16 000-80 000), and 40 000-75 000 AUD for Australia (US$32 000-60 000). Cost-effectiveness and WTP thresholds vary between countries. Compared with the other countries examined, US drug prices were found to be the highest, leading to the highest ICER. With standard WTP thresholds, pembrolizumab may be considered cost-effective in the US but not in the other countries examined. This article assessed the cost-effectiveness of pembrolizumab for the treatment of patients with metastatic bladder cancer who had previously failed one treatment regimen. It would cost $122 557 in the United States, $91 995 in the United Kingdom, $90 099 in Canada, and $99 966 in Australia to gain one quality-adjusted life-year with pembrolizumab versus chemotherapy in these patients, which may be considered cost-effective only in the United States because of the differences in willingness-to-pay thresholds. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Genetic heterogeneity of RPMI-8402, a T-acute lymphoblastic leukemia cell line

PubMed Central

STOCZYNSKA-FIDELUS, EWELINA; PIASKOWSKI, SYLWESTER; PAWLOWSKA, ROZA; SZYBKA, MALGORZATA; PECIAK, JOANNA; HULAS-BIGOSZEWSKA, KRYSTYNA; WINIECKA-KLIMEK, MARTA; RIESKE, PIOTR

2016-01-01

Thorough examination of genetic heterogeneity of cell lines is uncommon. In order to address this issue, the present study analyzed the genetic heterogeneity of RPMI-8402, a T-acute lymphoblastic leukemia (T-ALL) cell line. For this purpose, traditional techniques such as fluorescence in situ hybridization and immunocytochemistry were used, in addition to more advanced techniques, including cell sorting, Sanger sequencing and massive parallel sequencing. The results indicated that the RPMI-8402 cell line consists of several genetically different cell subpopulations. Furthermore, massive parallel sequencing of RPMI-8402 provided insight into the evolution of T-ALL carcinogenesis, since this cell line exhibited the genetic heterogeneity typical of T-ALL. Therefore, the use of cell lines for drug testing in future studies may aid the progress of anticancer drug research. PMID:26870252

Association mapping of iron deficiency chlorosis loci in soybean (Glycine max L. Merr.) advanced breeding lines.

PubMed

Wang, Ju; McClean, Phillip E; Lee, Rian; Goos, R Jay; Helms, Ted

2008-04-01

Association mapping is an alternative to mapping in a biparental population. A key to successful association mapping is to avoid spurious associations by controlling for population structure. Confirming the marker/trait association in an independent population is necessary for the implementation of the marker in other genetic studies. Two independent soybean populations consisting of advanced breeding lines representing the diversity within maturity groups 00, 0, and I were screened in multi-site, replicated field trials to discover molecular markers associated with iron deficiency chlorosis (IDC), a major yield-limiting factor in soybean. Lines with extreme phenotypes were initially screened to identify simple sequence repeat (SSR) markers putatively associated with the IDC. Marker data collected from all lines were used to control for population structure and kinship relationships. Single factor analysis of variance (SFA) and mixed linear model (MLM) analyses were used to discover marker/trait associations. The MLM analyses, which include population structure, kinship or both factors, reduced the number of markers significantly associated with IDC by 50% compared with SFA. With the MLM approach, three markers were found to be associated with IDC in the first population. Two of these markers, Satt114 and Satt239, were also found to be associated with IDC in the second confirmation population. For both populations, those lines with the tolerance allele at both these two marker loci had significantly lower IDC scores than lines with one or no tolerant alleles.

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

PubMed

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

2016-01-01

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

Genomic Prediction of Seed Quality Traits Using Advanced Barley Breeding Lines

PubMed Central

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

2016-01-01

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

Biweekly irinotecan plus bolus 5-fluorouracil and folinic acid in patients with advanced stage colorectal cancer.

PubMed

Yalcin, Suayib; Oksuzoglu, Berna; Tekuzman, Gülten; Engin, Hüseyin; Celik, Ismail; Turker, Alev; Barista, Ibrahim; Gullu, Ibrahim; Guler, Nilufer; Altundag, Kadri; Ozisik, Yavuz; Kars, Ayse

2003-11-01

In this study, we evaluated the efficacy and tolerability of biweekly irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and folinic acid (FA) regimen (IFL) in patients with advanced stage colorectal cancer. A total of 28 patients were examined. The median age was 51 years (range, 30-74 years). One treatment cycle consisted of CPT-11 180 mg/m(2) on days 1 and 15; 5-FU 425 mg/m(2) on days 1, 2, 15 and 16; and FA 20 mg/m(2) on days 1, 2, 15 and 16, every 4 weeks. A total of 119 cycles (median, 4.0 cycles) were administered. Of the 28 patients, 18 received the chemotherapy as first line treatment, seven received it as second line and three received it as third line. An overall objective response rate of 21.5% was achieved in the patient group. However, the overall response rate for the 18 patients receiving first line treatment was 27.7%. The median response duration was 10.5 months (range, 3-19 months). An additional 28.6% of the patients had stable disease for a median duration of 6.5 months (range, 3-8 months). Median time to disease progression was 4.5 months (range, 1-22+ months) and median overall survival time was 11+ months (95% confidence interval, 9-15 months). Toxicities were mild and manageable. We conclude that biweekly IFL is a practical and tolerable treatment option with a disease control rate of 50.1% in patients with advanced stage colorectal cancer.

Cost effectiveness of EML4-ALK fusion testing and first-line crizotinib treatment for patients with advanced ALK-positive non-small-cell lung cancer.

PubMed

Djalalov, Sandjar; Beca, Jaclyn; Hoch, Jeffrey S; Krahn, Murray; Tsao, Ming-Sound; Cutz, Jean-Claude; Leighl, Natasha B

2014-04-01

ALK-targeted therapy with crizotinib offers significant improvement in clinical outcomes for the treatment of EML4-ALK fusion-positive non-small-cell lung cancer (NSCLC). We estimated the cost effectiveness of EML4-ALK fusion testing in combination with targeted first-line crizotinib treatment in Ontario. A cost-effectiveness analysis was conducted using a Markov model from the Canadian Public health (Ontario) perspective and a lifetime horizon in patients with stage IV NSCLC with nonsquamous histology. Transition probabilities and mortality rates were calculated from the Ontario Cancer Registry and Cancer Care Ontario New Drug Funding Program (CCO NDFP). Costs were obtained from the Ontario Case Costing Initiative, CCO NDFP, University Health Network, and literature. Molecular testing with first-line targeted crizotinib treatment in the population with advanced nonsquamous NSCLC resulted in a gain of 0.011 quality-adjusted life-years (QALYs) compared with standard care. The incremental cost was Canadian $2,725 per patient, and the incremental cost-effectiveness ratio (ICER) was $255,970 per QALY gained. Among patients with known EML4-ALK-positive advanced NSCLC, first-line crizotinib therapy provided 0.379 additional QALYs, cost an additional $95,043 compared with standard care, and produced an ICER of $250,632 per QALY gained. The major driver of cost effectiveness was drug price. EML4-ALK fusion testing in stage IV nonsquamous NSCLC with crizotinib treatment for ALK-positive patients is not cost effective in the setting of high drug costs and a low biomarker frequency in the population.

12 CFR 701.21 - Loans to members and lines of credit to members.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the decision to make a loan or establish a line of credit. A credit union may advance money to a... determines money market interest rates have risen over the preceding six-month period and prevailing interest... loan to finance the purchase of a mobile home if the mobile home will be used as the member-borrower's...

12 CFR 701.21 - Loans to members and lines of credit to members.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the decision to make a loan or establish a line of credit. A credit union may advance money to a... determines money market interest rates have risen over the preceding six-month period and prevailing interest... loan to finance the purchase of a mobile home if the mobile home will be used as the member-borrower's...

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…

TBT: Telecommunications-Based Training in the 90s (DELTA Programme--Action Line III). Proceedings of the Workshop (Madrid, Spain, January 21-22, 1991).

ERIC Educational Resources Information Center

Commission of the European Communities, Brussels (Belgium).

This report contains a collection of papers presented at a workshop on telecommunications-based training systems as part of the DELTA (Developing European Learning through Technological Advance) Action Line III, which addressed research in telecommunications for open and distance education. The following presentations are included: (1)…

Celebrating 40 Years. Early Developments. Volume 10, Number 1, Spring 2006

ERIC Educational Resources Information Center

Winton, Pam, Ed.; Buyssee, Virginia, Ed.; Hambrick, Catherine, Ed.

2006-01-01

Although the FPG Child Development Institute's primary mission is to generate new knowledge, this research is in the service of a higher goal: child and family well being. This goal is distilled in their tag line: "Advancing knowledge, enhancing lives." This phrase is not just a tag line--it encapsulates 40 years of striving to be an…

First-Line Atezolizumab Effective in Bladder Cancer.

PubMed

2016-08-01

Results from a phase II study indicate that the PD-L1 inhibitor atezolizumab, recently approved for advanced bladder cancer that's refractory to standard platinum chemotherapy, is effective as first-line therapy for this disease. Durable responses to atezolizumab were seen in nearly a quarter of the study patients, who were all ineligible to receive cisplatin. ©2016 American Association for Cancer Research.

Automatic Overset Grid Generation with Heuristic Feedback Control

NASA Technical Reports Server (NTRS)

Robinson, Peter I.

2001-01-01

An advancing front grid generation system for structured Overset grids is presented which automatically modifies Overset structured surface grids and control lines until user-specified grid qualities are achieved. The system is demonstrated on two examples: the first refines a space shuttle fuselage control line until global truncation error is achieved; the second advances, from control lines, the space shuttle orbiter fuselage top and fuselage side surface grids until proper overlap is achieved. Surface grids are generated in minutes for complex geometries. The system is implemented as a heuristic feedback control (HFC) expert system which iteratively modifies the input specifications for Overset control line and surface grids. It is developed as an extension of modern control theory, production rules systems and subsumption architectures. The methodology provides benefits over the full knowledge lifecycle of an expert system for knowledge acquisition, knowledge representation, and knowledge execution. The vector/matrix framework of modern control theory systematically acquires and represents expert system knowledge. Missing matrix elements imply missing expert knowledge. The execution of the expert system knowledge is performed through symbolic execution of the matrix algebra equations of modern control theory. The dot product operation of matrix algebra is generalized for heuristic symbolic terms. Constant time execution is guaranteed.

Advances in 7xx-nm fiber-coupled modules with application to Tm fiber laser pumping and DPAL (Conference Presentation)

NASA Astrophysics Data System (ADS)

Patterson, Steven G.; Guiney, Tina; Stapleton, Dean; Braker, Joseph; Alegria, Kim; Irwin, David A.; Ebert, Christopher

2017-02-01

DILAS has leveraged its industry-leading work in manufacturing low SWaP fiber-coupled modules extending the wavelength range to 793nm for Tm fiber laser pumping. Ideal for medical, industrial and military applications, modules spanning from single emitter-based 9W to TBar-based 200W of 793nm pump power will be discussed. The highlight is a lightweight module capable of <200W of 793nm pump power out of a package weighing < 400 grams. In addition, other modules spanning from single emitter-based 9W to TBar-based 200W of 793nm pump power will be presented. In addition, advances in DPAL modules, emitting at the technologically important wavelengths near 766nm and 780nm, will be detailed. Highlights include a fully microprocessor controlled fiber-coupled module that produces greater than 400W from a 600 micron core fiber and a line width of only 56.3pm. The micro-processor permits the automated center wavelength and line width tuning of the output over a range of output powers while retaining excellent line center and line width stability over time.

Swarm chondrosarcoma: a continued resource for chondroblastic-like extracellular matrix and chondrosarcoma biology research.

PubMed

Stevens, Jeff W

2013-01-01

Since its first description over four decades ago, the Swarm chondrosarcoma (Swarm rat chondrosarcoma, SRC) remains a valuable tool for studies of chondroblastic-like extracellular matrix (ECM) biology and as an animal model of human chondrosarcoma of histological grades I-III. Moreover, articular joints and skeletal anomalies such as arthritis as well as cartilage regeneration, skeletal development, tissue engineering, hard tissue tumorigenesis and space flight physiology are advanced through studies in hyaline cartilage-like models. With more than 500 articles published since the first report on the characteristics of mucopolysaccharides (glycosaminoglycans) of the tumor in 1971, several transplantable tumor and cell lines have been developed by multiple laboratories worldwide. This review describes the characterization of SRC tumors and cell lines, including the use of SRC lines as a resource for isolation and characterization of several ECM elements that have become vital for the advancement of our understanding of cartilage biology. Also presented is the importance of pertubation of ECM components and the influence of the tumor microenvironment on disease progression. Therapeutic failure and currently pursued avenues of intervention utilizing the SRC lines in treatment of chondrosarcoma are also discussed.

Flexible data registration and automation in semiconductor production

NASA Astrophysics Data System (ADS)

Dudde, Ralf; Staudt-Fischbach, Peter; Kraemer, Benedict

1997-08-01

The need for cost reduction and flexibility in semiconductor production will result in a wider application of computer based automation systems. With the setup of a new and advanced CMOS semiconductor line in the Fraunhofer Institute for Silicon Technology [ISIT, Itzehoe (D)] a new line information system (LIS) was introduced based on an advanced model for the underlying data structure. This data model was implemented into an ORACLE-RDBMS. A cellworks based system (JOSIS) was used for the integration of the production equipment, communication and automated database bookings and information retrievals. During the ramp up of the production line this new system is used for the fab control. The data model and the cellworks based system integration is explained. This system enables an on-line overview of the work in progress in the fab, lot order history and equipment status and history. Based on this figures improved production and cost monitoring and optimization is possible. First examples of the information gained by this system are presented. The modular set-up of the LIS system will allow easy data exchange with additional software tools like scheduler, different fab control systems like PROMIS and accounting systems like SAP. Modifications necessary for the integration of PROMIS are described.

Studies on low energy beam transport for high intensity high charged ions at IMP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Y., E-mail: yangyao@impcas.ac.cn; Lu, W.; Fang, X.

2014-02-15

Superconducting Electron Cyclotron Resonance ion source with Advanced design in Lanzhou (SECRAL) is an advanced fully superconducting ECR ion source at IMP designed to be operational at the microwave frequency of 18–24 GHz. The existing SECRAL beam transmission line is composed of a solenoid lens and a 110° analyzing magnet. Simulations of particle tracking with 3D space charge effect and realistic 3D magnetic fields through the line were performed using particle-in-cell code. The results of the beam dynamics show that such a low energy beam is very sensitive to the space charge effect and significantly suffers from the second-order aberrationmore » of the analyzing magnet resulting in large emittance. However, the second-order aberration could be reduced by adding compensating sextupole components in the beam line. On this basis, a new 110° analyzing magnet with relatively larger acceptance and smaller aberration is designed and will be used in the design of low energy beam transport line for a new superconducting ECR ion source SECRAL-II. The features of the analyzer and the corresponding beam trajectory calculation will be detailed and discussed in this paper.« less

A hybrid of B and T lymphoblastic cell line could potentially substitute dendritic cells to efficiently expand out Her-2/neu-specific cytotoxic T lymphocytes from advanced breast cancer patients in vitro.

PubMed

Chen, Sheng; Gu, Feifei; Li, Kang; Zhang, Kai; Liu, Yangyang; Liang, Jinyan; Gao, Wei; Wu, Gang; Liu, Li

2017-02-28

Adoptive transfer of cytotoxic T lymphocytes (CTLs) holds promises to cure cancer. However, this treatment is hindered by lacking a robust way to specifically expand out CTLs. Here, we developed a hybrid of B lymphoblastic cell line and T lymphoblastic cell line (T2 cells) as a substitute of dendritic cells, together with irradiated autologous peripheral blood mononuclear cell (PBMC) as feeder cells and rhIL-2, to activate and expand Her-2/neu-specific CD8 + T cells from human epidermal growth factor receptor 2 (Her-2/neu) and human leukocyte antigen (HLA)-A2 double positive advanced breast cancer patients in vitro. These Her-2/neu-loaded T2 cells reproducibly activated and expanded out Her-2/neu-specific CD8 + T cells to 10 7 in 8 weeks. Furthermore, these Her-2/neu-specific CD8 + T cells had good sensitivity of recognition and killing Her-2/neu-overexpressed breast cancer cell line SK.BR.3. This technique gives us another insight on how to rapidly obtain sufficient CTLs for adoptive cancer immunotherapy.

Raman Spectroscopy for In-Line Water Quality Monitoring — Instrumentation and Potential

PubMed Central

Li, Zhiyun; Deen, M. Jamal; Kumar, Shiva; Selvaganapathy, P. Ravi

2014-01-01

Worldwide, the access to safe drinking water is a huge problem. In fact, the number of persons without safe drinking water is increasing, even though it is an essential ingredient for human health and development. The enormity of the problem also makes it a critical environmental and public health issue. Therefore, there is a critical need for easy-to-use, compact and sensitive techniques for water quality monitoring. Raman spectroscopy has been a very powerful technique to characterize chemical composition and has been applied to many areas, including chemistry, food, material science or pharmaceuticals. The development of advanced Raman techniques and improvements in instrumentation, has significantly improved the performance of modern Raman spectrometers so that it can now be used for detection of low concentrations of chemicals such as in-line monitoring of chemical and pharmaceutical contaminants in water. This paper briefly introduces the fundamentals of Raman spectroscopy, reviews the development of Raman instrumentations and discusses advanced and potential Raman techniques for in-line water quality monitoring. PMID:25230309

Current therapeutic landscape for advanced gastroesophageal cancers

PubMed Central

Lopez, Anthony; Harada, Kazuto; Mizrak Kaya, Dilsa

2018-01-01

Treatment of advanced gastroesophageal cancers remains challenging for clinicians, patients, and caregivers alike. Despite considerable research, the therapeutic armamentarium is restricted and hardly personalized. In the first-line setting, trastuzumab with a fluoropyrimidine and platinum agent is the standard-of-care in patients with HER2-positive tumor. For the others, a platinum-based doublet (preferably with oxaliplatin) is recommended. Three-drug cytotoxic regimens should be reserved for exceptional cases where patients have good performance status. Triple combinations produce higher toxicity and provide marginal advantage. In the second line setting, the combination of paclitaxel and ramucirumab is preferred over all others. Currently, nothing is approved in the 3rd or later line. Nivolumab has resulted in an improved benefit in an Asian trial. Early trials of TAS-102, STAT3 inhibitors, anti-claudin 18.2 and other immune checkpoint inhibitors (alone or in combination) are ongoing. However, development of reproducible biomarkers for patient enrichment is critical for future progress. PMID:29666801

Raman spectroscopy for in-line water quality monitoring--instrumentation and potential.

PubMed

Li, Zhiyun; Deen, M Jamal; Kumar, Shiva; Selvaganapathy, P Ravi

2014-09-16

Worldwide, the access to safe drinking water is a huge problem. In fact, the number of persons without safe drinking water is increasing, even though it is an essential ingredient for human health and development. The enormity of the problem also makes it a critical environmental and public health issue. Therefore, there is a critical need for easy-to-use, compact and sensitive techniques for water quality monitoring. Raman spectroscopy has been a very powerful technique to characterize chemical composition and has been applied to many areas, including chemistry, food, material science or pharmaceuticals. The development of advanced Raman techniques and improvements in instrumentation, has significantly improved the performance of modern Raman spectrometers so that it can now be used for detection of low concentrations of chemicals such as in-line monitoring of chemical and pharmaceutical contaminants in water. This paper briefly introduces the fundamentals of Raman spectroscopy, reviews the development of Raman instrumentations and discusses advanced and potential Raman techniques for in-line water quality monitoring.

Clinical potential of nintedanib for the second-line treatment of advanced non-small-cell lung cancer: current evidence.

PubMed

Rothschild, Sacha I

2014-01-01

The therapeutic landscape in non-small-cell lung cancer (NSCLC) is changing. The description of molecular alterations leading to NSCLC carcinogenesis and progression (so-called oncogenic driver mutations) and the development of targeted agents interfering with the tumor-promoting intracellular signaling pathways have improved the outcome for many patients with advanced/metastatic NSCLC. However, many patients with stage IV NSCLC do not have one of the targetable predictive biomarkers, and are therefore in need of classical chemotherapy. This especially applies to squamous cell cancer. A platinum-based doublet chemotherapy is the standard of care for patients with stage IV NSCLC. As second-line therapies, docetaxel, pemetrexed, and the EGFR tyrosine-kinase inhibitor erlotinib have demonstrated benefit in Phase III randomized trials. Recently, the addition of the angiokinase inhibitor nintedanib to docetaxel has proven efficacious, and is a new treatment option in the second-line setting. Preclinical and clinical data of nintedanib for the treatment of lung cancer patients are reviewed here.

Clinical potential of nintedanib for the second-line treatment of advanced non-small-cell lung cancer: current evidence

PubMed Central

Rothschild, Sacha I

2014-01-01

The therapeutic landscape in non-small-cell lung cancer (NSCLC) is changing. The description of molecular alterations leading to NSCLC carcinogenesis and progression (so-called oncogenic driver mutations) and the development of targeted agents interfering with the tumor-promoting intracellular signaling pathways have improved the outcome for many patients with advanced/metastatic NSCLC. However, many patients with stage IV NSCLC do not have one of the targetable predictive biomarkers, and are therefore in need of classical chemotherapy. This especially applies to squamous cell cancer. A platinum-based doublet chemotherapy is the standard of care for patients with stage IV NSCLC. As second-line therapies, docetaxel, pemetrexed, and the EGFR tyrosine-kinase inhibitor erlotinib have demonstrated benefit in Phase III randomized trials. Recently, the addition of the angiokinase inhibitor nintedanib to docetaxel has proven efficacious, and is a new treatment option in the second-line setting. Preclinical and clinical data of nintedanib for the treatment of lung cancer patients are reviewed here. PMID:28210142

Perspectives for the high field approach in fusion research and advances within the Ignitor Program

NASA Astrophysics Data System (ADS)

Coppi, B.; Airoldi, A.; Albanese, R.; Ambrosino, G.; Belforte, G.; Boggio-Sella, E.; Cardinali, A.; Cenacchi, G.; Conti, F.; Costa, E.; D'Amico, A.; Detragiache, P.; De Tommasi, G.; DeVellis, A.; Faelli, G.; Ferraris, P.; Frattolillo, A.; Giammanco, F.; Grasso, G.; Lazzaretti, M.; Mantovani, S.; Merriman, L.; Migliori, S.; Napoli, R.; Perona, A.; Pierattini, S.; Pironti, A.; Ramogida, G.; Rubinacci, G.; Sassi, M.; Sestero, A.; Spillantini, S.; Tavani, M.; Tumino, A.; Villone, F.; Zucchi, L.

2015-05-01

The Ignitor Program maintains the objective of approaching D-T ignition conditions by incorporating systematical advances made with relevant high field magnet technology and with experiments on high density well confined plasmas in the present machine design. An additional objective is that of charting the development of the high field line of experiments that goes from the Alcator machine to the ignitor device. The rationale for this class of experiments, aimed at producing poloidal fields with the highest possible values (compatible with proven safety factors of known plasma instabilities) is given. On the basis of the favourable properties of high density plasmas produced systematically by this line of machines, the envisioned future for the line, based on novel high field superconducting magnets, includes the possibility of investigating more advanced fusion burn conditions than those of the D-T plasmas for which Ignitor is designed. Considering that a detailed machine design has been carried out (Coppi et al 2013 Nucl. Fusion 53 104013), the advances made in different areas of the physics and technology that are relevant to the Ignitor project are reported. These are included within the following sections of the present paper: main components issues, assembly and welding procedures; robotics criteria; non-linear feedback control; simulations with three-dimensional structures and disruption studies; ICRH and dedicated diagnostics systems; anomalous transport processes including self-organization for fusion burning regimes and the zero-dimensional model; tridimensional structures of the thermonuclear instability and control provisions; superconducting components of the present machine; envisioned experiments with high field superconducting magnets.

Cyclotron Lines in Accreting Neutron Star Spectra

NASA Astrophysics Data System (ADS)

Wilms, Jörn; Schönherr, Gabriele; Schmid, Julia; Dauser, Thomas; Kreykenbohm, Ingo

2009-05-01

Cyclotron lines are formed through transitions of electrons between discrete Landau levels in the accretion columns of accreting neutron stars with strong (1012 G) magnetic fields. We summarize recent results on the formation of the spectral continuum of such systems, describe recent advances in the modeling of the lines based on a modification of the commonly used Monte Carlo approach, and discuss new results on the dependence of the measured cyclotron line energy from the luminosity of transient neutron star systems. Finally, we show that Simbol-X will be ideally suited to build and improve the observational database of accreting and strongly magnetized neutron stars.

Implementation of immunotherapy in the treatment of advanced non-small cell lung cancer (NSCLC).

PubMed

Tsiara, Anna; Liontos, Michalis; Kaparelou, Maria; Zakopoulou, Roubini; Bamias, Aristotelis; Dimopoulos, Meletios-Athanasios

2018-04-01

Mechanisms of tumor immune surveillance and immune escape have been recently elucidated and led to the development of a new therapeutic field in oncology, that of immunotherapy. Immunotherapy aims to reactivate the immune system against cancer. Neoplasias like non-small cell lung cancer (NSCLC) are of particular interest and clinical studies with immunotherapeutic agents have shown significant survival benefit. Several agents have gained corresponding regulatory approvals. In particular, nivolumab, pembrolizumab and atezolizumab have been approved for second-line treatment of NSCLC, pembrolizumab is the only immune checkpoint inhibitor that has been approved in the first-line treatment and durvalumab is approved in the locally advanced disease. In this review, we aim to present the implementation of immunotherapy in the treatment of advanced NSCLC. We will discuss not only the approved regimens but also the future perspectives, the serious adverse events such as hyperprogression and the possible predictive markers that will aid the selection of the patients that will benefit from immunotherapy.

Implementation of immunotherapy in the treatment of advanced non-small cell lung cancer (NSCLC)

PubMed Central

Liontos, Michalis; Kaparelou, Maria; Zakopoulou, Roubini; Bamias, Aristotelis; Dimopoulos, Meletios-Athanasios

2018-01-01

Mechanisms of tumor immune surveillance and immune escape have been recently elucidated and led to the development of a new therapeutic field in oncology, that of immunotherapy. Immunotherapy aims to reactivate the immune system against cancer. Neoplasias like non-small cell lung cancer (NSCLC) are of particular interest and clinical studies with immunotherapeutic agents have shown significant survival benefit. Several agents have gained corresponding regulatory approvals. In particular, nivolumab, pembrolizumab and atezolizumab have been approved for second-line treatment of NSCLC, pembrolizumab is the only immune checkpoint inhibitor that has been approved in the first-line treatment and durvalumab is approved in the locally advanced disease. In this review, we aim to present the implementation of immunotherapy in the treatment of advanced NSCLC. We will discuss not only the approved regimens but also the future perspectives, the serious adverse events such as hyperprogression and the possible predictive markers that will aid the selection of the patients that will benefit from immunotherapy. PMID:29862233

Fieldcrest Cannon, Inc. Advanced Technical Preparation. Statistical Process Control (SPC). PRE-SPC 11: SPC & Graphs. Instructor Book.

ERIC Educational Resources Information Center

Averitt, Sallie D.

This instructor guide, which was developed for use in a manufacturing firm's advanced technical preparation program, contains the materials required to present a learning module that is designed to prepare trainees for the program's statistical process control module by improving their basic math skills in working with line graphs and teaching…

Lapatinib for treatment of advanced or metastasized breast cancer: systematic review.

PubMed

Riera, Rachel; Soárez, Patrícia Coelho de; Puga, Maria Eduarda Dos Santos; Ferraz, Marcos Bosi

2009-09-01

Around 16% to 20% of women with breast cancer have advanced, metastasized breast cancer. At this stage, the disease is treatable, but not curable. The objective here was to assess the effectiveness of lapatinib for treating patients with advanced or metastasized breast cancer. Systematic review of the literature, developed at Centro Paulista de Economia da Saúde (CPES), Universidade Federal de São Paulo (Unifesp). Systematic review with searches in virtual databases (PubMed, Lilacs [Literatura Latino-Americana e do Caribe em Ciências da Saúde], Cochrane Library, Scirus and Web of Science) and manual search. Only one clinical trial that met the selection criteria was found. This study showed that lapatinib in association with capecitabine reduced the risk of cancer progression by 51% (95% confidence interval, CI: 0.34-0.71; P < 0.001), compared with capecitabine alone, without any increase in severe adverse effects. The combination of lapatinib plus capecitabine was more effective than capecitabine alone for reducing the risk of cancer progression. Further randomized clinical trials need to be carried out with the aim of assessing the effectiveness of lapatinib as monotherapy or in association for first-line or second-line treatment of advanced breast cancer.

Summary and recent results from the NASA advanced High Speed Propeller Research Program

NASA Technical Reports Server (NTRS)

Mitchell, G. A.; Mikkelson, D. C.

1982-01-01

Advanced high-speed propellers offer large performance improvements for aircraft that cruise in the Mach 0.7 to 0.8 speed regime. The current status of the NASA research program on high-speed propeller aerodynamics, acoustics, and aeroelastics is described. Recent wind tunnel results for five 8- to 10-blade advanced models are compared with analytical predictions. Test results show that blade sweep was important in achieving net efficiencies near 80 percent at Mach 0.8 and reducing near-field cruise noise by dB. Lifting line and lifting surface aerodynamic analysis codes are under development and some initial lifting line results are compared with propeller force and probe data. Some initial laser velocimeter measurements of the flow field velocities of an 8-bladed 45 deg swept propeller are shown. Experimental aeroelastic results indicate that cascade effects and blade sweep strongly affect propeller aeroelastic characteristics. Comparisons of propeller near-field noise data with linear acoustic theory indicate that the theory adequate predicts near-field noise for subsonic tip speeds but overpredicts the noise for supersonic tip speeds. Potential large gains in propeller efficiency of 7 to 11 percent at Mach 0.8 may be possible with advanced counter-rotation propellers.

Advances of Molecular Targeted Therapy in Gastric Cancer.

PubMed

Cetin, Bulent; Gumusay, Ozge; Cengiz, Mustafa; Ozet, Ahmet

2016-06-01

Gastric cancer is the second most common cause of cancer-related death in the world, and its prognosis remains poor with a median overall survival of 12 months for advanced disease. Advances in the understanding of molecular genetics have led to the development of directed molecular targeted therapy in gastric cancer, leading to improve patient outcomes and quality of life. In the treatment of human epidermal growth factor receptor 2 (HER2)-positive gastric cancer, the addition of trastuzumab significantly improves survival in the first-line setting of therapy. Ramucirumab, an antibody directed against vascular endothelial growth factor receptor 2, significantly improved progression-free and overall survival and has been approved for second-line treatment of gastric cancer. Anti-mesenchymal-epithelial transition (c-MET), mammalian target of rapamycin inhibitors, and polo-like kinase 1 inhibitors are under investigation as a novel therapeutic option for the treatment of gastric cancer. The novel therapies target the key immune checkpoint interaction between a T cell co-inhibitory receptor called programmed death 1 (PD-1) and one of its immunosuppressive ligands, PD-L1. This article reviews molecular targeted therapies in gastric cancer, in light of recent advances.

Ifosfamide, mesna and epirubicin as second-line chemotherapy in advanced breast cancer.

PubMed

Kiraz, S; Baltali, E; Güler, N; Barista, I; Benekli, M; Celik, I; Güllü, I H; Kars, A; Tekuzman, G; Firat, D

1996-08-01

The ifosfamide, mesna and epirubicin (IMEpi) combination is administered to 16 patients having advanced metastatic breast carcinoma as second-line chemotherapy. We observed complete response in 6%, partial response in 44% (total overall response rate of 50%), stable disease in 12% and progressive disease in the remaining 38% of the patients. The median remission duration in responders was calculated to be 9.6 months. IMEpi regimen had a tolerable toxicity profile including alopecia, nausea and vomiting, microscopic hematuria, leukopenia and neurotoxicity in which serious complications necessitating discontinuation of the chemotherapy were not encountered. It might be concluded that IMEpi chemotherapy combination is an effective alternative among schedules in the management of patients with stage IV breast carcinoma without serious side effects.

Dynamic Responses and Vibration Control of the Transmission Tower-Line System: A State-of-the-Art Review

PubMed Central

Chen, Bo; Guo, Wei-hua; Li, Peng-yun; Xie, Wen-ping

2014-01-01

This paper presented an overview on the dynamic analysis and control of the transmission tower-line system in the past forty years. The challenges and future developing trends in the dynamic analysis and mitigation of the transmission tower-line system under dynamic excitations are also put forward. It also reviews the analytical models and approaches of the transmission tower, transmission lines, and transmission tower-line systems, respectively, which contain the theoretical model, finite element (FE) model and the equivalent model; shows the advances in wind responses of the transmission tower-line system, which contains the dynamic effects under common wind loading, tornado, downburst, and typhoon; and discusses the dynamic responses under earthquake and ice loads, respectively. The vibration control of the transmission tower-line system is also reviewed, which includes the magnetorheological dampers, friction dampers, tuned mass dampers, and pounding tuned mass dampers. PMID:25105161

Workable male sterility systems for hybrid rice: Genetics, biochemistry, molecular biology, and utilization.

PubMed

Huang, Jian-Zhong; E, Zhi-Guo; Zhang, Hua-Li; Shu, Qing-Yao

2014-12-01

The exploitation of male sterility systems has enabled the commercialization of heterosis in rice, with greatly increased yield and total production of this major staple food crop. Hybrid rice, which was adopted in the 1970s, now covers nearly 13.6 million hectares each year in China alone. Various types of cytoplasmic male sterility (CMS) and environment-conditioned genic male sterility (EGMS) systems have been applied in hybrid rice production. In this paper, recent advances in genetics, biochemistry, and molecular biology are reviewed with an emphasis on major male sterility systems in rice: five CMS systems, i.e., BT-, HL-, WA-, LD- and CW- CMS, and two EGMS systems, i.e., photoperiod- and temperature-sensitive genic male sterility (P/TGMS). The interaction of chimeric mitochondrial genes with nuclear genes causes CMS, which may be restored by restorer of fertility (Rf) genes. The PGMS, on the other hand, is conditioned by a non-coding RNA gene. A survey of the various CMS and EGMS lines used in hybrid rice production over the past three decades shows that the two-line system utilizing EGMS lines is playing a steadily larger role and TGMS lines predominate the current two-line system for hybrid rice production. The findings and experience gained during development and application of, and research on male sterility in rice not only advanced our understanding but also shed light on applications to other crops.

Microalgal process-monitoring based on high-selectivity spectroscopy tools: status and future perspectives.

PubMed

Podevin, Michael; Fotidis, Ioannis A; Angelidaki, Irini

2018-08-01

Microalgae are well known for their ability to accumulate lipids intracellularly, which can be used for biofuels and mitigate CO 2 emissions. However, due to economic challenges, microalgae bioprocesses have maneuvered towards the simultaneous production of food, feed, fuel, and various high-value chemicals in a biorefinery concept. On-line and in-line monitoring of macromolecules such as lipids, proteins, carbohydrates, and high-value pigments will be more critical to maintain product quality and consistency for downstream processing in a biorefinery to maintain and valorize these markets. The main contribution of this review is to present current and prospective advances of on-line and in-line process analytical technology (PAT), with high-selectivity - the capability of monitoring several analytes simultaneously - in the interest of improving product quality, productivity, and process automation of a microalgal biorefinery. The high-selectivity PAT under consideration are mid-infrared (MIR), near-infrared (NIR), and Raman vibrational spectroscopies. The current review contains a critical assessment of these technologies in the context of recent advances in software and hardware in order to move microalgae production towards process automation through multivariate process control (MVPC) and software sensors trained on "big data". The paper will also include a comprehensive overview of off-line implementations of vibrational spectroscopy in microalgal research as it pertains to spectral interpretation and process automation to aid and motivate development.

A LINE-1 Component to Human Aging: Do LINE elements exact a longevity cost for evolutionary advantage?

PubMed Central

Laurent, Georges St.; Hammell, Neil; McCaffrey, Timothy A.

2010-01-01

Advancing age remains the largest risk factor for devastating diseases, such as heart disease, stroke, and cancer. The mechanisms by which advancing age predisposes to disease are now beginning to unfold, due in part, to genetic and environmental manipulations of longevity in lower organisms. Converging lines of evidence suggest that DNA damage may be a final common pathway linking several proposed mechanisms of aging. The present review forwards a theory for an additional aging pathway that involves modes of inherent genetic instability. Long interspersed nuclear elements (LINEs) are endogenous non-LTR retrotransposons that compose about 20% of the human genome. The LINE-1 (L1) gene products, ORF1p and ORF2p, possess mRNA binding, endonuclease, and reverse transcriptase activity that enable retrotransposition. While principally active only during embryogenesis, L1 transcripts are detected in adult somatic cells under certain conditions. The present hypothesis proposes that L1s act as an ‘endogenous clock’, slowly eroding genomic integrity by competing with the organism’s double-strand break repair mechanism. Thus, while L1s are an accepted mechanism of genetic variation fueling evolution, it is proposed that longevity is negatively impacted by somatic L1 activity. The theory predicts testable hypotheses about the relationship between L1 activity, DNA repair, healthy aging, and longevity. PMID:20346965

Reinforcement Learning Strategies for Clinical Trials in Non-small Cell Lung Cancer

PubMed Central

Zhao, Yufan; Zeng, Donglin; Socinski, Mark A.; Kosorok, Michael R.

2010-01-01

Summary Typical regimens for advanced metastatic stage IIIB/IV non-small cell lung cancer (NSCLC) consist of multiple lines of treatment. We present an adaptive reinforcement learning approach to discover optimal individualized treatment regimens from a specially designed clinical trial (a “clinical reinforcement trial”) of an experimental treatment for patients with advanced NSCLC who have not been treated previously with systemic therapy. In addition to the complexity of the problem of selecting optimal compounds for first and second-line treatments based on prognostic factors, another primary goal is to determine the optimal time to initiate second-line therapy, either immediately or delayed after induction therapy, yielding the longest overall survival time. A reinforcement learning method called Q-learning is utilized which involves learning an optimal regimen from patient data generated from the clinical reinforcement trial. Approximating the Q-function with time-indexed parameters can be achieved by using a modification of support vector regression which can utilize censored data. Within this framework, a simulation study shows that the procedure can extract optimal regimens for two lines of treatment directly from clinical data without prior knowledge of the treatment effect mechanism. In addition, we demonstrate that the design reliably selects the best initial time for second-line therapy while taking into account the heterogeneity of NSCLC across patients. PMID:21385164

Factors Associated with Type 2 Diabetes Mellitus Treatment Choice Across Four European Countries.

PubMed

Heintjes, Edith M; Overbeek, Jetty A; Hall, Gillian C; Prieto-Alhambra, Daniel; Lapi, Francesco; Hammar, Niklas; Bezemer, Irene D

2017-11-01

The aim of this analysis was to identify factors associated with the choice of type 2 diabetes mellitus (T2DM) therapy at the time of intensification of antidiabetic treatment across 4 European countries. Antidiabetic drug prescription/dispensing records and patients' characteristics were obtained from the electronic health care records of patients with T2DM from the Netherlands (NL), Italy, and Spain (ES) (all, 2007-2011); and the United Kingdom (UK; 2008-2012). Oral monotherapy was defined as first-line; oral dual therapy, as second-line; >2 oral treatments or oral combined with an injectable, as third-line; and injectables only, as fourth-line treatment. Treatment intensification was defined as the start of a higher line of treatment. Comedication, comorbidities, clinical parameters, and other factors associated with treatment choice were identified using multivariate relative risk estimation by Poisson regression with robust error variance. In the 5-year study period, 485,120 patients (79% of the treated T2DM population) underwent treatment intensification. Changes in treatment choice were clearly visible over the study period, such as a decline in the use of thiazolidinediones (NL, ES, UK) and increases in the use of dipeptidyl peptidase-4 inhibitors (DPP4i) (NL, ES, UK) and glucagon-like peptide-1 receptor agonists (UK). With first-line treatment, advanced age and renal comorbidity were associated with the use of sulfonylureas (SUs; all countries), whereas high body mass index (BMI) was inversely associated with SU use in the United Kingdom and Spain. With second-line treatment, advanced age was associated with metformin + SU use (all countries); and renal comorbidity with SU + DPP4i use in the United Kingdom and the Netherlands. High BMI was associated with metformin + thiazolidinedione (TZD) use in the United Kingdom and Spain, and with metformin + DPP4i in the United Kingdom. With third-line treatment, advanced age and renal comorbidity were associated with the use of SU + insulin (NL, ES, UK). Hemoglobin A 1c >8.5% was positively associated, and high BMI was inversely associated, with the use of any third-line combination containing insulin. Across treatment lines TZD and metformin were negatively associated with renal and cardiac morbidity. Second and third line treatment choices strongly depended on prior treatments. With fourth-line treatment, women were more likely to receive glucagon-like peptide-1 receptor agonists than were men in the United Kingdom and Spain. The results suggest that the main factors driving treatment choice at any stage of intensification were age, hemoglobin A 1c , BMI, renal and cardiac morbidity, and treatment history. These drivers were consistent with guidelines on, and contraindications of, specific medications. Differences between countries were generally consistent with, but not solely attributable to, differences in local guidelines and reimbursement policies. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

The Evolving Treatment Landscape of Advanced Renal Cell Carcinoma in Patients Progressing after VEGF Inhibition

PubMed Central

Barata, Pedro C.; Ornstein, Moshe C.

2017-01-01

Despite significant changes in the therapeutic landscape of renal cell carcinoma, the majority of patients with metastatic disease eventually progress after first-line treatment with vascular endothelial growth factor receptors (VEGFR) tyrosine kinase inhibitor (TKI) therapy. Understanding existing data on subsequent therapies is crucial to define an optimal treatment sequence following first-line failure. This review examines the data supporting currently approved agents in this setting and provides a framework for decision-making regarding treatment sequencing beyond first-line therapy with VEGFR TKIs. PMID:28725539

Observation of EX Hydrae with ASCA

NASA Technical Reports Server (NTRS)

Ishida, Manabu; Mukai, Koji; Osborne, Julian P.

1994-01-01

We have observed the intermediate polar EX Hya with Advanced Satellite for Cosmology and Astrophysics (ASCA), and have clearly detected He-like and H-like K alpha emission lines from Mg to Fe. The intensity ratios of these pairs of lines are not compatible with an isothermal plasma, and a temperature distribution can no longer be parameterized by the conventional two emission component model. We have successfully decomposed iron line emission into thermal plasma component and flourescent component. The equivalent width of the flourescent component is approximately 80 eV.

Advanced On-the-Job Training System: Transition Plan

DTIC Science & Technology

1990-05-01

992NP. The 992NP is connected to the UDS CSU/DSU 56K modem with standard telephone wire (four wire). The 56K modem is connected to the 56K communications...UDS CSU/DSU 56K modems . One 56K line from Brooks is connected to Building 428 and the other line is connected to Building 1101. Building 1101 acts as...the central communications node at Bergstrom AFB as illustrated in Figure A- 4. The 56K lines from Brooks are connected to the 56K modems which are in

Neuropilin-2 mediates VEGF-C–induced lymphatic sprouting together with VEGFR3

PubMed Central

Xu, Yunling; Yuan, Li; Mak, Judy; Pardanaud, Luc; Caunt, Maresa; Kasman, Ian; Larrivée, Bruno; del Toro, Raquel; Suchting, Steven; Medvinsky, Alexander; Silva, Jillian; Yang, Jian; Thomas, Jean-Léon; Koch, Alexander W.; Alitalo, Kari

2010-01-01

Vascular sprouting is a key process-driving development of the vascular system. In this study, we show that neuropilin-2 (Nrp2), a transmembrane receptor for the lymphangiogenic vascular endothelial growth factor C (VEGF-C), plays an important role in lymphatic vessel sprouting. Blocking VEGF-C binding to Nrp2 using antibodies specifically inhibits sprouting of developing lymphatic endothelial tip cells in vivo. In vitro analyses show that Nrp2 modulates lymphatic endothelial tip cell extension and prevents tip cell stalling and retraction during vascular sprout formation. Genetic deletion of Nrp2 reproduces the sprouting defects seen after antibody treatment. To investigate whether this defect depends on Nrp2 interaction with VEGF receptor 2 (VEGFR2) and/or 3, we intercrossed heterozygous mice lacking one allele of these receptors. Double-heterozygous nrp2vegfr2 mice develop normally without detectable lymphatic sprouting defects. In contrast, double-heterozygote nrp2vegfr3 mice show a reduction of lymphatic vessel sprouting and decreased lymph vessel branching in adult organs. Thus, interaction between Nrp2 and VEGFR3 mediates proper lymphatic vessel sprouting in response to VEGF-C. PMID:20065093

Dahl (S × R) Rat Congenic Strain Analysis Confirms and Defines a Chromosome 17 Spatial Navigation Quantitative Trait Locus to <10 Mbp

PubMed Central

Herrera, Victoria L.; Pasion, Khristine A.; Tan, Glaiza A.; Ruiz-Opazo, Nelson

2013-01-01

A quantitative trait locus (QTL) linked with ability to find a platform in the Morris Water Maze (MWM) was located on chromosome 17 (Nav-5 QTL) using intercross between Dahl S and Dahl R rats. We developed two congenic strains, S.R17A and S.R17B introgressing Dahl R-chromosome 17 segments into Dahl S chromosome 17 region spanning putative Nav-5 QTL. Performance analysis of S.R17A, S.R17B and Dahl S rats in the Morris water maze (MWM) task showed a significantly decreased spatial navigation performance in S.R17B congenic rats when compared with Dahl S controls (P = 0.02). The S.R17A congenic segment did not affect MWM performance delimiting Nav-5 to the chromosome 17 65.02–74.66 Mbp region. Additional fine mapping is necessary to identify the specific gene variant accounting for Nav-5 effect on spatial learning and memory in Dahl rats. PMID:23469157

Genome Sequencing and Mapping Reveal Loss of Heterozygosity as a Mechanism for Rapid Adaptation in the Vegetable Pathogen Phytophthora capsici

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamour, Kurt H.; Mudge, Joann; Gobena, Daniel

2012-02-07

The oomycete vegetable pathogen Phytophthora capsici has shown remarkable adaptation to fungicides and new hosts. Like other members of this destructive genus, P. capsici has an explosive epidemiology, rapidly producing massive numbers of asexual spores on infected hosts. In addition, P. capsici can remain dormant for years as sexually recombined oospores, making it difficult to produce crops at infested sites, and allowing outcrossing populations to maintain significant genetic variation. Genome sequencing, development of a high-density genetic map, and integrative genomic or genetic characterization of P. capsici field isolates and intercross progeny revealed significant mitotic loss of heterozygosity (LOH) in diversemore » isolates. LOH was detected in clonally propagated field isolates and sexual progeny, cumulatively affecting >30percent of the genome. LOH altered genotypes for more than 11,000 single-nucleotide variant sites and showed a strong association with changes in mating type and pathogenicity. Overall, it appears that LOH may provide a rapid mechanism for fixing alleles and may be an important component of adaptability for P. capsici.« less

Structural origin underlying poor glass forming ability of Al metallic glass

NASA Astrophysics Data System (ADS)

Li, F.; Liu, X. J.; Hou, H. Y.; Chen, G.; Chen, G. L.

2011-07-01

We performed molecular dynamics simulations to study the glass formation and local atomic structure of rapidly quenched Al. Both potential energy and structural parameters indicate that the glass transition temperature of amorphous Al is as low as 300 K, which may lead to the poor thermal stability of the amorphous Al as it is prone to crystallize even at room temperature. Voronoi polyhedra analysis reveals that the most popular polyhedron is the deformed body-centered cubic (bcc) cluster characterized by the index < 0, 3, 6, 4 > in the amorphous Al, while the icosahedron with the index < 0, 0, 12, 0 > is always predominant in bulk metallic glass formers with excellent glass forming ability (GFA). Moreover, these deformed-bcc short-range orders can make up medium-range orders via the linkage of vertex-, edge-, face-, intercrossed-shared atoms, which are believed to more easily transform into face-centered cubic (fcc) Al nanocrystal compared with the icosahedral clusters in terms of the symmetrical similarity between bcc and fcc structures. This finding could unveil the structural origin of poor GFA of Al-based alloys.

Air traffic control by distributed management in a MLS environment

NASA Technical Reports Server (NTRS)

Kreifeldt, J. G.; Parkin, L.; Hart, S.

1977-01-01

The microwave landing system (MLS) is a technically feasible means for increasing runway capacity since it could support curved approaches to a short final. The shorter the final segment of the approach, the wider the variety of speed mixes possible so that theoretically, capacity would ultimately be limited by runway occupance time only. An experiment contrasted air traffic control in a MLS environment under a centralized form of management and under distributed management which was supported by a traffic situation display in each of the 3 piloted simulators. Objective flight data, verbal communication and subjective responses were recorded on 18 trial runs lasting about 20 minutes each. The results were in general agreement with previous distributed management research. In particular, distributed management permitted a smaller spread of intercrossing times and both pilots and controllers perceived distributed management as the more 'ideal' system in this task. It is concluded from this and previous research that distributed management offers a viable alternative to centralized management with definite potential for dealing with dense traffic in a safe, orderly and expeditious manner.

No clustering for linkage map based on low-copy and undermethylated microsatellites.

PubMed

Zhou, Yi; Gwaze, David P; Reyes-Valdés, M Humberto; Bui, Thomas; Williams, Claire G

2003-10-01

Clustering has been reported for conifer genetic maps based on hypomethylated or low-copy molecular markers, resulting in uneven marker distribution. To test this, a framework genetic map was constructed from three types of microsatellites: low-copy, undermethylated, and genomic. These Pinus taeda L. microsatellites were mapped using a three-generation pedigree with 118 progeny. The microsatellites were highly informative; of the 32 markers in intercross configuration, 29 were segregating for three or four alleles in the progeny. The sex-averaged map placed 51 of the 95 markers in 15 linkage groups at LOD > 4.0. No clustering or uneven distribution across the genome was observed. The three types of P. taeda microsatellites were randomly dispersed within each linkage group. The 51 microsatellites covered a map distance of 795 cM, an average distance of 21.8 cM between markers, roughly half of the estimated total map length. The minimum and maximum distances between any two bins was 4.4 and 45.3 cM, respectively. These microsatellites provided anchor points for framework mapping for polymorphism in P. taeda and other closely related hard pines.

Observation and analysis of self-amplified spontaneous emission at the APS low-energy undulator test line

NASA Astrophysics Data System (ADS)

Arnold, N. D.; Attig, J.; Banks, G.; Bechtold, R.; Beczek, K.; Benson, C.; Berg, S.; Berg, W.; Biedron, S. G.; Biggs, J. A.; Borland, M.; Boerste, K.; Bosek, M.; Brzowski, W. R.; Budz, J.; Carwardine, J. A.; Castro, P.; Chae, Y.-C.; Christensen, S.; Clark, C.; Conde, M.; Crosbie, E. A.; Decker, G. A.; Dejus, R. J.; DeLeon, H.; Den Hartog, P. K.; Deriy, B. N.; Dohan, D.; Dombrowski, P.; Donkers, D.; Doose, C. L.; Dortwegt, R. J.; Edwards, G. A.; Eidelman, Y.; Erdmann, M. J.; Error, J.; Ferry, R.; Flood, R.; Forrestal, J.; Freund, H.; Friedsam, H.; Gagliano, J.; Gai, W.; Galayda, J. N.; Gerig, R.; Gilmore, R. L.; Gluskin, E.; Goeppner, G. A.; Goetzen, J.; Gold, C.; Gorski, A. J.; Grelick, A. E.; Hahne, M. W.; Hanuska, S.; Harkay, K. C.; Harris, G.; Hillman, A. L.; Hogrefe, R.; Hoyt, J.; Huang, Z.; Jagger, J. M.; Jansma, W. G.; Jaski, M.; Jones, S. J.; Keane, R. T.; Kelly, A. L.; Keyser, C.; Kim, K.-J.; Kim, S. H.; Kirshenbaum, M.; Klick, J. H.; Knoerzer, K.; Koldenhoven, R. J.; Knott, M.; Labuda, S.; Laird, R.; Lang, J.; Lenkszus, F.; Lessner, E. S.; Lewellen, J. W.; Li, Y.; Lill, R. M.; Lumpkin, A. H.; Makarov, O. A.; Markovich, G. M.; McDowell, M.; McDowell, W. P.; McNamara, P. E.; Meier, T.; Meyer, D.; Michalek, W.; Milton, S. V.; Moe, H.; Moog, E. R.; Morrison, L.; Nassiri, A.; Noonan, J. R.; Otto, R.; Pace, J.; Pasky, S. J.; Penicka, J. M.; Pietryla, A. F.; Pile, G.; Pitts, C.; Power, J.; Powers, T.; Putnam, C. C.; Puttkammer, A. J.; Reigle, D.; Reigle, L.; Ronzhin, D.; Rotela, E. R.; Russell, E. F.; Sajaev, V.; Sarkar, S.; Scapino, J. C.; Schroeder, K.; Seglem, R. A.; Sereno, N. S.; Sharma, S. K.; Sidarous, J. F.; Singh, O.; Smith, T. L.; Soliday, R.; Sprau, G. A.; Stein, S. J.; Stejskal, B.; Svirtun, V.; Teng, L. C.; Theres, E.; Thompson, K.; Tieman, B. J.; Torres, J. A.; Trakhtenberg, E. M.; Travish, G.; Trento, G. F.; Vacca, J.; Vasserman, I. B.; Vinokurov, N. A.; Walters, D. R.; Wang, J.; Wang, X. J.; Warren, J.; Wesling, S.; Weyer, D. L.; Wiemerslage, G.; Wilhelmi, K.; Wright, R.; Wyncott, D.; Xu, S.; Yang, B.-X.; Yoder, W.; Zabel, R. B.

2001-12-01

Exponential growth of self-amplified spontaneous emission at 530 nm was first experimentally observed at the Advanced Photon Source low-energy undulator test line in December 1999. Since then, further detailed measurements and analysis of the results have been made. Here, we present the measurements and compare these with calculations based on measured electron beam properties and theoretical expectations.

Genetic variation in salt tolerance during seed germination in a backcross inbred line population and advanced breeding lines derived from upland cotton x pima cotton

USDA-ARS?s Scientific Manuscript database

Seed germination is a crucial phase of the plant life cycle that affects its establishment and productivity. However, information on salt tolerance at this phase is limited. Pima cotton (Gossypium barbadense L.) may be more salt tolerant during germination than Upland cotton (G. hirsutum L.) based o...

ANIMAL COGNITION. Response to Comments on "Number-space mapping in the newborn chick resembles humans' mental number line".

PubMed

Rugani, Rosa; Vallortigara, Giorgio; Priftis, Konstantinos; Regolin, Lucia

2015-06-26

Mangalam and Karve raise concerns on whether our results demonstrate a mental number line, suggesting auxiliary experiments. Further data analyses show that their methodological concerns are not founded. Harshaw suggests that a side bias could have affected our results. We show that this concern is also unfounded. Copyright © 2015, American Association for the Advancement of Science.

ANIMAL COGNITION. Comment on "Number-space mapping in the newborn chick resembles humans' mental number line".

PubMed

Harshaw, Christopher

2015-06-26

Rugani et al. (Reports, 30 January 2015, p. 534) presented evidence that domestic chicks employ a "mental number line." I argue that the hypothesis testing used to support this claim unjustifiably assumes that domestic chicks are unbiased when choosing between identical stimuli presented to their left and right. Copyright © 2015, American Association for the Advancement of Science.

Real-world practice patterns for patients with advanced non-small cell lung cancer: multicenter retrospective cohort study in Japan.

PubMed

Isobe, Hiroshi; Mori, Kiyoshi; Minato, Koichi; Katsura, Hideki; Taniguchi, Kazuko; Arunachalam, Ashwini; Kothari, Smita; Cao, Xiting; Kato, Terufumi

2017-01-01

Recommended therapies for advanced/metastatic non-small cell lung cancer (NSCLC) have changed with the advent of targeted therapies. The objectives of this retrospective chart review study were to describe treatment patterns, biomarker testing practices, and health care resource use for advanced NSCLC at 5 sites in Japan. We studied anonymized medical record data of patients aged ≥18 years who initiated systemic therapy for newly diagnosed stage IIIB or IV NSCLC from January 2011 through June 2013. Data were analyzed descriptively by histology and mutation status. Overall survival was estimated using the Kaplan-Meier method. We studied 175 patients, including 43 (25%), 129 (74%), and 3 (2%) with squamous, nonsquamous, and unknown NSCLC histology, respectively; 83% had stage IV NSCLC. Overall, 123 patients (70%) were male; the median age was 70 years (range, 47-86); and 33 (19%) were never-smokers. In the nonsquamous cohort, 105 (81%) and 25 (19%) of patients were tested for epidermal growth factor receptor ( EGFR ) mutation and anaplastic lymphoma kinase ( ALK ) rearrangement, respectively; 44 (42%) had EGFR -positive NSCLC and 2 (8%) had ALK -positive NSCLC, including 26/46 (57%) women and 21/46 (46%) never-smokers. In the squamous cohort, 17 (40%) and 4 (9%), respectively, were tested; 1 EGFR -positive tumor was detected. After first-line therapy, 105 (60%) patients received second-line, and 54/105 (51%; or 31% overall) received third-line therapy. EGFR tyrosine kinase inhibitors were most commonly prescribed for EGFR -positive NSCLC across all lines. In the nonsquamous EGFR / ALK -negative/unknown cohort, most received first-line platinum combinations, particularly younger patients (78% ≥75 years vs 93% <75 years old). The average hospitalization was 21 days/admission. The median (95% CI) overall survival from start of first-line therapy was 9.9 months (7.6-11.7) for all patients and 17.9 months (9.9-24.4) for patients with EGFR / ALK -positive status. Biomarker testing is common for nonsquamous NSCLC at the 5 Japanese study sites. Treatment is personalized by mutation status and age, per guideline recommendations.

Third-Line Chemotherapy for Metastatic Urothelial Cancer: A Retrospective Observational Study

PubMed Central

Di Lorenzo, Giuseppe; Buonerba, Carlo; Bellelli, Teresa; Romano, Concetta; Montanaro, Vittorino; Ferro, Matteo; Benincasa, Alfonso; Ribera, Dario; Lucarelli, Giuseppe; De Cobelli, Ottavio; Sonpavde, Guru; De Placido, Sabino

2015-01-01

Abstract The prognosis of locally advanced (T3/T4 or N1) and metastatic disease urothelial carcinoma is poor. In this retrospective study, we reviewed data about patients receiving third-line chemotherapy for metastatic disease, in view of the lack of data in this setting. We retrospectively analyzed medical records of patients with a pathologic diagnosis of urothelial carcinoma treated with systemic chemotherapy for metastatic disease at 4 participating Institutions between January, 2010, and January, 2015. Cox proportional hazards regression was used to evaluate the association of the chemotherapy agent used versus others with overall survival, adjusted for 5 externally validated prognostic factors in advanced urothelial carcinoma. Of 182 patients that received first-line chemotherapy/adjuvant chemotherapy as defined above, 116 patients (63.73%) received second-line salvage treatment. Fifty-two patients were finally included in this analysis, whereas 9 were excluded due to missing data. Third-line chemotherapy was based on cyclophosphamide, platinum, vinflunine, taxanes, and gemcitabine in 16, 12, 11, 10, and 3 patients, respectively. Median PFS (progression-free survival) and OS (overall survival) of the population were 13 (10–17) and 31 (28–36) weeks. Single-agent cyclophosphamide was associated with a PFS of 18 (13–22) and an OS of 38 (33–41) weeks, whereas platinum-based combinations were associated with a PFS of 5 weeks and an OS of 8 weeks. Multivariate analysis showed improved survival in patients treated with cyclophosphamide (hazard ratio (HR) = 0.42; 95% CI: 0.20–0.89; P = 0.025) and a worse survival in those treated with platinum-based regimens (HR: 4.37; 95% CI = 1.95–9.77; P < 0.01). We observed a significantly longer overall survival in patients receiving single-agent cyclophosphamide, with few grade 3 to 4 toxicities. Further studies should assess the efficacy of metronomic single-agent cyclophosphamide in advanced lines of treatment, as it may yield a survival benefit with low costs and no detrimental effects on quality of life. PMID:26705213

Targeted erlotinib for first-line treatment of advanced non-small cell lung cancer: a budget impact analysis.

PubMed

Bajaj, Preeti S; Veenstra, David L; Goertz, Hans-Peter; Carlson, Josh J

2014-08-01

A recent phase III trial showed that patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor specific EGFR mutations significantly benefit from first-line treatment with erlotinib compared to chemotherapy. This study sought to estimate the budget impact if coverage for EGFR testing and erlotinib as first-line therapy were provided in a hypothetical 500,000-member managed care plan. The budget impact model was developed from a US health plan perspective to evaluate administration of the EGFR test and treatment with erlotinib for EGFR-positive patients, compared to non-targeted treatment with chemotherapy. The eligible patient population was estimated from age-stratified SEER incidence data. Clinical data were derived from key randomized controlled trials. Costs related to drug, administration, and adverse events were included. Sensitivity analyses were conducted to assess uncertainty. In a plan of 500,000 members, it was estimated there would be 91 newly diagnosed advanced NSCLC patients annually; 11 are expected to be EGFR-positive. Based on the testing and treatment assumptions, it was estimated that 3 patients in Scenario 1 and 6 patients in Scenario 2 receive erlotinib. Overall health plan expenditures would increase by $0.013 per member per month (PMPM). This increase is largely attributable to erlotinib drug costs, in part due to lengthened progression-free survival and treatment periods experienced in erlotinib-treated patients. EGFR testing contributes slightly, whereas adverse event costs mitigate the budget impact. The budget impact did not exceed $0.019 PMPM in sensitivity analyses. Coverage for targeted first-line erlotinib therapy in NSCLC likely results in a small budget impact for US health plans. The estimated impact may vary by plan, or if second-line or maintenance therapy, dose changes/interruptions, or impact on patients' quality-of-life were included.

[Efficacy and Survival Analysis of Apatinib in Patients with Advanced Nonsquamous Non-small Cell Lung Cancer after Failure of First-line Treatment].

PubMed

Wang, Xuemin; Zhang, Weihong; Du, Weijiao; Zhang, Xinwei; Ren, Xiubao; Cao, Shui

2017-11-20

The efficacy of second or third-line chemotherapy in advanced non-small cell lung cancer (NSCLC) patients is low. The use of targeted drugs brings survival benefit for some patients. Apatinib, as a novel small molecule antiangiogenic drug, has demonstrated satisfactory anticancer activity across a broad range of malignancies. The aim of this study is to evaluate the efficacy and safety of apatinib in patients with advanced NSCLC after first-line treatment failure. A retrospective study of 128 patients was conducted to evaluate the safety, short-term efficacy and survival status with different regimens. Kaplan-Meier method and Cox regression model were used for analysis. Compared with chemotherapy alone, the median progression free survival (PFS) in apatinib monotherapy, chemotherapy alone and apatinib combined with chemotherapy were 3.0 (P=0.381), 3.7 and 6.0 months (P<0.001), respectively. The median overall survival (OS) were 6.0 (P=0.494), 6.5 and 9.0 months (P=0.001), respectively. The incidence of adverse events in grades 3-4 were 18.5%, 15.8% and 16.0%, respectively (P=0.947). Different treatment regimens (P=0.018) and performance status (PS)(P<0.001) were the independent factors of PFS. The smoking history (P=0.014), treatment regimens (P=0.002) and PS (P<0.001) were independent influencing factors of OS. Apatinib has a good security. After first-line treatment failure of lung cancer, chemotherapy combined with apatinib in second or third-line is beneficial in PFS and OS when compared with chemotherapy alone. But when making comparison between apatinib monotherapy and chemotherapy alone, there is no significant difference in PFS and OS. Patients who never smoke or has a better PS or use combination therapy have longer survival time.
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Effect of first-line endocrine therapy in patients with hormone-sensitive advanced breast cancer: a network meta-analysis.

PubMed

Zhang, Tingting; Feng, Fubin; Zhao, Wenge; Tian, Jinhui; Yao, Yan; Zhou, Chao; Dong, Shengjie; Wang, Congcong; Zang, Chuanxin; Lv, Qingliang; Sun, Changgang

2018-01-01

Endocrine therapy is the cornerstone treatment for patients with hormone receptor-positive advanced breast cancer. We aimed to assess the effectiveness of various first-line endocrine monotherapies or combinations to determine the optimal sequence in a network meta-analysis. We searched PubMed, EMBASE, and the Cochrane Library for randomized controlled trials (RCTs) from inception up to November 21, 2017. We included only RCTs that assessed the effectiveness of the following treatments as a monotherapy or in combination as the first-line treatment: tamoxifen, anastrozole, letrozole, exemestane, fulvestrant, palbociclib, and ribociclib. The results were presented with pooled odds ratio or hazard ratio (HR), and 95% credible interval (CrI). The primary outcomes were objective response rate (ORR) and progression-free survival/time to progression. A total of 16 eligible articles (14 RCTs) involving 6,602 patients treated with 10 different first-line endocrine therapies were assessed in our network meta-analysis. Palbociclib plus letrozole was superior to anastrozole, letrozole, exemestane, fulvestrant 500 mg, and anastrozole plus fulvestrant (loading dose) (HR=0.44, 95% CrI: 0.33-0.58; HR=0.56, 95% CrI: 0.45-0.68; HR=0.45, 95% CrI: 0.32-0.61; HR=0.58, 95% CrI: 0.42-0.81; HR=0.50, 95% CrI: 0.37-0.68; respectively). However, there is no significant advantage compared with ribociclib plus letrozole (HR=1.00, 95% CrI: 0.72-1.39). In terms of ORR, ribociclib plus letrozole is more effective than palbociclib plus letrozole (odds ratio=1.30, 95% CrI: 0.83-2.02). Palbociclib plus letrozole and ribociclib plus letrozole might be the optimal first-line endocrine therapeutic choices for hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer due to a longer progression-free survival/time to progression and a more efficacious ORR.

No evidence for involvement of SDHD in neuroblastoma pathogenesis

PubMed Central

De Preter, Katleen; Vandesompele, Jo; Hoebeeck, Jasmien; Vandenbroecke, Caroline; Smet, Jöel; Nuyts, Annick; Laureys, Geneviève; Combaret, Valérie; Van Roy, Nadine; Roels, Frank; Van Coster, Rudy; Praet, Marleen; De Paepe, Anne; Speleman, Frank

2004-01-01

Background Deletions in the long arm of chromosome 11 are observed in a subgroup of advanced stage neuroblastomas with poor outcome. The deleted region harbours the tumour suppressor gene SDHD that is frequently mutated in paraganglioma and pheochromocytoma, which are, like neuroblastoma, tumours originating from the neural crest. In this study, we sought for evidence for involvement of SDHD in neuroblastoma. Methods SDHD was investigated on the genome, transcriptome and proteome level using mutation screening, methylation specific PCR, real-time quantitative PCR based homozygous deletion screening and mRNA expression profiling, immunoblotting, functional protein analysis and ultrastructural imaging of the mitochondria. Results Analysis at the genomic level of 67 tumour samples and 37 cell lines revealed at least 2 bona-fide mutations in cell lines without allelic loss at 11q23: a 4bp-deletion causing skip of exon 3 resulting in a premature stop codon in cell line N206, and a Y93C mutation in cell line NMB located in a region affected by germline SDHD mutations causing hereditary paraganglioma. No evidence for hypermethylation of the SDHD promotor region was observed, nor could we detect homozygous deletions. Interestingly, SDHD mRNA expression was significantly reduced in SDHD mutated cell lines and cell lines with 11q allelic loss as compared to both cell lines without 11q allelic loss and normal foetal neuroblast cells. However, protein analyses and assessment of mitochondrial morphology presently do not provide clues as to the possible effect of reduced SDHD expression on the neuroblastoma tumour phenotype. Conclusions Our study provides no indications for 2-hit involvement of SDHD in the pathogenesis of neuroblastoma. Also, although a haplo-insufficient mechanism for SDHD involvement in advanced stage neuroblastoma could be considered, the present data do not provide consistent evidence for this hypothesis. PMID:15331017

Impact of the number of prior lines of therapy and prior perioperative chemotherapy in patients receiving salvage therapy for advanced urothelial carcinoma: implications for trial design.

PubMed

Pond, G R; Bellmunt, J; Rosenberg, J E; Bajorin, D F; Regazzi, A M; Choueiri, T K; Qu, A Q; Niegisch, G; Albers, P; Necchi, A; Di Lorenzo, G; Fougeray, R; Wong, Y-N; Sridhar, S S; Ko, Y-J; Milowsky, M I; Galsky, M D; Sonpavde, G

2015-02-01

The differential impact of the number of prior lines of therapy and the setting of prior therapy (perioperative or metastatic) is unclear in advanced urothelial carcinoma. Ten phase II trials of salvage chemotherapy, biologic agent therapy, or both, enrolling 731 patients, were available. Data on the number of prior lines of therapy and the setting of prior therapy were required in addition to known previously recognized prognostic factors: time from prior chemotherapy, hemoglobin level, performance status, and liver metastasis status. Cox proportional hazards regression was used to evaluate the association of the number of prior lines and prior perioperative therapy with overall survival (OS) as the primary clinical endpoint. Trial was a stratification factor. A total of 711 patients were evaluable. The overall median progression-free survival and OS were 2.7 and 6.8 months, respectively. The number of prior lines was 1 in 559 patients (78.6%), 2 in 111 (15.6%), 3 in 29 (4.1%), 4 in 10 (1.4%), and 5 in 2 (0.3%). Prior perioperative chemotherapy was given to 277 (39.1%) and chemotherapy for metastatic disease to 454 (64.1%). The number of prior lines was not independently associated with OS (hazard ratio, 0.99; 95% CI, 0.86-1.14). Prior perioperative chemotherapy was a favorable factor for OS on univariate but not multivariate analysis. The number of prior lines of therapy and prior perioperative chemotherapy were not independently prognostic in patients with urothelial carcinoma receiving salvage therapy. Adoption of these data in salvage therapy trials should enhance accrual, the interpretability of results, and drug development. Copyright © 2015 Elsevier Inc. All rights reserved.

Rapid Cycling Genomic Selection in a Multiparental Tropical Maize Population

PubMed Central

Zhang, Xuecai; Pérez-Rodríguez, Paulino; Burgueño, Juan; Olsen, Michael; Buckler, Edward; Atlin, Gary; Prasanna, Boddupalli M.; Vargas, Mateo; San Vicente, Félix; Crossa, José

2017-01-01

Genomic selection (GS) increases genetic gain by reducing the length of the selection cycle, as has been exemplified in maize using rapid cycling recombination of biparental populations. However, no results of GS applied to maize multi-parental populations have been reported so far. This study is the first to show realized genetic gains of rapid cycling genomic selection (RCGS) for four recombination cycles in a multi-parental tropical maize population. Eighteen elite tropical maize lines were intercrossed twice, and self-pollinated once, to form the cycle 0 (C0) training population. A total of 1000 ear-to-row C0 families was genotyped with 955,690 genotyping-by-sequencing SNP markers; their testcrosses were phenotyped at four optimal locations in Mexico to form the training population. Individuals from families with the best plant types, maturity, and grain yield were selected and intermated to form RCGS cycle 1 (C1). Predictions of the genotyped individuals forming cycle C1 were made, and the best predicted grain yielders were selected as parents of C2; this was repeated for more cycles (C2, C3, and C4), thereby achieving two cycles per year. Multi-environment trials of individuals from populations C0, C1, C2, C3, and C4, together with four benchmark checks were evaluated at two locations in Mexico. Results indicated that realized grain yield from C1 to C4 reached 0.225 ton ha−1 per cycle, which is equivalent to 0.100 ton ha−1 yr−1 over a 4.5-yr breeding period from the initial cross to the last cycle. Compared with the original 18 parents used to form cycle 0 (C0), genetic diversity narrowed only slightly during the last GS cycles (C3 and C4). Results indicate that, in tropical maize multi-parental breeding populations, RCGS can be an effective breeding strategy for simultaneously conserving genetic diversity and achieving high genetic gains in a short period of time. PMID:28533335

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.

On-Line Thermal Barrier Coating Monitoring for Real-Time Failure Protection and Life Maximization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dennis H. LeMieux

2005-04-01

Under the sponsorship of the U. S. Department of Energy's National Energy Laboratory, Siemens Westinghouse Power Corporation proposes a four year program titled, ''On-Line Thermal Barrier Coating (TBC) Monitor for Real-Time Failure Protection and Life Maximization'', to develop, build and install the first generation of an on-line TBC monitoring system for use on land-based advanced gas turbines (AGT). Federal deregulation in electric power generation has accelerated power plant owner's demand for improved reliability availability maintainability (RAM) of the land-based advanced gas turbines. As a result, firing temperatures have been increased substantially in the advanced turbine engines, and the TBCs havemore » been developed for maximum protection and life of all critical engine components operating at these higher temperatures. Losing TBC protection can therefore accelerate the degradation of substrate components materials and eventually lead to a premature failure of critical component and costly unscheduled power outages. This program seeks to substantially improve the operating life of high cost gas turbine components using TBC; thereby, lowering the cost of maintenance leading to lower cost of electricity. Siemens Westinghouse Power Corporation has teamed with Indigo Systems, a supplier of state-of-the-art infrared camera systems, and Wayne State University, a leading research organization in the field of infrared non-destructive examination (NDE), to complete the program.« less

ON-LINE THERMAL BARRIER COATING MONITORING FOR REAL-TIME FAILURE PROTECTION AND LIFE MAXIMIZATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dennis H. LeMieux

2003-10-01

Under the sponsorship of the U. S. Department of Energy's National Energy Laboratory, Siemens Westinghouse Power Corporation proposes a four year program titled, ''On-Line Thermal Barrier Coating (TBC) Monitor for Real-Time Failure Protection and Life Maximization,'' to develop, build and install the first generation of an on-line TBC monitoring system for use on land-based advanced gas turbines (AGT). Federal deregulation in electric power generation has accelerated power plant owner's demand for improved reliability, availability, and maintainability (RAM) of the land-based advanced gas turbines. As a result, firing temperatures have been increased substantially in the advanced turbine engines, and the TBCsmore » have been developed for maximum protection and life of all critical engine components operating at these higher temperatures. Losing TBC protection can, therefore, accelerate the degradation of substrate component materials and eventually lead to a premature failure of critical components and costly unscheduled power outages. This program seeks to substantially improve the operating life of high cost gas turbine components using TBC; thereby, lowering the cost of maintenance leading to lower cost of electricity. Siemens Westinghouse Power Corporation has teamed with Indigo Systems, a supplier of state-of-the-art infrared camera systems, and Wayne State University, a leading research organization in the field of infrared non-destructive examination (NDE), to complete the program.« less

ON-LINE THERMAL BARRIER COATING MONITORING FOR REAL-TIME FAILURE PROTECTION AND LIFE MAXIMIZATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dennis H. LeMieux

2003-07-01

Under the sponsorship of the U. S. Department of Energy's National Energy Laboratory, Siemens Westinghouse Power Corporation proposes a four year program titled, ''On-Line Thermal Barrier Coating (TBC) Monitor for Real-Time Failure Protection and Life Maximization,'' to develop, build and install the first generation of an on-line TBC monitoring system for use on land-based advanced gas turbines (AGT). Federal deregulation in electric power generation has accelerated power plant owner's demand for improved reliability, availability, and maintainability (RAM) of the land-based advanced gas turbines. As a result, firing temperatures have been increased substantially in the advanced turbine engines, and the TBCsmore » have been developed for maximum protection and life of all critical engine components operating at these higher temperatures. Losing TBC protection can, therefore, accelerate the degradation of substrate component materials and eventually lead to a premature failure of critical components and costly unscheduled power outages. This program seeks to substantially improve the operating life of high cost gas turbine components using TBC; thereby, lowering the cost of maintenance leading to lower cost of electricity. Siemens Westinghouse Power Corporation has teamed with Indigo Systems, a supplier of state-of-the-art infrared camera systems, and Wayne State University, a leading research organization in the field of infrared non-destructive examination (NDE), to complete the program.« less

On-Line Thermal Barrier Coating Monitoring for Real-Time Failure Protection and Life Maximization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dennis H. LeMieux

2005-10-01

Under the sponsorship of the U. S. Department of Energy's National Energy Laboratory, Siemens Power Generation, Inc proposed a four year program titled, ''On-Line Thermal Barrier Coating (TBC) Monitor for Real-Time Failure Protection and Life Maximization'', to develop, build and install the first generation of an on-line TBC monitoring system for use on land-based advanced gas turbines (AGT). Federal deregulation in electric power generation has accelerated power plant owner's demand for improved reliability availability maintainability (RAM) of the land-based advanced gas turbines. As a result, firing temperatures have been increased substantially in the advanced turbine engines, and the TBCs havemore » been developed for maximum protection and life of all critical engine components operating at these higher temperatures. Losing TBC protection can therefore accelerate the degradation of substrate components materials and eventually lead to a premature failure of critical component and costly unscheduled power outages. This program seeks to substantially improve the operating life of high cost gas turbine components using TBC; thereby, lowering the cost of maintenance leading to lower cost of electricity. Siemens Power Generation, Inc. has teamed with Indigo Systems, a supplier of state-of-the-art infrared camera systems, and Wayne State University, a leading research organization in the field of infrared non-destructive examination (NDE), to complete the program.« less

A multicenter survey of first-line treatment patterns and gene aberration test status of patients with unresectable Stage IIIB/IV nonsquamous non-small cell lung cancer in China (CTONG 1506).

PubMed

Zhou, Qing; Song, Yong; Zhang, Xin; Chen, Gong-Yan; Zhong, Dian-Sheng; Yu, Zhuang; Yu, Ping; Zhang, Yi-Ping; Chen, Jian-Hua; Hu, Yi; Feng, Guo-Sheng; Song, Xia; Shi, Qiang; Yang, Lu Lu; Zhang, Ping Hai; Wu, Yi-Long

2017-07-03

In recent years, systemic chemotherapy and molecular targeted therapy have become standard first-line treatments for locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). The objective of this survey was to investigate first-line anticancer treatment patterns and gene aberration test status of patients with advanced nonsquamous NSCLC in China. Patients included in this study had unresectable Stage IIIB/IV nonsquamous NSCLC and were admitted during August 2015 to March 2016 into one of 12 tertiary hospitals throughout China for first-line anticancer treatment. Patient data (demographics, NSCLC histologic type, Eastern Cooperative Oncology Group [ECOG] Performance Status [PS], gene aberration test and results [if performed], and first-line anticancer treatment regimen) were extracted from medical charts and entered into Medical Record Abstraction Forms (MERAFs), which were collated for analysis. Overall, 1041 MERAFs were collected and data from 932 MERAFs were included for analysis. Patients with unresectable Stage IIIB/IV nonsquamous NSCLC had a median age of 59 years, 56.4% were male, 58.2% were never smokers, 95.0% had adenocarcinoma, and 92.9% had an ECOG PS ≤1. A total of 665 (71.4%) patients had gene aberration tests; 46.5% (309/665) had epidermal growth factor receptor (EGFR) gene mutations, 11.5% (48/416) had anaplastic lymphoma kinase (ALK) gene fusions, and 0.8% (1/128) had a c-ros oncogene 1 gene fusion. The most common first-line treatment regimen for unresectable Stage IIIB/IV nonsquamous NSCLC was chemotherapy (72.5%, 676/932), followed by tyrosine kinase inhibitors (TKIs; 26.1%, 243/932), and TKIs plus chemotherapy (1.4%, 13/932). Most chemotherapy regimens were platinum-doublet regimens (93.5%, 631/676) and pemetrexed was the most common nonplatinum chemotherapy-backbone agent (70.2%, 443/631) in platinum-doublet regimens. Most EGFR mutation-positive patients (66.3%, 205/309) were treated with EGFR-TKIs. Findings from our survey of 12 tertiary hospitals throughout China showed an increased rate of gene aberration testing, compared with those rates reported in previous surveys, for patients with advanced nonsquamous NSCLC. In addition, pemetrexed/platinum-doublet chemotherapy was the predominant first-line chemotherapy regimen for this population. Most patients were treated based on their gene aberration test status and results.

Knowledge and Interaction in On-Line Discussions in Spanish by Advanced Language Learners

ERIC Educational Resources Information Center

McCabe, Anne

2017-01-01

This article provides results of analysis of data collected from online Spanish-medium subject courses taught in Spanish by the same teacher to students whose first language is English. The students are at a high-intermediate to advanced level (B2-C1), and are enrolled at an American university in Madrid in courses centring on topics of Spanish…

Development of Medical Technology for Contingency Response to Marrow Toxic Agents

DTIC Science & Technology

2012-07-26

Armed Forces Radiobiology Research Institute’s (AFRRI) conference on advances in treating combined injuries resulting from a radiological disaster... Research on Health Effects of Radiation B-LCLs B-Lymphoblastoid Cell Lines IND Investigational New Drug BARDA Biomedical Advanced Research and...Naval Research (ONR 342) 875 N. Randolph St. Arlington, VA 22203-1995 Subject: Quartcrl~ Performance/Technical Report of the National Marrow Donor

Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study.

PubMed

Crinò, Lucio; Dansin, Eric; Garrido, Pilar; Griesinger, Frank; Laskin, Janessa; Pavlakis, Nick; Stroiakovski, Daniel; Thatcher, Nick; Tsai, Chun-Ming; Wu, Yi-long; Zhou, Caicun

2010-08-01

Results of two phase 3 trials have shown first-line bevacizumab in combination with chemotherapy improves clinical outcomes in patients with advanced or recurrent non-squamous non-small-cell lung cancer (NSCLC). The SAiL (MO19390) study was undertaken to assess the safety and efficacy of first-line bevacizumab combined with standard chemotherapy regimens in clinical practice. Between August, 2006, and June, 2008, patients with untreated locally advanced, metastatic, or recurrent non-squamous NSCLC were recruited to this open-label, single group, phase 4 study from centres in 40 countries. Eligible patients had histologically or cytologically documented inoperable, locally advanced, metastatic, or recurrent disease (stage IIIB-IV); an Eastern Cooperative Oncology Group performance status of 0-2; and adequate haematological, hepatic, and renal function. Patients received bevacizumab (7.5 or 15 mg/kg every 3 weeks) plus standard chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety; analysis was by intention to treat (ITT). This study is registered with ClinicalTrials.gov, number NCT00451906. At the final data cutoff (July 24, 2009), an ITT population of 2212 patients was assessed. The incidence of clinically significant (grade > or = 3) adverse events of special interest was generally low; thromboembolism occurred in 172 (8%) patients, hypertension in 125 (6%), bleeding in 80 (4%), proteinuria in 67 (3%), and pulmonary haemorrhage in 15 (1%). 57 (3%) patients died because of these adverse events, with thromboembolism (26 patients, 1%) and bleeding (17, 1%) as the most common causes. The most common grade 3 or higher serious adverse events deemed by investigators to be associated with bevacizumab were pulmonary embolism (28 patients; 1%) and epistaxis, neutropenia, febrile neutropenia, and deep vein thrombosis (all of which occurred in 13 patients [1%]). Bevacizumab was temporarily interrupted after 28 (2%) of 1347 bleeding events and 72 (7%) of 1025 hypertension events, and permanently discontinued after 110 (8%) bleeding events and 40 (4%) hypertension events. No new safety signals were reported. Our results confirm the manageable safety profile of first-line bevacizumab in combination with various standard chemotherapy regimens for treatment of advanced non-squamous NSCLC. F Hoffmann-La Roche Ltd. 2010 Elsevier Ltd. All rights reserved.

Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3.

PubMed

Slamon, Dennis J; Neven, Patrick; Chia, Stephen; Fasching, Peter A; De Laurentiis, Michelino; Im, Seock-Ah; Petrakova, Katarina; Bianchi, Giulia Val; Esteva, Francisco J; Martín, Miguel; Nusch, Arnd; Sonke, Gabe S; De la Cruz-Merino, Luis; Beck, J Thaddeus; Pivot, Xavier; Vidam, Gena; Wang, Yingbo; Rodriguez Lorenc, Karen; Miller, Michelle; Taran, Tetiana; Jerusalem, Guy

2018-06-03

Purpose This phase III study evaluated ribociclib plus fulvestrant in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer who were treatment naïve or had received up to one line of prior endocrine therapy in the advanced setting. Patients and Methods Patients were randomly assigned at a two-to-one ratio to ribociclib plus fulvestrant or placebo plus fulvestrant. The primary end point was locally assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. Results A total of 484 postmenopausal women were randomly assigned to ribociclib plus fulvestrant, and 242 were assigned to placebo plus fulvestrant. Median progression-free survival was significantly improved with ribociclib plus fulvestrant versus placebo plus fulvestrant: 20.5 months (95% CI, 18.5 to 23.5 months) versus 12.8 months (95% CI, 10.9 to 16.3 months), respectively (hazard ratio, 0.593; 95% CI, 0.480 to 0.732; P < .001). Consistent treatment effects were observed in patients who were treatment naïve in the advanced setting (hazard ratio, 0.577; 95% CI, 0.415 to 0.802), as well as in patients who had received up to one line of prior endocrine therapy for advanced disease (hazard ratio, 0.565; 95% CI, 0.428 to 0.744). Among patients with measurable disease, the overall response rate was 40.9% for the ribociclib plus fulvestrant arm and 28.7% for placebo plus fulvestrant. Grade 3 adverse events reported in ≥ 10% of patients in either arm (ribociclib plus fulvestrant v placebo plus fulvestrant) were neutropenia (46.6% v 0%) and leukopenia (13.5% v 0%); the only grade 4 event reported in ≥ 5% of patients was neutropenia (6.8% v 0%). Conclusion Ribociclib plus fulvestrant might represent a new first- or second-line treatment option in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer.

The HITRAN molecular data base - Editions of 1991 and 1992

NASA Technical Reports Server (NTRS)

Rothman, Laurence S.; Gamache, R. R.; Tipping, R. H.; Rinsland, C. P.; Smith, M. A. H.; Benner, D. C.; Devi, V. M.; Flaud, J.-M.; Camy-Peyret, C.; Perrin, A.

1992-01-01

We describe in this paper the modifications, improvements, and enhancements to the HITRAN molecular absorption database that have occurred in the two editions of 1991 and 1992. The current database includes line parameters for 31 species and their isotopomers that are significant for terrestrial atmospheric studies. This line-by-line portion of HITRAN presently contains about 709,000 transitions between 0 and 23,000/cm and contains three molecules not present in earlier versions: COF2, SF6, and H2S. The HITRAN compilation has substantially more information on chlorofluorocarbons and other molecular species that exhibit dense spectra which are not amenable to line-by-line representation. The user access of the database has been advanced, and new media forms are now available for use on personal computers.

Genotypic variability for root/shoot parameters under water stress in some advanced lines of cotton (Gossypium hirsutum L.).

PubMed

Riaz, M; Farooq, J; Sakhawat, G; Mahmood, A; Sadiq, M A; Yaseen, M

2013-02-27

Research pertaining to genetic variability parameters, heritability, and genotypic, phenotypic, simple, and environmental correlations for various seedling traits in five elite advanced cotton (Gossypium hirsutum L.) lines (FH-113, FH-114, FH-941, FH-942, and FH-2015) and one check (CIM-496) was carried out during October and November 2010 under greenhouse conditions at the Cotton Research Institute (Faisalabad, Pakistan). Material was raised in plastic tubes with a randomized complete block design replicated three times. Three drought shocks were applied by withholding water from the tube-sown plants for 8-, 10-, and 12-day intervals. After 60 days of sowing, data on root/shoot traits like root length (cm), shoot length (cm), root weight (g), shoot fresh weight (g), lateral root number, root dry weight (g) shoot dry weight (g), and total plant weight (g) were recorded. Considerable genotypic variations existed between genotypes for all seedling characters. Higher broad-sense heritability estimates were found for all traits studied. Maximum broad-sense heritability coupled with high genetic advance in root length (0.99, 17.34), lateral root number (0.91, 2.89), and shoot length (0.90, 4.35) suggested a potential for genetic improvement through breeding and selection. The correlation coefficients among root length, shoot length, root dry weight, fresh shoot weight, and total plant weight were positively and significantly correlated; thus, they can be selected simultaneously as drought tolerance selection indexes owing to the absence of undesired relationships. Genotypes FH-942 and FH-113 had the lowest excised leaf water loss during the first 4 h and also for the next 4 h. Therefore, these two advanced lines (FH-942 and FH-113) with high initial water content and lower excised leaf water loss had better adaptation to water stress.

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

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

PubMed

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

2016-01-01

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

Treatment patterns and cost-effectiveness of first line treatment of advanced non-squamous non-small cell lung cancer in Medicare patients.

PubMed

Gilden, Daniel M; Kubisiak, Joanna M; Pohl, Gerhardt M; Ball, Daniel E; Gilden, David E; John, William J; Wetmore, Stewart; Winfree, Katherine B

2017-02-01

To assess the cost-effectiveness of first-line pemetrexed/platinum and other commonly administered regimens in a representative US elderly population with advanced non-squamous non-small cell lung cancer (NSCLC). This study utilized the Surveillance Epidemiology and End Results (SEER) cancer registry linked to Medicare claims records. The study population included all SEER-Medicare patients diagnosed in 2008-2009 with advanced non-squamous NSCLC (stages IIIB-IV) as their only primary cancer and who started chemotherapy within 90 days of diagnosis. The study evaluated the four most commonly observed first-line regimens: paclitaxel/carboplatin, platinum monotherapy, pemetrexed/platinum, and paclitaxel/carboplatin/bevacizumab. Overall survival and total healthcare cost comparisons as well as incremental cost-effectiveness ratios (ICERs) were calculated for pemetrexed/platinum vs each of the other three. Unstratified analyses and analyses stratified by initial disease stage were conducted. The final study population consisted of 2,461 patients. Greater administrative censorship of pemetrexed recipients at the end of the study period disproportionately reduced the observed mean survival for pemetrexed/platinum recipients. The disease stage-stratified ICER analysis found that the pemetrexed/platinum incurred total Medicare costs of $536,424 and $283,560 per observed additional year of life relative to platinum monotherapy and paclitaxel/carboplatin, respectively. The pemetrexed/platinum vs triplet comparator analysis indicated that pemetrexed/platinum was associated with considerably lower total Medicare costs, with no appreciable survival difference. Limitations included differential censorship of the study regimen recipients and differential administration of radiotherapy. Pemetrexed/platinum yielded either improved survival at increased cost or similar survival at reduced cost relative to comparator regimens in the treatment of advanced non-squamous NSCLC. Limitations in the study methodology suggest that the observed pemetrexed survival benefit was likely conservative.

Apparel Manufacture

NASA Technical Reports Server (NTRS)

1995-01-01

Marshall Space Flight Center teamed with the University of Alabama in Huntsville (UAH) in 1989 on a program involving development of advanced simulation software. Concurrently, the State of Alabama chartered UAH to conduct a technology advancement program in support of the state's apparel manufacturers. In 1992, under contract to Marshall, UAH developed an apparel-specific software package that allows manufacturers to design and analyze modules without making an actual investment -- it functions on ordinary PC equipment. By 1995, Marshall had responded to requests for the package from more than 400 companies in 36 states; some of which reported savings up to $2 million. The National Garment Company of Missouri, for example, uses the system to design and balance a modular line before committing to expensive hardware; for setting up sewing lines; and for determining the composition of a new team.

Review and perspectives of electrostatic turbulence and transport studies in the basic plasma physics device TORPEX

NASA Astrophysics Data System (ADS)

Avino, Fabio; Bovet, Alexandre; Fasoli, Ambrogio; Furno, Ivo; Gustafson, Kyle; Loizu, Joaquim; Ricci, Paolo; Theiler, Christian

2012-10-01

TORPEX is a basic plasma physics toroidal device located at the CRPP-EPFL in Lausanne. In TORPEX, a vertical magnetic field superposed on a toroidal field creates helicoidal field lines with both ends terminating on the torus vessel. We review recent advances in the understanding and control of electrostatic interchange turbulence, associated structures and their effect on suprathermal ions. These advances are obtained using high-resolution diagnostics of plasma parameters and wave fields throughout the whole device cross-section, fluid models and numerical simulations. Furthermore, we discuss future developments including the possibility of generating closed field line configurations with rotational transform using an internal toroidal wire carrying a current. This system will also allow the study of innovative fusion-relevant configurations, such as the snowflake divertor.

IMPEDANCE MEASUREMENT OF VACUUM CHAMBER COMPONENTS FOR THE ADVANCE PHOTON SOURCE (APS) UPGRADE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sangroula, M.; Lindberg, R.; Lill, R.

2017-06-16

The proposed Advance Photon Source Upgrade (APS-U) employs a multi-bend achromat (MBA) lattice to increase the photon brightness by two to three orders of magnitude. One of the main design challenges of the upgrade is to minimize rf heating and collective instabilities associated with the impedance of small-aperture vacuum components. As part of this effort, my research focuses on impedance measurement and simulation of various MBA vacuum components. Here, we present the summary of the impedance contributions for the APS-U and describe our planned impedance measurement technique, including some measurement results for the non-evaporative getter (NEG)-coated copper chamber and simulationmore » results for other critical components using a novel Goubau line (G-line) set up.« less

Recent advances in systemic therapy: Advances in systemic therapy for HER2-positive metastatic breast cancer.

PubMed

Morrow, Phuong Khanh H; Zambrana, Francisco; Esteva, Francisco J

2009-01-01

Human epidermal growth factor receptor (HER)2 over-expression is associated with a shortened disease-free interval and poor survival. Although the addition of trastuzumab to chemotherapy in the first-line setting has improved response rates, progression-free survival, and overall survival, response rates declined when trastuzumab was used beyond the first-line setting because of multiple mechanisms of resistance. Studies have demonstrated the clinical utility of continuing trastuzumab beyond progression, and further trials to explore this concept are ongoing. New tyrosine kinase inhibitors, monoclonal antibodies, PTEN (phosphatase and tensin homolog) pathway regulators, HER2 antibody-drug conjugates, and inhibitors of heat shock protein-90 are being evaluated to determine whether they may have a role to play in treating trastuzumab-resistant metastatic breast cancer.

Impedance measurement of vacuum chamber components for the Advance Photon Source(APS) Upgrade

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sangroula, M.; Lindberg, R.; Lill, R.

2017-01-01

The proposed Advance Photon Source Upgrade (APS-U) employs a multi-bend achromat (MBA) lattice to increase the photon brightness by two to three orders of magnitude. One of the main design challenges of the upgrade is to minimize rf heating and collective instabilities associated with the impedance of small-aperture vacuum components. As part of this effort, my research focuses on impedance measurement and simulation of various MBA vacuum components. Here, we present the summary of the impedance contributions for the APS-U and describe our planned impedance measurement technique, including some measurement results for the non-evaporative getter (NEG)-coated copper chamber and simulationmore » results for other critical components using a novel Goubau line (G-line) set up.« less

Publicity campaign, wellness event raise awareness of Michigan home health company, products.

PubMed

2007-01-01

HoMedics, a home healthcare and wellness company in Commerce Township, MI, had a problem. As a leading manufacturer of personal wellness and home healthcare products, its product line was constantly evolving with new and innovative technological advances. But with so many rapid changes, HoMedics had trouble educating the media about its new product lines quickly enough. The solution? A multiphase public relations campaign.

The Potential of the MAGIC TOM Parental Accessions to Explore the Genetic Variability in Tomato Acclimation to Repeated Cycles of Water Deficit and Recovery

PubMed Central

Ripoll, Julie; Urban, Laurent; Bertin, Nadia

2016-01-01

Episodes of water deficit (WD) during the crop cycle of tomato may negatively impact plant growth and fruit yield, but they may also improve fruit quality. Moreover, a moderate WD may induce a plant “memory effect” which is known to stimulate plant acclimation and defenses for upcoming stress episodes. The objective of this study was to analyze the positive and negative impacts of repeated episodes of WD at the plant and fruit levels. Three episodes of WD (–38, –45, and –55% of water supply) followed by three periods of recovery (“WD treatments”), were applied to the eight parents of the Multi-Parent Advanced Generation Inter-Cross population which offers the largest allelic variability observed in tomato. Predawn and midday water potentials, chlorophyll a fluorescence, growth and fruit quality traits [contents in sugars, acids, carotenoids, and ascorbic acid (AsA)] were measured throughout the experiment. Important genotypic variations were observed both at the plant and fruit levels and variations in fruit and leaf traits were found not to be correlated. Overall, the WD treatments were at the origin of important osmotic regulations, reduction of leaf growth, acclimation of photosynthetic functioning, notably through an increase in the chlorophyll content and in the quantum yield of the electron transport flux until PSI acceptors (J0RE1/JABS). The effects on fruit sugar, acid, carotenoid and AsA contents on a dry matter basis ranged from negative to positive to nil depending on genotypes and stress intensity. Three small fruit size accessions were richer in AsA on a fresh matter basis, due to concentration effects. So, fruit quality was improved under WD mainly through concentration effects. On the whole, two accessions, LA1420 and Criollo appeared as interesting genetic resources, cumulating adaptive traits both at the leaf and fruit levels. Our observations show that the complexity involved in plant responses, when considering a broad range of physiological traits and the variability of genotypic effects, represent a true challenge for upcoming studies aiming at taking advantage of, not just dealing with WD. PMID:26779213

High-Throughput Genome Editing and Phenotyping Facilitated by High Resolution Melting Curve Analysis

PubMed Central

Thomas, Holly R.; Percival, Stefanie M.; Yoder, Bradley K.; Parant, John M.

2014-01-01

With the goal to generate and characterize the phenotypes of null alleles in all genes within an organism and the recent advances in custom nucleases, genome editing limitations have moved from mutation generation to mutation detection. We previously demonstrated that High Resolution Melting (HRM) analysis is a rapid and efficient means of genotyping known zebrafish mutants. Here we establish optimized conditions for HRM based detection of novel mutant alleles. Using these conditions, we demonstrate that HRM is highly efficient at mutation detection across multiple genome editing platforms (ZFNs, TALENs, and CRISPRs); we observed nuclease generated HRM positive targeting in 1 of 6 (16%) open pool derived ZFNs, 14 of 23 (60%) TALENs, and 58 of 77 (75%) CRISPR nucleases. Successful targeting, based on HRM of G0 embryos correlates well with successful germline transmission (46 of 47 nucleases); yet, surprisingly mutations in the somatic tail DNA weakly correlate with mutations in the germline F1 progeny DNA. This suggests that analysis of G0 tail DNA is a good indicator of the efficiency of the nuclease, but not necessarily a good indicator of germline alleles that will be present in the F1s. However, we demonstrate that small amplicon HRM curve profiles of F1 progeny DNA can be used to differentiate between specific mutant alleles, facilitating rare allele identification and isolation; and that HRM is a powerful technique for screening possible off-target mutations that may be generated by the nucleases. Our data suggest that micro-homology based alternative NHEJ repair is primarily utilized in the generation of CRISPR mutant alleles and allows us to predict likelihood of generating a null allele. Lastly, we demonstrate that HRM can be used to quickly distinguish genotype-phenotype correlations within F1 embryos derived from G0 intercrosses. Together these data indicate that custom nucleases, in conjunction with the ease and speed of HRM, will facilitate future high-throughput mutation generation and analysis needed to establish mutants in all genes of an organism. PMID:25503746

Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sustarsic, Elahu G.; Department of Biological Sciences, Ohio University, Athens, OH; Junnila, Riia K.

2013-11-08

Highlights: •Most cancer types of the NCI60 have sub-sets of cell lines with high GHR expression. •GHR is highly expressed in melanoma cell lines. •GHR is elevated in advanced stage IV metastatic tumors vs. stage III. •GH treatment of metastatic melanoma cell lines alters growth and cell signaling. -- Abstract: Accumulating evidence implicates the growth hormone receptor (GHR) in carcinogenesis. While multiple studies show evidence for expression of growth hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of quantification and only a few cancer types have been investigated. The National Cancer Institute’s NCI60 panel includesmore » 60 cancer cell lines from nine types of human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung, ovarian, prostate and renal. We utilized this panel to quantify expression of GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real-time RT qPCR. Both GHR and PRLR show a broad range of expression within and among most cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma than in the panel as a whole. Analysis of human metastatic melanoma biopsies confirmed GHR gene expression in melanoma tissue. In these human biopsies, the level of GHR mRNA is elevated in advanced stage IV tumor samples compared to stage III. Due to the novel finding of high GHR in melanoma, we examined the effect of GH treatment on three NCI60 melanoma lines (MDA-MB-435, UACC-62 and SK-MEL-5). GH increased proliferation in two out of three cell lines tested. Further analysis revealed GH-induced activation of STAT5 and mTOR in a cell line dependent manner. In conclusion, we have identified cell lines and cancer types that are ideal to study the role of GH and PRL in cancer, yet have been largely overlooked. Furthermore, we found that human metastatic melanoma tumors express GHR and cell lines possess active GHRs that can modulate multiple signaling pathways and alter cell proliferation. Based on this data, GH could be a new therapeutic target in melanoma.« less

Journal of Special Operations Medicine, Volume 7, Edition 2, Spring 2007

DTIC Science & Technology

2007-01-01

to help preclude dislodgement. Single-lumen central venous /jugular catheters are not difficult to place in an otherwise fit and well-conditioned MWD...progressively lost favor since the intro- duction of the Seldinger technique of central venous line placement. In fact, recent editions of the Advanced...latest advancements in medicine and the history of unconventional warfare medicine. Disclosure Statement: The JSOM presents both medical and nonmedical

The use of drug-coated balloons in the treatment of femoropopliteal and infrapopliteal disease.

PubMed

Li, Jun; Karim, Adham; Shishehbor, Mehdi

2018-05-25

While the field of endovascular interventions has evolved in the last decade, technological advancements have rendered drug-coated balloons (DCBs) to be the first line therapy for femoropopliteal artery disease. As the knowledge continues to advance, the application of DCB to the infrapopliteal segments and its role in the setting of plaque modification atherectomy to minimize stent utilization will be further elucidated.

Progression-free survival as surrogate and as true end point: insights from the breast and colorectal cancer literature.

PubMed

Saad, E D; Katz, A; Hoff, P M; Buyse, M

2010-01-01

Significant achievements in the systemic treatment of both advanced breast cancer and advanced colorectal cancer over the past 10 years have led to a growing number of drugs, combinations, and sequences to be tested. The choice of surrogate and true end points has become a critical issue and one that is currently the subject of much debate. Many recent randomized trials in solid tumor oncology have used progression-free survival (PFS) as the primary end point. PFS is an attractive end point because it is available earlier than overall survival (OS) and is not influenced by second-line treatments. PFS is now undergoing validation as a surrogate end point in various disease settings. The question of whether PFS can be considered an acceptable surrogate end point depends not only on formal validation studies but also on a standardized definition and unbiased ascertainment of disease progression in clinical trials. In advanced breast cancer, formal validation of PFS as a surrogate for OS has so far been unsuccessful. In advanced colorectal cancer, in contrast, current evidence indicates that PFS is a valid surrogate for OS after first-line treatment with chemotherapy. The other question is whether PFS sufficiently reflects clinical benefit to be considered a true end point in and of itself.

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.;

Current and proposed molecular diagnostics in a genitourinary service line laboratory at a tertiary clinical institution.

PubMed

Udager, Aaron M; Alva, Ajjai; Mehra, Rohit

2014-01-01

The idea that detailed knowledge of molecular oncogenesis will drive diagnostic, prognostic, and therapeutic clinical decision making in an increasingly multidisciplinary practice of oncologic care has been anticipated for many years. With the recent rapid advancement in our understanding of the molecular underpinnings of genitourinary malignancies, this concept is now starting to take shape in the fields of prostate, kidney, bladder, testicular, and penile cancer. Such breakthroughs necessitate the development of robust clinical-grade assays that can be quickly made available for patients to facilitate diagnosis in challenging cases, risk-stratify patients for subsequent clinical management, select the appropriate targeted therapy from among increasingly diverse and numerous options, and enroll patients in advanced clinical trials. This rapid translation of basic and clinical cancer research requires a streamlined, multidisciplinary approach to clinical assay development, termed here the molecular diagnostics service line laboratory. In this review, we summarize the current state and explore the future of molecular diagnostics in genitourinary oncology to conceptualize a genitourinary service line laboratory at a tertiary clinical institution.

Resolving the Cygnus X-3 iron K line

NASA Technical Reports Server (NTRS)

Kitamoto, Shunji; Kawashima, Kenji; Negoro, Hitoshi; Miyamoto, Sigenori; White, N. E.; Nagase, Fumiaki

1994-01-01

An Advanced Satellite for Cosmology and Astrophysics (ASCA) observation of Cygnus X-3 on 1993 June 11, in its X-ray high intensity state, has for the first time resolved the broad iron K line emission into three components: a He-like line at 6.67 +/- 0.01 keV, a H-like line at 6.96 +/- 0.02 keV, and a neutral line at 6.37 +/- 0.03 keV. The line intensities of the 6.67 keV and 6.96 keV lines are modulated with the 4.8 hr orbital period and are maximum when the continuum intensity is minimum. There is a sharp minimum of the line intensity on the rising phase of the continuum intensity. An iron absorption edge is observed at 7.19 +/- 0.02 keV. The optical depth of the absorption edge varies from 0.3 to 0.5 and is in anti-phase with the overall X-ray continuum modulation. The observed complexity of the iron K line region is greater than that had been assumed in previous spectral modeling based on observations with lower resolution detectors.

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

PubMed

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-effective strategies if we consider an ICER below $50,000 per QALY an acceptable threshold. We need, probably on a countrywide level, to have a debate involving public health organizations and pharmaceutical companies, as well as clinicians and patients, to challenge the rising costs of managing lung cancer.

Evolution of checkpoint inhibitors for the treatment of metastatic gastric cancers: Current status and future perspectives.

PubMed

Taieb, Julien; Moehler, Markus; Boku, Narikazu; Ajani, Jaffer A; Yañez Ruiz, Eduardo; Ryu, Min-Hee; Guenther, Silke; Chand, Vikram; Bang, Yung-Jue

2018-05-01

Standard treatment options for patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC) are associated with limited efficacy and some toxicity. Recently, immunotherapy with antibodies that inhibit the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) interaction has emerged as a new treatment option. This manuscript reviews early-phase and late-phase trials of immunotherapy in advanced GC/GEJC. Searches for studies of immunotherapy in GC/GEJC were performed using PubMed, ClinicalTrials.gov, and abstract databases for select annual congresses. Findings were interpreted based on expert opinion. Monotherapy with anti-PD-1/PD-L1 antibodies, including pembrolizumab, nivolumab, avelumab, durvalumab, and atezolizumab, has shown interesting objective response rates (ORRs; 7-26%) across varying GC/GEJC populations, with ORRs potentially higher in PD-L1 + vs PD-L1 - tumors. Safety profiles compare favorably with chemotherapy, with grade ≥3 treatment-related adverse events occurring in 5-17%. Based on a large phase 2 study, pembrolizumab was approved in the United States for third-line treatment of patients with PD-L1 + GC/GEJC. In a phase 3 trial, third-line or later nivolumab increased overall survival vs placebo in an Asian population, leading to regulatory approval in Japan, although other completed phase 3 trials did not show superiority for pembrolizumab or avelumab monotherapy vs chemotherapy. Other trials in advanced GC/GEJC are assessing various anti-PD-1/PD-L1-based strategies, including administration in first-line and later-line settings and as combination (with chemotherapy or agents targeting other immune checkpoint proteins, eg, CTLA-4, LAG-3, and IDO) or switch-maintenance regimens. Anti-PD-1/PD-L1 antibodies have shown encouraging clinical activity in advanced GC/GEJC. Results from ongoing phase 3 trials are needed to further evaluate the potential roles of these agents within the continuum of care. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

Créquit, Perrine; Trinquart, Ludovic; Ravaud, Philippe

2016-08-03

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. 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. 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. CRD42015017592. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A single-arm, multicenter, safety-monitoring, phase IV study of icotinib in treating advanced non-small cell lung cancer (NSCLC).

PubMed

Hu, Xingsheng; Han, Baohui; Gu, Aiqin; Zhang, Yiping; Jiao, Shun Chang; Wang, Chang-Li; He, Jintao; Jia, Xueke; Zhang, Li; Peng, Jiewen; Wu, Meina; Ying, Kejing; Wang, Junye; Ma, Kewei; Zhang, Shucai; You, Changxuan; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Sun, Yan

2014-11-01

The phase 3 ICOGEN trial established the non-inferiority of icotinib to gefitinib in terms of progression-free survival (PFS) in non-small cell lung cancer (NSCLC) patients, and this led to the approval of icotinib for NSCLC by the China Food and Drug Administration. A phase 4 study was conducted to assess the safety and efficacy of icotinib in a broad range of patients with advanced NSCLC across China. This study retrospectively analyzed data from unresectable, recurrent, and/or advanced NSCLC patients who received oral icotinib 125 mg three times per day. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR) and disease control rate (DCR), which were investigated overall and in subgroups such as patients with an EGFR mutation and elderly patients. Between August, 2011 and August, 2012, a total of 6087 advanced NSCLC patients were registered in this study, of which 5549 were evaluable for safety and tumor response. The median age was 63 years (range 21-95 years), and 1571 (28.3%) patients were over the age of 70. The majority of patients were non-smokers, and had adenocarcinoma and stage IV disease. The overall incidence of adverse drug reactions (ADRs) of any grade was 31.5%. The most common ADRs included rash (17.4%) and diarrhea (8.5%), and three patients experienced interstitial lung disease (ILD). The ORR and DCR were 30.0% and 80.6%, respectively, for the overall population, and 33.4% and 81.2%, 30.3% and 80.3%, and 30.4% and 89.3%, for first-line, second-line, and third-line or multiple line subsets, respectively. In 665 EGFR-mutated patients who were evaluable for tumor response, the ORR and DCR were 49.2% (327/665) and 92.3% (614/665), respectively. The data from over 6000 patients was consistent with the results of the ICOGEN study. Icotinib demonstrated a favorable toxicity profile and efficacy in the routine clinical setting. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A novel Smac mimetic APG-1387 demonstrates potent antitumor activity in nasopharyngeal carcinoma cells by inducing apoptosis.

PubMed

Li, Ning; Feng, Lin; Han, Hui-Qiong; Yuan, Jing; Qi, Xue-Kang; Lian, Yi-Fan; Kuang, Bo-Hua; Zhang, Yu-Chen; Deng, Cheng-Cheng; Zhang, Hao-Jiong; Yao, You-Yuan; Xu, Miao; He, Gui-Ping; Zhao, Bing-Chun; Gao, Ling; Feng, Qi-Sheng; Chen, Li-Zhen; Yang, Lu; Yang, Dajun; Zeng, Yi-Xin

2016-10-10

Despite advances in the development of radiation against nasopharyngeal carcinoma (NPC), the management of advanced NPC remains a challenge. Smac mimetics are designed to neutralize inhibitor of apoptosis (IAP) proteins, thus reactivating the apoptotic program in cancer cells. In this study, we investigated the effect of a novel bivalent Smac mimetic APG-1387 in NPC. In vitro, APG-1387 in combination with TNF-α potently decreased NPC cell viability by inducing apoptosis in majority of NPC cell lines. The in vitro antitumor effect was RIPK1-dependent, whereas it was independent on IAPs, USP11, or EBV. Of note, the inhibition of NF-κB or AKT pathway rendered resistant NPC cells responsive to the treatment of APG-1387/TNF-α. In vivo, APG-1387 displayed antitumor activity as a single agent at well-tolerated doses, even in an in vitro resistant cell line. In summary, our results demonstrate that APG-1387 exerts a potent antitumor effect on NPC. These findings support clinical evaluation of APG-1387 as a potential treatment for advanced NPC. Copyright © 2016. Published by Elsevier Ireland Ltd.

Current state and future perspectives on coupled ice-sheet - sea-level modelling

NASA Astrophysics Data System (ADS)

de Boer, Bas; Stocchi, Paolo; Whitehouse, Pippa L.; van de Wal, Roderik S. W.

2017-08-01

The interaction between ice-sheet growth and retreat and sea-level change has been an established field of research for many years. However, recent advances in numerical modelling have shed new light on the precise interaction of marine ice sheets with the change in near-field sea level, and the related stability of the grounding line position. Studies using fully coupled ice-sheet - sea-level models have shown that accounting for gravitationally self-consistent sea-level change will act to slow down the retreat and advance of marine ice-sheet grounding lines. Moreover, by simultaneously solving the 'sea-level equation' and modelling ice-sheet flow, coupled models provide a global field of relative sea-level change that is consistent with dynamic changes in ice-sheet extent. In this paper we present an overview of recent advances, possible caveats, methodologies and challenges involved in coupled ice-sheet - sea-level modelling. We conclude by presenting a first-order comparison between a suite of relative sea-level data and output from a coupled ice-sheet - sea-level model.

Progression-free survival as primary endpoint in randomized clinical trials of targeted agents for advanced renal cell carcinoma. Correlation with overall survival, benchmarking and power analysis.

PubMed

Bria, Emilio; Massari, Francesco; Maines, Francesca; Pilotto, Sara; Bonomi, Maria; Porta, Camillo; Bracarda, Sergio; Heng, Daniel; Santini, Daniele; Sperduti, Isabella; Giannarelli, Diana; Cognetti, Francesco; Tortora, Giampaolo; Milella, Michele

2015-01-01

A correlation, power and benchmarking analysis between progression-free and overall survival (PFS, OS) of randomized trials with targeted agents or immunotherapy for advanced renal cell carcinoma (RCC) was performed to provide a practical tool for clinical trial design. For 1st-line of treatment, a significant correlation was observed between 6-month PFS and 12-month OS, between 3-month PFS and 9-month OS and between the distributions of the cumulative PFS and OS estimates. According to the regression equation derived for 1st-line targeted agents, 7859, 2873, 712, and 190 patients would be required to determine a 3%, 5%, 10% and 20% PFS advantage at 6 months, corresponding to an absolute increase in 12-month OS rates of 2%, 3%, 6% and 11%, respectively. These data support PFS as a reliable endpoint for advanced RCC receiving up-front therapies. Benchmarking and power analyses, on the basis of the updated survival expectations, may represent practical tools for future trial' design. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Developments in space power components for power management and distribution

NASA Technical Reports Server (NTRS)

Renz, D. D.

1984-01-01

Advanced power electronic components development for space applications is discussed. The components described include transformers, inductors, semiconductor devices such as transistors and diodes, remote power controllers, and transmission lines.

IUE and Einstein survey of late-type giant and supergiant stars and the dividing line

NASA Technical Reports Server (NTRS)

Haisch, Bernhard M.; Bookbinder, Jay A.; Maggio, A.; Vaiana, G. S.; Bennett, Jeffrey O.

1990-01-01

Results are presented on an IUE UV survey of 255 late-type G, K, and M stars, complementing the Maggio et al. (1990) Einstein X-ray survey of 380 late-type stars. The large data sample of X-ray and UV detections make it possible to examine the activity relationship between the X-ray and the UV emissions. The results confirm previous finding of a trend involving a steeply-dropping upper envelope of the transition region line fluxes, f(line)/f(V), as the dividing line is approached. This suggests that a sharp decrease in maximum activity accompanies the advancing spectral type, with the dividing line corresponding to this steep gradient region. The results confirm the rotation-activity connection for stars in this region of the H-R diagram.

EGFR TKI as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer

PubMed Central

Nan, Xueli; Xie, Chao; Yu, Xueyan; Liu, Jie

2017-01-01

After the discovery of activating mutations in EGFR, EGFR tyrosine kinase inhibitors (TKIs) have been introduced into the first-line treatment of non-small-cell lung cancer (NSCLC). A series of studies have shown that EGFR TKI monotherapy as first-line treatment can benefit NSCLC patients harbouring EGFR mutations. Besides, combination strategies based on EGFR TKIs in the first line treatment have also been proved to delay the occurrence of resistance. In this review, we summarize the scientific literature and evidence of EGFR TKIs as first-line therapy from the first-generation EGFR TKIs to conceptually proposed fourth-generation EGFR TKI, and also recommend the application of monotherapy and combination therapies of the EGFR-based targeted therapy with other agents such as chemotherapy, anti-angiogenic drugs and immunecheckpoint inhibitors. PMID:29088904

Mini-Uav LIDAR for Power Line Inspection

NASA Astrophysics Data System (ADS)

Teng, G. E.; Zhou, M.; Li, C. R.; Wu, H. H.; Li, W.; Meng, F. R.; Zhou, C. C.; Ma, L.

2017-09-01

Light detection and ranging (LIDAR) system based on unmanned aerial vehicles (UAVs) recently are in rapid advancement, meanwhile portable and flexible mini-UAV-borne laser scanners have been a hot research field, especially for the complex terrain survey in the mountains and other areas. This study proposes a power line inspection system solution based on mini-UAV-borne LIDAR system-AOEagle, developed by Academy of Opto-Electronics, Chinese Academy of Sciences, which mounted on a Multi-rotor unmanned aerial vehicle for complex terrain survey according to real test. Furthermore, the point cloud data was explored to validate its applicability for power line inspection, in terms of corridor and line laser point clouds; deformation detection of power towers, etc. The feasibility and advantages of AOEagle have been demonstrated by the promising results based on the real-measured data in the field of power line inspection.

Design optimization of RF lines in vacuum environment for the MITICA experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Muri, Michela, E-mail: michela.demuri@igi.cnr.it; Consorzio RFX, Corso Stati Uniti, 4, I-35127 Padova; Pavei, Mauro

This contribution regards the Radio Frequency (RF) transmission line of the Megavolt ITER Injector and Concept Advancement (MITICA) experiment. The original design considered copper coaxial lines of 1″ 5/8, but thermal simulations under operating conditions showed maximum temperatures of the lines at regime not compatible with the prescription of the component manufacturer. Hence, an optimization of the design was necessary. Enhancing thermal radiation and increasing the conductor size were considered for design optimization: thermal analyses were carried out to calculate the temperature of MITICA RF lines during operation, as a function of the emissivity value and of other geometrical parameters.more » Five coating products to increase the conductor surface emissivity were tested, measuring the outgassing behavior of the selected products and the obtained emissivity values.« less

Advanced CFD Methods for Hypervelocity Wind Tunnels

DTIC Science & Technology

2011-03-10

Mach 14 nozzle produces non-uniformities in the test section flow that are not desirable [1,2]. Calibration runs with Pitot pressure rakes suggest...flows is presented. The grid is based on the characteristic lines of the supersonic regions of the flow. This allows for grid alignment and clustering...novel grid generation scheme for hypersonic nozzle flows is presented. The grid is based on the characteristic lines of the supersonic regions of the

MODTRAN6: a major upgrade of the MODTRAN radiative transfer code

NASA Astrophysics Data System (ADS)

Berk, Alexander; Conforti, Patrick; Kennett, Rosemary; Perkins, Timothy; Hawes, Frederick; van den Bosch, Jeannette

2014-06-01

The MODTRAN6 radiative transfer (RT) code is a major advancement over earlier versions of the MODTRAN atmospheric transmittance and radiance model. This version of the code incorporates modern software ar- chitecture including an application programming interface, enhanced physics features including a line-by-line algorithm, a supplementary physics toolkit, and new documentation. The application programming interface has been developed for ease of integration into user applications. The MODTRAN code has been restructured towards a modular, object-oriented architecture to simplify upgrades as well as facilitate integration with other developers' codes. MODTRAN now includes a line-by-line algorithm for high resolution RT calculations as well as coupling to optical scattering codes for easy implementation of custom aerosols and clouds.

Beam line BL11 for LIGA process at the NewSUBARU

NASA Astrophysics Data System (ADS)

Mekaru, Harutaka; Utsumi, Yuichi; Hattori, Tadashi

2001-07-01

A beam line BL11 is constructed for exposure Hard X-ray Lithography (HXL) in the LIGA (German acronym for Lithographite Galvanoformung and Abformung) process at the synchrotron radiation (SR) facility NewSUBARU of the Laboratory of Advanced Science and Technology for Industry (LASTI) in Himeji Institute of Technology (HIT). This beam line was designed by the criteria; photon energy range 4-6 keV, a beam spot size on the exposure stage ⩾60×5 mm 2, a density of total irradiated photons ⩾10 11 photons/cm 2. The PMMA sheet etching was successfully demonstrated by using the output beam. We conclude that this beam line performs sufficiently well to study the exposure of HXL in the LIGA process.

Recent advances in enhancing the sensitivity of electrophoresis and electrochromatography in capillaries and microchips (2014-2016).

PubMed

Breadmore, Michael C; Wuethrich, Alain; Li, Feng; Phung, Sui Ching; Kalsoom, Umme; Cabot, Joan M; Tehranirokh, Masoomeh; Shallan, Aliaa I; Abdul Keyon, Aemi S; See, Hong Heng; Dawod, Mohamed; Quirino, Joselito P

2017-01-01

One of the most cited limitations of capillary (and microchip) electrophoresis is the poor sensitivity. This review continues to update this series of biennial reviews, first published in Electrophoresis in 2007, on developments in the field of on-line/in-line concentration methods in capillaries and microchips, covering the period July 2014-June 2016. It includes developments in the field of stacking, covering all methods from field amplified sample stacking and large volume sample stacking, through to isotachophoresis, dynamic pH junction, and sweeping. Attention is also given to on-line or in-line extraction methods that have been used for electrophoresis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gene expression profiling of breast cancer cell lines treated with proton and electron radiations.

PubMed

Bravatà, Valentina; Minafra, Luigi; Cammarata, Francesco Paolo; Pisciotta, Pietro; Lamia, Debora; Marchese, Valentina; Manti, Lorenzo; Cirrone, Giuseppe Ap; Gilardi, Maria Carla; Cuttone, Giacomo; Forte, Giusi Irma; Russo, Giorgio

2018-06-11

Technological advances in radiation therapy are evolving with the use of hadrons, such as protons, indicated for tumors where conventional radiotherapy does not give significant advantages or for tumors located in sensitive regions, which need the maximum of dose-saving of the surrounding healthy tissues. The genomic response to conventional and non conventional Linear Energy Transfer exposure is a poor investigated topic and became an issue of radiobiological interest. The aim of this work was to analyze and compare molecular responses in term of gene expression profiles, induced by electron and proton irradiation in breast cancer cell lines. We studied the gene expression profiling differences by cDNA microarray activated in response to electron and proton irradiation with different Linear Energy Transfer values, among three breast cell lines (the tumorigenic MCF7 and MDA-MB-231 and the non tumorigenic MCF10A), exposed to the same sub-lethal dose of 9 Gy. Gene expression profiling pathway analyses showed the activation of different signaling and molecular networks in a cell line and radiation type-dependent manner. MCF10A and MDA-MB-231 cell lines were found to induce factors and pathways involved in the immunological process control. Here we describe in a detailed way the gene expression profiling and pathways activated after electron and proton irradiation in breast cancer cells. Summarizing, although specific pathways are activated in a radiation type-dependent manner, each cell line activates overall similar molecular networks in response to both these two types of ionizing radiation. Advances in knowledge: In the era of personalized medicine and breast cancer target-directed intervention, we trust that this study could drive radiation therapy towards personalized treatments, evaluating possible combined treatments, based on the molecular characterization.

Treatment algorithm in 2014 for advanced non-small cell lung cancer: therapy selection by tumour histology and molecular biology.

PubMed

Manegold, Christian

2014-09-01

The availability of antineoplastic monoclonal antibodies, small molecules and newer cytotoxics such as pemetrexed, the EGFR-tyrosine kinase inhibitors erlotinib, gefitinib, afatinib as well as the anti-angiogenic bevacizumab and the ALK-inhibitor crizotinib has recently changes the treatment algorithm of advanced non-small cell lung cancer. Decision making in 2014 is characterized by customizing therapy, by selecting a specific therapeutic regimen based on the histotype and the genotype of the tumour. This refers to first-line induction therapy and maintenance therapy as well, but also to subsequent lines of therapy since anti-neoplastic drugs and regimens used upfront clinically influence the selection of agents/regimes considered for second-/third-line treatment. Consequently, therapy customization through tumour histology and molecular markers has significantly influenced the work of pathologists around the globe and the process of obtaining an extended therapeutically relevant tumour diagnosis. Not only histological sub-typing became standard but molecular information is also considered of increasing importance for treatment selection. Routine molecular testing in certified laboratories must be established, and the diagnostic process should ideally be performed under the guidance of evidence based recommendation. The process of investigating and implementing medical targeting in lung cancer therefore, requires advanced diagnostic techniques and expertise and because of its large dimension is costly and influenced by the limitation of financial and clinical resources. Copyright © 2014. Published by Elsevier Urban & Partner Sp. z o.o.

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

PubMed

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

2016-01-01

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. 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. 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. 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.

[The therapeutic value and safety of icotinib as first-line therapy for advanced non-small cell lung cancer patients].

PubMed

Chen, H; Wang, H P; Zhang, L; Si, X Y

2017-01-01

Objective: To evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations. Methods: Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study. The response rates, progress free survival (PFS), overall survival (OS), and the safety were analyzed. Results: Ninety advanced adenocarcinoma patients were enrolled in this study, 44 patients had partial response (PR), 42 patients had stable disease (SD), 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48.9%, and a disease control rate (DCR) of 95.6%. The median PFS was 14.9 months (95% CI 13.5-16.3) and the OS was 37.0 weeks (95% CI 27.9-46.1). Patients with brain metastases showed higher ORR( P =0.049). Patients with stage ⅢB had longer PFS than those with stage Ⅳ( P =0.007). The most common adverse events were grade 1-2 skin rash (38 patients, 40.9%). Other adverse events included dry skin, oral mucositis, diarrhea and liver function injury. Three patients withdrew because of severe liver injury or skin rash. No treatment related mortality occurred. Conclusions: Icotinib is effective and safe as first-line treatment for Chinese advanced NSCLC patients with EGFR sensitive mutation.

Collaboration in Research and Engineering for Advanced Technology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vrieling, P. Douglas

SNL/CA proposes the Collaboration in Research and Engineering for Advanced Technology and Education (CREATE) facility to support customer-driven national security mission requirements while demonstrating a fiscally responsible approach to cost-control. SNL/CA realizes that due to the current backlog of capital projects in NNSA that following the normal Line Item process to procure capital funding is unlikely and therefore SNL/CA will be looking at all options including Alternative Financing.

Good Governance Matters: Optimizing U.S. PRTs in Afghanistan to Advance Good Governance

DTIC Science & Technology

2009-04-01

a new school. Partnering is critical to ensure the synchronized application of aid. In this case ensuring that teachers ...traces the origins of the U.S. Afghanistan PRT Model from its inception in 2002 to today. The paper will take a critical look at all the three lines...Captain, U.S. Navy A paper submitted to the Faculty of the Joint Advanced Warfighting School in partial satisfaction of the

Navy Shipboard Lasers for Surface, Air, and Missile Defense: Background and Issues for Congress

DTIC Science & Technology

2013-06-27

include silicon carbide ( SiC )- based transistors, transformers and power converters. “ SiC is important because it improves power quality and reduces size...existing shipboard gun systems. An airborne mirror , perhaps mounted on an aerostat,11 could bounce light from a shipboard laser, so as to permit non-line...super conducting RF electron beam injectors, advanced high power cathode technologies, high power compact amplifiers, and advanced mirrors

An Assessment of Early Competitive Prototyping for Major Defense Acquisition Programs

DTIC Science & Technology

2016-04-30

with 20/80 share ratio for EMD; CPFF for test execution. o Percent change in PAUC from development baseline. -2.3%. 3. FAB -T–FET. The Air Force’s...Family of Advanced Beyond Line-of-Sight Terminals ( FAB -T) provides for survivable terminals for communicating strategic nuclear execution orders via...jam-resistant, low probability of intercept waveforms through the Milstar and Advanced Extremely High Frequency (AEHF) satellite constellations. FAB

Pressure Safety: Advanced Self-Study 30120

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glass, George

2016-02-29

Pressure Safety Advance Self-Study (Course 30120) consists of an introduction, five modules, and a quiz. To receive credit in UTrain for completing this course, you must score 80% or better on the 15-question quiz (check UTrain). Directions for initiating the quiz are appended to the end of this training manual. This course contains several links to LANL websites. UTrain might not support active links, so please copy links into the address line in your browser.

Effects of color scheme and message lines of variable message signs on driver performance.

PubMed

Lai, Chien-Jung

2010-07-01

The advancement in variable message signs (VMS) technology has made it possible to display message with various formats. This study presented an ergonomic study on the message design of Chinese variable message signs on urban roads in Taiwan. Effects of color scheme (one, two and three) and number of message lines (single, double and triple) of VMS on participants' response performance were investigated through a laboratory experiment. Results of analysis showed that color scheme and number of message lines are significant factors for participants' response time to VMS. Participants responded faster for two-color than for one- and three-color scheme. Participants also took less response time for double line message than for single and triple line message. Both color scheme and number of message lines had no significant effect on participants' response accuracy. The preference survey after the experiment showed that most participants preferred two-color scheme and double line message to the other combinations. The results can assist in adopting appropriate color scheme and number of message lines of Chinese VMS. Copyright 2009 Elsevier Ltd. All rights reserved.

Warthog: Progress on Coupling BISON and PROTEUS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hart, Shane W.D.

The Nuclear Energy Advanced Modeling and Simulation (NEAMS) program from the Office of Nuclear Energy at the Department of Energy (DOE) provides a robust toolkit for modeling and simulation of current and future advanced nuclear reactor designs. This toolkit provides these technologies organized across product lines, with two divisions targeted at fuels and end-to-end reactor modeling, and a third for integration, coupling, and high-level workflow management. The Fuels Product Line (FPL) and the Reactor Product Line (RPL) provide advanced computational technologies that serve each respective field effectively. There is currently a lack of integration between the product lines, impeding futuremore » improvements of simulation solution fidelity. In order to mix and match tools across the product lines, a new application called Warthog was produced. Warthog is built on the Multi-physics Object-Oriented Simulation Environment (MOOSE) framework developed at Idaho National Laboratory (INL). This report details the continuing efforts to provide the Integration Product Line (IPL) with interoperability using the Warthog code. Currently, this application strives to couple the BISON fuel performance application from the FPL using the PROTEUS Core Neutronics application from the RPL. Warthog leverages as much prior work from the NEAMS program as possible, enabling interoperability between the independently developed MOOSE and SHARP frameworks, and the libMesh and MOAB mesh data formats. Previous work performed on Warthog allowed it to couple a pin cell between the two codes. However, as the temperature changed due to the BISON calculation, the cross sections were not recalculated, leading to errors as the temperature got further away from the initial conditions. XSProc from the SCALE code suite was used to calculate the cross sections as needed. The remainder of this report discusses the changes to Warthog to allow for the implementation of XSProc as an external code. It also discusses the changes made to Warthog to allow it to fit more cleanly into the MultiApp syntax of the MOOSE framework. The capabilities, design, and limitations of Warthog will be described, in addition to some of the test cases that were used to demonstrate the code. Future plans for Warthog will be discussed, including continuation of the modifications to the input and coupling to other SHARP codes such as Nek5000.« less

Meta-analysis Exploring the Effectiveness of S-1-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer.

PubMed

Sun, Xin; Sun, Li; Zhang, Shu-Ling; Xiong, Zhi-Cheng; Ma, Jie-Tao; Han, Cheng-Bo

2017-01-01

S-1 is a new oral fluoropyrimidine formulation that comprises tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. S-1 is designed to enhance antitumor activity and to reduce gastrointestinal toxicity. Several studies have demonstrated that both S-1 monotherapy and S-1 combination regimens showed encouraging efficacies and mild toxicities in the treatment of lung squamous cell carcinoma and adenocarcinoma. However, it is unclear whether S-1 can be used as standard care in advanced non-small cell lung cancer (NSCLC). The purpose of this meta-analysis was to assess the efficacy and safety of S-1-based chemotherapy, compared with standard chemotherapy, in patients with locally advanced or metastatic NSCLC. Thirteen randomized controlled trials (RCTs) involving 2,134 patients with a similar ratio of different pathological types were included. In first-line or second-line chemotherapy, compared with standard chemotherapy, S-1-based chemotherapy showed similar efficacy in terms of median overall survival (mOS), median progression free survival (mPFS), and objective response rate (ORR) (all P > 0.1), and significantly reduced the incidence of grade ≥ 3 hematological toxicities. In patients with locally advanced NSCLC receiving concurrent chemoradiotherapy, compared with standard chemoradiotherapy, significantly improved survival in the S-1-based chemotherapy was noted in terms of mOS and mPFS (risk radio [RR] = 1.289, P = 0.009; RR = 1.289, P = 0.000, respectively) with lower incidence of grade ≥ 3 neutropenia (RR = 0.453, P = 0.000). The present meta-analysis demonstrates that S-1-based chemotherapy shows similar benefits in advanced NSCLC and improves survival in locally advanced NSCLC, compared with standard treatment.

Real-World Data on Prognostic Factors for Overall Survival in EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Gefitinib.

PubMed

Yao, Zong-Han; Liao, Wei-Yu; Ho, Chao-Chi; Chen, Kuan-Yu; Shih, Jin-Yuan; Chen, Jin-Shing; Lin, Zhong-Zhe; Lin, Chia-Chi; Chih-Hsin Yang, James; Yu, Chong-Jen

2017-09-01

This study aimed to identify independent prognostic factors for overall survival (OS) of patients with advanced non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation and receiving gefitinib as first-line treatment in real-world practice. We enrolled 226 patients from June 2011 to May 2013. During this period, gefitinib was the only EGFR-tyrosine kinase inhibitor reimbursed by the Bureau of National Health Insurance of Taiwan. The median progression-free survival and median OS were 11.9 months (95% confidence interval [CI]: 9.7-14.2) and 26.9 months (21.2-32.5), respectively. The Cox proportional hazards regression model revealed that postoperative recurrence, performance status (Eastern Cooperative Oncology Grade [ECOG] ≥2), smoking index (≥20 pack-years), liver metastasis at initial diagnosis, and chronic hepatitis C virus (HCV) infection were independent prognostic factors for OS (hazard ratio [95% CI] 0.3 [0.11-0.83], p  = .02; 2.69 [1.60-4.51], p  < .001; 1.92 [1.24-2.97], p  = .003; 2.26 [1.34-3.82], p  = .002; 3.38 [1.85-7.78], p  < .001, respectively). However, brain metastasis (BM) at initial diagnosis or intracranial progression during gefitinib treatment had no impact on OS (1.266 [0.83-1.93], p  = .275 and 0.75 [0.48-1.19], p  = .211, respectively). HCV infection, performance status (ECOG ≥2), newly diagnosed advanced NSCLC without prior operation, and liver metastasis predicted poor OS in EGFR mutation-positive advanced NSCLC patients treated with first-line gefitinib; however, neither BM at initial diagnosis nor intracranial progression during gefitinib treatment had an impact on OS. The finding that chronic hepatitis C virus (HCV) infection might predict poor overall survival (OS) in epidermal growth factor receptor mutation-positive advanced non-small cell lung cancer (NSCLC) patients treated with first-line gefitinib may raise awareness of benefit from anti-HCV treatment in this patient population. Brain metastasis in the initial diagnosis or intracranial progression during gefitinib treatment is not a prognostic factor for OS. This study, which enrolled a real-world population of NSCLC patients, including sicker patients who were not eligible for a clinical trial, may have impact on guiding usual clinical practice. © AlphaMed Press 2017.

Nuclear astrophysics lessons from INTEGRAL.

PubMed

Diehl, Roland

2013-02-01

Measurements of high-energy photons from cosmic sources of nuclear radiation through ESA's INTEGRAL mission have advanced our knowledge: new data with high spectral resolution showed that characteristic gamma-ray lines from radioactive decays occur throughout the Galaxy in its interstellar medium. Although the number of detected sources and often the significance of the astrophysical results remain modest, conclusions derived from this unique astronomical window of radiation originating from nuclear processes are important, complementing the widely-employed atomic-line based spectroscopy. We review the results and insights obtained in the past decade from gamma-ray line measurements of cosmic sources in the context of their astrophysical questions.

Communication: Visible line intensities of the triatomic hydrogen ion from experiment and theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petrignani, Annemieke; Berg, Max H.; Grussie, Florian

2014-12-28

The visible spectrum of H{sub 3}{sup +} is studied using high-sensitivity action spectroscopy in a cryogenic radiofrequency multipole trap. Advances are made to measure the weak ro-vibrational transitions from the lowest rotational states of H{sub 3}{sup +} up to high excitation energies providing visible line intensities and, after normalisation to an infrared calibration line, the corresponding Einstein B coefficients. Ab initio predictions for the Einstein B coefficients are obtained from a highly precise dipole moment surface of H{sub 3}{sup +} and found to be in excellent agreement, even in the region where states have been classified as chaotic.

Spectral comb mitigation to improve continuous-wave search sensitivity in Advanced LIGO

NASA Astrophysics Data System (ADS)

Neunzert, Ansel; LIGO Scientific Collaboration; Virgo Collaboration

2017-01-01

Searches for continuous gravitational waves, such as those emitted by rapidly spinning non-axisymmetric neutron stars, are degraded by the presence of narrow noise ``lines'' in detector data. These lines either reduce the spectral band available for analysis (if identified as noise and removed) or cause spurious outliers (if unidentified). Many belong to larger structures known as combs: series of evenly-spaced lines which appear across wide frequency ranges. This talk will focus on the challenges of comb identification and mitigation. I will discuss tools and methods for comb analysis, and case studies of comb mitigation at the LIGO Hanford detector site.

Automated detection of jet contrails using the AVHRR split window

NASA Technical Reports Server (NTRS)

Engelstad, M.; Sengupta, S. K.; Lee, T.; Welch, R. M.

1992-01-01

This paper investigates the automated detection of jet contrails using data from the Advanced Very High Resolution Radiometer. A preliminary algorithm subtracts the 11.8-micron image from the 10.8-micron image, creating a difference image on which contrails are enhanced. Then a three-stage algorithm searches the difference image for the nearly-straight line segments which characterize contrails. First, the algorithm searches for elevated, linear patterns called 'ridges'. Second, it applies a Hough transform to the detected ridges to locate nearly-straight lines. Third, the algorithm determines which of the nearly-straight lines are likely to be contrails. The paper applies this technique to several test scenes.

Latest evolution in a 300mm graphoepitaxy pilot line flow for L/S applications

NASA Astrophysics Data System (ADS)

Claveau, G.; Argoud, M.; Pimenta-Barros, P.; Chamiot-Maitral, G.; Tiron, R.; Chevalier, X.; Navarro, C.

2017-03-01

Directed Self Assembly (DSA) of block-copolymers (BCPs) used as a complementary technique to the 193nm immersion lithography has demonstrated sub-10nm node applications in both via and line/space patterning. We propose however to study the performance of graphoepitaxy which allows DSA with thicker initial BCP layer, higher multiplication factors and stronger orientation control of lamellae. The aim of this work is to use the 300mm pilot line available at LETI and Arkema's advanced materials to evaluate the performances of a novel graphoepitaxy process based on the work on a 38nm period lamellar PS-b-PMMA (L38) reported before.

Development of Advanced Technologies for Complete Genomic and Proteomic Characterization of Quantized Human Tumor Cells

DTIC Science & Technology

2014-07-01

establishment of Glioblastoma ( GBM ) cell lines from GBM patient’s tumor samples and quantized cell populations of each of the parental GBM cell lines, we... GBM patients are now well established and from the basis of the molecular characterization of the tumor development and signatures presented by these...analysis of these quantized cell sub populations and have begun to assemble the protein signatures of GBM tumors underpinned by the comprehensive

ANIMAL COGNITION. Comment on "Number-space mapping in the newborn chick resembles humans' mental number line".

PubMed

Mangalam, Madhur; Karve, Shraddha Madhav

2015-06-26

Rugani et al. (Reports, 30 January 3015, p. 534) tested 3-day-old domestic chicks using an innovative experimental setup and demonstrate the presence of the mental number line. We raise concerns regarding this conclusion by highlighting the possible loopholes in the experimental design and the data analysis procedures. We further suggest auxiliary experiments that can substantiate the authors' claim. Copyright © 2015, American Association for the Advancement of Science.

Spectrum of Transient ASASSN-13at

NASA Astrophysics Data System (ADS)

Garnavich, Peter; Deal, Shanel

2013-06-01

We observed the transient ASASSN-13at (ATEL 5168) on June 28.3 (UT) with the Vatican Advanced Technology Telescope (VATT) and VATTSPEC instrument. The resulting spectrum covers the wavelength range between 365 nm and 750 nm with a resolution of 1100. The spectrum of ASASSN-13at shows a blue continuum with strong Balmer absorption lines. Helium absorption at 447 nm and 588 nm is also seen. Blue-shifted emission lines are visible within the Halpha and Hbeta absorption features.

Advances in modeling aerodynamic decelerator dynamics.

NASA Technical Reports Server (NTRS)

Whitlock, C. H.

1973-01-01

The Viking entry vehicle uses a lines-first type of deployment in which the parachute, packed in a deployment bag, gets ejected rearward from the vehicle by a mortar. As the bag moves rearward, first the lines are unfurled and then the canopy. An analysis of the unfurling process is conducted, giving attention to longitudinal and rotational dynamics. It is shown that analytical modeling of aerodynamic systems provides significant information for a better understanding of the physics of the deployment process.

Importing, caring, breeding, genotyping, and phenotyping a genetic mouse in a Chinese university.

PubMed

Kuo, S T; Wu, Q H; Liu, B; Xie, Z L; Wu, X; Shang, S J; Zhang, X Y; Kang, X J; Liu, L N; Zhu, F P; Wang, Y S; Hu, M Q; Xu, H D; Zhou, L; Liu, B; Chai, Z Y; Zhang, Q F; Liu, W; Teng, S S; Wang, C H; Guo, N; Dou, H Q; Zuo, P L; Zheng, L H; Zhang, C X; Zhu, D S; Wang, L; Wang, S R; Zhou, Z

2014-07-01

The genetic manipulation of the laboratory mouse has been well developed and generated more and more mouse lines for biomedical research. To advance our science exploration, it is necessary to share genetically modified mouse lines with collaborators between institutions, even in different countries. The transfer process is complicated. Significant paperwork and coordination are required, concerning animal welfare, intellectual property rights, colony health status, and biohazard. Here, we provide a practical example of importing a transgenic mice line, Dynamin 1 knockout mice, from Yale University in the USA to Perking University in China for studying cell secretion. This example including the length of time that required for paper work, mice quarantine at the receiving institution, and expansion of the mouse line for experiments. The procedure described in this paper for delivery live transgenic mice from USA to China may serve a simple reference for transferring mouse lines between other countries too.

Rate of Mass Loss Across the Instability Threshold for Thwaites Glacier Determines Rate of Mass Loss for Entire Basin

NASA Astrophysics Data System (ADS)

Waibel, M. S.; Hulbe, C. L.; Jackson, C. S.; Martin, D. F.

2018-01-01

Rapid change now underway on Thwaites Glacier (TG) raises concern that a threshold for unstoppable grounding line retreat has been or is about to be crossed. We use a high-resolution ice sheet model to examine the mechanics of TG self-sustained retreat by nudging the grounding line just past the point of instability. We find that by modifying surface slope in the region of the grounding line, the rate of the forcing dictates the rate of retreat, even after the external forcing is removed. Grounding line retreats that begin faster proceed more rapidly because the shorter time interval for the grounding line to erode into the grounded ice sheet means relatively thicker ice and larger driving stress upstream of the boundary. Retreat is sensitive to short-duration re-advances associated with reduced external forcing where the bathymetry allows regrounding, even when an instability is invoked.

Practical Repair Method for Unilateral Cleft Lips: Straight-Line Advanced Release Technique.

PubMed

Baek, Rong-Min; Choi, Jun-Ho; Kim, Baek-Kyu

2016-04-01

Straight-line closure repair of unilateral cleft lips was first introduced in the 1840s, and since then, many different techniques have been attempted for cleft repair. However, these methods have several disadvantages and are difficult to adopt. In this study, we describe our novel technique, known as Straight-Line Advanced Release Technique (StART), and its application in treating several cases of unilateral cleft lip. The preoperative design of the surgical method is drawn on the skin, the vermilion, and the oral mucosa. A total of 13 points are marked (points 0-12). The A flap, B flap, triangular flap, M (medial mucosal) flap, and L (lateral mucosal) flap are designed. After completion of the preoperative marking, the wide dissection is performed to separate the orbicularis oris muscle completely from the abnormally inserted bony structure and the enveloped skin-mucosal flap. The freed orbicularis oris muscle is then reconstructed with full width. After all planes of the lip wound are closed, a straight vertical skin suture line is achieved without any unnecessary transverse scar. Unilateral cleft lip repair using StART was conducted in 145 patients between 1993 and 2012. Cases of microform cleft lip were excluded. A total of 21 patients (14%) required a secondary operation on the lip after the first unilateral cheiloplasty. In all patients, satisfactory surgical outcomes were obtained with an indistinct straight-lined scar and a well-aligned lip contour. To acquire a natural and balanced shape in unilateral cleft lip repair, we recommend the novel StART.

EUV microexposures at the ALS using the 0.3-NA MET projectionoptics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Naulleau, Patrick; Goldberg, Kenneth A.; Anderson, Erik

2005-09-01

The recent development of high numerical aperture (NA) EUV optics such as the 0.3-NA Micro Exposure Tool (MET) optic has given rise to a new class of ultra-high resolution microexposure stations. Once such printing station has been developed and implemented at Lawrence Berkeley National Laboratory's Advanced Light Source. This flexible printing station utilizes a programmable coherence illuminator providing real-time pupil-fill control for advanced EUV resist and mask development. The Berkeley exposure system programmable illuminator enables several unique capabilities. Using dipole illumination out to {sigma}=1, the Berkeley tool supports equal-line-space printing down to 12 nm, well beyond the capabilities of similarmore » tools. Using small-sigma illumination combined with the central obscuration of the MET optic enables the system to print feature sizes that are twice as small as those coded on the mask. In this configuration, the effective 10x-demagnification for equal lines and spaces reduces the mask fabrication burden for ultra-high-resolution printing. The illuminator facilitates coherence studies such as the impact of coherence on line-edge roughness (LER) and flare. Finally the illuminator enables novel print-based aberration monitoring techniques as described elsewhere in these proceedings. Here we describe the capabilities of the new MET printing station and present system characterization results. Moreover, we present the latest printing results obtained in experimental resists. Limited by the availability of high-resolution photoresists, equal line-space printing down to 25 nm has been demonstrated as well as isolated line printing down to 29 nm with an LER of approaching 3 nm.« less

Operational Arctic: The Potential for Crisis or Conflict in the Arctic Region and Application of Operational Art

DTIC Science & Technology

2014-05-22

PRC Peoples Republic of China SAMS School of Advanced Military Studies SLOC Sea Lines of Communication SSI Strategic Studies Institute UN...the North” (Monograph, School of Advanced Military Studies, 2013), 1. 5Robert Sibley, “Arrival of China in Arctic puts Canada on Alert,” Ottawa...the possibility of resource wealth or shipping opportunities.10 Some of the world’s more powerful and wealthy nations, Russia, Canada, China , and

Improved Foundry Castings Utilizing CAD/CAM (Computer Aided Design/ Computer Aided Manufacture). Volume 1. Overview

DTIC Science & Technology

1988-06-30

casting. 68 Figure 1-9: Line printer representation of roll solidification. 69 Figure I1-1: Test casting model. 76 Figure 11-2: Division of test casting...writing new casting analysis and design routines. The new routines would take advantage of advanced criteria for predicting casting soundness and cast...properties and technical advances in computer hardware and software. 11 2. CONCLUSIONS UPCAST, a comprehensive software package, has been developed for

Targeting fibroblast growth factor receptors and immune checkpoint inhibitors for the treatment of advanced bladder cancer: New direction and New Hope.

PubMed

Morales-Barrera, Rafael; Suárez, Cristina; de Castro, Ana Martínez; Racca, Fabricio; Valverde, Claudia; Maldonado, Xavier; Bastaros, Juan Maria; Morote, Juan; Carles, Joan

2016-11-01

Bladder cancer is one of the leading causes of death in Europe and the United States. About 25% of patients with bladder cancer have advanced disease (muscle-invasive or metastatic disease) at presentation and are candidates for systemic chemotherapy. In the setting of metastatic disease, use of cisplatin-based regimens improves survival. However, despite initial high response rates, the responses are typically not durable leading to recurrence and death in the vast majority of these patients with median overall survival of 15months and a 5-year survival rate of ⩽10%. Furthermore, unfit patients for cisplatin have no standard of care for first line therapy in advance disease Most second-line chemotherapeutic agents tested have been disappointing. Newer targeted drugs and immunotherapies are being studied in the metastatic setting, their usefulness in the neoadjuvant and adjuvant settings is also an intriguing area of ongoing research. Thus, new treatment strategies are clearly needed. The comprehensive evaluation of multiple molecular pathways characterized by The Cancer Genome Atlas project has shed light on potential therapeutic targets for bladder urothelial carcinomas. We have focused especially on emerging therapies in locally advanced and metastatic urothelial carcinoma with an emphasis on immune checkpoints inhibitors and FGFR targeted therapies, which have shown great promise in early clinical studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Theory-based modifications of an advanced notification letter improves screening for bowel cancer in men: A randomised controlled trial.

PubMed

Zajac, Ian T; Duncan, Amy C; Flight, Ingrid; Wittert, Gary A; Cole, Stephen R; Young, Graeme P; Wilson, Carlene J; Turnbull, Deborah A

2016-09-01

Male participation in screening for bowel cancer is sub-optimal. Theory-based interventions provide a means of improving screening uptake. To test the efficacy of modifying consumer invitation material in line with continuum and stage theories of health behaviour on screening participation. N = 9216 Australian men aged 50-74 years were randomised to one of four trial arms in a 2 × 2 factorial design randomised controlled trial. Participants received either standard invitation material (control group), or combinations of modified advance-notification and invitation letters. A subsample completed baseline and endpoint behavioural surveys. Participants who received the modified advance notification letter were 12% more likely to screen than those who received the standard version (RR = 1.12, χ(2)(1) = 10.38, p = 0.001). The modified invitation letter did not impact screening uptake (RR = 0.97, χ(2)(1) = 0.63, p = 0.424). No significant changes in psychological variables due to the intervention were observed. Modifications to advance notification letters in line with health behaviour theories significantly improves screening uptake in men. Australian New Zealand Clinical Trials Registry: ACTRN12612001122842 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362688. Copyright © 2016 Elsevier Ltd. All rights reserved.

Retrotransposons as regulators of gene expression.

PubMed

Elbarbary, Reyad A; Lucas, Bronwyn A; Maquat, Lynne E

2016-02-12

Transposable elements (TEs) are both a boon and a bane to eukaryotic organisms, depending on where they integrate into the genome and how their sequences function once integrated. We focus on two types of TEs: long interspersed elements (LINEs) and short interspersed elements (SINEs). LINEs and SINEs are retrotransposons; that is, they transpose via an RNA intermediate. We discuss how LINEs and SINEs have expanded in eukaryotic genomes and contribute to genome evolution. An emerging body of evidence indicates that LINEs and SINEs function to regulate gene expression by affecting chromatin structure, gene transcription, pre-mRNA processing, or aspects of mRNA metabolism. We also describe how adenosine-to-inosine editing influences SINE function and how ongoing retrotransposition is countered by the body's defense mechanisms. Copyright © 2016, American Association for the Advancement of Science.

Experimental study of spectral and spatial distribution of solar X-rays

NASA Technical Reports Server (NTRS)

Acton, L. W.; Catura, R. C.; Culhane, J. L.

1972-01-01

The study of the physical conditions within the solar corona and the development of instrumentation and technical expertise necessary for advanced studies of solar X-ray emission are reported. Details are given on the Aerobee-borne-X-ray spectrometer/monochromator and also on the observing program. Preliminary discussions of some results are presented and include studies of helium-like line emission, mapping O(VII) and Ne(IX) lines, survey of O(VII) and Ne(IX) lines, study of plage regions and small flares, and analysis of line emission from individual active regions. It is concluded that the use of large-area collimated Bragg spectrometers to scan narrow wavelength intervals and the capability of the SPARCS pointing control to execute a complex observing program are established.

The genome editing toolbox: a spectrum of approaches for targeted modification.

PubMed

Cheng, Joseph K; Alper, Hal S

2014-12-01

The increase in quality, quantity, and complexity of recombinant products heavily drives the need to predictably engineer model and complex (mammalian) cell systems. However, until recently, limited tools offered the ability to precisely manipulate their genomes, thus impeding the full potential of rational cell line development processes. Targeted genome editing can combine the advances in synthetic and systems biology with current cellular hosts to further push productivity and expand the product repertoire. This review highlights recent advances in targeted genome editing techniques, discussing some of their capabilities and limitations and their potential to aid advances in pharmaceutical biotechnology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Haploinsufficiency of E-selectin ligand-1 is Associated with Reduced Atherosclerotic Plaque Macrophage Content while Complete Deficiency Leads to Early Embryonic Lethality in Mice

PubMed Central

Luo, Wei; Wang, Hui; Guo, Chiao; Wang, Jintao; Kwak, Jeffrey; Bahrou, Kristina L; Eitzman, Daniel T.

2012-01-01

E-selectin-1 (ESL-1), also known as golgi complex-localized glycoprotein-1 (GLG1), homocysteine-rich fibroblast growth factor receptor (CGR-1), and latent transforming growth factor-β complex protein 1 (LTCP-1), is a multifunctional protein with widespread tissue distribution. To determine the functional consequences of ESL-1 deficiency, mice were generated carrying an ESL-1 gene trap. After backcrossing to C57BL6/J for 6 generations, mice heterozygous for the gene trap (ESL-1+/-) were intercrossed to produce ESL-1-/- mice, however ESL-1-/- mice were not viable, even at embryonic day E10.5. To determine the effect of heterozygous ESL-1 deficiency on atherosclerosis, apolipoprotein E deficient (ApoE-/-), ESL-1+/- mice were generated and fed western diet. Compared to ApoE-/-, ESL-1++ mice, atherosclerotic lesions from ApoE-/-, ESL-1+/- contained more collagen and fewer macrophages, suggesting increased plaque stability. In conclusion, heterozygous deficiency of ESL-1 is associated with features of increased atherosclerotic plaque stability while complete deficiency of ESL-1 leads to embryonic lethality. PMID:22939356

Studying the evolutionary relationships and phylogenetic trees of 21 groups of tRNA sequences based on complex networks.

PubMed

Wei, Fangping; Chen, Bowen

2012-03-01

To find out the evolutionary relationships among different tRNA sequences of 21 amino acids, 22 networks are constructed. One is constructed from whole tRNAs, and the other 21 networks are constructed from the tRNAs which carry the same amino acids. A new method is proposed such that the alignment scores of any two amino acids groups are determined by the average degree and the average clustering coefficient of their networks. The anticodon feature of isolated tRNA and the phylogenetic trees of 21 group networks are discussed. We find that some isolated tRNA sequences in 21 networks still connect with other tRNAs outside their group, which reflects the fact that those tRNAs might evolve by intercrossing among these 21 groups. We also find that most anticodons among the same cluster are only one base different in the same sites when S ≥ 70, and they stay in the same rank in the ladder of evolutionary relationships. Those observations seem to agree on that some tRNAs might mutate from the same ancestor sequences based on point mutation mechanisms.

The congenic normal R/APfd and jaundiced R/APfd-j/j rat strains: a new animal model of hereditary non-haemolytic unconjugated hyperbilirubinaemia due to defective bilirubin conjugation.

PubMed

Leyten, R; Vroemen, J P; Blanckaert, N; Heirwegh, K P

1986-10-01

In this paper the production of the R/APfd-j/j strain which is congenic with the R/APfd strain is reported. The R/APfd-j/j completely lacks hepatic bilirubin UDP-glucuronyltransferase activity, as do our GUNNXR/Pfd-j/j rat strain and various other stocks of GUNN rats (j/j) described in the literature. Our recombinant inbred strain GUNNXR/Pfd-j/j was produced from non-inbred GUNN (j/j) rats. This GUNNXR/Pfd-j/j rat was used as a donor of the jaundice gene j, the R/APfd rat serving as the recipient. After eight backcross-intercross cycles (16 generations) the R/APfd-j/j strain was obtained which is congenic with the R/APfd strain. Congenicity was demonstrated by various techniques including transplantation of skin tissue, strain-specific tumour cells and hepatocytes, the mixed lymphocyte reaction, and comparison of biochemical markers. The potential of the novel inbred strain of jaundiced rat, R/APfd-j/j, and the corresponding control strain R/APfd for biochemical and clinical studies of bilirubin metabolism are briefly discussed.

Differential detection of genetic Loci underlying stem and root lignin content in Populus.

PubMed

Yin, Tongming; Zhang, Xinye; Gunter, Lee; Priya, Ranjan; Sykes, Robert; Davis, Mark; Wullschleger, Stan D; Tuskan, Gerald A

2010-11-22

In this study, we established a comprehensive genetic map with a large number of progeny from a three-generation hybrid Populus intercross, and phenotyped the lignin content, S/G ratio and 28 cell wall subcomponents both in stems and roots for the mapping individuals. Phenotypic analysis revealed that lignin content and syringyl-to-guaiacyl (S/G) ratio using pyrolysis molecular beam mass spectroscopy (pyMBMS) varied among mapping individuals. Phenotypic analysis revealed that stem lignin content is significantly higher than that in root and the quantified traits can be classified into four distinct groups, with strong correlations observed among components within organs. Altogether, 179 coordinating QTLs were detected, and they were co-localized into 49 genetic loci, 27 of which appear to be pleiotropic. Many of the detected genetic loci were detected differentially in stem and root. This is the first report of separate genetic loci controlling cell wall phenotypes above and below ground. These results suggest that it may be possible to modify lignin content and composition via breed and/or engineer as a means of simultaneously improving Populus for cellulosic ethanol production and carbon sequestration.

Identification of novel mouse genes conferring posthypoxic pauses

PubMed Central

Gillombardo, C. Barton; Yamauchi, Motoo; Adams, Mark D.; Dostal, Jesse; Chai, Sam; Moore, Michael W.; Donovan, Lucas M.; Han, Fang

2012-01-01

Although central to the susceptibility of adult diseases characterized by abnormal rhythmogenesis, characterizing the genes involved is a challenge. We took advantage of the C57BL/6J (B6) trait of hypoxia-induced periodic breathing and its absence in the C57BL/6J-Chr 1A/J/NaJ chromosome substitution strain to test the feasibility of gene discovery for this abnormality. Beginning with a genetic and phenotypic analysis of an intercross study between these strains, we discovered three quantitative trait loci (QTLs) on mouse chromosome 1, with phenotypic effects. Fine-mapping reduced the genomic intervals and gene content, and the introgression of one QTL region back onto the C57BL/6J-Chr 1A/J/NaJ restored the trait. mRNA expression of non-synonymous genes in the introgressed region in the medulla and pons found evidence for differential expression of three genes, the highest of which was apolipoprotein A2, a lipase regulator; the apo a2 peptide fragment (THEQLTPLVR), highly expressed in the liver, was expressed in low amounts in the medulla but did not correlate with trait expression. This work directly demonstrates the impact of elements on mouse chromosome 1 in respiratory rhythmogenesis. PMID:22539170

Mapping of quantitative trait loci using the skew-normal distribution.

PubMed

Fernandes, Elisabete; Pacheco, António; Penha-Gonçalves, Carlos

2007-11-01

In standard interval mapping (IM) of quantitative trait loci (QTL), the QTL effect is described by a normal mixture model. When this assumption of normality is violated, the most commonly adopted strategy is to use the previous model after data transformation. However, an appropriate transformation may not exist or may be difficult to find. Also this approach can raise interpretation issues. An interesting alternative is to consider a skew-normal mixture model in standard IM, and the resulting method is here denoted as skew-normal IM. This flexible model that includes the usual symmetric normal distribution as a special case is important, allowing continuous variation from normality to non-normality. In this paper we briefly introduce the main peculiarities of the skew-normal distribution. The maximum likelihood estimates of parameters of the skew-normal distribution are obtained by the expectation-maximization (EM) algorithm. The proposed model is illustrated with real data from an intercross experiment that shows a significant departure from the normality assumption. The performance of the skew-normal IM is assessed via stochastic simulation. The results indicate that the skew-normal IM has higher power for QTL detection and better precision of QTL location as compared to standard IM and nonparametric IM.

Chromosome Rearrangements That Involve the Nucleolus Organizer Region in Neurospora

PubMed Central

Perkins, D. D.; Raju, N. B.; Barry, E. G.; Butler, D. K.

1995-01-01

In ~3% of Neurospora crassa rearrangements, part of a chromosome arm becomes attached to the nucleolus organizer region (NOR) at one end of chromosome 2 (linkage group V). Investigations with one inversion and nine translocations of this type are reported here. They appear genetically to be nonreciprocal and terminal. When a rearrangement is heterozygous, about one-third of viable progeny are segmental aneuploids with the translocated segment present in two copies, one in normal position and one associated with the NOR. Duplications from many of the rearrangements are highly unstable, breaking down by loss of the NOR-attached segment to restore normal chromosome sequence. When most of the rearrangements are homozygous, attenuated strands can be seen extending through the unstained nucleolus at pachytene, joining the translocated distal segment to the remainder of chromosome 2. Although the rearrangements appear genetically to be nonreciprocal, molecular evidence shows that at least several of them are physically reciprocal, with a block of rDNA repeats translocated away from the NOR. Evidence that NOR-associated breakpoints are nonterminal is also provided by intercrosses between pairs of translocations that transfer different-length segments of the same donor-chromosome arm to the NOR. PMID:8582636

Path lumping: An efficient algorithm to identify metastable path channels for conformational dynamics of multi-body systems

NASA Astrophysics Data System (ADS)

Meng, Luming; Sheong, Fu Kit; Zeng, Xiangze; Zhu, Lizhe; Huang, Xuhui

2017-07-01

Constructing Markov state models from large-scale molecular dynamics simulation trajectories is a promising approach to dissect the kinetic mechanisms of complex chemical and biological processes. Combined with transition path theory, Markov state models can be applied to identify all pathways connecting any conformational states of interest. However, the identified pathways can be too complex to comprehend, especially for multi-body processes where numerous parallel pathways with comparable flux probability often coexist. Here, we have developed a path lumping method to group these parallel pathways into metastable path channels for analysis. We define the similarity between two pathways as the intercrossing flux between them and then apply the spectral clustering algorithm to lump these pathways into groups. We demonstrate the power of our method by applying it to two systems: a 2D-potential consisting of four metastable energy channels and the hydrophobic collapse process of two hydrophobic molecules. In both cases, our algorithm successfully reveals the metastable path channels. We expect this path lumping algorithm to be a promising tool for revealing unprecedented insights into the kinetic mechanisms of complex multi-body processes.

Low power femtosecond tip-based nanofabrication with advanced control

NASA Astrophysics Data System (ADS)

Liu, Jiangbo; Guo, Zhixiong; Zou, Qingze

2018-02-01

In this paper, we propose an approach to enable the use of low power femtosecond laser in tip-based nanofabrication (TBN) without thermal damage. One major challenge in laser-assisted TBN is in maintaining precision control of the tip-surface positioning throughout the fabrication process. An advanced iterative learning control technique is exploited to overcome this challenge in achieving high-quality patterning of arbitrary shape on a metal surface. The experimental results are analyzed to understand the ablation mechanism involved. Specifically, the near-field radiation enhancement is examined via the surface-enhanced Raman scattering effect, and it was revealed the near-field enhanced plasma-mediated ablation. Moreover, silicon nitride tip is utilized to alleviate the adverse thermal damage. Experiment results including line patterns fabricated under different writing speeds and an "R" pattern are presented. The fabrication quality with regard to the line width, depth, and uniformity is characterized to demonstrate the efficacy of the proposed approach.

Identification and mitigation of narrow spectral artifacts that degrade searches for persistent gravitational waves in the first two observing runs of Advanced LIGO

NASA Astrophysics Data System (ADS)

Covas, P. B.; Effler, A.; Goetz, E.; Meyers, P. M.; Neunzert, A.; Oliver, M.; Pearlstone, B. L.; Roma, V. J.; Schofield, R. M. S.; Adya, V. B.; Astone, P.; Biscoveanu, S.; Callister, T. A.; Christensen, N.; Colla, A.; Coughlin, E.; Coughlin, M. W.; Crowder, S. G.; Dwyer, S. E.; Eggenstein, H.-B.; Hourihane, S.; Kandhasamy, S.; Liu, W.; Lundgren, A. P.; Matas, A.; McCarthy, R.; McIver, J.; Mendell, G.; Ormiston, R.; Palomba, C.; Papa, M. A.; Piccinni, O. J.; Rao, K.; Riles, K.; Sammut, L.; Schlassa, S.; Sigg, D.; Strauss, N.; Tao, D.; Thorne, K. A.; Thrane, E.; Trembath-Reichert, S.; Abbott, B. P.; Abbott, R.; Abbott, T. D.; Adams, C.; Adhikari, R. X.; Ananyeva, A.; Appert, S.; Arai, K.; Aston, S. M.; Austin, C.; Ballmer, S. W.; Barker, D.; Barr, B.; Barsotti, L.; Bartlett, J.; Bartos, I.; Batch, J. C.; Bejger, M.; Bell, A. S.; Betzwieser, J.; Billingsley, G.; Birch, J.; Biscans, S.; Biwer, C.; Blair, C. D.; Blair, R. M.; Bork, R.; Brooks, A. F.; Cao, H.; Ciani, G.; Clara, F.; Clearwater, P.; Cooper, S. J.; Corban, P.; Countryman, S. T.; Cowart, M. J.; Coyne, D. C.; Cumming, A.; Cunningham, L.; Danzmann, K.; Costa, C. F. Da Silva; Daw, E. J.; DeBra, D.; DeRosa, R. T.; DeSalvo, R.; Dooley, K. L.; Doravari, S.; Driggers, J. C.; Edo, T. B.; Etzel, T.; Evans, M.; Evans, T. M.; Factourovich, M.; Fair, H.; Galiana, A. Fernández; Ferreira, E. C.; Fisher, R. P.; Fong, H.; Frey, R.; Fritschel, P.; Frolov, V. V.; Fulda, P.; Fyffe, M.; Gateley, B.; Giaime, J. A.; Giardina, K. D.; Goetz, R.; Goncharov, B.; Gras, S.; Gray, C.; Grote, H.; Gushwa, K. E.; Gustafson, E. K.; Gustafson, R.; Hall, E. D.; Hammond, G.; Hanks, J.; Hanson, J.; Hardwick, T.; Harry, G. M.; Heintze, M. C.; Heptonstall, A. W.; Hough, J.; Inta, R.; Izumi, K.; Jones, R.; Karki, S.; Kasprzack, M.; Kaufer, S.; Kawabe, K.; Kennedy, R.; Kijbunchoo, N.; Kim, W.; King, E. J.; King, P. J.; Kissel, J. S.; Korth, W. Z.; Kuehn, G.; Landry, M.; Lantz, B.; Laxen, M.; Liu, J.; Lockerbie, N. A.; Lormand, M.; MacInnis, M.; Macleod, D. M.; Márka, S.; Márka, Z.; Markosyan, A. S.; Maros, E.; Marsh, P.; Martin, I. W.; Martynov, D. V.; Mason, K.; Massinger, T. J.; Matichard, F.; Mavalvala, N.; McClelland, D. E.; McCormick, S.; McCuller, L.; McIntyre, G.; McRae, T.; Merilh, E. L.; Miller, J.; Mittleman, R.; Mo, G.; Mogushi, K.; Moraru, D.; Moreno, G.; Mueller, G.; Mukund, N.; Mullavey, A.; Munch, J.; Nelson, T. J. N.; Nguyen, P.; Nuttall, L. K.; Oberling, J.; Oktavia, O.; Oppermann, P.; Oram, Richard J.; O'Reilly, B.; Ottaway, D. J.; Overmier, H.; Palamos, J. R.; Parker, W.; Pele, A.; Penn, S.; Perez, C. J.; Phelps, M.; Pierro, V.; Pinto, I.; Principe, M.; Prokhorov, L. G.; Puncken, O.; Quetschke, V.; Quintero, E. A.; Radkins, H.; Raffai, P.; Ramirez, K. E.; Reid, S.; Reitze, D. H.; Robertson, N. A.; Rollins, J. G.; Romel, C. L.; Romie, J. H.; Ross, M. P.; Rowan, S.; Ryan, K.; Sadecki, T.; Sanchez, E. J.; Sanchez, L. E.; Sandberg, V.; Savage, R. L.; Sellers, D.; Shaddock, D. A.; Shaffer, T. J.; Shapiro, B.; Shoemaker, D. H.; Slagmolen, B. J. J.; Smith, B.; Smith, J. R.; Sorazu, B.; Spencer, A. P.; Staley, A.; Strain, K. A.; Sun, L.; Tanner, D. B.; Tasson, J. D.; Taylor, R.; Thomas, M.; Thomas, P.; Toland, K.; Torrie, C. I.; Traylor, G.; Tse, M.; Tuyenbayev, D.; Vajente, G.; Valdes, G.; van Veggel, A. A.; Vecchio, A.; Veitch, P. J.; Venkateswara, K.; Vo, T.; Vorvick, C.; Wade, M.; Walker, M.; Ward, R. L.; Warner, J.; Weaver, B.; Weiss, R.; Weßels, P.; Willke, B.; Wipf, C. C.; Wofford, J.; Worden, J.; Yamamoto, H.; Yancey, C. C.; Yu, Hang; Yu, Haocun; Zhang, L.; Zhu, S.; Zucker, M. E.; Zweizig, J.; LSC Instrument Authors

2018-04-01

Searches are under way in Advanced LIGO and Virgo data for persistent gravitational waves from continuous sources, e.g. rapidly rotating galactic neutron stars, and stochastic sources, e.g. relic gravitational waves from the Big Bang or superposition of distant astrophysical events such as mergers of black holes or neutron stars. These searches can be degraded by the presence of narrow spectral artifacts (lines) due to instrumental or environmental disturbances. We describe a variety of methods used for finding, identifying and mitigating these artifacts, illustrated with particular examples. Results are provided in the form of lists of line artifacts that can safely be treated as non-astrophysical. Such lists are used to improve the efficiencies and sensitivities of continuous and stochastic gravitational wave searches by allowing vetoes of false outliers and permitting data cleaning.

Space station data system analysis/architecture study. Task 2: Options development DR-5. Volume 1: Technology options

NASA Technical Reports Server (NTRS)

1985-01-01

The second task in the Space Station Data System (SSDS) Analysis/Architecture Study is the development of an information base that will support the conduct of trade studies and provide sufficient data to make key design/programmatic decisions. This volume identifies the preferred options in the technology category and characterizes these options with respect to performance attributes, constraints, cost, and risk. The technology category includes advanced materials, processes, and techniques that can be used to enhance the implementation of SSDS design structures. The specific areas discussed are mass storage, including space and round on-line storage and off-line storage; man/machine interface; data processing hardware, including flight computers and advanced/fault tolerant computer architectures; and software, including data compression algorithms, on-board high level languages, and software tools. Also discussed are artificial intelligence applications and hard-wire communications.

Immunostimulatory monoclonal antibodies for hepatocellular carcinoma therapy. Trends and perspectives.

PubMed

Mazzolini, Guillermo D; Malvicini, Mariana

2018-01-01

Hepatocellular carcinoma (HCC) is the second cause of cancer-related death in the world and is the main cause of death in cirrhotic patients. Unfortunately, the incidence of HCC has grown significantly in the last decade. Curative treatments such as surgery, liver transplantation or percutaneous ablation can only be applied in less than 30% of cases. The multikinase inhibitor sorafenib is the first line therapy for advanced HCC. Regorafenib is the standard of care for second-line patients. However, novel and more specific potent therapeutic approaches for advanced HCC are still needed. The liver constitutes a unique immunological microenvironment, although anti-tumor immunity seems to be feasible with the use of checkpoint inhibitors such as nivolumab. Efficacy may be further increased by combining checkpoint inhibitors or by applying loco-regional treatments. The success of immune checkpoint blockade has renewed interest in immunotherapy in HCC.

Asymmetric and speed-dependent contact angle hysteresis and relaxation of a suddenly stopped moving contact line

NASA Astrophysics Data System (ADS)

Guan, Dongshi; Wang, Yong Jian; Charlaix, Elisabeth; Tong, Penger

We report direct atomic-force-microscope measurements of capillary force hysteresis and relaxation of a circular moving contact line (CL) formed on a long micron-sized hydrophobic fiber intersecting a water-air interface. The measured capillary force hysteresis and CL relaxation show a strong asymmetric speed dependence in the advancing and receding directions. A unified model based on force-assisted barrier-crossing is utilized to find the underlying energy barrier Eb and size λ associated with the defects on the fiber surface. The experiment demonstrates that the pinning (relaxation) and depinning dynamics of the CL can be described by a common microscopic frame-work, and the advancing and receding CLs are influenced by two different sets of relatively wetting and non-wetting defects on the fiber surface. Work supported in part by the Research Grants Council of Hong Kong SAR.

Mitochondria, Cybrids, Aging, and Alzheimer’s Disease

PubMed Central

Swerdlow, Russell H.; Koppel, Scott; Weidling, Ian; Hayley, Clay; Ji, Yan; Wilkins, Heather M.

2018-01-01

Mitochondrial and bioenergetic function change with advancing age and may drive aging phenotypes. Mitochondrial and bioenergetic changes are also documented in various age-related neurodegenerative diseases, including Alzheimer’s disease (AD). In some instances AD mitochondrial and bioenergetic changes are reminiscent of those observed with advancing age, but are greater in magnitude. Mitochondrial and bioenergetic dysfunction could, therefore, link neurodegeneration to brain aging. Interestingly, mitochondrial defects in AD patients are not brain-limited, and mitochondrial function can be linked to classic AD histologic changes including amyloid precursor protein processing to beta amyloid. Also, transferring mitochondria from AD subjects to cell lines depleted of endogenous mitochondrial DNA (mtDNA) creates cytoplasmic hybrid (cybrid) cell lines that recapitulate specific biochemical, molecular, and histologic AD features. Such findings have led to the formulation of a “mitochondrial cascade hypothesis” that places mitochondrial dysfunction at the apex of the AD pathology pyramid. Data pertinent to this premise are reviewed. PMID:28253988